RESUMEN
Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Genotipo , Anciano , Polimorfismo GenéticoRESUMEN
BACKGROUND AND OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. MATERIAL AND METHOD: We conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. RESULTS: A total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. CONCLUSIONS: The mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.
Asunto(s)
Carcinoma de Células Escamosas , Progresión de la Enfermedad , Metástasis Linfática , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Anciano , Estudios Longitudinales , Persona de Mediana Edad , Metástasis Linfática/patología , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/epidemiología , AdultoRESUMEN
BACKGROUND AND OBJECTIVE: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity. METHODS: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire. RESULTS: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6). CONCLUSIONS: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit.
Asunto(s)
Artritis Psoriásica , Diagnóstico Precoz , Humanos , Artritis Psoriásica/diagnóstico , Femenino , Estudios Transversales , Masculino , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Psoriasis/diagnóstico , Psoriasis/complicaciones , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , España , Traducciones , Estudios de FactibilidadRESUMEN
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
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Neoplasias de Células Escamosas/mortalidad , Melanoma/mortalidad , Neoplasias Cutáneas/mortalidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Betacoronavirus , Pandemias , Cuarentena , Análisis de Supervivencia , Estudios Retrospectivos , Estudios de CohortesRESUMEN
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.
Asunto(s)
Betacoronavirus , Carcinoma de Células Escamosas/patología , Infecciones por Coronavirus/epidemiología , Neoplasias de Cabeza y Cuello/patología , Melanoma/patología , Neumonía Viral/epidemiología , Neoplasias Cutáneas/patología , Carga Tumoral , Factores de Edad , Algoritmos , COVID-19 , Carcinoma de Células Escamosas/mortalidad , Diagnóstico Tardío/efectos adversos , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Melanoma/mortalidad , Pandemias , Vigilancia en Salud Pública/métodos , Cuarentena , Estudios Retrospectivos , SARS-CoV-2 , Factores Sexuales , Neoplasias Cutáneas/mortalidad , España/epidemiología , Factores de Tiempo , Tiempo de TratamientoRESUMEN
No disponible
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Humanos , Masculino , Anciano , Psoriasis/etiología , Anticuerpos Monoclonales Humanizados/efectos adversos , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Edema/fisiopatología , Sistema Nervioso Periférico/inmunología , Sistema Nervioso Periférico/fisiopatologíaRESUMEN
The interaction of lectin-like transcript 1 (LLT1) with CD161 inhibits Natural Killer cell activation. Overexpression of LLT1 contributes to the immunosuppressive properties of tumor cells. However, there are little data about LLT1 expression in human solid tumors. The objective of this paper is to investigate the relationship between LLT1 expression with the clinicopathologic features and its impact on the prognosis of head and neck cutaneous squamous cell carcinoma (cSCC). LLT1 expression was analyzed on paraffin-embedded tissue samples obtained from 100 patients with cSCC by immunohistochemistry. The estimator of Fine and Gray was used to estimate the cumulative incidence curves for relapse. Proportional Hazard models and Hazard ratios (HRs) were used for studying the risk of tumor relapse and mortality. LLT1 strong expression was a significant risk factor for nodal metastasis with crude and adjusted ratios (HRs) of 3.40 (95% CI 1.39-9.28) and 3.25 (95% CI 1.15-9.16); and for cSCC specific death of 6.17 (95% CI 1.79-21.2) and 6.10 (95% CI 1.45-25.7). Strong LLT1 expression is an independent predictor of nodal metastasis and poor disease-specific survival and it might be helpful for risk stratification of patients with cSCC.
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Biomarcadores de Tumor/metabolismo , Lectinas Tipo C/metabolismo , Metástasis Linfática/patología , Receptores de Superficie Celular/metabolismo , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Medición de Riesgo/métodos , Factores de Riesgo , Piel/patología , Neoplasias Cutáneas/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidadRESUMEN
No disponible
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Humanos , Femenino , Persona de Mediana Edad , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/cirugía , Tumores Fibrosos Solitarios/complicaciones , Tumores Fibrosos Solitarios/inmunología , Tumores Fibrosos Solitarios/mortalidadRESUMEN
No disponible
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Humanos , Masculino , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/patología , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/patología , Carcinoma/complicaciones , Carcinoma/diagnóstico , Carcinoma/patología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/fisiopatología , Células Epiteliales/patología , Neoplasias Glandulares y Epiteliales/complicaciones , Inmunohistoquímica/instrumentación , Inmunohistoquímica/métodos , Inmunohistoquímica/tendenciasRESUMEN
BACKGROUND: Sentinel lymph node biopsy and wide local excision of the primary melanoma (SLNB) is now a standard staging procedure for patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear. OBJECTIVE: To determine whether there is an association between performance of SLNB and patient prognosis. METHODS: Studies assessing the association between performance of SLNB and patient prognosis were pooled from MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar. From each study, first author's last name, publication year, origin country, type of study design, characteristics of participants and the Hazard risk (HR) for melanoma specific survival (MSS) with the corresponding 95% confidence interval (95% CI) were collected. Methodological assessment of the studies was evaluated using the Newcastle-Ottawa scale (NOS) and the 'Risk of bias' tool detailed in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses for the global HR were performed. In addition, in order to explore the sources of heterogeneity among the studies, sensitivity analyses are also provided. RESULTS: A total of six studies with 8764 patients who had undergone SLNB and 11054 patients who had undergone wide location excision alone (WLEA) were identified for the analysis. The indicators suggest that the heterogeneity is low: τ2 = 0; H = 1 [1; 1.74]; I2 = 0% [0%; 66.5%]. Evidence for publication bias was not found (Egger's test P = 0.4654). The pooled MSS HR from fixed effects analysis was determined to be 0.88 (95% CI = 0.80-0.96). CONCLUSIONS: Although no significant survival difference was observed in four of the six series, the pooling summary data from all the studies that deal with this issue suggested that SLNB is associated with a significantly better outcome compared with WLEA for localized melanoma.
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Melanoma/patología , Melanoma/cirugía , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Humanos , PronósticoAsunto(s)
Neoplasias Faciales/diagnóstico , Melanoma Amelanótico/diagnóstico , Tumor Rabdoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano de 80 o más Años , Neoplasias Faciales/cirugía , Resultado Fatal , Frente/cirugía , Humanos , Masculino , Márgenes de Escisión , Melanoma Amelanótico/cirugía , Tumor Rabdoide/cirugía , Neoplasias Cutáneas/cirugía , Colgajos QuirúrgicosRESUMEN
Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first author's last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle-Ottawa scale. Crude RR was calculated from the data provided in each article. Meta-analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta-regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random-effects analysis was determined to be 6.32 (95% CI, 4.02-9.93). Global proportions of positive samples were 0.79 (95% CI, 0.72-0.84) and 0.12 (95% CI, 0.08-0.19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non-negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found.
Asunto(s)
Carcinoma de Células de Merkel/complicaciones , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus/complicaciones , Neoplasias Cutáneas/complicaciones , Infecciones Tumorales por Virus/complicaciones , HumanosRESUMEN
Complete androgen insensitivity syndrome is an extremely infrequent disease. The patients exhibit female phenotype because of insensitivity to the androgen receptor and may develop tumors, especially in their undescended gonads. We report a case of bilateral Sertoli cell adenoma in gonads with unilateral serous cystadenoma, in an elderly phenotypic woman with primary amenorrhea. We also provide radiological and pathological studies.