PERIOCULAR HIGH RISK BCCS AFTER ADDITIONAL/PARALLEL INTAKE OF TORASEMIDE, MOXONIDINE AND MIRABEGRON: IMPORTANT LINKS TO SKIN CANCER RELATED (PHOTO-) NITROSOGENESIS IN THE CONTEXT OF PHARMACO-ONCOGENESIS.

The Nitrosogenesis of skin cancer is a modern newly introduced concept in medicine, mainly concerning melanoma, but also keratinocytic cancers such as basal cell carcinoma. The nitroso-contamination of more than 300 drugs worldwide and the permanent (relatively short-term) intake of mutagen-contaminated drugs could create serious prerequisites for the development of skin cancer. Retrospective but also prospective analyses following potentially contaminated polymedication with a heterogeneous type of nitrosamines in real patients are indicative of a causal connection rather than a sporadic association between 1) intake of a possibly nitrosamine-contaminated drug and 2) generation of keratinocytic skin cancer. The pathogenesis of high-risk periocular localized basal cell carcinomas was until recently shrouded in mystery as it was mainly and until now associated with 1) intake of phototoxic drugs and 2) intense exposure to UV radiation (without intake of drugs), 3) congenital or acquired immunodeficiencies, and 4) Goltz Gorlin syndrome or 5) Xeroderma pigmentosum. Nitrosamines/ NDSRIs within the framework of polycotaminated drug intake appear to be one reasonable additional explanation for the association between carcinogen intake and subsequent skin cancer development and progression, and a relatively short-term one at that. Recently published scientific data provide information on a new ability of some of the nitrosamines - namely that some of them are photocarcinogenic or genotoxic after activation with UVA radiation. We present 4 patients who developed high-risk periocular localized basal cell carcinomas of the skin after/within the intake of potentially nitrosamine-contaminated drugs. The presented data are confirmatory with respect to previously published scientific observations on the carcinogenic effects of valsartan, candesartan, bisoprolol, metoprolol, perindopril, lisinopril and amlodipine. The contribution of newly validated data concerning potential/actual carcinogenic/genotoxic activity in the article is also due to the following newly announced nitroso preparations: torasemide, moxonidine and mirabegron. The expansion of the ˝bases of the pyramid˝ determining the stability of drug related (Photo) Nitrosogenesis/ Carcinogenesis (in terms of skin cancer generation) is growing daily. Exogenously/drug-induced Nitrosogenesis and the subsequently triggered carcinogenesis are a completely new explanatory concepts concerning the pathogenesis of skin tumors that remained unanalyzed and hidden for decades. Until now. The official lack of 1) availability, and of 2) precise concentrations regarding nitrosamines in medicinal preparations, are some of the most unexplained acts of irresponsibility to end-users and remain for the moment without a definitive answer from either regulators and manufacturers respectively. Polycontamination of polymedication in polymorbid patients remains highly problematic, at least as a cofactor in the development and progression of keratinocytic cancers, and this in the short term. Recently published data but also data from the past are suggestive that nitrosamines in tobacco are pivotal in the development of acquired mutations in p53 and RAS oncogenes in humans and rodents. The same genes are also affected by mutations in keratinocytic cancer patients. The overlapping mutation patterns of UV radiation-induced mutations in target genes such as p53 and RAS with those caused by some nitrosamines is indicative of a synergism available in terms of gene toxicity or possibly photocarcinogenicity of the latter. What leads the scientific community to believe that the nitrosamines in drugs, similar in composition and carcinogenic potency, act differently, is unclear. The link between drug intake, nitrosamine contamination, generation of some acquired mutations and subsequent cancer development becomes more than obvious and logically conditioned. The thesis of the controlled spread of cancer sounds more than logical today because: whoever controls and regulates the spread of carcinogens/mutagens/nitrosamines is also able to control the occurrence and spread of skin cancer. The Pharmaco-oncogenesis of skin cancer is determined by exogenously mediated Nitrosogenesis or the permissive availability for certain nitrosamines in drugs worldwide.

Treatments on the horizon for locally advanced basal cell carcinoma.

Basal cell carcinoma (BCC) is one of the most common human cancers. Most cases of BCC are amenable to surgical and topical treatments with excellent prognosis if diagnosed timely and managed appropriately. However, in a small percentage of cases, it could be locally advanced BBC (laBCC) and not amenable to surgery or radiation, including recurrent, large tumors or tumors that invade deeper tissue. Hedgehog inhibitors (vismodegib and sonidegib) are approved as the first-line treatment of laBCC. PD-1 inhibitor immunotherapy (cemiplimab) is indicated for cases that progressed on or could not tolerate hedgehog inhibitors or when hedgehog inhibitors are contraindicated. Given the modest response and bothersome side effects of some of the agents above, there are reports of novel treatments, and clinical trials are currently evaluating multiple agents.

Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma.

BACKGROUND AND OBJECTIVES: Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7 years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. RESULTS: Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients. CONCLUSIONS: This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.

Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis.

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Association between statins exposure and risk of skin cancer: an updated meta-analysis.

This study aimed to investigate the relationship between statin (lipophilic statin and hydrophilic statin) exposure and the risk of skin cancer. The incidence of skin cancer under statin exposure was used as the primary outcome, and the relevant studies were screened from Web of Science, PubMed, Cochrane Library, and EBSCO electronic database until September 2022. Ten observational studies and two randomized controlled trials (RCTs) were included. The statistical results indicated that in lipophilic statins, the exposed group had a higher risk of skin cancer than the non-exposed group (OR: 1.09, P = 0.003). However, compared with the non-exposed group, there was no significant difference between hydrophilic statins exposure and the incidence of skin cancer (OR: 1.02, P = 0.341). Further subgroup analysis of the subtypes of statins revealed that compared with the non-exposed group, exposure to lovastatin (OR: 1.18, P = 0.048) or simvastatin (OR: 1.11, P < 0.001) was a risk factor for skin cancer. Besides, subgroup analysis based on the subtypes of skin cancer demonstrated that the risks of melanoma (OR: 1.13, P = 0.009), basal cell carcinoma (BCC) (OR: 1.05, P = 0.036), and squamous cell carcinoma (SCC) (OR: 1.13, P = 0.026) under lipophilic statin exposure were significantly higher than those in the non-exposed group. On the contrary, compared with the non-exposed group, the risk of BCC was significantly reduced under the exposure of hydrophilic statins (OR: 0.93, P = 0.031). This study showed that the relationship between statin exposure and skin cancer risk was affected by the subtypes of statins and skin cancer subtypes.

Chronic Use of Hydrochlorothiazide and Risk of Skin Cancer in Caucasian Adults: A PharmLines Initiative Inception Cohort Study.

Photosensitizing properties of hydrochlorothiazide may increase skin cancer risk. To date, study findings on the association between hydrochlorothiazide use and skin cancer risk are inconsistent, notably regarding confounding and dose-response. The aim of this study was to investigate the association between hydrochlorothiazide use and incidence of skin cancer in a cohort of unselected Caucasian adults, taking dosing into account. As part of the PharmLines Initiative, which links data from the Lifelines Cohort Study and prescription database IADB.nl, patients aged ≥ 40 years were included from Lifelines, a prospective population-based cohort study in the north of the Netherlands. Skin cancer incidence was compared between subjects starting hydrochlorothiazide treatment (n = 608), subjects starting treatment with other antihypertensives (n = 508), and non-antihypertensive long-term medication users (n = 1,710). Cox regression analyses were performed to obtain hazard ratios, adjusted for potential confounders. The risk of any skin cancer, keratinocyte carcinoma, basal cell carcinoma and squamous cell carcinoma was not significantly increased in general hydrochlorothiazide users. A clear association was observed between high cumulative hydrochlorothiazide use (≥ 5,000 defined daily dose; ≥ 125,000 mg) and the risk of any skin cancer (adjusted hazard ratio 5.32, 95% confidence interval (95% CI) 2.40-11.81), keratinocyte carcinoma (adjusted hazard ratio 7.31, 95% CI 3.12-17.13), basal cell carcinoma (adjusted hazard ratio 7.72, 95% CI 3.11-19.16) and squamous cell carcinoma (adjusted hazard ratio 19.63, 95% CI 3.12-123.56). These findings should lead to awareness with high use of hydrochlorothiazide in Caucasian adults.

Use of methotrexate and risk of skin cancer: a nationwide case-control study.

BACKGROUND: Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM). METHODS: In a nationwide Danish case-control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use. RESULTS: Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20-1.38), 1.61 (1.37-1.89) and 1.35 (1.13-1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23-1.67), 1.18 (0.80-1.74) and 1.15 (0.77-1.72), respectively. CONCLUSIONS: We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose-response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis.

The effect of menopausal hormone therapy on the risk of melanoma and keratinocyte skin cancer: A systematic review and meta-analysis of observational studies.

BACKGROUND: Whether menopausal hormone therapy (MHT) increases the risk of skin cancer is controversial. AIM: To systematically review and meta-analyze evidence regarding the association of MHT with the risk of melanoma and keratinocyte cancer (KC). MATERIAL AND METHODS: A comprehensive literature search was conducted of the PubMed, Scopus and Cochrane databases, through to 30 October 2021. Skin neoplasms were divided into melanoma and KC. In the latter category, both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were considered. The results are presented as hazard ratios (HR) with 95 % confidence intervals (CI). The I2 index was used to assess heterogeneity. Subgroup analysis and sensitivity analysis were also conducted in order to explore potential differences among studies. RESULTS: Twenty-seven studies were included in the qualitative and 23 in the quantitative analysis, with a total of 2,612,712 menopausal women (25,126 with skin cancer; 20,150 with melanoma). MHT was associated with an increased risk of melanoma (HR 1.11; 95 % CI 1.05-1.19; I2 45%). With regard to MHT type, both estrogen monotherapy (HR 1.22, 95 % CI 1.16-1.29; I2 0%) and estrogen in combination with progestogen (HR 1.11, 95 % CI 1.05-1.18, I2 26%) significantly increased that risk. Regarding melanoma subtype, superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) were the only histologic subtypes associated with MHT use. MHT was also associated with an increased risk of KC (HR 1.17, 95 % CI 1.04-1.31, I2 83%), specifically BCC (HR 1.22, 95 % CI 1.12-1.32; I2 29%). Longer duration (>5 years) of MHT, current use and estrogen monotherapy were associated with an increased KC risk compared with no use. CONCLUSION: The use of MHT by postmenopausal women was associated with an increased risk of melanoma and KC. This risk was higher for current MHT users and those treated for over 5 years.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report.

BACKGROUND: The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers. CASE PRESENTATION: A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient's inadequate compliance, and within 2 years, the patient's cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient's basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection. CONCLUSIONS: Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

Antidiabetic Treatment in Patients at High Risk for a Subsequent Keratinocyte Carcinoma.

BACKGROUND: Metformin and sulfonylureas are the most commonly prescribed drugs used for the treatment of type II diabetes. Type II diabetes has been linked to the development of keratinocyte carcinoma (KC), consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Previously we have demonstrated lower risk for a subsequent KC in metformin users. In this study, we aim to investigate the association between sulfonylureas use and the development of KC in patients with KC history. We performed a retrospective cohort study of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, which was a randomized double-blind vehicle-control cream originally investigating the effect of 5-fluorouracil on KC development. 932 patients with a history of KC were enrolled (98% male, 99% white, median age of 70 years) and followed for a median duration of 2.8 years. 153 patients were on metformin and 94 on sulfonylureas. We performed a survival analysis with cox regression and controlled for body mass index and known predictors: number of prior BCCs and age (for BCC) and for number of prior SCCs (invasive and in situ), number of actinic keratoses at baseline (for SCC). Sulfonylurea-users com-pared to non-users had a HR of 0.67 (CI: 0.40–1.56; P=0.49) and 0.94 (CI: 0.63–1.40; P= 0.77), for SCC and BCC, respectively. Diabetic patients at high risk for KC might benefit from the use of metformin versus sulfonylureas. J Drugs Dermatol. 2022;21(5):502-505. doi:10.36849/JDD.6087.

Does hydrochlorothiazide increase the incidence of skin, lip and oral cancer in a UK population?

Data sources Data was from The Health Improvement Network (THIN) database from January 1999 to May 2016.Study selection This was a series of population-based, case-control studies looking to evaluate the association between hydrochlorothiazide (HCTZ) exposure and skin, lip and oral cancer in the UK population.Case/control selection Using the THIN database, patients with the following outcomes were grouped: squamous cell carcinoma (SCC) skin cancer; basal cell carcinoma (BCC) skin cancer; melanoma; lip cancer and oral cancer. Patients within the lip cancer and oral cancer groups were accepted with a history of non-melanoma skin cancer (NMSC). Patients in the SCC and BCC groups were not accepted with a history of cancer. Patients with a history of organ transplantation, human immunodeficiency virus (HIV) or immunosuppressant drug use before the index date were not accepted, due to the risk of predisposition to cancer. Controls were randomly selected using incidence density sampling. Up to 100 controls were randomly selected, matched on sex, exact year of birth and calendar year of cohort entry for lip cancer. However, for the remaining outcomes, only 20 controls were matched as above. Adults with incident NMSC, melanoma, lip cancer and oral cancer were matched to controls. Incidence rate ratios (IRRs) for the aforementioned outcomes were calculated for every cumulative HCTZ exposure.Data analysis Odds ratios were calculated using conditional logistic regression. Associations were presented using a two-year HCTZ exposure lag-time and a five-year HCTZ exposure lag-time. Associations were evaluated using sensitivity analysis, restricted to patients with at least ten years' follow-up. There was adjustment for smoking status and BMI. Published incidence rates were used to calculate the absolute risk estimate for SCC as the incidence of SCC in the cohort was less than expected. For high-dose cumulative HCTZ exposure, the number of patients needed to treat to cause one additional cancer (number needed to harm) per year overall was estimated using rate differences. Analysis was carried out using SAS Enterprise Guidev7.1 and STATAv15.Results Relative incidence of SCC, BCC and lip cancer was significantly elevated with every use of HCTZ. Relative incidence of melanoma and oral cancer was not significantly elevated with HCTZ exposure. Smoking was inversely associated with BCC and melanoma risk, but significantly increased the risk of lip and oral cavity cancers. SCC risk was not strongly associated with smoking. Significantly reduced risk of SCC, BCC melanoma and oral cavity cancer was associated with a BMI ≥30 kg/m2.Conclusions The risk of NMSC and lip cancer in a UK population is increased with cumulative high-dose HCTZ exposure. It is therefore important for dentists to note as it may increase suspicion of lesions in patients taking these medications.

The use of HCT and/or ACE inhibitors significantly increases the risk of non-melanotic skin cancer in the periocular region.

BACKGROUND/AIMS: To investigate a possible association between the use of hydrochlorothiazide (HCT) and/or angiotensin-converting enzyme inhibitors (ACE inhibitors) and the occurrence of periocular non-melanoma skin cancer. METHODS: The files of 929 patients from the University Medical Center Hamburg-Eppendorf who were surgically treated for suspected periocular malignancy were evaluated retrospectively regarding the occurrence of non-melanoma skin cancer and concomitant medication. To be able to put the data in an overall context, we also analyzed age-matched routine data of the DAK-Gesundheit (DAK-G), a nationwide operating German health insurance company. RESULTS: Of the 929 patient records examined, who underwent surgical excision for suspected non-melanotic malignancy, non-melanocytic skin cancer could actually be determined by histology in 199 patients. In total, 176 patients (103 women, 72 men) had a basal cell carcinoma and 23 patients (16 women, 7 men) suffered from squamous cell carcinoma. The rate of intake of HCT or ACE inhibitors in our patient collective with non-melanotic skin cancer is significantly higher than in the general age-matched population (ORACE: 2.51, p < 0.001; ORHCT: 7.24, p < 0.001, ORBOTH: 4.61, p < 0.001). CONCLUSION: The rate of intake of HCT or ACE inhibitors is significantly higher in our patient collective with non-melanotic skin cancer compared to the group from the age-matched general population (DAK insured (p < 0.001)) compared to the routine data of the DAK-G. This leads us to the conclusion that taking the medication is associated with an increased risk for non-melanotic skin cancer. We recommend regular skin cancer screening, moderate ordination of photosensitizing medication, but above all comprehensive clarification of possible risks.

COX-2 inhibitors show no preventive effect in the development of skin cancer.

BACKGROUND: Some clinical trials found that cyclooxygenase-2 (COX-2) inhibitor use lowered the risk of skin cancer in high-risk groups. PATIENTS AND METHODS: To determine whether COX-2 inhibitor use is associated with lower risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, we analyzed COX-2 inhibitor use and risk of skin cancer based on three prospective cohort studies, the Nurses' Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, including 153,882 participants. Multivariable hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of COX-2 inhibitor use with risk of BCC, cSCC, and melanoma were estimated using Cox proportional hazards models. We pooled the results using a fixed effects model. RESULTS: 16,142 BCC, 1,973 cSCC, and 631 melanoma cases were documented. Ever vs. never use of COX-2 inhibitor was associated with a modestly increased risk of BCC (multivariable HR 1.09, 95 % CI 1.05-1.14). The hazard ratio was similar for cSCC (multivariable HR 1.12, 95 % CI 1.00-1.27) and melanoma (multivariable HR 1.10, 95 % CI 0.89-1.38), but was not statistically significant. CONCLUSIONS: Ever use of COX-2 inhibitor was not associated with a decreased skin cancer risk but was instead associated with a modest, increased risk of BCC.

Clinicopathological evaluation of intralesional methotrexate in different subtypes of basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common malignant skin tumor. While slowly growing, it can cause major skin disfigurement. Therefore, novel cosmetically acceptable treatment options, other than surgery require investigation. The aim of the study was to evaluate efficacy and safety of intralesional methotrexate (MTX) as a convenient modality for BCC treatment clinically and pathologicaly. A total of 20 patients with BCC of any clinical variant underwent intralesional MTX injection at a maximum 1 mL of 25 mg/mL MTX per session. Histopathological assessments were performed before and 1 month after treatment. Forty percent of patients showed >50% clinical improvement after 1-4 sessions. Intralesional MTX is a suitable and safe treatment modality for BCC and may be used as an adjuvant to surgery.

Statin Use and Skin Cancer Risk: A Prospective Cohort Study.

Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925-1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants' statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004-2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94-1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66-1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79-0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings.

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

AIMS: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BACKGROUND: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. OBJECTIVE: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. METHODS: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. RESULTS: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. CONCLUSION: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Long-term efficacy and safety of imiquimod 5% and fluorouracil 1% creams in medical monotherapy of complex eyelid basal cell carcinomas.

PURPOSE: To study the long-term efficacy and safety of local application of imiquimod 5% and fluorouracil 1% creams in complex eyelid basal cell carcinomas (BCCs). METHODS: A retrospective, non-comparative study in biopsy-proven, complex (involving canthi or >50% of eyelid length) eyelid BCC patients who were medically unfit for surgical procedures. All patients were medically treated with either of the creams using fixed-dose regimens for a minimum of 3 months. All received oral vitamin C 500 mg QID for 3 months as an adjunct for collagen healing. A minimum of "post-treatment" follow-up of 12 months was observed. RESULTS: Of total 30 patients, imiquimod 5% and fluorouracil 1% were used in 16 and 14 patients, respectively. The mean age of our patients was 70.5 years. The co-morbidities included - severe coronary artery disease using blood-thinners (n = 19), poorly controlled diabetes (n = 12), poorly controlled hypertension (n = 6), on nebulization (n = 3), and tuberculosis with pulmonary fibrosis (n = 2). Complete clinical tumor resolution was noted in 10 and 8 patients over 12 and 16.5 weeks, respectively, in imiquimod and fluorouracil groups. Periocular skin erythema, chemical conjunctivitis, and skin depigmentation were seen in all the patients of imiquimod group. On the other hand, the local side-effect profile in fluorouracil patients was limited. CONCLUSION: The medical treatment of complex eyelid BCC is a useful alternative to surgery in the elderly with significant co-morbidities. It provides a promising long-term relief with a tolerable side-effect profile. A prospective, randomized, double-blinded trial would provide stronger evidence for the efficacy of these drugs.