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1.
Clin Adv Hematol Oncol ; 21(8): 400-409, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37530614

RESUMO

Acral melanoma is a rare subtype of melanoma with unique histologic and biologic characteristics. Given its relative rarity compared with nonacral cutaneous melanoma, acral melanoma has been understudied and underrepresented in modern-day prospective clinical trials that have shaped the contemporary management of advanced cutaneous melanoma. Therefore, treatment principles for advanced acral melanoma are mostly derived from retrospective analyses or extrapolated from data largely based on nonacral cutaneous melanoma. Further studies are warranted to evaluate the efficacy of systemic immune and targeted molecular therapies, and to identify molecular targets for patients with advanced acral melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/terapia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Melanoma Maligno Cutâneo
2.
Cancer ; 128(21): 3764-3771, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36066835

RESUMO

Currently accepted principles of surgical management-margin width, use of sentinel node biopsy, performance of radical node dissections for node-positive cases-and some aspects of postoperative management (use of radiation for desmoplastic melanoma primaries and for clinically node-positive disease) will change in the future with the potential widespread adoption of adjuvant and neoadjuvant therapies.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Excisão de Linfonodo , Margens de Excisão , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
3.
J Am Acad Dermatol ; 85(2): 423-441, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33931288

RESUMO

A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.


Assuntos
Procedimentos Cirúrgicos Dermatológicos/normas , Neoplasias Cutâneas/cirurgia , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como Assunto
4.
Dermatol Surg ; 47(7): 891-907, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34228675

RESUMO

SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.


Assuntos
Procedimentos Cirúrgicos Dermatológicos/normas , Medicina Baseada em Evidências , Neoplasias Cutâneas/cirurgia , Humanos , Guias de Prática Clínica como Assunto
5.
N Engl J Med ; 376(23): 2211-2222, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28591523

RESUMO

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).


Assuntos
Excisão de Linfonodo , Melanoma/secundário , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/cirurgia , Conduta Expectante , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Análise de Intenção de Tratamento , Excisão de Linfonodo/efeitos adversos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico , Linfedema/etiologia , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Complicações Pós-Operatórias , Prognóstico , Modelos de Riscos Proporcionais , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/efeitos adversos , Análise de Sobrevida , Ultrassonografia , Adulto Jovem
6.
Mol Pharmacol ; 93(3): 190-196, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29242354

RESUMO

Drug combinations acting synergistically to kill cancer cells have become increasingly important in melanoma as an approach to manage the recurrent resistant disease. Protein kinase B (AKT) is a major target in this disease but its inhibitors are not effective clinically, which is a major concern. Targeting AKT in combination with WEE1 (mitotic inhibitor kinase) seems to have potential to make AKT-based therapeutics effective clinically. Since agents targeting AKT and WEE1 have been tested individually in the clinic, the quickest way to move the drug combination to patients would be to combine these agents sequentially, enabling the use of existing phase I clinical trial toxicity data. Therefore, a rapid preclinical approach is needed to evaluate whether simultaneous or sequential drug treatment has maximal therapeutic efficacy, which is based on a mechanistic rationale. To develop this approach, melanoma cell lines were treated with AKT inhibitor AZD5363 [4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide] and WEE1 inhibitor AZD1775 [2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one] using simultaneous and sequential dosing schedules. Simultaneous treatment synergistically reduced melanoma cell survival and tumor growth. In contrast, sequential treatment was antagonistic and had a minimal tumor inhibitory effect compared with individual agents. Mechanistically, simultaneous targeting of AKT and WEE1 enhanced deregulation of the cell cycle and DNA damage repair pathways by modulating transcription factors p53 and forkhead box M1, which was not observed with sequential treatment. Thus, this study identifies a rapid approach to assess the drug combinations with a mechanistic basis for selection, which suggests that combining AKT and WEE1 inhibitors is needed for maximal efficacy.


Assuntos
Proteína Forkhead Box M1/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Esquema de Medicação , Antagonismo de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Quimioterapia Combinada , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Mieloma Múltiplo/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Pirimidinonas , Pirróis/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Nanomedicine ; 14(3): 863-873, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29317343

RESUMO

Drug resistance and toxicity are major limitations of cancer treatment and frequently occurs during melanoma therapy. Nanotechnology can decrease drug resistance by improving drug delivery, with limited toxicity. This study details the development of nanoparticles containing arachidonyl trifluoromethyl ketone (ATK), a cytosolic phospholipase A2 inhibitor, which can inhibit multiple key pathways responsible for the development of recurrent resistant disease. Free ATK is toxic, limiting its efficacy as a therapeutic agent. Hence, a novel nanoliposomal delivery system called NanoATK was developed, which loads 61.7% of the compound and was stable at 4oC for 12 weeks. The formulation decreased toxicity-enabling administration of higher doses, which was more effective at inhibiting melanoma cell growth compared to free-ATK. Mechanistically, NanoATK decreased cellular proliferation and triggered apoptosis to inhibit melanoma xenograft tumor growth without affecting animal weight. Functionally, it inhibited the cPLA2, AKT, and STAT3 pathways. Our results suggest the successful preclinical development of a unique nanoliposomal formulation containing ATK for the treatment of melanoma.


Assuntos
Ácidos Araquidônicos/farmacologia , Sistemas de Liberação de Medicamentos , Lipossomos/administração & dosagem , Melanoma/tratamento farmacológico , Nanopartículas/administração & dosagem , Inibidores de Fosfolipase A2/farmacologia , Fosfolipases A2 Citosólicas/antagonistas & inibidores , Animais , Ácidos Araquidônicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Lipossomos/química , Melanoma/enzimologia , Melanoma/patologia , Camundongos , Camundongos Nus , Nanopartículas/química , Inibidores de Fosfolipase A2/administração & dosagem , Células Tumorais Cultivadas
8.
Oncologist ; 21(10): 1218-1229, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27511905

RESUMO

Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1-2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. IMPLICATIONS FOR PRACTICE: The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described, with the goal of enabling health care professionals to provide appropriate counseling and supportive care interventions to their patients.


Assuntos
Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Carcinoma Basocelular/tratamento farmacológico , Proteínas Hedgehog/antagonistas & inibidores , Piridinas/efeitos adversos , Alopecia/induzido quimicamente , Astenia/induzido quimicamente , Proteínas Hedgehog/fisiologia , Humanos , Transdução de Sinais/efeitos dos fármacos , Espasmo/induzido quimicamente , Distúrbios do Paladar/induzido quimicamente , Redução de Peso/efeitos dos fármacos
9.
J Craniofac Surg ; 27(7): 1642-1646, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27763969

RESUMO

BACKGROUND: Congenital anophthalmia is a rare anomaly that results in micro-orbitism and craniofacial microsomia. Treatment with static conformers is labor-intensive and provides minimal stimulation for orbital growth that requires eventual reconstruction with orbital osteotomies after skeletal maturity. METHODS: A protocol for the treatment of congenital anophthalmia is presented. Patients underwent a preoperative low-dose radiation computed tomography (CT) scan of the facial bones to assess orbital volume. An intraorbital expander was placed and was filled on a monthly basis. Quantitative changes in the affected and unaffected orbits were assessed by a repeat CT scan obtained 1 year postoperatively. RESULTS: Two patients with left unilateral congenital anophthalmia were prospectively followed. In a 4-month-old, the affected orbital width and height increased by 171.6% and 116.7% respectively compared with the unaffected orbit. In a 4-year-old, the affected orbital width increased by 36.1% but the height decreased by 35.3% compared with the unaffected orbit. At 18 months follow-up, no complications, ruptures, infections, or extrusions have been observed. CONCLUSIONS: Our results support that accelerated expansion can be achieved in a 4-month-old orbit reversing the effects of anophthalmia. However, in a 4-year-old, minimal growth was observed. The lack of accelerated growth in this study may be explained by synostosis of the orbital sutures. As such, expansion should be initiated at the earliest age possible. Further longitudinal study is ongoing to determine if sustained catch-up growth will obviate or reduce the complexity of a secondary correction.


Assuntos
Anoftalmia/cirurgia , Expansão de Tecido/métodos , Anoftalmia/diagnóstico por imagem , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Expansão de Tecido/instrumentação , Dispositivos para Expansão de Tecidos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Am J Pathol ; 182(4): 1151-62, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23416158

RESUMO

BRAF is the most mutated gene in melanoma, with approximately 50% of patients containing V600E mutant protein. (V600E)B-RAF can be targeted using pharmacological agents, but resistance develops in patients by activating other proteins in the signaling pathway. Identifying downstream members in this signaling cascade is important to design strategies to avoid the development of resistance. Unfortunately, downstream proteins remain to be identified and therapeutic potential requires validation. A kinase screen was undertaken to identify downstream targets in the (V600E)B-RAF signaling cascade. Involvement of aurora kinase B (AURKB) and Wee1-like protein kinase (WEE1) as downstream proteins in the (V600E)B-RAF pathway was validated in xenografted tumors, and mechanisms of action were characterized in size- and time-matched tumors. Levels of only AURKB and WEE1 decreased in melanoma cells, when (V600E)B-RAF, mitogen-activated protein kinase 1/2, or extracellular signal-regulated kinase 1/2 protein levels were reduced using siRNA compared with other identified kinases. AURKB and WEE1 were expressed in tumors of patients with melanoma at higher levels than observed in normal human melanocytes. Targeting these proteins reduced tumor development by approximately 70%, similar to that observed when inhibiting (V600E)B-RAF. Furthermore, protein or activity levels of AURKB and WEE1 decreased in melanoma cells when pharmacological agents targeting upstream (V600E)B-RAF or mitogen-activated protein kinase were used to inhibit the (V600E)B-RAF pathway. Thus, AURKB and WEE1 are targets and biomarkers of therapeutic efficacy, lying downstream of (V600E)B-RAF in melanomas.


Assuntos
Substituição de Aminoácidos/genética , Proteínas de Ciclo Celular/metabolismo , Melanoma/enzimologia , Melanoma/patologia , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Aurora Quinase B , Aurora Quinases , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Citometria de Fluxo , Fase G2/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Camundongos , Camundongos Nus , Mitose/efeitos dos fármacos , Terapia de Alvo Molecular , Estadiamento de Neoplasias , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Skinmed ; 12(1): 54-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24720087
12.
Ann Plast Surg ; 71(3): 274-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23788150

RESUMO

With a rise in tissue expander-based breast reconstructions (TEBRs) using acellular dermal matrix (ADM), we have seen an increase in ADM-specific complications. In this study, we aimed to evaluate clinically significant seroma (CSS) formation-defined by the need for a drainage procedure-to determine if there was a difference in incidence between product types: AlloDerm (AL), DermaMatrix (DM), and FlexHD (FHD). This was a retrospective review of consecutive patients who underwent TEBR at a single institution. The total number of reconstructed breasts was separated into the following 4 groups according to the product type: AL, DM, FHD, or no ADM. We identified the total number of CSSs and compared these data between product types. A logistic regression was performed in an attempt to identify independent risk factors associated with seroma formation. In total, we identified 284 consecutive TEBRs. Overall, there were 17 (7.7%) seromas in 220 breast reconstructions in which ADM was used. When comparing the number of CSS between groups-AL (n = 2, 4.0%), DM (n = 6, 5.4%), FHD (n = 9, 14.75%), and no ADM (n = 1, 1.5%)-we found a significant difference in seroma incidence between product types (P = 0.016). Multivariate analysis identified a strong trend toward FHD as an independent predictor of seroma formation (P = 0.061). Our review suggests that there is strong trend in CSS formation with the use of FHD as compared to other product types and reconstructions in which no ADM was used.


Assuntos
Derme Acelular/efeitos adversos , Colágeno/efeitos adversos , Mamoplastia/métodos , Complicações Pós-Operatórias/etiologia , Seroma/etiologia , Adulto , Idoso , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Drenagem , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Mamoplastia/instrumentação , Mastectomia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de Risco , Seroma/epidemiologia , Seroma/terapia , Expansão de Tecido/instrumentação , Dispositivos para Expansão de Tecidos , Resultado do Tratamento
13.
Ann Plast Surg ; 69(4): 347-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22868313

RESUMO

Acellular dermal matrix (ADM) is frequently used in tissue expander breast reconstruction (TEBR) for coverage of the inferior pole. Several published studies have suggested increased rates of complications with the use of ADM. It is unknown, however, if the type of ADM used for TEBR impacts complication rates. The aim of this study is to compare 3 different types of ADM for TEBR in regard to clinically significant complications, specifically infection. We performed a retrospective analysis of primary breast cancer-related TEBR with or without ADM. Exclusion criteria consisted of prior major breast surgery, inadequate data, or loss to follow-up. Reconstructions were grouped by dermal sling type, AlloDerm, DermaMatrix (DM), FlexHD (FHD), or no ADM. Complications included cellulitis, abscess, seroma, expander leak or puncture, skin necrosis, wound dehiscence, or hematoma. Those requiring admission to hospital or reoperation were considered significant. Of 284 breasts reconstructed, 49 used AlloDerm, 110 used DM, 62 used FHD, and 64 used no ADM. The total complication rate with AlloDerm was 22% [95% confidence interval (CI), 11-34], with DM was 15% (95% CI, 8-21), and with FHD was 18% (95% CI, 8-28) (P=0.47). Infectious complication rates for AlloDerm, DM, and FHD were equal at 10% (P=0.97). The total complication rate of all ADM reconstructions as a grouped cohort was 17% compared to 11% without ADM (P=0.48). The overall incidence of infectious complications with ADM was 10% compared to 2% without ADM (P=0.09). There is no difference in the clinically significant overall complication rate or incidence of infection between AlloDerm, DM, and FHD. Isolating infectious complications, there is a trend toward increased incidence with ADM compared to reconstructions without.


Assuntos
Derme Acelular , Implante Mamário/métodos , Complicações Pós-Operatórias/etiologia , Transplante de Pele , Expansão de Tecido , Adulto , Idoso , Neoplasias da Mama/cirurgia , Colágeno , Feminino , Humanos , Incidência , Mastectomia , Pessoa de Meia-Idade , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos
14.
JAMA Surg ; 157(9): 835-842, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35921122

RESUMO

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.


Assuntos
Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Melanoma/patologia , Prognóstico , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
15.
J Surg Oncol ; 103(5): 421-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21400527

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SNLB) is the standard of care in staging of melanoma and other skin cancers. Early studies used lymphazurin (LZ) for SLNB. A national shortage of LZ promoted methylene blue (MB) as an alternate stain. OBJECTIVE: This study compares complication rates between LZ and MB in SLNB patients, and the reliability dyes in locating sentinel lymph nodes. METHODS: Charts were reviewed for patients who underwent SLNB for skin cancers between September 2006 and November 2008 at Penn State Hershey Medical Center. The type and quantity of dye, the presence of blue stained sentinel nodes, and any complications were recorded. RESULTS: Ninety-three patients underwent SLNB (46 LZ, 47 MB). The amount of dye used was similar (avg. 0.93 ml LZ, 1.24 ml MB). The complication rate of LZ was 8.7%, and MB was 25.5%. There was significantly more (P = 0.003) skin graft complications in the MB patients (6/12) versus LZ (0/15). CONCLUSIONS: There is a higher rate of complications with MB, especially with skin grafting. The reported risk of anaphylaxis with LZ has not been reported in volumes <2 ml. The sentinel lymph node identification rate is historically similar between dyes, and in this study was noted to be higher with LZ.


Assuntos
Linfonodos/patologia , Melanoma/diagnóstico , Azul de Metileno , Complicações Pós-Operatórias , Corantes de Rosanilina , Neoplasias Cutâneas/diagnóstico , Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Corantes , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Melanoma/cirurgia , Prognóstico , Cintilografia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/cirurgia , Padrão de Cuidado
16.
Clin Plast Surg ; 48(4): 713-733, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34503732

RESUMO

Great strides in immunotherapy and targeted therapy have revolutionized the management of previously devastating, advanced melanomas. Although these subfields continue to progress, novel approaches in intratumoral oncolytic therapy, adoptive cell therapy, and vaccine therapies are being developed as adjuncts or alternatives. Cytokines, meanwhile, are seeing a resurgence as a viable option as well. The array of effective agents will, in the next few years, provide options for therapy not only in the adjuvant or unresectable settings but also in the neoadjuvant settings. Perhaps, too, in earlier stage melanomas.


Assuntos
Melanoma , Humanos , Imunoterapia , Melanoma/terapia , Terapia Neoadjuvante
17.
Plast Reconstr Surg ; 147(5): 812e-829e, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33890904

RESUMO

SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Medicina Baseada em Evidências , Neoplasias Cutâneas/cirurgia , Humanos , Guias de Prática Clínica como Assunto
18.
Clin Cancer Res ; 27(15): 4195-4204, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33753453

RESUMO

PURPOSE: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma. PATIENTS AND METHODS: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v., 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery. RESULTS: A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5-85.8], with a 43% (95% CI: 27.3-60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively). CONCLUSIONS: Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.See related commentary by Menzies et al., p. 4133.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Interferon alfa-2/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia
19.
J Immunother Cancer ; 8(2)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33199512

RESUMO

Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells. There have been few guidelines or consensus statements on how to optimally collect and manage biospecimens and source material being used for immunotherapy and related research. The Society for Immunotherapy of Cancer Surgery Committee has brought together surgical experts from multiple subspecialty disciplines to identify best practices and to provide consensus on how best to access and manage specific tissues for immuno-oncology treatments and clinical investigation. In addition, the committee recommends early integration of surgeons and other interventional physicians with expertise in biospecimen collection, especially in clinical trials, to optimize the quality of tissue and the validity of correlative clinical studies in cancer immunotherapy.


Assuntos
Imunoterapia/métodos , Oncologia/normas , Obtenção de Tecidos e Órgãos/métodos , Ensaios Clínicos como Assunto , Humanos
20.
Am J Surg ; 216(3): 558-561, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29395022

RESUMO

BACKGROUND: Infrared fluorescence imaging with indocyanine green (ICG) is a novel method for sentinel node localization. Our objective was to assess ICG and fluorescence imaging for preoperative and intraoperative utility. METHODS: 87 eligible patients participated in this prospective study. All patients received injection of ICG dye in addition to both methylene blue and 99mTc. Each sentinel node was assessed for the presence of each dye. RESULTS: ICG was visible prior to incision in 44% of subjects. 99mTc identified a mean of 1.89 SLN per patient. ICG identified a mean of 1.87 SLN while methylene blue (MB) dye identified a mean of 0.71 SLN. 99mTc and ICG identified the same number of sentinel nodes per patient (P = .73) while methylene blue was inferior in its ability to localize sentinel nodes (P < .001). CONCLUSION: Our findings indicate that ICG/fluorescence imaging has limited ability to identify the nodal basin preoperatively, but is equivalent to 99mTc for intraoperative identification of sentinel nodes and superior to MB.


Assuntos
Angiofluoresceinografia/métodos , Verde de Indocianina/farmacologia , Linfografia/métodos , Melanoma/secundário , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
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