Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most frequent types of cancer, and both originate from the keratinocyte transformation, giving rise to the group of ...tumors called keratinocyte carcinomas (KCs). The invasive behavior is different in each group of KC and may be influenced by their tumor microenvironment. The principal aim of the study is to characterize the protein profile of the tumor interstitial fluid (TIF) of KC to evaluate changes in the microenvironment that could be associated with their different invasive and metastatic capabilities. We obtained TIF from 27 skin biopsies and conducted a label-free quantitative proteomic analysis comparing seven BCCs, 16 SCCs, and four normal skins. A total of 2945 proteins were identified, 511 of them quantified in more than half of the samples of each tumoral type. The proteomic analysis revealed differentially expressed TIF proteins that could explain the different metastatic behavior in both KCs. In detail, the SCC samples disclosed an enrichment of proteins related to cytoskeleton, such as Stratafin and Ladinin-1. Previous studies found their upregulation positively correlated with tumor progression. Furthermore, the TIF of SCC samples was enriched with the cytokines S100A8/S100A9. These cytokines influence the metastatic output in other tumors through the activation of NF-kB signaling. According to this, we observed a significant increase in nuclear NF-kB subunit p65 in SCCs but not in BCCs. In addition, the TIF of both tumors was enriched with proteins involved in the immune response, highlighting the relevance of this process in the composition of the tumor environment. Thus, the comparison of the TIF composition of both KCs provides the discovery of a new set of differential biomarkers. Among them, secreted cytokines such as S100A9 may help explain the higher aggressiveness of SCCs, while Cornulin is a specific biomarker for BCCs. Finally, the proteomic landscape of TIF provides key information on tumor growth and metastasis, which can contribute to the identification of clinically applicable biomarkers that may be used in the diagnosis of KC, as well as therapeutic targets.
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•SCC samples disclosed an enrichment of proteins related to cytoskeleton.•Secreted cytokines such as S100A9 may help explain the higher aggressiveness of SCC.•The proteomic landscape of TIF provides key information on tumor growth & metastasis.
In brief, the principal aim of the study is to characterize the protein profile of the TIF of KC to evaluate changes in the microenvironment that could be associated with their invasive and metastatic capabilities. In detail, the SCC samples disclosed an enrichment of proteins related to cytoskeleton, such as Stratafin and Ladinin-1, previously correlated with tumor progression. Furthermore, the TIF of SCC samples was enriched with the cytokines S100A8/S100A9 that may help explain the higher aggressiveness of SCCs.
Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited.
To assess the DSS and outcomes of surgical and nonsurgical ...therapeutic modalities in a large cohort of EMPD patients.
Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals.
Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively.
Retrospective design.
EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.
Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups.
To ...determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific–death.
A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death.
Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio SHR: 2.89 95% CI, 1.44-5.83; P = .003, 2.32 95% CI, 1.13-4.77; P = .021, and 2.863 95% CI, 1.25-6.55; P = .013), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 95% CI, 1.18-10.2; P = .023).
Retrospective study and heterogeneity of treatments.
The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.
Survival analyses can provide valuable insights into effectiveness and safety as perceived by prescribers. Here, we aimed to evaluate adalimumab (ADA) survival and the interruption risk factors in a ...multicentre cohort of patients with hidradenitis suppurativa (HS). Moreover, we performed a subanalysis considering the periods before and after the onset of the COVID-19 pandemic.
We conducted a retrospective study including 539 adult patients with HS who received ADA from 1 May 2015 to 31 December 2022. Overall drug survival was analysed using Kaplan-Meier survival curves and compared between the subgroups via stratified log-rank test. Possible predictors for overall drug survival and reasons for discontinuation were assessed using univariate and multivariate Cox regression.
Overall, 50.1% were females with a mean age of 43.5 ± 1 years and a mean BMI of 29.5 ± 6.7. At the start of ADA, 95.29% were biologic-naïve and 24.63% had undergone surgical treatment. During follow-up, 9.46% of patients required dose escalation, while 39.92% interrupted ADA. Concomitant therapy was used in 64.89% of cases. A subanalyses comparing pre- and post-pandemic periods revealed a tendency to initiate ADA treatment at a younger age, among patient with higher BMI and at a lower HS stage after COVID-19 pandemic. Interestingly, ADA demonstrated extended survival compared to previous studies, with a median overall drug survival of 56.2 months (95% CI 51.2 to 80.3). The primary causes for discontinuation were inefficacy (51.69%), followed by adverse effects (21.35%). Female sex, longer delay in HS diagnosis, higher baseline IHS4 score and concomitant spondyloarthritis were associated with poorer ADA survival or increased risk of discontinuation.
ADA demonstrated prolonged survival (median 56.2 months). While addition of antibiotics did not have a positive effect on survival rate, basal IHS4 proved useful in predicting ADA survival.
Abstract Background Topical imiquimod has been shown to be an effective treatment for extramammary Paget disease (EMPD), although available evidence supporting its use is based on case reports and ...small series of patients. Objectives To investigate the therapeutic outcomes and analyse potential clinicopathological factors associated with the imiquimod response in a large cohort of patients with EMPD. Methods Retrospective chart review of 125 patients with EMPD treated with imiquimod at 20 Spanish tertiary-care hospitals. Results During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) treatments achieving a complete response (CR), 41 (30.6%) a partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥ 6 cm; P = 0.04) and EMPD affecting > 1 anatomical site (P = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤ 4 vs. > 4 times per week; P = 0.112). Among patients who achieved CR, 30 of 69 (43%) treatments resulted in local recurrences during a mean follow-up period of 36 months, with an estimated 3- and 5-year recurrence-free survival of 55.7% and 36.4%, respectively. Conclusions Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favourable therapeutic response could be expected in larger lesions and those affecting > 1 anatomical site. Based on our results, a three to four times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for patients with EMPD.
La activación del paciente es un concepto que se refiere a la voluntad de gestionar su salud y atención médica. Para evaluarla, se ha desarrollado y validado una medida de activación del paciente ...(PAM). Diversos estudios informan baja activación en pacientes con enfermedades crónicas. No obstante, la información sobre activación de pacientes en tratamiento con hemodiálisis es escasa. El objetivo del presente estudio es describir el nivel de activación de pacientes en tratamiento crónico de una unidad de hemodiálisis (HD) y su relación con los parámetros de control de la enfermedad.
Estudio observacional transversal en pacientes con enfermedad renal crónica avanzada en tratamiento crónico con HD. Se incluyeron 96 pacientes. La activación se midió con el cuestionario PAM-13. Se estudió su relación con variables descriptivas (edad, sexo, comorbilidad, estudios, hábitat) y variables de control de la enfermedad (acceso vascular, flujo sangre, potasemia, fosfatemia, ganancia interdialítica). Para ello se emplearon como métodos estadísticos la prueba de correlación de Spearman, modelo de retrogresión lineal múltiple y modelo logístico.
La puntuación media (desviación estándar SD) de PAM-13 fue de 63,19 (15,21). La activación se asociaba significativamente con el acceso vascular (p = 0,003), flujo de sangre (p = 0,024), y ganancia interdialítica de los pacientes (p = 0,008).
La activación de pacientes en tratamiento crónico con hemodiálisis es baja. Una mayor activación se relaciona con disponer de fístula arteriovenosa, con mayor flujo sanguíneo y con menor ganancia interdialítica. Son necesarios futuros estudios que confirmen y apliquen nuestros resultados.
Patient activation is a concept that refers to the willingness to manage one's health and medical care. To assess it, a patient activation measure (PAM) has been developed and validated. Several studies report low activation in patients with chronic diseases. However, information on activation in hemodialysis patients is scarce. The aim of the present study is to describe the activation level of patients on chronic treatment in an HD unit and its relationship with disease control parameters.
Cross-sectional observational study in patients with advanced chronic kidney disease on chronic HD treatment. Ninety-six patients were included. Activation was measured with the PAM-13 questionnaire. Its relationship with descriptive variables (age, sex, comorbidity, studies, habitat) and disease control variables (vascular access, blood flow, potassaemia, phosphataemia, interdialytic gain) was studied. For this purpose, Spearman's correlation test, multiple linear regression model and logistic model were used as statistical methods.
The mean (SD) PAM-13 score was 63.19 (15.21). Activation was significantly associated with vascular access (P = .003), blood flow (P = .024), and interdialytic gain of patients (P = .008).
Activation in patients on chronic hemodialysis treatment is low. Higher activation is related having an arteriovenous fistula, higher blood flow and lower interdialytic gain. Future studies are needed to confirm and apply our results.
Summary
Background
A dramatic rise in the incidence rates of basal cell carcinoma (BCC) in young women has been reported.
Objectives
We investigate potential risk factors (RF) for sporadic BCC in ...young patients and the current distribution of such RF in the general population of Catalonia, comparing the differences among men and women.
Patients and Methods
A case‐control study was performed, 69 BCCs diagnosed in patients ≤ 45 years of age vs. 69 healthy controls. Afterward, 1,078 participants from the general population completed an RF questionnaire.
Results
Repeated sunburns were more frequent in instances of early‐onset BCC in covered skin than in sun‐exposed skin (P = 0.029). In the general population, 39.1 % of participants reported sunbed use (50.1 % in women, 10.9 % in men). Sunbed use was the only relevant RF more predominant in women than men, favoring the trend to female predominance of BCCs above other RF. Additionally, we found a significant trend in young participants for reduced sunbed use (P < 0.001), although they had the same percentage of repeated sunburns. Repeated sunburns are the most relevant RF for early‐onset BCCs that can be targeted in prevention campaigns.
Conclusions
We should be aware of the more relevant RF for early‐onset BCCs and their distribution among the general population to address preventive campaigns.
Zusammenfassung
Hintergrund
Es gibt Berichte über einen dramatischen Anstieg der Inzidenz von Basalzellkarzinomen (BZK) bei jungen Frauen.
Ziele
Wir untersuchten potenzielle Risikofaktoren (RF) für ...sporadische BZK bei jungen Patienten sowie die gegenwärtige Verteilung dieser RF in der Allgemeinbevölkerung Kataloniens. Dabei verglichen wir Männer und Frauen.
Patienten und Methodik
Es wurde eine Fall‐Kontroll‐Studie mit 69 Patienten ≤ 45 Jahren mit BZK‐Diagnose und 69 gesunden Kontrollen durchgeführt. Anschließend füllten 1078 Teilnehmer aus der Allgemeinbevölkerung einen RF‐Fragebogen aus.
Ergebnisse
Wiederholte Sonnenbrände waren bei BZK mit frühem Beginn an bedeckter Haut häufiger als an sonnenexponierten Hautbereichen (p = 0,029). In der Allgemeinbevölkerung gaben 39,1 % der Teilnehmer an, Solarien zu nutzen (50,1 % der Frauen, 10,9 % der Männer). Die Solariumnutzung war der einzige relevante RF, der bei Frauen häufiger auftrat als bei Männern und dementsprechend den Trend zu einer weiblichen Prädominanz bei BZK mehr als andere RF begünstigt. Zudem ermittelten wir bei jungen Teilnehmern einen signifikanten Trend hin zu verringerter Solariumnutzung (p < 0,001). Der Prozentsatz wiederholter Sonnenbrände war jedoch unverändert. Wiederholter Sonnenbrand war der wichtigste RF für BZK mit frühem Beginn, der mittels Präventionskampagnen gezielt angegangen werden kann.
Schlussfolgerungen
Wir sollten uns der wichtigsten RF für BZK mit frühem Beginn sowie ihrer Verteilung in der Allgemeinbevölkerung bewusst sein, um sie in Präventionskampagnen anzugehen.
