About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview.

Periodontitis is linked to the onset and progression of oral squamous cell carcinoma (OSCC), an epidemiologically frequent and clinically aggressive malignancy. In this context, Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis, two bacteria that cause periodontitis, are found in OSCC tissues as well as in oral premalignant lesions, where they exert pro-tumorigenic activities. Since the two bacteria are present also in endodontic diseases, playing a role in their pathogenesis, here we analyze the literature searching for information on the impact that endodontic infection by P. gingivalis or F. nucleatum could have on cellular and molecular events involved in oral carcinogenesis. Results from the reviewed papers indicate that infection by P. gingivalis and/or F. nucleatum triggers the production of inflammatory cytokines and growth factors in dental pulp cells or periodontal cells, affecting the survival, proliferation, invasion, and differentiation of OSCC cells. In addition, the two bacteria and the cytokines they induce halt the differentiation and stimulate the proliferation and invasion of stem cells populating the dental pulp or the periodontium. Although most of the literature confutes the possibility that bacteria-induced endodontic inflammatory diseases could impact on oral carcinogenesis, the papers we have analyzed and discussed herein recommend further investigations on this topic.

Blocking the ATR-SerRS-VEGFA pathway targets angiogenesis for UV-induced cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, with an escalating incidence rate and a notable potential (up to 5%) for metastasis. Ultraviolet radiation (UVA and UVB) exposure is the primary risk factor for cSCC carcinogenesis, with literature suggesting ultraviolet radiation (UVR) promotes vascular endothelial growth factor A (VEGFA) expression. This study aims to investigate UVR-induced upregulation of VEGFA and explore combination therapeutic strategies. The skin squamous cell carcinoma cell line A431 was exposed to specific durations of ultraviolet radiation. The effect of emodin on ATR/SerRS/VEGFA pathway was observed. The cell masses were also transplanted subcutaneously into mice (n = 8). ATR inhibitor combined with emodin was used to observe the growth and angiogenesis of the xenografts. The results showed that UV treatment significantly enhanced the phosphorylation of SerRS and the expression level of VEGFA in A431 cells (p < 0.05). Treatment with emodin significantly inhibited this expression (p < 0.05), and the combination of emodin and ATR inhibitor further enhanced the inhibitory effect (p < 0.05). This phenomenon was further confirmed in the xenograft model, which showed that the combination of ATR inhibitor and emodin significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.05), thus showing an inhibitory effect on cSCC. This study innovatively reveals the molecular mechanism of UV-induced angiogenesis in cSCC and confirms SerRS as a novel target to inhibit cSCC angiogenesis and progression in vitro and in vivo studies.

A prospective cohort study exploring the joint influence of sunlight exposure and tanning bed use on basal cell carcinoma, squamous cell carcinoma, and melanoma risk.

Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR = 1.53, 95% CI 1.37-1.71, Pinteraction=0.01; vs. low sun exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR = 1.62, 95% CI 1.47-1.79, Pinteraction=0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.

Voriconazole metabolism is associated with the number of skin cancers per patient.

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two (p < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure (p < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19-2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14-2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.

Unravelling drivers of cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa.

Epidermolysis bullosa (EB) is an umbrella term for a group of rare inherited skin disorders characterised by mucocutaneous fragility. Patients suffer from blisters and chronic wounds that arise spontaneously or following minor mechanical trauma, often resulting in inflammation, scarring and fibrosis due to poor healing. The recessive form of dystrophic EB (RDEB) has a particularly severe phenotype and is caused by mutations in the COL7A1 gene, encoding the collagen VII protein, which is responsible for adhering the epidermis and dermis together. One of the most feared and devastating complications of RDEB is the development of an aggressive form of cutaneous squamous cell carcinoma (cSCC), which is the main cause of mortality in this patient group. However, pathological drivers behind the development and progression of RDEB-associated cSCC (RDEB-cSCC) remain somewhat of an enigma, and the evidence to date points towards a complex process. Currently, there is no cure for RDEB-cSCC, and treatments primarily focus on prevention, symptom management and support. Therefore, there is an urgent need for a comprehensive understanding of this cancer's pathogenesis, with the aim of facilitating the discovery of drug targets. This review explores the current knowledge of RDEB-cSCC, emphasising the important role of the immune system, genetics, fibrosis, and the tumour-promoting microenvironment, all ultimately intricately interconnected.

Common skin cancers and their association with other non-cutaneous primary malignancies: a review of the literature.

It has long been recognized that a history of skin cancer puts one at risk for additional primary skin cancers. However, more variable data exists for the risk of developing a non-cutaneous primary cancer following a diagnosis of skin cancer. The data are most variable for Basal Cell Carcinoma (BCC), the most common and least aggressive type of skin cancer. While early studies imply that BCC does not impart a larger risk of other primary non-cutaneous cancers, more recent studies with larger populations suggest otherwise. The cancers most significantly associated with BCC are lip, oropharyngeal, and salivary gland cancer. There is also burgeoning evidence to suggest a link between BCC and prostate, breast, and colorectal cancer, but more data are needed to draw a concrete conclusion. Squamous Cell Carcinoma (SCC), the second most common type of skin cancer, has a slightly more defined risk to other non-cutaneous primary malignancies. There is a notable link between SCC and non-Hodgkin's lymphoma (NHL), possibly due to immunosuppression. There is also an increased risk of other cancers derived from squamous epithelium following SCC, including oropharyngeal, lip, and salivary gland cancer. Some studies also suggest an increased risk of respiratory tract cancer following SCC, possibly due to shared risk factors. Melanoma, a more severe type of skin cancer, shows a well-defined risk of additional primary non-cutaneous malignancies. The most significant of these risks include NHL, thyroid cancer, prostate cancer, and breast cancer along with a host of other cancers. Each of these three main skin cancer types has a profile of genetic mutations that have also been linked to non-cutaneous malignancies. In this review, we discuss a selection of these genes to highlight the complex interplay between different tumorigenesis processes.

Updates in Skin Cancer in Transplant Recipients and Immunosuppressed Patients: Review of the 2022-2023 Scientific Symposium of the International Immunosuppression and Transplant Skin Cancer Collaborative.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) and its European counterpart, Skin Care in Organ Transplant Patients-Europe (SCOPE) are comprised of physicians, surgeons, and scientist who perform integrative collaborative research focused on cutaneous malignancies that arise in solid organ transplant recipients (SOTR) and patients with other forms of long-term immunosuppression. In October 2022, ITSCC held its biennial 4-day scientific symposium in Essex, Massachusetts. This meeting was attended by members of both ITSCC and SCOPE and consisted of specialists including Mohs micrographic and dermatologic oncology surgeons, medical dermatologists, transplant dermatologists, transplant surgeons, and transplant physicians. During this symposium scientific workshop groups focusing on consensus standards for case reporting of retrospective series for invasive squamous cell carcinoma (SCC), defining immunosuppressed patient status for cohort reporting, development of multi-institutional registry for reporting rare tumors, and development of a KERACON clinical trial of interventions after a SOTRs' first cutaneous SCC were developed. The majority of the symposium focused on presentation of the most up to date research in cutaneous malignancy in SOTR and immunosuppressed patients with specific focus on chemoprevention, immunosuppression regimens, immunotherapy in SOTRs, spatial transcriptomics, and the development of cutaneous tumor registries. Here, we present a summary of the most impactful scientific updates presented at the 2022 ITSCC symposium.

Malignancy around implants in patients with a history of a potentially malignant or malignant lesion: a systematic review.

The majority of problematic conditions resulting from dental implant treatment are inflammatory in character, but certain isolated occurrences of primary oral squamous cell carcinoma (OSCC) have been discovered in the area of implants. The goal of this study was to examine whether there is a link between dental implants and the development of OSCC in patients who have a history of a potentially malignant lesion (PML) or malignancy. Using the keywords "carcinoma" AND "dental implants," a search was conducted in the MEDLINE (PubMed), National Center for Biotechnology Information, and Google Scholar databases for case reports and case series in which OSCC was discovered as a primary cancer in the region of dental implants. An initial search identified 260 articles, 247 of which were excluded based on study inclusion or exclusion criteria, leaving 13 articles chosen for inclusion and a total of 30 patients who developed primary oral cancer surrounding osseointegrated titanium-based dental implants. In the studies included in the present review, 22 (73%) of 30 patients with peri-implant cancer had a history of PML or carcinoma. There is no statistical evidence of a direct association between dental implants and OSCC in patients with a history of a PML or malignant lesion. There have been some case reports of OSCC in the region of dental implants in patients with a history of a PML or malignant lesion, but further studies are needed to prove a definitive relationship.

Oral Cavity Squamous Cell Carcinoma: Review of Pathology, Diagnosis, and Management.

Squamous cell carcinoma of the oral cavity presents a significant global health burden, primarily due to risk factors such as tobacco smoking, smokeless tobacco use, heavy alcohol consumption, and betel quid chewing. Common clinical manifestations of oral cavity cancer include visible lesions and sores, often accompanied by pain in advanced stages. Diagnosis relies on a comprehensive assessment involving detailed history, physical examination, and biopsy. Ancillary imaging studies and functional evaluations aid in accurate staging and facilitate treatment planning. Prognostic information is obtained from histopathological factors, such as tumor grade, depth of invasion, lymphovascular invasion, and perineural invasion. Notably, lymph node metastasis, found in approximately half of the patients, carries significant prognostic implications. Effective management necessitates a multidisciplinary approach to optimize patient outcomes. Surgical resection is the backbone of treatment, aimed at complete tumor removal while preserving functional outcomes. Adjuvant therapies, including radiation and chemotherapy, are tailored according to pathological factors. Further work in risk stratification and treatment is necessary to optimize outcomes in squamous cell carcinoma of the oral cavity.

Real-World Treatment Patterns and Clinical Outcomes After Platinum-Doublet Chemotherapy and Immunotherapy in Metastatic Non-Small Cell Lung Cancer: A Multiregional Chart Review in the United States, Europe, and Japan.

PURPOSE: To characterize treatment patterns and real-world clinical outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) who developed progression on an anti-PD-1/anti-PD-L1, herein referred to as anti-PD-(L)1, and platinum-doublet chemotherapy. METHODS: Eligible oncologists/pulmonologists in the United States, Europe (France, Germany, and United Kingdom), and Japan completed electronic case report forms for patients with mNSCLC (no evidence of EGFR/ALK/ROS1 alterations). Eligible patients had disease progression on/after an anti-PD-(L)1 and platinum-doublet chemotherapy (received concurrently or sequentially), initiated a subsequent line of therapy (LOT) between 2017 and 2021, and had an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at this subsequent LOT initiation (index date). Overall survival (OS), time to treatment discontinuation (TTD), and real-world progression-free survival (rwPFS) after index were assessed using Kaplan-Meier analysis. RESULTS: Overall, 160 physicians (academic, 54.4%; community, 45.6%) provided deidentified data from 487 patient charts (United States, 141; Europe, 218; Japan, 128; at mNSCLC diagnosis: median age 66 years, 64.7% male, 81.3% nonsquamous, 86.2% de novo mNSCLC; at line of interest initiation: 86.0% ECOG 0-1, 39.6% liver metastases, 18.9% brain metastases, 79.1% smoking history). The most common treatment regimens upon progression after anti-PD-(L)1/platinum-doublet chemotherapy were nonplatinum chemotherapy (50.5%), nonplatinum chemotherapy plus vascular endothelial growth factor receptor inhibitor (12.9%), and platinum-doublet chemotherapy (6.6%). Median OS was 8.8 months (squamous, 7.8 months; nonsquamous, 9.5 months). Median TTD was 4.3 months (squamous, 4.1 months; nonsquamous, 4.3 months). Median rwPFS was 5.1 months (squamous, 4.6 months; nonsquamous, 5.4 months). CONCLUSION: In this multiregional, real-world analysis of pooled patient chart data, patients with mNSCLC who had disease progression after anti-PD-(L)1/platinum-doublet chemotherapy had poor clinical outcomes with various treatment regimens, demonstrating an unmet clinical need for effective options after failure on anti-PD-(L)1 and platinum-doublet chemotherapy treatments.

European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

The Use of Immune Regulation in Treating Head and Neck Squamous Cell Carcinoma (HNSCC).

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review.

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.

Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice.

Squamous cell carcinoma represents the second most common type of keratinocyte carcinoma with ultraviolet radiation (UVR) making up the primary risk factor. Oral photoprotection aims to reduce incidence rates through oral intake of photoprotective compounds. Recently, drug repurposing has gained traction as an interesting source of chemoprevention. Because of their reported photoprotective properties, we investigated the potential of bucillamine, carvedilol, metformin, and phenformin as photoprotective compounds following oral intake in UVR-exposed hairless mice. Tumour development was observed in all groups in response to UVR, with only the positive control (Nicotinamide) demonstrating a reduction in tumour incidence (23.8%). No change in tumour development was observed in the four repurposed drug groups compared to the UV control group, whereas nicotinamide significantly reduced carcinogenesis (P = 0.00012). Metformin treatment significantly reduced UVR-induced erythema (P = 0.012), bucillamine and phenformin increased dorsal pigmentation (P = 0.0013, and P = 0.0005), but no other photoprotective effect was observed across the repurposed groups. This study demonstrates that oral supplementation with bucillamine, carvedilol, metformin, or phenformin does not affect UVR-induced carcinogenesis in hairless mice.

Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review.

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU-SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK.

Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer: A Bidirectional 2-Sample Mendelian Randomization.

BACKGROUND: Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. METHODS: We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. RESULTS: Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10 -5 ), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. CONCLUSION: Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.

[Oral cavity cancer: A distinct entity]. / Le cancer de la cavité orale : une entité spécifique ?

Oral Squamous cell carcinoma represent the 17th most frequent cancer in the world. The main risk factors are alcohol and tobacco consumption but dietary, familial, genetic, or oral diseases may be involved in oral carcinogenesis. Diagnosis is made on biopsy, but detection remains late, leading to a poor prognosis. New technologies could reduce these delays, notably Artificial Intelligence and the quantitative evaluation of salivary biological markers. Currently, management of oral cancer consists in surgery, which can be mutilating despite possible reconstructions. In the future, immunotherapies could become a therapeutic alternative and the immune microenvironment could constitute a source of prognostic markers.

Title: Le cancer de la cavité orale : une entité spécifique ? Abstract: Les carcinomes épidermoïdes de la cavité orale sont le 17e cancer le plus fréquent dans le monde. Les facteurs de risque principaux sont l'alcool et le tabac mais des facteurs alimentaires, familiaux, génétiques ou certaines maladies orales peuvent intervenir dans la genèse de ces cancers. Le diagnostic est tardif, entraînant un pronostic sombre. De nouvelles approches, comme l'utilisation de l'intelligence artificielle ou de marqueurs biologiques salivaires pourraient réduire ces délais. La prise en charge actuelle de ces cancers repose sur la chirurgie, la chimiothérapie et la radiothérapie, mais avec une iatrogénie importante. Les immunothérapies pourraient devenir une alternative à ces traitements et certaines caractéristiques du microenvironnement immunitaire pourraient constituer un/des marqueurs pronostiques.

Epidemiological and clinical analysis of exposure-related factors in non-melanoma skin cancer: A retrospective cohort study.

BACKGROUND: The incidence of non-melanoma skin cancers (NMSCs) increased over last decades, probably due to environmental concerns or to the increase of frail patients with age related comorbidities. Currently, the relationship of increasing global skin cancer rates with increased ultraviolet radiations (UVRs) resulting from stratospheric ozone depletion, global warming, and air pollution from fossil-fuel combustion. AIMS: We conducted a retrospective epidemiological study including 546 NMSC patients managed at the Dermatology Unit of the Tor Vergata Hospital to highlight different trends of sun exposure or different comorbidities. METHODS: Descriptive and inferential statistical analyses were performed to evidence differences between continous variable and Spearman rank test for dicotomical variables. Charlson Comorbidity Index was calculated to obtain the 10-years survival rate in order to identify the mean comorbidity burden of our patients. RESULTS: Considering patients with comorbidities (73.81%), actinic keratoses (AKs) was the most frequent lesion. In patients with a history of previous melanoma, basal cell carcinoma (BCC) was predominant (ANOVA test, p < 0.05) with a statistically significant correlation (rho = 0.453; p < 0.01). Squamous cell carcinoma (SCC) showed a higher rate in arterial hypertension patients, followed by the chronic heart failure and hematologic neoplasms (60%, 29.7% and 32.1%, respectively) groups. Men were more affected than women, representing 61.54% of patients. Chronic sun exposure is directly correlated with SCC rho = 0.561; p < 0.01), whereas BCC correlated with a history of sunburns (rho = 0.312; p < 0.05). CONCLUSIONS: History of photo-exposition had an important role on NMSC development especially for work or recreational reasons. Sex, age, and presence of comorbidities influenced different NMSC types. BCC was more frequent in younger patients, associated with melanoma and sunburns. The presence of SCC is associated with older patients and the hypertension group. AKs were diagnosed predominantly in oldest men, with a chronic sun-exposure history, and hematologic neoplasms group.

Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.

Squamous Neoplastic Precursor Lesions of the Esophagus.

Clinicopathological and molecular studies have demonstrated that dysplasia is a precancerous and/or neoplastic lesion with malignant potential. Further, it is subclassified into two grades: high-grade and low-grade dysplasia. High-grade dysplasia is a clinically significant lesion requiring resection or ablation. Low-grade dysplasia has a much lower risk of carcinoma; thus, it should be followed by endoscopic surveillance. Because squamous dysplasia may progress to squamous cell carcinoma, periodic endoscopy is useful to detect the lesion in patients with risk factors. Squamous dysplasia is diagnosed histopathologically by evaluating both cytologic and structural changes.