To further characterize the micromorphometric immunological pattern to metastatic melanoma in sentinel lymph node (SLN) biopsies and completion lymph node (CLN) dissections and their relation to 5-year overall survival (OS).

Retrospective cohort of 49 patients from 1996 to 2005 with a positive SLN who underwent CLN dissection (CLD) was studied. Micromorphometric characteristics included follicular center count (FCC)/profile, sinus histiocytosis, metastatic size, tumor infiltrating lymphocytes (intranodal), paracortical dendritic cells, germinal center reaction and morphology. Comparison of Kaplan-Meier survival curves used the exact log-rank statistic.

In the high-FCC (n = 5-51) vs the low-FCC (n < 5) lymph nodes, a delayed separation occurred at 3 years, with 5-year OS rates being 73% vs 54% in the high- and low-FCC groups, respectively. Improved survival up to 3 years was also noted in CLDs that showed a higher FCC when compared to the prior SLN. Patients with metastatic deposits >2 mm had significantly lower 5-year survival (both <.001).

Nodal micromorphometric features (ie, FCC) are probably related to host immune response to metastasis. Quantitative evaluation of lymphoid follicular centers could provide valuable prognostic information to help to stratify patients.

In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. (99m)Tc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10(-11)M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), that the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 min to bind more tilmanocept (acting as intracellular "drug compilers" of tilmanocept into non-degraded vesicles), gives serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate (99m)Tc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for imaging approaches. Beyond the elements of imaging applications of these agents is their evolution to therapeutic agents as well, and even in the neo-logical realm of theranostics. Characteristics of agents such as tilmanocept that exploit the natural history of diseases with remarkably high specificity are the expectations for the future of patient- and disease-centered diagnosis and therapy.

We previously developed a method for sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC), based on the magnetic force produced by a magnetite tracer already approved for use as a contrast material for magnetic resonance imaging. However, it is difficult to use that technique with video-assisted thoracic surgery (VATS) because the sensing element of the magnetometer is large and thick. The purpose of the present study was to develop a smaller, thinner VATS-compatible magnetometer.

The tracer employed was Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points around the tumor. The magnetic force within the sampling lymph nodes was measured using the new VATS-compatible magnetometer.

SLNs were detected in 11 (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average number of SLNs identified per patient was 1.8 (range 0-4). No complications related to the SLN detection method were observed.

The new VATS-compatible magnetometer appears to have substantial advantages over techniques using a radioisotope and our earlier magnetometer, as it can be inserted through the small VATS port site.

Development of the sentinel lymph node (SLN) biopsy the last 10 years has changed surgical approach of solid tumor treatment and particularly of melanoma. The aim of our study was to analyze in our hospital, the feasibility of the SLN biopsy technique in order to define a better prognostic classification of melanomas.

Between July 1999 and October 2003, 97 patients were included in this study in our center. Criteria for inclusion were cutaneo-mucosal melanoma of Breslow >or=1,5 mm, and/or Clarck >or=IV, and/or ulceration, and/or signs of regression, before any surgical margins.

Lymphoscintigraphy (LS) identified at least 1 SLN in 94 cases/97 (97%), thus permitting intraoperative SLN mapping and sentinel node biopsy of at least 1 lymph node in 88 cases/94 (94%). Failure of the SLN procedure was noted in 9 cases: in 3 cases, no lymph node was individualized by LS, in 1 patient, intraoperative SLN mapping failed to find the previously identified SLN and in 5 cases, a SLN was identified by LS and intraoperative mapping but could not be removed because of its deep location and difficulty of dissection. In 17 patients, removal of one or two "non sentinel lymph node(s)" was (were) made by the surgeon because of its (their) suspected aspect (black or large). Among the 88 patients who had dissection of at least 1 SLN, a micrometastasis was detected by standard histological evaluation and/or immunohistochemical stains in 14 cases (16%) and into a "non SLN" in 2 cases (2,3%). The median follow up of patients was 16 months (1- 48 months). Among the 14 patients with positive SLN, 6 (43%) relapsed. The other eight were in complete remission of their melanoma with a mean follow up of 11,44 months . Among the 74 patients with negative SLN, 7 (9,5%) developed a recurrence. Among the 9 patients in whom any sentinel lymph node have been removed, 3 had a relapse (one in transit than on lymph nodes, and two on lymph nodes).

Our results are in accordance with the literature, and confirm the feasibility of SLN mapping and of SLN histological analysis in our center. We described in this study technical problems we encountered. Our study also show the prognostic value of this technique. However, advantage in global survey of sentinel node dissection and regional lymph node dissection in cases of micrometastases has still to be demonstrated.

We analyzed the outcomes and factors associated with false-negative (FN) results of sentinel lymph node (SLN) biopsy findings in patients with cutaneous melanoma. SLN biopsy failure rate was defined as nodal recurrence in the biopsied regional basin without previous local or in-transit recurrence.

Between April 1997 and December 2004, a total of 1207 patients with cutaneous melanoma with a median Breslow thickness of 2.4 mm underwent SLN biopsy by preoperative and intraoperative lymphoscintigraphy combined with dye injection. In 228 cases, we found positive SLNs; of these, 220 underwent completion lymph node dissection (CLND). Median follow-up was 3 years.

The SLN biopsy failure rate was 5.8% (57 of 979 SLN negative). Median time to occurrence of FN relapse after SLN biopsy was 16 months (range, 3-74 months). The FN SLN biopsy results correlated with primary tumor thickness >4 mm (P = .0012), primary tumor ulceration (P = .0002), primary tumor level of invasion Clark stage IV/V (P = .0005), and nodular melanoma histological type (P = .0375). Five-year overall survival, calculated from the date of primary tumor excision, in the FN group was 53.7%, which was not statistically significantly worse than the CLND group (56.8%; P = .9). The FN group was characterized by a higher ratio of two or more metastatic nodes and extracapsular involvement of lymph nodes after LND compared with the CLND group (P < .0001 and P < .0001, respectively). Additional detailed pathological review of FN SLN revealed metastatic disease in 14 patients, which decreased the SLN biopsy failure rate to 4.4% (43 of 979).

Survival of patients with FN results of SLN biopsy does not differ statistically significantly from that of patients undergoing CLND, although it is slightly lower. The SLN biopsy failure rate is approximately 5.0% in long-term follow-up and is associated mainly with the same factors that indicate a poor prognosis in primary melanoma.

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.

Lymphatic flux from a primary tumor initially flows into a tumor-draining lymph node (LN), the so-called sentinel LN (SLN). Carried by the lymph fluid are a variety of mediators produced by the tumor that can influence immune responses within the SLN, making it a good model with which to investigate tumor-related immunology. For instance, dendritic cell (DC) numbers are reduced in SLNs from melanoma and breast cancer patients. In the present study, we investigated the mechanism by which DC numbers were reduced within SLNs from patients with non-small cell lung cancer. We found that the incidence of apoptosis among DCs was higher in SLNs than in non-SLNs, as were levels of TGFbeta-1. In contrast, levels of TGFbeta-1 mRNA did not differ between SLNs and non-SLNs, but were 30 times higher in tumors than in either LN type. In vitro, incubation for 2 days with TGFbeta-1 induced apoptosis among both cultured DCs and DCs acutely isolated from normal thoracic LNs, effects that were blocked by the TGFbeta-1 inhibitor DAN/Fc chimera. Taken together, these results suggest that tumor-derived TGFbeta-1 induces immunosuppression within SLNs before the movement of tumor cells into the SLNs, thereby facilitating metastasis within those nodes.

We recently developed a novel method for sentinel lymph node mapping using magnetic force. However, problems with the sterility and sensitivity of the magnetometer made intraoperative sentinel lymph node mapping impossible. The purpose of this study was to test the utility of a new, more sensitive, sterilizable magnetometer developed in our institute for in vivo sentinel lymph node mapping in patients with nonsmall cell lung cancer.

Ferumoxides (magnetite) served as the tracer. Twenty patients with nonsmall cell lung cancer participated in the study. Each received 5 mL of ferumoxides, which were injected around their tumor. Magnetic force was then measured intraoperatively using the new sterilizable magnetometer.

The in vivo sentinel lymph node detection rate was 80.0% (16 of 20). The accuracy, sensitivity, and false-negative rates were 100% (16 of 16), 100% (4 of 4) and 0% (0 of 12), respectively. Our preliminary study indicates that our new magnetometer enables in vivo sentinel lymph node mapping in patients with nonsmall cell lung cancer.

This device safely and accurately detected sentinel lymph nodes in nonsmall cell lung cancer patients.

The diagnostic usefulness of sentinel lymph node biopsy (SLNB) has been well established, but its therapeutic value remains unproven. First introduced by Morton and colleagues, the SLNB procedure is now widely available, and markedly enhances our ability to pathologically stage the regional nodes. Although the SLN status is acknowledged as the most powerful indicator of prognosis in melanoma, there is no evidence to-date, of survival advantage for complete lymphadenectomy in SLN-positive patients. Also, there is no effective adjuvant therapy that could benefit these sentinel node-positive patients, as yet. Additionally, new data have emerged indicating a possible increase in local/in-transit recurrence following complete lymphadenectomy in sentinel node-positive patients. To understand fully and to evaluate these observations we need information from randomized controlled trials. Major changes have occurred following the latest revision of melanoma staging system (AJCC, 6th edition). Concerning N category, these include the incorporation of the number of metastatic lymph nodes, the tumour burden of nodal metastases, and the ulceration of the primary tumour. The data obtained from the new staging system will reflect differences in prognosis that were not previously emphasized and which, we hope, will serve as a guide to more accurate analysis of metastatic pathways in cutaneous melanoma as well as a rationale for new forms of treatment.

Melanoma is a malignant tumor, with dominant lymphatic extension. Sentinel lymph node is the first lymph node touched by melanoma. Our retrospective and monocentric study is about 87 patients, between July 1999 and July 2003. The inclusion criteria were malignant melanoma with Breslow level superior or equal 1.5 mm, and/or Clark level superior or equal IV, and/or ulcerated, and/or in regression. Sentinel lymph node has been negative on histological analysis in 75 patients (86.2%). About these 75 patients, we found five metastatic lymph node recurrence (6.66%) in a short notice (median 10.2 months). For the five patients with recurrence, the original slides and tissue blocks were available for reexamination. Then, we found micrometastasis in two patients (40% of occult metastasis). Our rate of lymph node recurrence in patients with sentinel lymph node negative is about 6.66%. Our analysis make us believe that early recurrence are essentially linked to histological analysis limits, and maybe to skip metastasis existence.

To date, selective sentinel lymphadenectomy (SSL) should be considered a standard approach for staging patients with primary invasive melanoma greater than or equal to 1 mm. It is imperative that the multidisciplinary team master the techniques of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and postoperative pathologic evaluation of the sentinel lymph nodes (SLNs). An SLN is defined as a blue, "hot" and any subsequent lymph node greater than 10% of the ex vivo count of the hottest lymph node. Any enlarged or indurated lymph node in the nodal basin should be excised. Frozen sections are not recommended. For extremity melanoma, delayed SSL may be performed. Preoperative lymphoscintigraphy for extremity melanoma may be done the night before so that the surgery can be scheduled as the first case of the following day. Every surgeon who uses blue dye should be aware of the potential adverse reaction to isosulfan blue and treatment for such a potential fatal reaction. A complete lymph node dissection is done if the SLN is found to be positive. Elective lymph node dissection (ELND) should not be done if an SSL can be performed as a staging procedure. SSL has further been applied to stage the nodal basin for Merkel cell carcinoma and high-risk squamous cell carcinoma. It is important for investigators involved with the SSL to follow the clinical outcome of these patients, so that the role of SSL can be further defined.

We report the first case of detection of sentinel node in a 54 year-old woman presenting an adenocarcinoma of Bartholin's gland. Primary carcinoma of Bartholin's gland is rare and represents 2-7% of vulvar malignant lesions; this could explain the lack of consensus about treatment. The best attitude could be vulvectomy and inguinal lymphadenectomy. Pelvic lymphadenectomy is not required when no pelvic sentinel node is observed or when no metastatic inguinal node can be detected.

The introduction of sentinel lymph node biopsy (SLNB) has been an important development in the management of malignant melanoma. Lymph nodes have long been known to play a key role in melanoma metastasis. The importance of nodal staging accounted for the previous surgical practice of elective lymph node dissection (ELND) even with its controversial impact on final outcomes and associated morbidity. Although this morbidity has been reduced with the ability to identify the SLN, numerous questions have subsequently surfaced with respect to this procedure's utility and therapeutic efficacy. This chapter will focus on the indications for SLNB, as well as the current controversies surrounding this procedure.

Childhood and adolescent melanoma is rare, accounting for only 1.3% for all cases of cancer in patients under the age of 20 years. However, in 15-19 year olds, melanoma accounts for up to 7% of all cancers. Review of reported cases in this age group reveals that predisposing 'paediatric' conditions such as a giant congenital melanocytic naevi or xeroderma pigmentosum are rarely present. Furthermore, inactivating germ-line mutations of the gene CDKN2A have only been reported in 1.5% of cases of early onset melanoma. Epidemiological studies suggest that interactions between solar exposure, development of naevi, pigmentary traits, and a family history of melanoma are the main determinants of melanoma development during the first 20 years of life. As yet, there are no available staging or treatment strategies for this group of patients so treatment recommendations are based on the adult experience. To improve our understanding of the natural history of melanoma and to identify the most appropriate therapies for young patients with this disease, practising physicians are encouraged to enroll their patients, especially those with advanced stage disease, in cooperative group trials which incorporate newer staging systems and promising therapies.

The detection rate of sentinel lymph nodes in patients with non-small cell lung cancer using isosulfan blue dye is too low for clinical use. Although exposure to radioactivity is reportedly minimal, special procedures are nonetheless required when a radioactive isotope is used as a tracer. Therefore, to eliminate the need for a radioactive tracer and to obtain a better detection rate than is obtained with isosulfan blue dye, we have developed a novel method that employs magnetite as the tracer. The aim of the present study was to test the feasibility of this technique.

The tracer employed was ferumoxides, a colloidal superparamagnetic iron oxide of nonstoichiometric magnetite. Thirty-eight non-small cell lung cancer patients participated in the study; each received 5 mL of ferumoxides, injected around the tumor intraoperatively. Fifteen minutes after injection, lung resection and lymph node dissection were carried out. The magnetic force within the lymph nodes was measured using a highly sensitive handheld magnetometer ex vivo. All lymph nodes were also subjected to conventional histological analysis.

The rate of detection of sentinel lymph nodes was 81.6% (31/38). The accuracy, sensitivity, and false-negative rates were 96.8% (30/31), 85.7% (6/7), and 14.3% (1/7), respectively.

Intraoperative sentinel lymph node mapping using ferumoxides and a highly sensitive magnetometer is a safe, accurate, and sensitive way to detect sentinel lymph nodes in non-small cell lung cancer patients.

To date, selective sentinel lymphadenectomy (SSL) should be considered a standard approach for staging patients with primary invasive melanoma greater than or equal to 1 mm. It is imperative that the multidisciplinary team master the techniques of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and postoperative pathologic evaluation of the sentinel lymph nodes (SLNs). A SLN is defined as a blue, "hot", or any subsequent lymph node greater than 10% of the in vivo count of the hottest lymph node and as an enlarged or indurated lymph node. Frozen sections are not recommended. For extremity melanoma, delayed SSL may be performed. Preoperative lymphoscintigraphy for extremity melanoma may be done the night before so that surgery can be scheduled as the first case of the following day. Every surgeon who uses blue dye should be cognizant of the potential adverse reaction to isosulfan blue and treatment for such a potential fatal reaction. A complete lymph node dissection is done if the SLN is found to be positive. Elective lymph node dissection should not be done if SSL can be done as a staging procedure. It is important for investigators involved with SSL to follow the clinical outcome of their patients so that the role of SSL can be further defined.