Synergism between mTOR pathway and ultraviolet radiation in the pathogenesis of squamous cell carcinoma and its implication for solid‐organ transplant recipients

Nonmelanoma skin cancers (NMSCs) are the most common malignancies in the United States in immunocompetent patients. Among the solid‐organ transplant recipients, NMSCs represent a significant disease burden, and they tend to be multiple and more aggressive. While the precise mechanisms responsible for the higher risk of developing cutaneous squamous cell carcinomas (SCCs) have not been completely elucidated, ultraviolet (UV) light has been established to be critical in initiation and promotion of tumor development. More recently, significant emphasis has been placed on the role of the mammalian target of rapamycin (mTOR) pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population. In this review, we will highlight and examine the most recent available data on the role of UV radiation and its interaction with mTOR pathway signaling in SCC pathogenesis.     

Status report on antibiotic resistance: implications for the dermatologist

In the United States and worldwide, public awareness of the progressive rise in antibiotic resistance has increased among public health officials, the medical community, and the lay public. The common use of systemic antibiotic therapy in dermatology warrants a closer look at how prescribing patterns impact on the development of antibiotic resistant bacteria and outcomes in clinical practice.     

Skin cancer: preventive photodynamic therapy in patients with face and scalp cancerization. A randomized placebo-controlled study

Background  Patients with a previous medical history of nonmelanoma skin cancers (NMSCs) often develop multiple or recurrent malignant lesions around the site of the primary tumour. This finding led to the field cancerization theory, which suggests that the entire epithelial surface of the regional skin has an increased risk for the development of malignant lesions. Management of field change is challenging, taking into account the high impact of NMSCs on public health and healthcare costs.
Objectives  We sought to investigate whether field-photodynamic therapy (PDT) of extreme photodamaged skin would prevent new NMSCs, in comparison with a control area receiving placebo-PDT, in patients with clinical and histological signs of field cancerization.
Methods  Forty-five patients, previously diagnosed as having NMSCs of the face or scalp, with actinic keratoses symmetrically distributed over the same regions, were randomized for field treatment with 20% aminolaevulinic acid (ALA)-PDT on one side and placebo-PDT on the other. During the next 12-month period of follow up, patients were clinically evaluated for new NMSCs.
Results  A significant delay in the mean time of appearance and a reduction in the total number of new lesions were observed in the field-PDT protocol, when compared with the control.
Conclusions  The results obtained showed that field therapy with ALA-PDT confers a significant preventive potential against the formation of new NMSCs in patients with field changes.     

Models of care and organization of services

This article examines the overall organization of services and delivery of health care in the United States. Health maintenance organization, fee-for-service, preferred provider organizations, and the Veterans Health Administration are discussed, with a focus on structure, outcomes, and areas for improvement. An overview of wait times, malpractice, telemedicine, and the growing population of physician extenders in dermatology is also provided.     

Prospective follow-up after curettage–cryosurgery for scalp and face skin cancers

Background  Cryosurgery (CS) in the treatment of nonmelanoma skin cancers (NMSCs), especially in the face and on the scalp, has several advantages vs. other methods. Prospectively gathered long-term results after CS are, however, scarce.
Objectives  To establish long-term results after curettage and CS (CCS) of NMSCs in the face and on the scalp considering complication rate, patient tolerance, cosmetic outcome and rate of recurrence.
Methods  Seven hundred and twenty-six patients with 962 face and scalp NMSCs were prospectively followed after CCS (1 week, 3 months, and then annually) during the time period December 1994–September 2008.
Results  Mean/median follow-up time was 42/34 months (range 1 month–14 years). Forty-two of 962 (4·4%) received antibiotics due to clinical, superficial infections. No serious complications were recorded. Ninety-nine per cent of the women and 100% of the men graded the cosmetic outcome as 'good' on a three-level scale, follow-up rate 99%. Fifty-six (14%) women and 78 (23%) men ( P  =   0·001) developed one or more new NMSCs during the study period. Fourteen of 962 (1·5%) recurrences were recorded, in nine women and five men. An expected recurrence-free rate/cure rate of > 97% after 14 years was calculated (Kaplan–Meier).
Conclusions  CCS in the treatment of NMSCs is expedient and well tolerated, with no major and few minor complications. When performed as in the present study it produces good cosmetic results in virtually all cases, with an anticipated 97% cure rate after 14 years. CCS is thus a highly viable alternative in the treatment of NMSCs in the face and on the scalp.     

Treatment of leprosy/Hansen's disease in the early 21st century

Leprosy, or Hansen's disease (HD), is caused by Mycobacterium leprae , a slowly dividing mycobacterium that has evolved to be an intracellular parasite, causing skin lesions and nerve damage. Less than 5% of people exposed to M. leprae develop clinical disease. Host cell-mediated resistance determines whether an individual will develop paucibacillary or multibacillary disease. Hansen's disease is a worldwide disease with about 150 new cases reported annually in the United States. Effective anti-mycobacterial treatments are available, and many patients experience severe reversal and erythema nodosum leprosum reactions that also require treatment. Leprosy has been the target of a World Health Organization multiple drug therapy campaign to eliminate it as a national public health problem in member countries, but endemic regions persist. In the United States, the National Hansen's Disease Program has primary responsibility for medical care, research, and information.     

Contact dermatitis in the United States: epidemiology, economic impact, and workplace prevention

Contact dermatitis in the United States poses a significant public health concern. This article provides a definition of contact dermatitis and its associated risk factors. The authors discuss the epidemiology of occupational contact dermatitis including its incidence and prevalence, and describe how estimates are calculated in the United States. The burden of disease on the individual, and its economic impact and cost to society, are also elucidated. A review of preventive measures to help reduce contact dermatitis in the workplace and an additional section on patch testing concludes the article.     

Basal cell carcinoma: evidence-based medicine and review of treatment modalities

Non-melanoma skin cancers (NMSCs) are the most common type of human cancer, with basal cell carcinomas representing the majority of these cancers. The following article will focus on a review of the current knowledge regarding incidence, risk factors, and pathogenesis, including genetics, clinical features, and treatment options of basal cell carcinomas.     

Prognostic variables in high‐risk cutaneous squamous cell carcinoma: a review

Cutaneous squamous cell carcinoma (SCC) is a growing public health problem in the United States. A subset of high‐risk SCC exhibits a more aggressive clinical trajectory including increased local recurrence and lymph node metastasis. However, there are no universally accepted criteria to help define and manage these patients. This review provides an overview of the high‐risk features of cutaneous SCC, prognostic stratification of various staging systems and treatment options. It further examines the prognostic factors influencing the staging of cutaneous head and neck SCC.     

Conclusions and recommendations: United States dermatologic health care need assessment

This United States skin disease health care needs assessment (HCNA) focuses on the most common and severe skin conditions. The purpose of this article is to highlight these skin conditions in a concise manner for efficient use by policy makers. Brief summaries of each article in this issue of Dermatologic Clinics are provided along with recommendations for better addressing dermatologic care needs.     

Chronic kidney disease prediction is an inexact science: The concept of “progressors” and “nonprogressors”

In 2002, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) instituted new guidelines that established a novel chronic kidney disease (CKD) staging paradigm. This set of guidelines, since updated, is now very widely accepted around the world. Nevertheless, the authoritative United States Preventative Task Force had in August 2012 acknowledged that we know surprisingly little about whether screening adults with no signs or symptoms of CKD improve health outcomes and that we deserve better information on CKD. More recently, the American Society of Nephrology and the American College of Physicians, two very well respected United States professional physician organizations were strongly at odds coming out with exactly opposite recommendations regarding the need or otherwise for ”CKD screening” among the asymptomatic population. In this review, we revisit the various angles and perspectives of these conflicting arguments, raise unanswered questions regarding the validity and veracity of the NKF KDOQI CKD staging model, and raise even more questions about the soundness of its evidence-base. We show clinical evidence, from a Mayo Clinic Health System Renal Unit in Northwestern Wisconsin, United States, of the pitfalls of the current CKD staging model, show the inexactitude and unpredictable vagaries of current CKD prediction models and call for a more cautious and guarded application of CKD staging paradigms in clinical practice. The impacts of acute kidney injury on CKD initiation and CKD propagation and progression, the effects of such phenomenon as the syndrome of late onset renal failure from angiotensin blockade and the syndrome of rapid onset end stage renal disease on CKD initiation, CKD propagation and CKD progression to end stage renal disease all demand further study and analysis. Yet more research on CKD staging, CKD prognostication and CKD predictions is warranted. Finally and most importantly, cognizant of the very serious limitations and drawbacks of the NKF K/DOQI CKD staging model, the need to individualize CKD care, both in terms of patient care and prognostication, cannot be overemphasized.     

Infectious skin diseases: a review and needs assessment

Infectious skin diseases pose considerable treatment challenges, especially given the recent appearance of several highly virulent pathogens as well as the rising number of immunocompromised patients in the United States. This article discusses common bacterial, fungal, and viral skin infections with an emphasis on cellulitis, dermatophyte infections, and herpes simplex viral infections. Disease pathogenesis, treatment, and cost of treatment are addressed with an emphasis on therapeutic needs and future research directions. Common priorities for all infectious skin disease categories include increased disease surveillance, study of existing treatments, and efforts in drug development.     

Issues in the delivery of dermatologic surgery for skin cancer

Significant financial resources need to be dedicated to treating the large numbers of skin cancers in the United States. The goal of the surgical treatment of skin cancer is to provide a high cure rate in a manner that is minimally morbid, convenient, and inherently of high value. Cost-effective delivery of this skin cancer care is critical given the prevalence of cutaneous neoplasia. Dermatologists are the best-trained physicians in the identification and management of melanoma and NMSCs. They are the most highly skilled judges of when intervention is indicated, of which lesions warrant biopsy, and of which treatment techniques are applicable for each individual tumor. These skills take years to develop and are necessary to provide the highest standard of medical and surgical management of skin cancer. As dermatologic surgery continues to evolve and dermatologists in residency receive even more surgical training, the dermatologist will prove to be the surgical skin cancer specialist well into the new millennium.     

Photographic utilization in dermatology clinics in the United States: a survey of university-based dermatology residency programs.

BACKGROUND: Photography has recently been introduced as an adjunct to the clinical management of patients with the dysplastic nevus syndrome (DNS). OBJECTIVE: Our purpose was to evaluate the methods used and the extent of clinical photography in dermatology residency programs in the United States. METHODS: Nonmilitary accredited dermatology residency programs in the United States were surveyed (73% response rate) regarding utilization and technical aspects of clinical photography. RESULTS: Forty-one percent of respondents used photography for the clinical management of 90% or more of patients with DNS. Twenty-four percent of respondents used photography for the clinical management of all patients with DNS. Eighty-one percent of respondents used slides, and 62% utilized total body photographs. The median number of photographs taken for a patient with DNS was 20. CONCLUSION: Dermatologic photography has been widely adopted for the clinical management of patients with DNS. Failure of the health insurance industry to recognize the value of this procedure may result in its underutilization.     

Choice of dialysis modality prior to kidney transplantation: Does it matter?

The population of patients with end stage renal disease (ESRD) is increasing, lengthening waiting lists for kidney transplantation. Majority of the patients are not able to receive a kidney transplant in timely manner even though it is well established that patient survival and quality of life after kidney transplantation is far better when compared to being on dialysis. A large number of patients who desire a kidney transplant ultimately end up needing some form of dialysis therapy. Most of incident ESRD patients choose hemodialysis (HD) over peritoneal dialysis (PD) as the modality of choice in the United States, even though studies have favored PD as a better choice of pre-transplant dialysis modality than HD. PD is largely underutilized in the United States due to variety of reasons. As a part of the decision making process, patients are often educated how the choice regarding modality of dialysis would fit into their life but it is not clear and not usually discussed, how it can affect eventual kidney transplantation in the future. In this article we would like to discuss ESRD demographics and outcomes, modality of dialysis and kidney transplant related events. We have summarized the data comparing PD and HD as the modality of dialysis and its impact on allograft and recipient outcomes after kidney transplantation.     

Abnormal aquaporin-3 protein expression in hyperproliferative skin disorders

Non-melanoma skin cancers (NMSCs) and psoriasis represent common hyperproliferative skin disorders, with approximately one million new NMSC diagnoses each year in the United States alone and a psoriasis prevalence of about 2% worldwide. We recently demonstrated that the glycerol channel, aquaporin-3 (AQP3) and the enzyme phospholipase D2 (PLD2) interact functionally in epidermal keratinocytes of the skin to inhibit their proliferation. However, others have suggested that AQP3 is pro-proliferative in keratinocytes and is upregulated in the NMSC, squamous cell carcinoma (SCC). To evaluate the AQP3/PLD2 signaling module in skin diseases, we determined their levels in SCC, basal cell carcinoma (BCC) and psoriasis as compared to normal epidermis. Skin biopsies with the appropriate diagnoses (10 normal, 5 SCC, 13 BCC and 10 plaque psoriasis samples) were obtained from the pathology archives and examined by immunohistochemistry using antibodies recognizing AQP3 and PLD2. In normal epidermis AQP3, an integral membrane protein, was localized mainly to the plasma membrane and PLD2 to the cell periphery, particularly in suprabasal layers. In BCC, AQP3 and PLD2 levels were reduced as compared to the normal-appearing overlying epidermis. In SCC, AQP3 staining was “patchy,” with areas of reduced AQP3 immunoreactivity exhibiting positivity for Ki67, a marker of proliferation. PLD2 staining was unchanged in SCC. In psoriasis, AQP3 staining was usually observed in the cytoplasm rather than in the membrane. Also, in the majority of psoriatic samples, PLD2 showed weak immunoreactivity or aberrant localization. These results suggest that abnormalities in the AQP3/PLD2 signaling module correlate with hyperproliferation in psoriasis and the NMSCs.     

Host risk factors for the development of multiple non‐melanoma skin cancers

Non‐melanoma skin cancer (NMSC) is the most common cancer in the US, and having multiple lesions conveys substantial cost and morbidity for the individual involved. Although there are data available on risk factors for NMSC, there are currently few studies that identify specific risk factors for development of multiple NMSCs. We evaluated host risk factors for multiple NMSCs among men (Health Professionals Follow‐up Study) and women (Nurses’ Health Study). Compared with individuals with a single NMSC, having greater number of sunburns was a risk factor for developing ≥2 NMSCs [≥10 sunburns, cumulative relative risk (RR) = 1.21, 95% confidence interval (CI): 1.07–1.36] and a higher risk of developing ≥11 NMSCs (≥10 sunburns, RR = 2.33, 95% CI: 1.57–3.46). Inability‐to‐tan was associated with risk of developing ≥2 NMSCs (cumulative RR = 1.29, 95% CI: 1.18–1.40) and a higher risk of developing ≥11 NMSCs (RR = 1.91, 95% CI: 1.50–2.43). Men had an increased risk of developing ≥2 NMSCs (cumulative RR = 1.53, 95% CI: 1.40–1.66). Risk of developing 2–4, 5–10 and ≥11 NMSCs increased with age. Other risk factors for developing ≥2 NMSCs included red natural hair colour (cumulative RR = 1.23, 95% CI: 1.07–1.42), family history of melanoma (cumulative RR = 1.15, 95% CI: 1.03–1.28), and having ≥6 nevi on the left arm (cumulative RR = 1.22, 95% CI: 1.07–1.40). In conclusion, physicians caring for individuals with incident NMSCs may consider paying special attention to those at highest risk for developing additional tumours, especially males and those with a history of ≥10 lifetime sunburns, by performing routine full skin examinations and counselling for aggressive photoprotection.     

Giant neglected squamous cell carcinoma of the skin

Nonmelanoma skin cancers (NMSCs) are the most common type of skin tumor, representing about one‐third of all malignancies diagnosed worldwide each year. Cutaneous squamous cell carcinoma (cSCC) is the second most common form of NMSCs and the risk of cSCC invasiveness should be assessed on the basis of tumor size, anatomical location, and histological subtype. Although most cSCCs are early diagnosed and successfully treated, in a small percentage of patients with giant cSCC (maximum diameter >5 cm), metastases may occur; treatment options are limited and not really effective. We report the case of a giant metastatic cSCC that had been neglected for more than 20 years. Radiotherapy or surgery were not feasible and polichemotherapy (cisplatin, 5‐fluorouracil and paclitaxel) was not effective. Therefore, the patient was treated with palliative electrochemotherapy (ECT) achieving a partial reduction of cutaneous metastasis and pain relief but unfortunately the patient died 3 months after the second ECT treatment.     

Management of acute partial-thickness bums

More than 1 million burns occur annually in the United States. The management of first-degree burns is limited to minor pain control whereas third-degree burns require skin grafting. However, second-degree/partial-thickness burns disrupt the epidermis and part of the dermis, thereby requiring acute wound care, pain control, and infection control. There are many different topical treatments and dressings for acute partial-thickness burns, and the clinical superiority of any one treatment is unclear. Because dermatologists may manage acute outpatient burns, we review the most widely utilized treatments that may be administered on an outpatient basis.