Search Results (508)

Epidermolysis bullosa (EB) is a group of debilitating, genetic skin disorders characterized by excessive skin fragility, blistering, and ulcerations that cause a cyclical wound healing process. EB presents itself in various subtypes, such as EB simplex (EBS), junctional EB (JEB), dystrophic (DEB), and Kindler Syndrome (KS), which all differ in their genetic cause, severity, and harbor different causes of mortality. Of these variants, JEB and DEB are the most severe, with EBS being the mildest form of the disease and KS presenting in extremely rare cases. The JEB variant tends to cause mortality early on in children less than two years of age due to failure to thrive, sepsis from wound infections, and airway obstruction. In the recessive form of DEB (RDEB), cutaneous squamous cell carcinoma (cSCC) is the major cause of death in patients, with one study reporting a mere 4-year survival after the first EB-cSCC diagnosis. Cutaneous SCCs in the setting of RDEB are particularly concerning because they are often more aggressive and show greater metastatic potential, as compared to ultraviolet-induced SCCs. This review aims to explore the pathophysiology of these EB variants as well as their implications for developing cSCCs. It will also discuss elements of the clinical presentation of such lesions in EB patients and the challenges associated with making a definitive diagnosis. Additionally, we will illuminate various diagnostic techniques, current and future management and treatment strategies for both cSCC and EB, and the importance of early screening and education for patients with EB to maximize patient lifespan and quality of life. Full article

Background/Objectives: In spite of substantial treatment progress, cancer persists as a leading health challenge. With the slow advancement in developing new anticancer agents, drug repurposing provides a promising strategy to enhance cancer therapy. This study investigates the antiproliferative and antimetastatic properties of two 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, atorvastatin and rosuvastatin, which represent lipophilic and hydrophilic statins, respectively. Methods: Growth inhibition was evaluated in a panel of human cancer cells using the standard MTT assay. Apoptotic effects were determined through flow cytometry, caspase-3 activity assay, mitochondrial membrane potential assessment, and Hoechst/Propidium iodide fluorescent double staining. Migration and invasion assays were conducted using wound-healing and Boyden chamber assays, respectively. Results: Atorvastatin demonstrated more pronounced growth-inhibitory effects than rosuvastatin, with the IC₅₀ values in the range of 2.57–61.01 µM. Atorvastatin exhibited both biochemical and morphological indicators of apoptosis. Flow cytometry revealed cell cycle disruptions and increased sub-G1 apoptotic populations in HPV-positive oral squamous carcinoma cells (UPCI-SCC-154) and HPV-negative cervical cancer cells (C33A). Atorvastatin also significantly inhibited cell migration and invasion in the tested cell lines. Conclusions: Our results highlight the promising anticancer potential of atorvastatin in cervical cancer and oral squamous carcinoma cells. However, these findings are limited to in vitro models and warrant further in vivo validation. Full article

Background/Objectives: Lymph node metastases represent the most important prognostic factor for survival in patients with localized squamous cell carcinoma (SCC) of the oral cavity. In patients with carcinoma of the tongue or floor of the mouth, elective neck dissection (END) has been the standard of care, but it has been replaced at many centers by sentinel lymph node biopsy (SLNB). This study’s purpose was to measure and compare recurrence rates between END and SLNB in patients with early SCC of the oral cavity. Methods: Patients were included in this retrospective monocenter cohort study, performed at the University Hospital of Zürich, if they underwent either END or SLNB for oral squamous cell carcinoma (OSCC) of the tongue or floor of the mouth between January 2008 and December 2018. Only patients with early-stage tumors and a clinically negative neck (T1 or T2; cN0) who had a follow-up period of at least 5 years were included. Patients with a T3 or T4 tumor or a clinically positive neck were excluded, as were those who previously underwent therapy for another head and neck carcinoma. The predictor variable was the surgical treatment used, with subjects divided into two groups: END and SLNB. The main outcome variable was the time to recurrent disease, defined as the time between the primary surgical treatment and the diagnosis of recurrence. The covariates were primary tumor location, pT status, pN status, histopathological grade and postoperative radiotherapy. We used descriptive analysis, univariate analysis and the logrank test, with a p-value < 0.05 considered statistically significant. We deliberately refrained from multivariate analysis due to insignificant statistical results in the univariate analysis. Results: In total, 82 patients (46 male, 36 female; median age at the time of surgery: 58.9 years) were included, with a median observation period of 4.3 years. The main primary tumor location was the floor of the mouth (62.2%). The SLNB cohort had smaller primary tumors in comparison to the END cohort (20% vs. 37% pT2, respectively). Furthermore, pN+ disease was more prevalent in the END group in comparison to the SLNB group (81.8% vs. 74.1% pN0, respectively). Recurrence-free survival was not significantly different between the two groups. Subgroup analysis demonstrated a higher risk of recurrent disease in pN+ groups undergoing SLNB compared to those undergoing END. Conclusions: We demonstrate that SLNB is a useful tool for assessing lymph nodes of the neck. In cases of pN+ necks after SLNB and subsequent neck dissection, patients need to be closely followed up with due to the risk of recurrent disease. Full article

Background/Objectives: Non-melanoma skin cancer (NMSC) is the most common malignancy globally, with cutaneous squamous cell carcinoma (cSCC) posing a significant risk of regional metastasis, especially in high-risk anatomical areas such as the head and neck. While general risk factors for metastasis are well known, few studies have directly compared the clinical and pathological features of synchronous versus metachronous metastatic behavior. This study aimed to evaluate the clinicopathological characteristics and reconstructive implications associated with these two metastatic patterns in head and neck NMSC. Methods: We conducted a retrospective observational study of 46 patients with histologically confirmed metastatic NMSC of the head and neck, treated between January 2022 and May 2024 at a tertiary care center. Patients were stratified into synchronous or metachronous metastasis groups. Clinical data, histopathological features, metastatic sites, and surgical approaches were analyzed. Comparative statistics were applied using chi-square and t-tests, with significance set at p < 0.05. Results: Of the 46 patients, 50% had synchronous and 50% had metachronous metastases. The lower lip was the most common primary tumor site in both groups. Perineural and lymphovascular invasion were more frequent in synchronous metastases. Metachronous cases often required more complex reconstructive procedures, including free flap reconstructions and mandibular resections. Patients with metachronous metastases were significantly older (p = 0.024), and approximately one-third developed metastases more than four years after initial treatment. Conclusions: Head and neck NMSC, particularly involving the lower lip, may exhibit late-onset metastatic potential. Risk-adapted surveillance extending beyond current guidelines is warranted to improve long-term outcomes in high-risk patients. Full article

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article

Grade 304L stainless steel canisters are susceptible to crevice corrosion in marine environments. In the present study, white emery was utilized to create a simulation of dust accumulation. The corrosion testing was conducted at two distinct temperatures (35 °C and 45 °C) and three levels of relative humidity (45%, 55%, and 70% relative humidity). The chloride deposition density levels tested were 0.1 g/m² and 1 g/m². The test durations were 8000 h and 23,000 h. It is evident that with a chloride deposition density of 0.1 g/m² at a temperature of 45 °C and a relative humidity of 70%, the onset of stress corrosion cracking (SCC) occurred after 8000 h in the white emery deposition tests. In contrast, at a 1 g/m² chloride deposition density, the polytetrafluoroethylene (PTFE) crevice former test specimen exhibited continuous transgranular SCC within the same period. These quantitative findings emphasize the critical roles of salt load and environmental severity in the initiation of SCC. Full article

The UV-induced photolysis of 2-aminothiazole-4-carboxylic acid (ACA), a biologically active molecule, was studied using the infrared matrix isolation method. As the first step of photolysis, a decarboxylation reaction occurred. Subsequently, two main photolysis pathways of 2-aminothiazole were observed, during which a number of new molecules, including potential prebiotic carbodiimides or molecular complexes, were identified. The CS–CN bond cleavage path produced N-(1-sulfanylethen-2-yl)carbodiimide (fp1), N-(thiiran-2-yl)carbodiimide (fp3), N-(1-thioethan-2-yl)carbodiimide (fp2), N-(1-thioethan-1-yl)carbodiimide (fp4) and N-(1-thioethan-2-yl)cyanamide (fp33), which were identified for the first time. In this channel, additional disruption of the N–C bond produced cyanamide (fp27) and thiirene (fp28) and subsequent photoreactions generated carbodiimide (fp29) or ethynethiol (fp30). The CS–CC bond cleavage path occurred simultaneously and produced several new molecules: N’-ethynylcarbamimidothioic acid (fp14), N-ethynylcarbamimidothioic acid (fp17), N-ethenylidenecarbamimidothioic acid (fp18) and N-ethenylidenethiourea (fp15). In this channel, additional disruption of the N–C bond produced acetylene (fp23) and N-thiolcarbodiimide (fp26). Among the small molecules, N-thiolcarbodiimide and thiirene, as well as all molecular complexes, were observed for the first time. Full article

The combined effect of sulfate-reducing bacteria (SRB) and a microstructure on the stress corrosion behavior of heat-affected zones (HAZs) in pipeline steel for shale gas field applications was investigated. The results show that when the peak heating temperature reached 1020 °C, a coarse microstructure formed during multiple thermal cycles (MTCs), and Widmanstätten structures appeared in the HAZ. In the simulated environment, SRB intensified localized pitting corrosion of both the base metal and the HAZ. The welding HAZ was softened by the MTCs, and significant microcrack growth was observed in the presence of SRB. Among all subzones, the coarse-grained HAZ (CGHAZ) was the most susceptible to stress corrosion cracking (SCC) under shale gas service conditions. Cracks initiated at the metal surface and propagated vertically into the material. SRB activity further increased the SCC sensitivity of the CGHAZ. Full article

Objectives: Tobacco has been associated with the development of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). This study aimed to evaluate the in vitro and in vivo changes caused by carcinogen 4-nitroquinoline 1-oxide (4NQO), simulating smoking conditions. Materials and Methods: In the in vitro study, normal keratinocytes were exposed to 1.3 µM and 2.6 µM concentrations of 4NQO to induce dysplastic transformation (H-DISP) and malignant transformation (H-SCC), respectively. The cells were collected and subjected to hematoxylin and eosin (H&E) staining and immunocytochemistry with Ki-67. For the in vivo study, female C57BL/6J mice were divided into a pure control (PC) group and experimental groups exposed to 50 µg/mL (NQ) and 100 µg/mL (CM) of 4NQO in autoclaved drinking water. Each group was euthanized after 8, 12, 16, and 20 weeks of exposure. The tongues were collected, processed, stained with H&E, and analyzed using conventional light microscopy. Results: In vitro, significant morphological changes were observed in the H-DISP and H-SCC groups, with a cell proliferation index exceeding 30% in the H-DISP group. In vivo, the CM group showed greater progression to severe dysplasia/carcinoma within a shorter treatment period compared to the NQ group. Conclusions: We established critical doses and exposure durations for 4NQO, both in vitro and in vivo, to induce cellular changes and the formation of OL and OSCC, providing a standardized model for studies related to oral carcinogenesis. Full article

Background: Actinic keratosis (AK) is a common UV-induced intraepidermal neoplasm and a precursor to cutaneous squamous cell carcinoma (cSCC). Accurate, non-invasive assessment of AK severity is crucial for early intervention and risk stratification. Objective: To evaluate the relationship between clinical severity of AK, as defined by the Olsen grading scale, and predefined dermoscopic and reflectance confocal microscopy (RCM) features. Methods: This cross-sectional study enrolled 50 patients with clinically diagnosed AK at a tertiary dermatology center between April 2024 and July 2025. Each lesion was assessed clinically using the Olsen scale (grades 1–3), dermoscopically (five features scored 0–3; total score 0–15), and via RCM (five RCM parameters scored 0–3; total score 0–15). Statistical correlations between clinical grade and imaging features were analyzed using Pearson’s χ² test with effect size metrics. Results: Diffuse erythema (p < 0.001), micro-erosions (p = 0.002), strawberry pattern (p = 0.038), and scales (p = 0.012) correlated significantly with Olsen grade, whereas vessels (p = 0.566) did not. All five RCM parameters showed strong associations with clinical severity. Composite dermoscopic and RCM scores correlated with Olsen grade (both p < 0.001). Abnormal honeycomb pattern, parakeratosis, inflammation, and solar elastosis were the best RCM predictors of high dermoscopic severity (all p < 0.001); conversely, erosions, erythema, and scales were the strongest dermoscopic predictors of high RCM severity (all p < 0.001). Conclusions: This study demonstrates strong, statistically significant associations between clinical, dermoscopic, and confocal features of AK. This supports the integration of multimodal scoring into unified AK severity frameworks. Full article

Background/Objectives: Accurate surgical margin delineation is essential in the treatment of non-melanoma skin cancers (NMSCs), particularly basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), to reduce recurrence and metastasis. Dermoscopy improves diagnostic accuracy for skin tumors, but its utility for preoperative margin assessment remains underexplored. To compare dermoscopy-guided versus clinical visual inspection for preoperative margin assessment in NMSC excision, focusing on histological clearance rates and surgical outcomes. Methods: This systematic review and meta-analysis followed PRISMA 2020 guidelines. MEDLINE, Cochrane CENTRAL, Scopus, and Web of Science were searched from inception to 1 July 2025. Eligible studies included adult patients undergoing surgical excision of histologically confirmed BCC or cSCC, with preoperative margin evaluation using either dermoscopy or clinical examination. The primary outcome was the rate of complete histological excision. Study quality was assessed using the Newcastle–Ottawa Scale. A random-effects meta-analysis using the Freeman–Tukey transformation was performed. Results: Nine cohort studies comprising 900 NMSC lesions were included. Dermoscopy-guided excision demonstrated pooled histological clearance of 98.7% (95% CI: 97–99.8%), compared to 80–94% with clinical assessment. Moderate heterogeneity was observed (I² = 42%). However, variability in study design and limited data for cSCC restricted broader conclusions. Conclusions: Dermoscopy may enhance margin assessment and histological clearance in NMSC surgery, especially for BCC. Further standardized, high-quality studies are needed to confirm its role in surgical planning and extend evidence to SCC. Full article

Skin cancer is the most common cancer form worldwide, and it is primarily divided into melanoma and non-melanoma types, with non-melanoma being the most prevalent condition. Cutaneous squamous cell carcinoma (cSCC) accounts for 50% of primary skin cancers and is characterized by uncontrolled keratinocyte proliferation. cSCC’s current standard treatment is surgical resection and chemotherapy. Unfortunately, these methods often lead to disfigurement, functional morbiditly, and compromised function. In contrast to immunotherapy, emerging scenarios have shown promising results, especially in neoadjuvant settings. Cemiplimab (Libtayo^®; Regeneron, Tarrytown, NY, USA), a PD-1 monoclonal antibody, has shown efficacy in treating advanced or metastatic cSCC, and its use as a neoadjuvant therapy has been recently explored. This review aims to evaluate Cemiplimab in the neoadjuvant setting for cSCC treatment. The Methodology followed PRISMA guidelines, this review analyzed studies on Cemiplimab as a neoadjuvant therapy for cSCC that were sourced from PubMed, Web of Science, and Scopus. Only controlled trials, cohort studies, case series, and systematic reviews were included. From 341 records, 21 studies were included, and six clinical trials provided key data about neoadjuvant Cemiplimab’s response rates, efficacy, adverse effects, and safety considerations. The targeted data revealed a neoadjuvant Cemiplimab mean pathologic response rate of 72%, with a 62% objective response rate. Treatment-related adverse events (TRAEs) affect 66% of patients, though most cases are not severe. The most common include fatigue, maculopapular rash, and diarrhea. The studies showed high rates of complete pathological responses (cPRs) and major pathological responses (mPRs), suggesting a strong therapeutic potential. Neoadjuvant Cemiplimab for cSCC therapy shows high response rates, low recurrence, improved survival, and manageable side effects. The current literature indicates that Cemiplimab may also be effective when used in immunosuppressed patients. Despite more research still being needed to confirm its long-term benefits and the effects of the drug’s use outside of clinical trials, there is strong evidence to consider neoadjuvant Cemiplimab as a promising and efficient treatment. Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer entity in Germany, following basal cell carcinoma. Its incidence has increased fourfold over the past three decades. Early diagnosis and treatment are essential for achieving favorable outcomes. Our study aims to identify prognostic factors based on real-world data to improve follow-up protocols and raise clinical vigilance. Methods: We conducted a retrospective, monocenter analysis with a total of 124 patients with at least one cSCC thicker than 3 mm, treated at the Department of Dermatology, University Medical Center Mainz, between 2010 and 2020. Tumor-specific criteria were correlated with patient-specific data, such as gender, age, immunosuppression, UV exposure and mortality. Results: A higher incidence of cSCC was found on UV-exposed skin (91.1%); however, tumors on non-UV-exposed skin were on average thicker (6.55 mm vs. 9.25 mm, p = 0.011) and associated with higher metastasis rates (10.6% vs. 63.3%, p < 0.001). Immunosuppression was strongly associated with a younger age at diagnosis (74 years vs. 81 years), a higher metastasis rate (29% vs. 10.8%, p = 0.021) and a worse 5Y-OS-rate (36.1% vs. 97.8%, p = 0.04). SLNB was performed in eight patients, with one positive SLN identified (12.5%). Local recurrence was observed in 18.1% (n = 21) of patients who did not experience SLNB, whereas no local recurrences (0%) were reported in patients with SLNB (p = 0.349). Discussion: Tumors on non-UV-exposed areas were thicker and more often metastatic, suggesting delayed detection or more aggressive tumor subtypes. Immunosuppression was associated with worse outcomes, underscoring the need for intensified follow-up. SLNB was rarely performed, and larger studies are needed to assess its role. Full article

The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the field of antimicrobial photodynamic therapy. The photodynamic and sonodynamic activity of 3-(3-(diethylamino)phenoxy)propanoxy substituted silicon(IV) Pc were evaluated against bacteria and cancer cells. Stability and singlet oxygen generation upon light irradiation and ultrasound (1 MHz, 3 W) were assessed with 1,3-diphenylisobenzofuran. The phthalocyanine revealed high photostability in DMF and DMSO, although the singlet oxygen yields under light irradiation were low. On the other hand, the phthalocyanine revealed excellent sonostability and caused a high rate of DPBF degradation upon excitation by ultrasounds at 1 MHz. The silicon phthalocyanine presented significant bacterial reduction growth, up to 5 log against MRSA and S. epidermidis upon light excitation, whereas the sonodynamic effect was negligible. The phthalocyanine revealed high activity in both photodynamic and sonodynamic manner toward hypopharyngeal tumor (FaDu, 95% and 42% reduction, respectively) and squamous cell carcinoma (SCC-25, 96% and 62% reduction, respectively). The sensitizer showed ca. 30% aldehyde dehydrogenase inhibition in various concentrations and up to 85% platelet-activating factor acetylhydrolase for 0.25 μM, while protease-activated protein C was stimulated up to 66% for 0.75 μM. Full article