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Biomedical subjects

Stanley P L Leong

Publications and source records attributed to Stanley P L Leong.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic significance of nuclear receptor coactivator-3 overexpression in primary cutaneous melanoma.

PURPOSE: To assess the prognostic significance of nuclear receptor coactivator-3 (NCOA3) overexpression in primary cutaneous melanoma. PATIENTS AND METHODS: NCOA3 expression was assessed using immunohistochemical analysis of a melanoma tissue microarray (TMA) containing primary melanomas from 343 patients with defined histology and follow-up. The impact of the presence or absence of various prognostic factors on relapse-free survival (RFS) and disease-specific survival (DSS) of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. The impact of presence or absence of various factors on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS: Increasing degree of NCOA3 expression was significantly predictive of SLN metastasis (P = .013) and the mean number of SLN metastases (P = .031). Kaplan-Meier analysis demonstrated a significant association between NCOA3 overexpression and reduced RFS (P = .021) and DSS (P = .030). Logistic regression analysis revealed increasing degree of NCOA3 expression to be an independent predictor of SLN status (P = .017). Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS (P = .0095) and DSS (P = .021). NCOA3 was the most powerful factor predicting DSS, outperforming tumor thickness and ulceration. CONCLUSION: These results identify NCOA3 as a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and DSS.

Biomarkers, Tumor↗
PubMed2006

Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study.

BACKGROUND: Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND. METHODS: Surgeons from 16 centers contributed data on 134 positive-SLN patients who did not undergo CLND. SLN biopsy was performed by using each institution's established protocols. Patients were followed up for recurrence and survival. RESULTS: In this study population, the median age was 59 years, and 62% were male. The median tumor thickness was 2.6 mm, 77% of tumors had invasion to Clark level IV/V, and 33% of lesions were ulcerated. The primary melanoma was located on the extremities, trunk, and head/neck in 45%, 43%, and 12%, respectively. The median follow-up was 20 months. The median time to recurrence was 11 months. Nodal recurrence was a component of the first site of recurrence in 20 patients (15%). Nodal recurrence-free survival was statistically insignificantly worse than that seen in a contemporary cohort of patients who underwent CLND. Disease-specific survival for positive-SLN patients who did not undergo CLND was 80% at 36 months, which was not significantly different from that of patients who underwent CLND. CONCLUSIONS: This study underscores the importance of ongoing prospective randomized trials in determining the therapeutic value of CLND after positive SLN biopsy in melanoma patients.

Cohort Studies↗
PubMed2006

Impact of sentinel node status and other risk factors on the clinical outcome of head and neck melanoma patients.

OBJECTIVE: To determine the impact of sentinel lymph node (SLN) status and other risk factors on recurrence and overall survival in head and neck melanoma patients. DESIGN: The SLN Working Group, based in San Francisco, Calif, with its 11 member centers, the John Wayne Cancer Institute, and The University of Texas M. D. Anderson Cancer Center pooled data on 629 primary head and neck melanoma patients who had selective sentinel lymphadenectomy. A total of 614 subjects were analyzable. All centers obtained internal review board approval and adhered to the Health Insurance Portability and Accountability Act of 1996 regulations. A Cox proportional hazards model was used to identify factors associated with overall and disease-free survival. SETTING: Tertiary care medical centers. MAIN OUTCOME MEASURE: Clinical outcome of head and neck melanoma patients undergoing selective sentinel lymphadenectomy. RESULTS: Overall, 10.1% (n = 62) of the subjects had at least 1 positive node. Subjects with positive SLN status had significantly thicker tumors (mean thickness, 2.8 vs 2.1 mm; P < .001), and were more likely to have ulcerated tumors (P = .004). During the median follow-up of 3.3 years, the overall mortality from head and neck melanoma was 10%, with more than 20% experiencing at least 1 recurrence. Multivariate analysis showed that tumor site was an independent predictor of mortality; location on the scalp had a more than 3-fold (P < .001) greater mortality than tumors on the face. Tumor thickness was also an independent predictor of overall survival, and SLN status was the most important predictor of disease-free survival in the multivariate model (P < .001). Tumors on the scalp had the highest rate of recurrence, while those on the neck had the lowest. Tumor ulceration was the significant predictor of time to recurrence or disease-free survival (P < .001). CONCLUSION: In this multicenter study, SLN status and other risk factors have an effect on recurrence and/or overall survival.

Adult↗
PubMed2006

Clinical patterns of metastasis.

In human solid cancer, lymph node status is the most important indicator for clinical outcome. Recent developments in the sentinel lymph node concept and technology have resulted in a more precise way of examining micrometastasis in the sentinel lymph node and the role of lymphovascular system in the facilitation of cancer metastasis. Different patterns of metastasis are described with respect to different types of solid cancer. Expect perhaps for papillary carcinoma and sarcoma, the overwhelming evidence is that solid cancer progresses in an orderly progression from the primary site to the regional lymph node or the sentinel lymph node in the majority of cases with subsequent dissemination to the systemic sites. The basic mechanisms of cancer metastasis through the lymphovascular system form the basis of rational therapy against cancer. Beyond the clinical patterns of metastasis, it is imperative to understand the biology of metastasis and to characterize patterns of metastasis perhaps due to heterogeneous clones based on their molecular signatures.

Animals↗
PubMed2006

Tumour-induced immune modulation of sentinel lymph nodes.

Sentinel lymph nodes (SLNs), being the first nodes to receive lymph from a primary tumour and the preferential site of initial tumour metastases, are intensively exposed to the bioactive products of tumour cells and other associated cells. This makes them ideal for studies of the factors that determine selective tissue susceptibility to metastases. We postulate that tumour-induced immune modulation of SLNs facilitates lymph-node metastases by inhibiting the generation of tumour-specific cytotoxic T cells that are active against tumour cells of primary and metastatic melanomas. Immune modulation of the lymph nodes can be reversed by granulocyte/macrophage colony-stimulating factor (GM-CSF), a finding that has implications for the future therapy of lymph-node metastases.

Animals↗
PubMed2006

Prognostic significance of extent of ulceration in primary cutaneous melanoma.

Ulceration has been shown to be an adverse prognostic factor in primary cutaneous melanoma. However, the extent of ulceration required for histologic identification and biologic significance is unclear. We examined the impact of extent of ulceration on melanoma outcome in a cohort of 235 melanoma patients by evaluating the relationship between percentage of ulceration in the vertical growth phase of the primary tumor and 2 outcome parameters: sentinel lymph node status and overall survival. We measured the diameter of the ulcerated area in millimeters over the diameter of the entire vertical growth phase. There was a statistically significant relationship between increasing percentage of tumor ulceration and both sentinel lymph node status as well as overall survival, with a binary cut-off point of 2% for sentinel lymph node status and 5% for overall survival. The percentage of ulceration provides additional prognostic information in predicting sentinel lymph node status and in determining survival in melanoma patients. These results suggest that no more than minimal ulceration is required to have a prognostic impact on melanoma survival.

Adolescent↗
PubMed2005

The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer.

BACKGROUND: Routine axillary lymph node dissection (ALND) after selective sentinel lymphadenectomy (SSL) in the treatment of breast cancer remains controversial. We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node (SLN) and non-SLN (NSLN) status. We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden. METHODS: This was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002. RESULTS: Of the 390 patients, 115 received both SSL and ALND. The percentage of additional positive NSLNs in the SLN-positive group (34.2%) was significantly higher than in the SLN-negative group (5.1%; P = .0004). The SLN macrometastasis group had a significantly higher rate of positive NSLNs (39.7%) compared with the SLN-negative group (5.1%; P = .0001). Sixteen patients developed recurrences during follow-up, including 6.1% of SLN-positive and 3.3% of SLN-negative patients. Among the SLN macrometastasis group, 8.7% had recurrence, compared with 2.2% of SLN micrometastases over a median follow-up period of 31.1 months. One regional failure developed out of 38 SLN-positive patients who did not undergo ALND. CONCLUSIONS: ALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs. Higher recurrence rates are also seen in these patients. However, the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospective randomized trials.

Adult↗
PubMed2005

The gene expression signatures of melanoma progression.

Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.

Biopsy↗
PubMed2005

Selective sentinel lymphadenectomy for malignant melanoma, Merkel cell carcinoma, and squamous cell carcinoma.

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.

Carcinoma, Merkel Cell↗
PubMed2005

Clinical significance of occult metastatic melanoma in sentinel lymph nodes and other high-risk factors based on long-term follow-up.

Selective sentinel lymphadenectomy (SSL) following preoperative lymphoscintigraphy is the most significant recent advance in the management of patients with primary melanoma. This study evaluates the prognostic value of sentinel lymph node (SLN) status and other risk factors in predicting survival and recurrence in patients with primary cutaneous melanoma. From October 1993 to July 1998 a series of 412 patients with primary invasive melanoma underwent SSL at the UCSF/ Mt. Zion Melanoma Center. The outcome of 363 evaluable patients is summarized in this study. The factors related to survival and disease recurrence were analyzed by Cox proportional hazard regression models. The overall incidence of patients with positive SLNs was 18%. Over a median follow-up of 4.8 years, the overall mortality rate in patients with primary cutaneous melanoma was 18.7%, and 74 recurrences occurred (20.4%). Mortality was significantly related to SLN status [HR = 2.06; 95% Confidence interval (CI) 1.18, 3.58], angiolymphatic invasion (HR = 2.21; 95% CI 1.08, 4.55), ulceration (HR = 1.79; 95% CI 1.02, 3.15), mitotic index (HR =1.38; 95% CI 1.01, 1.90), and tumor thickness (HR = 2.20, 95% CI 1.21, 3.99). Factors significantly related to disease-free survival included SLN status (HR = 2.09; 95% CI 1.31, 3.34), tumor thickness (HR = 1.89; 95%. CI 1.20,2.98), and age (HR= 1.26 95% CI 1.08, 1.47). SLN status was the most significant factor for melanoma recurrence and death. Other important predictors include tumor thickness, ulceration, lymphatic invasion, and mitotic index.

Adult↗
PubMed2005

Heterogeneous patterns of lymphatic drainage to sentinel lymph nodes by primary melanoma from different anatomic sites.

UNLABELLED: We want to define the patterns of lymphatic drainage for primary melanoma to sentinel lymph nodes (SLNs) based on a large lymphoscintigraphic database. Preoperative lymphoscintigraphy was used to identify and classify SLN drainage basins and patterns of drainage. METHODS: Lymphoscintigraphy using intradermally administered technetium-99m labeled sulfur colloid was performed on 400 consecutive patients with malignant melanoma to define lymphatic drainage channels and draining SLN basins before surgery. Primary tumor sites consisted of head and neck, upper extremity, trunk, and lower extremity. Different types of drainage patterns were classified and correlated with different anatomic sites. RESULTS: SLN(s) were identified in over 98% of the patients, whereas lymphatic drainage channels were successfully identified in 90% of the patients. Drainage from the primary site to a single SLN through a single lymphatic channel (type IA) was seen in 186 of 400 patients (47%) as the most common type. In patients with a single SLN within a single basin (type I-V), the percentage of patients with primary lesions in the head and neck, upper extremity, trunk, and lower extremity regions were 61%, 79%, 55%, and 78%, respectively. In cases of multiple lymphatic channels (type VI-VII), the percentages of patients with primary lesions in the head and neck, upper extremity, trunk, and lower extremity regions were 24%, 8%, 36%, and 19%, respectively. CONCLUSION: Various drainage patterns were noted from primary melanomas in different anatomic sites. Preoperative lymphoscintigraphy is important in establishing the SLN basins for harvesting the SLN(s).

Humans↗
PubMed2004

Routine imaging of asymptomatic melanoma patients with metastasis to sentinel lymph nodes rarely identifies systemic disease.

HYPOTHESIS: The diagnostic yield of chest radiography; computed tomography (CT) of the chest, abdomen, and pelvis; and CT or magnetic resonance imaging of the brain in the initial evaluation of melanoma with metastasis to sentinel lymph nodes may not identify systemic disease. DESIGN: Retrospective analysis. SETTING: Tertiary care referral center. PATIENTS: Of 1183 patients identified from a database of individuals who underwent selective sentinel lymphadenectomy for primary melanoma (Breslow thickness, 0.2-30 mm), we studied 185 with at least 1 sentinel lymph node positive for metastatic melanoma (Breslow thickness, 0.8-14.5 mm). INTERVENTIONS: Chest radiography; CT of the chest, abdomen, and pelvis; and CT or magnetic resonance imaging of the brain after selective sentinel lymphadenectomy with positive sentinel lymph nodes. The medical records of the 185 patients were systematically reviewed by 4 physician reviewers, and data were extracted primarily from pathology and radiology reports. When medical records were unavailable, information was taken from formal clinic and inpatient progress notes. MAIN OUTCOME MEASURE: Diagnostic yield of imaging studies. RESULTS: The results of 0.5% of the imaging studies were positive for metastatic disease, 86% were negative, and 14% were indeterminate. Indeterminate results were confirmed to be negative by additional studies ranging from repeated imaging to invasive procedures, including thoracotomy and brain biopsy. The yields are as follows: chest radiography, 0%; chest CT, 0.7%; abdominal and pelvic CT, 0.7%; brain CT, 0%; and brain magnetic resonance imaging, 0%. Only 1 patient (0.5%) had detectable metastatic disease, and he had symptoms of systemic disease at the time of imaging. CONCLUSIONS: Computed tomography of the chest, abdomen and pelvis, and brain rarely reveals systemic metastasis at the time of selective sentinel lymphadenectomy. Routine imaging of asymptomatic patients at the time of selective sentinel lymphadenectomy is not indicated.

Brain Neoplasms↗
PubMed2004

Paradigm of metastasis for melanoma and breast cancer based on the sentinel lymph node experience.

Lymph node status is the most reliable prognostic indicator for patients with melanoma and breast cancer. Because it is the first node draining the primary cancer, the sentinel lymph node (SLN) is most likely to harbor metastatic cancer cells. The Breslow thickness of the primary melanoma and the size of primary breast cancer are highly correlated with SLN metastasis. If the SLN is negative, its negative predictive value for the remaining nodal basin exceeds 95%; thus, survival rates for melanoma and breast cancer increase when the SLN is negative. The rate of SLN identification is more than 95%, and the false-negative rate is about 5%. SLN data from melanoma and breast cancer are so convincing that they have been incorporated into the new American Joint Committee on Cancer classification of these cancers. The therapeutic value of additional lymph node dissection after a positive SLN for melanoma or breast cancer is still controversial. In melanoma, a 3-year follow-up may confirm better survival when the SLN is negative. However, about 25% of histologically negative SLNs may be upstaged by molecular techniques, and patients whose SLNs are positive by polymerase chain reaction (PCR) assay may develop recurrence. In most cases, melanoma and breast cancer follow an orderly progression of metastasis to the SLN; however, a small subgroup may develop systemic dissemination without SLN involvement. Current SLN experience has confirmed that the earlier the cancer, the less its potential for metastasis. Since treatments for metastatic cancer are still limited, early detection and resection are imperative. Better understanding of the molecular and genetic mechanisms of metastasis will be critical to select high-risk patients for adjuvant therapy.

Breast Neoplasms↗
PubMed2004

Sentinel lymph node mapping and selective lymphadenectomy: the standard of care for melanoma.

Selective sentinel lymphadenectomy (SSL) should be considered a standard of care approach for staging patients with primary invasive melanoma 1 mm or greater. It is essential that multidisciplinary teams should master the techniques of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and pathologic evaluation of the sentinel lymph nodes (SLNs). An SLN may be blue, hot, or any lymph node (LN) greater than 10% of the in-vivo count of the hottest LN. An enlarged or indurated LN should be removed because it may contain metastatic cancer cells that block blue dye or radiotracer entry. Frozen sections are not recommended. Surgeons who use isosulfan blue dye should be cognizant of treatment for a potentially fatal reaction. Prophylactic LN dissection should not be performed if a SSL can be performed as a staging procedure. A complete LN dissection is performed if the SLN is positive. It is important to follow the clinical outcome of patients undergoing SSL, thus its role can be further defined.

Humans↗
PubMed2004

Selective sentinel lymphadenectomy for breast cancer in the United States.

Lymph node status is the most reliable prognostic indicator for breast cancer patients. Sentinel lymph nodes (SLNs) are the first draining lymph nodes for metastatic breast cancer to spread from the primary site. Although the therapeutic role of selective sentinel lymphadenectomy (SSL) in breast cancer has not been determined, the practical significance is that it is being used as a staging procedure, so that a negative SLN can spare a patient more extensive axillary lymph node dissection (ALND) with its associated morbidity. If the SLN is negative, the negative predictive value of the remaining nodal basin for breast cancer exceeds 95%. SSL selects out one or a few SLNs and permits more extensive study of the nodes by the pathologist. Such extensive examination would not be practical for the many nodes yielded by a standard ALND. SSL is rapidly evolving into a standard approach for staging primary breast cancer in the United States, without the maturation of results from clinical trials.

Axilla↗
PubMed2004

Laparoscopic surgery for melanoma metastases to the adrenal gland.

The probability of developing cutaneous melanoma is now predicted to be one in 55 for males and one in 88 for females. Although melanoma is relatively uncommon compared with other malignancies such as breast (one in seven) or prostate cancer (one in six), the incidence is growing at an alarming rate. The development of novel strategies for the management of advanced disease will become even more urgent and require continued and controlled investigations over the next 10 years. Surgery is effective for the palliation of isolated resectable metastases. However, most patients with Stage IV melanoma have widespread disease and are not cured by metastasectomy. For the few individuals with isolated adrenal metastases from melanoma, complete resection appears to confer a survival advantage. New data are emerging about the efficacy and outcome of laparoscopic adrenalectomy for malignant lesions. However, the natural history of laparoscopic surgery for these lesions is still unknown. The indications for and limitations of laparoscopic adrenalectomy for metastatic melanoma are discussed.

Adrenal Gland Neoplasms↗