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Complete lymphadenectomy following positive sentinel lymph node biopsy in cutaneous melanoma: a critical review.

ABSTRACT: Cutaneous melanoma is the solid neoplasia with the highest growing incidence among all tumors. It spreads predictably to the lymphatic vessels and sentinel lymph node, and when the latter is affected the prognosis worsens dramatically. Sentinel lymph node biopsy is considered when thickness of the primary tumor exceeds 1mm and/or when there are adverse features in thinner melanomas. When there is nodal metastasis, current evidence in the literature recommends complete lymphadenectomy, although this procedure has its intrinsic risks (i.e., lymphedema and cellulitis), and there are no published clinical trials proving additional overall survival benefits. The current in-depth literature review thus aims to identify patients that will benefit most from the procedure, including those with the highest likelihood of presenting additional affected lymph nodes in the same nodal basin. The authors also discuss techniques for identification of the sentinel lymph node, false-negative rates, and predictive models for lymph node involvement. In conclusion, complete elective lymphadenectomy should always be discussed on a case-by-case basis when metastases are detected in the sentinel lymph node.

SUBMITTER: Eiger D

PROVIDER: S-EPMC6063107 | biostudies-other | 2018 Jul-Aug

REPOSITORIES: biostudies-other

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Complete lymphadenectomy following positive sentinel lymph node biopsy in cutaneous melanoma: a critical review.

Eiger Daniel D Oliveira Daniel Arcuschin de DA Oliveira Renato Leão de RL Sousa Murilo Costa MC Brandão Mireille Darc Cavalcante MDC Oliveira Filho Renato Santos de RS

Anais brasileiros de dermatologia 20180701 4

Cutaneous melanoma is the solid neoplasia with the highest growing incidence among all tumors. It spreads predictably to the lymphatic vessels and sentinel lymph node, and when the latter is affected the prognosis worsens dramatically. Sentinel lymph node biopsy is considered when thickness of the primary tumor exceeds 1mm and/or when there are adverse features in thinner melanomas. When there is nodal metastasis, current evidence in the literature recommends complete lymphadenectomy, although t ...[more]

PMID: 30066763

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Project description:ImportanceAcral lentiginous melanoma (ALM) is a rare subtype of malignant melanoma typically occurring on the palmar and plantar surfaces. Although it has distinctive genetic, prognostic, and behavioral characteristics relative to cutaneous melanomas overall, owing to its rarity, treatment is largely guided by data extrapolated from more common subtypes. Although sentinel lymph node (SLN) status has been shown to be a significant prognostic factor for ALM, the independent effect of ALM-subtype disease on the likelihood of SLN positivity and the stage-specific positivity rates for ALM are not well characterized.ObjectiveTo evaluate the association of ALM with SLN status as well as to characterize the clinical stage-specific rates of SLN positivity for ALM based on the AJCC Cancer Staging Manual, 8th edition (AJCC-8).Design, setting, and participantsThe National Cancer Database (NCDB) includes all reportable cases from Commission on Cancer accredited facilities and represents approximately 50% of all newly diagnosed melanoma cases in the US. This retrospective cohort study included cases of AJCC-8 clinical stage I to II melanomas from the NCDB diagnosed from 2012 to 2015. The analysis took place between April 2021 and September 2021.ExposuresMelanoma histopathologic subtype.Main outcomes and measuresSentinel lymph node status.ResultsWe identified 60 148 patients with malignant melanomas, 959 of whom had ALM-subtype disease. Among patients in the cohort, 25 550 (42.5%) were women and the mean (SD) age was 64 (16) years. Multivariable logistic regression controlling for demographic and histopathologic characteristics revealed that ALM was independently associated with the highest risk for SLN positivity among included subtypes (vs superficial spreading melanoma: odds ratio, 1.91; 95% CI, 1.59-2.28). Subgroup analysis by AJCC clinical stage demonstrated that ALM was independently associated with the highest risk for SLN positivity for both stage IB and II disease. The rate of SLN positivity for patients with stage IB and II ALM was 18.39% (95% CI, 13.82%-24.03%) and 39.53% (34.98%-44.26%), respectively.Conclusions and relevanceIn this cohort study ALM was independently associated with SLN positivity and had relatively high positivity rates at clinical stage IB and II. This suggests that SLNB should be encouraged for all patients with clinical stage IB and II ALM, and such patients should receive appropriate counseling about the higher regional metastatic risk of their cancers. Future work with a larger cohort is required to elucidate the risk of SLN positivity for stage IA ALM.

Project description:Sentinel lymph node, the first node draining the primary tumor, is a key component of tumor microenvironment promoting immune tolerance. In melanoma, sentinel node is one of the most important prognostic factors and the most frequent site of regional metastasis. To unravel the immunomodulatory pathways that are triggered by melanoma cells in the draining node that allow tumor spreading, transcriptional profiles associated to disease progression were analyzed in archival sentinel node biopsies (SNB). Gene expression profiles of melanoma-positive and negative SNB selected to maximize the differences in terms of disease stage and course, revealed subgroups correlating with regional node involvement and disease progression within positive biopsies. Transcriptional profiles revealed that genes showing differential expression between tumor-positive SNB with/without disease progression were mainly related to inflammatory response and that were mostly down regulated in patients with poor prognosis. TNFRSF8 encoding CD30 showing up regulation in SNB from patients with progressing disease displayed higher expression by immunohistochemical staining compared to SNB from non progressing patients. Subpopulations of CD30 positive CD4/CD8 double negative and CD4 Foxp3/PD-1 CD147 positive T cells were identified by flow cytometry analysis in metastatic nodes, suggesting a potential role of regulatory and tolerogenic T cells in melanoma progression. Cutaneous melanoma patients undergoing SNB biopsy in 2001-2004 with available 5–year follow-up clinical data were selected. Data relative to 752 cases was extracted, 80% (n= 603) with a negative SNB and 20% (n=149) with SNB positivity for melanoma metastases. The latter underwent regional lymphadenectomy by CLND and 30% (n=44) resulted positive for melanoma metastases at non-sentinel regional lymph nodes while 70% (n=105) resulted negative. Analysis of follow-up data showed that disease recurrence at 5 yrs occurred in 9% SNB negative patients, 14% of the patients with positive SNB resulting negative at CLND, and in 57% of the patients with positive SNB resulting positive at CLND, consistent to the range of previously reported rates (Santinami M 2009, Balch CM 2009). In order to exploit gene expression profiles to unravel molecular modifications occurring in SNB from patients with progressing disease we selected two groups of cases representing the extremes of the survey, i.e. patients positive at CLND (stage IIIB-C) recurring within 5 years follow-up (SNB-PP), and patients negative at CLND (stage IIIA-B) and non-relapsing at 5 years (SNB-PN). In addition, a group of negative SNB patients without disease recurrence at 5 years was selected and analysed for comparison as tumor negative SNB (SNB-N).

Project description:The aim of this study was to asses quality of life (QoL) after axillary or inguinal sentinel lymph node biopsy (SLNB) with or without completion lymph node dissection (CLND) in patients with cutaneous melanoma by comparing patients to a norm group of the general population and by comparing QoL between four patient groups depending on surgical procedure and location, i.e., patients receiving an axillary or groin SLNB, or an axillary or groin CLND.Between 1995 and 2003, a total of 242 axillary and inguinal SLNBs were performed. Of the 127 patients eligible for the study, 116 patients participated (91%). QoL was measured by the 30-item European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the McGill Pain Questionnaire and the Groningen Activity Restriction Scale.Median age at diagnosis was 50 (range, 18-77) years; median Breslow thickness 2.0 (range, 1-13) mm; median follow-up 56 (range, 4-94) months. SLNB only was performed in 89 patients (77%): 48 in the groin and 41 in the axilla. CLND was performed in 27 patients (23%): 13 in the axilla and 14 in the groin. More postoperative complications (13 vs. 5; P < 0.001) and lymphedema (10 vs. 8; P < 0.001) occurred in the CLND group than in the SLNB group. The total group of patients reported better physical (P < 0.001), role (P < 0.001), emotional (P < 0.001), and social functioning (P = 0.049), global QoL (P < 0.001), and less fatigue (P < 0.001) and pain (P < 0.001) than a German norm group. Analysis of variance revealed significant differences in role functioning (P = 0.02) and tendencies toward physical problems (P = 0.051) and fatigue (P = 0.051) between the four groups. Post hoc Bonferroni tests showed that the axillary CLND group had more problems than the axillary and inguinal SLNB groups. Kruskal-Wallis tests showed that the axillary CLND group reported most pain.QoL in melanoma survivors after axillary or inguinal SLNB with or without CLND was better than that in a norm group. Patients who underwent CLND in the axilla after SLNB reported most problems.

Project description:Sentinel lymph node, the first node draining the primary tumor, is a key component of tumor microenvironment promoting immune tolerance. In melanoma, sentinel node is one of the most important prognostic factors and the most frequent site of regional metastasis. To unravel the immunomodulatory pathways that are triggered by melanoma cells in the draining node that allow tumor spreading, transcriptional profiles associated to disease progression were analyzed in archival sentinel node biopsies (SNB). Gene expression profiles of melanoma-positive and negative SNB selected to maximize the differences in terms of disease stage and course, revealed subgroups correlating with regional node involvement and disease progression within positive biopsies. Transcriptional profiles revealed that genes showing differential expression between tumor-positive SNB with/without disease progression were mainly related to inflammatory response and that were mostly down regulated in patients with poor prognosis. TNFRSF8 encoding CD30 showing up regulation in SNB from patients with progressing disease displayed higher expression by immunohistochemical staining compared to SNB from non progressing patients. Subpopulations of CD30 positive CD4/CD8 double negative and CD4 Foxp3/PD-1 CD147 positive T cells were identified by flow cytometry analysis in metastatic nodes, suggesting a potential role of regulatory and tolerogenic T cells in melanoma progression. Cutaneous melanoma patients undergoing SNB biopsy in 2001-2004 with available 5M-bM-^@M-^Syear follow-up clinical data were selected. Data relative to 752 cases was extracted, 80% (n= 603) with a negative SNB and 20% (n=149) with SNB positivity for melanoma metastases. The latter underwent regional lymphadenectomy by CLND and 30% (n=44) resulted positive for melanoma metastases at non-sentinel regional lymph nodes while 70% (n=105) resulted negative. Analysis of follow-up data showed that disease recurrence at 5 yrs occurred in 9% SNB negative patients, 14% of the patients with positive SNB resulting negative at CLND, and in 57% of the patients with positive SNB resulting positive at CLND, consistent to the range of previously reported rates (Santinami M 2009, Balch CM 2009). In order to exploit gene expression profiles to unravel molecular modifications occurring in SNB from patients with progressing disease we selected two groups of cases representing the extremes of the survey, i.e. patients positive at CLND (stage IIIB-C) recurring within 5 years follow-up (SNB-PP), and patients negative at CLND (stage IIIA-B) and non-relapsing at 5 years (SNB-PN). In addition, a group of negative SNB patients without disease recurrence at 5 years was selected and analysed for comparison as tumor negative SNB (SNB-N).

Project description:ImportanceWhether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear.ObjectiveTo examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC.Design, setting, and participantsIn this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada.ExposuresAll patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND).Main outcomes and measuresThe primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events.ResultsThe study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis.Conclusions and relevanceIn this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.

Dataset Information

Complete lymphadenectomy following positive sentinel lymph node biopsy in cutaneous melanoma: a critical review.

Publications

Complete lymphadenectomy following positive sentinel lymph node biopsy in cutaneous melanoma: a critical review.

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