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BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.
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INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.
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BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.
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Melanoma , Proteínas de Unión al ARN , Neoplasias Cutáneas , Apnea Obstructiva del Sueño , Humanos , Hipoxia , Melanoma/patología , Paraspeckles , Proteínas de Unión al ARN/metabolismo , Neoplasias Cutáneas/complicaciones , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba , Melanoma Cutáneo MalignoRESUMEN
The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).
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Anticuerpos Monoclonales , Psoriasis , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Anticuerpos Monoclonales/efectos adversos , Resultado del Tratamiento , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Índice de Severidad de la EnfermedadRESUMEN
Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.
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Psoriasis , Calidad de Vida , Anticuerpos Monoclonales Humanizados , Estudios de Cohortes , Humanos , Medición de Resultados Informados por el Paciente , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis. A total of 22 articles corresponding to population PK/PD models of tumor necrosis factor (TNF)-α inhibitors (adalimumab and golimumab), interleukin (IL)-23 inhibitors (guselkumab, tildrakizumab, and risankizumab), IL-23/IL-12 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) were collected. A summary of the clinical trials conducted so far in psoriasis was included, together with the current structural population PK and PD models. The most significant and clinical covariates were body weight (BW) and the presence of immunogenicity on clearance (CL). The lack of consensus on PK/PD relationships has prevented establishing an adequate dosage and, therefore, accentuates the need for TDM in psoriasis.
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Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Anciano , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/cirugía , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/cirugía , Humanos , Cirugía de Mohs , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/cirugíaRESUMEN
Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.
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Dermatofibrosarcoma/cirugía , Procedimientos Quirúrgicos Dermatologicos/métodos , Cirugía de Mohs/métodos , Sistema de Registros , Neoplasias Cutáneas/cirugía , Dermatofibrosarcoma/patología , Humanos , Invasividad Neoplásica , Estudios Prospectivos , Factores de Riesgo , Neoplasias Cutáneas/patologíaRESUMEN
Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non-OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81-61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells.
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Proliferación Celular/fisiología , Melanoma/metabolismo , Midkina/metabolismo , Neovascularización Patológica/metabolismo , Neoplasias Cutáneas/metabolismo , Apnea Obstructiva del Sueño/metabolismo , Adulto , Anciano , Línea Celular Tumoral , Células Cultivadas , Estudios Transversales , Femenino , Humanos , Hipoxia/metabolismo , Hipoxia/patología , Masculino , Melanoma/patología , Persona de Mediana Edad , Neovascularización Patológica/patología , Neoplasias Cutáneas/patología , Apnea Obstructiva del Sueño/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Melanoma Cutáneo MalignoRESUMEN
Active transforming growth factor-ß1 (TGF-ß1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-ß1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-ß1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-ß1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-ß1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-ß1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-ß1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-ß1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-ß1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients.
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Melanoma/patología , Obesidad/sangre , Neoplasias Cutáneas/patología , Apnea Obstructiva del Sueño/sangre , Factor de Crecimiento Transformador beta1/sangre , Adulto , Anciano , Línea Celular Tumoral , Femenino , Humanos , Leptina/sangre , Masculino , Melanoma/sangre , Melanoma/complicaciones , Persona de Mediana Edad , Obesidad/complicaciones , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Recommendations on when to perform sentinel lymph node (SLN) biopsy in cutaneous squamous cell carcinoma (cSCC) are lacking despite the tumor's clear predilection for lymphatic spread. OBJECTIVE: To analyze the frequency of SLN metastasis in published series of cSCC in the context of the eighth edition of the American joint Committee on Cancer (AJCC-8) and the Brigham and Women's Hospital (BWH) staging criteria. METHODS: Systematic review of studies of patients with cSCC who underwent SLN biopsy that described biopsy results. RESULTS: In total, 153 patients with 24 positive SLN biopsies (15.7%) were included. Based on the AJCC-8 criteria positivity rates in the T2 and T3 categories were 8.3% (1/12 patients) and 25% (8/32), respectively. Using the BWH system there were, 2/33 in category T2a (6.5%), and 5/17 in category T2b (29.8%). On applying the same criteria to tumors of the trunk and extremities the results were similar. CONCLUSION: It would seem reasonable to recommend SLN biopsy for patients with AJCC-8 Stage T3+ disease or BWH Stage T2b/T3 disease. Both the AJCC-8 and the BWH systems would appear to be useful for staging cSCC of the trunk and extremities.
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Carcinoma de Células Escamosas/patología , Estadificación de Neoplasias/métodos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Humanos , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Secukinumab is a first-in-class interleukin 17A monoclonal antibody that has demonstrated an excellent safety and efficacy profile in phase 3 studies. OBJECTIVE: To evaluate the effectiveness of secukinumab in daily clinical practice and to understand the clinical and epidemiologic characteristics of patients treated with secukinumab in clinical settings. METHODS: In this multicenter prospective observational study, we recruited adult patients with moderate-to-severe plaque psoriasis from 12 hospitals in Spain during January-December 2016. These patients were treated with secukinumab and prospectively followed at 12-week intervals for 52 weeks. RESULTS: In total, 158 patients were recruited to the study. A Psoriasis Area and Severity Index (PASI) score improvement ≥75% over baseline (PASI-75) was achieved by 57%, 83.5%, 89%, and 78.5% of patients at weeks 4, 12, 24, and 52, respectively. PASI-90 was achieved in 27.8%, 62%, 64.6%, and 63.2% of patients at weeks 4, 12, 24, and 52, respectively; PASI-75 and PASI-90 responders were significantly more common among patients with a body mass index <30 kg/cm2 and patients without previous biologic therapy failures. LIMITATIONS: Observational study. Time from onset of psoriasis was not evaluated. CONCLUSION: Secukinumab is a safe treatment with effectiveness rates similar to those found in its phase 3 studies. These rates endure up to a year from start of treatment.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Índice de Masa Corporal , Fármacos Dermatológicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Obstructive sleep apnoea (OSA) upregulates the programmed cell death-1 receptor and its ligand (PD-L1) pathway, potentially compromising immunosurveillance. We compared circulating levels of soluble PD-L1 (sPD-L1) in patients with cutaneous melanoma according to the presence and severity of OSA, and evaluated relationships with tumour aggressiveness and invasiveness.In a multicentre observational study, 360 patients with cutaneous melanoma underwent sleep studies, and serum sPD-L1 levels were assayed using ELISA. Cutaneous melanoma aggressiveness indices included mitotic rate, Breslow index, tumour ulceration, Clark level and tumour stage, and sentinel lymph node (SLN) metastasis was recorded as a marker of invasiveness.sPD-L1 levels were higher in severe OSA compared to mild OSA or non-OSA patients. In OSA patients, sPD-L1 levels correlated with Breslow index and were higher in patients with tumour ulceration, advanced primary tumour stages or with locoregional disease. The incorporation of sPD-L1 to the classic risk factors to SLN metastasis led to net improvements in the classification of 27.3%.Thus, sPD-L1 levels are increased in melanoma patients with severe OSA, and, in addition, might serve as a potential biomarker of cutaneous melanoma aggressiveness and invasiveness in this group of subjects.
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Antígeno B7-H1/sangre , Biomarcadores de Tumor/sangre , Melanoma/sangre , Neoplasias Cutáneas/sangre , Apnea Obstructiva del Sueño/sangre , Adulto , Anciano , Antropometría , Estudios Transversales , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/complicaciones , Melanoma/patología , Persona de Mediana Edad , Mitosis , Invasividad Neoplásica , Metástasis de la Neoplasia , Obesidad , Sobrepeso , Curva ROC , Análisis de Regresión , Factores de Riesgo , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patología , Apnea Obstructiva del Sueño/complicacionesRESUMEN
BACKGROUND: Folliculitis decalvans (FD) is a rare neutrophilic cicatricial alopecia that poses a therapeutic challenge. OBJECTIVES: To describe the therapeutic response in a large number of cases of FD with long-term follow-up and analyze potential prognostic factors associated with severity of form and with a better therapeutic response. METHODS: This multicenter prospective study included patients with FD who had a minimum of 5 years of follow-up. Severity was assessed by the maximum diameter of the cicatricial area. Therapeutic response was evaluated according to stabilization of the size of the cicatricial areas and the improvement in clinical symptoms. RESULTS: A total of 60 patients (37 men [61.7%] and 23 women [38.3%]) with a mean age of 40 years were included. Earlier age of onset (P = .01) was statistically associated with severity of form. Treatment with rifampicin and clindamycin, tetracyclines, and intralesional steroids was the most effective. No statistically significant prognostic factors predicting a better therapeutic response were found. LIMITATIONS: Because FD is a rare disease, the main limitation was the sample size. CONCLUSIONS: An earlier age of onset was associated with the severe form of the disease. The proposed specific therapeutic protocol can be a very useful tool in clinical dermatologic practice.
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Alopecia/patología , Foliculitis/tratamiento farmacológico , Foliculitis/patología , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/patología , Corticoesteroides/uso terapéutico , Alopecia/tratamiento farmacológico , Alopecia/etiología , Antibacterianos/uso terapéutico , Cicatriz/tratamiento farmacológico , Cicatriz/patología , Estudios de Cohortes , Terapia Combinada , Femenino , Foliculitis/complicaciones , Estudios de Seguimiento , Humanos , Isotretinoína/uso terapéutico , Masculino , Minoxidil/uso terapéutico , Análisis Multivariante , Fotoquimioterapia/métodos , Estudios Retrospectivos , Medición de Riesgo , Dermatosis del Cuero Cabelludo/complicaciones , España , Factores de Tiempo , Resultado del TratamientoRESUMEN
Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, <25, 25-50, 51-75, >75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those <6%, and VEGF expression >75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Dermatitis Exfoliativa/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Piel/efectos de los fármacos , Adulto , Anticuerpos Monoclonales Humanizados , Dermatitis Exfoliativa/diagnóstico , Dermatitis Exfoliativa/inmunología , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/inmunología , Piel/inmunología , Piel/patología , Resultado del TratamientoRESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and its incidence is rising. The prognosis is mostly good but patients with high-risk cSCC have a greater risk of recurrence and death. The aim of the present study was to conduct a systematic review analyzing the prevalence, predictors and prognostic utility of sentinel lymph node (SLN) involvement in cSCC. We performed a published work search in Ovid MEDLINE and reviewed the reference lists of selected studies. Based on the 23 studies included in the systematic review, the proportion of patients with cSCC and positive SLN biopsy findings was 8% (95% confidence interval, 5.1-10.8%; I2 = 44.51%). We found no studies reporting on predictors of SLN involvement in cSCC or on the prognostic utility of this finding following adjustment for confounders. The rate of positive SLN in cSCC is less than previously reported. Criteria for recommending SLN biopsy as a staging tool for cSCC vary considerably from study to study, and none of the studies were large enough to reliably identify predictors of SLN positivity. No randomized controlled trials have yet analyzed whether SLN biopsy may improve the prognosis of cSCC. More studies are required on the prognostic value of SLN positivity and the associated risk factors in cSCC.
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Carcinoma de Células Escamosas/epidemiología , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/epidemiología , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Neoplasias Cutáneas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Humanos , Metástasis Linfática , Recurrencia Local de Neoplasia/patología , Prevalencia , Pronóstico , Factores de Riesgo , Neoplasias Cutáneas/patologíaRESUMEN
Melanoma is a highly prevalent cancer that is associated with substantial mortality. Although clinical staging procedures can serve as relatively robust prognostic indicators, we aimed to determine whether assessments of the abundance of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF) in postexcisional melanoma tumor tissues may enable more accurate determination of tumor aggressiveness. We carried out a multicenter prospective study, in which we systematically evaluated 376 consecutive patients diagnosed with melanoma, and performed histochemical assessments for both HIF-1α and VEGF immunoreactivity in the tumor biopsies. Multivariate analyses showed that higher HIF-1α expression, but not high VEGF, were associated significantly and independently with increased tumor aggressiveness as derived from several well-established aggressiveness criteria. A limitation of this study was that this was a descriptive prospective study lacking a post-hoc verification arm. Thus, the presence of increased numbers of positively labeled HIF-1α cells in melanoma tumors may potentially serve as an indicator of tumor phenotype and prognosis, and accordingly guide therapy.