Biomedical subjects

J E Gershenwald

Publications and source records attributed to J E Gershenwald.

At least 19 recordsLinked to original sources

PubMed2003

Epidermal hyperplasia overlying human melanoma correlates with tumour depth and angiogenesis.

The aim of this study was to determine whether epidermal hyperplasia overlying cutaneous human melanoma is associated with increased tumour angiogenesis, tumour growth and the potential for metastasis. Forty-two surgical specimens of cutaneous human melanoma of different depths, each containing epidermis present in the tumour-free margin, were analysed by immunohistochemistry for the expression of the pro-angiogenic molecules basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) and the anti-angiogenic molecule interferon-beta (IFN-beta). The epidermis overlying intermediate and thick (1.0-10.0 mm), but not thin (0.5-1.0 mm), melanoma specimens was hyperplastic. Although the expression level of bFGF, VEGF and IL-8 in the epidermis directly overlying the tumour was similar to that in the distant epidermis, the expression of IFN-beta was significantly decreased in keratinocytes overlying intermediate and thick, but not thin, melanomas. The microvessel density was also increased in intermediate and thick specimens. Human melanoma cells were injected subcutaneously into nude mice. The resulting tumours were used to determine the association between overlying epidermal hyperplasia and neoplastic angiogenesis. Similar to human autochthonous melanomas, epidermal hyperplasia was found only over lesions produced by metastatic cells. Although there was no change in the expression of the pro-angiogenic molecules, the expression of IFN-beta was significantly decreased in the hyperplastic epidermis. Conditioned medium collected from cultures of the metastatic cell line induced in vitro proliferation of mouse keratinocytes, whereas conditioned medium collected from cultures of the non-metastatic cell line did not. Collectively, the data demonstrate that metastatic melanoma cells induce keratinocyte proliferation, leading to decreased expression of the negative regulator of angiogenesis, IFN-beta, and hence to increased angiogenesis.

Animals↗

PubMed2003

[Effects of vascular endothelial growth factor D on the signaling cascade of sentinel lymphatic endothelial cells from melanoma patients undergoing sentinel lymphadenectomy].

Advances in surgical treatment, including sentinel lymphadenectomy, permit the pathologic staging of regional lymph nodes most likely to contain metastasis by identifying afferent lymphatic channels, which specifically drain the primary tumor site. Recently, a new member of the angiogenic molecule in VEGF family, VEGF-D, has been identified that induces lymphangiogenesis via high-affinity binding to VEGFR-3. VEGF-D is predominantly expressed in lymphatic endothelium. We have previously developed a novel method for the isolation of anatomically-defined lymphatic endothelial cells (LECs) from human sentinel lymphatic channel during SLN biopsy. The effect of VEGF-D on the extracellular signal-regulated kinases (Erk)-1/2 and Akt signaling pathway was examined by Western blot analysis. VEGF-D (500 ng/ml) apparently upregulated phospho-p44/phospho-p42 activity in human isolated LECs by Western blot analysis, while phospho-Akt activity was not at all changed by VEGF-D exposure without the change of total p44/p42 and Akt expression. U0126 (20 microM), the MEK1/2 inhibitor, could completely block the VEGF-D induced phospholylation of Erk1/2 signaling pathway. These data demonstrate that VEGF-D induces p44/p42 in human LECs and suggests that this signaling pathway activation may be important in LEC biology and lymphoangiogenesis, which may lead to the progression of new strategies of cancer treatment.

Endothelium, Lymphatic↗

PubMed2001

Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system.

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients. CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.

Adolescent↗

PubMed2001

Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma.

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. CONCLUSION: This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.

Humans↗

PubMed2001

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo.

We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was confirmed by RT--PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated filters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.

Alternative Splicing↗

PubMed2001

Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement.

Although sentinel lymph node (SLN) biopsy for melanoma has been adopted throughout the United States and abroad as a standard method of determining the pathologic status of the regional lymph nodes, some controversy still exists regarding the validity and utility of this procedure. SLN biopsy is a minimally invasive procedure, performed on an outpatient basis at the time of wide local excision of the melanoma, with little morbidity. Numerous studies have documented the accuracy of this procedure for identifying nodal metastases. There are four major reasons to perform SLN biopsy. First, SLN biopsy improves the accuracy of staging and provides valuable prognostic information for patients and physicians to guide subsequent treatment decisions. Second, SLN biopsy facilitates early therapeutic lymph node dissection for those patients with nodal metastases. Third, SLN biopsy identifies patients who are candidates for adjuvant therapy with interferon alfa-2b. Fourth, SLN biopsy identifies homogeneous patient populations for entry onto clinical trials of novel adjuvant therapy agents. Overall, the benefit of accurate nodal staging obtained by SLN biopsy far outweighs the risks and has important implications for patient management.

Chemotherapy, Adjuvant↗

PubMed2001

Significance of plasma cytokine levels in melanoma patients with histologically negative sentinel lymph nodes.

INTRODUCTION: Although sentinel lymph node (SLN) status is the most powerful predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will still recur. It is hypothesized that tumor response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, IL-6, IL-10, TNF-alpha, or IFN-gamma would predict disease recurrence in melanoma patients with histologically negative SLNs. METHODS: This prospective cohort study involved 218 patients with clinically localized melanoma who underwent a histologically negative SLN biopsy. Preoperative plasma cytokine levels were determined by enzyme-linked immunosorbent assay on these patients, as well as on 90 healthy controls. Kaplan-Meier life tables were constructed, and Cox proportional hazards analyses were performed to assess predictors of disease-free survival (DFS). RESULTS: At a median follow-up of 43 months, 33 of 218 patients (15%) had suffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-6, and IL-10 compared to healthy controls; levels of IFN-gamma were less elevated in melanoma patients compared to controls. Despite this, melanoma patients with detectable IFN-gamma levels were at significantly higher risk for recurrence compared to patients with undetectable levels (5-year DFS 70% vs. 86%, P = .03). On multivariate analysis including standard melanoma prognostic factors, only tumor thickness (P = .004) and the presence of detectable IFN-gamma levels (P = .05) were significant independent prognostic factors for disease-free survival. CONCLUSIONS: Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectable plasma level of IFN-gamma is an independent predictor of disease recurrence. Elevated levels of IFN-gamma may identify a group of early-stage melanoma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.

Adolescent↗

PubMed2001

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Chi-Square Distribution↗

PubMed2001

Improved staging of node-negative patients with intermediate to thick melanomas (>1 mm) with the use of lymphatic mapping and sentinel lymph node biopsy.

BACKGROUND: Elective lymph node dissection (ELND) may contribute to a survival benefit in certain stratified subsets of melanoma patients. We hypothesized that lymphatic mapping and sentinel lymph node (SLN) biopsy (with complete node dissection if metastases are present) may improve both staging and survival of patients with clinically negative nodes, without subjecting all patients to the morbidity associated with complete ELND. METHODS: We reviewed the data for all 14,914 N0 patients of the AJCC Melanoma Staging Database to determine the effect of SLN biopsy and ELND on staging and survival. RESULTS: Retrospective analysis revealed that there was an apparent statistically significant survival advantage to SLN biopsy in patients with melanomas > 1 mm (n = 9024; 68.5% and 26.2% reduction in mortality compared with patients staged to be N0 by clinical exam and ELND, respectively; P < .0001). Five-year survivals were 90.5%, 77.7%, and 69.8%, respectfully, for patients staged by SLN biopsy (n = 2552), ELND (n = 2014), and clinical examination alone (n = 5192). The survival advantage of SLN biopsy was statistically significant for each T-stage category (T2, T3, and T4) and ulceration status. There was no advantage to SLN biopsy in patients with melanomas <1 mm (n = 5890). CONCLUSIONS: SLN biopsy provides more accurate staging and may contribute to a survival benefit in populations of patients with melanoma.

Adult↗

PubMed2001

Patterns of regional and distant metastasis in patients with conjunctival melanoma: experience at a cancer center over four decades.

OBJECTIVE: The regional lymph nodes generally are believed to be the most common first site of metastasis for conjunctival malignant melanoma, but the pattern of nodal metastasis in this disease has not been well established. The goal of this study was to determine the frequency, location, and timing of regional lymph node metastasis in patients with conjunctival melanoma treated at one cancer center over four decades. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-seven patients. METHODS: The clinical records of 27 patients with conjunctival malignant melanoma were reviewed retrospectively. MAIN OUTCOME MEASURES: The rates of local conjunctival recurrence, regional nodal metastasis, and distant metastasis were analyzed along with overall survival. The follow-up time ranged from 2.5 to 17 years (median, 6 years). RESULTS: Eleven patients (41%) experienced clinical regional lymph node metastasis 1.5 to 6.0 years (mean, 3.2 years) after the initial diagnosis. The involved lymphatics were the preauricular (parotid) nodes in 8 patients (73%), the submandibular nodes in 1 patient (9%), and the deeper cervical nodes in 2 patients (18%). In seven patients (26%), distant metastasis developed without evidence of prior or concurrent regional nodal disease. Patients in whom distant metastasis developed without clinical evidence of regional nodal involvement were more likely to have had local conjunctival recurrence (P = 0.03) and a higher number of local recurrences (P = 0.05) compared with patients with regional lymph nodes as the site of first metastasis. The 5- and 10-year overall survival rates were 74% and 41%, respectively. CONCLUSIONS: Regional lymph node metastasis occurred in a higher percentage of patients with conjunctival malignant melanoma than has been reported previously. Preauricular lymph nodes were most commonly involved. Distant metastasis without prior or concurrent lymph node involvement was not a rare event.

Adult↗

PubMed2001

Sentinel lymph node biopsy for conjunctival melanoma.

OBJECTIVE: To investigate the feasibility and safety of preoperative lymphoscintigraphy and sentinel lymph node (SLN) biopsy for conjunctival melanoma. METHODS: A 49-year-old man with a biopsy-proven malignant melanoma of the conjunctiva (caruncle) underwent preoperative lymphoscintigraphy and SLN biopsy using a technique in which both isosulfan blue dye and technetium Tc 99 m sulfur colloid were injected in the subconjunctival space around the primary lesion. The conjunctival melanoma was excised just before identification and removal of the SLNs. The SLNs were excised along with concomitant dissection of their associated lymph node basins. The SLNs were evaluated histologically using serial sectioning and immunohistochemical staining with antisera against the S-100 protein and the melanoma antigen HMB-45. RESULTS: Three SLNs were identified in the left submandibular and the left upper and middle jugular lymph node basins during the preoperative lymphoscintigraphy. The same three SLNs were successfully identified in the operating room. The SLNs were histologically negative, and the immunohistochemical staining against S-100 and HMB-45 was also negative. We did not observe any immediate adverse effects on the globe or the periocular structures from lymphatic mapping and SLN biopsy. By 24 hours after injection of blue dye, only a faint trace of blue was visible on the ocular surface. CONCLUSIONS: Preoperative lymphoscintigraphy and SLN biopsy can be performed safely in patients with conjunctival melanoma. A larger study is planned to determine the sensitivity of this technique for the detection of occult regional nodal disease in patients with conjunctival melanoma.

Antigens, Neoplasm↗

PubMed2001

Melanoma.

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).

Antineoplastic Agents↗

PubMed2000

A new American Joint Committee on Cancer staging system for cutaneous melanoma.

The Melanoma Staging Committee of the AJCC has proposed major revisions of the melanoma TNM and stage grouping criteria. The committee members represent most of the major cooperative groups and cancer centers worldwide with a special interest in melanoma; the committee also collectively has had clinical experience with over 40,000 patients. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include 1) melanoma thickness and ulceration, but not level of invasion, to be used in the T classification; 2) the number of metastatic lymph nodes, rather than their gross dimensions, the delineation of microscopic versus macroscopic lymph node metastases, and presence of ulceration of the primary melanoma to be used in the N classification; 3) the site of distant metastases and the presence of elevated serum LDH, to be used in the M classification; 4) an upstaging of all patients with Stage I,II, and III disease when a primary melanoma is ulcerated; 5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into Stage III disease; and 6) a new convention for defining clinical and pathologic staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel lymph node biopsy. The AJC Melanoma Staging Committee invites comments and suggestions regarding this proposed staging system before a final recommendation is made.

Biopsy↗

PubMed2000

Regional nodal basin control is not compromised by previous sentinel lymph node biopsy in patients with melanoma.

BACKGROUND: Regional nodal basin control is an important goal of lymphadenectomy in the management of melanoma patients with nodal disease. The purpose of this study was to determine if previous sentinel lymph node (SLN) biopsy compromises the ultimate regional nodal control achieved by subsequent therapeutic lymph node dissection in melanoma patients with microscopic lymph node metastases. METHODS: A surgical melanoma database and hospital records were reviewed for 602 patients with primary cutaneous melanoma who underwent successful lymphatic mapping and SLN biopsy between 1991 and 1997. RESULTS: A total of 105 (17%) of 602 patients had histologically positive SLNs and were offered therapeutic lymphadenectomy; 101 (96%) underwent this procedure. Thirty-six patients (36%) developed recurrent melanoma at one or more sites. The median follow-up period was 30 months. Recurrence in the previously dissected nodal basin was observed in 10 patients (10%); none had recurrence at only that site. Nodal basin disease appeared after local/in-transit (n = 6) or distant (n = 1) failure in seven patients and, as a component of the first site of failure, simultaneously with local/in-transit (n = 2) or distant (n = 1) recurrence in three patients. CONCLUSIONS: Nodal basin failure after lymphadenectomy in patients who underwent previous biopsy of a histologically positive SLN is primarily a function of aggressive locoregional disease rather than of contamination from previous surgery. Because regional nodal control was comparable with that in other series, we conclude that SLN biopsy with selective lymphadenectomy does not compromise regional nodal basin control.

Adolescent↗

PubMed2000

Role for lymphatic mapping and sentinel lymph node biopsy in patients with thick (> or = 4 mm) primary melanoma.

BACKGROUND: Historically, patients with thick (> or =4 mm) primary melanoma have not been considered candidates for elective lymph node dissection, because their risk for occult distant disease is significant. Sentinel lymph node (SLN) biopsy offers an alternative approach to assess disease in the regional nodal basin, but no studies have specifically addressed the role for this technique in patients with thick melanoma. Although adjuvant therapy benefits patients who develop nodal metastases, data that supports its routine use in all patients with thick melanoma is both limited and controversial. This study was performed to determine whether pathological status of the SLN is an important risk factor in this heterogeneous group and, thus, provides a rationale for SLN biopsy. METHODS: The records of 131 patients with primary cutaneous melanoma whose primary tumors were at least 4 mm thick and who underwent lymphatic mapping and SLN biopsy were reviewed. Several known prognostic factors, i.e., tumor thickness, ulceration, Clark level, location, sex, as well as SLN pathological status were analyzed with respect to disease-free and overall survival. RESULTS: Lymphatic mapping and SLN biopsy was successful in 126 (96%) of 131 patients who underwent the procedure. In 49 patients (39%), the SLN biopsy was positive by conventional histology, although it was negative in 77 patients (61%). The median follow-up was 3 years. Although presence of ulceration and SLN status were independent prognostic factors with respect to disease-free and overall survival, SLN status was the most powerful predictor of overall survival by univariate and multivariate analyses. CONCLUSIONS: Lymphatic mapping and SLN biopsy is a highly accurate method of staging lymph node basins at risk for regional metastases in patients with thick melanoma and identifies those patients who may benefit from earlier lymphadenectomy as well as patients with a more favorable prognosis. Pathological status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for survival and is essential to establish stratification criteria for future adjuvant trials in this high-risk group.

Adolescent↗

PubMed2000

Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.

BACKGROUND: Although previous studies have demonstrated that truncal site is associated with an adverse prognosis, explanations for such risk are lacking. In addition, the number of nodal basins as well as the number of lymph nodes containing regional metastases are important prognostic factors in these patients. Because the lymphatic drainage pattern of truncal melanoma often includes more than one basin, we designed a study to evaluate (1) whether patients with multiple nodal basin drainage (MNBD) were at an increased risk of lymph node metastases identified by sentinel lymph node (SLN) biopsy, and (2) whether the histological status of an individual basin reliably predicted the status of the other draining basins in patients with MNBD. METHODS: The records of 295 consecutive truncal melanoma patients who were managed primarily with intraoperative lymphatic mapping and SLN biopsy, between 1991 and 1997, were reviewed. All patients underwent preoperative lymphoscintigraphy, which established the number and location of draining nodal basins. Univariate and multivariate analyses of relevant clinicopathological factors were performed to assess which factors may predict the presence of a pathologically positive SLN. RESULTS: At least one SLN was identified in 281 patients. MNBD was present in 86 (31%) patients, and a pathologically positive SLN was found in 56 (20%) patients. By multivariate analysis, the presence of MNBD (relative risk = 1.9; P = .03), tumor thickness (P = .007), and tumor ulceration (relative risk = 2.4; P = .01) were significant independent risk factors for the presence of at least one pathologically positive SLN. SLN pathology in one basin did not predict the histology of other basins in 19 (22%) of 86 patients with MNBD. CONCLUSIONS: MNBD is independently associated with an increased risk of nodal metastases in truncal melanoma patients. Because the histological status of an individual basin did not reliably predict the status of the other draining basins in patients with MNBD, it is important to adequately identify and completely assess all nodal basins at risk, as defined by lymphoscintigraphy, in truncal melanoma patients.

Biopsy↗

PubMed2000

How many lymph nodes are enough during sentinel lymphadenectomy for primary melanoma?

BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to reliably identify nodal metastases and the subsequent need for further surgical and adjuvant therapy in patients with cutaneous melanoma. Although SLN identification rates have improved with the addition of radioactive colloid to the blue dye technique, it remains unclear how many lymph nodes should be removed to accurately determine the histologic status of the nodal basin. The objective of this study was to determine the optimal extent of SLN biopsy in these patients. METHODS: The records of 633 consecutive patients with melanoma (765 nodal basins) whose primary treatment included SLN biopsy with the use of a combination of blue dye and technetium Tc 99 labeled sulfur colloid were reviewed. SLN biopsy consisted of the removal of all of the blue-stained nodes and all nodes with radiotracer uptake activity of at least twice background. RESULTS: SLN biopsy was successful in 765 of 772 basins (99%). A mean of 1.9 SLNs (median, 2 SLNs) per basin were excised. At least 3 SLNs were removed in 176 basins (23%). The overall histologic status of a basin was always established by the first or second SLN harvested (ie, in no patient was the third or subsequent SLN positive when 1 of the first 2 was not). Of the 124 basins containing lymphatic metastases, the SLN that contained the maximal radiotracer uptake (hottest) and/or stained blue was pathologically positive in 118 basins (95%). In only 6 of the 124 positive basins (5%) was the sole evidence of occult nodal metastases identified in an SLN that was neither blue-stained nor the hottest. All but 1 of these SLNs had counts that were at least 66% of the hottest node in the basin. CONCLUSIONS: With a combined modality approach to SLN biopsy, removal of more than 2 SLNs did not provide information that upstaged any patient with primary melanoma. Removal of additional nonblue SLN(s) that contained radioactive counts of at least twice background but lower than two thirds of the SLNs with maximal radiotracer uptake affected patient management in less than 0.2% of all cases. These findings may be helpful in minimizing the extent of surgery and perhaps in reducing the costs and resource use associated with operating room time and pathologic examination.

Biopsy↗

PubMed2000

Clinical classification and staging.

The identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. Changes in the staging system are anticipated as more refined prognostic factors are identified. This article provides an overview of the system, including a brief history and an introduction to recent advances in staging of patients with primary melanoma (i.e., sentinel lymphadenectomy). Practical recommendations for a stage-specific workup for the patient, which are especially important given the need for quality care in an increasingly cost-conscious environment, are provided.

Humans↗