Superficial Basal Cell Carcinoma Research Articles

Topical 5-fluorouracil in dermatologic disease.

5-fluorouracil (5-FU) has proven to be an effective therapy in the treatment of a variety of dermatologic conditions. Approved by the United States Food and Drug Administration for the treatment of actinic keratoses and superficial basal cell carcinoma, topical 5-FU has also demonstrated efficacy in the treatment of a variety of other dermatologic diseases. A search of the MEDLINE standard computer database, MEDLINE advanced database, and EMBASE database was conducted. Thirty-four articles met criteria for inclusion in this review. These articles represented 16 randomized controlled trials and 18 case series. Each article was reviewed and summarized. Topical 5-FU is used in a variety of dermatologic disease processes with a wide range of efficacy and levels of evidence. Based on extent and level of evidence, our disease-specific systematic review found that the evidence is strongest for topical 5-FU use in the treatment of actinic keratosis, squamous cell carcinoma, and basal cell carcinoma. This review serves as a comprehensive summary of topical 5-FU use in dermatology.

Differentiation of Different Nonmelanoma Skin Cancer Types Using OCT

Background: Early detection of various types of nonmelanoma skin cancer has been a challenge in dermatology. Noninvasive examination procedures such as optical coherence tomography (OCT) play an increasingly important role, besides the established gold standard of histological tissue sample analysis. OCT is a noninvasive, cross-sectional, real-time technique that allows conclusions to be drawn with regard to the presence of pathologies. Objective: The objective of this study was to investigate whether it is possible to distinguish between different types of nonmelanoma skin cancer using OCT or not. Methods: A study population of a total of 25 cases, comprising 5 cases, each, of 5 tumor entities (i.e., basal cell carcinoma, superficial basal cell carcinoma, actinic keratosis, squamous cell carcinoma, and Bowen disease) was examined. Relevant lesions were scanned both centrally and peripherally in the multislice mode. All OCT images were blinded, randomized, analyzed, and evaluated by 2 clinicians experienced in OCT. Results: This study demonstrated that it is possible to determine correlations between various types of tumors and recurring tumor characteristics. Conclusion: This study showed that it is possible to distinguish between the different nonmelanoma skin cancers by using OCT, but further prospective studies have to be conducted to validate the sensitivity and specificity of the criteria.

Immune consequences induced by photodynamic therapy in non-melanoma skin cancers: a review.

Photodynamic therapy (PDT) is widely used in dermatology to treat precancerous skin lesions and superficial non-melanoma skin cancers (NMSCs), including premalignant actinic keratosis, cutaneous squamous cell carcinoma in situ, and superficial basal cell carcinoma. The long-term cure rates of PDT range from 70 to 90% in NMSC patients, with excellent cosmetic results and good tolerance. However, the mechanism of action of PDT on tumors is complex. PDT not only kills tumor cells directly but also rapidly recruits immune cells to release inflammatory mediators to activate antitumor immunity. PDT-induced tumor death, also called immunogenic cell death, can trigger both innate and adaptive immune response, further enhancing the antitumor effect. For instance, inoculation of tumor cells killed via PDT to animals triggered a stronger antitumor immunity in vivo than tumor cell lysates produced by other treatments. More importantly, many immunotherapy regimens based on the immune effect of PDT have been developed and demonstrated to be a promising therapeutic method for cancer in pre-clinical trials. Therefore, increasing efforts have been undertaken to investigate the immune responses associated with PDT. In the present review, we first introduce the antitumor effect and the associated mechanisms of PDT in cancers. Then, we summarize studies on the immune responses induced by PDT in NMSCs. We also discuss the potential mechanisms underlying the process.

Simple 3‐criteria‐based ex vivo confocal diagnosis of basal cell carcinoma

Fast and simple microscopic evaluation of basal cell carcinoma (BCC) together with its subtype determination would accelerate diagnostic and therapeutic procedures in dermatology including Mohs surgery. Assessing whether simplified 3-criteria-based ex vivo confocal microscopic (CM) examination can reliably predict BCC diagnosis and subtype. Analyzing interobserver agreement between expert and novice examiner. CM images of 235 skin samples from 150 patients were prospectively evaluated by 2 blinded examiners for the presence of 3 predefined BCC criteria namely presence of tumor mass, peripheral palisading and clefting. Out of 235 skin samples 116 showed histological presence of BCC, confocally expert diagnosed a BCC in 110 and novice examiner in 107 samples. The overall sensitivity and specificity of detecting residual BCC was 96.6% and 98.7%, respectively. Confocally, examiners diagnosed correctly nodular BCC in 96.6%, respectively, 98.3%, superficial BCC in 96.8%, respectively, 93.5%, infiltrating BCC in 88.9%, respectively, 83.3% and other BCC subtype in 22.2%, respectively, 0% (expert and novice examiner, respectively). Ex vivo CM allowed intraoperative examination of BCC based on only 3-criteria with high sensitivity and specificity, provided useful information on tumor subtype and showed that both experienced and non-experienced examiners may use this diagnostic approach with excellent results.

Daylight Photodynamic Therapy for Actinic Keratoses.

Topical photodynamic therapy (PDT) using daylight is effective in the treatment of actinic keratoses (AKs), offering the potential for treatment of large fields such as full face and balding scalp, but with minimal therapy-associated pain. Comparison with conventional PDT indicates similar efficacy for thin and moderate-thickness AKs, but with significantly less discomfort/pain, driving a patient preference for daylight-mediated PDT (DL-PDT) compared with conventional PDT using high-intensity office/hospital-based light sources. Treatment protocol involves the application of a photosensitizing agent without occlusion and subsequent exposure to ambient daylight within 30min, with patients exposed to daylight for 1.5-2.0h. Pivotal randomized controlled trials in Europe and Australia have confirmed the efficacy of methyl aminolevulinic acid (MAL) DL-PDT in comparison with conventional MAL-PDT for mild and moderate-thickness lesions on the face and scalp. Initial clearance rates of 70-89% are reported. DL-PDT using a nanoemulsion aminolevulinic acid (ALA) has recently been shown to be at least as effective as MAL DL-PDT in treating mild and moderate-thickness AKs. DL-PDT may offer a better-tolerated method for treating patients with extensive AK disease. There is emerging literature on the potential for field PDT to reduce the number of new AKs developing, potentially preventing/slowing skin cancer development. Conventional PDT remains established as a therapy for Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas (BCCs), and AKs. The evidence for the use of DL-PDT beyond AK is limited, although has been reported in actinic cheilitis, superficial BCC, and acne and cutaneous leishmaniasis. There is emerging interest in combination therapy for AK, using one or more field therapies such as DL-PDT as an option to complement with localized treatment for residual lesions. We review current recommendations and consider the appropriate place for DL-PDT in our treatment armamentarium.

Comparison of long-term cosmetic outcomes for different treatments of superficial basal cell carcinoma

Comparison of long-term cosmetic outcomes for different treatments of superficial basal cell carcinoma

Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial

Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial

Nodular basal cell carcinoma of the face successfully treated with ingenol mebutate 0.015% gel.

Surgical excision is the first-choice treatment for basal cell carcinoma (BCC). Other treatments with topical agents such as 5-fluorouracil or imiquimod have also been suggested for use in superficial BCC (sBCC). Ingenol mebutate (IM) is a novel agent employed in the treatment of superficial actinic keratoses. The drug has been also successfully used in the treatment of sBCC. A case of large nodular BCC (nBCC) of the face in a 100-year-old inoperable woman is described. IM 0.015% gel was applied once daily for three consecutive days. This dose regimen was repeated for seven rounds within 11 months, with complete cure of the tumor. Mild local skin reactions, which were tolerated well, were observed. Selected cases of nBCC could be treated with IM gel, but the optimal concentration of the drug and the standard dose regimen of treatment are yet to be determined.

Cutaneous carcinogenic risk evaluation in 375 patients treated with narrowband-UVB phototherapy: A 15-year experience from our Institute.

Narrowband-ultraviolet B (NB-UVB) is widely used for the treatment of several dermatological diseases. A cutaneous carcinogenic effect has been hypothesized, but not proved. We retrospectively reviewed the data of patients treated with NB-UVB between January 1998 and December 2013 at the Dermatology Unit of our University Hospital, to evaluate the cutaneous carcinogenic risk of NB-UVB. In all, 375 patients were included, each receiving a mean follow-up of 6.9years. Vitiligo and psoriasis were the most common diseases. In total, 19 non-melanoma skin cancers (NMSCs) were diagnosed in eight patients, after a mean latency of 5.2years after the first radiation. No malignant melanoma (MM) was observed. The incidence rates of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were 620.2/100 ̇000 p/y and 116.3/100 ̇000 p/y. NMSCs were more frequent in patients affected by psoriasis (P=.0232), with older age at the first radiation (mean=68.8years, P=.0001). Despite the small number of patients and limited follow-up, our data suggest that NB-UVB may trigger cutaneous carcinogenesis, mainly in patients at risk for NMSCs, increasing their personal risk for single and multiple neoplasms, usually superficial BCCs. MM risk does not seem to be enhanced.

Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial.

Basal cell carcinoma (BCC) is the most common type of skin cancer and incidence rates are increasing. Photodynamic therapy (PDT) is a frequently used treatment, especially for superficial BCC (sBCC). Two topical photosensitizing agents are currently used to treat sBCC, namely 5-aminolaevulinic acid (ALA) and its ester, methyl aminolaevulinate (MAL). Previous research showed a high efficacy for ALA-PDT using a twofold fractionated illumination scheme in which two light fractions of 20 J cm-2 and 80 J cm-2 were delivered 4 h and 6 h after ALA application. To evaluate whether twofold ALA-PDT is superior to conventional MAL-PDT for sBCC. We performed a single-blind, randomized, multicentre trial in the Netherlands. Overall, 162 patients were randomized either to conventional MAL-PDT or twofold ALA-PDT. After 12 months, a total of six treatment failures occurred following ALA-PDT and 13 treatment failures occurred following MAL-PDT. The 12-month cumulative probability of remaining free from treatment failure was 92·3% [95% confidence interval (CI) (83·7-96·5)] for ALA-PDT and 83·4% (95% CI 73·1-90·0) for MAL-PDT (P = 0·091). The twofold ALA-PDT scheme resulted in fewer recurrences, although the difference between both treatment groups was not statistically significant. However, ALA-PDT resulted in higher pain scores and more post-treatment side-effects compared with MAL-PDT.

Accuracy of Dermoscopic Criteria for the Diagnosis of Melanoma In Situ

The accuracy of melanoma-specific dermoscopic criteria has been tested mainly in studies including invasive tumors. Scarce evidence exists on the usefulness of these criteria for the diagnosis of melanoma in situ (MIS). To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of MIS. A diagnostic accuracy study with retrospective patient enrollment was conducted in 3 centers specializing in skin cancer diagnosis and management. A total of 1285 individuals with histopathologically diagnosed MIS or other flat, pigmented skin tumors that were histopathologically diagnosed or monitored for at least 1 year were included. Dermoscopic images of MIS and other flat, pigmented skin tumors were evaluated by 3 independent investigators for the presence of predefined criteria. Evaluators were blinded to the clinic dermoscopic and histopathologic diagnosis. Frequencies of dermoscopic criteria per diagnosis were calculated. Crude odds ratios, adjusted odds ratios, and corresponding 95% CIs were calculated by univariate and multivariate logistic regression, respectively. A total of 1285 patients were included in the study (642 [50%] male); mean age was 45.9 years (range, 9-91 years). Of a total of 1285 lesions obtained from these patients, 325 (25.3%) were MIS; 574 (44.7%) were nevi (312 [24.3%] excised and 262 [20.4%] not excised); 67 (5.2%) were seborrheic keratoses, solar lentigines, or lichen planus-like keratoses; 91 (7.1%) were pigmented superficial basal cell carcinomas; 26 (2.0%) were pigmented intraepithelial carcinomas; 100 (7.8%) were Reed nevi; and 102 (7.9%) were invasive melanomas with a Breslow thickness less than 0.75 mm. The most frequent dermoscopic criteria for MIS were regression (302 [92.9%]), atypical network (278 [85.5%]), and irregular dots and/or globules (163 [50.2%]). The multivariate analysis revealed 5 main positive dermoscopic indicators of MIS: atypical network (3.7-fold; 95% CI, 2.5-5.4), regression (4.7-fold; 95% CI, 2.8-8.1), irregular hyperpigmented areas (5.4-fold; 95% CI, 3.7-8.0), prominent skin markings (3.4-fold; 95% CI, 1.9-6.1), and angulated lines (2.2-fold; 95% CI, 1.2-4.1). When compared only with excised nevi, 2 of these criteria remained potent MIS indicators, namely, irregular hyperpigmented areas (4.3-fold; 95% CI, 2.7-6.8) and prominent skin markings (2.7-fold; 95% CI, 1.3-5.7). Clinicians should take into consideration the aforementioned dermoscopic indicators for the diagnosis of MIS.

Cryosurgery + 5% 5-Fluorouracil for Treatment of Superficial Basal Cell Carcinoma and Bowen's Disease [Formula: see text

Superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis) are 2 types of nonmelanoma skin cancers (NMSCs) that are amenable to treatment with topical 5-fluorouracil, cryosurgery, or topical imiquimod, among other destructive and surgical modalities. There are few studies examining the effectiveness of combination therapy with 5% 5-fluorouracil and cryosurgery for the treatment of sBCC and SCCis. Our objective was to study the clinical cure rate achieved with the regimen of cryosurgery and a 3-week course of 5% 5-fluorouracil in the treatment of biopsy-proven sBCC and SCCis. A retrospective chart review of patients treated with cryosurgery and a 3-week course of 5% 5-fluorouracil was performed. Immunocompetent patients with biopsy-proven sBCC or SCCis who completed the treatment and attended a follow-up appointment at 6 months were included in the study. On clinical examination, 30 sBCC lesions of the 34 that were assessed and 31 SCCis lesions of the 33 that were assessed demonstrated no evidence of recurrence. The clinical cure rates were found to be 73% (sBCC) and 82% (SCCis), with the inclusion of patients that were lost to follow-up. This approach may represent a suitable option for select patients for the treatment of SCCis. Further studies with a longer follow-up duration, documentation of histologic cure, and tolerability of this regimen for SCCis are needed. The effectiveness of cryosurgery and 5-fluorouracil for sBCC requires further study.

Photodynamic Therapy Activated by Intense Pulsed Light in the Treatment of Nonmelanoma Skin Cancer.

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK), Bowen’s disease (BD), and superficial basal cell carcinoma (sBCC). PDT is traditionally performed in association with broad-spectrum continuous-wave light sources, such as red or blue light. Recently, intense pulsed light (IPL) devices have been investigated as an alternative light source for PDT in the treatment of nonmelanoma skin cancers (NMSC). We herein report our observational findings in a cohort of patients with a diagnosis of AK, sBCC, and BD that is treated with MAL-PDT using IPL, as well as we review published data on the use of IPL-PDT in NMSC.

A synthesis of the world's guidelines on photodynamic therapy for non-melanoma skin cancer.

Photodynamic therapy (PDT), using topically administered photosensitizing agents, is widely approved as a treatment for certain nonmelanoma skin cancers. As a tissue-sparing non-surgical modality, there is great potential for PDT to enhance the choice of therapies available to treat, and potentially prevent, skin cancer. Treatment-specific guidelines have assessed the evidence for various photosensitizing agents and light sources, dosimetry, and evaluate reported adverse effects. Discomfort is frequently experienced during treatment but no analgesia was required in most pivotal lesion-directed studies. Durability of response has been assessed with studies of PDT for basal cell carcinomas (BCC) extending to 5 years and beyond, 2 years for Bowen's disease and up to 1 year for actinic keratoses (AK). Disease-specific guidelines consider the place for topical PDT in routine clinical practice recognizing that PDT is typically office/clinic-based and usually initiated by specialists. Where updated guidelines are awaited, national and international consensus publications offer recommendations, including on the use of daylight to activate the photosensitizer for treating AK. Reviewed studies indicate equivalent efficacy of daylight PDT, but greatly reduced pain compared with conventional PDT. Guidelines and consensus publications also consider the place of PDT in treating skin lesions arising in organ transplant recipients and in the potential for PDT to delay/prevent the development of nonmelanoma skin cancers. There is now a substantial evidence-base to support the use of topical PDT in routine clinical practice with daylight PDT indicated for AK, providing suitable outside climate, whilst conventional PDT remains suitable for AK, Bowen's Disease, superficial and certain thin nodular BCC.

Comparing Topical Treatments for Basal Cell Carcinoma

Superficial basal cell carcinoma is a type of keratinocyte carcinoma that has increasing incidence and substantial morbidity. Jansen etal. report on a randomized trial with 5 years of follow-up that found imiquimod to be more effective than 5-fluorouracil or methyl aminolevulinate photodynamic therapy in preventing superficial basal cell carcinoma recurrence. However, the toxicity and cost of topical treatments, as well as patient preferences, need to be evaluated when making treatment decisions in clinical practice.

Dermoscopy of basal cell carcinoma.

Dermoscopy is widely used in dermatological practice. The method increases the accuracy of basal cell carcinoma (BCC) detection. Pigmented and nonpigmented variants of basal cell carcinoma present different dermoscopic features. Specific dermoscopy criteria have been recognized in different subtypes of BCC. Differentiation of superficial BCC from other subtypes is the most important issue, as it may determine further management decisions.

In vivo differentiation of common basal cell carcinoma subtypes by microvascular and structural imaging using dynamic optical coherence tomography.

The subtype of basal cell carcinoma (BCC) influences the choice of treatment. Optical coherence tomography (OCT) is a non-invasive imaging tool, and a recent development of an angiographic version of OCT has extended the application of OCT to image the cutaneous microvasculature (so-called dynamic OCT, D-OCT). This study explores D-OCT's ability to differentiate the common BCC subtypes by microvascular and structural imaging. Eighty-one patients with 98 BCC lesions, consisting of three subtypes: 27 superficial BCC (sBCC), 55 nodular BCC (nBCC) and 16 infiltrative BCC (iBCC) were D-OCT scanned at three European dermatology centres. Blinded evaluations of microvascular and structural features were performed, followed by extensive statistical analysis of risk ratio (RR) and multiple correspondence analysis. nBCC lesions displayed most characteristic structural and vascular features. Serpiginous vessels, branching vessels, vessels creating a circumscribed figure and sharply demarcated hyporeflective ovoid structures in the dermis were all associated with a higher risk of the subtype being nBCC. The presence of highly present lines and dark peripheral borders at the margin of ovoid structures was negatively associated with iBCC. Lastly, the finding of hyporeflective ovoid structures protruding from epidermis correlated with sBCC. We identified various microvascular and structural D-OCT features that may aid non-invasive identification of BCC subtypes. This would allow clinicians to individualize and optimize BCC treatment as well as aid follow-up of non-surgical treatment.

The Amelioration Effect of the Ethanolic Extract of Cnidium officinale in Mice with Imiquimod-induced Psoriasis-like Skin Lesion

Psoriasis is an auto-immune skin disease, which is characterized by the excessive generation of plaques on the skin with typically a long-lasting red, itchy and scaly symptoms. Imiquimod, which has been used for the treatment of external genital warts, actinic keratosis, and superficial basal cell carcinoma, induced of psoriasis-like skin disorders with skin erythema and thickness in mice. In the present study, we tried to find the bioactive herbal extract against imiquimod-induced psoriasis-like skin disorder in mice. During the searching of the herbal extract with anti-psoriatic effect, the ethanolic extract of Cnidium officinale ameliorated imiquimodinduced psoriasis-like skin disorder in mice. The morphological evaluation, H&E staining and Psoriasis Area and Severity Index (PASI) score showed that ear and back thickness, and erythema induced by imiquimod were significantly reversed after the treatment of the cream of the ethanolic extract of C. officinale. The overexpressed myeloperoxidase (MPO) and keratin 6A levels were decreased by the treatment of C. officinale cream. Also, IFN- γ, c-fos and IκB-α mRNA levels, which are related to the progression of psoriasis, were reduced by C. officinale cream. Thus, the ethanolic extract of C. officinale ameliorated psoriasis-like skin disorder induced by imiquimod and might be the therapeutic agent for psoriasis.

Trends in basal cell carcinoma incidence rates: a 16-year retrospective study of a population in central Poland.

IntroductionBasal cell carcinoma (BCC) is the most commonly occurring cancer worldwide, and the overall incidence is still rising. Unfortunately, the cancer registry in Poland does not record BCC individually. Thus, the incidence of BCC in a defined population is unknown.AimAnalysis of incidence rates of primary BCC in central Poland during 16 years considering sex, site distribution and age to determine trends.Material and methodsWe retrospectively included all cases of BCC which were diagnosed and treated in the Department of Dermatology and Venereology, Medical University of Lodz, during the 16-year period from 1999 to 2015.ResultsWe recorded 945 BCCs occurring in 890 patients (504 females – 57%, 386 males – 43%). Patient’s age was between 21 and 94. A distinct increase in BCC was observed after 1999, while after 2010 during the next 2-year period a slight decrease was noted. A statistically significant correlation was observed between histopathological types of BCC and the location of the lesions. The superficial type predominates on photoprotected areas, especially on the trunk, while the nodular type occurs mainly in facial areas. No statistically significant correlation was observed between histopathological types of BCC and sex. We found a significant increase in incidence for superficial BCC among middle-age patients, while the nodular type was observed more frequently among elderly subjects.ConclusionsBasal cell carcinoma is quite common in Poland and predominantly develops in the facial area. In middle-age patients the most common is superficial BCC, while in elderly people the nodular type is most common. Based on our results we assume that there is a strong need to educate general physicians to enable them to diagnose BCC in the early stages.

A systematic review on the use of cryotherapy versus other treatments for basal cell carcinoma

Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities. To determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non-intervention. We systematically searched PubMed, OVID, Cochrane Library, EMBASE, CINHAL, and CANCERLIT databases for the following terms: "cryotherapy", AND "basal cell carcinoma", OR "cryosurgery" OR "cryoablation" up to April 2018. Two independent reviewers screened the results and extracted the data. Study endpoints included basal cell carcinoma recurrence, cosmetic outcome, and healing time. Study quality was assessed using the Jadad scale. Six clinical studies met our inclusion criteria. The efficacy and safety of cryotherapy alone or with curettage in the treatment of primary superficial and nodular basal cell carcinoma was comparable to photodynamic therapy and surgery, respectively. Cryotherapy was inferior to radiation in terms of recurrence rate. Most patients had better cosmetic outcomes with photodynamic therapy and surgery compared to cryotherapy alone, and cryotherapy with curettage. Current available data suggests equivalent efficacy of cryotherapy alone compared to photodynamic therapy or surgery, but inferior to radiotherapy. More studies are necessary to draw definitive conclusions.