Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)?

Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.

Pembrolizumab combined with axitinib in the treatment of skin metastasis of renal clear cell carcinoma to nasal ala:A case report

BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.

Facial Merkel cell carcinoma in a patient with diabetes and hepatitis B:A case report

BACKGROUND Patients with chronic inflammatory disorders are at a higher risk of developing aggressive Merkel cell carcinoma(MCC). Diabetes is a common chronic inflammatory disease that is possibly associated with MCC;however, there are still no reports on the association between hepatitis B virus(HBV) infection and MCC. Whether there is an association between these three diseases and the specific mechanisms behind their effects is worth further research in the future.CASE SUMMARY We herein report a rare case of MCC with extracutaneous and nodal invasion in an Asian individual with type 2 diabetes mellitus and chronic HBV infection, but no immunosuppression or other malignancies. Such cases are uncommon and have rarely been reported in the literature. A 56-year-old Asian male presented with a significant mass on his right cheek and underwent extensive resection combined with parotidectomy, neck lymphadenectomy, and split-thickness skin grafting. Based on the histopathological findings, a diagnosis of MCC involving the adipose tissue, muscle, nerve, and parotid gland with lymphovascular invasion was made. Subsequently, he received radiotherapy with no adverse reactions.CONCLUSION MCC is a rare, aggressive skin cancer with frequent local recurrence, nodal invasion, and metastasis, which usually arises in older people of the white race. Patients with chronic inflammatory disorders are at a higher risk of developing aggressive MCC. The diagnosis can be confirmed with histology and immunohistochemistry. For localized MCC, surgery is the preferred treatment option. However, for advanced MCC, radiotherapy and chemotherapy have proven to be effective. In cases where chemotherapy is not effective or in the advanced stages of MCC, immune therapy plays an important role in treatment. As with any rare disease, the management of MCC remains an enormous challenge for clinicians;thus, follow-up should be individualized and future progress needs multidisciplinary collaborative efforts. Furthermore, physicians should include MCC in their list of possible diagnoses when they come across painless, rapidly growing lesions, particularly in patients with chronic HBV infection or diabetes, as these patients are more susceptible to the development of this condition and it tends to be more aggressive in them.

Squamous cell carcinoma of the skin: Emerging need for novel biomarkers

The incidence of non-melanoma skin cancers(NMSC)is rising worldwide resulting in demand for clinically useful prognostic biomarkers for these malignant tumors,especially for invasive and metastatic cutaneous squamous cell carcinoma(cSCC).Important risk factors for the development and progression of cSCC include ultraviolet radiation,chronic skin ulcers and immunosuppression.Due to the role of cumulative long-term sun exposure,cSCC is usually a disease of the elderly,but the incidence is also growing in younger individuals due to increased recreational exposure to sunlight.Although clinical diagnosis of cSCC is usually easy and treatment with surgical excision curable,it is responsible for the majority of NMSC related deaths.Clinicians treating skin cancer patients are aware that certain cSCCs grow rapidly and metastasize,but the underlying molecular mechanisms responsible for the aggressive progression of a subpopulation of cSCCs remain incompletely understood.Recently,new molecular markers for progresprogression of cSCC have been identified.

The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment

The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.

Unique Clinical Features of Curaderm when Treating Skin Cancers

Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.

Peroxidative Activity in Patients with Skin Basal Cell Carcinoma

Oxidative status assessment is an initial step in tumor related studies. To the best of our knowledge, this is the first study considering oxidative activity of both serum and tissue specimens in human basal cell carcinoma (BCC), which is the most common tumor in the world. Concentration of Malondialdehide (MDA) in human basal cell carcinoma (BCC) and individually matched normal skin tissue were examined with spectrophotometery method. Fresh normal and cancerous skin paired tissue was obtained from 60 patients who underwent curative BCC resection at one center in Tehran (Razi hospital). Serum Concentration of Malondialdehide (MDA) in these patients and 55 normal subjects were also measured. MDA level in cancerous tissue of patients with skin BCC (1.0 ± 0.14 ng/g) was significantly (p = 0.001) higher than normal neighboring skin tissue (0.3 ± 0.07 ng/g). A remarkable (Not significant, P = 0.18) increase was found in the serum MDA level in patients with skin BCC (8.0 ± 2.3 ng/ml) in comparison with the control subjects (7.3 ± 2.9 ng/ml). A significant positive correlation (r = 0.276, p = 0.03) was found between Serum MDA and skin tissue MDA for non-affected skin tissue (normal neighboring skin), whereas no significant correlation (p > 0.05) was found for cancerous tissue. Cut-point of 5.2 ng/ml of serum MDA concentration showed a screening sensitivity of 95%. There is an active oxidative process in BCC lesions. Serum MDA concentration can be used either as a screening test or a predictor for tissue MDA concentration.

Grape Skin Polyphenols （GSPs） Inhibit the Migration of Mouse Mammary Carcinoma 4T1 Cells in Vitro

OBJECTIVE 1） To study the efficacy of GSPs on the migration of highly metastatic mammary carcinoma cells and 2） To investigate inhibition mechanisms.METHODS Cell migration was assessed using a 24-well transwell assay. Cells with different concentrations of GSPs were suspended （5×105 cell/mL） in RPMI 1640 media in the upper chamber, and RPMI 1640 media with 10% FBS was supplemented in the lower chamber. Then, cells were allowed to migrate for 24 h.RESULTS GSPs inhibited the migration of 4T1 cells in a dosedependent manner. The migration of 4T1 cells was obviously inhibited by GSPs, even at a very low concentration （5 μg/mL）,and was totally inhibited when the concentration was 20 μg/mL.Also, 20 μg/mL of GSPs inhibited cell viability by only 11.4% and induced early apoptosis by only 5.6% compared with a percentage of 4.0% in control cells. GSPs suppressed the activation of PDK1,Akt and Erk1/2 in a dose-dependent manner.CONCLUSION GSPs significantly inhibit the migration of highly metastatic mammary carcinoma 4T1 cells in vitro. This inhibition is independent of decreased cell viability or apoptosis induction. The inhibition of migration by GSPs is involved in blocking the PI3k/Akt and MAPK pathways.

Giant cutaneous squamous cell carcinoma of the popliteal fossa skin:A case report

BACKGROUND Cutaneous squamous cell carcinoma(cSCC)is a common malignant hyperplasia of the skin epithelium.However,cSCC progressing to giant squamous cell carcinoma of the popliteal fossa skin has not been reported.We used full-thickness skin graft from the lower left quadrant of the abdomen to reconstruct the popliteal fossa skin defect in our patient.CASE SUMMARY A 64-year-old woman presented with a 3-year history of a progressively enlarged integumentary tumor located on her left popliteal fossa,which was surgically treated.The resultant defect(15 cm×25 cm)was repaired using full-thickness skin graft from the lower left quadrant of the abdomen.CONCLUSION Full-thickness skin graft is a good choice to repair popliteal fossa defect.

Meis1 Is Required for c-Met Inhibition to Suppress Cell Proliferation of Skin Squamous Cell Carcinoma Cells

Previous studies have shown that Meis1 plays an important role in the pathogenesis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Meis1 belongs to the TALE family, the members of which are used as biomarkers for AML. Meis1 has been shown to play a functional role in epithelial tissues, such as skin. However, its functions in skin carcinogenesis remain poorly understood. On the other hand, the c-Met inhibitor SU11274 has been identified through drug screening with HOXA9/Meis1-induced AML cell lines. SU11274 altered cell proliferation and the cell cycle status in human AML cell lines. Thus, we hypothesized that the effects of SU11274 are dependent on Meis1 and that its knockdown may diminish the effects of SU11274 not only in AML cell lines, but also in skin cancer cell lines. In order to test our hypothesis, we established Meis1 knockdown cell lines using two skin squamous cell carcinoma cell lines (B9 and D3) and treated these cell lines with SU11274. The results obtained showed that SU11274 suppressed cell proliferation by modulating cell cycle progression in the presence of Meis1, but not in its absence. Furthermore, an expression analysis showed that SU11274 activated the transcription of Meis1, which led to the transcription of Hif1α and Cdkn2a (p16Ink4a and p19Arf). These results suggest that Meis1 is required for the c-Met inhibitor SU11274 to suppress the proliferation of the skin squamous cell carcinoma cell lines.

Scrotal Skin Metastases of Renal Cell Carcinoma: A Case Report

Cutaneous metastasis from renal cell carcinoma is believed to be rare. We present a 66-year-old man operated for kidney cancer 20 years ago and has consulted for a scrotal lesion that had started 20 days. The physical examination revealed an erythematous lesion. A biopsy of the scrotal skin was made. We found a scrotal metastasis of renal cell carcinoma.

Circulating Tumor Cell Cultures as a Predictive Marker during Salvage Therapy of Refractory Merkel Cell Carcinoma with Chemotherapy and Electron Beam Radiation

Metastatic Merkel Cell carcinoma (MCC) is a highly unusual and aggressive skin cancer that presents as a small, pink to violet skin lesion and metastasizes early in its growth. Metastatic MCC is generally treated with small cell lung cancer chemotherapy regimens, because the tumor consists of neuroendocrine cells, but patients generally do not have durable responses. The pathogenesis of MCC has recently been attributed to the Merkel Cell polyoma virus. This virus activates the cellular retinoblastoma oncoprotein and cell cycle machinery, triggering continual cellular proliferation. A 77-year-old man developed extensive MCC metastases, involving more than one fourth of his scalp and numerous cervical lymph nodes. Following failure of initial chemotherapy and radiation, effective palliation was achieved by using a sequence of electron-beam radiotherapy, low dose gemcitabine, and etoposide, resulting in significant periods of tumor regression and prolonged survival. A novel circulating tumor cell (CTC) culture assay was performed on four separate clinic visits during the treatment period. Tumor colonies were cultured from the patient’s peripheral blood and CTC colony counts were correlated with clinical treatment response. Not only did the patient respond to palliative cell cycle directed chemotherapy and electron beam radiation, but we demonstrated that CTC can be cultured from peripheral blood of MCC patients and serve as a predictive marker to monitor treatment response.

Merkel Cell Carcinoma of Eyelid: A Rare Clinical Presentation and Diagnostic Challenge

The purpose of this paper is to report a case of rare localised (limited to eyelid) malignant eyelid tumor in a 70 year old Indian male. Histopathology confirmed it to be a Merkel cell carcinoma. Surgical excision and eyelid reconstruction was done successfully. No local or systemic recurrence has been noted at a follow up of 2 years. The well defined nature of a highly malignant tumor, its localised presentation and management is being described in following report.

Diabetic ulcer with cutaneous squamous cell carcinoma:A case report

BACKGROUND Chronic skin ulcers are a risk factor for the development of skin tumors.In patients with diabetes,chronic refractory ulcers may also contribute to higher susceptibility to skin tumors.Timely surgical removal of chronic and nonhealing diabetic foot ulcers can effectively prevent progression to squamous cell carcinoma.Such cases may be misdiagnosed owing to currently insufficient clinical evidence.However,in cases of chronic ulcer wounds,it is crucial to enhance clinical awareness regarding their potential progression into malignant lesions.CASE SUMMARY An 84-year-old male patient with diabetes presented with a significantly ulcerated area on his foot.The ulcer had been present to varying degrees since 1996.Between 2012 and July 2019,even after receiving treatments such as herbal medicines or heat clearance and detoxification complete healing of the wound was not achieved.In July 2020,histopathological analysis confirmed a well-differentiated cutaneous squamous cell carcinoma.After the treatments,the ulcer wound healed slowly and did not expand.CONCLUSION Potentially malignant lesions in chronic ulcer wounds should be identified and treated in a timely manner to prevent their progression.

Fluorescence lifetime imaging microscopy and its applications in skin cancer diagnosis

Fluorescence lifetime(FLT)of fluorophores is sensitive to the changes in their surrounding microenvironment,and hence it can quantitatively reveal the physiological characterization of the tissue under investigation.Fluorescence lifetime imaging microscopy(FLIM)provides not only morphological but also functional information of the tisse by producing spatially resolved image of fuorophore lifetime,which can be used as a signature of disorder and/or malignancy in diseased tissues.In this paper,we begin by introducing the basic principle and common detection methods of FLIM.Then the recent advances in the FLIM-based diagnosis of three different skin cancers,including basal cell carcinoma(BCC),squamous cell carcinoma(SCC)and malignant melanoma(MM)are reviewed.Furthermore,the potential advantages of FLIM in skin cancer diagnosis and the challenges that may be faced in the future are prospected.

Management and Clinico-Pathologic Aspects of Non-Melanoma Skin Cancer of the Head and Neck: A Retrospective Institutional Based Study at the Egyptian National Cancer Institute

Background: Reviewing and analyzing the Clinico-pathologic aspects of non-melanoma skin cancer of the head and neck (NMSCHN), type of management, prognostic factors, and disease-free survival (DFS) in a period of 5 years at the National Cancer Institute—Cairo University—Egypt. Materials and Methods: A retrospective study of two hundred patients with NMSCHN was treated at the National Cancer Institute—Cairo University—Egypt from January 2008 to December 2012. The mean follow-up was 6 months (1 - 84 months). Results: 117 males and 83 females with 90% ≥ 50 years old. The scalp (27.5%), the periorbital region (13%), the cheek (12.5%) and the nose (12.5%) are the main anatomical sites affected. BCC represented 71.5% with nodular type (79%) predominance;SCC represented 21% with GII (61.1%) the commonest grade. Surgery was the main modality of treatment (93%) with local flaps only (63.9%) and primary closure (14.7%) were the main surgical options following wide local excision. Positive and close margins were detected in 23.5% of excised specimens. No significant association was found between disease-free survival (DFS) and pathology, treatment modality, the occurrence of complications or safety margin status. Conclusion: NMSCHN lesions should be surgically excised in specialized high volume centers with readily available peripheral margin control and should be operated by senior experienced surgeons.

Topical Curaderm^BEC5Therapy for Periocular Nonmela-noma Skin Cancers: A Review of Clinical Outcomes

Approximately 5 to 10 percent of all skin cancers occur in the periocular region. Basal cell carcinoma is the most frequent malignant periocular tumor, followed by squamous cell carcinoma, sebaceous gland carcinoma, and malignant melanoma. Nonmelanoma skin tumors at the periocular area often cause disfigurement with destruction of soft conjunctival tissue. Many therapeutic methods have been recommended to combat the morbidity and mortality associated with these lesions. Excisions with frozen-section control or Mohs micrographic surgery are regarded as the gold-standard treatments for periocular basal cell and squamous cell carcinomas. However, these treatment modalities have various limitations and reconstruction surgery is often associated with these treatment options. The chemotherapeutic agents solasodine rhamnosides in a cream formulation CuradermBEC5 are specific, effective and safe treatments for nonmelanoma skin cancers with excellent cosmesis. The antineoplastic mode of action is by apoptosis. In this review it is shown that CuradermBEC5 also treats periocular basal cell carcinoma and squamous cell carcinoma with impressive cosmetic outcomes and no reconstructive surgery is required.

Diabetes and skin cancers: Risk factors, molecular mechanisms and impact on prognosis

Diabetes and skin cancers have emerged as threats to public health worldwide.However,their association has been less intensively studied.In this narrative review,we explore the common risk factors,molecular mechanisms,and prognosis of the association between cutaneous malignancies and diabetes.Hyperglycemia,oxidative stress,low-grade chronic inflammation,genetic,lifestyle,and environmental factors partially explain the crosstalk between skin cancers and this metabolic disorder.In addition,diabetes and its related complications may interfere with the appropriate management of cutaneous malignancies.Antidiabetic medication seems to exert an antineoplastic effect,however,future large,observation studies with a prospective design are needed to clarify its impact on the risk of malignancy in diabetes.Screening for diabetes in skin cancers,as well as close follow-up for the development of cutaneous malignancies in subjects suffering from diabetes,is warranted.

Facial basal cell carcinoma:A retrospective study of 67 cases

BACKGROUND Basal cell carcinoma(BCC)is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential.It ideally affects sun-exposed skin of older patients with more propensity for the facial region.AIM To evaluate the different clinicopathological characteristics of the facial BCC and the efficacy and safety of diode laser for the treatment of these lesions.METHODS We retrospectively reviewed facial BCC lesions of<1.5 cm in diameter and subjected them to diode laser ablation during the period from September 2016 to August 2021 at Al-Ramadi Teaching Hospital,Ramadi City,Iraq.Data matching the age,gender,duration,site,and clinical and histological types were registered for every subject.The functional and aesthetic outcomes and complications following diode laser ablation for each patient were also recorded.RESULTS Of 67 patients with facial BCC,there was 65.67%from the age group≥60 years and 58.21%males.The mean duration of the lesions was 5.15±1.836 mo.The most involved location was the nose(29.85%).About half of the cases belong to the noduloulcerative type.Solid histological type comprises 40.3%of the cases,while the least was keratotic(13.4%).Moreover,65.2%of the solid cases were from the age group≤60 years and 38.6%of the adenoid type from the age group>60 years(P value=0.007).Excellent aesthetic and functional outcomes were reported in all cases after 6 mo of follow-up.Few complications were reported after diode laser ablation.CONCLUSION Facial BCC was mostly seen in the elderly and men.The mean duration was 5.15 mo.The nose was the commonest involved site.Noduloulcerative lesions were seen in approximately half of the lesions.The age of the patients determined the histological type of the lesion(solid type was mostly seen in the age group≤60 years,while,adenoid in the age group>60 years).Diode laser ablation showed excellent functional and aesthetic outcomes following a 6-mo follow-up.

Ectopic Cushing's syndrome in a patient with metastatic Merkel cell carcinoma:A case report

BACKGROUND Ectopic Cushing syndrome(ECS)is a rare condition commonly associated with neuroendocrine tumors(NET),mainly bronchial carcinoids.The association of paraneoplastic syndrome with Merkle cell carcinoma(MCC)is limited to individual case reports.CASE SUMMARY In this article we report an unusual and striking presentation of ECS in a patient with known metastatic MCC.An elderly patient presented with new onset severe hypertension,hyperglycemia and hypokalemia,muscle wasting,and peripheral edema.A diagnosis of adrenocorticotropic hormone dependent,non-pituitary,Cushing syndrome was established.Medical therapy inhibiting adrenal function was promptly started but unfortunately the patient survived only a few days after diagnosis.CONCLUSION The occurrence of an aggressive form of ECS in patients with NET should be recognized as an ominous event.To our knowledge,the association of this complication in a patient with MCC had not been reported.