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1.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(8): 629-638, oct. 2020.
Artigo em Espanhol | IBECS | ID: ibc-188364

RESUMO

BACKGROUND AND OBJECTIVES: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. MATERIAL AND METHODS: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. RESULTS: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five-and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. CONCLUSIONS: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect tosee to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays


ANTECEDENTES Y OBJETIVOS: La pandemia del coronavirus COVID-19 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las patologías comunes. El objetivo de este estudio es estimar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para los carcinomas de células escamosas (CCE) como de los melanomas. MATERIAL Y MÉTODO: Estudio observacional retrospectivo de cohortes multicéntrico. Se desarrolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. RESULTADOS: Se incluyeron un total de 200 pacientes con CCEs localizados en la cabeza y el cuello y 1000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 mes tras el diagnóstico. En la muestra, los CCE mayores de 4 cm o > 6 mm de grosor (definidos como T3) pasaron de 83 (41.5%) en el grupo de estudio real a una estimación de 58,5%, 70,5% y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2%, 8,2% y 5,2% a los 2, 5 y 10 años, respectivamente, tras tres meses de retraso. Para los melanomas, los melanomas ultragruesos (> 6 mm) pasaron del 6,9% en el grupo de estudio al 21,9%, 30,2% y 30,2% tras 1,2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. CONCLUSIONES: En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes. Palabras clave: melanoma, pronóstico, diagnóstico precoz, carcinoma de células escamosas cutáneo, COVID-19, confinamiento


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Neoplasias de Células Escamosas/mortalidade , Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Betacoronavirus , Pandemias , Quarentena , Análise de Sobrevida , Estudos Retrospectivos , Estudos de Coortes
2.
Adv Exp Med Biol ; 1268: 143-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918217

RESUMO

Solar UV exposure is critical and complex in the etiology and prognosis of skin cancer, particularly cutaneous malignant melanoma. Sun exposure and one of its "derivatives," vitamin D, have been implicated in protection against mortality from melanoma. However, the relationships are inconsistent. At this time, it is not possible to make clear recommendations for or against sun exposure in relationship to melanoma prognosis. However, this relationship deserves continued exploration.


Assuntos
Neoplasias Cutâneas/mortalidade , Raios Ultravioleta , Humanos , Melanoma/etiologia , Melanoma/mortalidade , Melanoma/prevenção & controle , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/mortalidade , Neoplasias Induzidas por Radiação/prevenção & controle , Prognóstico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Vitamina D
3.
Zhonghua Fu Chan Ke Za Zhi ; 55(6): 395-401, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842246

RESUMO

Objective: To assess the treatment and prognosis of vulvar melanoma. Methods: A total of 59 cases of primary vulvar melanoma admitted to Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1st, 1981 to November 30th, 2019 were collected. The clinical characteristics, treatment, survival and prognostic factors of vulvar melanoma were analyzed retrospectively. The end date of follow-up was January 15th, 2020.The median follow-up time was 26.0 months (range:2-198 months). Results: (1) Clinical characteristics: the median age of 59 patients with vulvar melanoma was 56 years old (range:18-83 years old). According to the American Joint Committee on Cancer stage manual, there were 18, 7, 26 and 8 cases of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. The lesion of 38 cases was single and the other 21 cases were multiple. The largest diameter of the tumor ranged from 0.3 to 17.0 cm.The surface of the lesion was ulcerated in 17 cases. (2) Treatment: a total of 59 cases with vulvar melanoma, 56 patients received surgery, 36 cases of them received radical resection of vulva and 20 received local extended resection of vulvar tumor due to unilateral vulva lesion. Three patients did not receive surgery,one received chemotherapy combined with interferon, one received interferon, and one received radiotherapy. Lymph node management: among the 56 patients treated by surgery, 37 patients received inguinal lymphadenectomy, 24 (65%, 24/37) of whom were confirmed with inguinal lymph node metastasis by postoperative pathological examination. Inguinal lymph nodes enlargement were not found in 19 cases by preoperative imaging and clinical examination. In these 19 patients, three patients received inguinal lymph node biopsy, among them, one (1/3) patient was confirmed with inguinal lymph node metastasis by postoperative pathological examination, and the remaining 16 patients did not receive inguinal lymph node surgery. Postoperative adjuvant treatment: among the 56 patients who received surgery, 31 received adjuvant chemotherapy,one received adjuvant radiotherapy, four received interferon therapy, 17 received combination therapy including chemotherapy, and three did not receive postoperative adjuvant therapy. (3) Survival:during the follow-up period, the median survival time of 59 patients with vulvar melanoma was 30.0 months (range:2.0-198.0 months). The 3-year survival rate was 42.5%, and the 5-year survival rate was 23.8%. The median survival time of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 72.0, 45.0, 24.0 and 23.0 months, respectively. The difference among stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ were statistically significant (P<0.01). The median survival time of patients undergoing radical resection of the vulva (35.0 months) and local enlarged tumor resection (29.0 months) were significantly longer than that of patients without surgery (9.0 months, P<0.01). The median survival time of the patients who underwent inguinal lymphadenectomy, lymph node biopsy and those who did not undergo surgery were 35.0, 32.0 and 30.0 months, respectively. There were no significant differences among the 3 groups (P>0.05). The median survival time of postoperative adjuvant chemotherapy patients (49.0 months) were significantly longer than that of postoperative adjuvant radiotherapy, interferon,and combination therapy including chemotherapy (9.0, 14.0 and 26.0 months, respectively, all P<0.01). (4) Prognostic factors: the univariate analysis showed that stage, vulvar operation and postoperative adjuvant treatment were the risk factors affecting the prognosis of patients with vulvar melanoma (P<0.01). Multivariate analysis revealed that stage alone was an independent risk factor affecting the prognosis of patients with vulvar melanoma (P<0.01). Conclusions: The prognosis of patients with vulvar melanoma is poor, and stage is an independent prognostic factor.Surgery combined with postoperative adjuvant chemotherapy may achieve relatively good results.


Assuntos
Excisão de Linfonodo , Melanoma/cirurgia , Neoplasias Vulvares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia , Adulto Jovem
4.
Medicine (Baltimore) ; 99(28): e20957, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664098

RESUMO

Primary malignant melanoma of esophagus (PMME) is a rare malignant tumor of esophagus. This study aimed to investigate the clinic pathologic characteristics and analyze the factors that might affect the prognosis of PMME patients.A total of 20 PMME patients who underwent surgical treatment in our hospital from 1975 to 2017 were analyzed. The clinical data, surgical and pathologic features of all patients were collected.For 20 PMME patients, the average age was 57.3 ±â€Š10.7 years, and the male patients account for 75%. Most of the tumors (95%) were located in the middle and lower of the esophagus. There were 7 patients with primary tumor invasion beyond the muscular layer (T3 + T4) and 10 patients with lymph node metastasis (LNM). The median survival time of 20 patients was 12 months, and the 1-year and 5-year survival rates were 50% and 16.9%, respectively. The probability of LNM in tumors confined to submucosa (T1) and myometrium (T2) was lower than that in tumors with deeper invasion (T3, T4) (P = .035). Multivariate analysis showed that tumor node metastasis (TNM) staging was the independent prognostic factor for survival of PMME patients (hazard ratio [95% confidence interval], 4.15 [1.36-12.67]; P = .012).For PMME patients, tumors with deeper invasion were more likely to have LNM, and TNM staging was an independent predictor of prognosis for survival. Early detection of the disease and radical resection of the tumor are critical for better survival of the PMME patients.


Assuntos
Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Melanoma/mortalidade , Melanoma/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
5.
BMC Bioinformatics ; 21(1): 329, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703153

RESUMO

BACKGROUND: Melanoma phenotype and the dynamics underlying its progression are determined by a complex interplay between different types of regulatory molecules. In particular, transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) interact in layers that coalesce into large molecular interaction networks. Our goal here is to study molecules associated with the cross-talk between various network layers, and their impact on tumor progression. RESULTS: To elucidate their contribution to disease, we developed an integrative computational pipeline to construct and analyze a melanoma network focusing on lncRNAs, their miRNA and protein targets, miRNA target genes, and TFs regulating miRNAs. In the network, we identified three-node regulatory loops each composed of lncRNA, miRNA, and TF. To prioritize these motifs for their role in melanoma progression, we integrated patient-derived RNAseq dataset from TCGA (SKCM) melanoma cohort, using a weighted multi-objective function. We investigated the expression profile of the top-ranked motifs and used them to classify patients into metastatic and non-metastatic phenotypes. CONCLUSIONS: The results of this study showed that network motif UCA1/AKT1/hsa-miR-125b-1 has the highest prediction accuracy (ACC = 0.88) for discriminating metastatic and non-metastatic melanoma phenotypes. The observation is also confirmed by the progression-free survival analysis where the patient group characterized by the metastatic-type expression profile of the motif suffers a significant reduction in survival. The finding suggests a prognostic value of network motifs for the classification and treatment of melanoma.


Assuntos
Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Melanoma/genética , RNA Longo não Codificante/metabolismo , Biologia Computacional/métodos , Humanos , Melanoma/metabolismo , Melanoma/mortalidade , Melanoma/patologia , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Fenótipo , RNA-Seq , Fatores de Transcrição/metabolismo
6.
Medicine (Baltimore) ; 99(29): e21329, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702928

RESUMO

In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure.This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included.Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%.Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Melanoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
7.
Anticancer Res ; 40(7): 3839-3846, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620623

RESUMO

BACKGROUND/AIM: Because 50% of uveal melanoma metastasize within 10 years of diagnosis, there is urgent need for accurate prognostic factors. MATERIALS AND METHODS: To identify genes that can act as prognostic factors in uveal melanoma, we performed survival analyses using three independent cohorts. Using log-rank test and univariate cox regression, genes which could stratify the prognosis in all cohorts simultaneously depending on their expression levels were selected as novel biomarkers. Hub genes were obtained by analyzing the interaction and relationship between the selected genes using String and Cytoscape. Additionally, prognostic power was calculated by using C-indices and AUC. RESULTS: A total of 37 oncogene-like and 14 tumor suppressor-like genes were selected. Protein-protein analysis revealed that NDUFB9, NDUFV2, CYC1 among oncogene-like genes, CTNNB1 among tumor suppressor-like genes were found to be hub genes and core biomarkers in uveal melanoma. CONCLUSION: NDUFB9, NDUFV2, CYC1 and CTNNB1 genes may act as prognostic factors in uveal melanoma.


Assuntos
Biomarcadores Tumorais/genética , Melanoma/genética , Neoplasias Uveais/genética , Estudos de Coortes , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Oncogenes , Prognóstico , Mapas de Interação de Proteínas , Transcriptoma , Neoplasias Uveais/mortalidade
8.
Cancer Invest ; 38(7): 415-423, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32643437

RESUMO

The aim of the study was to investigate if there was an association between intraoperative NSAID use and recurrence or survival. A cohort of patients who underwent sentinel lymph node biopsy for the treatment of cutaneous melanoma was retrospectively recruited. After applying inclusion and exclusion criteria, 516 were included (NSAIDs = 307). The 10-year melanoma-specific survival was 63.2%. Log-rank test showed no statistically significant differences in time to treatment failure, melanoma-specific survival, disease-free survival, and overall survival between the study groups. The current study did not support the use of intraoperative NSAIDs in preventing death or recurrence in patients with melanoma.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Idoso , Estudos de Coortes , Feminino , Humanos , Isoxazóis/uso terapêutico , Estimativa de Kaplan-Meier , Cetorolaco/uso terapêutico , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Período Perioperatório , Piroxicam/análogos & derivados , Piroxicam/uso terapêutico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Resultado do Tratamento
9.
Hum Cell ; 33(4): 1264-1272, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32686068

RESUMO

Biological understanding of pigmentation and its association with clinicopathological implications in uveal melanoma (UM) risk is still unexplored. HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 2 (HERC2) and Pink-eyed dilution protein (P-protein) are the important markers that regulate pigmentation in eye. Therefore, our aim of the study was to investigate the expression of HERC2 and P-protein in the UM patients and correlate with patient outcome. Fifty-two formalin-fixed paraffin-embedded UM tissue samples were included to detect the expression of HERC2 and P-protein by immunohistochemistry and validated by western blot. Cox proportional hazard model and log-rank test were used to determine the prognostic potential of these proteins. High pigmentation was seen in 67% of the UM cases. The expression of HERC2 and P-protein was present in 44% and 71% cases, respectively. On statistical analysis, increased pigmentation, epithelioid cell type, and ciliary body invasion were significant with the protein expressions (p < 0.05). Metastasis-free survival was reduced in UM cases which expressed HERC2 and P-protein. On multivariate analysis, P-protein expression was found to be an independent prognostic factor. Our findings suggest that HERC2 and P-protein could be used as novel predictors of high pigmentation in UM cases which have high metastatic potential.


Assuntos
Biomarcadores Tumorais/análise , Fatores de Troca do Nucleotídeo Guanina/análise , Melanoma/diagnóstico , Proteínas de Membrana Transportadoras/análise , Neoplasias Uveais/diagnóstico , Adulto , Intervalo Livre de Doença , Feminino , Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Imuno-Histoquímica , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Neoplasias Uveais/genética , Neoplasias Uveais/mortalidade , Neoplasias Uveais/patologia
10.
Surgery ; 168(3): 518-526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32669204

RESUMO

BACKGROUND: It is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. METHODS: We queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. RESULTS: There were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P < .05), but for melanomas >6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P < .05). For melanomas >10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P < .05). CONCLUSION: Prognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Melanoma/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/mortalidade , Pele/patologia , Idoso , Vasos Sanguíneos/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
11.
Anticancer Res ; 40(6): 3505-3512, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487651

RESUMO

AIM: To assess the prognostic significance of nucleolar morphological parameters in a large cohort of patients with uveal melanoma. PATIENTS AND METHODS: The presence, size and number of nucleoli of cancer cells were assessed in haematoxylin and eosin (HE)-stained slides of 164 formalin-fixed paraffin-embedded primary uveal melanoma tissue specimens. The results were correlated with clinicopathological features and patient survival. RESULTS: The presence of macronucleoli and multiple nucleoli significantly correlated with the epithelioid type of uveal melanoma, high mitotic rate, and marked pleomorphism. There was a positive correlation between the presence of macronucleoli as well as the number of nucleoli and the largest tumour basal diameter. The increased nucleolus count in tumour cells positively correlated with primary tumour (pT) staging. The presence of both prominent and multiple nucleoli was associated with significantly reduced overall and disease-free survival. CONCLUSION: Histological assessment of nucleolar morphology in routine HE staining would be a helpful low-cost method to obtain reliable prognostic information.


Assuntos
Nucléolo Celular/patologia , Melanoma/patologia , Neoplasias Uveais/patologia , Idoso , Nucléolo Celular/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/ultraestrutura , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral , Neoplasias Uveais/mortalidade , Neoplasias Uveais/ultraestrutura
12.
Medicine (Baltimore) ; 99(21): e19936, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481257

RESUMO

Rapid growth of cutaneous melanoma is associated with aggressive histopathologic features and poor prognosis. However, the impact of growth rate (GR) in acral melanoma (AM) remains largely unknown.We performed this study to identify the impact of GR on lymph node metastasis and survival in AM.We analyzed cases of invasive AM diagnosed at our institution between 1998 and 2017. We investigated the impact of GR on the prognosis of AM.A total of 126 cases of invasive AM were included. Log (GR) was significant associated with lymph node metastasis in the univariate logistic regression analysis (P = .005). The log-rank test revealed statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) among the GR quartiles. In the Cox regression analysis, log (GR) was an independent predictor for DFS (P = .041), but not for DSS in multivariate analysis. In the subgroup analysis, log (GR) was an independent predictor for early-stage (≤2A) AM (DFS, P = .002; DSS, P = .004).The limitations of this study include the retrospective design of the study and possible recall bias.Our results suggest that GR is an important prognostic factor for DFS and DSS in AM patients and an independent predictor for early-stage AM.


Assuntos
Doenças do Pé/mortalidade , Doenças do Pé/patologia , Mãos , Melanoma/mortalidade , Melanoma/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Prognóstico , República da Coreia , Estudos Retrospectivos , Taxa de Sobrevida
13.
Actas Dermosifiliogr ; 111(8): 629-638, 2020 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-32513393

RESUMO

Background and objectives: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. Material and methods: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. Results: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter >4cm or thickness >6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (>6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. Conclusions: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays.


Assuntos
Betacoronavirus , Carcinoma de Células Escamosas/patologia , Infecções por Coronavirus/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Pneumonia Viral/epidemiologia , Neoplasias Cutâneas/patologia , Carga Tumoral , Fatores Etários , Algoritmos , Carcinoma de Células Escamosas/mortalidade , Diagnóstico Tardio/efeitos adversos , Diagnóstico Tardio/estatística & dados numéricos , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Acesso aos Serviços de Saúde , Humanos , Masculino , Melanoma/mortalidade , Pandemias , Vigilância em Saúde Pública/métodos , Quarentena , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Cutâneas/mortalidade , Espanha/epidemiologia , Fatores de Tempo , Tempo para o Tratamento
14.
Rev Assoc Med Bras (1992) ; 66(2): 100-107, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428140

RESUMO

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Humanos , Melanoma/mortalidade , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Resultado do Tratamento
15.
J Surg Oncol ; 122(3): 555-561, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32441371

RESUMO

BACKGROUND AND OBJECTIVES: Metastasectomy for melanoma provides durable disease control in carefully selected patients. Similarly, BRAF-targeted and immune checkpoint inhibition has improved median overall survival (OS) in metastatic patients. We hypothesized that there is an increasing role for metastasectomy in melanoma patients responding to these therapies. METHODS: Retrospective analysis of a prospectively maintained database identified 128 patients with stage IV melanoma who received targeted molecular and/or checkpoint inhibitors at an academic institution from 2006 to 2017. Records were reviewed to characterize clinicopathologic characteristics, response to treatment, and intent of surgery for those who underwent metastasectomy. OS was analyzed by the Kaplan-Meier method. RESULTS: Median OS from stage IV diagnosis was 31.3 months. A total of 81 patients received checkpoint inhibitors, 11 received targeted inhibitors, and 36 received both. A total of 73 patients underwent metastasectomy. Indications for surgery included the intent to render disease-free (54%), palliation (34%), and diagnostic confirmation (11%). Responders to systemic therapy who underwent metastasectomy had improved OS compared to responders who did not (84.3 vs. 42.9 months, P = .018). CONCLUSIONS: Metastasectomy for melanoma is associated with improved OS in patients that respond to targeted molecular or immunotherapy. Resection should be strongly considered in this cohort as multimodality treatment results in excellent OS.


Assuntos
Melanoma/secundário , Melanoma/terapia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Melanoma/mortalidade , Melanoma/cirurgia , Metastasectomia , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188380, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32461135

RESUMO

Cellular communication through gap junctions and hemichannels formed by connexins and through channels made by pannexins allows for metabolic cooperation and control of cellular activity and signalling. These channel proteins have been described to be tumour suppressors that regulate features such as cell death, proliferation and differentiation. However, they display cancer type-dependent and stage-dependent functions and may facilitate tumour progression through junctional and non-junctional pathways. The accumulated knowledge and emerging strategies to target connexins and pannexins are providing novel clinical opportunities for the treatment of cancer. Here, we provide an updated overview of the role of connexins and pannexins in malignant melanoma. We discuss how targeting of these channel proteins may be used to potentiate antitumour effects in therapeutic settings, including through improved immune-mediated tumour elimination.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Conexinas/metabolismo , Melanoma/secundário , Neoplasias Cutâneas/patologia , Pele/patologia , Animais , Antineoplásicos Imunológicos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Carcinogênese/patologia , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/imunologia , Linhagem Celular Tumoral , Conexinas/agonistas , Conexinas/antagonistas & inibidores , Modelos Animais de Doenças , Progressão da Doença , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/patologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Melanoma/tratamento farmacológico , Melanoma/imunologia , Melanoma/mortalidade , Microbiota/imunologia , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/imunologia , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Estadiamento de Neoplasias , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Pele/citologia , Pele/microbiologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
18.
Eur J Cancer ; 133: 94-103, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32470710

RESUMO

BACKGROUND: Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79). PATIENTS AND METHODS: In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 µg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20). RESULTS: Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32-1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7-88.8%) and 72.9% (95% CI: 58.3-83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15-0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9-96.0%) vs 76.4% (95% CI: 62.1-85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons. CONCLUSIONS: The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for patients with ulcerated melanomas without palpable nodes.


Assuntos
Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Melanoma/terapia , Polietilenoglicóis/administração & dosagem , Neoplasias Cutâneas/terapia , Úlcera Cutânea/terapia , Conduta Expectante , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Esquema de Medicação , Europa (Continente)/epidemiologia , Feminino , Humanos , Injeções Subcutâneas , Masculino , Oncologia/organização & administração , Melanoma/complicações , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Recombinantes/administração & dosagem , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Úlcera Cutânea/complicações , Úlcera Cutânea/mortalidade , Úlcera Cutânea/patologia , Sociedades Médicas/organização & administração , Análise de Sobrevida , Conduta Expectante/métodos
19.
Biochim Biophys Acta Rev Cancer ; 1873(2): 188364, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275934

RESUMO

Hyperactivation of the Mitogen Activated Protein Kinase (MAPK) pathway is prevalent in melanoma, principally due to mutations in the BRAF and NRAS genes. MAPK inhibitors are effective only short-term, and recurrence occurs due to functional redundancies or intertwined pathways. The remodeling of Ca2+ signaling is also common in melanoma cells, partly through the increased expression of T-type channels (TTCCs). Here we summarize current knowledge about the prognostic value and molecular targeting of TTCCs. Furthermore, we discuss recent evidence pointing to TTCCs as molecular switches for melanoma chemoresistance, which set the grounds for novel combined therapies against the advanced disease.


Assuntos
Antineoplásicos/uso terapêutico , Canais de Cálcio Tipo T/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Linhagem Celular Tumoral , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , GTP Fosfo-Hidrolases/antagonistas & inibidores , GTP Fosfo-Hidrolases/genética , Humanos , Estimativa de Kaplan-Meier , Sistema de Sinalização das MAP Quinases/genética , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Mutação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Resultado do Tratamento
20.
Am J Ophthalmol ; 216: 156-164, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278769

RESUMO

PURPOSE: To evaluate the consistency of hepatic ultrasonography (US) with staging computed tomography (CT) and magnetic resonance imaging (MRI), to analyze why US was inconsistent with CT/MRI, and to compare CT/MRI. DESIGN: Reliability analysis. METHODS: Two hundred fifteen patients whose primary uveal melanoma was managed in the Helsinki University Hospital and who were diagnosed with hepatic metastases by US within 60 days of staging CT/MRI from January 1999 to December 2016 were included. Patients attended a real-life follow-up schedule including hepatic US, liver function tests (LFT), and a confirmatory CT/MRI. We evaluated the consistency of US with staging CT/MRI regarding the presence and number of metastases. RESULTS: The enrolled patients underwent 215 US, 167 CT, and 69 MRI examinations, and 67% of them had biopsy-confirmed metastases. Screening was regular for 98% of the patients, and 66% were asymptomatic. US was fully consistent with CT/MRI in detecting metastases in 113 (53%) patients, in 63 (29%) CT/MRI showed more metastases, and in 16 (7%) CT/MRI showed fewer metastases than US. CT/MRI was inconsistent with US in 23 (11%) patients. The sensitivity of US in detecting metastases was 96% (95% confidence interval, 92-98). US failed to suggest metastases in 10 patients. LFT were abnormal in 6 of them, and a newly detected hepatic lesion was present by US in 4. CONCLUSIONS: Hepatic US is a sensitive screening modality in detecting metastases in patients with primary uveal melanoma, if combined with LFT and, in case of any newly detected lesion, a confirmatory MRI.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética , Melanoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia , Neoplasias Uveais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Uveais/mortalidade , Neoplasias Uveais/patologia , Adulto Jovem
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