Treatment Of BCC Research Articles

Chemoprevention of basal cell carcinoma: reply from authors

The review started from the question whether early detection of BCC in the general (asymptomatic) population could lead to any benefit in terms of outcome and cost. In other words, should early detection efforts for skin cancer (secondary prevention) also include BCC? Review of available literature suggests that early detection and adequate treatment of BCC of the face could increase cost-effectiveness. Although these results could also pertain to patients who have had already a history of BCC, their setting is different since they may already be in a follow-up programme (tertiary prevention). This article is protected by copyright. All rights reserved.

English

There are reports of treatment of primary BCC by cryosurgery ; however, very few data are available on the successful treatment

A case report of eyelid basal cell carcinoma with orbital invasion: an alternative to exenteration

PurposeBasal cell carcinoma (BCC) is the most common periocular skin cancer affecting eyelids. Lateral canthus location is very rare. The gold standard treatment consists in an extensive surgery which allows the lowest recurrence rate. We report the case of a man suffering of a lateral canthus eyelid BCC with intraorbital invasion and who declined exenteration.MethodsA 78‐year old man consulted his ophthalmologist for a painless right ptosis associated with a tumefaction of the external orbital angle. He had neither oculomotor disorders nor decreased visual acuity. He was refered to our clinic 6 months later; we noticed a worsening of the ptosis up to visual axis and an abduction limitation. Visual acuity was steady. Pathological analysis revealed the diagnosis of BCC. Orbital tomography showed a location near the lacrimal gland with posterior invasion along the lateral rectus muscle. Multidisciplinary meeting suggested performing an exenteration. The patient refused this treatment. A conservative surgery was then suggested. The patient has been informed about risks of dissemination.ResultsWe performed a tumorectomy with large excision including the lateral part of upper and lower eyelids, the tumor itself, the lacrimal gland and the lateral orbital wall adjacent to the tumor. Pathological analysis revealed clear resection margins on all samples.The 4‐month control revealed no complications.ConclusionsExenteration is the gold standard treatment of orbital invasive BCC. In case of lateral canthus lesions, radiotherapy is not recommended because of major risks of orbital recurrences and side effects. Several authors showed that in case of bone‐adjacent tumors, bone resection is necessary, because tomography is not specific enough to rule out bone invasion. Despite a complete tumor resection, a long term follow‐up is mandatory patients with invasive BCC.

How to enhance the efficacy of topic photodynamic therapy for the treatment of nodular facial BCC

How to enhance the efficacy of topic photodynamic therapy for the treatment of nodular facial BCC

Biofilm-grown Burkholderia cepacia complex cells survive antibiotic treatment by avoiding production of reactive oxygen species.

The presence of persister cells has been proposed as a factor in biofilm resilience. In the present study we investigated whether persister cells are present in Burkholderia cepacia complex (Bcc) biofilms, what the molecular basis of antimicrobial tolerance in Bcc persisters is, and how persisters can be eradicated from Bcc biofilms. After treatment of Bcc biofilms with high concentrations of various antibiotics often a small subpopulation survived. To investigate the molecular mechanism of tolerance in this subpopulation, Burkholderia cenocepacia biofilms were treated with 1024 µg/ml of tobramycin. Using ROS-specific staining and flow cytometry, we showed that tobramycin increased ROS production in treated sessile cells. However, approximately 0.1% of all sessile cells survived the treatment. A transcriptome analysis showed that several genes from the tricarboxylic acid cycle and genes involved in the electron transport chain were downregulated. In contrast, genes from the glyoxylate shunt were upregulated. These data indicate that protection against ROS is important for the survival of persisters. To confirm this, we determined the number of persisters in biofilms formed by catalase mutants. The persister fraction in ΔkatA and ΔkatB biofilms was significantly reduced, confirming the role of ROS detoxification in persister survival. Pretreatment of B. cenocepacia biofilms with itaconate, an inhibitor of isocitrate lyase (ICL), the first enzyme in the glyoxylate shunt, reduced the persister fraction approx. 10-fold when the biofilms were subsequently treated with tobramycin. In conclusion, most Bcc biofilms contain a significant fraction of persisters that survive treatment with high doses of tobramycin. The surviving persister cells downregulate the TCA cycle to avoid production of ROS and at the same time activate an alternative pathway, the glyoxylate shunt. This pathway may present a novel target for combination therapy.

Vismodegib Is Effective in the Treatment and Prevention of BCC

Abstract Phase II studies show that vismodegib induces BCC regression and blocks new lesion growth.

Basal Cell Carcinoma: A Retrospective Clinicopathological Analysis of 100 Cases Derived from the Histopathological Registry of the Institute of Pathology in Niš / Bazocelularni karcinom: retrospektivna kliničko-histološka analiza 100 slučajeva na osnovu Histopatološkog registra Instituta za patologiju u Nišu

AbstractBasal cell carcinoma (BCC) is the most common malignant tumor of the skin. This study was conducted to analyze patients with BCC, their age and sex distribution, occupation, site distribution of tumors, clinical types, and histopathological characteristics of lesions. Based on the data obtained from the Histopathological Registry, a clinical and histopathological analysis of the surgically excised BCCs was performed.The study included 100 randomly selected patients out of 263 consecutive patients with histopathologically diagnosed BCC at the Institute of Pathology of the Clinical Center in Niš in the period of 15 months. The sex ratio was 1.4:1 in favor of men (p<0.05). Two thirds of patients were over the age of 60 (p<0.0001). The average age of patients was 66.6 ± 12.2 years (range 23 - 90). In agreement with the age distribution, 53 patients were retired (mostly retired farmers), 12 were workers, 14 farmers, 12 without permanent employment, 5 were housewives, and 4 clerks. A substantial majority of 61% of examinees lived in the country (p<0.001). The employment status was related to the age of examinees, but also with the altered demographic structure in the country: many workers lived in the country, or returned to the country after retirement.BCC was commonly found on the face (77%), and rarely on the trunk (11%) and extremities (2%).There were no data about exposition to X-rays or chemicals (except for pesticides and insecticides), scars resulting from burns or genodermatoses. In 87% of cases, BCC was significantly most often found at sites continually exposed to the sun (head including face and scalp, and neck). The most commonly diagnosed was the nodular type (57%), then the superficial (7%), ulcerative (5%), ulcero-sclerotic (4%), pigmented (1%), and morpheaform (1%). In 27% of cases, there were no data about the histopathological type of BCC in the Histopathological Registry, based on which accurate histological type of BCC could have been established. Based on histopathological analysis, apart from the nodular (40%), other types were rarely diagnosed, like the adenoid (12%) (p<0.0001), mixed types (nodular-adenoid, nodular-adenoid-fibroblastic and mixed) (9%), superficial (7%), fibroblastic (2%), infiltrative (1%), pigmented (1%), and morpheaform (1%). Surgical excision is the gold standard in the treatment of BCC: conventional, conducted in our patients, and Mohs micrographic surgery, which takes an important place in the treatment of high-risk BCCs. In 6% of cases, the tumor process was found in the margins of the excision.In conclusion: Basal cell carcinoma was more common in males than in females. Significantly more patients with excised basal cell carcinoma lived in the country. An age-related increase in the number of patients with BCC has been established, and most patients with excised basal cell carcinomas belonged to the age group of 61 to 81 years of age. In most patients the tumor site was on the face, whereas clinically and histopathologically, nodular type was the most common.

Pulsed dye laser as a novel non‐surgical treatment for basal cell carcinomas: Response and follow up 12–21 months after treatment

We showed previously that pulsed dye laser (PDL) is a potentially effective therapy for BCCs <15 mm on trunk and extremities. To follow-up, we conducted a study based on optimized parameters and expanded the duration of the study to at least 1 year after treatment. Fourteen patients with 20 biopsy-proven BCCs on trunk and extremities, 8-35 mm in diameter, were treated. Each BCC received four consecutive PDL treatments at 3-4 week intervals. A 4 mm margin of clinically normal skin was also treated. Standardized photography was performed prior to each treatment and follow up visit. Patients were asked to consent for standard excision or at least scouting biopsies after treatment completion. Complete clinical response was seen with 19 of 20 treated BCCs, regardless of size and histologic subtype. One did not respond completely to therapy. All remaining 19 BCCs were followed between 12 and 21 months (median = 18 months) after the last PDL treatment. Of these 19 BCCs, only one recurred at 17 months follow up. The remaining 18 BCCs did not show any clinical signs of residual or recurrent tumor at 12-21 months follow-up. Overall, 90% (18/20 tumors) of treated BCCs in this study showed no clinical or histologic evidence of BCC more than 12 months after PDL treatment. Additionally, 18/19 (95%) BCCs less than or equal to 17 mm showed no evidence of residual or recurrent tumor clinically or on histology 12-21 months post-laser treatment. PDL treatment of BCC represents a novel, quick, and relatively non-painful treatment that does not usually produce scar and may represent an alternative treatment for certain types of BCC in the appropriate clinical setting. This study confirms prior findings regarding the efficacy of PDL in the treatment of BCC, with longer follow-up period.

Genital superficial basall cell carcinoma - a case report / Bazocelularni karcinom kože u genitalnoj regiji - prikaz slučaja

Abstract Basal cell carcinoma (BCC) is the most common type of skin cancer in the Caucasian population. However, BCC of the genitalia is extremely rare. To the best of our knowledge, only 30 patients with BCC of the genitalia have been reported in the literature so far. BCC usually occurs in individuals over the age of 50, on sun-exposed areas of the body, and it is more prevalent in females. Superficial BCCs account for approximately 10% of BCC, and are commonly found on the trunk or limbs. This is a report on a 55-year-old male patient with penile BCC, and a literature review on this condition. The patient presented with asymptomatic skin lesions in the genital area which progressed during the last 15 years. Before admission, the patient received: antimycotics, antiviral, antibacterial and corticosteroid therapy, but without any improvement. Examination of the proximal penile skin revealed a sharply marked, smooth and shiny erythematous plaque of about 3.3 x 2 cm, with whitish squamae in the central zone. The histopathology finding revealed a superficial BCC and total excision was recommended. Treatment of the superficial BCC depends on its size and location. It includes surgical removal with possible reconstruction, radiotherapy, application of immunomodulators, local chemotherapy and local retinoid therapy. Although this is an extremely rare type of BCC, it is important to keep in mind that it may affect body areas seldom exposed to direct sunlight.

Abstract 4929: Hypermethylation of tumor suppressor gene promoters in basal cell carcinoma

Abstract Background Basal-cell carcinoma (BCC) is the most frequent malignancy in Caucasians, with increasing incidence. Overactivity of the Sonic Hedgehog pathway is implicated in BCC etiology, however recent literature suggests that BCC carcinogenesis may be more complex. Silencing of tumor suppressor genes by promoter hypermethylation, influenced by hypoxia, results in deregulation of cancer-related pathways. Since BCC arises in a hypoxic micro-environment, we assumed that epigenetic modifications may play a major part in BCC tumorigenesis. In this pilot we investigated promoter hypermethylation of tumor suppressor genes selected for their possible involvement in BCC. Eventually, knowledge of epigenetic modifications in BCC may impact diagnosis, classification, and treatment. Methods DNA was isolated from 33 formalin fixed paraffin-embedded BCC of 3 different histological subtypes. Marked tumor tissue was macroscopically scraped from slides and collected. CpG island methylation status of 10 promoter regions was analysed by methylation-specific PCR on sodium bisulfite-treated DNA. Data were compared with 36 normal skin tissue samples. All data were analysed with SPSS version 17.0. We used the Pearson Chi-Square test. Statistical significance was defined as a p-value ≤0.05. Results DNA methylation levels of the examined candidate gene promoters in tumor tissue compared to normal skin tissue were significantly higher for the following genes: APC 100% vs. 47,1% (p&amp;lt;0,001); sFRP5 93,9% vs. 42,4% (p&amp;lt;0,001); SHH 90,9% vs. 50,0% (p&amp;lt; 0,001) and 81,8% vs. 56,3% (p= 0,029) for CylD. In addition, the PTCH1 promoter showed a tendency to hypermethylation. The remaining promoters of sFRP1, sFRP2, sFRP4, TSC1 and RASSF1A showed no hypermethylation. Conclusions From our preliminary data we conclude that in BCC, promoters of several tumor suppressor genes, which may normally inhibit BCC growth, show aberrant methylation resulting in silencing of these genes. As a consequence, signalling pathways implicated in cancerous growth such as the SHH-, WNT- and NFκB- routes may be affected. Our data provide evidence that epigenetic modifications may play a role in BCC tumorigenesis. Genome-wide analyses will be our next step to screen for more relevant genes and to chart the full extent of genomic methylation changes in BCC. This entirely new approach may lead to new insights into development and treatment of BCC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4929.

GDC-0449—A potent inhibitor of the hedgehog pathway

SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC.

Induction of the members of Notch pathway in superficial basal cell carcinomas treated with imiquimod

Basal cell carcinoma of the skin (BCC) is the most common skin tumor in Caucasians worldwide. Different therapeutic options are available to treat BCC, including topical immunotherapy. Imiquimod is topical Toll-like receptor 7 agonist that activates anti-tumor immune response and has been recently approved for the treatment of superficial BCC (sBCC). We sought to investigate the influence of imiquimod treatment on the members of the Notch signaling pathway, whose activity is known to be decreased in BCCs. Six patients with sBCC were evaluated for Notch1, Jagged1 and Delta1 expression before (pre-treatment) and after the beginning of the topical treatment (post-treatment) with imiquimod using real-time PCR and immunohistochemistry. We show selective transcriptional up-regulation of Notch pathway members (Notch1, Jagged1 and Delta1) in tumor cells of the sBCC post-treatment. Furthermore, we demonstrate minor increase of Notch1 protein expression on infiltrating cells as well as strong increase in Jagged1 protein expression in regressing sBCC tumors post-treatment. In this way, imiquimod may act as a stimulator of the Notch pathway in sBCC tumor cells by up-regulating protein expression of the Notch ligand, Jagged1. Via induction of Notch signaling imiquimod may exert tumor suppressor function, which together with its proinflammatory properties results in tumor regression.

Imiquimod 5% cream effective in the treatment of large superficial BCC

Imiquimod 5% cream effective in the treatment of large superficial BCC