Sentinel lymph node biopsy does not change melanoma-specific survival among patients with Breslow thickness greater than four millimeters.

PubMed

Caracò, Corrado; Celentano, Egidio; Lastoria, Secondo; Botti, Gerardo; Ascierto, Paolo Antonio; Mozzillo, Nicola

2004-03-01

Management of patients with cutaneous melanoma in the absence of lymph node metastases is still controversial. The experience at the National Cancer Institute in Naples was analyzed to evaluate 3-year disease-free survival and overall survival for all patients who underwent sentinel lymph node biopsy (SLB) with Breslow thickness greater than 4 mm. Data from 359 sentinel biopsies performed in the past 5 years were reviewed to determine the effect of the treatment on disease-free survival and overall survival after stratifying patients for node status, tumor ulceration, and Breslow thickness. Statistical analysis showed a better 3-year survival for sentinel node-negative patients than for sentinel node-positive cases (88.4% and 72.9%, respectively; P <.05). Tumor ulceration retained its prognostic significance despite lymph node status, indicating a higher risk for development of distant metastases. Survival curves associated with thicker melanomas did not show significant differences between negative- and positive-SLB patients. SLB provides accurate staging of nodal status in melanoma patients who have no clinical evidence of metastases. Longer follow-up and final results from ongoing trials are necessary to definitively clarify the role of this procedure.

Sentinel Lymph Node Biopsy for Cutaneous Head and Neck Melanoma: Mapping the Parotid Gland.

PubMed

Picon, Antonio I; Coit, Daniel G; Shaha, Ashok R; Brady, Mary S; Boyle, Jay O; Singh, Bhuvanesh B; Wong, Richard J; Busam, Klaus J; Shah, Jatin P; Kraus, Dennis H

2016-12-01

Sentinel lymph node biopsy (SLNB) for primary cutaneous head and neck melanoma (CHNM) has been shown to be successful and is the current standard of care for intermediate-thickness melanoma. We evaluated our experience with CHNM associated with SLNB mapping to the region of the parotid gland. Retrospective review of a prospectively collected melanoma database identified 1014 CHNMs. Two-hundred twenty-three patients underwent SLNB, and 72 (32%) had mapping in the region of the parotid gland between May 1995 and June 2003. The mean number of SLNs per patient was 2.5. A sentinel lymph node (SLN) was successfully identified in 94% of patients, and in 12%, the SLN was positive for metastatic disease. Biopsy of intraparotid SLNs was performed in 51.4% and of periparotid SLNs in 26.4%, and a superficial parotidectomy was performed in 22.2%. Ten patients were found to have lymph nodes in the parotid region with metastatic disease (eight identified by SLNB), and two (20%) patients developed intraparotid lymph node recurrence in the setting of a negative SLNB. Same-basin recurrence in SLN-negative patients was 3.3% with a median follow-up of 26 months. Facial nerve dysfunction was identified in seven (10%) patients. Facial nerve function returned to preoperative status in all patients. SLNB for patients with primary CHNM mapping to the parotid gland can be performed with a high degree of accuracy and a low morbidity consisting of temporary facial nerve paresis.

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

A critical reappraisal of false negative sentinel lymph node biopsy in melanoma.

PubMed

Manca, G; Romanini, A; Rubello, D; Mazzarri, S; Boni, G; Chiacchio, S; Tredici, M; Duce, V; Tardelli, E; Volterrani, D; Mariani, G

2014-06-01

Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. 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. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the prognosis

Excision margins and sentinel lymph node status as prognostic factors in thick melanoma of the head and neck: A retrospective analysis.

PubMed

Ruskin, Olivia; Sanelli, Alexandra; Herschtal, Alan; Webb, Angela; Dixon, Ben; Pohl, Miklos; Donahoe, Simon; Spillane, John; Henderson, Michael A; Gyorki, David E

2016-09-01

Recommended margins for thick cutaneous melanoma (Breslow thickness >4 mm; T4) have decreased over recent decades. Optimal margins and the role of sentinel node biopsy (SNB) in thick head and neck melanoma remain controversial. A single-center review was conducted of patients treated between 2002 and 2012 assessing the impact of excision margins and sentinel lymph node status on locoregional recurrence and melanoma-specific survival (MSS). One hundred eight patients were identified. Median age was 71.1 years and median Breslow thickness was 6.0 mm. Median follow-up was 40 months. Locoregional recurrence occurred in 27% and there was no significant reduction in recurrence with margins ≥2 cm (p = .17). Increasing margins did not improve survival (p = .58). Fifty-nine patients (55%) underwent SNB, of which 27% were positive. There was a trend toward longer survival for patients who were sentinel lymph node-negative (p = .097). Wider margins do not significantly improve locoregional recurrence or MSS. Sentinel lymph node involvement reflects a poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1373-1379, 2016. © 2016 Wiley Periodicals, Inc.

The Prognostic Significance of Sentinel Lymph Node Status for Patients with Thick Melanoma.

PubMed

Bello, Danielle M; Han, Gang; Jackson, Laura; Bulloch, Kaleigh; Ariyan, Stephan; Narayan, Deepak; Rothberg, Bonnie Gould; Han, Dale

2016-12-01

Sentinel lymph node biopsy (SLNB) is recommended for patients with intermediate-thickness melanoma, but the use of SLNB for patients with thick melanoma is debated. This report presents a single-institution study investigating factors predictive of sentinel lymph node (SLN) metastasis and outcome for thick-melanoma patients . A retrospective review of a single-institution database from 1997 to 2012 identified 147 patients with thick primary cutaneous melanoma (≥4 mm) who had an SLNB. Clinicopathologic characteristics were correlated with nodal status and outcome. The median age of the patients was 67 years, and 61.9 % of the patients were men. The median tumor thickness was 5.5 mm, and 54 patients (36.7 %) had a positive SLN. Multivariable analysis showed that only tumor thickness significantly predicted SLN metastasis (odds ratio 1.14; 95 % confidence interval (CI) 1.02-1.28; P = 0.02). The overall median follow-up period was 34.6 months. Overall survival (OS) and melanoma-specific survival (MSS) were significantly worse for the positive versus negative-SLN patients. Multivariable analysis showed that age [hazard ratio (HR) 1.04; 95 % CI 1.01-1.07; P = 0.02] and SLN status (HR 2.24; 95 % CI 1.03-4.88; P = 0.04) significantly predicted OS, whereas only SLN status (HR 3.85; 95 % CI 2.13-6.97; P < 0.01) significantly predicted MSS. Tumor thickness predicts SLN status in thick melanomas. Furthermore, SLN status is prognostic for OS and MSS in thick-melanoma patients, with positive-SLN patients having significantly worse OS and MSS. These findings show that SLNB should be recommended for thick-melanoma patients, particularly because detection of SLN metastasis can identify patients for potential systemic therapy and treatment of nodal disease at a microscopic stage.

Transected thin melanoma: Implications for sentinel lymph node staging.

PubMed

Herbert, Garth; Karakousis, Giorgos C; Bartlett, Edmund K; Zaheer, Salman; Graham, Danielle; Czerniecki, Brian J; Fraker, Douglas L; Ariyan, Charlotte; Coit, Daniel G; Brady, Mary S

2018-03-01

Indications for sentinel lymph node (SLN) biopsy in patients with thin melanoma (≤1 mm thick) are controversial. We asked whether deep margin (DM) positivity at initial biopsy of thin melanoma is associated with SLN positivity. Cases were identified using prospectively maintained databases at two melanoma centers. Patients who had undergone SLN biopsy for melanoma ≤1 mm were included. DM status was assessed for association with SLN metastasis in univariate and multivariate analyses. 1413 cases were identified, but only 1129 with known DM status were included. 39% of patients had a positive DM on original biopsy. DM-positive and DM-negative patients did not differ significantly in primary thickness, ulceration, or mitotic activity. DM-positive and DM-negative patients had similar incidence of SLN metastasis (5.7% vs 3.5%; P = 0.07). Positive DM was not associated with SLN metastasis on univariate analysis (OR 1.69, 95% CI: 0.95-3.00, P = 0.07) or on multivariate analysis adjusted for Breslow depth, Clark level, mitotic rate, and ulceration (OR = 1.59, 95% CI: 0.89-2.85; P = 0.12). For patients with thin melanoma, a positive DM on initial biopsy is not associated with risk of SLN metastasis, so DM positivity should not be considered an indication for SLN staging in an otherwise low-risk patient. © 2017 Wiley Periodicals, Inc.

Clinical relevance of sentinel lymph node status examined with conventional histology and molecular biology.

PubMed

Micciolo, Rocco; Boi, Sebastiana; Paoli, Loredana; Cristofolini, Paolo; Girlando, Salvatore; Dalla Palma, Paolo; Cristofolini, Mario

2009-01-01

The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.

Sentinel Node Biopsy in Melanoma: A Short Update

PubMed Central

Ferrara, Gerardo; Partenzi, Antonietta; Filosa, Alessandra

2018-01-01

Several controversies are still ongoing about sentinel node biopsy in melanoma. It is basically a staging procedure for melanoma > 0.75 mm in thickness or for thinner melanoma in the presence of ulceration, high mitotic rate, and/or lymphovascular invasion. Complete lymph node dissection after a positive sentinel node can also allow a better locoregional disease control but seems not to prevent the development of distant metastases. The use of sentinel node biopsy in atypical Spitz tumors should be discouraged because of their peculiar biological properties. PMID:29719827

Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

PubMed

Hunger, Robert E; Michel, Aude; Seyed Jafari, S Morteza; Shafighi, Maziar

2015-01-01

The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. We evaluated the clinical effect of SLNB in patients with thick melanoma. We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

Impact of Completion Lymph Node Dissection on Patients with Positive Sentinel Lymph Node Biopsy in Melanoma

PubMed Central

Lee, David Y; Lau, Briana J; Huynh, Kelly T; Flaherty, Devin C; Lee, Ji-Hey; Stern, Stacey L; Day, Steve J O'; Foshag, Leland J; Faries, Mark B

2016-01-01

Background The need for complete lymph node dissection (CLND) in patients with positive sentinel lymph node biopsy (SNB) is an important unanswered clinical question. Study Design Patients diagnosed with positive SNB at a melanoma referral center from 1991 to 2013 were studied. Outcomes of patients who underwent CLND were compared to those who did not undergo immediate CLND (observation group, OBS). Results There were 471 patients who had positive SNB; 375 (79.6%) in the CLND group and 96 (20.4%) in the OBS group. The groups were similar except that the CLND group was younger and had more sentinel nodes removed. Five-year nodal recurrence free survival was significantly better in the CLND group compared to the OBS group (93.1% vs 84.4%, p= 0.005). However, the 5- (66.4% vs 55.2%) and 10- year (59.5% vs 45.0%) distant metastasis free survival was not significantly different (p= 0.061). The CLND group's melanoma specific survival (MSS) was superior to the OBS group; 5 year MSS was (73.7 vs 65.5%) and10 year MSS- (66.8 vs 48.3%, p=0.015). On multivariate analysis, CLND was associated with improved MSS (HR 0.60, 95% CI 0.40-0.89, p= 0.011) and lower nodal recurrence (HR 0.46, 95% CI 0.24-0.86, p=0.016). Increased Breslow thickness, older age, ulceration, and trunk melanoma were all associated with worse outcomes. On subgroup analysis, following factors were associated with better outcomes from CLND- male gender, non-ulcerated primary, intermediate thickness, Clark level IV or lower extremity tumors. Conclusions Treatment of positive SNB with CLND was associated with improved MSS and nodal recurrence rate. Follow up beyond 5 years was needed to see a significant difference in MSS. PMID:27236435

Intraoperative evaluation of sentinel lymph nodes for metastatic melanoma by imprint cytology.

PubMed

Soo, Victoria; Shen, Perry; Pichardo, Rita; Azzazy, Hossam; Stewart, John H; Geisinger, Kim R; Levine, Edward A

2007-05-01

Sentinel lymph node biopsy (SLN) has revolutionized nodal staging. Accurate intraoperative evaluation of SLN permits a single procedure, with lymphadenectomy being performed during the initial operative procedure when the SLN is positive. There is a paucity of literature on intraoperative imprint cytology (IIC) evaluation of the SLN in melanoma. The purpose of this article is to present an update to our experience with IIC for SLN in melanoma. Melanoma patients had SLNs examined by IIC. SLNs were bisected, and imprints were made from each half. Imprints were stained with hematoxylin and eosin and with Diff-Quik. Paraffin-embedded sections were examined with multiple hematoxylin and eosin-stained sections from the SLNs in conjunction with immunohistochemical staining for S-100, Melan-A, and HMB-45 proteins. Metastases were identified in 40 (17%) of 229 patients. Of these, 13 patients were detected by IIC (sensitivity, 33%). The negative predictive value was 88%. No false-positive results were identified (specificity, 100%). The positive predictive value was 100%. The accuracy of IIC was 78%. The sensitivity for detecting macrometastases (>2 mm) was better than that for detecting micrometastases (< or =2 mm): 62% vs. 16% (P < .01). Patients with positive SLNs by IIC had lymphadenectomy under the same anesthetic. A total of 533 nonsentinel lymph nodes were identified in 42 patients. Only two patients (8%) had positive nonsentinel lymph nodes after a negative IIC. IIC is a viable alternative to frozen sectioning when intraoperative evaluation is desired. IIC is significantly more sensitive for macrometastases. IIC evaluation of SLNs in melanoma makes a single operative procedure possible for a significant proportion of patients with regional nodal metastases.

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

PubMed

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

2014-01-01

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

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. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2008-10-01

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

[The historical perspective of the sentinel lymph node concept].

PubMed

Bekker, J; Meijer, S

2008-01-05

The sentinel lymph node procedure is currently standard care in the treatment of breast cancer. The introduction of this procedure in 1992 would not have been possible without the pioneering discoveries regarding lymph nodes and cancer. The Italian surgeon Gaspar Asellius (1581-1626) visualized the lymphatic vessels of a dog after it had been fed and shortly before dissection. At the end of the 17th century, the French anatomists Lauth and Sappey visualized the lymphatics by injecting deceased criminals with mercury. In 1858, the German pathologist Virchow (1821-1902) launched the theory that lymph nodes act as defensive barriers. He also made the first microscopical illustration ofa sentinel lymph node. Gould et al. and Cabaãs independently launched the precursors of the current modern sentinel lymph node concept in 1959 and 1977 respectively. Gould et al. were the first people to use the term "sentinel node'. Cabañas used lymphangiography for the visualisation of the sentinel lymph node. Controversies about the barrier function of the lymph nodes, the fear of skip metastasis and the difficulties of performing the Cabañas procedure, prevented a breakthrough of this concept. In 1992 Morton et al. rediscovered the valuable sentinel node biopsy concept and introduced blue dye for the investigation of patients with melanoma. The combination of lymphoscintigraphy, intra-operative gamma probe guidance and patent blue further increased the reliability of the sentinel lymph node biopsy procedure. Unnecessary lymph gland dissection procedures with considerable morbidity can be prevented by this procedure.

Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

PubMed

Kucher, Cynthia; Zhang, Paul J; Acs, Geza; Roberts, Shelley; Xu, Xiaowei

2006-09-01

The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.

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

PubMed

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

2016-01-01

Melanoma is a disease that has an increasing incidence worldwide. Sentinel lymph node scintigraphy is a diagnostic tool that offers important information regarding the localization of the sentinel lymph nodes offering important input data to establish a pertinent and personalized therapeutic strategy. The golden standard in body contouring for sentinel lymph node scintigraphy is to use a planar flood source of Cobalt-57 (Co-57) placed behind the patients, against the gamma camera. The purpose of the study was to determine the performance of the procedure using a flood calibration planar phantom filled with aqueous solution of Technetion-99m (Tc-99m) in comparison with the published data in literature where the gold standard was used. The study was conducted in the Department of Nuclear Medicine of Oncology Institute "Prof. Dr. Ion Chiricuţă" Cluj-Napoca in 95 patients, 31 males and 64 females. The localization of the lesions was grouped by anatomical regions as follows: 23 on lower limbs, 17 on upper limbs, 45 on thorax and 10 on abdomen. The calibration flood phantom containing aqueous solution of Tc-99m pertechnetate was used as planar source to visualize the body contour of the patients for a proper anatomic localization of detected sentinel lymph nodes. The radiopharmaceutical uptake in sentinel lymph nodes has been recorded in serial images following peritumoral injection of 1 ml solution of Tc-99m albumin nanocolloids with an activity of 1 mCi (37 MBq). The used protocol consisted in early acquired planar images within 15 minutes post-injection and delayed images at 2-3 hours and when necessary, additional images at 6-7 hours. The acquisition matrix used was 128×128 pixels for an acquisition time of 5 - 7 minutes. The skin projection of the sentinel lymph nodes was marked on the skin and surgical removal of detected sentinel lymph nodes was performed the next day using a gamma probe for detection and measurements. The sentinel lymph nodes were detected in

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

PubMed

Boada, Aram; Tejera-Vaquerizo, Antonio; Ribero, Simone; Puig, Susana; Moreno-Ramírez, David; Descalzo-Gallego, Miguel A; Fierro, María T; Quaglino, Pietro; Carrera, Cristina; Malvehy, Josep; Vidal-Sicart, Sergi; Bennássar, Antoni; Rull, Ramón; Alos, Llucìa; Requena, Celia; Bolumar, Isidro; Traves, Víctor; Pla, Ángel; Fernández-Figueras, María T; Ferrándiz, Carlos; Pascual, Iciar; Manzano, José L; Sánchez-Lucas, Marina; Giménez-Xavier, Pol; Ferrandiz, Lara; Nagore, Eduardo

2018-02-01

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. © 2017 UICC.

Sentinel lymph node biopsy in cutaneous head and neck melanoma.

PubMed

Evrard, D; Routier, E; Mateus, C; Tomasic, G; Lombroso, J; Kolb, F; Robert, C; Moya-Plana, A

2018-05-01

Sentinel lymph node biopsy (SLNB) is now a standard of care for cutaneous melanoma, but it is still controversial for cutaneous head and neck melanoma (CHNM). This study aims to confirm the feasibility, accuracy and low morbidity of SLNB in CHNM and evaluate its prognostic value. A monocentric and retrospective study on patients with CHNM treated in our tertiary care center (Gustave Roussy) between January 2008 and December 2012 was performed. The feasibility, morbidity and prognostic value of this technique were analysed. One hundred and twenty-four consecutive patients were included. SLNB was realized in 97.6% of the cases. No significant post-operative morbidity was observed. Nineteen percents of patients had a positive SN while only 14.3% of complete lymph node dissections (CLND) had additional nodal metastasis. The risk of recurrence after positive SN was significantly higher (69.2 vs 30.8%, p = 0.043). The false omission rate was low with 7.1%. Overall survival and disease-free survival were better in the negative SN group (82 vs 49%, p < 0.001 and 69.3 vs 41.8%, p = 0.0131). The risk of recurrence was significantly higher in the positive SN group (p = 0.043) and when primary tumour was ulcerated (p = 0.031). Only the mitotic rate of the primary tumour was associated with SN positivity (p = 0.049). As in other sites, SLNB status is a strong prognostic factor with comparable false omission rate and no superior morbidity.

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

PubMed

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

2017-06-08

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

Impact of sentinel lymphadenectomy on survival in a murine model of melanoma.

PubMed

Rebhun, Robert B; Lazar, Alexander J F; Fidler, Isaiah J; Gershenwald, Jeffrey E

2008-01-01

Lymphatic mapping and sentinel lymph node biopsy-also termed sentinel lymphadenectomy (SL)-has become a standard of care for patients with primary invasive cutaneous melanoma. This technique has been shown to provide accurate information about the disease status of the regional lymph node basins at risk for metastasis, provide prognostic information, and provide durable regional lymph node control. The potential survival benefit afforded to patients undergoing SL is controversial. Central to this controversy is whether metastasis to regional lymph nodes occurs independent of or prior to widespread hematogenous dissemination. A related area of uncertainty is whether tumor cells residing within regional lymph nodes have increased metastatic potential. We have used a murine model of primary invasive cutaneous melanoma based on injection of B16-BL6 melanoma cells into the pinna to address two questions: (1) does SL plus wide excision of the primary tumor result in a survival advantage over wide excision alone; and (2) do melanoma cells growing within lymph nodes produce a higher incidence of hematogenous metastases than do cells growing at the primary tumor site? We found that SL significantly improved the survival of mice with small primary tumors. We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.

Age as predictor in patients with cutaneous melanoma submitted to sentinel lymph node biopsy.

PubMed

Caracò, C; Marone, U; Botti, G; Celentano, E; Lastoria, S; Mozzillo, N

2006-11-01

To analyse the age as prognostic factor exploring the melanoma database at the National Cancer Institute in Naples. Three hundred and ninety-nine patients with cutaneous melanoma were treated with sentinel lymph node biopsy from 1996 to 2003 at the National Cancer Institute of Naples. The results were analysed with particular attention to the overall survival among patients younger or older than 50 years of age. No differences were recorded between the younger and older group in terms of the identification rate and incidence of metastases. The analyses of disease-free survival and overall survival showed a significantly more favourable outcome in younger patients. The 5-year overall survival and the 5-year disease free survival were 81.8% vs. 68.0% and 76.3% vs. 59.1% for the younger and older group, respectively. The results suggest that in the management of cutaneous melanoma, age might be considered as prognostic factor both for disease free survival and overall survival.

Use of Lymph Node Ultrasound Prior to Sentinel Lymph Node Biopsy in 384 Patients with Melanoma: A Cost-Effectiveness Analysis.

PubMed

Olmedo, D; Brotons-Seguí, M; Del Toro, C; González, M; Requena, C; Traves, V; Pla, A; Bolumar, I; Moreno-Ramírez, D; Nagore, E

2017-12-01

Locoregional lymph node ultrasound is not typically included in guidelines as part of the staging process prior to sentinel lymph node biopsy (SLNB). The objective of the present study was to make a clinical and economic analysis of lymph node ultrasound prior to SLNB. We performed a retrospective study of 384 patients with clinical stage I-II primary melanoma who underwent locorregional lymph node ultrasound (with or without ultrasound-guided biopsy) prior to SLNB between 2004 and 2015. We evaluated the reliability and cost-effectiveness of the strategy. Use of locorregional lymph node ultrasound avoided SLNB in 23 patients (6%). Ultrasound had a sensitivity of 46% and specificity of 76% for the detection of metastatic lymph nodes that were not clinically palpable. False negatives were significantly more common in patients aged over 60 years and in tumors with a thickness of less than 2mm. The staging process using SLNB and ultrasound with ultrasound-guided biopsy produced an increase of €16.30 in the unit price. Our cost-effectiveness analysis identified the staging protocol with ultrasound and SLNB as the dominant strategy, with a lower cost-effectiveness ratio than the alternative, consisting of SLNB alone (8,095.24 vs. €28,605.00). Ultrasound with ultrasound-guided biopsy for the diagnostic staging of melanoma prior to SLNB is a useful and cost-effective tool. This procedure does not substitute SLNB, though it does allow to avoid SLNB in a not insignificant proportion of patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

PubMed

Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

2016-01-01

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

Validation of statistical predictive models meant to select melanoma patients for sentinel lymph node biopsy.

PubMed

Sabel, Michael S; Rice, John D; Griffith, Kent A; Lowe, Lori; Wong, Sandra L; Chang, Alfred E; Johnson, Timothy M; Taylor, Jeremy M G

2012-01-01

To identify melanoma patients at sufficiently low risk of nodal metastases who could avoid sentinel lymph node biopsy (SLNB), several statistical models have been proposed based upon patient/tumor characteristics, including logistic regression, classification trees, random forests, and support vector machines. We sought to validate recently published models meant to predict sentinel node status. We queried our comprehensive, prospectively collected melanoma database for consecutive melanoma patients undergoing SLNB. Prediction values were estimated based upon four published models, calculating the same reported metrics: negative predictive value (NPV), rate of negative predictions (RNP), and false-negative rate (FNR). Logistic regression performed comparably with our data when considering NPV (89.4 versus 93.6%); however, the model's specificity was not high enough to significantly reduce the rate of biopsies (SLN reduction rate of 2.9%). When applied to our data, the classification tree produced NPV and reduction in biopsy rates that were lower (87.7 versus 94.1 and 29.8 versus 14.3, respectively). Two published models could not be applied to our data due to model complexity and the use of proprietary software. Published models meant to reduce the SLNB rate among patients with melanoma either underperformed when applied to our larger dataset, or could not be validated. Differences in selection criteria and histopathologic interpretation likely resulted in underperformance. Statistical predictive models must be developed in a clinically applicable manner to allow for both validation and ultimately clinical utility.

Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin?

PubMed Central

Rios-Cantu, Andrei; Lu, Ying; Melendez-Elizondo, Victor; Chen, Michael; Gutierrez-Range, Alejandra; Fadaki, Niloofar; Thummala, Suresh; West-Coffee, Carla; Cleaver, James; Kashani–Sabet, Mohammed

2018-01-01

Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49–62%) for patients with no additional LN on CLND versus 14% (95% CI 8–26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4–15+ years) and 1.2 years with positive CLND (95% CI 1.0–1.8 years). The 5-year overall survival rates were 67% (95% CI 61–74%) for negative CLND versus 38% (95% CI 28–52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3–15+ years) and 2.5 years for positive CLND (95% CI 2.2–5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non

Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin?

PubMed

Rios-Cantu, Andrei; Lu, Ying; Melendez-Elizondo, Victor; Chen, Michael; Gutierrez-Range, Alejandra; Fadaki, Niloofar; Thummala, Suresh; West-Coffee, Carla; Cleaver, James; Kashani-Sabet, Mohammed; Leong, Stanley P L

2017-06-01

Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8-26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4-15+ years) and 1.2 years with positive CLND (95% CI 1.0-1.8 years). The 5-year overall survival rates were 67% (95% CI 61-74%) for negative CLND versus 38% (95% CI 28-52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3-15+ years) and 2.5 years for positive CLND (95% CI 2.2-5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non

EANM-EORTC general recommendations for sentinel node diagnostics in melanoma.

PubMed

Chakera, Annette H; Hesse, Birger; Burak, Zeynep; Ballinger, James R; Britten, Allan; Caracò, Corrado; Cochran, Alistair J; Cook, Martin G; Drzewiecki, Krzysztof T; Essner, Richard; Even-Sapir, Einat; Eggermont, Alexander M M; Stopar, Tanja Gmeiner; Ingvar, Christian; Mihm, Martin C; McCarthy, Stanley W; Mozzillo, Nicola; Nieweg, Omgo E; Scolyer, Richard A; Starz, Hans; Thompson, John F; Trifirò, Giuseppe; Viale, Giuseppe; Vidal-Sicart, Sergi; Uren, Roger; Waddington, Wendy; Chiti, Arturo; Spatz, Alain; Testori, Alessandro

2009-10-01

The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, (8) use of dye, (9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.

Re and 99mTc Tricarbonyl Probes for Target-Specific Detection of Melanoma and Sentinel Lymph Node

NASA Astrophysics Data System (ADS)

Morais, Mauricio da Silva

The work described in this thesis aimed at the development of M(I) (M = 99mTc, Re) specific probes for the detection of malignant melanoma and sentinel lymph node (SLN) through the in vivo targeting of membrane receptors. In the former case we have designed M(CO)3-complexes stabilized by tridentate chelators containing a pyrazolyl-diamine chelating unit (N,N,N donor atom set) and pendant alpha-melanocyte-stimulating hormone (alpha-MSH) derivatives for targeting the melanocortin receptor 1 (MC1R), which is overexpressed in melanotic and amelanotic human melanoma cells. (Abstract shortened by ProQuest.). None None None None None None None None None None None None None None None None None

Portable gamma camera guidance in sentinel lymph node biopsy: prospective observational study of consecutive cases.

PubMed

Peral Rubio, F; de La Riva, P; Moreno-Ramírez, D; Ferrándiz-Pulido, L

2015-06-01

Sentinel lymph node biopsy is the most important tool available for node staging in patients with melanoma. To analyze sentinel lymph node detection and dissection with radio guidance from a portable gamma camera. To assess the number of complications attributable to this biopsy technique. Prospective observational study of a consecutive series of patients undergoing radioguided sentinel lymph node biopsy. We analyzed agreement between nodes detected by presurgical lymphography, those detected by the gamma camera, and those finally dissected. A total of 29 patients (17 women [62.5%] and 12 men [37.5%]) were enrolled. The mean age was 52.6 years (range, 26-82 years). The sentinel node was dissected from all patients; secondary nodes were dissected from some. In 16 cases (55.2%), there was agreement between the number of nodes detected by lymphography, those detected by the gamma camera, and those finally dissected. The only complications observed were seromas (3.64%). No cases of wound dehiscence, infection, hematoma, or hemorrhage were observed. Portable gamma-camera radio guidance may be of use in improving the detection and dissection of sentinel lymph nodes and may also reduce complications. These goals are essential in a procedure whose purpose is melanoma staging. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

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. © 2015 Royal Australasian College of Surgeons.

Predictors of false negative sentinel lymph node biopsy in trunk and extremity melanoma.

PubMed

Sinnamon, Andrew J; Neuwirth, Madalyn G; Bartlett, Edmund K; Zaheer, Salman; Etherington, Mark S; Xu, Xiaowei; Elder, David E; Czerniecki, Brian J; Fraker, Douglas L; Karakousis, Giorgos C

2017-12-01

Nodal recurrence following negative sentinel lymph node biopsy (SLNB) for melanoma is known as false-negative (FN) SLNB. Risk factors for FN SLNB among patients with trunk and extremity melanoma have not been well-defined. After retrospective review, SLNB procedures were classified FN, true positive (TP; positive SLNB), or true negative (TN; negative SLNB without recurrence). Factors associated with high false negative rate (FNR) and low negative predictive value (NPV) were identified by comparing FNs to TPs and TNs, respectively. Survival was evaluated using Kaplan-Meier methods. Of 1728 patients, 234 were TP and 37 were FN for overall FNR of 14% and NPV of 97.5%. Age ≥65 years was independently associated with high FNR (FNR 20% in this group). Breslow thickness >1 mm and ulceration were independently associated with low NPV. Among patients with ulcerated tumors >4 mm, NPV was 88%. Median time to recurrence for FNs was 13 months. Among patients with primary melanomas ≤2 mm in depth, overall and distant disease-free survival were significantly shorter with FN SLNB than TP SLNB. Older age is associated with increased FNR; patients with thick, ulcerated lesions should be considered for increased nodal surveillance after negative SLNB given low NPV in this group. © 2017 Wiley Periodicals, Inc.

Tumour mutation status and melanoma recurrence following a negative sentinel lymph node biopsy.

PubMed

Adler, Nikki R; Wolfe, Rory; McArthur, Grant A; Kelly, John W; Haydon, Andrew; McLean, Catriona A; Mar, Victoria J

2018-05-14

A proportion of patients develop recurrence following a tumour-negative sentinel lymph node biopsy (SLNB). This study aimed to explore whether melanoma patients with BRAF or NRAS mutant tumours have an increased risk of developing disease recurrence following a negative SLNB compared to patients with wild-type tumours. Prospective cohort study of melanoma patients at three tertiary referral centres in Melbourne, who underwent SLNB. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded. Multivariate Cox proportional hazards regression models estimated the adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) for the association between mutation status and development of recurrence following a negative-SLNB. Overall, 344/477 (72.1%) patients had a negative SLNB. Of these, 54 (15.7%) developed subsequent recurrence. The risk of disease recurrence following a negative SLNB was increased for patients with either a BRAF or NRAS mutant tumour compared to wild-type tumours (aHR 1.92, 95% CI: 1.02-3.60, p = 0.04). Melanoma patients with BRAF or NRAS mutant tumours had an increased risk compared to patients with BRAF/NRAS wild-type tumours of developing disease recurrence following a tumour-negative SLNB. The findings also confirm the importance of continued surveillance to monitor for disease recurrence among SLNB-negative patients.

Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma.

PubMed

Maruyama, Hiroshi; Tanaka, Ryota; Fujisawa, Yasuhiro; Nakamura, Yasuhiro; Ito, Shusaku; Fujimoto, Manabu

2017-04-01

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2-T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. © 2016 Japanese Dermatological Association.

Immune cell profile of sentinel lymph nodes in patients with malignant melanoma – FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome

PubMed Central

2013-01-01

Background Besides being a preferential site of early metastasis, the sentinel lymph node (SLN) is also a privileged site of T-cell priming, and may thus be an appropriate target for investigating cell types involved in antitumor immune reactions. Methods In this retrospective study we determined the prevalence of OX40+ activated T lymphocytes, FOXP3+ (forkhead box P3) regulatory T cells, DC-LAMP+ (dendritic cell-lysosomal associated membrane protein) mature dendritic cells (DCs) and CD123+ plasmacytoid DCs by immunohistochemistry in 100 SLNs from 60 melanoma patients. Density values of each cell type in SLNs were compared to those in non-sentinel nodes obtained from block dissections (n = 37), and analyzed with regard to associations with clinicopathological parameters and disease outcome. Results Sentinel nodes showed elevated amount of all cell types studied in comparison to non-sentinel nodes. Metastatic SLNs had higher density of OX40+ lymphocytes compared to tumor-negative nodes, while no significant difference was observed in the case of the other cell types studied. In patients with positive sentinel node status, high amount of FOXP3+ cells in SLNs was associated with shorter progression-free (P = 0.0011) and overall survival (P = 0.0014), while no significant correlation was found in the case of sentinel-negative patients. The density of OX40+, CD123+ or DC-LAMP+ cells did not show significant association with the outcome of the disease. Conclusions Taken together, our results are compatible with the hypothesis of functional competence of sentinel lymph nodes based on the prevalence of the studied immune cells. The density of FOXP3+ lymphocytes showed association with progression and survival in patients with positive SLN status, while the other immune markers studied did not prove of prognostic importance. These results, together with our previous findings on the prognostic value of activated T cells and mature DCs infiltrating primary

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

PubMed

Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

2016-08-01

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. © 2016 UICC.

Reliability and cost-effectiveness of sentinel lymph node excision under local anaesthesia versus general anaesthesia for malignant melanoma: a retrospective analysis in 300 patients with malignant melanoma AJCC Stages I and II.

PubMed

Stoffels, I; Dissemond, J; Körber, A; Hillen, U; Poeppel, T; Schadendorf, D; Klode, J

2011-03-01

Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions, as it is a cost-intensive surgical intervention with potentially significant morbidity. The present retrospective study seeks to clarify the effectiveness and reliability of SLNE performed under tumescent local anaesthesia (TLA) and whether SLNE performed under TLA can reduce costs and morbidity. Therefore, our study is a comparison of SLNE performed under TLA and general anaesthesia (GA). We retrospectively analysed data from 300 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm. Altogether, 211 (70.3%) patients underwent SLNE under TLA and 89 (29.7%) patients underwent SLNE under GA. A total of 637 sentinel lymph nodes (SLN) were removed. In the TLA group 1.98 SLN/patient and in the GA group 2.46 SLN/patient were removed (median value). Seventy patients (23.3%) had a positive SLN. No major complications occurred. The costs for SLNE were significantly less for the SLNE in a procedures room performed under TLA (mean € 30.64) compared with SLNE in an operating room under GA (mean € 326.14, P<0.0001). In conclusion, SLNE performed under TLA is safe, reliable, and cost-efficient and could become the new gold standard in sentinel lymph node diagnostic procedures. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

PubMed

Rossi, Carlo Riccardo; Mocellin, Simone; Campana, Luca Giovanni; Borgognoni, Lorenzo; Sestini, Serena; Giudice, Giuseppe; Caracò, Corrado; Cordova, Adriana; Solari, Nicola; Piazzalunga, Dario; Carcoforo, Paolo; Quaglino, Pietro; Caliendo, Virginia; Ribero, Simone

2018-01-01

Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

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

PubMed

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

2014-01-01

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

Value of planar lymphoscintigraphy versus SPECT/CT in evaluation of sentinel lymph node in trunk melanoma - one center, large series, retrospective study.

PubMed

Benke, Małgorzata; Wocial, Krzysztof; Lewandowska, Weronika; Rutkowski, Piotr Łukasz; Teterycz, Paweł; Jarek, Piotr; Dedecjus, Marek

2018-06-29

Background Localization and histopathological examination of sentinel lymph node (SLN) is a standard of melanoma treatment. The first stage of identification of the SLN is the preoperative lymphoscintigraphy. The aim of this study was to assess and compare diagnostic value of planar lymphoscintigraphy (PL) and SPECT/CT in sentinel lymph node biopsy (SLNB) procedure performed in patients with cutaneous trunk melanoma. Material and Methods Between 2015 and 2016, patients with trunk melanoma (N=255, F/M 95/160), aged from 17 to 88 after an excisional biopsy, with primary tumor ≥ pT1b (AJCC 2009, median Breslow thickness 2.0± 3.13) were included in the study. In all the patients PL was followed by SPECT/CT 1-3 h after injection of 99mTc- colloid particles, and SLNB was performed the next day. Results SPECT-CT revealed 78 (18.6%) SLN more than PL, and in 40 patients showed additional lymph drainage regions leading to surgical adjustments. In 18 patients (7.1%) SPECT-CT revealed SLN not visible in the PL (false-negative PL) and in 22 patients (8.6%), foci of uptake interpreted in PL as hot SLNs were found to be non-nodal sites of uptake when assessed on SPECT/CT (false positive PL). SPECT-CT vs. PL mismatch was observed in 31 patients (12.2%) and was the most common in patients with primary lesions located in the anterior inferior medial region (75%). Conclusions Results of the presented study indicates the high diagnostic value of SPECT-CT in assessment of SLNs and proved that SPECT-CT increases the sensitivity and accuracy of SLN identification as compared to PL even in very experienced hands.

[Risk factors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node ≤ 2].

PubMed

Gao, Yajun; He, Yingjian; Fan, Zhaoqing; Ouyang, Tao

2014-08-13

To explore retrospectively the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with sentinel lymph node metastasis ≤ 2 and examine the likelihood of non-sentinel lymph node prediction. A sentinel lymph node biopsy database containing 455 breast cancer patients admitted between July 2005 and February 2012 at Beijing Cancer Hospital was analyzed retrospectively. The patients had ≤ 2 positive sentinel lymph node and complete axillary lymph node dissection. The SLNS⁺/SLNS ratio (P = 0.001), histological grade (P = 0.075), size of mass (P = 0.023) and onset age (P = 0.074) were correlated with NSLN metastases. Only SLNS⁺/SLNS (OR 0.502 95% CI 0.322-0.7844) , histological grade ratio (histological grade ratio II, III and others vs grade I OR 2.696, 2.102, 3.662) were significant independent predictors for NSLN metastases . The ROC value was 0.62 (0.56, 0.68). For ≤ 2 positive sentinel lymph nodes of breast cancer, ratio of SLNS⁺/SLNS and histological grading are independent factors affecting NSLN metastases. However, the results remain unsatisfactory for predicting the status of NSLN.

Sentinel Lymph Nodes for Breast Carcinoma A Paradigm Shift

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

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

Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.

PubMed

Maguire, Aoife; Brogi, Edi

2016-08-01

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

Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

PubMed

Gerami, Pedram; Cook, Robert W; Russell, Maria C; Wilkinson, Jeff; Amaria, Rodabe N; Gonzalez, Rene; Lyle, Stephen; Jackson, Gilchrist L; Greisinger, Anthony J; Johnson, Clare E; Oelschlager, Kristen M; Stone, John F; Maetzold, Derek J; Ferris, Laura K; Wayne, Jeffrey D; Cooper, Chelsea; Obregon, Roxana; Delman, Keith A; Lawson, David

2015-05-01

A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively. Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-04-01

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

Histomorphologic parameters and CXCR4 mRNA and protein expression in sentinel node melanoma metastasis are correlated to clinical outcome.

PubMed

Franco, Renato; Cantile, Monica; Scala, Stefania; Catalano, Elisabetta; Cerrone, Margherita; Scognamiglio, Giosuè; Pinto, Antonio; Chiofalo, Maria Grazia; Caracò, Corrado; Anniciello, Anna Maria; Abbruzzese, Alberto; Caraglia, Michele; Botti, Gerardo

2010-03-15

Sentinel lymph node (SLN) biopsy is an important independent prognostic factor for invasive cutaneuos melanoma, although its role is strongly debated. In clinical practice SLN leads to complete lymph node dissection of basin draining melanoma site. However only 7-30% of positive sentinel node patients present additional non SLN metastasis. Melanoma cells diffusion through SLN and extranodal spreading depends upon biological features, such as cell chemokine receptors and adhesion molecules. CXCR4 has been proposed in melanoma patients as prognostic marker. Therefore we have analyzed both histopathological parameters and CXCR4 expression in melanoma infiltrate of SLN, in order to evaluate its potential prognostic role. Micrometastases were detected in 23 cases (48.93%); metastases >2 mm in 23 cases (48.93%) and isolated metastatic cells in one case (2.01%). High CXCR4 expression was observed in 21 nodal metastases. Node metastases in complete dissection were associated to >10% relative tumor area (RTA) in all lymph nodes (p = 0.006). Extranodal invasion (p = 0.006) and >2 mm centripetal metastasis thickness (p = 0.01), while shorter Disease Free Survival (DFS) was significantly associated to high CXCR4 expression (p = 0.02). Forty-seven positive lymph node metastases were collected and analysed for both histopathological parameters and CXCR4 expression. More than 10% RTA in SLN, extranodal invasion and centripetal metastasis thickness all predict additional lymph node metastases in melanoma site draining basins. Moreover, high CXCR4 expression is correlated to shorter DFS and could be used as a prognostic marker in order to stratify melanoma patients at higher progression risk.

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

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

PubMed

Mozzillo, Nicola; Caracò, Corrado; Marone, Ugo; Di Monta, Gianluca; Crispo, Anna; Botti, Gerardo; Montella, Maurizio; Ascierto, Paolo Antonio

2013-02-04

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. 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. 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). 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.

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

PubMed

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

2016-01-01

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

Sentinel lymph node biopsy in gastrointestinal malignancies-where do we stand?

PubMed

Maharaj, R; Shukla, P J; Naraynsingh, V; Dan, D; Hariharan, S

2011-01-01

Sentinel lymph nodes (SLNs) are the nodes in direct communication with the primary tumor and are therefore the first group of nodes to be involved in lymphatic metastasis. Though the role of SLN biopsy is well established in cancers of the breast and melanoma, its role in gastrointestinal malignancies is still evolving and controversial. In this paper, the literature is reviewed with respect to the status of SLN biopsy in gastrointestinal malignancies.

Discordance in histopathologic evaluation of melanoma sentinel lymph node biopsy with clinical follow-up: results from a prospectively collected database.

PubMed

Dandekar, Monisha; Lowe, Lori; Fullen, Douglas R; Johnson, Timothy M; Sabel, Michael S; Wong, Sandra L; Patel, Rajiv M

2014-10-01

Sentinel lymph node (SLN) status currently represents the single most important prognostic factor in clinically localized melanoma and is widely used in patients with melanoma at significant risk for nodal micrometastasis. Although several studies have looked at the rates and implications of inaccuracies in the histopathologic diagnosis of melanocytic lesions, accuracy in the histologic interpretation of the SLN in melanoma has not been addressed. The goal of this study was to determine the rates of discordance in the histopathologic evaluation of the SLN and the potential clinical impact on patients referred to a comprehensive melanoma center. A prospectively collected database was queried for melanoma patients who had SLN biopsies performed at outside institutions before referral to the University of Michigan Multidisciplinary Melanoma Program between 2006 and 2009. These cases were reviewed and clinical follow-up obtained. After internal review of the SLN material, 13 (8 %) of 167 cases had major discrepancies in diagnosis that impacted patient management and prognosis. The disease of five patients was subsequently downstaged and the disease of eight patients was upstaged after internal review of the SLNs and reversal in diagnoses. There appears to be a small yet significant rate of discordance in diagnosis of the SLN for melanoma after expert histopathologic review. The implications of this discordance and revision of diagnosis is substantial. Expert histopathologic review of the SLN warrants consideration to provide the most accurate prognostic information and optimal patient care.

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

PubMed Central

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

2016-01-01

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

Utilization of sentinel lymph node biopsy for uterine cancer.

PubMed

Wright, Jason D; Cham, Stephanie; Chen, Ling; Burke, William M; Hou, June Y; Tergas, Ana I; Desai, Vrunda; Hu, Jim C; Ananth, Cande V; Neugut, Alfred I; Hershman, Dawn L

2017-06-01

To limit the potential short and long-term morbidity of lymphadenectomy, sentinel lymph node biopsy has been proposed for endometrial cancer. The principle of sentinel lymph node biopsy relies on removal of a small number of lymph nodes that are the first drainage basins from a tumor and thus the most likely to harbor tumor cells. While the procedure may reduce morbidity, efficacy data are limited and little is known about how commonly the procedure is performed. We examined the patterns and predictors of use of sentinel lymph node biopsy and outcomes of the procedure in women with endometrial cancer who underwent hysterectomy. We used the Perspective database to identify women with uterine cancer who underwent hysterectomy from 2011 through 2015. Billing and charge codes were used to classify women as having undergone lymphadenectomy, sentinel lymph node biopsy, or no nodal assessment. Multivariable models were used to examine clinical, demographic, and hospital characteristics with use of sentinel lymph node biopsy. Length of stay and cost were compared among the different methods of nodal assessment. Among 28,362 patients, 9327 (32.9%) did not undergo nodal assessment, 17,669 (62.3%) underwent lymphadenectomy, and 1366 (4.8%) underwent sentinel lymph node biopsy. Sentinel lymph node biopsy was performed in 1.3% (95% confidence interval, 1.0-1.6%) of abdominal hysterectomies, 3.4% (95% confidence interval, 2.7-4.1%) of laparoscopic hysterectomies, and 7.5% (95% confidence interval, 7.0-8.0%) of robotic-assisted hysterectomies. In a multivariable model, more recent year of surgery was associated with performance of sentinel lymph node biopsy. Compared to abdominal hysterectomy, those undergoing laparoscopic (adjusted risk ratio, 2.45; 95% confidence interval, 1.89-3.18) and robotic-assisted (adjusted risk ratio, 2.69; 95% confidence interval, 2.19-3.30) hysterectomy were more likely to undergo sentinel lymph node biopsy. Among women who underwent minimally

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

PubMed

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

2018-05-03

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

Sentinel lymph node detection in patients with early cervical cancer.

PubMed

Acharya, B C; Jihong, L

2009-01-01

Lymph node status is the most important independent prognostic factor in early stage cervical cancer. Intraoperative lymphatic mapping and sentinel lymph node detection have been increasingly evaluated in the treatment of a variety of solid tumors, particularly breast cancer and cutaneous melanoma. This study evaluated the feasibility of these procedures in patients undergoing radical hysterectomy with pelvic lymphadenectomy for early cervical cancer. A total of 30 patients with histologically diagnosed FIGO stage IA to IIA cervical cancer were enrolled to this study. They were scheduled to undergo radical abdominal hysterectomy and pelvic lymphadenectomy after injecting patent blue dye in cervix. A total of 60 SLNs (mean 2.5) were detected in 24 patients with detection rate of 80%. Bilateral SLNs were detected in 70.1% of cases. SLNs were identified in obturator and external iliac areas in 50% and 31.7%, respectively; no SLNs were discovered in the common iliac region. Seven patients (23.3%) had lymph node metastases; one of these had false negative SLN.The false negative rate and negative predictive value were 14.3% and 94.4%, respectively. SLN detection procedure with blue dye technique is a feasible procedure in cervical cancer. Patent blue dye is cheap, safe and effective tracer to detect sentinel node in carcinoma of cervix.

Histologic pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

PubMed Central

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

2016-01-01

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 clinicopathologic 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. 3 (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. 4 (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 node (1 or 2 versus >2, p<.0001), age (<70 versus ≥70, p=.01), sentinel lymph node metastasis pattern (patterns 2–5 versus 1, p=.02), and immune status (immunocompetent versus suppressed, p=.03) were independent predictors of outcome, and could be used to stratify Stage III patients into 3 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 clinicopathologic features

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

Sentinel lymph node molecular ultrastaging in patients with melanoma: a systematic review and meta-analysis of prognosis.

PubMed

Mocellin, Simone; Hoon, Dave S B; Pilati, Pierluigi; Rossi, Carlo R; Nitti, Donato

2007-04-20

Molecular biology-based ultrastaging of cancer is already part of the standard management of patients with hematologic malignancies, whereas the evidence for solid tumors is much more debated. Polymerase chain reaction (PCR) -based detection of melanoma cells in sentinel lymph nodes (SLN) of patients with melanoma represents an appealing prognostic tool. However, no consensus exists on the clinical implementation of this prognostic indicator for the management of these patients. Twenty-two studies enrolling 4,019 patients who underwent SLN biopsy for clinical stage I to II cutaneous melanoma were reviewed. Correlation of PCR status with TNM stage, disease recurrence rates, and survival was assessed by means of association statistics and formal meta-analysis, respectively. PCR status correlated with both TNM stage (stage I to II v III; PCR positivity, 95.1% v 46.6%; P < .0001) and disease recurrence (PCR positive v negative; relapse rate, 16.8% v 8.7%; P < .0001). PCR positivity was also associated with worse overall (hazard ratio [HR], 5.08; 95% CI, 1.83 to 14.08; P = .002) and disease-free (HR, 3.41; 95% CI, 1.86 to 6.24; P < .0001) survival. Statistical heterogeneity was significant, underscoring the variability among overall effect estimates across studies; metaregression and subgroup analysis did not identify clear-cut sources of heterogeneity, although some study design variables were suggested as potential causes. PCR status of SLN appears to have a clinically valuable prognostic power in patients with melanoma. Although the heterogeneity of the studies so far published warrants caution to avoid overestimating the favorable results of pooled data, our findings strongly support additional investigation in this field.

Sentinel node biopsy status is strongly predictive of survival in cutaneous melanoma: Extended follow-up of Oxford patients from 1998 to 2014.

PubMed

Thomson, David R; Rughani, Milap G; Kuo, Rachel; Cassell, Oliver C S

2017-10-01

Sentinel lymph node biopsy (SLNB) is widely used as a key investigatory tool for cutaneous melanoma, with results incorporated into the latest AJCC staging guidelines. We present the results of our extended follow-up of sentinel lymph node biopsy for melanoma over a sixteen-year period. Data were collected prospectively from June 1998 to December 2014 from a single tertiary skin cancer referral centre. Chi-squared analysis was used to analyse patient demographics and primary tumour pathology. Survival analysis was conducted using Cox regression models and Kaplan-Meier survival curves. Over a sixteen-year period 1527 patients underwent SLNB in 1609 basins, with 2876 nodes harvested. 347 patients (23%) had a positive biopsy. The most common primary tumour sites for males was the back (32%); women had a significantly higher number of melanomas occurring on the lower and upper limbs (45% and 26% respectively) [all p < 0.0001, Chi-squared]. Mean follow-up time was 4.9 years. Patients with a positive SLNB at diagnosis were significantly more likely to die from melanoma (subhazard ratio 5.59, p = 0.000, 95% CI 3.59-8.69). Breslow thickness and ulceration were also significant predictors of melanoma-specific mortality. For patients with a primary Breslow >4.0 mm ten-year disease free survival was 52% for SLNB negative and 26% for SLNB positive patients. For Breslow thicknesses of 2.01-4 mm these values were 66% and 32% respectively. Sentinel lymph node biopsy status is strongly predictive of survival across all thicknesses of primary cutaneous melanoma. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Combination of dacarbazine and dimethylfumarate efficiently reduces melanoma lymph node metastasis.

PubMed

Valero, Teresa; Steele, Silvia; Neumüller, Karin; Bracher, Andreas; Niederleithner, Heide; Pehamberger, Hubert; Petzelbauer, Peter; Loewe, Robert

2010-04-01

Dimethylfumarate (DMF) has been shown to reduce melanoma growth and metastasis in animal models. We addressed the question of whether DMF is as effective in its antitumor activity as the US Food and Drug Administration-approved alkylating agent dacarbazine (DTIC). We also tested the possibility of an improved antitumoral effect when both therapeutics were used together. Using our severe combined immunodeficiency (SCID) mouse model, in which xenografted human melanoma cells metastasize from primary skin sites to sentinel nodes, we show that these treatments, alone or in combination, reduce tumor growth at primary sites. Our main finding was that metastasis to sentinel nodes is significantly delayed only in mice treated with a combination of DTIC and DMF. Subsequent experiments were able to show that a combination of DTIC/DMF significantly reduced lymph vessel density in primary tumors as examined by real-time PCR and immunohistochemistry. In addition, DTIC/DMF treatment significantly impaired melanoma cell migration in vitro. In vivo, DTIC/DMF therapy significantly reduced mRNA expression and protein concentration of the promigratory chemokines CXCL2 and CXCL11. In addition, our data suggest that this xenotransplantation model is suitable for preclinical testing of various combinations of antimelanoma agents.

The Utility of Sentinel Node Biopsy for Sinonasal Melanoma.

PubMed

Oldenburg, Michael S; Price, Daniel L

2017-10-01

Objective  Report two positive sentinel node biopsies for sinonasal melanoma. Design  Retrospective review. Setting  Academic tertiary care center. Participants  Patients who underwent sentinel node biopsy for sinonasal melanoma between November 1, 2014 and November 1, 2015. Main Outcome Measures  Clinical course. Results  Two patients were identified. Patient 1 (83M) presented with a sinonasal melanoma anterior to the left inferior turbinate and was clinically N0 neck. Lymphoscintigraphy revealed two sentinel nodes in the ipsilateral and three in the contralateral cervical basins. The left level I sentinel node was positive for melanoma and lymphadenectomy showed no additional metastases. Patient 2 (71F) presented after incomplete resection of a sinonasal melanoma of the left posterior maxillary sinus wall and was clinically N0 neck. Lymphoscintigraphy with single-photon emission computed tomography (SPECT/CT) localization revealed one sentinel node in the parapharyngeal space and another in the ipsilateral cervical basin. Metastatic melanoma was found in both nodes and completion lymphadenectomy was negative for additional disease. Both patients developed distant metastasis in less than 1 year after surgical resection but responded well to adjuvant immunomodulatory chemotherapeutic agents. Conclusion  Sentinel node biopsy for sinonasal melanoma can provide crucial clinical evidence of regional metastasis prior to overt clinical signs and symptoms. This intraoperative tool has the potential to improve detection of regional metastasis and improve long-term outcomes of this aggressive malignancy.

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

PubMed

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

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0

Prognostic Role of Multiple Lymphatic Basin Drainage in Sentinel Lymph Node-Negative Trunk Melanoma Patients: A Multicenter Study from the Italian Melanoma Intergroup.

PubMed

Ribero, Simone; Osella-Abate, Simona; Pasquali, Sandro; Rossi, Carlo Riccardo; Borgognoni, Lorenzo; Piazzalunga, Dario; Solari, Nicola; Schiavon, Mauro; Brandani, Paola; Ansaloni, Luca; Ponte, Erica; Silan, Francesco; Sommariva, Antonio; Bellucci, Francesco; Macripò, Giuseppe; Quaglino, Pietro

2016-05-01

Multiple lymphatic basin drainage (MLBD) is frequently observed in patients with trunk melanoma undergoing sentinel lymph node (SLN) biopsy. Conflicting data regarding the prognostic association of MLBD in SLN-negative patients have been reported. This study aimed to investigate the prognostic role of MLBD in patients with negative SLN biopsy. Retrospective data from 656 melanoma patients who underwent a SLN biopsy (1991-2012) at six Italian centers were gathered in a multicenter database. MLBD was defined as lymphoscintigraphic and intraoperative identification of an SLN in more than one nodal basin. Clinical and pathologic variables were recorded and analyzed for their impact on survival. SLN-negative patients with MLBD were at lower risk of melanoma recurrence [hazard ratio (HR) 0.73, P = 0.05) and melanoma-related death (HR 0.68, P = 0.001) independent of common staging features. Multivariable Cox analyses of disease-free interval (DFI) and disease-specific survival (DSS) showed that MLBD maintained a favorable role and ulceration an unfavorable role. Histologic regression was independently associated only with DFI. When survival was stratified according to presence of MLBD, histologic regression and Breslow thickness <2 mm were associated with improved DFI (5-year DFI: 96.9 vs. 66,1 %, respectively; HR 0.48, P < 0.001) and DSS (5-year DSS: 96.7 vs. 71.8 %, respectively; HR 0.52, P = 0.005) compared to patients without these three favorable parameters. Patients with negative SLN biopsy results have better prognosis when two or more lymphatic basins are identified and analyzed. Further research is required to investigate the mechanisms behind this evidence.

Sentinel Lymph Node Evaluation in Women with Cervical Cancer

PubMed Central

Holman, Laura L.; Levenback, Charles F.; Frumovitz, Michael

2014-01-01

Lymph node status is the most important prognosticator of survival among women with early stage cervical cancer. This means that many cervical cancer patients will undergo pelvic lymphadenectomy as part of their treatment. Unfortunately, this procedure is associated with significant morbidity. Utilizing the sentinel lymph node technique for women with cervical cancer has the potential to decrease this morbidity. Multiple studies have suggested that sentinel lymph node mapping in these patients is feasible with excellent detection rates and sensitivity. This review examines the current body of literature regarding sentinel lymph node biopsy among women with cervical cancer. PMID:24407177

Sentinel Lymph Node Biopsy in Nonmelanoma Skin Cancer Patients

PubMed Central

Matthey-Giè, Marie-Laure; Boubaker, Ariane; Letovanec, Igor; Demartines, Nicolas; Matter, Maurice

2013-01-01

The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5–28% SCC (according to risk factors), in 9–42% MCC, and in 14–57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated. PMID:23476781

Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

PubMed

Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan

2018-03-01

To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.

Sentinel lymph node detection in patients with endometrial cancer.

PubMed

Niikura, Hitoshi; Okamura, Chikako; Utsunomiya, Hiroki; Yoshinaga, Kosuke; Akahira, Junichi; Ito, Kiyoshi; Yaegashi, Nobuo

2004-02-01

The purpose of this study was to examine the feasibility of sentinel lymph node (SLN) detection in patients with endometrial cancer using preoperative lymphoscintigraphy and an intraoperative gamma probe. Between June 2001 and January 2003, 28 consecutive patients with endometrial cancer who were scheduled for total abdominal hysterectomy, bilateral salpingo-oophorectomy, total pelvic lymphadenectomy, and paraaortic lymphadenectomy at Tohoku University School of Medicine underwent sentinel lymph node detection. On the day before surgery, preoperative lymphoscintigraphy was performed by injection of 99m-Technetium ((99m)Tc)-labeled phytate into the endometrium during hysteroscopy. At the time of surgery, a gamma-detecting probe was used to locate radioactive lymph nodes. At least one sentinel node was detected in each of 23 of the 28 patients (82%). The mean number of sentinel nodes detected was 3.1 (range, 1-9). Sentinel nodes could be identified in 21 of 22 patients (95%) whose tumor did not invade more than halfway into the myometrium. Eighteen patients had radioactive nodes in the paraaortic area. Most patients had a sentinel node in one of the following three sites: paraaortic, external iliac, and obturator. The sensitivity and specificity for detecting lymph node metastases were both 100%. The combination of preoperative lymphoscintigraphy with intraoperative gamma probe detection may be useful in identifying sentinel nodes in early-stage endometrial cancer.

Quantification of Radiation Exposure of Non-Dominant Index for the Surgeon Performing Sentinel Lymph-Node Removal Procedure.

PubMed

Peştean, Claudiu; Larg, Maria Iulia; Bărbuş, Elena; Bădulescu, Claudiu; Piciu, Doina

2018-01-01

Sentinel lymph-node scintigraphy is a useful method for accurate staging of different tumors and a helpful tool in personalized therapy for oncological patients. The radiation exposure for surgical staff has been a concern since the sentinel lymph-node detection method was developed. The objective of the study was to determine and quantify the exposure to radiation of the non-dominant index for the surgeon performing sentinel lymph-node removal and to determine, if there is an irradiation risk imposed during the surgical procedure. We performed a study over a period of one year, where we evaluated the exposure of surgeon's non-dominant index during 196 sentinel lymph-node removal procedures. The pharmaceutical was administrated via subcutaneous injection in four peritumoral or perilesional injection sites. The equipment we used consisted of EuroProbe3 for sentinel lymph-node detection and ring TLD dosimeter placed on the surgeon's non-dominant index. The clinical distribution was: 104 melanomas, 84 breast carcinomas, 6 vulvar carcinomas and 2 penial carcinomas. The administered activity showed an average of 39.55 MBq (SD ± 1.96) Tc-99m nanoalbumin compound. The non-dominant index exposure ranged between 0.10 mSv and 0.13 mSv/month with a cumulative dose of 1.31 mSv/year, thus 6.69 µSv per procedure. The surgeon received a minimal dose for the non-dominant index. The values we recorded did not pose any additional concerns or restrictions, the exposure being under the limits and constraints established by regulations, close to the detectability limit of the dosimeter. The procedure is safe in terms of radiation protection, respecting the limitation and optimization principles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Progression of cutaneous melanoma: implications for treatment

PubMed Central

Leong, Stanley P. L.; Mihm, Martin C.; Murphy, George F.; Hoon, Dave S. B.; Kashani-Sabet, Mohammed; Agarwala, Sanjiv S.; Zager, Jonathan S.; Hauschild, Axel; Sondak, Vernon K.; Guild, Valerie; Kirkwood, John M.

2015-01-01

The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials. PMID:22892755

Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens.

PubMed

Lean, Cynthia L; Bourne, Roger; Thompson, John F; Scolyer, Richard A; Stretch, Jonathan; Li, Ling-Xi Lawrence; Russell, Peter; Mountford, Carolyn

2003-06-01

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.

Results of Sentinel Lymph Node Biopsy in Patients with Breast Cancer in 10-Year Own Material of the 4th Military Teaching Hospital with Polyclinic in Wrocław.

PubMed

Kabziński, Piotr; Rac, Jacek; Dorobisz, Tadeusz; Pawłowski, Wiktor; Ziomek, Agnieszka; Chabowski, Mariusz; Janczak, Dawid; Leśniak, Michał; Janczak, Dariusz

2016-05-01

At present, sentinel lymph node biopsy is a standard procedure to assess the advancement of breast cancer and cutaneous melanoma. The aim of the study was to assess the role of the sentinel lymph node biopsy in the treatment of patients with breast cancer in our own material. Analyzed was medical documentation of 258 patients with initially operable breast cancer, qualified for operation with sentinel lymph node biopsy in 2004-2014 in the Department of Surgery of the 4th Military Teaching Hospital. A few hours prior to the planned surgery, radioisotope (technitium-99 sulfur colloid) was applied in the area of tumor or under the areola. 1-2 hours after administering the tracer, the lymphoscintigraphy with the labelling of the sentinel lymph node on the skin was performed. On the basis of the gathered material, obtained were the following parameters: sensitivity - 100%, and specificity - 94.6%. Four cases were false negative (5.5%). 1. Marking the sentinel lymph node in breast cancer, based on the single visualisation method with the use of radioisotope, is a useful and effective technique. 2. The factor influencing the results of the sentinel lymph node biopsy (true positive and negative results and false negative result) was the number of the excised lymph nodes except for the sentinel lymph node. 3. Patients with estrogen receptor expression had often metastases to sentinel lymph node (145 cases - 56%). 4. The false negative rate, i.e. 5.5% in our material, is within the limits of acceptability given in the literature. 5. The sentinel lymph node biopsy performed by the experienced surgical team is a reliable diagnostic tool with a low complication rate.

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

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.

Subungual melanoma: Management in the modern era.

PubMed

Reilly, D J; Aksakal, G; Gilmour, R F; Gyorki, D E; Chauhan, A; Webb, A; Henderson, M A

2017-12-01

Subungual melanoma is a rare subtype of cutaneous melanoma that arises from the structures of the nail apparatus. It presents most commonly in older patients and at an advanced stage. A retrospective review of all patients with subungual melanoma in a single institution over a 15-year period was performed. In total, 54 patients were included (26 males, average age 62.9 years), of which 28 cases involved the upper limb. Median tumour thickness was 4.5 mm. Eighteen patients had lymph node metastasis at diagnosis, including 11 of 36 patients with positive sentinel lymph node biopsy. Median survival was 4.6 years. Subungual melanoma has a poor prognosis that is strongly associated with presence of nodal disease at diagnosis. Sentinel lymph node biopsy should be considered to determine stage and prognosis. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

PubMed

Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma.

PubMed

Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

2015-01-01

Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation.

The Value of Sentinel Lymph Node Biopsy in Oral Cavity Cancers

PubMed Central

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

2015-01-01

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

Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

PubMed

Joyce, K M; McInerney, N M; Piggott, R P; Martin, F; Jones, D M; Hussey, A J; Kerin, M J; Kelly, J L; Regan, P J

2017-11-01

Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

Factors predictive of pelvic lymph node involvement and outcomes in melanoma patients with metastatic sentinel lymph node of the groin: A multicentre study.

PubMed

Mozzillo, N; Pasquali, S; Santinami, M; Testori, A; Di Marzo, M; Crispo, A; Patuzzo, R; Verrecchia, F; Botti, G; Montella, M; Rossi, C R; Caracò, C

2015-07-01

The optimal extent of the groin lymph node (LN) dissection for melanoma patients with positive sentinel LN biopsy is still debated and no agreement exist on dissection of pelvic LN. This study aimed at investigating predictors of pelvic LN metastasis and prognostic significance of having metastasis in the pelvic LNs. Clinicopathologic data of 740 patients with positive groin sentinel LN who underwent ilioinguinal completion LN dissection at four Italian centre were analysed. Multivariable logistic and Cox regression analysis was used to identify independent predictors of pelvic LN metastasis and to adjust prognostic significance of pelvic LN metastasis. More than a quarter (26%) of patients had positive non-SLNs after inguinal and pelvic lymphadenectomy, which were located in their pelvis in the 12% of cases. Older patients [(OR) 1.69; 95% confidence interval (CI) 1.02-2.78] having thick primary (OR 1.6; 95% CI, 1.01-2.53) and ≥ 2 positive SLNs (OR 2.5; 95% CI, 1.4-4.47) were more likely to harbour pelvic LN metastasis. Interestingly, 4% of all patients (34% of patients with positive pelvic LNs) had pelvic LN metastasis with negative inguinal LNs. Pelvic LN metastasis was independently associated with higher risk of recurrence and lower survival. 5-year disease free and overall survival was 30% and 50%, respectively, for patients with pelvic LN metastasis. Pelvic LNs are frequently positive after ilioinguinal lymphadenectomy and it should be considered for all patients, especially those who are older, have thick primary and ≥ 2 positive SLN. Patients with pelvic LN metastasis have worse prognosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

PubMed

Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

2014-01-01

Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

PubMed

Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

2010-01-01

Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

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

Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.

PubMed

Koskivuo, I; Vihinen, P; Mäki, M; Talve, L; Vahlberg, T; Suominen, E

2017-03-01

Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.

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

PubMed

Nandu, Vipul V; Chaudhari, Milind S

2017-06-01

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

Sentinel lymph node biopsy in periocular merkel cell carcinoma: a case report.

PubMed

Filitis, Dan C; Paragh, Gyorgy; Samie, Faramarz H; Zeitouni, Nathalie C

2017-09-20

The National Comprehensive Cancer Network guidelines for Merkel cell carcinoma recommend performance of the sentinel lymph node biopsy in all patients with clinically negative nodal disease for staging and treatment. Nevertheless, sentinel lymph node biopsy in the periocular region is debated as tumors are typically smaller and lymphatic variability can make performance procedurally problematic. We present a case of a Caucasian patient in their seventies who presented with a 1.0 cm periocular Merkel cell carcinoma, who underwent Mohs surgery with a Tenzel flap repair, that was found to have a positive sentinel lymph node biopsy, but who, despite parotidectomy, selective neck dissection, and radiation, succumbed to the disease. Evidence in both the site-specific and non-specific literature demonstrates: (1) Worsening prognosis with extent of lymph node burden, (2) improvements in our abilities to perform lymphoscintigraphy, (3) locoregional and distant metastatic disease in patients with tumor sizes ≤1 cm, and (4) significant rates of sentinel lymph node positivity in patients with tumor sizes ≤1 cm. Our case supports that sentinel lymph node biopsy should be considered in all clinically nodal negative periocular Merkel cell carcinoma, regardless of size, and despite limited site-specific studies on the subject.

[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. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67.

PubMed

Thangarajah, Fabinshy; Malter, Wolfram; Hamacher, Stefanie; Schmidt, Matthias; Krämer, Stefan; Mallmann, Peter; Kirn, Verena

2016-12-01

Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity. We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files. Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403). In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

Dengel, Lynn T; Judy, Patricia G; Petroni, Gina R

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 sensitivitymore » 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.« less

Lymphoscintigraphy defines new lymphatic pathways from cutaneous melanoma site: clinical implications and surgical management.

PubMed

Marone, Ugo; Aloj, Luigi; Di Monta, Gianluca; Caracò, Corrado

2011-01-01

Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called "uncommon/interval" nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement.

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

PubMed

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

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

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

PubMed

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

2016-11-03

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

Histopathology report of cutaneous melanoma and sentinel lymph node in Europe: a web-based survey by the Dermatopathology Working Group of the European Society of Pathology.

PubMed

Batistatou, Anna; Cook, Martin G; Massi, Daniela

2009-05-01

In order to survey the diagnostic reporting of melanomas by European pathologists and assess their current practice and opinions on the information required in the final report, a web-based questionnaire was diffused through the members of the Dermatopathology Working Group of the European Society of Pathology. Forty replies from different pathology laboratories were collected (49%). Main prognostic parameters related to the primary tumor, including Breslow thickness, presence of ulceration, and Clark's level, as well as additional features, are reported by a large majority of laboratories. Presence of regression is reported by 90% of respondents but with different recording items. For sentinel lymph node (SLN) biopsy for melanoma, the conventional panel of antibodies includes S-100, Melan A, and HMB45. Dissection of the SLN is performed by "bivalve" or "bread loaf" approach. The number of sections cut and stained varies. Forty-four percent of respondents report depths of metastases from the capsule, while the majority report maximum dimension of the largest deposit. Results indicate that pathology reports for primary cutaneous melanoma and SLN vary between laboratories across Europe. Although the most important prognostic features are universally reported, key features which impact on prognosis and treatment are often omitted and others still require standardization.

Lymphoscintigraphy Defines New Lymphatic Pathways from Cutaneous Melanoma Site: Clinical Implications and Surgical Management

PubMed Central

Marone, Ugo; Aloj, Luigi; Di Monta, Gianluca; Caracò, Corrado

2011-01-01

Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called “uncommon/interval” nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement. PMID:22242203

Melanoma metastases in regional lymph nodes are accurately detected by proton magnetic resonance spectroscopy of fine-needle aspirate biopsy samples.

PubMed

Stretch, Jonathan R; Somorjai, Ray; Bourne, Roger; Hsiao, Edward; Scolyer, Richard A; Dolenko, Brion; Thompson, John F; Mountford, Carolyn E; Lean, Cynthia L

2005-11-01

Nonsurgical assessment of sentinel nodes (SNs) would offer advantages over surgical SN excision by reducing morbidity and costs. Proton magnetic resonance spectroscopy (MRS) of fine-needle aspirate biopsy (FNAB) specimens identifies melanoma lymph node metastases. This study was undertaken to determine the accuracy of the MRS method and thereby establish a basis for the future development of a nonsurgical technique for assessing SNs. FNAB samples were obtained from 118 biopsy specimens from 77 patients during SN biopsy and regional lymphadenectomy. The specimens were histologically evaluated and correlated with MRS data. Histopathologic analysis established that 56 specimens contained metastatic melanoma and that 62 specimens were benign. A linear discriminant analysis-based classifier was developed for benign tissues and metastases. The presence of metastatic melanoma in lymph nodes was predicted with a sensitivity of 92.9%, a specificity of 90.3%, and an accuracy of 91.5% in a primary data set. In a second data set that used FNAB samples separate from the original tissue samples, melanoma metastases were predicted with a sensitivity of 87.5%, a specificity of 90.3%, and an accuracy of 89.1%, thus supporting the reproducibility of the method. Proton MRS of FNAB samples may provide a robust and accurate diagnosis of metastatic disease in the regional lymph nodes of melanoma patients. These data indicate the potential for SN staging of melanoma without surgical biopsy and histopathological evaluation.

Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma.

PubMed

Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Puig, Susana; Robert, Caroline; Saiag, Philippe; Martín-Cuevas, Paula; Gallego, Elena; Herrera-Acosta, Enrique; Aguilera, José; Malvehy, Josep; Carrera, Cristina; Cavalcanti, Andrea; Rull, Ramón; Vilalta-Solsona, Antonio; Lannoy, Emilie; Boutros, Celine; Benannoune, Naima; Tomasic, Gorana; Aegerte, Philippe; Vidal-Sicart, Sergi; Palou, Josep; Alos, L Lúcia; Requena, Celia; Traves, Víctor; Pla, Ángel; Bolumar, Isidro; Soriano, Virtudes; Guillén, Carlos; Herrera-Ceballos, Enrique

2015-09-01

In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾ 2 mm, HR, > 3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

PubMed

van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Sentinel Lymph Node Biopsy in Breast Cancer: A Clinical Review and Update

PubMed Central

Haji, Altaf; Battoo, Azhar; Qurieshi, Mariya; Mir, Wahid; Shah, Mudasir

2017-01-01

Sentinel lymph node biopsy has become a standard staging tool in the surgical management of breast cancer. The positive impact of sentinel lymph node biopsy on postoperative negative outcomes in breast cancer patients, without compromising the oncological outcomes, is its major advantage. It has evolved over the last few decades and has proven its utility beyond early breast cancer. Its applicability and efficacy in patients with clinically positive axilla who have had a complete clinical response after neoadjuvant chemotherapy is being aggressively evaluated at present. This article discusses how sentinel lymph node biopsy has evolved and is becoming a useful tool in new clinical scenarios of breast cancer management. PMID:28970846

Sentinel Lymph Node Biopsy in Breast Cancer: A Clinical Review and Update.

PubMed

Zahoor, Sheikh; Haji, Altaf; Battoo, Azhar; Qurieshi, Mariya; Mir, Wahid; Shah, Mudasir

2017-09-01

Sentinel lymph node biopsy has become a standard staging tool in the surgical management of breast cancer. The positive impact of sentinel lymph node biopsy on postoperative negative outcomes in breast cancer patients, without compromising the oncological outcomes, is its major advantage. It has evolved over the last few decades and has proven its utility beyond early breast cancer. Its applicability and efficacy in patients with clinically positive axilla who have had a complete clinical response after neoadjuvant chemotherapy is being aggressively evaluated at present. This article discusses how sentinel lymph node biopsy has evolved and is becoming a useful tool in new clinical scenarios of breast cancer management.

[Role of sentinel lymph nodes and lymphatic mapping of colorectal cancer].

PubMed

Ivanov, K; Kolev, N; Ignatov, V; Temelkov, T; Madzhov, R

2005-01-01

The accuracy of staging of colorectal cancer is dependable of number of lymph nodes, colected and investegated from the pathologist. Moreover 50% of newfounded cases with colorectal cancer are diagnosed as I or II stage of the desease. Between 15% and 20% of these patients develop regional or distant metastases around 5 years after the examination, despite of the radical surgery. This may be due to pathological "understaging" (decrease of the stage), becouse of missed micrometastases, which size often is smaller than 5 mm. High accurate and specific pathologoanatomical methods for "ultrastaging" are cost-expensive, therefore their selective application to labeled sentinel lymph nodes has a economical benefit and saves a time. Moreover it is decreasing the understaging effect, assosiated with convectional pathologoanatomical investigaton. In the future, the technical progress will develop the intensive competiton between the sentinel lymph node mapping and the improved imaging diagnostic techniques as flurodeoxyglucose (18FDG), positron emision tomography (PET), or the other molecular imaging techniques. Unfortunately, the limited spatial resolution of these techniques, do not allow to be used for tumor staging as sentinel lymph node techniques. Therefore the sentinel lymphnode mapping become the choice of the lymphnode staging technique.

The prognostic significance of nonsentinel lymph node metastasis in melanoma.

PubMed

Brown, Russell E; Ross, Merrick I; Edwards, Michael J; Noyes, R Dirk; Reintgen, Douglas S; Hagendoorn, Lee J; Stromberg, Arnold J; Martin, Robert C G; McMasters, Kelly M; Scoggins, Charles R

2010-12-01

We hypothesized that metastasis beyond the sentinel lymph nodes (SLN) to the nonsentinel nodes (NSN) is an important predictor of survival. Analysis was performed of a prospective multi-institutional study that included patients with melanoma ≥ 1.0 mm in Breslow thickness. All patients underwent SLN biopsy; completion lymphadenectomy was performed for all SLN metastases. Disease-free survival (DFS) and overall survival (OS) were computed by Kaplan-Meier analysis; univariate and multivariate analyses were performed to identify factors associated with differences in survival among groups. A total of 2335 patients were analyzed over a median follow-up of 68 months. We compared 3 groups: SLN negative (n = 1988), SLN-only positive (n = 296), and both SLN and NSN positive (n = 51). The 5-year DFS rates were 85.5, 64.8, and 42.6% for groups 1, 2, and 3, respectively (P < 0.001). The 5-year OS rates were 85.5, 64.9, and 49.4%, respectively (P < 0.001). On univariate analysis, predictors of decreased OS included: SLN metastasis, NSN metastasis, increased total number of positive LN, increased ratio of positive LN to total LN, increased age, male gender, increased Breslow thickness, presence of ulceration, Clark level ≥ IV, and axial primary site (in all cases, P < 0.01). When the total number of positive LN and NSN status were evaluated using multivariate analysis, NSN status remained statistically significant (P < 0.01), while the total number of positive LN and LN ratio did not. NSN melanoma metastasis is an independent prognostic factor for DFS and OS, which is distinct from the number of positive lymph nodes or the lymph node ratio.

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Validation of Statistical Predictive Models Meant to Select Melanoma Patients for Sentinel Lymph Node Biopsy

PubMed Central

Sabel, Michael S.; Rice, John D.; Griffith, Kent A.; Lowe, Lori; Wong, Sandra L.; Chang, Alfred E.; Johnson, Timothy M.; Taylor, Jeremy M.G.

2013-01-01

Introduction To identify melanoma patients at sufficiently low risk of nodal metastases who could avoid SLN biopsy (SLNB). Several statistical models have been proposed based upon patient/tumor characteristics, including logistic regression, classification trees, random forests and support vector machines. We sought to validate recently published models meant to predict sentinel node status. Methods We queried our comprehensive, prospectively-collected melanoma database for consecutive melanoma patients undergoing SLNB. Prediction values were estimated based upon 4 published models, calculating the same reported metrics: negative predictive value (NPV), rate of negative predictions (RNP), and false negative rate (FNR). Results Logistic regression performed comparably with our data when considering NPV (89.4% vs. 93.6%); however the model’s specificity was not high enough to significantly reduce the rate of biopsies (SLN reduction rate of 2.9%). When applied to our data, the classification tree produced NPV and reduction in biopsies rates that were lower 87.7% vs. 94.1% and 29.8% vs. 14.3%, respectively. Two published models could not be applied to our data due to model complexity and the use of proprietary software. Conclusions Published models meant to reduce the SLNB rate among patients with melanoma either underperformed when applied to our larger dataset, or could not be validated. Differences in selection criteria and histopathologic interpretation likely resulted in underperformance. Development of statistical predictive models must be created in a clinically applicable manner to allow for both validation and ultimately clinical utility. PMID:21822550

Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.

PubMed

Kang, Young-Joon; Han, Wonshik; Park, Soojin; You, Ji Young; Yi, Ha Woo; Park, Sungmin; Nam, Sanggeun; Kim, Joo Heung; Yun, Keong Won; Kim, Hee Jeong; Ahn, Sei Hyun; Park, Seho; Lee, Jeong Eon; Lee, Eun Sook; Noh, Dong-Young; Lee, Jong Won

2017-11-01

Many breast cancer patients with positive axillary lymph nodes achieve complete node remission after neoadjuvant chemotherapy. The usefulness of sentinel lymph node biopsy in this situation is uncertain. This study evaluated the outcomes of sentinel biopsy-guided decisions in patients who had conversion of axillary nodes from clinically positive to negative following neoadjuvant chemotherapy. We reviewed the records of 1247 patients from five hospitals in Korea who had breast cancer with clinically axillary lymph node-positive status and negative conversion after neoadjuvant chemotherapy, between 2005 and 2012. Patients who underwent axillary operations with sentinel biopsy-guided decisions (Group A) were compared with patients who underwent complete axillary lymph node dissection without sentinel lymph node biopsy (Group B). Axillary node recurrence and distant recurrence-free survival were compared. There were 428 cases in Group A and 819 in Group B. Kaplan-Meier analysis showed that recurrence-free survivals were not significantly different between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%; p = 0.148). Multivariate analysis also indicated the two groups had no significant difference in axillary and distant recurrence-free survival. For breast cancer patients who had clinical conversion of axillary lymph nodes from positive to negative following neoadjuvant chemotherapy, sentinel biopsy-guided axillary surgery, and axillary lymph node dissection without sentinel lymph node biopsy had similar rates of recurrence. Thus, sentinel biopsy-guided axillary operation in breast cancer patients who have clinically axillary lymph node positive to negative conversion following neoadjuvant chemotherapy is a useful strategy.

Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients.

PubMed

Lind, Guro E; Guriby, Marianne; Ahlquist, Terje; Hussain, Israr; Jeanmougin, Marine; Søreide, Kjetil; Kørner, Hartwig; Lothe, Ragnhild A; Nordgård, Oddmund

2017-01-01

Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage ( P  = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P  = 3.0E-4; time to recurrence P  = 3.1E-4), although not significant. The same trend was observed in multivariate analyses ( P  = 1.4E-1 and P  = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse. Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

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

PubMed

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

2016-07-01

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

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

PubMed

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

2018-06-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2015-08-01

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

In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

PubMed

Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard; Eriksen, Jens Ravn; Eiholm, Susanne; Toxværd, Anders; Riis, Lene Buhl; Rosenberg, Jacob; Gögenur, Ismail

2017-07-01

Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

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

PubMed

Tani, Tohru; Sonoda, Hiromichi; Tani, Masaji

2016-03-14

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.

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

PubMed

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

2016-03-01

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

Utilization and Outcomes of Sentinel Lymph Node Biopsy for Vulvar Cancer.

PubMed

Cham, Stephanie; Chen, Ling; Burke, William M; Hou, June Y; Tergas, Ana I; Hu, Jim C; Ananth, Cande V; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

2016-10-01

To examine the use and predictors of sentinel node biopsy in women with vulvar cancer. The Perspective database, an all-payer database that collects data from more than 500 hospitals, was used to perform a retrospective cohort study of women with vulvar cancer who underwent vulvectomy and lymph node assessment from 2006 to 2015. Multivariable models were used to determine factors associated with sentinel node biopsy. Length of stay and cost were compared between women who underwent sentinel node biopsy and lymphadenectomy. Among 2,273 women, sentinel node biopsy was utilized in 618 (27.2%) and 1,655 (72.8%) underwent inguinofemoral lymphadenectomy. Performance of sentinel node biopsy increased from 17.0% (95% confidence interval [CI] 12.0-22.0%) in 2006 to 39.1% (95% CI 27.1-51.0%) in 2015. In a multivariable model, women treated more recently were more likely to have undergone sentinel node biopsy, whereas women with more comorbidities and those treated at rural hospitals were less likely to have undergone the procedure. The median length of stay was shorter for those undergoing sentinel node biopsy (median 2 days, interquartile range 1-3) compared with women who underwent inguinofemoral lymphadenectomy (median 3 days, interquartile range 2-4). The cost of sentinel node biopsy was $7,599 (interquartile range $5,739-9,922) compared with $8,095 (interquartile range $5,917-11,281) for lymphadenectomy. The use of sentinel node biopsy for vulvar cancer has more than doubled since 2006. Sentinel lymph node biopsy is associated with a shorter hospital stay and decreased cost compared with inguinofemoral lymphadenectomy.

Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer

PubMed Central

Cardoso-Coelho, Lívio Portela; Borges, Rafael Soares; Alencar, Airlane Pereira; Cardoso-Campos-Verdes, Larysse Maira; da Silva-Sampaio, João Paulo; Borges, Umbelina Soares; Gebrim, Luiz Henrique; da Silva, Benedito Borges

2017-01-01

The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology. PMID:28521436

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

Sentinel lymph node mapping in minimally invasive surgery: Role of imaging with color-segmented fluorescence (CSF).

PubMed

Lopez Labrousse, Maite I; Frumovitz, Michael; Guadalupe Patrono, M; Ramirez, Pedro T

2017-09-01

Sentinel lymph node mapping, alone or in combination with pelvic lymphadenectomy, is considered a standard approach in staging of patients with cervical or endometrial cancer [1-3]. The goal of this video is to demonstrate the use of indocyanine green (ICG) and color-segmented fluorescence when performing lymphatic mapping in patients with gynecologic malignancies. Injection of ICG is performed in two cervical sites using 1mL (0.5mL superficial and deep, respectively) at the 3 and 9 o'clock position. Sentinel lymph nodes are identified intraoperatively using the Pinpoint near-infrared imaging system (Novadaq, Ontario, CA). Color-segmented fluorescence is used to image different levels of ICG uptake demonstrating higher levels of perfusion. A color key on the side of the monitor shows the colors that coordinate with different levels of ICG uptake. Color-segmented fluorescence may help surgeons identify true sentinel nodes from fatty tissue that, although absorbing fluorescent dye, does not contain true nodal tissue. It is not intended to differentiate the primary sentinel node from secondary sentinel nodes. The key ranges from low levels of ICG uptake (gray) to the highest rate of ICG uptake (red). Bilateral sentinel lymph nodes are identified along the external iliac vessels using both standard and color-segmented fluorescence. No evidence of disease was noted after ultra-staging was performed in each of the sentinel nodes. Use of ICG in sentinel lymph node mapping allows for high bilateral detection rates. Color-segmented fluorescence may increase accuracy of sentinel lymph node identification over standard fluorescent imaging. The following are the supplementary data related to this article. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of previous breast surgery in sentinel lymph node biopsy in patients with breast cancer.

PubMed

López-Prior, V; Díaz-Expósito, R; Casáns Tormo, I

The aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection. A retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables. The overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II). Sentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

[Application of digital 3D technique combined with nanocarbon-aided navigation in endoscopic sentinel lymph node biopsy for breast cancer].

PubMed

Zhang, Pu-Sheng; Luo, Yun-Feng; Yu, Jin-Long; Fang, Chi-Hua; Shi, Fu-Jun; Deng, Jian-Wen

2016-08-20

To study the clinical value of digital 3D technique combined with nanocarbon-aided navigation in endoscopic sentinel lymph node biopsy for breast cancer. Thirty-nine female patients with stage I/II breast cancer admitted in our hospital between September 2014 and September 2015 were recruited. CT lymphography data of the patients were segmented to reconstruct digital 3D models, which were imported into FreeForm Modeling Surgical System Platform for visual simulation surgery before operation. Endoscopic sentinel lymph node biopsy and endoscopic axillary lymph node dissection were then carried out, and the accuracy and clinical value of digital 3D technique in endoscopic sentinel lymph node biopsy were analyzed. s The 3D models faithfully represented the surgical anatomy of the patients and clearly displayed the 3D relationship among the sentinel lymph nodes, axillary lymph nodes, axillary vein, pectoralis major, pectoralis minor muscle and latissimus dorsi. In the biopsy, the detection rate of sentinel lymph nodes was 100% in the patients with a coincidence rate of 87.18% (34/39), a sensitivity of 91.67% (11/12), and a false negative rate of 8.33% (1/12). Complications such as limb pain, swelling, wound infection, and subcutaneouseroma were not found in these patients 6 months after the operation. Endoscopic sentinel lymph node biopsy assisted by digital 3D technique and nanocarbon-aided navigation allows a high detection rate of sentinel lymph nodes with a high sensitivity and a low false negative rate and can serve as a new method for sentinel lymph node biopsy for breast cancer.

Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

PubMed

Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

2010-12-01

This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study.

PubMed

Rossi, Emma C; Kowalski, Lynn D; Scalici, Jennifer; Cantrell, Leigh; Schuler, Kevin; Hanna, Rabbie K; Method, Michael; Ade, Melissa; Ivanova, Anastasia; Boggess, John F

2017-03-01

Sentinel-lymph-node mapping has been advocated as an alternative staging technique for endometrial cancer. The aim of this study was to measure the sensitivity and negative predictive value of sentinel-lymph-node mapping compared with the gold standard of complete lymphadenectomy in detecting metastatic disease for endometrial cancer. In the FIRES multicentre, prospective, cohort study patients with clinical stage 1 endometrial cancer of all histologies and grades undergoing robotic staging were eligible for study inclusion. Patients received a standardised cervical injection of indocyanine green and sentinel-lymph-node mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. 18 surgeons from ten centres (tertiary academic and community non-academic) in the USA participated in the trial. Negative sentinel lymph nodes (by haematoxylin and eosin staining on sections) were ultra-staged with immunohistochemistry for cytokeratin. The primary endpoint, sensitivity of the sentinel-lymph-node-based detection of metastatic disease, was defined as the proportion of patients with node-positive disease with successful sentinel-lymph-node mapping who had metastatic disease correctly identified in the sentinel lymph node. Patients who had mapping of at least one sentinel lymph node were included in the primary analysis (per protocol). All patients who received study intervention (injection of dye), regardless of mapping result, were included as part of the assessment of mapping and in the safety analysis in an intention-to-treat manner. The trial was registered with ClinicalTrials.gov, number NCT01673022 and is completed and closed. Between Aug 1, 2012, and Oct 20, 2015, 385 patients were enrolled. Sentinel-lymph-node mapping with complete pelvic lymphadenectomy was done in 340 patients and para-aortic lymphadenectomy was done in 196 (58%) of these patients. 293 (86%) patients had successful mapping of at least one sentinel lymph node. 41 (12

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

PubMed

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R; Chagpar, Anees B; Killelea, Brigid K; Lannin, Donald R

2017-01-01

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

PubMed Central

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R.; Chagpar, Anees B.

2017-01-01

Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient. PMID:28492062

Lymphatic drainage patterns of oral maxillary tumors: Approachable locations of sentinel lymph nodes mainly at the cervical neck level.

PubMed

Boeve, Koos; Schepman, Kees-Pieter; Vegt, Bert van der; Schuuring, Ed; Roodenburg, Jan L; Brouwers, Adrienne H; Witjes, Max J

2017-03-01

There is debate if the lymphatic drainage pattern of oral maxillary cancer is to the retropharyngeal lymph nodes or to the cervical lymph nodes. Insight in drainage patterns is important for the indication for neck treatment. The purpose of this study was to identify the lymphatic drainage pattern of oral maxillary cancer via preoperative lymphoscintigraphy. Eleven consecutive patients with oral maxillary cancer treated in our center between December 1, 2012, and April 22, 2016 were studied. Sentinel lymph nodes identified by preoperative lymphoscintigraphy after injection of 99m Tc-nanocolloid and by intraoperative detection using a γ-probe, were surgically removed and histopathologically examined. In 10 patients, sentinel lymph nodes were detected and harvested at cervical levels I, II, or III in the neck. In 2 patients, a parapharyngeal sentinel lymph node was detected. One of the harvested sentinel lymph nodes (1/19) was tumor positive. This study suggests the likelihood of 73% of exclusively cervical level I to III sentinel lymph nodes in oral maxillary cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 486-491, 2017. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2008-03-01

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

Locoregional spread of cutaneous melanoma: sonography findings.

PubMed

Catalano, Orlando; Caracò, Corrado; Mozzillo, Nicola; Siani, Alfredo

2010-03-01

This article reviews various aspects of locoregional spread of malignant cutaneous melanoma, as imaged with gray-scale sonography and Doppler techniques. The scenarios illustrated include disease staging (primary melanoma, satellite metastasis, in-transit metastasis, and lymphadenopathies), sentinel lymph node biopsy procedure, patient follow-up, recurrence detection, cutaneous metastasis, and sonographically guided intervention. High-resolution sonography allows recognition of small, clinically-occult melanomatous foci. It plays a major role in locoregional staging and follow-up of patients with cutaneous melanoma.

[The related factors of head and neck mocosal melanoma with lymph node metastasis].

PubMed

Yin, G F; Guo, W; Chen, X H; Huang, Z G

2017-12-05

Objective: To investigate the related factors of mucosal melanoma of head and neck with lymph node metastasis for early diagnosis and further treatments. Method: A retrospective analysis of 117 cases of head and neck mucosal malignant melanoma patients which received surgical treatment was performed. Eleven cases of patients with pathologically confirmed lymph node metastasis and 33 cases without lymph node metastasis (1∶3) were randomly selected to analyze. The related factors of lymph node metastasis of head and neck mucosal melanoma patients including age, gender, whether the existence of recurrence, bone invasion, lesion location were analyzed. The single factor and logistic regression analysis were performed, P <0.05 difference was statistically significant. Result: The lymph node metastasis rate of head and neck mucosal melanoma was 9.40%(11/117), the single factor analysis showed that there were 3 factors to be associated with lymph node metastasis, which was recurrence ( P =0.0000), bone invasion ( P =0.001), primary position ( P =0.007). Recurrence ( P =0.021) was a risk factor for lymph node metastasis according to the Logistic regression analysis, and the impact of bone invasion ( P =0.487) and primary location ( P =0.367) remained to be further explored. Conclusion: The patients of head and neck mucosal melanoma with the presence of recurrent usually accompanied by a further progression of the disease, such as lymph node metastasis, so for recurrent patients should pay special attention to the situation of lymph node and choose the reasonable treatment. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Multifunctional Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping

DTIC Science & Technology

2012-03-01

undesired PMA attached to microbubble surface. Figure 1: One-pot polymer -lipid microbubbles. (a) Synthesis of thiolated poly(acrylic acid) with...Award Number: W81XWH-11-1-0215 TITLE: Multifunctional Polymer Microbubbles for Advanced Sentinel...February 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Multifunctional Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping 5b

The Great Debate at "Melanoma Bridge", Napoli, December 2nd, 2017.

PubMed

Ascierto, Paolo A; Caracò, Corrado; Gershenwald, Jeffrey E; Hamid, Omid; Ross, Merrick; Sullivan, Ryan J; Puzanov, Igor

2018-04-17

As part of the 2017 Melanoma Bridge congress (November 30-December 2, 2017, Napoli, Italy), the great debate session featured counterpoint views from leading experts on three contemporary controversial clinical issues in the care of the melanoma patient. These were: (1) whether complete lymph node dissection should be routinely offered to all melanoma patients with sentinel lymph node-positive disease; (2) whether first-line treatment of BRAF-mutated melanoma should consist of BRAF-targeted therapy or immunotherapy with checkpoint inhibitors; and (3) whether combined or sequential administration of treatments should be the preferred option in the management of patients with advanced melanoma. Discussion of these three important issues and audience responses are reported here.

Simplified intraoperative sentinel-node detection performed by the urologist accurately determines lymph-node stage in prostate cancer.

PubMed

Kjölhede, Henrik; Bratt, Ola; Gudjonsson, Sigurdur; Sundqvist, Pernilla; Liedberg, Fredrik

2015-04-01

The reference standard for lymph-node staging in prostate cancer is currently an extended pelvic lymph-node dissection (ePLND), which detects most, but not all, regional lymph-node metastases. As an alternative to ePLND, sentinel-node dissection with preoperative isotope injection and imaging has been reported. The objective was to determine whether intraoperative sentinel-node detection with a simplified protocol can accurately determine lymph-node stage in prostate cancer patients. Patients with biopsy-verified high-risk prostate cancer with tumour stage T2-3 were included in the study. All patients underwent both ePLND and sentinel-node detection. (99m)Tc-marked nanocolloid was injected peritumourally by the operating urologist after induction of anaesthesia just before surgery. Sentinel nodes were detected both in vivo and ex vivo intraoperatively using a gamma probe. Sentinel nodes and metastases and their locations were recorded. Sensitivity and specificity were calculated. At least one sentinel node was detected in 72 (87%) of the 83 patients. In 13 (18%) of these 72 patients sentinel nodes were detected outside the ePLND template. In six of these 13 patients, the Sentinel nodes from outside the template contained metastases, which proved to be the only metastases in two. For 12 patients the only metastatic deposit found was a micrometastasis (≤2 mm) in a sentinel node. In the 72 patients with detectable sentinel nodes, pathological analysis of the sentinel node correctly categorized 71 and ePLND 70 patients. This protocol yielded results comparable to the commonly used technique of sentinel-node detection, but with more cases of non-detection.

Automated digital volume measurement of melanoma metastases in sentinel nodes predicts disease recurrence and survival.

PubMed

Riber-Hansen, Rikke; Nyengaard, Jens R; Hamilton-Dutoit, Stephen J; Sjoegren, Pia; Steiniche, Torben

2011-09-01

Total metastatic volume (TMV) is an important prognostic factor in melanoma sentinel lymph nodes (SLNs) that avoids both the interobserver variation and unidirectional upstaging seen when using semi-quantitative size estimates. However, it is somewhat laborious for routine application. Our aim was to investigate whether digital image analysis can estimate TMV accurately in melanoma SLNs. TMV was measured in 147 SLNs from 95 patients both manually and by automated digital image analysis. The results were compared by Bland-Altman plots (numerical data) and kappa statistics (categorical data). In addition, disease-free and melanoma-specific survivals were calculated. Mean metastatic volume per patient was 10.6 mm(3) (median 0.05 mm(3); range 0.0001-621.3 mm(3)) and 9.62 mm(3) (median 0.05 mm(3); range 0.00001-564.3 mm(3)) with manual and digital measurement, respectively. The Bland-Altman plot showed an even distribution of the differences, and the kappa statistic was 0.84. In multivariate analysis, both manual and digital metastasis volume measurements were independent progression markers when corrected for primary tumour thickness [manual: hazard ratio (HR): 1.21, 95% confidence interval (CI): 1.07-1.36, P = 0.002; digital: HR: 1.21, 95% CI: 1.06-1.37, P = 0.004]. Stereology-based, automated digital metastasis volume measurement in melanoma SLNs predicts disease recurrence and survival. © 2011 Blackwell Publishing Limited.

Sentinel lymph node mapping in endometrial cancer: a systematic review and meta-analysis.

PubMed

Lin, Hefeng; Ding, Zheyuan; Kota, Vishnu Goutham; Zhang, Xiaoming; Zhou, Jianwei

2017-07-11

Endometrial cancer is the most frequent tumor in the female reproductive system, while the sentinel lymph node (SLN) mapping for diagnostic efficacy of endometrial cancer is still controversial. This meta-analysis was conducted to evaluate the diagnostic value of SLN in the assessment of lymph nodal involvement in endometrial cancer. Forty-four studies including 2,236 cases were identified. The pooled overall detection rate was 83% (95% CI: 80-86%). The pooled sensitivity was 91% (95% CI: 87-95%). The bilateral pelvic node detection rate was 56% (95% CI: 48-64%). Use of indocyanine green (ICG) increased the overall detection rate to 93% (95% CI: 89-96%) and robotic-assisted surgery also increased the overall detection rate to 86% (95% CI: 79-93%). In summary, our meta-analysis provides strong evidence that sentinel node mapping is an accurate and feasible method that performs well diagnostically for the assessment of lymph nodal involvement in endometrial cancer. Cervical injection, robot-assisted surgery, as well as using ICG, optimized the sensitivity and detection rate of the technique. Sentinel lymph mapping may potentially leading to a greater utilization by gynecologic surgeons in the future.

Fluorescence-guided mapping of sentinel lymph nodes in gynecological malignancies

NASA Astrophysics Data System (ADS)

Hirsch, Ole; Szyc, Łukasz; Muallem, Mustafa Zelal; Ignat, Iulia; Chekerov, Radoslav; Macdonald, Rainer; Sehouli, Jalid; Braicu, Ioana; Grosenick, Dirk

2017-07-01

We have successfully applied a custom-made handheld fluorescence camera for intraoperative fluorescence detection of indocyanine green in a feasibility study on sentinel lymph node mapping in patients with vulvar, cervical, endometrial and ovarian cancer.

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.

[Exclusive use of blue dye to detect sentinel lymph nodes in breast cancer].

PubMed

Bühler H, Simón; Rojas P, Hugo; Cayazzo M, Daniela; Cunill C, Eduardo; Vesperinas A, Gonzalo; Hamilton S, James

2008-08-01

The use of a dye and radiocolloid to detect sentinel lymph nodes in breast cancer increases the detection rates. However the use of either method alone does not modify the false negative rate. Therefore there is no formal contraindication for the exclusive use of dye to detect nodes. To report a prospective analysis of the exclusive blue dye technique for sentinel node biopsy in patients with early breast cancer. We analyzed the first 100 women with pathologically proven breast cancer who met the inclusion criteria. Patent blue dye was used as colorant. In the first 25 cases sentinel node was identified using radiocolloid and blue dye an then an axillary dissection performed. In the next 25 women, blue dye was used exclusively for detection and an axillary dissection was performed. In the next 50 cases, blue dye was used and only isolated sentinel node biopsy was performed. In 92 of the 100 women a sentinel node was successfully detected. In the first 50 women, the false negative rate of sentinel lymph node detection was 6.9%. No complications occurred. During follow-up, lasting three to 29 months, no axillary relapse was observed. Sentinel node biopsy in patients with early breast cancer using exclusively blue dye is feasible and safe.

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2016-04-10

To study the indications for sentinel lymph node biopsy (SLNB) in clinically-detected ductal carcinoma in situ (CD-DCIS). 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. 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%. SLNB in CD-DCIS is

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

Laparoscopic Sentinel Lymph Node Mapping with Indocyanine Green Using the iSpies Platform: Initial Experience Argentina.

PubMed

Di Guilmi, Julian; Darin, Maria Cecilia; Toscano, Maria; Maya, Gustavo

To demonstrate the initial experience in Argentina using the iSpies indocyanine green (ICG) platform in sentinel lymph node mapping in patients with early-stage cervical cancer. Step-by-step demonstration of the technique using a video and pictures (educative video) (Canadian Task Force classification III). Laparoscopic and robotic sentinel lymph node mapping using ICG has been shown to be safe and feasible; however, in developing countries, the opportunities to use fluorescent imaging through a minimally invasive approach are very limited, given the cost restrictions of acquiring the near-infrared technology and the fluorescent dyes. A 47-year-old woman presented with a stage IB1 squamous cervical cancer. Physical examination revealed a 1.5-cm tumor without evidence of parametrial involvement. Magnetic resonance imaging did not show any evidence of metastatic disease. The patient underwent laparoscopic radical hysterectomy with sentinel lymph node mapping. On laparoscopic exposure of the pelvic spaces, a cervical injection of ICG (1 mL superficial and deep) was administered using a spinal needle at the 3 o'clock and 9 o'clock positions. Sentinel lymph node mapping was then performed using the ICG (Pulsion Medical Systems, Feldkirchen, Germany) and an iSpies near-infrared camera (Karl Storz Endoskope, Tuttlingen, Germany). Bilateral sentinel lymph nodes were detected on the left external iliac artery and in the right obturator space. Both were confirmed ex vivo. The total operative time was 170 minutes. No intraoperative or postoperative complications were reported, and the patient was discharged at 48 hours after surgery. Estimated blood loss was minimal. Sentinel lymph node mapping alone is not the standard of care in our institution, and thus bilateral lymphadenectomy was performed. Ultrastaging is routinely performed when a sentinel lymph node is evaluated. Final pathology revealed a tumor confined to the cervix, with tumor-free margins, and a total of 10

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

PubMed

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

2016-08-01

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

Time to Procedure, Nuclear Imaging and Clinicopathological Characteristics as Predictive Factors for Sentinel Lymph Node Metastasis in Cutaneous Melanoma: A Single-Center Analysis.

PubMed

Jaukovic, Ljiljana; Rajović, Milica; Kandolf Sekulovic, Lidija; Radulovic, Marija; Stepic, Nenad; Mijuskovic, Zeljko; Petrov, Nenad; Ajdinovic, Boris

2018-05-14

Sentinel lymph node (SLN) biopsy is a widely accepted staging procedure for cutaneous melanoma patients who are at risk of clinically occult nodal metastases. Numerous predictive factors for regional lymph node metastases have been identified; however, few have been found to be reproducibly significant. Also, the role of blue dye in identification was questioned in recent trials. Time to procedure was also found to be predictive of SLN positivity, but this was not confirmed in other studies. In our study, predictive factors for metastatic involvement of SLN were analyzed, together with the role of addition blue dye in imaging on detection rate and false-negative SLN rate. An impact of time interval to procedure on the rate of SLN positivity was also explored. Data analysis was done in 362 cutaneous melanoma patients who underwent lymphoscintigraphy and SLN biopsy at our institution from 2010 to 2016, with a median follow-up of 29 months (1-98 months). To delineate the relation of each variable (demographical, time to procedure, and clinical and pathological variables, as well as the presence of in-transit nodes, the number of draining basins, and SLN localization on scintigraphy) with positive SLN status, we used univariate logistic regression with odds ratios representing effect size. Metastatic involvement SLN was found in 67 (18.8%) of 356 patients. Detection rate was similar with or without further intraoperative SLN identification with blue dye (98.8% vs 98.17%, P > 0.05). Time to procedure was not associated with higher SLN positivity rate (P > 0.05). In univariate analysis, Breslow thickness (P < 0.001), primary ulceration lesion (P = 0.001), and lymphovascular invasion (P = 0.006) were strongly correlated with SLN positivity, as well as the site of primary tumor (P = 0.024), tumor-infiltrating lymphocytes (TILs) (P = 0.021), and sex (P = 0.026). In multivariate analysis, Breslow thickness and TILs were found to be significant independent predictors of SLN

Ultrasound-Guided Fine-Needle Aspiration of Non-palpable and Suspicious Axillary Lymph Nodes with Subsequent Removal after Tattooing: False-Negative Results and Concordance with Sentinel Lymph Nodes.

PubMed

Kim, Won Hwa; Kim, Hye Jung; Jung, Jin Hyang; Park, Ho Yong; Lee, Jeeyeon; Kim, Wan Wook; Park, Ji Young; Cheon, Hyejin; Lee, So Mi; Cho, Seung Hyun; Shin, Kyung Min; Kim, Gab Chul

2017-11-01

Ultrasonography-guided fine-needle aspiration (US-guided FNA) for axillary lymph nodes (ALNs) is currently used with various techniques for the initial staging of breast cancer and tagging of ALNs. With the implementation of the tattooing of biopsied ALNs, the rate of false-negative results of US-guided FNA for non-palpable and suspicious ALNs and concordance with sentinel lymph nodes were determined by node-to node analyses. A total of 61 patients with breast cancer had negative results for metastasis on US-guided FNA of their non-palpable and suspicious ALNs. The biopsied ALNs were tattooed with an injection of 1-3 mL Charcotrace (Phebra, Lane Cove West, Australia) ink and removed during sentinel lymph node biopsy or axillary dissection. We determined the rate of false-negative results and concordance with the sentinel lymph nodes by a retrospective review of surgical and pathologic findings. The association of false-negative results with clinical and imaging factors was evaluated using logistic regression. Of the 61 ALNs with negative results for US-guided FNA, 13 (21%) had metastases on final pathology. In 56 of 61 ALNs (92%), tattooed ALNs corresponded to the sentinel lymph nodes. Among the 5 patients (8%) without correspondence, 1 patient (2%) had 2 metastatic ALNs of 1 tattooed node and 1 sentinel lymph node. In multivariate analysis, atypical cells on FNA results (odds ratio = 20.7, p = 0.040) was independently associated with false-negative FNA results. False-negative ALNs after US-guided FNA occur at a rate of 21% and most of the tattooed ALNs showed concordance with sentinel lymph nodes. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Use of sentinel lymph node biopsy to select patients for local–regional therapy after neoadjuvant chemotherapy

PubMed Central

Erdahl, Lillian M.; Boughey, Judy C.

2014-01-01

Use of sentinel lymph node biopsy for axillary staging of patients with breast cancer treated with neoadjuvant chemotherapy has been widely debated. Questions arise regarding the accuracy of sentinel lymph node biopsy in axillary staging for these patients and its use to determine further local–regional therapy, including surgery and radiation therapy. For patients who are clinically node-negative at presentation, sentinel lymph node biopsy enables accurate staging of the axilla after neoadjuvant chemotherapy, and determination of which patients should go on to further axillary surgery and regional nodal radiation therapy. Importantly, performing axillary staging after completion of chemotherapy, rather than before chemotherapy, enables assessment of response to chemotherapy and the extent of residual disease. This information can assist the planning of adjuvant treatment. Recent data indicate that sentinel node biopsy can also be used to assess disease response after neoadjuvant chemotherapy for patients with clinical N1 disease at presentation. PMID:24683440

In transit sentinel node drainage as a prognostic factor for patients with cutaneous melanoma.

PubMed

Brandão, Paulo H D M; Bertolli, Eduardo; Doria-Filho, Eduardo; Santos Filho, Ivan D A O; de Macedo, Mariana P; Pinto, Clovis A L; Duprat Neto, João P

2018-02-26

Minor basin or in transit node drainage can be found in patients with cutaneous melanoma who undergo sentinel node biopsy. Its clinical impact is still unclear. Our objective is to evaluate clinical outcomes in patients who presented with in transit sentinel node (ITN) drainage. Retrospective analysis of patients who underwent sentinel node biopsy (SNB) in a single Brazilian institution between 2000 and 2015. Our cohort comprised 1223 SNB. There were 64 patients (5.2%) with ITN. Melanoma of the limbs (OR 10.61, P < 0.0001) and acral subtype (OR 3.49, P < 0.0001) were associated with ITN drainage. Among these 64 patients, 14 (21.9%) had a positive SNB. The ITN was positive for metastases in five patients, four in a popliteal basin and one on the trunk. Regarding completion node dissection (CND), two patients had positive non-sentinel nodes (NSN), both in major basins. In patients who developed recurrence, time to recurrence was shorter (mean time 18 vs 31.4 months, P = 0.001) and time to death was shorter (mean time 31.6 vs 40 months, P = 0.039) in those who had ITN drainage. ITN drainage was associated with earlier recurrences and deaths from melanoma. © 2018 Wiley Periodicals, Inc.

The Lymphatic Anatomy of the Breast and its Implications for Sentinel Lymph Node Biopsy: A Human Cadaver Study

PubMed Central

Pan, Wei-Ren; Mann, G. Bruce; Taylor, G. Ian

2007-01-01

Background Current understanding of the lymphatic system of the breast is derived mainly from the work of the anatomist Sappey in the 1850s, with many observations made during the development and introduction of breast lymphatic mapping and sentinel node biopsy contributing to our knowledge. Methods Twenty four breasts in 14 fresh human cadavers (5 male, 9 female) were studied. Lymph vessels were identified with hydrogen peroxide and injected with a lead oxide mixture and radiographed. The specimens were cross sectioned and radiographed to provide three dimensional images. Lymph (collecting) vessels were traced from the periphery to the first-tier lymph node. Results Lymph collecting vessels were found evenly spaced at the periphery of the anterior upper torso draining radially into the axillary lymph nodes. As they reached the breast some passed over and some through the breast parenchyma, as revealed in the cross-section studies. The pathways showed no significant difference between male and female specimens. We found also perforating lymph vessels that coursed beside the branches of the internal mammary vessels, draining into the ipsilateral internal mammary lymphatics. In some studies one sentinel node in the axilla drained almost the entire breast. In most more than one sentinel node was represented. Conclusion These anatomical findings are discordant with our current knowledge based on previous studies and demand closer examination by clinicians. These anatomical studies may help explain the percentage of false-negative sentinel node biopsy studies and suggest the peritumoral injection site for accurate sentinel lymph node detection. PMID:18043970

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

PubMed

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

2018-04-01

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

Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study

PubMed Central

Levenback, Charles F.; Ali, Shamshad; Coleman, Robert L.; Gold, Michael A.; Fowler, Jeffrey M.; Judson, Patricia L.; Bell, Maria C.; De Geest, Koen; Spirtos, Nick M.; Potkul, Ronald K.; Leitao, Mario M.; Bakkum-Gamez, Jamie N.; Rossi, Emma C.; Lentz, Samuel S.; Burke, James J.; Van Le, Linda; Trimble, Cornelia L.

2012-01-01

Purpose To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. Patients and Methods Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. Results In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). Conclusion Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva. PMID:22753905

Surgeon Training, Protocol Compliance, and Technical Outcomes From Breast Cancer Sentinel Lymph Node Randomized Trial

PubMed Central

Ashikaga, Takamaru; Harlow, Seth P.; Skelly, Joan M.; Julian, Thomas B.; Brown, Ann M.; Weaver, Donald L.; Wolmark, Norman

2009-01-01

Background The National Surgical Adjuvant Breast and Bowel Project B-32 trial was designed to determine whether sentinel lymph node resection can achieve the same therapeutic outcomes as axillary lymph node resection but with fewer side effects and is one of the most carefully controlled and monitored randomized trials in the field of surgical oncology. We evaluated the relationship of surgeon trial preparation, protocol compliance audit, and technical outcomes. Methods Preparation for this trial included a protocol manual, a site visit with key participants, an intraoperative session with the surgeon, and prerandomization documentation of protocol compliance. Training categories included surgeons who submitted material on five prerandomization surgeries and were trained by a core trainer (category 1) or by a site trainer (category 2). An expedited group (category 3) included surgeons with extensive experience who submitted material on one prerandomization surgery. At completion of training, surgeons could accrue patients. Two hundred twenty-four surgeons enrolled 4994 patients with breast cancer and were audited for 94 specific items in the following four categories: procedural, operative note, pathology report, and data entry. The relationship of training method; protocol compliance performance audit; and the technical outcomes of the sentinel lymph node resection rate, false-negative rate, and number of sentinel lymph nodes removed was determined. All statistical tests were two-sided. Results The overall sentinel lymph node resection success rate was 96.9% (95% confidence interval [CI] = 96.4% to 97.4%), and the overall false-negative rate was 9.5% (95% CI = 7.4% to 12.0%), with no statistical differences between training methods. Overall audit outcomes were excellent in all four categories. For all three training groups combined, a statistically significant positive association was observed between surgeons’ average number of procedural errors and their false

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.

Current status of sentinel lymph node navigation surgery in breast and gastrointestinal tract.

PubMed

Tangoku, Akira; Seike, Junichi; Nakano, Kiichiro; Nagao, Taeko; Honda, Junko; Yoshida, Takahiro; Yamai, Hiromichi; Matsuoka, Hisashi; Uyama, Kou; Goto, Masakazu; Miyoshi, Takanori; Morimoto, Tadaoki

2007-02-01

Sentinel lymph node biopsy (SLNB) has been developed as a new diagnostic and therapeutic modality in melanoma and breast cancer surgery. The purpose of the SLNB include preventing the operative morbidity and improving the pathologic stage by focusing on fewer lymph nodes using immunocytochemic and molecular technology has almost achieved in breast cancer surgery. The prognostic meaning of immunocytochemically detected micrometastases is also evaluating in the SLN and bone marrow aspirates of women with early-stage breast cancer. SLNB using available techniques have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent because of an aberrant lymphatic drainage outside of the basin exist. At the moment, the available data does not justify reduced extent of lymphadenectomy, but provides strong evidence for an improvement in tumor staging on the basis of SLNB. Two large scale prospective multi-center trials concerning feasibility of gamma-probe and dye detection for gastric cancer are ongoing in Japan. Recent studies have shown favorable results for identification of SLN in esophageal cancer. CT lymphography with endoscopic mucosal injection of iopamidol was applicable for SLN navigation of superficial esophageal cancer. The aim of surgical treatment is complete resection of the tumor-infiltrated organ including the regional lymph nodes. Accurate detection of SLN can achieve a selection of a more sophisticated tailor made approach. The patient can make a individualized choice from a broader spectrum of therapeutic options including endoscopic, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissection. Ultrastaging by detecting micrometastasis at the molecular level and the choice of an adequate treatment improve the postoperative quality of life and survival. However these issues require further

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.

Accurate evaluation of axillary sentinel lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid in breast cancer: a preliminary clinical trial.

PubMed

Matsuzawa, Fumihiko; Omoto, Kiyoka; Einama, Takahiro; Abe, Hironori; Suzuki, Takashi; Hamaguchi, Jun; Kaga, Terumi; Sato, Mami; Oomura, Masako; Takata, Yumiko; Fujibe, Ayako; Takeda, Chie; Tamura, Etsuya; Taketomi, Akinobu; Kyuno, Kenichi

2015-01-01

Breast cancer is the most common type of cancer in women. The 5-year survival rate in patients with breast cancer ranges from 74 to 82 %. Sentinel lymph node biopsy has become an alternative to axillary lymph node dissection for nodal staging. We evaluated the detection of the sentinel lymph node and metastasis of the lymph node using contrast enhanced ultrasonography with Sonazoid. Between December 2013 and May 2014, 32 patients with operable breast cancer were enrolled in this study. We evaluated the detection of axillary sentinel lymph nodes and the evaluation of axillary lymph nodes metastasis using contrast enhanced computed tomography, color Doppler ultrasonography and contrast enhanced ultrasonography with Sonazoid. All the sentinel lymph nodes were identified, and the sentinel lymph nodes detected by contrast enhanced ultrasonography with Sonazoid corresponded with those detected by computed tomography lymphography and indigo carmine method. The detection of metastasis based on contrast enhanced computed tomography were sensitivity 20.0 %, specificity 88.2 %, PPV 60.0 %, NPV 55.6 %, accuracy 56.3 %. Based on color Doppler ultrasonography, the results were sensitivity 36.4 %, specificity 95.2 %, PPV 80.0 %, NPV 74.1 %, accuracy 75.0 %. Based on contrast enhanced ultrasonography with Sonazoid, the results were sensitivity 81.8 %, specificity 95.2 %, PPV 90.0 %, NPV 90.9 %, accuracy 90.6 %. The results suggested that contrast enhanced ultrasonography with Sonazoid was the most accurate among the evaluations of these modalities. In the future, we believe that our method would take the place of conventional sentinel lymph node biopsy for an axillary staging method.

Indocyanine green detects sentinel lymph nodes in early breast cancer.

PubMed

Liu, Jun; Huang, Linping; Wang, Ning; Chen, Ping

2017-04-01

Objective To explore the clinical value of indocyanine green (ICG) for the fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel lymph node biopsy (SLNB) in patients with early breast cancer. Methods This retrospective study included female patients with breast cancer. Patients were administered methylene blue and ICG using standard techniques. All SLNs that were collected during surgery were submitted for pathological examination. SLNs were defined as those that were either fluorescent, blue, fluorescent and blue or palpably suspicious. Surgical complications, axillary recurrence, distant metastasis and overall survival rates were observed postoperatively. Results A total of 60 patients were enrolled in the study. The fluorescence detection rate of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient. Pathological assessment of intraoperative frozen specimens revealed SLN metastases in 10 patients, who immediately underwent axillary lymph node dissection. No patient had axillary recurrence or distant metastases, with a survival rate of 100%. Patients who underwent SLNB showed good appearance in the axillary wound, with no limited shoulder joint abduction and upper limb oedema. Conclusion Fluorescence-guided SLNB has several advantages and is suitable for clinical application.

Mucosal melanoma: an update.

PubMed

Ballester Sánchez, R; de Unamuno Bustos, B; Navarro Mira, M; Botella Estrada, R

2015-03-01

Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Mucosal melanoma: pathogenesis, clinical behavior, and management.

PubMed

Postow, Michael A; Hamid, Omid; Carvajal, Richard D

2012-10-01

Mucosal melanoma represents a rare subtype of melanoma with distinct biological, clinical, and management considerations. Knowledge regarding optimal treatment strategies for mucosal melanoma is limited and based primarily upon small case series and single-institution, retrospective analyses. Surgery remains the standard of care for loco-regional management, but the common presence of multifocal disease and the high rate of distant recurrence should be considered before pursuing aggressive surgical interventions associated with inherent significant morbidity. The role of sentinel lymph node biopsy and lymph node dissection remains unclear. Radiotherapy has not been shown to improve overall survival but may reduce the rate of local recurrence. Significant advances in the treatment of metastatic disease have been made with novel immunotherapeutic agents, the discovery of KIT and BRAF mutations and the development of targeted agents that inhibit these oncogenic pathways.

Effects of time interval between primary melanoma excision and sentinel node biopsy on positivity rate and survival.

PubMed

Oude Ophuis, Charlotte M C; van Akkooi, Alexander C J; Rutkowski, Piotr; Voit, Christiane A; Stepniak, Joanna; Erler, Nicole S; Eggermont, Alexander M M; Wouters, Michel W J M; Grünhagen, Dirk J; Verhoef, Cornelis Kees

2016-11-01

Sentinel node biopsy (SNB) is essential for adequate melanoma staging. Most melanoma guidelines advocate to perform wide local excision and SNB as soon as possible, causing time pressure. To investigate the role of time interval between melanoma diagnosis and SNB on sentinel node (SN) positivity and survival. This is a retrospective observational study concerning a cohort of melanoma patients from four European Organization for Research and Treatment of Cancer Melanoma Group tertiary referral centres from 1997 to 2013. A total of 4124 melanoma patients underwent SNB. Patients were selected if date of diagnosis and follow-up (FU) information were available, and SNB was performed in <180 d. A total of 3546 patients were included. Multivariable logistic regression and Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to positivity rate, disease-free survival (DFS) and melanoma-specific survival (MSS). Median time interval was 43 d (interquartile range [IQR] 29-60 d), and 705 (19.9%) of 3546 patients had a positive SN. Sentinel node positivity was equal for early surgery (≤43 d) versus late surgery (>43 d): 19.7% versus 20.1% (p = 0.771). Median FU was 50 months (IQR 24-84 months). Sentinel node metastasis (hazard ratio [HR] 3.17, 95% confidence interval [95% CI] 2.53-3.97), ulceration (HR 1.99, 95% CI 1.58-2.51), Breslow thickness (HR 1.06, 95% CI 1.04-1.08), and male gender (HR 1.58, 95% CI 1.26-1.98) (all p < 0.00001) were independently associated with worse MSS and DFS; time interval was not. No effect of time interval between melanoma diagnosis and SNB on 5-year survival or SN positivity rate was found for a time interval of up to 3 months. This information can be used to counsel patients and remove strict time limits from melanoma guidelines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular analysis of breast sentinel lymph nodes.

PubMed

Blumencranz, Peter W; Pieretti, Maura; Allen, Kathleen G; Blumencranz, Lisa E

2011-07-01

Lymphatic mapping and sentinel lymph node (SLN) biopsy have become the standard of care for staging the axilla in patients with invasive breast cancer. Current histologic methods for SLN evaluation have limitations, including subjectivity, limited sensitivity, and lack of standardization. The discovery of molecular markers to detect metastases has been reported over the last 2 decades. The authors review the historical development of these markers and the clinical use of one of the molecular platforms in 478 patients at their institution. Controversies and future directions are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Futility of fluorodeoxyglucose F 18 positron emission tomography in initial evaluation of patients with T2 to T4 melanoma.

PubMed

Clark, Paige B; Soo, Victoria; Kraas, Jonathan; Shen, Perry; Levine, Edward A

2006-03-01

Evaluation of newly diagnosed patients with melanoma for metastasis is requisite to treatment planning. The reported diagnostic yield of whole-body conventional radiological imaging in initial staging of patients with melanoma is low. However, the diagnostic yield of positron emission tomography (PET) for distant metastases is unclear. There is no utility of PET as part of a routine metastatic survey in patients with T2 to T4 melanoma. Retrospective review of a cohort study between December 1998 and July 2004. University hospital tertiary care center. There were 64 patients with T2 to T4 melanomas who underwent PET for detection of occult metastases at our institution. All patients underwent surgical excision of the primary lesion and sentinel lymph node dissection. Data included were pathologic findings of the primary lesion and sentinel lymph nodes, laboratory data, and radiological reports. None of the patients had clinically suspected regional or distant metastases prior to PET. The diagnostic yield of PET was evaluated through retrospective analysis. Positive scans were then correlated for accuracy with follow-up imaging, biopsy, and clinical information when available. Positron emission tomography did not reveal occult distant metastases in any of the patients. Positron emission tomographic scans showed no abnormalities in 94% of these patients. In 2 patients (3%), false-positive findings were reported on PET (muscular activity and intranodal melanocytic nevocellular inclusion). Further, PET was not useful in predicting regional lymph node metastases. Nineteen of 64 patients had positive sentinel lymph nodes, and only 2 (11%) were identified on PET. Overall, PET did not change clinical management in any of the patients. This study suggests no utility for PET in the detection of occult metastases in patients at initial diagnosis of melanoma. Omission of PET imaging from preoperative evaluations for patients with melanoma is recommended.

[Elective lymph node dissection in malignant melanoma--status of color Doppler findings].

PubMed

Omlor, G; Dill-Müller, D; Gross, G; Kautz, G; Schüder, G; Zaun, H; Feifel, G

1996-01-01

Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 < 1 mm tumor thickness). In comparison with a historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).

Preoperative lymphoscintigraphy and tumor histologic grade are associated with surgical detection of the sentinel lymph node.

PubMed

Arias Ortega, M; Torres Sousa, M Y; González García, B; Pardo García, R; González López, A; Delgado Portela, M

2014-01-01

To study which variables involved in the process of selective sentinel node biopsy (SSNB) influence the intraoperative detection of the sentinel lymph node. This was a prospective cross-sectional study in 210 patients (mean age, 54 years) diagnosed with breast cancer who underwent SSNB. We recorded clinical, radiological, radioisotope administration, surgical, and histological data as well as follow-up data. We did a descriptive analysis of the data and an associative analysis using multivariable regression. Deep injection alone was the most common route of radioisotope administration (72.7%). Most lesions were palpable (57.1%), presented as nodules (67.1%), measured less than 2 cm in diameter (64.8%), were located in the upper outer quadrant (49.1%), were ductal carcinomas (85.7%), were accompanied by infiltration (66.2%), and had a histologic grade of differentiation of ii (44.8%). Preoperative scintigraphy detected the sentinel node in 97.6% of cases and 95.7% were detected during the operation. One axillary relapse was observed. In the associative study, the variables "preoperative lymphoscintigraphy" and "histologic grade of differentiation of the tumor" were significantly associated with the detection of the sentinel lymph node during the operation. The probability of not detecting the sentinel lymph node during the surgical intervention is higher in patients with high histologic grade tumors or in patients in whom preoperative lymphoscintigraphy failed to detect the sentinel node. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.

PubMed

Paley, Pamela J; Veljovich, Dan S; Press, Joshua Z; Isacson, Christina; Pizer, Ellen; Shah, Chirag

2016-07-01

The accuracy of sentinel lymph node mapping has been shown in endometrial cancer, but studies to date have primarily focused on cohorts at low risk for nodal involvement. In our practice, we acknowledge the lack of benefit of lymphadenectomy in the low-risk subgroup and omit lymph node removal in these patients. Thus, our aim was to evaluate the feasibility and accuracy of sentinel node mapping in women at sufficient risk for nodal metastasis warranting lymphadenectomy and in whom the potential benefit of avoiding nodal procurement could be realized. To evaluate the detection rate and accuracy of fluorescence-guided sentinel lymph node mapping in endometrial cancer patients undergoing robotic-assisted staging. One hundred twenty-three endometrial cancer patients undergoing sentinel lymph node sentinel node mapping using indocyanine green were prospectively evaluated. Two mL (1.0 mg/mL) of dye were injected into the cervical stroma divided between the 2-3 and 9-10 o'clock positions at the time of uterine manipulator placement. Before hysterectomy, the retroperitoneal spaces were developed and fluorescence imaging was used for sentinel node detection. Identified sentinel nodes were removed and submitted for touch prep intraoperatively, followed by permanent assessment with routine hematoxylin and eosin levels. Patients then underwent hysterectomy, bilateral salpingo-oophorectomy, and completion bilateral pelvic and periaortic lymphadenectomy based on intrauterine risk factors determined intraoperatively (tumor size >2 cm, >50% myometrial invasion, and grade 3 histology). Of 123 patients enrolled, at least 1 sentinel node was detected in 119 (96.7%). Ninety-nine patients (80%) had bilateral pelvic or periaortic sentinel nodes detected. A total of 85 patients met criteria warranting completion lymphadenectomy. In 14 patients (16%) periaortic lymphadenectomy was not feasible, and the mean number of pelvic nodes procured was 13 (6-22). Of the 71 patients undergoing

Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

PubMed

Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

2017-12-01

For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2003-01-01

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

A prospective single-center study of sentinel lymph node detection in cervical carcinoma: is there a place in clinical practice?

PubMed

Devaja, Omer; Mehra, Gautam; Coutts, Michael; Montalto, Stephen Attard; Donaldson, John; Kodampur, Mallikarjun; Papadopoulos, Andreas John

2012-07-01

To establish the accuracy of sentinel lymph node (SLN) detection in early cervical cancer. Sentinel lymph node detection was performed prospectively over a 6-year period in 86 women undergoing surgery for cervical carcinoma by the combined method (Tc-99m and methylene blue dye). Further ultrastaging was performed on a subgroup of 26 patients who had benign SLNs on initial routine histological examination. The SLN was detected in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in 8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women (73.3%), and the external iliac region was the most common anatomic location (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with sentinel node detection, 65 also underwent bilateral pelvic lymph node dissection, and in none of these cases was a benign SLN associated with a malignant non-SLN (100% negative predictive value). The median non-SLN count for all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had positive lymph nodes on final histology. One patient had bulky pelvic nodes on preoperative imaging and underwent removal of the negative bulky malignant lymph nodes and a benign SLN on the contralateral side. This latter case confirms the unreliability of the SLN method with bulky nodes. The remaining 8 patients had positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26 patients, which were benign on initial routine histology, underwent ultrastaging, but no further disease was identified. Four patients (5%) relapsed after a median follow-up of 28 months (range, 8-80 months). Sentinel lymph node detection is an accurate and safe method in the assessment of nodal status in early cervical carcinoma.

Lymph node biophysical remodeling is associated with melanoma lymphatic drainage

PubMed Central

Rohner, Nathan Andrew; McClain, Jacob; Tuell, Sara Lydia; Warner, Alex; Smith, Blair; Yun, Youngho; Mohan, Abhinav; Sushnitha, Manuela; Thomas, Susan Napier

2015-01-01

Tissue remodeling is a characteristic of many solid tumor malignancies including melanoma. By virtue of tumor lymphatic transport, remodeling pathways active within the local tumor microenvironment have the potential to be operational within lymph nodes (LNs) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity and viscoelasticity, as measured by the response of whole LNs to compression. These remodeling responses, which quickly manifest in tumor-draining lymph nodes (TDLNs) after tumor inoculation and before apparent metastasis, were accompanied by changes in matrix composition, including up to 3-fold increases in the abundance of soluble collagen and hyaluronic acid. Intranodal pressures were also significantly increased in TDLNs (+1 cmH2O) relative to both non-tumor-draining LNs (−1 cmH2O) and LNs from naive animals (−1 to 2 cmH2O). These data suggest that the reorganization of matrix structure, composition, and fluid microenvironment within LNs associated with tumor lymphatic drainage parallels remodeling seen in primary malignancies and has the potential to regulate the adhesion, proliferation, and signaling function of LN-resident cells involved in directing melanoma disease progression.—Rohner, N. A., McClain, J., Tuell, S. L., Warner, A., Smith, B., Yun, Y., Mohan, A., Sushnitha, M., Thomas, S. N. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage. PMID:26178165

Sentinel Lymph Node Biopsy in Early Breast Cancer.

PubMed

Kühn, Thorsten

2011-01-01

The role of axillary surgery for the treatment of primary breast cancer is in a process of constant change. During the last decade, axillary dissection with removal of at least 10 lymph nodes (ALD) was replaced by sentinel lymph node biopsy (SLNB) as a staging procedure. Since then, the indication for SLNB rapidly expanded. Today's surgical strategies aim to minimize the rate of patients with a negative axillary status who undergo ALD. For some subgroups of patients, the indication for SLNB (e.g. multicentric disease, large tumors) or its implication for treatment planning (micrometastatic involvement, neoadjuvant chemotherapy) is being discussed. Although the indication for ALD is almost entirely restricted to patients with positive axillary lymph nodes today, the therapeutic effect of completion ALD is more and more questioned. On the other hand, the diagnostic value of ALD in node-positive patients is discussed. This article reflects today's standards in axillary surgery and discusses open issues on the diagnostic and therapeutic role of SLNB and ALD in the treatment of early breast cancer.

Surgical outcomes in patients with cutaneous malignant melanoma in Europe - a systematic literature review.

PubMed

Costa Svedman, F; Spanopoulos, D; Taylor, A; Amelio, J; Hansson, J

2017-04-01

There is limited comparative evidence of the outcomes of different types of surgical management in patients with malignant melanoma in Europe. To address that gap we conducted a systematic literature review to summarize studies reporting outcomes of surgical procedures in patients with malignant melanoma in Europe. Medline was searched for European studies published in English, between 2004 and 2014 reporting surgical outcomes in adults with cutaneous malignant melanoma. We identified 23 studies that evaluated 18 332 patients treated surgically between 1979 and 2009 from 11 European countries. Most of the studies (21/23) were observational; the two remaining studies were randomized controlled trials (RCTs). Studies compared the effect of a range of surgical interventions on a range of clinical outcomes, more commonly overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Wider excisions were not associated with improved survival in patients with melanoma thickness ≥2 mm in both studies (RCTs), however, recent results based on long-term follow-up data associate 3 cm excision margins (vs. 1 cm) with favourable survival outcomes. There was some evidence that complete lymph node dissection after positive sentinel lymph node offers survival benefits over therapeutic lymph node dissection. Sentinel lymph node biopsy was not shown to be associated with significant OS benefits, however, it was overly related with higher rates of DFS/RFS. This review highlights the difficulties of making comparisons between different types of surgical procedures for malignant melanoma. As surgery remains the main treatment, this is an important field, and further evidence, particularly from RCTs, is needed. © 2016 European Academy of Dermatology and Venereology.

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.

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

PubMed

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

2015-04-01

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

Clinicopathologic features and surgical management of primary umbilical melanoma: a case series.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Marone, Ugo; Grimaldi, Antonio Maria; Anniciello, Anna Maria; Di Marzo, Massimiliano; Simeone, Ester; Mori, Stefano

2015-04-15

Primary umbilical melanoma is an uncommon tumor that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary malignant neoplasms affecting the umbilicus require a different and more radical surgical approach compared with other melanomas. In this report, we describe a series of three patients of Caucasian ethnicity who presented with primary umbilical melanoma at the National Cancer Institute of Naples, Italy. All patients underwent wide excision of the tumor including the underlying peritoneum. No surgical complications, either immediate or delayed, were observed in any of the patients. Sentinel lymph node biopsy was negative in two cases. Two of the patients developed metastatic disease and died after systemic medical therapy. The other patient is currently in follow-up, and remains disease-free after 21 months. The umbilicus has vascular and embryological connections with the underlying peritoneum, so that early visceral involvement is more likely to occur with primary umbilical melanomas. As such, tumor resection including the underlying peritoneum is required to avoid local relapse, whilst sentinel lymph node biopsy appears to be of poor diagnostic value.

Sentinel lymph node navigation surgery for early stage gastric cancer.

PubMed

Mitsumori, Norio; Nimura, Hiroshi; Takahashi, Naoto; Kawamura, Masahiko; Aoki, Hiroaki; Shida, Atsuo; Omura, Nobuo; Yanaga, Katsuhiko

2014-05-21

We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.

Sentinel lymph node navigation surgery for early stage gastric cancer

PubMed Central

Mitsumori, Norio; Nimura, Hiroshi; Takahashi, Naoto; Kawamura, Masahiko; Aoki, Hiroaki; Shida, Atsuo; Omura, Nobuo; Yanaga, Katsuhiko

2014-01-01

We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient’s quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation. PMID:24914329

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

PubMed Central

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

2006-01-01

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

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

PubMed

Nguyen, Daniel P; Huber, Philipp M; Metzger, Tobias A; Genitsch, Vera; Schudel, Hans H; Thalmann, George N

2016-11-01

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND. Copyright © 2016. Published by Elsevier B.V.

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

PubMed

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

2014-01-01

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

[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.

Lymph node ratio predicts disease-specific survival in melanoma patients.

PubMed

Xing, Yan; Badgwell, Brian D; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2009-06-01

The objectives of this analysis were to compare various measures associated with lymph node (LN) dissection and to identify threshold values associated with disease-specific survival (DSS) outcomes in patients with melanoma. Patients with lymph node-positive melanoma who underwent therapeutic LN dissection of the neck, axilla, and inguinal region were identified from the SEER database (1988-2005). We performed Cox multivariate analyses to determine the impact of the total number of LNs removed, number of negative LNs removed, and LN ratio on DSS. Multivariate cut-point analyses were conducted for each anatomic region to identify the threshold values associated with the largest improvement in DSS. The LN ratio was significantly associated with DSS for all LN regions. The LN ratio thresholds resulting in the greatest difference in 5-year DSS were .07, .13, and .18 for neck, axillary, and inguinal regions, respectively, corresponding to 15, 8, and 6 LNs removed per positive lymph node. After adjustment for other clinicopathologic factors, the hazard ratios (HRs) were .53 (95% confidence interval [CI], .40 to .71) in the neck, .52 (95% CI, .42 to .65) in the axillary, and .47 (95% CI, .36 to .61) in the inguinal regions for patients who met the LN ratio threshold. Among the prognostic factors examined, LN ratio was the best indicator of the extent of LN dissection, regardless of anatomic nodal region. These data provide evidence-based guidelines for defining adequate LN dissections in melanoma patients. (c) 2009 American Cancer Society.

Selective sentinel lymph node biopsy in male breast cancer.

PubMed

Martin-Marcuartu, J J; Alvarez-Perez, R M; Sousa Vaquero, J M; Jimenez-Hoyuela García, J M

To evaluate the reproducibility of the sentinel lymph node (SLN) technique in male breast cancer. We retrospectively analysed 21 male patients diagnosed with breast cancer in our hospital from 2008 to 2016 with, at least, 18 months follow-up. Fifteen patients underwent selective sentinel lymph node biopsy (SLNB) following the usual protocols with peritumoral injection of 18.5-111MBq of 99m Tc-nanocoloides and acquisition of planar images 2hours after the injection. In 2 cases it was necessary to perform a SPECT/CT to locate the SLN. Immunohistochemistry and molecular techniques (OSNA) were used for their analysis. Six patients did not undergo SLNB because they had pathological nodes or distant disease at the time of diagnosis. SLNB was performed in 15 patients. The SLN was negative in 6 patients and positive in the remaining 9. Three patients with positive SLNB did not need axillary lymphadenectomy because of the low number of copies by molecular analysis OSNA. Axillary lymphadenectomy was performed in the remaining 6 patients with the result of 4 positive axillary lymphadenectomies and 2 that did not show further extension of the disease. According to our experience, SLNB in males is a reproducible, useful, safe and reliable technique which avoids unnecessary axillary lymphadenectomy and prevents the appearance of undesirable effects. Copyright © 2017. Publicado por Elsevier España, S.L.U.

In vivo photoacoustic and ultrasonic mapping of rat sentinel lymph nodes with a modified commercial ultrasound imaging system

NASA Astrophysics Data System (ADS)

Erpelding, Todd N.; Kim, Chulhong; Pramanik, Manojit; Guo, Zijian; Dean, John; Jankovic, Ladislav; Maslov, Konstantin; Wang, Lihong V.

2010-02-01

Sentinel lymph node biopsy (SLNB) has become the standard method for axillary staging in breast cancer patients, relying on invasive identification of sentinel lymph nodes (SLNs) following injection of blue dye and radioactive tracers. While SLNB achieves a low false negative rate (5-10%), it is an invasive procedure requiring ionizing radiation. As an alternative to SLNB, ultrasound-guided fine needle aspiration biopsy has been tested clinically. However, ultrasound alone is unable to accurately identify which lymph nodes are sentinel. Therefore, a non-ionizing and noninvasive detection method for accurate SLN mapping is needed. In this study, we successfully imaged methylene blue dye accumulation in vivo in rat axillary lymph nodes using a Phillips iU22 ultrasound imaging system adapted for photoacoustic imaging with an Nd:YAG pumped, tunable dye laser. Photoacoustic images of rat SLNs clearly identify methylene blue dye accumulation within minutes following intradermal dye injection and co-registered photoacoustic/ultrasound images illustrate lymph node position relative to surrounding anatomy. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken breast tissue on top of the rat skin surface. These results raise confidence that photoacoustic imaging can be used clinically for accurate, noninvasive SLN mapping.

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.

Improvement of the sentinel lymph node detection rate of cervical sentinel lymph node biopsy using real-time fluorescence navigation with indocyanine green in head and neck skin cancer.

PubMed

Nakamura, Yasuhiro; Fujisawa, Yasuhiro; Nakamura, Yoshiyuki; Maruyama, Hiroshi; Furuta, Jun-ichi; Kawachi, Yasuhiro; Otsuka, Fujio

2013-06-01

The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes (SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the "shine-through" phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1-4) in group A and three per basin (range, 1-5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false-negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary. © 2013 Japanese Dermatological Association.

Comparison of 2- and 4-wavelength methods for the optical detection of sentinel lymph node

NASA Astrophysics Data System (ADS)

Tellier, F.; Simon, H.; Blé, F. X.; Ravelo, R.; Chabrier, R.; Steibel, J.; Rodier, J. F.; Poulet, P.

2011-07-01

Sentinel lymph node biopsy is the gold standard method to detect a metastatic invasion from the primary breast cancer. This method can avoid patients to be submitted to full axillary chain dissection. In this study we present and compare two near-infrared optical probes for the sentinel lymph node detection, based on the recording of scattered photons. The two setups were developed to improve the detection of the dye injected in clinical routine: the Patent Blue V dye. Herein, we present results regarding clinical ex-vivo detection of sentinel lymph node after different volume injections. We have previously published results obtained with a two-wavelength probe on phantom and animal models. However this first generation device did not completely account for the optical absorption variations from biological tissue. Thus, a second generation probe has been equipped with four wavelengths. The dye concentration computation is then more robust to measurement and tissue property fluctuations. The detection threshold of the second setup was estimated at 8.10-3μmol/L, which is about 37 times lower than the eye visibility threshold. We present here the preliminary results and demonstrate the advantages of using four wavelengths compared to two on phantom suspensions simulating the optical properties of breast tissues.

Availability of tissue rinse liquid-based cytology for the rapid diagnosis of sentinel lymph node metastasis and improved bilateral detection by photodynamic eye camera.

PubMed

Kato, Hidenori; Ohba, Yoko; Yamazaki, Hiroyuki; Minobe, Shin-Ichiro; Sudo, Satoko; Todo, Yukiharu; Okamoto, Kazuhira; Yamashiro, Katsushige

2015-08-01

On sentinel lymph node navigation surgery for early invasive cervical cancers, to gain high sensitivity and specificity, the sentinel nodes should be detected bilaterally and pathological diagnosis should be sensitive to detect micrometastasis. To improve these problems, we tried tissue rinse liquid-based cytology and the photodynamic eye. From 2005 to 2013, 102 patients with Stage Ib1 uterine cervical cancer were subjected to sentinel lymph node navigation surgery with Technetium-99 m colloid and blue dye. For the recent 11 patients with whom bilateral sentinel node detection was not available, the photodynamic eye was selectively examined. The detected sentinel node was cut along the minor axis into 2 mm slices, soaked in 10 ml CytoRich red and then subjected to tissue rinse liquid-based cytology at the time of surgery. With the accumulation of 102 Ib1 patients subjected to sentinel lymph node navigation surgery, the bilateral sentinel node detection rate was 67.7%. The photodynamic eye was examined for the recent 11 patients who did not have bilateral signals. Out of the 11, 10 patients obtained bilateral signals successfully. During the period of examining the photodynamic eye, a total of 34 patients were subjected to sentinel lymph node navigation surgery. Thus, the overall bilateral detection rate increased to 97% in this subset. Two hundred and five lymph nodes were available as sentinel nodes. The sensitivity of tissue rinse liquid-based cytology was 91.7%, and the specificity was 100%. False positivity was 0% and false negativity was 8.3%. Detection failure was observed only with one micrometastasis and one case of isolated tumor cells. Combination of photodynamic eye detection and tissue rinse liquid-based cytology pathology can be a promising method for more rewarding sentinel node detection. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mitotic rate is associated with positive lymph nodes in patients with thin melanomas.

PubMed

Wheless, Lee; Isom, Chelsea A; Hooks, Mary A; Kauffmann, Rondi M

2018-05-01

The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018. Using a large nationally representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas. A total of 149,273 thin melanomas in the National Cancer Database were examined for their association of high-risk features of mitotic rate, ulceration, and Breslow depth with lymph node status. Among 17,204 patients with thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R 2  = 0.96, P < .0001, β = 3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (odds ratio, 1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean mitotic rate of 1.54 plus or minus 2.07 mitoses/mm 2 compared with 3.30 plus or minus 3.54 mitoses/mm 2 for those with positive nodes (P < .0001). The data collected do not allow for survival analyses. Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Melanoma.

PubMed

Gershenwald, J E

2001-01-01

The presentations at the American Society of Clinical Oncology 2001 meeting reported or updated the results of phase I, II, and III randomized trials and also reported important meta-analyses and retrospective studies impacting on the management of patients with melanoma. In the treatment of early stage melanoma, the prognostic significance of pathologic status of sentinel lymph nodes was affirmed. With respect to regional nodal involvement (American Joint Committee on Cancer [AJCC] stage III), investigators presented the interim results of the United Kingdom randomized low-dose interferon (IFN) trial, and up-to-date meta-analyses of several IFN trials including a pooled analysis of the Eastern Cooperative Oncology Group trials evaluating interferon in the adjuvant setting. In the advanced disease setting (AJCC stage IV), several studies elucidated the pros and cons of biochemotherapy in patients with metastatic melanoma, with an emphasis on seeking to improve response in the central nervous system and durability of response in general. Thought provoking was new data regarding the potential for lovastatin to act as a chemopreventive agent for melanoma. Translational studies were presented, one supporting the importance of HLA-typing in developing targeted vaccine therapy. Finally, the results of a novel experimental melanoma vaccine were presented using autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96).

Changing presentation of cutaneous malignant melanoma.

PubMed

Klit, Anders; Lassen, Cecilie Brandt; Olsen, Caroline Holkmann; Lock-Andersen, Jørgen

2015-10-01

The incidence of cutaneous malignant melanoma is rapidly increasing in Denmark like in other Northern and Western European countries. Our objective was to investigate the characteristics of current patients suffering from cutaneous malignant melanoma. We evaluated patient and tumour characteristics in a cross-sectional study based on data from the Danish Melanoma Register. We included all patients diagnosed with cutaneous malignant melanoma in Healthcare Region Zealand in 2012 and 2013. We identified 520 patients with invasive cutaneous malignant melanoma. More females than males suffered from cutaneous malignant melanoma. Furthermore, females were younger than males, and the anatomical distribution of malignant melanoma varied between the genders. Outcome of sentinel lymph node biopsy was associated with tumour thickness. When comparing findings in our study with earlier Danish studies, we see a trend towards an increase in age at diagnosis. Furthermore, tumour thickness is decreasing and the topical distribution of cutaneous malignant melanoma in females changes towards a male pattern. none. The study has been approved by the Danish National Data Protection Agency.

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

PubMed

Mahmood, Muhammad N; Lee, Min W; Linden, Michael D; Nathanson, S D; Hornyak, Thomas J; Zarbo, Richard J

2002-12-01

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.

PubMed

Abdul-Razak, Muzib; Chung, Hsiang; Wong, Eva; Palme, Carsten; Veness, Michael; Farlow, David; Coleman, Hedley; Morgan, Gary

2017-01-01

Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting. We performed a prospective cohort study consisting of 30 consecutive patients with cT 1 - 2 N 0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III). A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template. SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions. © 2016 Royal Australasian College of Surgeons.

Lymphatic mapping and sentinel node identification in squamous cell carcinoma and melanoma of the head and neck.

PubMed

Tartaglione, G; Potenza, C; Caggiati, A; Maggiore, M; Gabrielli, F; Migliano, E; Pagan, M; Concolino, F; Ruatti, P

2002-01-01

The aim of our study was to evaluate the role of scintigraphy in lymphatic mapping and in the identification of the sentinel lymph node (SLN) in patients with head and neck cancer. Between September 1999 and February 2001 we enrolled 22 consecutive patients with cancer in the head and neck region: five squamous cell carcinomas, one Merkel cell tumor of the cheek, and 16 malignant melanomas. Lymphoscintigraphy was performed three hours before surgery after injection of 30-50 MBq of 99mTc -Nanocoll in 0.3 mL; the dose was fractionated by injecting the radiotracer at two points around the lesion. Static acquisition (anterior and/or lateral views, 512 x 512 matrix, 5 mins pre-set time) was started immediately after the injections so as to visualize the pathways of lymphatic drainage. The skin projection of the SLN was marked with ink. Intraoperative SLN detection was performed with perilesional injection of patent blue. SLNs were found with lymphoscintigraphy in all patients. Thirty-three SLNs were identified: one occipital node, three nodes at the base of the tongue, 10 superficial lateral nodes (external jugular), five submandibular nodes, five submental nodes, three mastoid nodes and six supraclavicular nodes. Biopsy was performed in 21/22 patients. In 20/22 patients the first lymph nodes were visualized in the proximal cranial regions (retroauricular, jugular and submandibular) at five minutes post injection. The SLN positivity rate was 13.6% (three patients). All patients with tumor-positive SLNs were submitted to radical dissection. Poor concordance in the detection of sentinel nodes was observed with patent blue. The flow of nanocolloid in the lymph vessels of the head is rapid. In our experience immediate scintigraphic imaging was essential to visualize the pathways of lymphatic drainage and the first SLN. Radioguided SLN biopsy is therefore recommended within three hours. Injection of patent blue is inadvisable because of the poor concordance with

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

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

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.

Eliminating Preoperative Lymphoscintigraphy in Extremity Melanomas

PubMed Central

McGregor, Andrew; Pavri, Sabrina N.; Kim, Samuel; Xu, Xiaolu

2018-01-01

Background: Preoperative lymphoscintigraphy (LSG) is an imaging procedure routinely used to identify the draining nodal basin in melanomas. At our institute, we have traditionally performed preoperative LSG followed by intraoperative LSG for logistical and evaluative reasons. We sought to determine if preoperative LSG could be safely eliminated in the treatment of extremity melanomas, which exhibit consistent and predictable lymphatic drainage patterns. Methods: We reviewed the Yale Melanoma Registry 1308012545 for cutaneous extremity melanomas treated at our institution. From this registry, we calculated the incidence of atypical lymph node drainage patterns outside the axillary and inguinal regions. Based on these data, we eliminated preoperative LSG in 21 cases (8 upper extremities and 13 lower extremities). Additionally, we calculated the potential hospital charge reduction of forgoing preoperative LSG. Results: Upper and lower extremity melanomas treated at our institution exhibited atypical lymph node drainage at a rate of 3.4% and 2.0%, respectively. The sites of atypical drainage were to the epitrochlear and popliteal regions. In all 21 cases where preoperative LSG was eliminated, we were able to correctly identify the sentinel lymph node. The potential hospital charge reduction of forgoing preoperative LSG totaled $2,393. Conclusions: Preoperative LSG can be safely eliminated in the management of upper and lower extremity melanomas. Exceptions may be considered for primary lesions of the posterior calf, ankle, and heel as well as for patients with history of prior surgery or radiation. Forgoing preoperative LSG results in a hospital charge reduction of $2,393 and provides additional benefits to the patient. Ultimately, there is potential for significant charge reduction if applied across health care systems. PMID:29707448

Multifunctional Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping

DTIC Science & Technology

2012-06-01

of thiolated poly(acrylic acid) with fluorescein attached. (b) Bright field image of large bubbles stabilized by polymer and phospholipid...Page 1 of 6 AD_________________ Award Number: W81XWH-11-1-0215 TITLE:   Multifunctional Polymer Microbubbles for Advanced... Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping 5b. GRANT NUMBER W81XWH-11-1-0215   5c. PROGRAM ELEMENT NUMBER 6

Previous conization on patient eligibility of sentinel lymph node detection for early invasive cervical cancer.

PubMed

Kato, Hidenori; Todo, Yukiharu; Minobe, Shin-Ichiro; Suzuki, Yoshihiro; Nakatani, Makiko; Ohba, Yoko; Yamashiro, Katsusige; Okamoto, Kazuhira

2011-11-01

Sentinel lymph node (SLN) detection has been accepted as a common strategy to preserve the quality of life of the patients with gynecologic cancers. However, the feasibility of SLN detection after conization is not yet clarified. Accuracy of SLN after conization was evaluated. Eighteen cases with prior conization (cone group) and 32 cases without conization (noncone group), all of which belonged to IB1 except 1 case in IA stage, underwent SLN detection. Systemic pelvic and para-aortic lymphadenectomy was coincidently performed for the estimation of negative and positive predictive values. Detection rate in which at least unilateral nodes were identified or bilaterally identified was 100% and 72.2% in the cone group, 90.6% and 71.9% in the noncone group, respectively. The average number of the detected SLN was 2.4 in the cone group and 2.1 in the noncone group. Negative and positive predictive value was 100% in both groups. On the distribution of sentinel node stations, most of the detected nodes were internal iliac and obturator node in both groups. Less frequent detection was observed in superficial common iliac node (5.4% in the cone group, 3.1% in the noncone group), external iliac node (2.7% and 9.5%), and parauterine artery node (5.4% and 1.6%).In both groups, no other lymph nodes were identified as SLN except 1 case in the cone group with the node in cardinal ligament. No significant difference was observed on detection rate, predictive value, and the distribution of sentinel node between the cone and noncone groups. Sentinel lymph node detection after conization can be performed with a certain reliability.

Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.

PubMed

Wang, Xuejuan; Yang, Zhi; Lin, Baohe; Zhang, Yan; Zhai, Shizhen; Zhao, Qichao; Xie, Qing; Liu, Fei; Han, Xuedi; Li, Jinfeng; Ouyang, Tao

2016-06-21

We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.

A prediction tool incorporating the biomarker S-100B for patient selection for completion lymph node dissection in stage III melanoma.

PubMed

Damude, S; Wevers, K P; Murali, R; Kruijff, S; Hoekstra, H J; Bastiaannet, E

2017-09-01

Completion lymph node dissection (CLND) in sentinel node (SN)-positive melanoma patients is accompanied with morbidity, while about 80% yield no additional metastases in non-sentinel nodes (NSNs). A prediction tool for NSN involvement could be of assistance in patient selection for CLND. This study investigated which parameters predict NSN-positivity, and whether the biomarker S-100B improves the accuracy of a prediction model. Recorded clinicopathologic factors were tested for their association with NSN-positivity in 110 SN-positive patients who underwent CLND. A prediction model was developed with multivariable logistic regression, incorporating all predictive factors. Five models were compared for their predictive power by calculating the Area Under the Curve (AUC). A weighted risk score, 'S-100B Non-Sentinel Node Risk Score' (SN-SNORS), was derived for the model with the highest AUC. Besides, a nomogram was developed as visual representation. NSN-positivity was present in 24 (21.8%) patients. Sex, ulceration, number of harvested SNs, number of positive SNs, and S-100B value were independently associated with NSN-positivity. The AUC for the model including all these factors was 0.78 (95%CI 0.69-0.88). SN-SNORS was the sum of scores for the five parameters. Scores of ≤9.5, 10-11.5, and ≥12 were associated with low (0%), intermediate (21.0%) and high (43.2%) risk of NSN involvement. A prediction tool based on five parameters, including the biomarker S-100B, showed accurate risk stratification for NSN-involvement in SN-positive melanoma patients. If validated in future studies, this tool could help to identify patients with low risk for NSN-involvement. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

[Selective biopsy of the sentinel lymph node in patients with breast cancer and previous excisional biopsy: is there a change in the reliability of the technique according to time from surgery?].

PubMed

Sabaté-Llobera, A; Notta, P C; Benítez-Segura, A; López-Ojeda, A; Pernas-Simon, S; Boya-Román, M P; Bajén, M T

2015-01-01

To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection were 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24-75). Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

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

PubMed

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

2014-09-01

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

Sentinel Lymph Node Biopsy in Uterine Cervical Cancer Patients: Ready for Clinical Use? A Review of the Literature

PubMed Central

Palla, Viktoria-Varvara; Karaolanis, Georgios; Moris, Demetrios; Antsaklis, Aristides

2014-01-01

Sentinel lymph node biopsy has been widely studied in a number of cancer types. As far as cervical cancer is concerned, this technique has already been used, revealing both positive results and several issues to be solved. The debate on the role of sentinel lymph node biopsy in cervical cancer is still open although most of the studies have already revealed its superiority over complete lymphadenectomy and the best handling possible of the emerging practical problems. Further research should be made in order to standardize this method and include it in the clinical routine. PMID:24527233

Breast cancer lymphoscintigraphy: Factors associated with sentinel lymph node non visualization.

PubMed

Vaz, S C; Silva, Â; Sousa, R; Ferreira, T C; Esteves, S; Carvalho, I P; Ratão, P; Daniel, A; Salgado, L

2015-01-01

To evaluate factors associated with non identification of the sentinel lymph node (SLN) in lymphoscintigraphy of breast cancer patients and analyze the relationship with SLN metastases. A single-center, cross-sectional and retrospective study was performed. Forty patients with lymphoscintigraphy without sentinel lymph node identification (negative lymphoscintigraphy - NL) were enrolled. The control group included 184 patients with SLN identification (positive lymphoscintigraphy - PL). Evaluated factors were age, body mass index (BMI), tumor size, histology, localization, preoperative breast lesion hookwire (harpoon) marking and SLN metastases. The statistical analysis was performed with uni- and multivariate logistic regression models and matched-pairs analysis. Age (p=0.036) or having BMI (p=0.047) were the only factors significantly associated with NL. Being ≥60 years with a BMI ≥30 increased the odds of having a NL 2 and 3.8 times, respectively. Marking with hookwire seems to increase the likelihood of NL, but demonstrated statistical significance is lacking (p=0.087). The other tested variables did not affect the examination result. When controlling for age, BMI and marking with the harpoon, a significant association between lymph node metastization and NL was not found (p=0.565). The most important factors related with non identification of SLN in the patients were age, BMI and marking with hook wire. However, only the first two had statistical importance. When these variables were controlled, no association was found between NL and axillary metastases. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

PubMed

Eggermont, Alexander M M; Dummer, Reinhard

2017-11-01

The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinicopathologic features and survival in Spitzoid malignant melanoma and conventional malignant melanoma.

PubMed

Semkova, Kristina; Lott, Jason P; Lazova, Rossitza

2014-09-01

Although recent advances in genetics have revealed distinct mutational profiles and molecular signaling pathways associated with Spitzoid malignant melanoma (SMM), less is known about the clinicopathologic characteristics and behavior of SMM compared with conventional melanoma. We sought to determine the clinicopathologic characteristics and mortality risk associated with SMM and conventional malignant melanoma. We conducted a retrospective study of 30 patients with SMM and 30 patients with conventional melanoma. The two groups were matched by age, gender, and depth of tumor invasion. Additional patient- and tumor-level characteristics were compared between groups and regression modeling was used to assess relative mortality risk. Unadjusted analyses of SMM and conventional malignant melanoma revealed no significant differences in clinical impression, anatomic location, mitotic rate, and presence of ulceration. Sentinel lymph node biopsy, completion lymphadenectomy, and visceral metastases did not differ between groups. Cox proportional hazards regression showed no differences in mortality between Spitzoid and conventional melanoma. Small sample size, short follow-up duration, and residual confounding may limit the accuracy and generalizability of our results. SMM and conventional malignant melanoma differ in some clinicopathologic features. We did not find a statistically significant difference in mortality between the two. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Evaluation of Sentinel Lymph Node Dose Distribution in 3D Conformal Radiotherapy Techniques in 67 pN0 Breast Cancer Patients.

PubMed

Witucki, Gerlo; Degregorio, Nikolaus; Rempen, Andreas; Schwentner, Lukas; Bottke, Dirk; Janni, Wolfgang; Ebner, Florian

2015-01-01

Introduction. The anatomic position of the sentinel lymph node is variable. The purpose of the following study was to assess the dose distribution delivered to the surgically marked sentinel lymph node site by 3D conformal radio therapy technique. Material and Method. We retrospectively analysed 70 radiotherapy (RT) treatment plans of consecutive primary breast cancer patients with a successful, disease-free, sentinel lymph node resection. Results. In our case series the SN clip volume received a mean dose of 40.7 Gy (min 28.8 Gy/max 47.6 Gy). Conclusion. By using surgical clip markers in combination with 3D CT images our data supports the pathway of tumouricidal doses in the SN bed. The target volume should be defined by surgical clip markers and 3D CT images to give accurate dose estimations.

Sentinel lymph node biopsy in atypical Spitz nevi: is it useful?

PubMed

Caracò, C; Mozzillo, N; Di Monta, G; Botti, G; Anniciello, A M; Marone, U; Di Cecilia, M L; Staibano, S; De Rosa, G

2012-10-01

The aim of this study was to evaluate the incidence of lymph node metastases in patients with atypical Spitz nevi (ASN) after sentinel lymph node biopsy (SLNB) and during follow-up, and to assess the diagnostic value of the surgical procedure. At the National Cancer Institute of Naples, Italy, 40 patients with ASN underwent SLNB between 2003 and 2011. Medical records were reviewed and all slides of the primary tumours were retrieved, rendered separately, and assessed by four experienced dermatopathologists from two different academic institutions. Each member of the review panel assessed slides separately without recourse to medical notes and blinded to each others' diagnosis. All patients were treated with wide local excision and SLN biopsy according to the standard procedure. All cases were followed up to assess outcomes. The original diagnosis of ASN was confirmed in all 40 cases. No sentinel node positivity was recorded, and no patients developed nodal involvement during a median follow-up of 46 months (range 16-103). All patients were alive and without evidence of locoregional or distant relapse at time of review. In our experience, ASN were not associated with metastatic potential. Surgical staging procedures are not justified and careful clinical surveillance is adequate. Published by Elsevier Ltd.

Sentinel lymph node mapping in gynecological oncology

PubMed Central

Du, Jiang; Li, Yaling; Wang, Qing; Batchu, Nasra; Zou, Junkai; Sun, Chao; Lv, Shulan; Song, Qing; Li, Qiling

2017-01-01

The intraoperative mapping of sentinel lymph nodes (SLNs) is part of the treatment strategy for a number of types of tumor. To retrospectively compare results from the mapping of pelvic SLNs for gynecological oncology, using distinct dyes, the present review was conducted to determine the clinical significance of SLN mapping for gynecological oncology. In addition, the present study aimed at identifying an improved choice for SLN mapping tracers in clinical application. Each dye exhibits demerits when applied in the clinical environment. The combination of radioisotopes and blue dyes was identified to exhibit the most accurate detection rate of SLN drainage of gynecological oncology. However, contrast agents were unable to identify whether a SLN is positive or negative for metastasis prior to pathologic examination; additional studies are required. PMID:29344213

Sentinel Lymph Nodes for Breast Carcinoma: An Update on Current Practice

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1-T2 disease and cN0 who undergo breast conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2mm). Gross sectioning SLNs at 2 mm intervals and microscopic examination of one H&E-stained section from each SLN block is the preferred method of pathologic evaluation of SLNs. The role and timing of SLN biopsy for patients having neoadjuvant chemotherapy is controversial and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists. PMID:26768036

Handheld magnetic probe with permanent magnet and Hall sensor for identifying sentinel lymph nodes in breast cancer patients.

PubMed

Sekino, Masaki; Kuwahata, Akihiro; Ookubo, Tetsu; Shiozawa, Mikio; Ohashi, Kaichi; Kaneko, Miki; Saito, Itsuro; Inoue, Yusuke; Ohsaki, Hiroyuki; Takei, Hiroyuki; Kusakabe, Moriaki

2018-01-19

The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet. Numerical and experimental results show that the longitudinal detection length is approximately 10 mm, for 140 μg of iron. Clinical tests were performed, for the first time, using magnetic and blue dye tracers-without radioisotopes-in breast cancer patients to demonstrate the performance of the probe. The nodes were identified through transcutaneous and ex-vivo measurements, and the iron accumulation in the nodes was quantitatively revealed. These results show that the handheld magnetic probe is useful in sentinel lymph node biopsy and that magnetic techniques are widely being accepted as future standard methods in medical institutions lacking nuclear medicine facilities.

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

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?

PubMed

Sullivan, Stephanie A; Rossi, Emma C

2017-09-18

Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment in endometrial cancer (EMCA). Unfortunately, full lymphadenectomy bears significant surgical and postoperative risks. The majority of patients with clinical stage I disease will not have metastatic disease; thus, a full lymphadenectomy only increases morbidity in this population of patients. The use of the sentinel lymph node (SLN) biopsy has emerged as an alternative to complete lymphadenectomy in EMCA. By removing the highest yield lymph nodes, the SLN biopsy has the same diagnostic ability as lymphadenectomy while minimizing morbidity. The sensitivity of sentinel lymph node identification with robotic fluorescence imaging for detecting metastatic endometrial and cervical cancer (FIRES) trial published this year is the largest prospective, multi-institution trial investigating the accuracy of the SLN biopsy for endometrial and cervical cancer. Results of this trial found an excellent sensitivity (97.2%) and false negative rate (3%) with the technique. The conclusions from the FIRES trial and those of a recent meta-analysis are that SLN biopsy has an acceptable diagnostic accuracy in detecting lymphatic metastases, and can replace lymphadenectomy for this diagnostic purpose. There remains controversy surrounding the SLN biopsy in high-risk disease and the use of adjuvant therapy in the setting of low volume disease detected with ultrastaging. Current data suggests that the technique is accurate in high-risk disease and that the increased detection of metastasis helps guide adjuvant therapy such that oncologic outcomes are likely not affected by forgoing a full lymphadenectomy. Further prospective study is needed to investigate the impact of low volume metastatic disease on oncologic outcomes and the need for adjuvant therapy in these patients.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

PubMed

van Roozendaal, L M; Vane, M L G; van Dalen, T; van der Hage, J A; Strobbe, L J A; Boersma, L J; Linn, S C; Lobbes, M B I; Poortmans, P M P; Tjan-Heijnen, V C G; Van de Vijver, K K B T; de Vries, J; Westenberg, A H; Kessels, A G H; de Wilt, J H W; Smidt, M L

2017-07-01

Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

A systematic review on external ear melanoma.

PubMed

Toia, Francesca; Garbo, Giuseppe; Tripoli, Massimiliano; Rinaldi, Gaetana; Moschella, Francesco; Cordova, Adriana

2015-07-01

External ear melanoma accounts for only 1% of all cutaneous melanomas, and data on its optimal management and prognosis are limited. We aim to review the literature on external ear melanoma to guide surgeons in the treatment of this uncommon and peculiar pathology. A systematic review of English language studies on ear melanoma published from 1993 to 2013 was performed using the PubMed electronic database. Data on epidemiology, oncological treatment (tumor resection and regional lymph nodes management), and reconstruction were extrapolated from selected papers. The total number of patients was 858 (30 studies). The helix was the most common location (57%); superficial spreading melanoma was the most common histopathological subtype (41%). The mean Breslow thickness was 2.01 mm, with 88% of stage I-II patients. Sentinel lymph node biopsy was performed in 45% of patients, with 8% of positive nodes. Available data on its prognosis are fragmentary and contrasting, but the Breslow thickness appears to be the main prognostic factor. There is a tendency towards reduced resection margins and preservation of the underlying perichondrium and cartilage. Local flaps are the most popular reconstructive option. To the best of our knowledge, this systematic review presents the largest data series on external ear melanoma. There is no general agreement on its surgical management, but a favorable prognosis seems to justify the tendency towards conservative treatments. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Nonsentinel lymph node status in patients with cutaneous melanoma: results from a multi-institution prognostic study.

PubMed

Pasquali, Sandro; Mocellin, Simone; Mozzillo, Nicola; Maurichi, Andrea; Quaglino, Pietro; Borgognoni, Lorenzo; Solari, Nicola; Piazzalunga, Dario; Mascheroni, Luigi; Giudice, Giuseppe; Patuzzo, Roberto; Caracò, Corrado; Ribero, Simone; Marone, Ugo; Santinami, Mario; Rossi, Carlo Riccardo

2014-03-20

We investigated whether the nonsentinel lymph node (NSLN) status in patients with melanoma improves the prognostic accuracy of common staging features; then we formulated a proposal for including the NSLN status in the current melanoma staging system. We retrospectively collected the clinicopathologic data of 1,538 patients with positive SLN status who underwent completion lymph node dissection (CLND) at nine Italian centers. Multivariable Cox regression survival analysis was used to identify independent prognostic factors. Literature meta-analysis was used to summarize the available evidence on the prognostic value of the NSLN status in patients with positive SLN. NSLN metastasis was observed in 353 patients (23%). After a median follow-up of 45 months, NSLN status was an independent prognostic factor for melanoma-specific survival (hazard ratio [HR] = 1.34; 95% CI, 1.18 to 1.52; P < .001). NSLN status efficiently stratified the prognosis of patients with two to three positive lymph nodes (n = 387; HR = 1.39; 95% CI, 1.07 to 1.81; P = .013), independently of other staging features. Searching the literature, this patient subgroup was investigated in other two studies. Pooling the results (n = 620 patients; 284 NSLN negative and 336 NSLN positive), we found that NSLN status is a highly significant prognostic factor (summary HR = 1.59; 95% CI, 1.27 to 1.98; P < .001) in patients with two to three positive lymph nodes. These findings support the independent prognostic value of the NSLN status in patients with two to three positive lymph nodes, suggesting that this information should be considered for the routine staging in patients with melanoma.

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

PubMed Central

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

2011-01-01

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

Sentinel lymph node biopsy as a prognostic factor in non-metastatic colon cancer: a prospective study.

PubMed

Estrada, O; Pulido, L; Admella, C; Hidalgo, L-A; Clavé, P; Suñol, X

2017-04-01

Around a third of node-negative patients with colon cancer experience a recurrence after surgery, suggesting poor staging. Sentinel lymph node techniques combined with immunochemistry could improve colon cancer staging. We prospectively assessed the effect of Sentinel node mapping on staging and survival in patients with non-metastatic colon cancer. An observational and prospective study was designed. 105 patients with colon cancer were selected. Patients were classified according to node involvement as: N1, with node invasion detected by the conventional techniques; up-staged, with node invasion detected only by sentinel node mapping; and N0, with negative lymph node involvement by both techniques. Five-year survival and disease-free survival rates were analysed. Multivariate regression analyses were performed to identify prognostic factors for disease-free and overall survival. Sentinel node mapping was successfully applied in 78 patients: 33 % were N1; 24.5 % were up-staged (18 patients with isolated tumour cells and 1 patient with micrometastases); and 42.5 % were N0. N1 patients had the poorest overall 5-year survival (65.4 %) and 5-year disease-free survival (69.2 %) rates compared with the other two groups. No significant 5-year survival differences were observed between N0 patients (87.9 %) and up-staged patients (84.2 %). Patients up-staged after sentinel node mapping do not have a poorer prognosis than patients without node involvement. Detection of isolated cancer cells was not a poor prognosis factor in these patients.

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol☆

PubMed Central

Wallace, Anne M.; Hoh, Carl K.; Limmer, Karl K.; Darrah, Denise D.; Schulteis, Gery; Vera, David R.

2014-01-01

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [99mTc]sulfur colloid (TcSC) using a “2-day” protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of 99mTc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18±1.09 h compared to 57.4±92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5±1.7%) and TcSC (3.5±3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [99mTc]sulfur colloid and persistent SLN accumulation for at least 24 h. PMID:19647175

Contrast-enhanced ultrasound mapping of sentinel lymph nodes in oral tongue cancer-a pilot study.

PubMed

Gvetadze, Shalva R; Xiong, Ping; Lv, Mingming; Li, Jun; Hu, Jingzhou; Ilkaev, Konstantin D; Yang, Xin; Sun, Jian

2017-03-01

To assess the usefulness of contrast-enhanced ultrasound (CEUS) with peritumoral injection of microbubble contrast agent for detecting the sentinel lymph nodes for oral tongue carcinoma. The study was carried out on 12 patients with T1-2cN0 oral tongue cancer. A radical resection of the primary disease was planned; a modified radical supraomohyoid neck dissection was reserved for patients with larger lesions (T2, n = 8). The treatment plan and execution were not influenced by sentinel node mapping outcome. The Sonovue ™ contrast agent (Bracco Imaging, Milan, Italy) was utilized. After detection, the position and radiologic features of the sentinel nodes were recorded. The identification rate of the sentinel nodes was 91.7%; one patient failed to demonstrate any enhanced areas. A total of 15 sentinel nodes were found in the rest of the 11 cases, with a mean of 1.4 nodes for each patient. The sentinel nodes were localized in: Level IA-1 (6.7%) node; Level IB-11 (73.3%) nodes; Level IIA-3 (20.0%) nodes. No contrast-related adverse effects were observed. For oral tongue tumours, CEUS is a feasible and potentially widely available approach of sentinel node mapping. Further clinical research is required to establish the position of CEUS detection of the sentinel nodes in oral cavity cancers.

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.

An Ultralow-Dose 1-Day Protocol With Activities Lower Than 20 MBq for the Detection of Sentinel Lymph Nodes in Breast Cancer-Experiences After 150 Cases.

PubMed

Kolberg, Hans-Christian; Afsah, Shabnam; Kuehn, Thorsten; Winzer, Ute; Akpolat-Basci, Leyla; Stephanou, Miltiades; Wetzig, Sarah; Hoffmann, Oliver; Liedtke, Cornelia

2017-01-01

Common protocols for the detection of sentinel lymph nodes in early breast cancer often include the injection of the tracer 1 day before surgery. In order to detect enough activity on the day of surgery, the applied activity in many protocols is as high as several hundred MBq. So far, very few protocols with an activity below 20 MBq have been reported. We developed an ultralow-dose 1-day protocol with a mean activity lower than 20 MBq in order to reduce radiation exposure for patients and staff. Here, we are presenting our experiences in 150 consecutive cases. A total of 150 patients with clinically and sonographically negative axilla and no multicentricity underwent a sentinel lymph node biopsy using an ultralow-dose protocol performed on the day of surgery. No patient received systemic therapy prior to sentinel node biopsy. After peritumoral injection of the tracer Technetium-99m, a lymphoscintigraphy was performed in all cases. Seven minutes before the first cut, we injected 5 mL of blue dye in the region of the areola. In 148 (98.7%) of 150 patients, at least 1 sentinel lymph node could be identified by lymphoscintigraphy; the detection rate during surgery with combined tracers Technetium-99m and blue dye was 100%. The mean applied activity was 17.8 MBq (9-20). A mean number of 1.3 (0-5) sentinel lymph nodes were identified by lymphoscintigraphy and a mean number of 1.8 (1-5) sentinel lymph nodes were removed during sentinel lymph node biopsy. Ultralow-dose 1-day protocols with an activity lower than 20 MBq are a safe alternative to 1-day or 2-day protocols with significantly higher radiation doses in primary surgery for early breast cancer. Using Technetium-99m and blue dye in a dual tracer approach, detection rates of 100% are possible in clinical routine in order to reduce radiation exposure for patients and staff.

PREOPERATIVE MRI IMPROVES PREDICTION OF EXTENSIVE OCCULT AXILLARY LYMPH NODE METASTASES IN BREAST CANCER PATIENTS WITH A POSITIVE SENTINEL LYMPH NODE BIOPSY

PubMed Central

Loiselle, Christopher; Eby, Peter R.; Kim, Janice N.; Calhoun, Kristine E.; Allison, Kimberly H.; Gadi, Vijayakrishna K.; Peacock, Sue; Storer, Barry; Mankoff, David A.; Partridge, Savannah C.; Lehman, Constance D.

2014-01-01

Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy. PMID:24331270

Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: a systematic review and meta-analysis.

PubMed

Glechner, Anna; Wöckel, Achim; Gartlehner, Gerald; Thaler, Kylie; Strobelberger, Michaela; Griebler, Ursula; Kreienberg, Rolf

2013-03-01

The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1 year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Technical details of sentinel lymph node mapping in colorectal cancer and its impact on staging.

PubMed

Saha, S; Wiese, D; Badin, J; Beutler, T; Nora, D; Ganatra, B K; Desai, D; Kaushal, S; Nagaraju, M; Arora, M; Singh, T

2000-03-01

Sentinel lymph node (SLN) mapping for melanoma and breast cancer has greatly enhanced the identification of micrometastases in many patients, thereby upstaging a subset of these patients. The purpose of this study was to see if SLN mapping technique could be used to identify SLNs in colorectal cancer and to assess its impact on pathological staging and treatment. At the time of surgery, 1 ml of Lymphazurin 1% was injected subserosally around the tumor without injecting into the lumen. The first to fourth blue nodes identified were considered the SLNs, which have the highest probability to contain metastases. A standard oncological resection of the bowel was then performed. Multilevel microsections of the SLNs, including a detailed pathological examination of the entire specimen, was performed. SLN was successfully identified in 85 (98.8%) of 86 patients. In 85 patients, there were 1,367 (16 per patient) lymph nodes examined, of which 140 (1.6 per patient) were identified as SLNs. In 53 (95%) of 56, of whom the SLNs were without metastases (negative), all other non-SLNs also were negative. In 29 (34% of 85) patients, SLNs were positive for metastases; in 14 of the 29 patients, other non-SLNs also were positive in addition to the SLNs. In the other 15 of the 29 patients (18% of 85 patients), SLNs were the only site of metastases, and all other non-SLNs were negative. In 7 patients (8.2% of 85 patients), micrometastases were identified only in 1 or 2 of the 10 sections of a single SLN. In five of seven patients, such micrometastases were detected by hematoxylin and eosin staining and immunohistochemistry; in the other two patients, it was detected only by immunohistochemistry. In patients with negative SLNs, the rate of occurrence of micrometastases in non-SLNs was 5 (0.4%) of 1,184 lymph nodes. SLN mapping can be performed easily in colorectal cancer patients, with an accuracy of more than 95%. The identification of submicroscopic lymph node metastases by this

Sentinel lymph node mapping reduces practice pattern variations in surgical staging for endometrial adenocarcinoma: A before and after study.

PubMed

Liu, Christina Y; Elias, Kevin M; Howitt, Brooke E; Lee, Larissa J; Feltmate, Colleen M

2017-05-01

To examine the effects of universal sentinel lymph node mapping on the use of nodal staging in endometrial adenocarcinoma. Two approaches to laparoscopic staging for endometrial adenocarcinoma were compared using a before and after study design. The before cohort underwent selective lymphadenectomy from January 1, 2014-October 1, 2015 while the after cohort underwent universal sentinel lymph node (SLN) mapping from October 2, 2015-September 29, 2016. The before cohort comprised 215 patients and the after cohort 166 patients. In women undergoing SLN mapping, a sentinel node was identified at least unilaterally in 146/153 cases (95.4%), and bilaterally in 114/153 (74.5%) of cases. Pelvic nodes were removed in 35.8% of the before cohort versus 92.2% of the after cohort (p<0.0001) with more nodal evaluation among both low risk (9.6% vs. 91%, p<0.0001) and high risk cases (66% vs. 94%, p<0.0001). While the proportion of low risk cases diagnosed with nodal involvement did not significantly change (0.9% to 3.1%, p=0.32), there was a trend toward more diagnoses of nodal involvement in high risk cases (5% to 13.2%, p=0.06). Mean number of pelvic lymph nodes removed (15 vs. 4, p<0.0001), mean operative time (181min vs. 137min, p<0.0001), estimated blood loss (80ml vs. 56ml, p=0.004), and rate of post-operative complications (13% vs. 5.2%, p=0.04) all decreased after the adoption of SLN dissection. Universal sentinel lymph node dissection for laparoscopic endometrial cancer staging reduces heterogeneity in surgeon staging practice, increases nodal detection, and lowers post-operative complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Reliability and cost-effectiveness of complete lymph node dissection under tumescent local anaesthesia vs. general anaesthesia: a retrospective analysis in patients with malignant melanoma AJCC stage III.

PubMed

Stoffels, I; Dissemond, J; Schulz, A; Hillen, U; Schadendorf, D; Klode, J

2012-02-01

Complete lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) is currently being debated, as it is a cost-intensive surgical intervention with potentially high morbidity. This clinical study seeks to clarify the effectiveness, reliability and cost-effectiveness of CLND performed under tumescent local anaesthesia (TLA) compared with procedures under general anaesthesia (GA). We retrospectively analysed the data from 60 patients with primary malignant melanoma American Joint Committee on Cancer stage III who underwent CLND. Altogether 26 (43.3%) patients underwent CLND under TLA and 34 (56.7%) patients underwent CLND under GA. Fifteen of 43 (34.9%) patients had a complication, such as development of seromas and/or wound infections. The rate of complications was 25.0% (3/12) in the axilla subgroup and 28.6% (4/14) in the groin subgroup of the TLA group. In the GA group, the complication rate was 31.3% (5/16) in the axilla subgroup and 44.4% (8/18) in the groin subgroup. The costs for CLND were significantly less for the CLND in a procedure room performed under TLA (mean €67.26) compared with CLND in an operating room under GA (mean €676.20, P < 0.0001). In conclusion, this study confirms that TLA is an excellent, safe, effective and cost-efficient alternative to GA for CLND in melanoma patients. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Sentinel Lymph Node Detection Using Carbon Nanoparticles in Patients with Early Breast Cancer

PubMed Central

Lu, Jianping; Zeng, Yi; Chen, Xia; Yan, Jun

2015-01-01

Purpose Carbon nanoparticles have a strong affinity for the lymphatic system. The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy using carbon nanoparticles in early breast cancer and to optimize the application procedure. Methods Firstly, we performed a pilot study to demonstrate the optimized condition using carbon nanoparticles for sentinel lymph nodes (SLNs) detection by investigating 36 clinically node negative breast cancer patients. In subsequent prospective study, 83 patients with clinically node negative breast cancer were included to evaluate SLNs using carbon nanoparticles. Another 83 SLNs were detected by using blue dye. SLNs detection parameters were compared between the methods. All patients irrespective of the SLNs status underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. Results In pilot study, a 1 ml carbon nanoparticles suspension used 10–15min before surgery was associated with the best detection rate. In subsequent prospective study, with carbon nanoparticles, the identification rate, accuracy, false negative rate was 100%, 96.4%, 11.1%, respectively. The identification rate and accuracy were 88% and 95.5% with 15.8% of false negative rate using blue dye technique. The use of carbon nanoparticles suspension showed significantly superior results in identification rate (p = 0.001) and reduced false-negative results compared with blue dye technique. Conclusion Our study demonstrated feasibility and accuracy of using carbon nanoparticles for SLNs mapping in breast cancer patients. Carbon nanoparticles are useful in SLNs detection in institutions without access to radioisotope. PMID:26296136

Sentinel Lymph Node Biopsy Use Among Melanoma Patients 75 Years of Age and Older.

PubMed

Sabel, Michael S; Kozminski, David; Griffith, Kent; Chang, Alfred E; Johnson, Timothy M; Wong, Sandra

2015-07-01

While SLN biopsy is recommended for melanoma ≥1 mm in depth, its use among the elderly population is more controversial. We reviewed our experience at the University of Michigan with melanoma patients ≥75 years of age. A total of 952 melanoma patients ≥75 years of age from 1996 to 2011 were identified from our institutional review board-approved database. In addition to clinicopathologic features and outcome data, comorbidity data were collected to calculate the Charlson comorbidity index (CCI). Univariate and multivariate Cox regression analysis was performed to characterize predictors of outcome. Kaplan-Meier analysis was used to generate survival curves. Among 553 clinically node-negative patients with melanoma ≥1 mm in Breslow thickness, 213 had wide excision alone, whereas 340 had excision and SLN biopsy, with 83 (24 %) having a positive SLN. SLN biopsy was less likely with older age (p < 0.0001) and H&N location (p = 0.007), but not CCI. SLN involvement was associated with female gender [odds ratio (OR) 2.15, p = 0.009], Breslow thickness [OR 1.23/mm increase, p = 0.004], and satellitosis (OR 4.43, p = 0.004). Distant disease-specific survival was negatively associated with male gender (OR 1.5, p = 0.007), increasing age (OR 1.05/year, p < 0.001), increasing Breslow thickness (OR 1.07/year, p = 0.013), ulceration (OR 1.51, p = 0.004), a positive SLN (OR 2.61, p < 0.001), and not having a SLN biopsy (OR 1.72, p < 0.001). CCI did not predict worse disease-free or melanoma-specific survival. WLE and SLN biopsy was not only strongly prognostic, but compared with WLE alone was associated with improved outcome, even after factoring for age and comorbidities. If otherwise healthy, SLN biopsy should be strongly considered for this population.

Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

PubMed

Riber-Hansen, Rikke; Hastrup, Nina; Clemmensen, Ole; Behrendt, Nille; Klausen, Siri; Ramsing, Mette; Spaun, Eva; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

2012-02-01

Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50μm apart (EORTC Protocol) followed by complete 250μm step-sectioning. Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

The natural history of thin melanoma and the utility of sentinel lymph node biopsy.

PubMed

Durham, Alison B; Schwartz, Jennifer L; Lowe, Lori; Zhao, Lili; Johnson, Andrew G; Harms, Kelly L; Bichakjian, Christopher K; Orsini, Amy P; McLean, Scott A; Bradford, Carol R; Cohen, Mark S; Johnson, Timothy M; Sabel, Michael S; Wong, Sandra L

2017-12-01

Current literature may overestimate the risk of nodal metastasis from thin melanoma due to reporting of data only from lesions treated with SLNB. Our objective was to define the natural history of thin melanoma, assessing the likelihood of nodal disease, in order to guide selection for SLNB. Retrospective review. The primary outcome was the rate of nodal disease. Clinicopathologic factors were evaluated to find associations with nodal disease. Five hundred and twelve lesions, follow up available for 488 (median: 48 months). Lesions treated with WLE/SLNB compared to WLE alone were more likely to have high-risk features. The rate of nodal disease was higher in the WLE/SLNB group (24 positive SLNB, five false-negative SLNB with nodal recurrence: 10.2%) compared to WLE alone (four nodal recurrences: 2.0%). Univariate analysis showed age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm 2 , and ulceration were associated with nodal disease. Multivariate analysis confirmed the association of age ≤45 and ulceration. SLNB for melanoma 0.75-0.99 mm should be considered in patients age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm 2 , and/or with ulceration. Thin melanoma <0.85 mm without high-risk features may be treated with WLE alone. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2008-03-04

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. 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. 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 invasion and size of SLN

Optimization of dendrimer structure for sentinel lymph node imaging: Effects of generation and terminal group.

PubMed

Niki, Yuichiro; Ogawa, Mikako; Makiura, Rie; Magata, Yasuhiro; Kojima, Chie

2015-11-01

The detection of the sentinel lymph node (SLN), the first lymph node draining tumor cells, is important in cancer diagnosis and therapy. Dendrimers are synthetic macromolecules with highly controllable structures, and are potent multifunctional imaging agents. In this study, 12 types of dendrimer of different generations (G2, G4, G6, and G8) and different terminal groups (amino, carboxyl, and acetyl) were prepared to determine the optimal dendrimer structure for SLN imaging. Radiolabeled dendrimers were intradermally administrated to the right footpads of rats. All G2 dendrimers were predominantly accumulated in the kidney. Amino-terminal, acetyl-terminal, and carboxyl-terminal dendrimers of greater than G4 were mostly located at the injection site, in the blood, and in the SLN, respectively. The carboxyl-terminal dendrimers were largely unrecognized by macrophages and T-cells in the SLN. Finally, SLN detection was successfully performed by single photon emission computed tomography imaging using carboxyl-terminal dendrimers of greater than G4. The early detection of tumor cells in the sentinel draining lymph nodes (SLN) is of utmost importance in terms of determining cancer prognosis and devising treatment. In this article, the authors investigated various formulations of dendrimers to determine the optimal one for tumor detection. The data generated from this study would help clinicians to fight the cancer battle in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

Support vector machine learning model for the prediction of sentinel node status in patients with cutaneous melanoma.

PubMed

Mocellin, Simone; Ambrosi, Alessandro; Montesco, Maria Cristina; Foletto, Mirto; Zavagno, Giorgio; Nitti, Donato; Lise, Mario; Rossi, Carlo Riccardo

2006-08-01

Currently, approximately 80% of melanoma patients undergoing sentinel node biopsy (SNB) have negative sentinel lymph nodes (SLNs), and no prediction system is reliable enough to be implemented in the clinical setting to reduce the number of SNB procedures. In this study, the predictive power of support vector machine (SVM)-based statistical analysis was tested. The clinical records of 246 patients who underwent SNB at our institution were used for this analysis. The following clinicopathologic variables were considered: the patient's age and sex and the tumor's histological subtype, Breslow thickness, Clark level, ulceration, mitotic index, lymphocyte infiltration, regression, angiolymphatic invasion, microsatellitosis, and growth phase. The results of SVM-based prediction of SLN status were compared with those achieved with logistic regression. The SLN positivity rate was 22% (52 of 234). When the accuracy was > or = 80%, the negative predictive value, positive predictive value, specificity, and sensitivity were 98%, 54%, 94%, and 77% and 82%, 41%, 69%, and 93% by using SVM and logistic regression, respectively. Moreover, SVM and logistic regression were associated with a diagnostic error and an SNB percentage reduction of (1) 1% and 60% and (2) 15% and 73%, respectively. The results from this pilot study suggest that SVM-based prediction of SLN status might be evaluated as a prognostic method to avoid the SNB procedure in 60% of patients currently eligible, with a very low error rate. If validated in larger series, this strategy would lead to obvious advantages in terms of both patient quality of life and costs for the health care system.

Financial aspects of sentinel lymph node biopsy in early breast cancer.

PubMed

Severi, S; Gazzoni, E; Pellegrini, A; Sansovini, M; Raulli, G; Corbelli, C; Altini, M; Paganelli, G

2012-02-01

At present, early breast cancer is treated with conservative surgery of the primary lesion (BCS) along with axillary staging by sentinel lymph node biopsy (SLNB). Although the scintigraphic method is standardized, its surgical application is different for patient compliance, work organization, costs, and diagnosis related group (DRG) reimbursements. We compared four surgical protocols presently used in our region: (A) traditional BCS with axillary lymph node dissection (ALND); (B) BCS with SLNB and concomitant ALND for positive sentinel nodes (SN); (C) BCS and SLNB under local anaesthesia with subsequent ALND under general anaesthesia according to the SN result; (D) SLNB under local anaesthesia with subsequent BCS under local anaesthesia for negative SN, or ALND under general anaesthesia for positive SN. For each protocol, patient compliance, use of consumables, resources and time spent by various dedicated professionals, were analyzed. Furthermore, a detailed breakdown of 1-/2-day hospitalization costs was calculated using specific DRGs. We reported a mean costs variation that ranged from 1,634 to 2,221 Euros (protocols C and D). The number of procedures performed and the pathologists' results are the most significant variables affecting the rate of DRG reimbursements, that were the highest for protocol D and the lowest for protocol B. In our experience protocol C is the most suitable in terms of patient compliance, impact of surgical procedures, and work organization, and is granted by an appropriate DRG. We observed that a multidisciplinary approach enhances overall patient care and that a revaluation of DRG reimbursements is opportune.

Detection of sentinel lymph nodes in patients with early stage cervical cancer.

PubMed

Seong, Seok Ju; Park, Hyun; Yang, Kwang Moon; Kim, Tae Jin; Lim, Kyung Taek; Shim, Jae Uk; Park, Chong Taik; Lee, Ki Heon

2007-02-01

The purpose of this study was to determine the feasibility of identifying the sentinel lymph nodes (SNs) as well as to evaluate factors that might influence the SN detection rate in patients with cervical cancer of the uterus. Eighty nine patients underwent intracervical injection of 1% isosulfan blue dye at the time of planned radical hysterectomy and lymphadenectomy between January 2003 and December 2003. With the visual detection of lymph nodes that stained blue, SNs were identified and removed separately. Then all patients underwent complete pelvic lymph node dissection and/or para-aortic lymph node dissection. SNs were identified in 51 of 89 (57.3%) patients. The most common site for SN detection was the external iliac area. Metastatic nodes were detected in 21 of 89 (23.5%) patients. One false negative SN was obtained. Successful SN detection was more likely in patients younger than 50 yr (p=0.02) and with a history of preoperative conization (p=0.05). However, stage, histological type, surgical procedure and neoadjuvant chemotherapy showed no significant difference for SN detection rate. Therefore, the identification of SNs with isosulfan blue dye is feasible and safe. The SN detection rate was high in patients younger than 50 yr or with a history of preoperative conization.

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

Sentinel lymph nodes in endometrial cancer: is hysteroscopic injection valid?

PubMed

Clement, D; Bats, A S; Ghazzar-Pierquet, N; Le Frere Belda, M A; Larousserie, F; Nos, C; Lecuru, F

2008-01-01

We aimed to describe hysteroscopic peritumoral tracer injection for detecting sentinel lymph nodes (SLNs) in patients with endometrial cancer and to evaluate tolerance of the procedure, detection rate and location of SLNs. Five patients with early endometrial cancer underwent hysteroscopic radiotracer injection followed by lymphoscintigraphy, then by surgery with hysteroscopic peritumoral blue dye injection, and radioactivity measurement using an endoscopic handheld gamma probe. SLNs and other nodes were sent separately to the pathology laboratory. SLNs were evaluated by hematoxylin-eosin-saffron staining and, when negative, by immunohistochemistry. Tolerance of the injection by the patients was poor (mean visual analog scale score, 8/10). SLNs were detected in only two patients (external iliac and common iliac+paraaortic, respectively). Detection rates were 1/5 by radiotracer, 1/5 by dye, and 2/5 by the combined method. One SLN was involved in a patient whose other nodes were negative. In three patients no SLNs were found by radiotracer or blue dye. Of the 83 non sentinel nodes removed from these patients, none was involved. Hysteroscopic peritumoral injection may be more difficult than cervical injection and, in our experience, carries a lower SLN detection rate.

HSP-70, C-myc and HLA-DR expression in patients with cutaneous malignant melanoma metastatic in lymph nodes.

PubMed

Kalogeraki, A; Garbagnati, F; Darivianaki, K; Delides, G S; Santinami, M; Stathopoulos, E N; Zoras, O

2006-01-01

HSP-70, C-myc and HLA-DR were examined in patients with cutaneous malignant melanoma metastatic to lymph nodes. Lymph-nodal fine-needle aspiration biopsies (FNABs) were analyzed and the results were correlated to other variables, such as the gender of the patients, Clark level and Breslow thickness of the primary tumor. Thirty cases of metastatic melanoma in lymph nodes from 30 patients with cutaneous malignant melanoma were studied. All patients (100%) had microscopic regional nodal metastasis and a recurrence of the lesion during the first two years. The HSP-70, C-myc and HLA-DR expressions were investigated immunocytologically, using the APAAP (alkaline phosphatase) method on the FNAB samples. The immunocytochemical expressions of HSP-70 protein, C-myc oncogene, and HLA-DR antigen were found in 18 cases (60%), in 14 cases (43.3%) and in 12 cases (40%), respectively. Clark levels were significantly associated with HSP-70 protein (< 0.01), C-myc oncogene expression (< 0.05) and HLA-DR antigen (< 0.01) expression. The HLA-DR antigen was also found to be related (< 0.05) to higher Breslow thickness (> 1.5 mm). The clinical course of malignant cutaneous melanoma is related to the expression of these indices, which seem to play a significant role in the metastasis and prognosis of this aggressive tumor. The immunocytochemical expression of HSP-70 in the malignant melanoma tumor could be of particular value in the identification of patients with poor prognosis.

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

PubMed

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

2016-01-01

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

Laparoendoscopic Single-Site Sentinel Lymph Node Detection in Endometrial Cancer.

PubMed

Demirayak, Gökhan; Comba, Cihan; Özdemir, İsa Aykut

2017-11-13

To demonstrate the feasibility of sentinel lymph node (SLN) biopsy using a laparoendoscopic single-site (LESS) approach in endometrial cancer (EC). A step-by-step video demonstration of the surgical procedure (Canadian Task Force Classification III). The satisfaction of patients who undergo LESS hysterectomy is greater than that reported by patients who undergo multiport laparoscopic hysterectomy, owing to better cosmesis and reduced postoperative analgesic requirements [1]. SLN biopsy is associated with significantly lower estimated blood loss, shorter operation time, and less morbidity compared with systematic lymphadenectomy [2]. LESS surgery can be more feasible and safer with the use of SLN biopsy compared with complete lymphadenectomy in patients with early-stage EC. This 69-year-old woman with grade 2 endometrioid EC underwent SLN mapping followed by LESS SLN biopsy, total hysterectomy, and bilateral salpingo-oophorectomy. Before the umbilical incision was made, 1.25 mg/mL of indocyanine green was injected into the cervical stroma at the 3 o'clock and 9 o'clock positions to both deep and superficial levels. A 10-mm 30° standard-length optical camera for near-infrared fluorescence imaging was used. The total operative time was 75 minutes, and the estimated blood loss was 20 mL. SLNs were detected bilaterally between proximal parts of the external iliac arteries and veins. After SLN resection, total hysterectomy and bilateral salpingo-oophorectomy were performed. No postoperative complications occurred. The patient was discharged at 30 hours after surgery. In the final pathology, stage 1A G2 EC was detected. LESS SLN biopsy and TLH-BSO is a feasible procedure and sentinel lymph node concept may increase the use of LESS in EC. Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

PubMed

Gjorup, Caroline A; Groenvold, Mogens; Hendel, Helle W; Dahlstroem, Karin; Drzewiecki, Krzysztof T; Klausen, Tobias W; Hölmich, Lisbet R

2017-11-01

To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sentinel lymph node detection in gynecologic malignancies by a handheld fluorescence camera

NASA Astrophysics Data System (ADS)

Hirsch, Ole; Szyc, Lukasz; Muallem, Mustafa Zelal; Ignat, Iulia; Chekerov, Radoslav; Macdonald, Rainer; Sehouli, Jalid; Braicu, Ioana; Grosenick, Dirk

2017-02-01

Near-infrared fluorescence imaging using indocyanine green (ICG) as a tracer is a promising technique for mapping the lymphatic system and for detecting sentinel lymph nodes (SLN) during cancer surgery. In our feasibility study we have investigated the application of a custom-made handheld fluorescence camera system for the detection of lymph nodes in gynecological malignancies. It comprises a low cost CCD camera with enhanced NIR sensitivity and two groups of LEDs emitting at wavelengths of 735 nm and 830 nm for interlaced recording of fluorescence and reflectance images of the tissue, respectively. With the help of our system, surgeons can observe fluorescent tissue structures overlaid onto the anatomical image on a monitor in real-time. We applied the camera system for intraoperative lymphatic mapping in 5 patients with vulvar cancer, 5 patients with ovarian cancer, 3 patients with cervical cancer, and 3 patients with endometrial cancer. ICG was injected at four loci around the primary malignant tumor during surgery. After a residence time of typically 15 min fluorescence images were taken in order to visualize the lymph nodes closest to the carcinomas. In cases with vulvar cancer about half of the lymph nodes detected by routinely performed radioactive SLN mapping have shown fluorescence in vivo as well. In the other types of carcinomas several lymph nodes could be detected by fluorescence during laparotomy. We conclude that our low cost camera system has sufficient sensitivity for lymphatic mapping during surgery.

Dermoscopic features of thin melanomas: a comparative study of melanoma in situ and invasive melanomas smaller than or equal to 1mm*

PubMed Central

da Silva, Vanessa Priscilla Martins; Ikino, Juliana Kida; Sens, Mariana Mazzochi; Nunes, Daniel Holthausen; Di Giunta, Gabriella

2013-01-01

BACKGROUND Dermoscopy allows the early detection of melanomas. The preoperative determination of Breslow index by dermoscopy could be useful in planning the surgical approach and in selecting patients for sentinel lymph node biopsy. OBJECTIVES This study aims at describing the dermoscopic features of thin melanomas and comparing melanomas in situ with invasive melanomas less than or equal to 1 mm thick. METHODS This was an observational retrospective study in which the dermoscopy photographs of 41 thin melanomas were evaluated. Three observers evaluated together 14 dermoscopic criteria. RESULTS Among thin melanomas, the most frequent criteria were presence of asymmetry in two axes in 95% of cases (39 cases), 3 or more colors in 80.4% of cases (33 cases), atypical dots or globules in 58.5% of cases (24 cases) and atypical network or streaks in 53.6% of cases (22 cases). The group of invasive melanomas presented with a higher frequency and statistical significance (p <0.05) 3 or more colors (OR: 16.1), milky red areas (OR: 4.8) and blue-white veil (OR: 20.4), and a greater tendency to have streaks or atypical network (OR: 3.66). CONCLUSIONS Thin melanomas tend to have asymmetry in the two axes, 3 or more colors, atypical dots or globules and atypical network or streaks. Melanomas in situ tend to have up to 2 colors, no blue-white veil and no milky red area. Invasive melanomas tend to have 3 or more colors, a milky red area, blue-white veil, and atypical network or streaks. Further studies are needed to confirm these findings. PMID:24173175

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.

Sentinel lymph node biopsy in the management of early-stage cervical carcinoma.

PubMed

Diaz, John P; Gemignani, Mary L; Pandit-Taskar, Neeta; Park, Kay J; Murray, Melissa P; Chi, Dennis S; Sonoda, Yukio; Barakat, Richard R; Abu-Rustum, Nadeem R

2011-03-01

We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer. A prospective, non-randomized study of women with early-stage (FIGO stage IA1 with lymphovascular space involvement--IIA) cervical carcinoma was conducted from June 2003 to August 2009. All patients underwent an intraoperative intracervical blue dye injection. Patients who underwent a preoperative lymphoscintigraphy received a 99m Tc sulfur colloid injection in addition. All patients underwent sentinel lymph node (SLN) identification followed by a complete pelvic node and parametrial dissection. SLN were evaluated using our institutional protocol that included pathologic ultrastaging. SLN mapping was successful in 77 (95%) of 81 patients. A total of 316 SLN were identified, with a median of 3 SLN per patient (range, 0-10 SLN). The majority (85%) of SLN were located at three main sites: the external iliac (35%); internal iliac (30%); and obturator (20%). Positive lymph nodes (LN) were identified in 26 (32%) patients, including 21 patients with positive SLN. Fifteen of 21 patients (71%) had SLN metastasis detected on routine processing. SLN ultrastaging detected metastasis in an additional 6/21 patients (29%). Two patients had grossly positive LN at exploration, and mapping was abandoned. Three of 26 (12%) patients had successful SLN mapping; however, the SLN failed to identify the metastatic LN. Of these 3 false negative cases, 2 patients had a metastatic parametrial node as the only positive LN with multiple negative pelvic nodes including negative SLN. One patient with stage IA1 disease and lymphovascular invasion had unilateral SLN mapping and a metastatic common iliac LN identified on completion lymphadenectomy of the contralateral side that did not map. The 4 (5%) patients with unsuccessful

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

[Presence of intramammary lymph nodes in the preoperative lymphoscintigraphy to locate the sentinel lymph node. Clinical significance].

PubMed

Nogareda, Z; Álvarez, A; Perlaza, P; Caparrós, F X; Alonso, I; Paredes, P; Vidal-Sicart, S

2015-01-01

The routes of lymphatic drainage from a breast cancer are the axilla (the most frequent) and the extra axillary regions. Among the latter, there are the so-called intrammamary lymph nodes (IMLN). This study has aimed to assess the incidence of IMLNs in our patients and study the evolution of these cases with IMLN in the lymphoscintigraphy. Thirty-eight patients (out of 1725) with IMLN in the pre-operative lymphoscintigraphy were assessed. During the surgical procedure, using a gamma probe, IMLNs were located and excised. After their harvesting, a meticulous surgical field scan was performed. When the axillary sentinel node was positive for metastasis, a complete axillary lymphadenectomy was performed. In those where the axillary sentinel node was negative and IMLN was positive (IMLN+), axillary lymphadenectomy was also performed, except for one case. Thirty-four out of the 38 IMLNs were obtained (89.5%), because no lymphatic tissue was found in pathology analysis in three cases (8%) and in one patient (3%) IMLN was not found during surgery. Ten (26%) metastatic IMLNs were located and the remaining 24 IMLNs cases (63%) were metastasis-free. During the clinical follow-up, one patient with IMLN+ developed hepatic metastases. The remaining 33 patients did not present any recurrence. No follow-up data were available for three patients. IMLN and axillary sentinel node biopsy are recommended when both are depicted in preoperative lymphoscintigraphy. The axilla treatment will only depend on the axillary sentinel node status. Based on the data from other authors and our own experience, avoiding the axillary lymphadenectomy when a metastatic IMLN without axillary involvement seems reasonable. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

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

Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer

PubMed Central

Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin

2016-01-01

An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20–24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice. PMID:27374088

Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer.

PubMed

Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin; Yu, Jin-Ming; Wang, Yong-Sheng

2016-07-26

An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20-24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice.

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

PubMed

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

2009-06-01

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

Tumour mutation status and sites of metastasis in patients with cutaneous melanoma.

PubMed

Adler, Nikki R; Wolfe, Rory; Kelly, John W; Haydon, Andrew; McArthur, Grant A; McLean, Catriona A; Mar, Victoria J

2017-09-26

Cutaneous melanoma can metastasise haematogenously and/or lymphogenously to form satellite/in-transit, lymph node or distant metastasis. This study aimed to determine if BRAF and NRAS mutant and wild-type tumours differ in their site of first tumour metastasis and anatomical metastatic pathway. Prospective cohort of patients with a histologically confirmed primary cutaneous melanoma at three tertiary referral centres in Melbourne, Australia from 2010 to 2015. Multinomial regression determined clinical, histological and mutational factors associated with the site of first metastasis and metastatic pathway. Of 1048 patients, 306 (29%) developed metastasis over a median 4.7 year follow-up period. 73 (24%), 192 (63%) and 41 (13%) developed distant, regional lymph node and satellite/in-transit metastasis as the first site of metastasis, respectively. BRAF mutation was associated with lymph node metastasis (adjusted RRR 2.46 95% CI 1.07-5.69, P=0.04) and sentinel lymph node positivity (adjusted odds ratio [aOR] OR 1.55, 95% CI 1.14-2.10, P=0.005). BRAF mutation and NRAS mutation were associated with increased odds of developing liver metastasis (aOR 3.09, 95% CI 1.49-6.42, P=0.003; aOR 3.17, 95% CI 1.32-7.58, P=0.01) and central nervous system (CNS) metastasis (aOR 4.65, 95% CI 2.23-9.69, P<0.001; aOR 4.03, 95% CI 1.72-9.44, P=0.001). NRAS mutation was associated with lung metastasis (aOR 2.44, 95% CI 1.21-4.93, P=0.01). BRAF mutation was found to be associated with lymph node metastasis as first metastasis and sentinel lymph node positivity. BRAF and NRAS mutations were associated with CNS and liver metastasis and NRAS mutation with lung metastasis. If these findings are validated in additional prospective studies, a role for heightened visceral organ surveillance may be warranted in patients with tumours harbouring these somatic mutations.

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

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients With an Initial Diagnosis of Cytology-Proven Lymph Node-Positive Breast Cancer.

PubMed

Enokido, Katsutoshi; Watanabe, Chie; Nakamura, Seigo; Ogiya, Akiko; Osako, Tomo; Akiyama, Futoshi; Yoshimura, Akiyo; Iwata, Hiroji; Ohno, Shinji; Kojima, Yasuyuki; Tsugawa, Koichiro; Motomura, Kazuyoshi; Hayashi, Naoki; Yamauchi, Hideko; Sato, Nobuaki

2016-08-01

Sentinel lymph node biopsy (SNB) is the standard treatment of node-negative breast cancer; however, whether SNB should be performed for patients with node-positive disease before neoadjuvant chemotherapy (NAC) is controversial. We evaluated the accuracy of SNB after NAC in patients with breast cancer with nodal metastasis before chemotherapy to determine the false-negative rate (FNR) and detection rate for SNB. In the present multicenter prospective study performed from September 2011 to April 2013, 143 patients with breast cancer and positive axillary nodes, proved by fine needle aspiration cytology at the initial diagnosis (stage T1-T3N1M0), were enrolled. All patients underwent breast surgery with SNB and complete axillary lymph node dissection. After NAC, the pathologic complete nodal response rate was 52.4%. The sentinel lymph node could be identified in 130 cases (90.9%); the FNR was 16.0% (13 of 81). The FNR of each clinical subtype was 42.1% (8 of 19) for the estrogen receptor-positive and human epithelial growth factor 2 (HER2)-negative (luminal type), 16.7% (2 of 12) for ER-positive and HER2-positive (luminal-HER2 type), 3.2% (1 of 31) for HER2-positive (HER2-enriched type), and 10.5% (2 of 19) for ER-negative and HER2-negative (triple-negative breast cancer; P = .003). The FNR was significantly greater in the luminal than in the nonluminal type (odds ratio, 9.91; 95% confidence interval, 6.77-14.52). SNB after NAC in patients with initially node-positive breast cancer was technically feasible but should not be recommended for the luminal subtype. However, the tumor subtype can guide patient selection, and axillary lymph node dissection could be omitted for the luminal-HER2, HER2-enriched, and triple-negative breast cancer subtypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

New Safety Margins for Melanoma Surgery: Nice Possibility for Drinking of "Just That Cup of Coffee"?

PubMed

Tchernev, Georgi; Chokoeva, Anastasiya Atanasova

2017-06-15

The American Joint Committee on Cancer (AJCC's) skin melanoma surgical treatment recommendations from 2011 are characterised by a prima facie "freedom of choice" regarding how extensive should be the excisions for melanomas with tumour thickness up to 2 mm and melanoma in situ. It is unclear why the recommended surgical security margins vary between 0.5 and 1 cm for melanoma in situ, whereas for melanomas with a tumour thickness of up to 1.99 mm, the range of variation is also between 1 and 2 cm, without specifying when the surgical field should be broader and, narrower, accordingly. This "uncertainty or lack of intent" of the guilders often leads to the same surgical approach to melanomas at different stages, or to a different approach in cases of melanomas at the same stage, in contrast. Therefore, this should be defined as wrong, logically. We present 3 patients with cutaneous melanomas, treated with similar fields of surgical security. Current issues, generated within the framework of melanoma's surgery guided by the recommendations of the AJCC are also discussed. A new surgical approach in patients with melanoma is recommended, discussed for the first time in world literature. We hypothesize that the introduction of a certain recommendations for a 2 cm surgical field in all directions during the initial excision, combined with the parallel performance of a sentinel lymph node biopsy, will lead in fact to several important advantages: 1) avoiding of the secondary excision in at least 70% - 90% of the patients (depending on the tumor thickness), 2) minimizing the risk of lymphatic effusion change and misinterpretation of the sentinel lymph node biopsy's results in patients with secondary excision; 3) optimization of the surgical team's work; 4) minimizing the possibility of unprepared/uninformed personnel to take part in decisions for treating a specific disease such as skin melanoma, 4) facilitating the appropriate patients' group selection at the appropriate

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

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.

A handheld SPIO-based sentinel lymph node mapping device using differential magnetometry

NASA Astrophysics Data System (ADS)

Waanders, S.; Visscher, M.; Wildeboer, R. R.; Oderkerk, T. O. B.; Krooshoop, H. J. G.; ten Haken, B.

2016-11-01

Sentinel lymph node biopsy has become a staple tool in the diagnosis of breast cancer. By replacing the morbidity-plagued axillary node clearance with removing only those nodes most likely to contain metastases, it has greatly improved the quality of life of many breast cancer patients. However, due to the use of ionizing radiation emitted by the technetium-based tracer material, the current sentinel lymph node biopsy has serious drawbacks. Most urgently, the reliance on radioisotopes limits the application of this procedure to small parts of the developed world, and it imposes restrictions on patient planning and hospital logistics. Magnetic alternatives have been tested in recent years, but all have their own drawbacks, mostly related to interference from metallic instruments and electromagnetic noise coming from the human body. In this paper, we demonstrate an alternative approach that utilizes the unique nonlinear magnetic properties of superparamagnetic iron oxide nanoparticles to eliminate the drawbacks of both the traditional gamma-radiation centered approach and the novel magnetic techniques pioneered by others. Contrary to many other nonlinear magnetic approaches however, field amplitudes are limited to 5 mT, which enables handheld operation without additional cooling. We show that excellent mass sensitivity can be obtained without the need for external re-balancing of the probe to negate any influences from the human body. Additionally, we show how this approach can be used to suppress artefacts resulting from the presence of metallic instruments, which are a significant dealbreaker when using conventional magnetometry-based approaches.

Penile Cancer: Contemporary Lymph Node Management.

PubMed

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

2017-06-01

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

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

PubMed

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

2018-06-01

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

Breast sentinel lymph node navigation with three-dimensional computed tomography-lymphography: a 12-year study.

PubMed

Yamamoto, Shigeru; Suga, Kazuyoshi; Maeda, Kazunari; Maeda, Noriko; Yoshimura, Kiyoshi; Oka, Masaaki

2016-05-01

To evaluate the utility of three-dimensional (3D) computed tomography (CT)-lymphography (LG) breast sentinel lymph node navigation in our institute. Between 2002 and 2013, we preoperatively identified sentinel lymph nodes (SLNs) in 576 clinically node-negative breast cancer patients with T1 and T2 breast cancer using 3D CT-LG method. SLN biopsy (SLNB) was performed in 557 of 576 patients using both the images of 3D CT-LG for guidance and the blue dye method. Using 3D CT-LG, SLNs were visualized in 569 (99%) of 576 patients. Of 569 patients, both lymphatic draining ducts and SLNs from the peritumoral and periareolar areas were visualized in 549 (96%) patients. Only SLNs without lymphatic draining ducts were visualized in 20 patients. Drainage lymphatic pathways visualized with 3D CT-LG (549 cases) were classified into four patterns: single route/single SLN (355 cases, 65%), multiple routes/single SLN (59 cases, 11%) single route/multiple SLNs (62 cases, 11%) and multiple routes/multiple SLNs (73 cases, 13%). SLNs were detected in 556 (99.8%) of 557 patients during SLNB. CT-LG is useful for preoperative visualization of SLNs and breast lymphatic draining routes. This preoperative method should contribute greatly to the easy detection of SLNs during SLNB.

Sentinel node detection in pre-operative axillary staging.

PubMed

Trifirò, Giuseppe; Viale, Giuseppe; Gentilini, Oreste; Travaini, Laura Lavinia; Paganelli, Giovanni

2004-06-01

The concept of sentinel lymph node biopsy in breast cancer surgery is based on the fact that the tumour drains in a logical way via the lymphatic system, from the first to upper levels. Since axillary node dissection does not improve the prognosis of patients with breast cancer, sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Subdermal or peritumoural injection of small aliquots (and very low activity) of radiotracer is preferred to intratumoural administration, and (99m)Tc-labelled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. The success rate of radioguidance in localising the sentinel lymph node in breast cancer surgery is about 97% in institutions where a high number of procedures are performed, and the success rate of lymphoscintigraphy in sentinel node detection is about 100%. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when necessary, immune staining with anti-cytokeratin antibody. Nowadays, lymphoscintigraphy is a useful procedure in patients with different clinical evidence of breast cancer.

Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for Predicting Nonsentinel Lymph Node Metastasis.

PubMed

Ryu, Jai Min; Lee, Se Kyung; Kim, Ji Young; Yu, Jonghan; Kim, Seok Won; Lee, Jeong Eon; Han, Se Hwan; Jung, Yong Sik; Nam, Seok Jin

2017-11-01

Axillary lymph node (ALN) status is an important prognostic factor for breast cancer patients. With increasing numbers of patients undergoing neoadjuvant chemotherapy (NAC), issues concerning sentinel lymph node biopsy (SLNB) after NAC have emerged. We analyzed the clinicopathologic features and developed a nomogram to predict the possibility of nonsentinel lymph node (NSLN) metastases in patients with positive SLNs after NAC. A retrospective medical record review was performed of 140 patients who had had clinically positive ALNs at presentation, had a positive SLN after NAC on subsequent SLNB, and undergone axillary lymph node dissection (ALND) from 2008 to 2014. On multivariate stepwise logistic regression analysis, pathologic T stage, lymphovascular invasion, SLN metastasis size, and number of positive SLN metastases were independent predictors for NSLN metastases (P < .05). The NAC nomogram was based on these 4 variables. A receiver operating characteristic curve was plotted, and the area under the curve (AUC) was 0.791 for the NAC nomogram. In the internal validation of performance, the AUCs for the training and test sets were 0.801 and 0.760, respectively. The nomogram was validated in an external patient cohort, with an AUC of 0.705. The Samsung Medical Center NAC nomogram was developed to predict the likelihood of additional positive NSLNs. The Samsung Medical Center NAC nomogram could provide information to surgeons regarding whether to perform additional ALND when the permanent biopsy revealed positive findings, although the intraoperative SLNB findings were negative. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Optimising probe holder design for sentinel lymph node imaging using clinical photoacoustic system with Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Periyasamy, Vijitha; Wen, Kew Kok; Pramanik, Manojit

2017-03-01

Photoacoustic tomography is a hybrid imaging modality that combines optical and ultrasound imaging. It is rapidly gaining attention in the field of medical imaging. The challenge is to translate it into a clinical setup. In this work, we report the development of a handheld clinical photoacoustic imaging system. A clinical ultrasound imaging system is modified to integrate photoacoustic imaging with the ultrasound imaging. Hence, light delivery has been integrated with the ultrasound probe. The angle of light delivery is optimized in this work with respect to the depth of imaging. Optimization was performed based on Monte Carlo simulation for light transport in tissues. Based on the simulation results, the probe holders were fabricated using 3D printing. Similar results were obtained experimentally using phantoms. Phantoms were developed to mimic sentinel lymph node imaging scenario. Also, in vivo sentinel lymph node imaging was done using the same system with contrast agent methylene blue up to a depth of 1.5 cm. The results validate that one can use Monte Carlo simulation as a tool to optimize the probe holder design depending on the imaging needs. This eliminates a trial and error approach generally used for designing a probe holder.

Updated evidence-based clinical practice guidelines for the diagnosis and management of melanoma: definitive excision margins for primary cutaneous melanoma.

PubMed

Sladden, Michael J; Nieweg, Omgo E; Howle, Julie; Coventry, Brendon J; Thompson, John F

2018-02-19

Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.8 mm if other high risk features) in which case lymphoscintigraphy must be performed before wider excision of the primary melanoma site. The 2008 evidence-based clinical practice guidelines for the management of melanoma (http://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalPracticeGuidelines-ManagementofMelanoma.pdf) are currently being revised and updated in a staged process by a multidisciplinary working party established by Cancer Council Australia. The guidelines for definitive excision margins for primary melanomas have been revised as part of this process. Main recommendations: The recommendations for definitive wide local excision of primary cutaneous melanoma are: melanoma in situ: 5-10 mm margins invasive melanoma (pT1) ≤ 1.0 mm thick: 1 cm margins invasive melanoma (pT2) 1.01-2.00 mm thick: 1-2 cm margins invasive melanoma (pT3) 2.01-4.00 mm thick: 1-2 cm margins invasive melanoma (pT4) > 4.0 mm thick: 2 cm margins Changes in management as a result of the guideline: Based on currently available evidence, excision margins for invasive melanoma have been left unchanged compared with the 2008 guidelines. However, melanoma in situ should be excised with 5-10 mm margins, with the aim of achieving complete histological clearance. Minimum clearances from all margins should be assessed and stated. Consideration should be given to further excision if necessary; positive or close histological margins are unacceptable.

[Diagnostic validity of the intraoperative analysis in frozen section of the sentinel lymph node in the surgical management of breast cancer].

PubMed

Bañuelos-Andrío, Luis; Rodríguez-Caravaca, Gil; Argüelles-Pintos, Miguel; Mitjavilla-Casanovas, Mercedes

2014-01-01

The method for intraoperative sentinel lymph node (SLN) evaluation has still not been established in breast cancer staging. This study has evaluated the diagnostic validity and impact of intraoperative analysis using the frozen section (FS) of SLN. We performed a descriptive study of the diagnostic validity of the FS of the SLN in patients with breast cancer and selective sentinel node biopsy (SSNB) from October-2006 to October-2012. The diagnostic validity indexes were evaluated using sensitivity, specificity, positive and negative predictive values and global value. Gold standard was considered as the final histopathological results of the biopsies. A total of 370 patients were studied. Sensitivity and specificity for detection of metastasis by FS in the SLN were 67% and 100%, respectively. Global diagnostic validity was 95%. There was a correlation between detection of metastasis and tumor size (p<0.05). Twelve of the 15 patients with SLN micro-metastases underwent axillary lymph node dissection (ALND). Metastatic lymph nodes were not found in any of them. Intraoperative FS examination of the SLN is a useful and reliable predictor of axillary lymph node staging in patients with initial stages of breast cancer. FS reduces the need for second interventions, at least for most patients who have breast cancer with identifiable positive SLN and unequivocal evidence of positive lymph node disease. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

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

PubMed

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

2016-01-01

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

Experimental study of {sup 99m}Tc-aluminum oxide use for sentinel lymph nodes detection

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

Chernov, V. I., E-mail: Chernov@oncology.tomsk.ru; Sinilkin, I. G.; Zelchan, R. V.

The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis was researched on 50 white male rats. The possibility of the use of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particlemore » was 52–77 nm for {sup 99m}Tc-Al{sub 2}O{sub 3} and 16.7–24.5 nm for {sup 99m}Tc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of {sup 99}mTc-Al{sub 2}O{sub 3} was 8.6% in it, and the accumulation of {sup 99m}Tc-Nanocis was significantly lower—1.8% (p < 0.05). In all study points the average uptake of {sup 99m}Tc-Al{sub 2}O{sub 3} in the lymph node was significantly higher than {sup 99m}Tc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis actively accumulated into the lymphatic system. By using {sup 99m}Tc-Al{sub 2}O{sub 3} 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 {sup 99m}Tc-Al{sub 2}O{sub 3} 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 {sup 99m}Tc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the

Saccharide substituted zinc phthalocyanines: optical properties, interaction with bovine serum albumin and near infrared fluorescence imaging for sentinel lymph nodes.

PubMed

Lu, Li; Lv, Feng; Cao, Bo; He, Xujun; Liu, Tianjun

2014-01-03

Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1-(β-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and [2,9(10), 16(17),23(24)-tetrakis((1-(β-D-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared fluorescence agents. Their interaction with bovine serum albumin was investigated by fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. Near infrared imaging for sentinel lymph nodes in vivo was performed using nude mice as models. Results show that saccharide- substituted zinc phthalocyanines have favourable water solubility, good optical stability and high emission ability in the near infrared region. The interaction of lactose-substituted phthalocyanine with bovine serum albumin displays obvious differences to that of glucose- substituted phthalocyanine. Moreover, lactose-substituted phthalocyanine possesses obvious imaging effects for sentinel lymph nodes in vivo.

Clinical applications of sentinel lymph-node biopsy for the staging and treatment of solid neoplasms.

PubMed

Gipponi, M

2005-08-01

A review of the clinical applications of sentinel lymph node (sN) biopsy has been performed with the aim of defining the rationale, the methods of detection, the accuracy, and the current indications to sN biopsy in different solid neoplasms. In melanoma patients, sN biopsy represents a standard procedure for staging purpose, although its therapeutic value is still under examination. The sN is an accurate method for the pathologic staging of the axilla in patients with early stage breast cancer, and it can be useful for the selection of patients with axillary metastasis who should undergo standard axillary dissection. In gynecologic malignancies, appreciable results are available in patients with vulvar and cervical cancer only. Patients with squamous cell vulvar cancer may benefit by sN biopsy because a complete bilateral inguino-femoral lymph-node dissection may be avoided whenever the sN is free of metastasis. As regards to cervical cancer, further studies are required with the combined technique (blue dye injection and gamma-probe guided surgery), which seems more promising, before abandoning pelvic lymphadenectomy in patients with histologically-negative sN. The experience in urologic cancer deals mainly with penile and prostate cancer; the modern procedures for the dynamic detection of sN are going to clarify its role in the surgical management of penile cancer; as regards to prostate cancer, very preliminary results suggest that the sN biopsy may enhance the pathologic staging of this neoplasm compared to modified pelvic lymphadenectomy, due to the individual variability of the lymphatic drainage of this cancer. In patients with clinically node-negative squamous head and neck cancer, the reliability of sN-guided neck lymph node dissection seems promising. The sN biopsy is also technically feasible in patients with differentiated thyroid cancer; however, the future role of this procedure in the clinical decision-making of these patients remains to be defined

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

PubMed

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

2016-11-01

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

Congenital nevi versus metastatic melanoma in a newborn to a mother with malignant melanoma - diagnosis supported by sex chromosome analysis and Imaging Mass Spectrometry.

PubMed

Alomari, Ahmed K; Glusac, Earl J; Choi, Jennifer; Hui, Pei; Seeley, Erin H; Caprioli, Richard M; Watsky, Kalman L; Urban, Jennifer; Lazova, Rossitza

2015-10-01

A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no ulceration. Following induction of labor, the patient underwent re-excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)-based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2011-10-15

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

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

PubMed

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

2017-01-01

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

Paired-agent fluorescent imaging to detect micrometastases in breast sentinel lymph node biopsy: experiment design and protocol development

NASA Astrophysics Data System (ADS)

Li, Chengyue; Xu, Xiaochun; Basheer, Yusairah; He, Yusheng; Sattar, Husain A.; Brankov, Jovan G.; Tichauer, Kenneth M.

2018-02-01

Sentinel lymph node status is a critical prognostic factor in breast cancer treatment and is essential to guide future adjuvant treatment. The estimation that 20-60% of micrometastases are missed by conventional pathology has created a demand for the development of more accurate approaches. Here, a paired-agent imaging approach is presented that employs a control imaging agent to allow rapid, quantitative mapping of microscopic populations of tumor cells in lymph nodes to guide pathology sectioning. To test the feasibility of this approach to identify micrometastases, healthy pig lymph nodes were stained with targeted and control imaging agent solution to evaluate the potential for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody was labeled with IRDye 800CW (LICOR) as targeted agent and IRDye 700DX was hydrolyzed as a control agent. Lymph nodes were stained and rinsed by directly injecting the agents into the lymph nodes after immobilization in agarose gel. Subsequently, lymph nodes were frozen-sectioned and imaged under an 80-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. The binding potentials were acquired by a pixel-by-pixel calculation and was found to be 0.02 +/- 0.06 along the lymph node in the absence of binding. The results demonstrate this approach's potential to enhance the sensitivity of lymph node pathology by detecting fewer than 1000 cell in a whole human lymph node.

Low-molecular-weight hyaluronan (LMW-HA) accelerates lymph node metastasis of melanoma cells by inducing disruption of lymphatic intercellular adhesion.

PubMed

Du, Yan; Cao, Manlin; Liu, Yiwen; He, Yiqing; Yang, Cuixia; Wu, Man; Zhang, Guoliang; Gao, Feng

2016-01-01

Endothelial integrity defects initiate lymphatic metastasis of tumor cells. Low-molecular-weight hyaluronan (LMW-HA) derived from plasma and interstitial fluid was reported to be associated with tumor lymphatic metastasis. In addition, LMW-HA was proved to disrupt lymphatic vessel endothelium integrity, thus promoting lymphatic metastasis of tumor cells. Until now, there are few reports on how LMW-HA modulates lymphatic endothelial cells adhesion junctions and affects cancer cells metastasizing into lymph vessels. The aim of our study is to unravel the novel mechanism of LMW-HA in mediating tumor lymphatic metastasis. Here, we employed a melanoma metastasis model to investigate whether LMW-HA facilitates tumor cells transferring from foci to remote lymph nodes by disrupting the lymphatic endothelial integrity. Our data indicate that LMW-HA significantly induces metastasis of melanoma cells to lymph nodes and accelerates interstitial-lymphatic flow in vivo . Further experiments show that increased migration of melanoma cells across human dermal lymphatic endothelial cell (HDLEC) monolayers is accompanied by impaired lymphatic endothelial barrier function and increased permeability. The mechanism study reveals that VE-cadherin-β-catenin pathway and relevant signals are involved in modulating the interactions between endothelial cells and that a significant inhibition of lymphatic endothelium disruption is observed when antibodies to the LMW-HA receptor (LYVE-1) are present. Thus, our findings demonstrate a disruptive effect of LMW-HA on lymphatic endothelium continuity which leads to a promotion on melanoma lymphatic metastasis and also suggest a cellular signaling mechanism associated with VE-cadherin-mediated lymphatic intercellular junctions.

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

PubMed

Mainiero, Martha B

2010-09-01

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

Sentinel Lymph Node (SLN) laparoscopic assessment early stage in endometrial cancer.

PubMed

Gargiulo, T; Giusti, M; Bottero, A; Leo, L; Brokaj, L; Armellino, F; Palladin, L

2003-06-01

The aim of the study was to demonstrate the validity of sentinel lymph node (SLN) detection after injection of radioactive isotope and patent blue dye in patients affected by early stage endometrial cancer. The second purpose was to compare radioactive isotope and patent blue dye migration. Between September 2000 and May 2001, 11 patients with endometrial cancer FIGO stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and pelvic bilateral systematic lymphadenectomy. Radioactive isotope injection was performed 24 ours before surgery and blue dye injection was performed just before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic gamma-scintiprobe MR 100 type 11, (99m)Tc setted (Pol.Hi.Tech.), was used intraoperatively for detecting SLN. Seventeen SLN were detected at lymphoscintigraphy (6 bilateral and 5 monolateral). At laparoscopic surgery the same locations were found belonging at internal iliac lymph nodes (the so called "Leveuf-Godard" area, lateral to the inferior vescical artery, ventral to the origin of uterine artery and medial or caudal to the external iliac vein). Fourteen SLN were negative at histological analysis and only 3 positive for micrometastasis (mean SLN sections = 60. All the other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with g-scintiprobe were observed during laparoscopy after patent blue dye injection. If the sensitivity of the assessment of SLN is confirmed to be 100%, this laparoscopic approach could change the management of early stage endometrial cancer. The clinical validity of this technique must be evaluated prospectively.

Intraoperative clinical assessment and pressure measurements of sentinel lymph nodes in breast cancer.

PubMed

Nathanson, S David; Shah, Rupen; Chitale, Dhananjay A; Mahan, Meredith

2014-01-01

Clinicians have long regarded firm enlarged axillary nodes as suspicious for metastasis, and this has been confirmed to represent increased pressure in sentinel lymph nodes (SLN) in vivo in breast cancer. We hypothesized that measuring intranodal pressure (INP) in the operating room would correlate with metastasis size and be more sensitive than clinical observation. Intranodal pressure mmHg was measured in SLNs #1 and #2 (N = 134 and 32) in 122 patients with T1/2 cN0 and 6 controls (T0) (8 bilateral). Clinical "Level of Suspicion" (LOS) was: 0 = benign; 1 = slightly suspicious; 2 = obvious metastasis. Statistical analysis was performed to compare INP, LOS, and SLN metastasis size mm. Sentinel lymph nodes met size correlated with INP (r = 0.65; p < 0.001). INP was 22.0 ± 1.3 mmHg in 35 SLNs with metastases compared with 9.3 ± 0.7 mmHg in 132 without (p < 0.001). Six groups created by combining LOS 0, 1, and 2 with INP >17 or ≤17 mmHg showed a significant (p < 0.001) correlation with SLN histology; sensitivity and specificity for LOS = 2/INP >17 mmHg = 100 % at predicting metastases; LOS = 0/INP ≤17 mmHg most often correct at predicting negative nodes (sensitivity 50 %, specificity 92.9 %, positive predictive value 55 %, negative predictive value 90.7 %). INP was better than LOS at predicting positive nodes in eight patients where INP was >17 mmHg. INP and LOS correlated significantly (p < 0.001). Clinical suspicion of metastasis correlated well with INP particularly at predicting macrometastases. INP was slightly better at predicting micrometastases. Measurement of INP may be valuable adjunct when performing SLN biopsy when further axillary surgery is contemplated.

Intraoperative imprint cytology for evaluation of sentinel lymph nodes from visceral malignancies.

PubMed

Levine, Edward A; Shen, Perry; Shiver, Stephen A; Waters, Gregory; Brant, Andrew; Geisenger, Kim R

2003-01-01

Although originally described for breast cancer and melanoma, sentinel lymph node (SLN) mapping techniques are being investigated in the treatment of visceral malignancies. There is no literature evaluating intraoperative analysis of SLNs from visceral sites. We evaluated the utility of touch preparation intraoperative imprint cytology (IIC) in evaluating SLNs harvested in the setting of visceral malignancy. SLN mapping procedures involving 50 cases of visceral malignancy (37 colon, 12 gastric, and 1 small bowel), from February 1999 through August 2001, were studied. In each case, subserosal injections of isosulfan blue were used to identify the SLN. The SLNs were then sent fresh to the pathology laboratory for evaluation by IIC. A standard lymphadenectomy was performed in all cases. Postoperatively, the SLNs were evaluated by means of using hematoxylin and eosin staining. If these stains were normal, immunohistochemical analyses using carcinoembryonic antigen and cytokeratin were subsequently performed. SLNs were successfully identified in 46 cases (92%), and a total of 95 SLNs were harvested. The average number of SLNs was 1.9 with a range of one to six. More SLNs were found with gastric than with colonic lesions (2.8 vs. 1.8; P=.017). Evaluable IIC in 41 cases revealed metastatic disease in 10 SLNs, representing seven patients. Of the 34 patients with normal IIC, five were found to have positive SLNs on hematoxylin and eosin staining. An additional three patients were found to have positive SLNs only on immunohistochemical analysis. The overall sensitivity and specificity of IIC was 64% and 100%, respectively. This resulted in a positive predictive value of 100% and a negative predictive value of 86%. The use of IIC to evaluate SLNs from visceral malignancies is clearly feasible. When the IIC of the SLN is positive, the surgeon may feel confident that disease is actually present in the SLN. If there is a negative result, the technique may miss disease that is

Validation of the prognostic value of lymph node ratio in patients with cutaneous melanoma: a population-based study of 8,177 cases.

PubMed

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo Riccardo; Nitti, Donato

2011-07-01

The proportion of positive among examined lymph nodes (lymph node ratio [LNR]) has been recently proposed as an useful and easy-to-calculate prognostic factor for patients with cutaneous melanoma. However, its independence from the standard prognostic system TNM has not been formally proven in a large series of patients. Patients with histologically proven cutaneous melanoma were identified from the Surveillance Epidemiology End Results database. Disease-specific survival was the clinical outcome of interest. The prognostic ability of conventional factors and LNR was assessed by multivariable survival analysis using the Cox regression model. Eligible patients (n = 8,177) were diagnosed with melanoma between 1998 and 2006. Among lymph node-positive cases (n = 3,872), most LNR values ranged from 1% to 10% (n = 2,187). In the whole series (≥5 lymph nodes examined) LNR significantly contributed to the Cox model independently of the TNM effect on survival (hazard ratio, 1.28; 95% confidence interval, 1.23-1.32; P < .0001). On subgroup analysis, the significant and independent prognostic value of LNR was confirmed both in patients with ≥10 lymph nodes examined (n = 4,381) and in those with TNM stage III disease (n = 3,658). In all cases, LNR increased the prognostic accuracy of the survival model. In this large series of patients, the LNR independently predicted disease-specific survival, improving the prognostic accuracy of the TNM system. Accordingly, the LNR should be taken into account for the stratification of patients' risk, both in clinical and research settings. Copyright © 2011 Mosby, Inc. All rights reserved.

[The clinical value of sentinel lymph node detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck by methylene blue method and radiolabeled tracer method].

PubMed

Zhao, Xin; Xiao, Dajiang; Ni, Jianming; Zhu, Guochen; Yuan, Yuan; Xu, Ting; Zhang, Yongsheng

2014-11-01

To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by methylene blue method, radiolabeled tracer method and combination of these two methods. Thirty-three patients with cN0 laryngeal carcinoma and six patients with cN0 hypopharyngeal carcinoma underwent SLN detection using both of methylene blue and radiolabeled tracer method. All these patients were accepted received the injection of radioactive isotope 99 Tc(m)-sulfur colloid (SC) and methylene blue into the carcinoma before surgery, then all these patients underwent intraopertive lymphatic mapping with a handheld gamma-detecting probe and blue-dyed SLN. After the mapping of SLN, selected neck dissections and tumor resections were peformed. The results of SLN detection by radiolabeled tracer, dye and combination of both methods were compared. The detection rate of SLN by radiolabeled tracer, methylene blue and combined method were 89.7%, 79.5%, 92.3% respectively. The number of detected SLN was significantly different between radiolabeled tracer method and combined method, and also between methylene blue method and combined method. The detection rate of methylene blue and radiolabeled tracer method were significantly different from combined method (P < 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The accuracy and negative rate of SLN detection of the combined method were 97.2% and 11.1%. The combined method using radiolabeled tracer and methylene blue can improve the detection rate and accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately represent the cervical lymph node status in cN0 laryngeal and hypopharyngeal carcinoma.

Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II*

PubMed Central

Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Giacomo, Thais Helena Bello Di; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel

2016-01-01

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed? PMID:26982779

The use of isotope injections in sentinel node biopsy for breast cancer: are the 1- and 2-day protocols equally effective?

PubMed

Dodia, Nazera; El-Sharief, Deena; Kirwan, Cliona C

2015-01-01

Sentinel lymph nodes are mapped using (99m)Technetium, injected on day of surgery (1-day protocol) or day before (2-day protocol). This retrospective cohort study compares efficacy between the two protocols. Histopathology for all unilateral sentinel lymph node biopsies (March 2012-March 2013) in a single centre were reviewed. Number of sentinel lymph nodes, non-sentinel lymph nodes and pathology was compared. 2/270 (0.7 %) in 1-day protocol and 8/192 (4 %) in 2-day protocol had no sentinel lymph nodes removed (p = 0.02). The median (range) number of sentinel lymph nodes removed per patient was 2 (0-7) and 1 (0-11) in the 1- and 2-day protocols respectively (p = 0.08). There was a trend for removing more non-sentinel lymph nodes in 2-day protocol [1-day: 52/270 (19 %); 2-day: 50/192 (26 %), p = 0.07]. Using 2-day, sentinel lymph node identification failure rate is higher, although within acceptable rates. The 1 and 2 day protocols are both effective, therefore choice of protocol should be driven by patient convenience and hospital efficiency. However, this study raises the possibility that 1-day may be preferable when higher sentinel lymph node count is beneficial, for example following neoadjuvant chemotherapy.

Subungual melanoma of the great toe in a Hispanic male with Down syndrome: a case report and review of the literature.

PubMed

Kwok-Oleksy, Christina; Berenji, Manijeh; Argerakis, Nicholas G; Trepal, Michael; Wallack, Marc K

2012-01-01

Solid mass tumors are not as common as leukemia in individuals with Down syndrome. In this report, we describe the rare case of an adult Hispanic male with Down syndrome who developed advanced subungual melanoma in the hallux. We also describe the course of treatment, which involved hallux amputation along with metastatic work-up and sentinel lymph node biopsy with eventual resection. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer.

PubMed

Andreis, D; Bonardi, S; Allevi, G; Aguggini, S; Gussago, F; Milani, M; Strina, C; Spada, D; Ferrero, G; Ungari, M; Rocca, A; Nanni, O; Roviello, G; Berruti, A; Harris, A L; Fox, S B; Roviello, F; Polom, K; Bottini, A; Generali, D

2016-10-01

Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of same day vs day before pre-operative lymphoscintigraphy for sentinel lymph node biopsy for early breast cancer (local Australian experience).

PubMed

Huang, Yang Yang; Maurel, Amelie; Hamza, Saud; Jackson, Lee; Al-Ogaili, Zeyad

2018-06-01

To assess the impact of delayed vs immediate pre-operative lymphoscintigraphy (LSG) for sentinel lymph node biopsy in a single Australian tertiary breast cancer centre. Retrospective cohort study analysing patients with breast cancer or DCIS who underwent lumpectomy or mastectomy with pre-operative LSG and intra-operative sentinel lymph node biopsy from January 2015 to June 2016. A total of 182 LSG were performed. Group A patients had day before pre-operative LSG mapping (n = 79) and Group B had LSG mapping on the day of surgery (n = 103). The overall LSG localisation rate was 97.3% and no statistical difference was detected between the two groups. The overall sentinel lymph node biopsies (SLN) were identified in 99.6% of patients. The number of nodes excised was slightly higher in Group A (1.90 vs 1.72); however, this was not statistically significant. In addition, the number of nodes on histopathology and the incidence of second echelon nodal detection were also similar between the two groups without statistical significance. In conclusion, the 2-day LSG protocol had no impact on overall SLNB and LSG detection rates although slightly higher second tier nodes but this did not translate to any difference between the number of harvest nodes between the two groups. The 2-day LSG allows for greater flexibility in theatre planning and more efficient use of theatre time. We recommend a dose of 40 Mbq of Tc99 m pertechnetate-labelled colloid be given day prior to surgery within a 24-hour timeframe. © 2017 The Royal Australian and New Zealand College of Radiologists.

Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer.

PubMed

Niikura, Hitoshi; Kaiho-Sakuma, Michiko; Tokunaga, Hideki; Toyoshima, Masafumi; Utsunomiya, Hiroki; Nagase, Satoru; Takano, Tadao; Watanabe, Mika; Ito, Kiyoshi; Yaegashi, Nobuo

2013-11-01

The aim of the present study was to clarify the most effective combination of injected tracer types and injection sites in order to detect sentinel lymph nodes (SLNs) in early endometrial cancer. The study included 100 consecutive patients with endometrial cancer treated at Tohoku University Hospital between June 2001 and December 2012. The procedure for SLN identification entailed either radioisotope (RI) injection into the endometrium during hysteroscopy (55 cases) or direct RI injection into the uterine cervix (45 cases). A combination of blue dye injected into the uterine cervix or uterine body intraoperatively in addition to preoperative RI injection occurred in 69 of 100 cases. All detected SLNs were recorded according to the individual tracer and the resultant staging from this method was compared to the final pathology of lymph node metastases including para-aortic nodes. SLN detection rate was highest (96%) by cervical RI injection; however, no SLNs were detected in para-aortic area. Para-aortic SLNs were detected only by hysteroscopic RI injection (56%). All cases with pelvic lymph node metastases were detected by pelvic SLN biopsy. Isolated positive para-aortic lymph nodes were detected in 3 patients. Bilateral SLN detection rate was high (96%; 26 of 27 cases) by cervical RI injection combined with dye. RI injection into the uterine cervix is highly sensitive in detection of SLN metastasis in early stage endometrial cancer. It is a useful and safe modality when combined with blue dye injection into the uterine body. © 2013.

The efficacy of sentinel lymph node mapping with indocyanine green in cervical cancer.

PubMed

Kim, Ju-Hyun; Kim, Dae-Yeon; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

2018-03-09

Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive

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

PubMed Central

2013-01-01

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

Additional Nodal Disease Prediction in Breast Cancer with Sentinel Lymph Node Metastasis Based on Clinicopathological Features.

PubMed

Orsaria, Paolo; Caredda, Emanuele; Genova, Federica; Materazzo, Marco; Capuano, Ilaria; Vanni, Gianluca; Granai, Alessandra Vittoria; DE Majo, Adriano; Portarena, Ilaria; Sileri, Pierpaolo; Petrella, Giuseppe; Palombi, Leonardo; Buonomo, Oreste Claudio

2018-04-01

The standard-of-care in breast cancer (BC) with positive sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND); however, almost half of such cases have no further tumor burden. This study aimed to assess the clinicopathological factors that predict non-SLN metastasis to define subgroups of SLN-positive patients in whom the axilla may be staged by SLN biopsy alone, while avoiding unnecessary overtreatment. The records of 191 patients with histologically-proven primary BC who underwent a positive (SLN) biopsy between 2005 and 2017 were reviewed. Patients with at least one tumor-involved SLN who underwent completion ALND were enrolled. Demographic and clinicopathological characteristics, including age, primary tumor size and histological grade, lymphovascular invasion, ratio of positive SLNs to the harvested SLNs, SLN metastasis size, and molecular subtype classification according to immunohistochemical biomarker status [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], were evaluated. Data were collected retrospectively and analyzed using the Mann-Whitney and Chi-square tests (statistical significance: p<0.05). The incidence of non-SLN metastasis associated with positive SLN was 48.6% (93/191). The risk of additional nodal spread correlated with high sentinel nodal ratio >0.67 [odds ratio (OR)=2.55, p=0.032], luminal BC subtype (OR=2.67, p=0.06), HER2 overexpression (OR=0.4, p=0.016), and ER + PR - HER2 - profile (OR=2.95, p=0.027). There was a tendency (statistically insignificant; p>0.05) toward higher incidence of non SLN metastasis with increasing age and histological grade, which could be attributed to the small sample size. According to this study, sentinel nodal ratio and BC subtypes as per ER, PR, and HER2 status significantly predicted the likelihood of additional lymphatic involvement. Validation of these parameters in prospective studies is indicated, and may

Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

PubMed

Aubuchon, M M F; Bolt, L J J; Janssen-Heijnen, M L G; Verleisdonk-Bolhaar, S T H P; van Marion, A; van Berlo, C L H

2017-02-01

Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue.

PubMed

Niikura, Hitoshi; Okamura, Chikako; Akahira, Junichi; Takano, Tadao; Ito, Kiyoshi; Okamura, Kunihiro; Yaegashi, Nobuo

2004-08-01

The purpose of this study was to examine sentinel lymph node (SLN) detection in patients with early stage cervical cancer using (99m)Tc phytate and patent blue dye and to compare our method with published findings utilizing other radioisotopic tracers. A total of 20 consecutive patients with cervical cancer scheduled for radical hysterectomy and total pelvic lymphadenectomy at our hospital underwent SLN detection study. The day before surgery, lymphoscintigraphy was performed with injection of 99m-technetium ((99m)Tc)-labeled phytate into the uterine cervix. At surgery, patients underwent lymphatic mapping with a gamma-detecting probe and patent blue injected into the same points as the phytate solution. At least one positive node was detected in 18 patients (90%). A total of 46 sentinel nodes were detected (mean, 2.3; range, 1-5). Most sentinel nodes were in one of the following sites: external iliac (21 nodes), obturator (15 nodes), and parametrial (7 nodes). Eleven (24%) sentinel nodes were detected only through radioactivity and two (4%) were detected only with blue dye. The sensitivity, specificity, and negative predictive value for SLN detection were all 100%. Nine published studies involving 295 patients had a summarized detection rate of 85%. Summarized sensitivity, specificity, and negative predictive value were 93%, 100%, and 99%, respectively. Combination of (99m)Tc phytate and patent blue is effective in SLN detection in early stage cervical cancer.

What Is a False Negative Sentinel Node Biopsy: Definition, Reasons and Ways to Minimize It?

PubMed

Kataria, Kamal; Srivastava, Anurag; Qaiser, Darakhshan

2016-10-01

Sentinel node biopsy helps in assessing the involvement of axillary lymph node without the morbidity of full axillary lymph node dissection, namely arm and shoulder pain, paraesthesia and lymphoedema. The various methods described in the literature identify the sentinel lymph nodes in approximately 96 % of cases and associated with a false negativity rate of 5 to 10 %. A false negative sentinel node is defined as the proportion of cases in whom sentinel node biopsy is reported as negative, but the rest of axillary lymph node(s) harbours cancer cells. The possible causes of a false negative sentinel lymph node may be because of blocked lymphatics either by cancer cells or following fibrosis of previous surgery/radiotherapy, and an alternative pathway opens draining the blue dye or isotope to another uninvolved node . The other reasons may be two lymphatic pathways for a tumour area, the one opening to a superficial node and the other in deep nodes. Sometimes, lymphatics do not relay into a node but traverse it going to a higher node. In some patients, the microscopic focus of metastasis inside a lymph node is so small-micrometastasis (i.e. between 0.2 and 2 mm) or isolated tumour cells (i.e. less than 0.2 mm) that is missed by the pathologist. The purpose of this review is to clear some fears lurking in the mind of most surgeons about the false negative sentinel lymph node (FNSLN).

Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

PubMed

Christianson, Dawn R; Dobroff, Andrey S; Proneth, Bettina; Zurita, Amado J; Salameh, Ahmad; Dondossola, Eleonora; Makino, Jun; Bologa, Cristian G; Smith, Tracey L; Yao, Virginia J; Calderone, Tiffany L; O'Connell, David J; Oprea, Tudor I; Kataoka, Kazunori; Cahill, Dolores J; Gershenwald, Jeffrey E; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2015-02-24

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

Are We Cutting Enough? A Five-Year Audit of Melanoma Excision Margins in the South East of Ireland.

PubMed

Cronin, Catherine Tracy; Allen, Jack; Patterson, Ken; O'Donoghue, Gerrard

2018-01-05

Malignant melanoma is the fifth commonest invasive cancer in Ireland. The British Association of Dermatology (BAD) guidelines are currently the recognized standard for melanoma related surgery. The aim was to examine adherence to BAD guidelines and establish contributing factors resulting in non-adherence to guidelines in a group of melanoma patients in the South East Region of Ireland. A retrospective review of a prospectively maintained melanoma registry of all patients undergoing surgery in the South East Region of Ireland from January 2011 to 2016 was performed. Data were analyzed using SPSS statistical software. Univariate analysis using logistic regression was performed to examine factors associated with not meeting the BAD margin excision guidelines Data with a p < 0.05 was analyzed using a multivariate logistic regression model. 459 patients underwent surgery for invasive cutaneous melanoma. 314 (68.4%) surgeries had excision margins adequately recorded and of these 234(74.5%) fulfilled the BAD guidelines. 267(58.2%) patients (2011-2016 inclusive) qualified for sentinel lymph node biopsy (SNLB) with a cancer staging of pT1b or higher. Of these patients 100(37%) agreed to proceed to a SNLB following informed discussion. 33 had a positive sentinel node. On multivariate analysis inadequate margins were independently associated with tumor thickness 2.01-4.00 mm (p = 0.0001) and >4.00 mm (p = 0.0001) and head and neck location (p < 0.0001). Adherence to BAD guidelines in the South East is good but requires optimization since centralization of melanoma treatment in 2013 to a single specialized center. It is important that Clinicians are fully aware of the implications of not achieving adequate excision margins in surgery. Improvements in melanoma data management is needed to fully evaluate current practices in Ireland.

Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study.

PubMed

Kogashiwa, Yasunao; Sakurai, Hiroyuki; Akimoto, Yoshihiro; Sato, Dai; Ikeda, Tetsuya; Matsumoto, Yoshifumi; Moro, Yorihisa; Kimura, Toru; Hamanoue, Yasuhiro; Nakamura, Takehiro; Yamauchi, Koichi; Saito, Koichiro; Sugasawa, Masashi; Kohno, Naoyuki

2015-01-01

Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models. This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted.

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

PubMed Central

Emerson, Derek K.; Limmer, Karl K.; Hall, David J.; Han, Sung-Ho; Eckelman, William C.; Kane, Christopher J.; Wallace, Anne M.

2012-01-01

Purpose: To determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection. Materials and Methods: The animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m (99mTc) -labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of 99mTc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of 99mTc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student t test. Results: In vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L ± 0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6 × 103 counts · sec−1 · μW−1 per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (P = .005 to P = .042) in the low-dose group than in the high-dose group; this finding was consistent with

Distribution of Prostate Sentinel Nodes: A SPECT-Derived Anatomic Atlas

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

Ganswindt, Ute, E-mail: ute.ganswindt@med.uni-muenchen.d; Schilling, David; Mueller, Arndt-Christian

2011-04-01

Purpose: The randomized Radiation Therapy Oncology Group 94-13 trial revealed that coverage of the pelvic lymph nodes in high-risk prostate cancer confers an advantage (progression-free survival and biochemical failure) in patients with {>=}15% risk of lymph node involvement. To facilitate an improved definition of the adjuvant target volume, precise knowledge regarding the location of the relevant lymph nodes is necessary. Therefore, we generated a three-dimensional sentinel lymph node atlas. Methods and Materials: In 61 patients with high-risk prostate cancer, a three-dimensional visualization of sentinel lymph nodes was performed using a single photon emission computed tomography system after transrectal intraprostatic injectionmore » of 150 to 362 (median 295) mega becquerel (MBq) {sup 99m}Technetium-nanocolloid (1.5-3h after injection) followed by an anatomic functional image fusion. Results: In all, 324 sentinel nodes in 59 of 61 patients (96.7%) were detected, with 0 to 13 nodes per patient (median 5, mean 5.3). The anatomic distribution of the sentinel nodes was as follows: external iliac 34.3%, internal iliac 17.9%, common iliac 12.7%, sacral 8.6%, perirectal 6.2%, left paraaortic 5.3%, right paraaortic 5.3%, seminal vesicle lymphatic plexus 3.1%, deep inguinal 1.5%, superior rectal 1.2%, internal pudendal 1.2%, perivesical 0.9%, inferior rectal 0.9%, retroaortic 0.3%, superficial inguinal 0.3%, and periprostatic 0.3%. Conclusions: The distribution of sentinel nodes as detected by single photon emission computed tomography imaging correlates well with the distribution determined by intraoperative gamma probe detection. A lower detection rate of sentinels in close proximity to the bladder and seminal vesicles is probably caused by the radionuclide accumulation in the bladder. In regard to intensity-modulated radiotherapy techniques, the presented anatomic atlas may allow optimized target volume definitions.« less

Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential

PubMed Central

Robles, Francisco E.; Deb, Sanghamitra; Wilson, Jesse W.; Gainey, Christina S.; Selim, M. Angelica; Mosca, Paul J.; Tyler, Douglas S.; Fischer, Martin C.; Warren, Warren S.

2015-01-01

Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pump-probe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct “dusty” quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas. PMID:26417529

Recognition of sentinel lymph nodes in patients with papillary thyroid cancer by nano-carbon and methylene blue.

PubMed

Liu, Fangzhou; Zhu, Yan; Qian, Yichuan; Zhang, Jia; Zhang, Yu; Zhang, Yuan

2017-01-01

To compare the accuracy and feasibility of methylene blue and nano-carbon in clinical tracing of sentinel lymph nodes (SLNs) in patients with papillary thyroid cancer (PTC). Ninety-six PTC patients were selected and randomly divided into a methylene blue group and a nano-carbon group (n=48). During surgery, tracer agent was injected around the tumor, and SLNs were resected and subjected to frozen pathological examination. The results were compared with those of routine pathological examination after surgery. Latent lymph node metastasis (level VI and lateral neck) was detected in both groups, with neck distribution of SLNs. There was no significant difference in the detection rate or accuracy of SLNs between two groups (P>0.05). The incorrect resection rate of parathyroid gland and incidence of temporary hypoparathyroidism in the methylene blue group were significantly higher than those of the nano-carbon group (t=4.137, P<0.05). The state of PTC lymph nodes can be well evaluated by SLN biopsy using both methylene blue and nano-carbon as tracers, but using nano-carbon has a lower incidence rate of parathyroid injury, with great clinical prospects accordingly.

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

PubMed

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

2017-04-01

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

Pregnancy and melanoma: a European-wide survey to assess current management and a critical literature overview.

PubMed

Ribero, S; Longo, C; Dika, E; Fortes, C; Pasquali, S; Nagore, E; Glass, D; Robert, C; Eggermont, A M; Testori, A; Quaglino, P; Nathan, P; Argenziano, G; Puig, S; Bataille, V

2017-01-01

Management of melanoma during pregnancy can be extremely challenging. The reported incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of melanoma during pregnancy. The survey was designed to investigate the opinions of melanoma physicians on decision making in relation to pregnancy and melanoma. A clinical scenario-based survey on management of pregnancy in melanoma was distributed all over Europe via the membership of the EORTC and other European melanoma societies. A total of 290 questionnaires were returned with a larger participation from southern Europe. A large heterogeneity was found for the answers given in the different clinical scenarios with 50% of the answers showing discordance, especially regarding sentinel lymph node biopsy during pregnancy. Discordant answers were also found for the counselling of women about a potential delay in getting pregnant after a high-risk melanoma (35% for a 2 year wait minimum vs. 57% no waiting needed), while for thin melanomas, as expected, there was more concordance with 70% of the physicians recommending no delay. Fifteen per cent of physicians recommended an abortion in stage II melanoma during the third month of pregnancy. Twenty per cent of the responders advised against hormonal replacement therapy in melanoma patients. The management of melanoma during pregnancy varies widely in Europe. At present, there is a lack of consensus in Europe, which may lead to very important decisions in women with melanoma, and guidelines are needed. © 2016 European Academy of Dermatology and Venereology.

History, present status and future of sentinel node biopsy in breast cancer. The Mary Béves Lecture.

PubMed

Mansel, R E; Khonji, N I; Clarke, D

2000-01-01

The word Sentinel' is defined in The Oxford English Dictionary as 'a guard, one who keeps watch or a sentry'. When translated to the concept of a tumour and its lymph node drainage, the sentinel node could be interpreted to mean the lymph node that guards or keeps watch over a tumour. The sentinel lymph node can thus be defined as the first lymph node that drains a primary tumour within the regional lymphatic basin of that tumour. We know that tumour progression in breast cancer often occurs in an orderly, progressive fashion. So in theory, if the sentinel node is tumour free then the rest of the nodes in the lymphatic basin should also be uninvolved by the tumour.

Sentinel Lymphadenectomy in Vulvar Cancer Using Near-Infrared Fluorescence From Indocyanine Green Compared With Technetium 99m Nanocolloid.

PubMed

Soergel, Philipp; Hertel, Hermann; Nacke, Anna Kaarina; Klapdor, Rüdiger; Derlin, Thorsten; Hillemanns, Peter

2017-05-01

Nowadays, sentinel diagnostic is performed using technetium 99m (Tc) nanocolloid as a radioactive marker and sometimes patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule that emits a light signal in the near-infrared band after excitation. Our study aimed to evaluate indocyanine green compared with the criterion-standard Tc-nanocolloid. We included patients with primary, unifocal vulvar cancer of less than 4 cm with clinically node-negative groins in this prospective trial. Sentinel diagnostic was carried out using Tc-nanocolloid, indocyanine green, and patent blue. We examined each groin for light signals from the near-infrared band, for radioactivity, and for blue staining. A sentinel lymph node was defined as a Tc-nanocolloid-positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested and then sent for histologic examination. In all, 27 patients were included in whom we found 91 sentinel lymph nodes in 52 groins. All these lymph nodes were positive for indocyanine green, also giving a sensitivity of 100% (95% confidence interval [CI], 96.0%-100%) compared with Tc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no Tc positivity, so that the positive predictive value was 91.9% (95% confidence interval, 84.6%-96.5%). In 1 patient, a false-negative sentinel missed by all 3 modalities was found. Our results show that indocyanine green is a promising approach for inguinal sentinel identification in vulvar cancer with a similar sensitivity as radioactive Tc-nanocolloid and worth to be evaluated in further studies.

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

PubMed

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

2005-05-01

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

Triple assessment of sentinel lymph node metastasis in early breast cancer using preoperative CTLG, intraoperative fluorescence navigation and OSNA.

PubMed

Mokhtar, Mohamed; Tadokoro, Yukiko; Nakagawa, Misako; Morimoto, Masami; Takechi, Hirokazu; Kondo, Kazuya; Tangoku, Akira

2016-03-01

Sentinel lymph node biopsy (SLNB) became a standard surgical procedure for patients with early breast cancer; however, the optimal method of sentinel lymph node (SLN) identification remains controversial. The current study presents the protocol of our institution for preoperative and intraoperative SLN detection. Fifty female patients with early breast cancer and clinically node-negative axilla were enrolled in this study. All patients underwent preoperative CT lymphography (CTLG), intraoperative SLNB using fluorescence navigation, intraoperative one-step nucleic acid amplification (OSNA) and postoperative hematoxylin and eosin histopathological analysis. Prediction of metastasis by CTLG and detection of metastasis by OSNA were compared to results of histopathology as standard reference. SLN were identified by preoperative CTLG and intraoperative SLNB with fluorescence navigation in all patients, the identification rate was 100 %. SLN metastases were detected as positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I). SLN metastases were detected as positive by histopathology in 10 patients (20 %). The concordance rate between OSNA and permanent sections was 90 %. The negative predictive value of CTLG was 80 %. Use of CTLG and fluorescence navigation made performing SLNB with high accuracy possible in institutions that cannot use the radioisotope method. OSNA provided accurate intraoperative method, allowing for completion of axillary node dissection during surgery and avoidance of second surgical procedure in patients with positive SLNs, thereby reducing patient distress and, finally, saving hospital costs.

A study on uterine lymphatic anatomy for standardization of pelvic sentinel lymph node detection in endometrial cancer.

PubMed

Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Arechvo, Anastasija; Persson, Jan

2017-05-01

To describe the anatomy of uterine lymphatic drainage following cervical or fundal tracer injection to enable standardization of a pelvic sentinel lymph node (SLN) concept in endometrial cancer (EC). A prospective consecutive study of women with EC was conducted. A fluorescent dye (Indocyanine green) was injected into the cervix (n=60) or the uterine fundus (n=30). A systematic trans- and retroperitoneal mapping of uterine lymphatic drainage was performed. Positions of the pelvic SLNs, defined by afferent lymph vessels, and lymph node metastases were compared. Two consistent lymphatic pathways with pelvic SLNs were identified irrespective of injection site; an upper paracervical pathway (UPP) with draining medial external and/or obturator lymph nodes and a lower paracervical pathway (LPP) with draining internal iliac and/or presacral lymph nodes. Bilateral display of at least one pelvic pathway following cervical and fundal injection occurred in 98% and 80% respectively (p=0.005). Bilateral display of both pelvic pathways occurred in 30% and 20% respectively (p=0.6) as the LPP was less often displayed. Nearly one third of the 19% node positive patients had metastases along the LPP. No false negative SLNs were identified. Based on uterine lymphatic anatomy a bilateral detection of at least one SLN in both the UPP and LPP should be aimed for. Absence of display of the LPP may warrant a full presacral lymphadenectomy. Although pelvic pathways and positions of SLNs are independent of the tracer injection site, cervical injection is preferable due to a higher technical success rate. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel Indocyanine Green-Phytate Colloid Technique for Sentinel Node Detection in Head and Neck: Mouse Study.

PubMed

Araki, Koji; Mizokami, Daisuke; Tomifuji, Masayuki; Yamashita, Taku; Ohnuki, Kazunobu; Umeda, Izumi O; Fujii, Hirofumi; Kosuda, Shigeru; Shiotani, Akihiro

2014-08-01

Sentinel node navigation surgery using real-time, near-infrared imaging with indocyanine green is becoming popular by allowing head and neck surgeons to avoid unnecessary neck dissection. The major drawback of this method is its quick migration through the lymphatics, limiting the diagnostic time window and undesirable detection of downstream nodes. We resolved this problem by mixing indocyanine green (ICG) with phytate colloid to retard its migration and demonstrated its feasibility in a nude mouse study. Experimental prospective animal study. Animal laboratory. Indocyanine green at 3 concentrations was tested to determine the optimal concentration for sentinel lymph node detection in a mouse model. Effect of indocyanine green with phytate colloid mixture solutions was also analyzed. Indocyanine green or mixture solution at different mixing ratios were injected into the tongue of nude mice and near-infrared fluorescence images were captured sequentially for up to 48 hours. The brightness of fluorescence in the sentinel lymph node and lymph nodes further downstream were assessed. Indocyanine green concentration >50 μg/mL did not improve sentinel lymph node detection. The addition of phytate colloid to indocyanine green extended the period when sentinel lymph node was detectable. Second echelon lymph nodes were not imaged in mice injected with the mixture, while these were visualized in mice injected with indocyanine green alone. This novel technique of ICG-phytate colloid mixture allows prolonged diagnostic time window, prevention of downstream subsequent nodes detection, and improved accuracy for the detection of true sentinel lymph nodes. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Intraoperative analysis of sentinel lymph nodes by imprint cytology for cancer of the breast.

PubMed

Shiver, Stephen A; Creager, Andrew J; Geisinger, Kim; Perrier, Nancy D; Shen, Perry; Levine, Edward A

2002-11-01

The utilization of lymphatic mapping techniques for breast carcinoma has made intraoperative evaluation of sentinel lymph nodes (SLN) attractive, because axillary lymph node dissection can be performed during the initial surgery if the SLN is positive. The optimal technique for rapid SLN assessment has not been determined. Both frozen sectioning and imprint cytology are used for rapid intraoperative SLN evaluation. A retrospective review of the intraoperative imprint cytology results of 133 SLN mapping procedures from 132 breast carcinoma patients was performed. SLN were evaluated intraoperatively by bisecting the lymph node and making imprints of each cut surface. Imprints were stained with hematoxylin and eosin (H&E) and Diff-Quik. Permanent sections were evaluated with up to four H&E stained levels and cytokeratin immunohistochemistry. Imprint cytology results were compared with final histologic results. Sensitivity and specificity of imprint cytology were 56% and 100%, respectively, producing a 100% positive predictive value and 88% negative predictive value. Imprint cytology was significantly more sensitive for macrometastasis than micrometastasis 87% versus 22% (P = 0.00007). Of 13 total false negatives, 11 were found to be due to sampling error and 2 due to errors in intraoperative interpretation. Both intraoperative interpretation errors involved a diagnosis of lobular breast carcinoma. The sensitivity and specificity of imprint cytology are similar to that of frozen section evaluation. Imprint cytology is therefore a viable alternative to frozen sectioning when intraoperative evaluation is required. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection.

PubMed

Martínez-Palones, José M; Gil-Moreno, Antonio; Pérez-Benavente, María A; Roca, Isabel; Xercavins, Jordi

2004-03-01

We investigated the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled human serum albumin and isosulfan blue dye injection in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between September 2000 and October 2002, 25 patients with cervical cancer FIGO stage I (n=24) or stage II (n=1) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (technetium-99m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with blue dye and a handheld or laparoscopic gamma probe. Complete pelvic or paraaortic lymphadenectomy was performed in all cases by open surgery or laparoscopic surgery. In 23 evaluable patients, a total of 51 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.21 nodes per patient). Intraoperatively, 61 sentinel lymph nodes were identified, with a mean of 2.52 nodes per patient by gamma probe and a mean of 1.94 nodes per patient after isosulfan blue injection. Forty percent of sentinel nodes were found in the interiliac region and 25% in the external iliac area. Microscopic nodal metastases (four nodes) were confirmed in 12% of cases. All these lymph nodes were previously detected as sentinel lymph nodes. The remaining 419 nodes after pelvic lymphadenectomy were histologically negative. Sentinel lymph node identification with technetium-99m-labeled nanocolloid combined with blue dye injection is feasible and showed a 100% negative predictive value, and potentially identified women in whom lymph node dissection can be avoided.

Sentinel node detection in cervical cancer with (99m)Tc-phytate.

PubMed

Silva, Lucas B; Silva-Filho, Agnaldo L; Traiman, Paulo; Triginelli, Sérgio A; de Lima, Carla Flávia; Siqueira, Cristiano Ferrari; Barroso, Adelanir; Rossi, Telma Maria F F; Pedrosa, Moises Salgado; Miranda, Dairton; Melo, José Renan Cunha

2005-05-01

The aim of this study was to investigate the feasibility of sentinel lymph node (SLN) identification using radioisotopic lymphatic mapping with technetium-99 m-labeled phytate in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between July 2001 and February 2003, 56 patients with cervical cancer FIGO stage I (n = 53) or stage II (n = 3) underwent sentinel lymph node detection with preoperative lymphoscintigraphy ((99m)Tc-labeled phytate injected into the uterine cervix, at 3, 6, 9, and 12 o'clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and intraoperative lymphatic mapping with a handheld gamma probe. Radical hysterectomy was aborted in three cases because parametrial invasion was found intraoperatively and we performed only sentinel node resection. The remaining 53 patients underwent radical hysterectomy with complete pelvic lymphadenectomy. Sentinel nodes were detected using a handheld gamma-probe and removed for pathological assessment during the abdominal radical hysterectomy and pelvic lymphadenectomy. One or more sentinel nodes were detected in 52 out of 56 eligible patients (92.8%). A total of 120 SLNs were detected by lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively by gamma probe. Forty-four percent of SLNs were found in the external iliac area, 39% in the obturator region, 8.3% in interiliac region, and 6.7% in the common iliac area. Unilateral sentinel nodes were found in thirty-one patients (59%). The remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal metastases were confirmed in 17 (32%) cases. In 10 of these patients, only SLNs had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin were submitted to cytokeratin immunohistochemical analysis. Five (5.1%) micrometastases were identified with this technique. The sensitivity of the sentinel node was 82.3% (CI 95% = 56.6-96.2) and the negative predictive value was 92

Is blue dye still required during sentinel lymph node biopsy for breast cancer?

PubMed

Peek, Mirjam Cl; Kovacs, Tibor; Baker, Rose; Hamed, Hisham; Kothari, Ash; Douek, Michael

2016-01-01

In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates. Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique. A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% ( n = 158/160), with blue dye alone 92.5% ( n = 148/160) and with radioisotope alone 97.5% ( n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients. The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation.

Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials.

PubMed

Faries, Mark B; Han, Dale; Reintgen, Michael; Kerivan, Lauren; Reintgen, Douglas; Caracò, Corrado

2018-05-18

While there is no doubt that regional lymph node metastases are an enormously important factor in melanoma staging and treatment, the biology behind this significance and its precise implications for treatment planning have been a leading controversy in melanoma and other solid tumors for over a century. Recent clinical data, including data from prospective randomized clinical trials have refined our understanding of the process of nodal metastases and the advantages and disadvantages of different clinical management strategies. This review presents two points of view in this debate and discusses the results of new data analyses as well as pivotal clinical trials informing the discussion.

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method.

PubMed

Otsubo, Ryota; Oikawa, Masahiro; Hirakawa, Hiroshi; Shibata, Kenichiro; Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe; Shigematsu, Kazuto; Hatachi, Toshiko; Yano, Hiroshi; Matsumoto, Megumi; Takagi, Katsunori; Tsuchiya, Tomoshi; Tomoshige, Koichi; Nakashima, Masahiro; Taniguchi, Hideki; Omagari, Takeyuki; Itoyanagi, Noriaki; Nagayasu, Takeshi

2014-02-15

We developed an easy, quick and cost-effective detection method for lymph node metastasis called the semi-dry dot-blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody, modifying dot-blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node-negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2-mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis. © 2013 UICC.

Technique for reliable sentinel node biopsy in squamous cell carcinomas of the floor of mouth.

PubMed

Stoeckli, Sandro J; Huebner, Thomas; Huber, Gerhard F; Broglie, Martina A

2016-09-01

Applicability of sentinel node biopsy (SNB) for tumors of the floor of mouth (FOM) is controversial. Prospective evaluation of the accuracy of gamma-probe-guided superselective neck dissection of the preglandular triangle of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative lymphoscintigraphy and single photon emission CT (SPECT)/CT. In total, 22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%) were only detected intraoperatively. In unilateral tumors, 20% were contralateral, and, in midline tumors, 93% showed bilateral level I sentinel lymph nodes. The false-negative rate was 8.3%, the negative predictive value was 96.4%, and the false-omission rate was 3.6%. The ultimate neck control rate, including salvage treatment, was 100%. SNB in FOM can be reliably performed using the presented surgical technique. Level I exploration, bilaterally in midline tumors, is mandatory irrespective of the visualization of sentinel lymph nodes in other levels. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1367-1372, 2016. © 2016 Wiley Periodicals, Inc.

Evaluation of Breast Sentinel Lymph Node Coverage by Standard Radiation Therapy Fields

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

Rabinovitch, Rachel; Ballonoff, Ari; Newman, Francis M.S.

2008-04-01

Background: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. Methods and Materials: A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standardmore » axillary fields in 106 data sets meeting these criteria. Results: The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. Conclusions: Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.« less

Sentinel lymph node detection using methylene blue in patients with early stage cervical cancer.

PubMed

Yuan, Song-Hua; Xiong, Ying; Wei, Mei; Yan, Xiao-Jian; Zhang, Hui-Zhong; Zeng, Yi-Xin; Liang, Li-Zhi

2007-07-01

To evaluate the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer using the low-cost methylene blue dye and to optimize the application procedure. Patients with stage Ib(1)-IIa cervical cancer and subjected to abdominal radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled. Methylene blue, 2-4 ml, was injected into the cervical peritumoral area in 77 cases (4 ml patent blue in the other four cases) 10-360 min before the incision, and surgically removed lymph nodes were examined for the blue lymph nodes that were considered as SLNs. High SLN detection rate was successfully achieved when 4 ml of methylene blue was applied (93.9%, 46/49). Bilaterally SLN detection rate was significantly higher (78.1% vs. 47.1% P=0.027) in cases when the timing of application was more than 60 min before surgery than those with timing no more than 30 min. The blue color of methylene blue-stained SLNs sustained both in vivo and ex vivo, compared with the gradually faded blue color of patent blue that detected in 3 of 4 cases unilaterally. In the total of 112 dissected sides, the most common location of SLNs was the obturator basin (65.2%, 73/112), followed by external iliac area (30.4%, 34/112) and internal iliac area (26.8%, 30/112). Three patients who gave false negative results all had enlarged nodes. Methylene blue is an effective tracer to detect SLNs in patients with early stage cervical cancer. The ideal dose and timing of methylene blue application are 4 ml and 60-90 min prior surgery, respectively.

A pilot study to assess near infrared laparoscopy with indocyanine green (ICG) for intraoperative sentinel lymph node mapping in early colon cancer.

PubMed

Currie, A C; Brigic, A; Thomas-Gibson, S; Suzuki, N; Moorghen, M; Jenkins, J T; Faiz, O D; Kennedy, R H

2017-11-01

Previous attempts at sentinel lymph node (SLN) mapping in colon cancer have been compromised by ineffective tracers and the inclusion of advanced disease. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping in T1/T2 clinically staged colonic malignancy. Consecutive patients with clinical T1/T2 stage colon cancer underwent endoscopic peritumoral submucosal injection of indocyanine green (ICG) for fluorescence detection of SLN using a near-infrared (NIR) camera. All patients underwent laparoscopic complete mesocolic excision surgery. Detection rate and sensitivity of the NIR-ICG technique were the study endpoints. Thirty patients mean age = 68 years [range = 38-80], mean BMI = 26.2 (IQR = 24.7-28.6) were studied. Mesocolic sentinel nodes (median = 3/patient) were detected by fluorescence within the standard resection field in 27/30 patients. Overall, ten patients had lymph node metastases, with one of these patients having a failed SLN procedure. Of the 27 patients with completed SLN mapping, nine patients had histologically positive lymph nodes containing malignancy. 3/9 had positive SLNs with 6 false negatives. In five of these false negative patients, tumours were larger than 35 mm with four also being T3/T4. ICG mapping with NIR fluorescence allowed mesenteric detection of SLNs in clinical T1/T2 stage colonic cancer. CLINICALTRIALS.GOV: ID: NCT01662752. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Fluorescence guided lymph node biopsy in large animals using direct image projection device

NASA Astrophysics Data System (ADS)

Ringhausen, Elizabeth; Wang, Tylon; Pitts, Jonathan; Akers, Walter J.

2016-03-01

The use of fluorescence imaging for aiding oncologic surgery is a fast growing field in biomedical imaging, revolutionizing open and minimally invasive surgery practices. We have designed, constructed, and tested a system for fluorescence image acquisition and direct display on the surgical field for fluorescence guided surgery. The system uses a near-infrared sensitive CMOS camera for image acquisition, a near-infra LED light source for excitation, and DLP digital projector for projection of fluorescence image data onto the operating field in real time. Instrument control was implemented in Matlab for image capture, processing of acquired data and alignment of image parameters with the projected pattern. Accuracy of alignment was evaluated statistically to demonstrate sensitivity to small objects and alignment throughout the imaging field. After verification of accurate alignment, feasibility for clinical application was demonstrated in large animal models of sentinel lymph node biopsy. Indocyanine green was injected subcutaneously in Yorkshire pigs at various locations to model sentinel lymph node biopsy in gynecologic cancers, head and neck cancer, and melanoma. Fluorescence was detected by the camera system during operations and projected onto the imaging field, accurately identifying tissues containing the fluorescent tracer at up to 15 frames per second. Fluorescence information was projected as binary green regions after thresholding and denoising raw intensity data. Promising results with this initial clinical scale prototype provided encouraging results for the feasibility of optical projection of acquired luminescence during open oncologic surgeries.

Beyond the Briganti nomogram: Individualisation of lymphadenectomy using selective sentinel node biopsy during radical prostatectomy for prostate cancer.

PubMed

Monserrat-Monfort, J J; Martinez-Sarmiento, M; Vera-Donoso, C D; Vera-Pinto, V; Sopena-Novales, P; Bello-Arqués, P; Boronat-Tormo, F

To validate the technique of selective sentinel node biopsy for diagnosing and staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. We applied the technique to 45 patients. After an intraprostatic injection of 99m Tc-nanocolloid and preoperative single-photon emission computed tomography (SPECT/CT), we extracted the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. SPECT/CT showed radiotracer deposits outside the eLFD territory in 73% of the patients and the laparoscopic gamma probe in 60%. The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The mean number of extracted sentinel lymph nodes was 4.3 (0-14), with 26% outside the eLFD territory. The lymph nodes were metastatic in 10 patients (22%), 6/40 (15%) when the prostatectomy was the primary treatment. In all cases with metastatic lymph nodes, there was at least one positive sentinel node. Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/10 patients (30%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%. Selective sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement and can avoid eLFD when metastatic sentinel lymph nodes are not found (85%), with the consequent functional advantages. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Photoacoustic sentinel lymph node imaging with self-assembled copper neodecanoate nanoparticles.

PubMed

Pan, Dipanjan; Cai, Xin; Yalaz, Ceren; Senpan, Angana; Omanakuttan, Karthik; Wickline, Samuel A; Wang, Lihong V; Lanza, Gregory M

2012-02-28

Photoacoustic tomography (PAT) is emerging as a novel, hybrid, and non-ionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. PAT combines the advantages of both optical and ultrasonic imaging methods. It opens up the possibilities for noninvasive staging of breast cancer and may replace sentinel lymph node (SLN) biopsy in clinic in the near future. In this work, we demonstrate for the first time that copper can be used as a contrast metal for near-infrared detection of SLN using PAT. A unique strategy is adopted to encapsulate multiple copies of Cu as organically soluble small molecule complexes within a phospholipid-entrapped nanoparticle. The nanoparticles assumed a size of 80-90 nm, which is the optimum hydrodynamic diameter for its distribution throughout the lymphatic systems. These particles provided at least 6-fold higher signal sensitivity in comparison to blood, which is a natural absorber of light. We also demonstrated that high SLN detection sensitivity with PAT can be achieved in a rodent model. This work clearly demonstrates for the first time the potential use of copper as an optical contrast agent.

Implementation of molecular intra-operative assessment of sentinel lymph node in breast cancer.

PubMed

Khaddage, Abir; Berremila, Sid-Ali; Forest, Fabien; Clemenson, Alix; Bouteille, Catherine; Seffert, Pierre; Peoc'h, Michel

2011-02-01

Sentinel lymph node (SLN) biopsy is used as a staging procedure in early breast cancer, however, histology based intra-operative assessment of the SLN status has a low sensitivity. The one-step nucleic acid amplification (OSNA) method was developed to detect metastases by amplification of cytokeratin (CK) 19 mRNA. Experience with OSNA during a French multi-centric prospective study, as well as intra-operative clinical routine use, is reported. For the clinical study 80 SLNs from 46 patients were assessed. During routine use, the central slice of the SLN from 197 patients was investigated by permanent histology and the remainder was assessed by OSNA. During the clinical study, OSNA detected 15/17 metastases, including all the macrometastases, reaching a 96.3% concordance rate, 88.2% sensitivity and 98.4% specificity. During routine use, both OSNA and histology detected 25 patients with metastasis. OSNA is an accurate tool for intra-operative assessment of SLN status and could reduce the need for second surgery.

Laparoscopic sentinel lymph node procedure using a combination of patent blue and radioisotope in women with cervical carcinoma.

PubMed

Barranger, Emmanuel; Grahek, Dany; Cortez, Annie; Talbot, Jean Noel; Uzan, Serge; Darai, Emile

2003-06-15

The authors evaluated the feasibility of a laparoscopic sentinel lymph node (SN) procedure with combined radioisotopic and patent blue labeling in patients with cervical carcinoma. Thirteen women (median age, 52.5 years) with cervical carcinoma (Stage Ia2 in 1 patient, Stage Ib1 in 10 patients, Stage Ib2 in 1 patient, and Stage IIa in 1 patient) underwent a laparoscopic SN procedure using an endoscopic gamma probe after both radioactive isotope and patent blue injections. After the procedure, all patients underwent complete laparoscopic pelvic lymphadenectomy and either laparoscopic radical hysterectomy (eight patients) or the Schauta-Amreich operation (five patients). SNs (mean, 1.7 SNs per patient; range, 1-3 SNs per patient) were identified in 12 of 13 patients. A median of 10.5 pelvic lymph nodes per patient (range, 4-17 pelvic lymph nodes per patient) were removed. No lymph node involvement was detected in SNs with hematoxylin and eosin staining. Immunohistochemical studies identified four metastatic SNs in two patients, with micrometastases in two SNs from the first patient and isolated tumor cells in two SNs from the second patient. No false-negative SN results were obtained. The results of this study suggest that SN detection with a combination of radiocolloid and patent blue is feasible in patients with cervical carcinoma. The combination of laparoscopy and the SN procedure permitted minimally invasive management of early-stage disease. Copyright 2003 American Cancer Society.

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

Radio-guided sentinel lymph node identification by lymphoscintigraphy fused with an anatomical vector profile: clinical applications.

PubMed

Niccoli Asabella, A; Antonica, F; Renna, M A; Rubini, D; Notaristefano, A; Nicoletti, A; Rubini, G

2013-12-01

To develop a method to fuse lymphoscintigraphic images with an adaptable anatomical vector profile and to evaluate its role in the clinical practice. We used Adobe Illustrator CS6 to create different vector profiles, we fused those profiles, using Adobe Photoshop CS6, with lymphoscintigraphic images of the patient. We processed 197 lymphoscintigraphies performed in patients with cutaneous melanomas, breast cancer or delayed lymph drainage. Our models can be adapted to every patient attitude or position and contain different levels of anatomical details ranging from external body profiles to the internal anatomical structures like bones, muscles, vessels, and lymph nodes. If needed, more new anatomical details can be added and embedded in the profile without redrawing them, saving a lot of time. Details can also be easily hidden, allowing the physician to view only relevant information and structures. Fusion times are about 85 s. The diagnostic confidence of the observers increased significantly. The validation process showed a slight shift (mean 4.9 mm). We have created a new, practical, inexpensive digital technique based on commercial software for fusing lymphoscintigraphic images with built-in anatomical reference profiles. It is easily reproducible and does not alter the original scintigraphic image. Our method allows a more meaningful interpretation of lymphoscintigraphies, an easier recognition of the anatomical site and better lymph node dissection planning.

Differential receipt of sentinel lymph node biopsy within practice-based research networks

PubMed Central

Meyer, Anne-Marie; Reeder-Hayes, Katherine E.; Liu, Huan; Wheeler, Stephanie B.; Penn, Dolly; Weiner, Bryan J.; Carpenter, William R.

2013-01-01

Background Provider-based research networks (PBRNs) are promising for accelerating not only research, but also dissemination of research-based evidence into broader community practice. Sentinel lymph node biopsy (SLNB) is an innovation in breast cancer care associated with equivalent survival and lower morbidity, as compared to standard axillary lymph node dissection. We examined the diffusion of SLNB into practice and whether affiliation with the Community Clinical Oncology Program (CCOP), a cancer-focused PBRN, was associated with more rapid uptake of SLNB. Research Design Surveillance Epidemiology and End Results(SEER)-Medicare data were used to study women diagnosed with stage I or II breast cancer in the years 2000 to 2005 and undergoing breast conserving surgery with axillary staging (n=6,226). The primary outcome was undergoing SLNB. CCOP affiliation of the surgical physician was ascertained from NCI records. Multivariable generalized linear modeling with generalized estimating equations was used to measure association between CCOP exposure and undergoing SLNB, controlling for potential confounders. Results Women treated by a CCOP physician had significantly higher odds of receiving SLNB compared to women treated by a non-CCOP physician (OR 2.68; 95% CI 1.35, 5.34). The magnitude of this association was larger than that observed among patients treated by physicians operating in medical school-affiliated hospitals (OR 1.76; 95% CI 1.30–2.39). Conclusion Women treated by CCOP-affiliated physicians were more likely to undergo SLNB irrespective of the hospital’s medical school affiliation, suggesting that the CCOP PBRN may play a role in the rapid adoption of research-based innovation in community practice. PMID:23942221

A critical assessment on the role of sentinel node mapping in endometrial cancer.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Perotto, Stefania; Lorusso, Domenica; Raspagliesi, Francesco

2015-10-01

Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features.

Up-regulation of hnRNP A1, Ezrin, tubulin β-2C and Annexin A1 in sentinel lymph nodes of colorectal cancer

PubMed Central

He, Zhen-Yu; Wen, Hao; Shi, Chuan-Bing; Wang, Jie

2010-01-01

AIM: To investigate the early metastasis-associated proteins in sentinel lymph node micrometastasis (SLNMM) of colorectal cancer (CRC) through comparative proteome. METHODS: Hydrophobic protein samples were extracted from individual-matched normal lymph nodes (NLN) and SLNMM of CRC. Differentially expressed protein spots were detected by two-dimensional electrophoresis and image analysis, and subsequently identified by matrix assisted laser desorption/ionization-time of flight mass spectrometry-mass spectrometry and Western blotting, respectively. RESULTS: Forty proteins were differentially expressed in NLN and SLNMM, and 4 metastasis-concerned proteins highly expressed in SLNMM were identified to be hnRNP A1, Ezrin, tubulin β-2C and Annexin A1. Further immunohistochemistry staining of these four proteins showed their clinicopathological characteristics in lymph node metastasis of CRC. CONCLUSION: Variations of hydrophobic protein expression in NLN and SLNMM of CRC and increased expression of hnRNP A1, Ezrin, tubulin β-2C and Annexin A1 in SLNMM suggest a significantly elevated early CRC metastasis. PMID:20872967

Squamous cell carcinoma of the scrotum in a radiation technologist and the use of sentinel lymph node biopsy in recurrent disease.

PubMed

Shifrin, David A; Lange, Marianne K; Kahnoski, Richard J; Avallone, Anthony N

2007-03-01

Squamous cell carcinoma (SCC) of the scrotum is an uncommon neoplasm. It has been described in many different occupations and is associated with a myriad of carcinogens, yet the etiology still remains a mystery. This is the first report of its occurrence in a radiation technologist. Additionally, the use of sentinel lymph node biopsy in SCC has been advocated as a safe method of limiting the morbidity associated with bilateral ilioinguinal dissections. This is the first report of its use in recurrent metastatic SCC of the scrotum.

Surgeon specialization and use of sentinel lymph node biopsy for breast cancer.

PubMed

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

2014-02-01

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in patients with clinically node-negative breast cancer. It is not known whether SLNB rates differ by surgeon expertise. If surgeons with less breast cancer expertise are less likely to offer SLNB to these patients, this practice pattern could lead to unnecessary axillary lymph node dissections and lymphedema. To explore potential measures of surgical expertise (including a novel objective specialization measure: percentage of a surgeon's operations performed for breast cancer determined from Medicare claims) on the use of SLNB for invasive breast cancer. A population-based prospective cohort study was conducted in California, Florida, and Illinois. Participants included elderly (65-89 years) women identified from Medicare claims as having had incident invasive breast cancer surgery in 2003. Patient, tumor, treatment, and surgeon characteristics were examined. Type of axillary surgery performed. Of 1703 women who received treatment by 863 surgeons, 56.4% underwent an initial SLNB, 37.2% initial axillary lymph node dissection, and 6.3% no axillary surgery. The median annual surgeon Medicare volume of breast cancer cases was 6.0 (range, 1.5-57.0); the median surgeon percentage of breast cancer cases was 4.5% (range, 0.4%-100.0%). After multivariable adjustment of patient and surgeon factors, women operated on by surgeons with higher volumes and percentages of breast cancer cases had a higher likelihood of undergoing SLNB. Specifically, women were most likely to undergo SLNB if the operation was performed by high-volume surgeons (regardless of percentage) or by lower-volume surgeons with a high percentage of breast cancer cases. In addition, membership in the American Society of Breast Surgeons (odds ratio, 1.98; 95% CI, 1.51-2.60) and Society of Surgical Oncology (1.59; 1.09-2.30) were independent predictors of women undergoing an initial SLNB. Patients who receive treatment from surgeons

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. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights

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

Tumor differentiation as related to sentinel lymph node status in gastric cancer

PubMed Central

Lavy, Ron; Kapiev, Andronik; Hershkovitz, Yehuda; Poluksht, Natan; Rabin, Igor; Chikman, Bar; Shapira, Zahar; Wasserman, Ilan; Sandbank, Judith; Halevy, Ariel

2014-01-01

AIM: To investigate the influence of tumor grade on sentinel lymph node (SLN) status in patients with gastric cancer (GC). METHODS: We retrospectively studied 71 patients with GC who underwent SLN mapping during gastric surgery to evaluate the relationship between SLN status and tumor grade. RESULTS: Poorly differentiated tumors were detected in 50/71 patients, while the other 21 patients had moderately differentiated tumors. SLNs were identified in 58/71 patients (82%). In 41 of the 58 patients that were found to have stained nodes (70.7%), the tumor was of the poorly differentiated type (group I), while in the remaining patients with stained nodes 17/58 (29.3%), the tumor was of the moderately differentiated type (group II). Positive SLNs were found in 22/41 patients in group I (53.7%) and in 7/17 patients in group II (41.2%) (P = 0.325). The rate of positivity for the SLNs in the two groups (53.7% vs 41.2%) was not statistically significant (P = 0.514). CONCLUSION: Most of our patients were found to have poorly differentiated adenocarcinoma of the stomach and there was no correlation between tumor grade and SLN involvement. PMID:24627734

Surgeon bias in sentinel lymph node dissection: Do tumor characteristics influence decision making?

PubMed

Robinson, Kristin A; Pockaj, Barbara A; Wasif, Nabil; Kaufman, Katie; Gray, Richard J

2014-12-01

Determining sentinel lymph nodes (SLNs) in breast cancer staging involves subjective interpretation by the surgeon. We hypothesized patient and tumor characteristics influence number of SLNs harvested. A single-institution, prospectively collected database was queried for breast cancer patients undergoing SLN surgery (2002-2013) and mean SLN counts were compared. There were 2394 SLN biopsies. Mean number of SLNs per patient for the entire cohort was 2.6. Mean number of SLNs removed was greater for patients ≤50 years (2.9 versus 2.6; p < 0.0001). Fewer SLNs were removed with tumors ≤1 cm (2.5 versus 2.6; p = 0.002). Patients with grades 2 or 3 tumors had more SLNs removed than grade 1 (2.6 versus 2.5; p = 0.03). Receipt of neoadjuvant therapy was associated with more SLNs removed (3.0 versus 2.6; p = 0.005). Number of SLNs removed varies based on risk factors for SLN metastasis or false-negative SLN biopsy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fluorescence imaging to study cancer burden on lymph nodes

NASA Astrophysics Data System (ADS)

D'Souza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue along with a cancer targeting tracer, Affibody labeled with IRDYE800CW and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

Supine MRI for regional breast radiotherapy: imaging axillary lymph nodes before and after sentinel-node biopsy

NASA Astrophysics Data System (ADS)

van Heijst, Tristan C. F.; Eschbach-Zandbergen, Debora; Hoekstra, Nienke; van Asselen, Bram; Lagendijk, Jan J. W.; Verkooijen, Helena M.; Pijnappel, Ruud M.; de Waard, Stephanie N.; Witkamp, Arjen J.; van Dalen, Thijs; Desirée van den Bongard, H. J. G.; Philippens, Marielle E. P.

2017-08-01

Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p  <  0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible.