The actinic keratosis. A perspective and update

BACKGROUND: Actinic keratosis (AK) is a common sun-induced precancerous neoplasm confined to the epidermis. It is the initial manifestation of a continuum of clinical and histologic abnormalities that progresses to invasive squamous cell carcinoma (SCC), a disorder that accounts for thousands of preventable deaths in America each year. OBJECTIVE: The purpose of this work is to describe the actinic keratosis. METHODS: This effort was performed by a literature review and analysis. RESULTS: Like SCCs, the vast majority of AKs are asymptomatic. Although some actinic keratoses may become clinically inapparent, possibly either due to immune rejection or simply having their external surface unknowingly scraped off, an untreated AK represents a potentially curable fatal cancer. CONCLUSIONS: Each AK should be treated before it progresses to invasive squamous cell carcinoma. Destructive modalities such as cryosurgery using liquid nitrogen and electrodesiccation and curettage are the mainstays of therapy. Each case must be individualized. LEARNING OBJECTIVES: After studying this article, participant should be able to: 1. Understand the concept of an actinic keratosis. 2. Learn how to recognize its clinical manifestations. 3. Be aware of the danger it poses as an easily curable papulonodule that may become a fatal cancer.     

Prospective use of intramuscular triamcinolone acetonide in pseudogout

OBJECTIVE: To prospectively assess the efficacy of intramuscular (i.m.) triamcinolone acetonide in the treatment of pseudogout. METHODS: Fourteen patients with crystal proven pseudogout presenting with an acute attack within 5 days of onset were treated with intramuscular triamcinolone acetonide 60 mg and followed for 30 days. Patients with inadequate response were eligible for a 2nd triamcinolone acetonide injection on Day 1-2. RESULTS: Twelve patients had contraindication to nonsteroidal antiinflammatory agents (NSAID). Acute arthritis was monoarticular in 10 patients, and involved 2 or more joints in 4 patients. All patients had good clinical response to triamcinolone acetonide based on restoration of near baseline joint range of motion and joint circumference, and at least 50% improvement in patient and physician global assessment. Major clinical improvement occurred by Day 1-2 (2 patients), Day 3-4 (11 patients), and Day 10-14 (one patient). Six patients required a 2nd triamcinolone acetonide injection on Day 1-2. Toxicities were not observed. CONCLUSION: I.m. triamcinolone acetonide appears to be safe, well tolerated, and effective in the treatment of pseudogout. It may be a reasonable alternative therapy when NSAID are contraindicated, and for polyarticular attacks where intraarticular corticosteroids are impractical.     

Corticosteroid-induced cutaneous atrophy and telangiectasia. Experimental production associated with weight loss in rats

A bioassay for the evaluation of certain adverse effects of various corticosteroids was performed. Twenty-eight daily topical applications of corticosteroids to young rats produced reduction in body-weight gain, atrophy of the skin as determined by double skin-fold thickness micrometer measurement, and mild to severe telangiectasia. This animal model demonstrates corticosteroid-induced skin atrophy and telangiectasia and the correlation of the degree of atrophy and telangiectasia to body-weight change. Nine corticosteroids were evaluated by this method and are listed in terms of increasing severity of side-effects as follows: 1.0% hydrocortisone cream, 0.1% betamethasone valerate cream, 0.025% betamethasone benzoate cream, 0.05% flurandrenolide cream, 0.05% fluocinonide cream, 0.1% dexamethasone cream, and 0.03% flumethasone pivalate cream. Triamcinolone acetonide cream, 0.5%, and 0.2% fluocinolone acetonide cream resulted in death of the animals prior to completion of 28 days of topical application.     

Treatment of urethral syndrome with triamcinolone acetonide

A new method for the treatment of the urethral syndrome is presented. Therapy involves the submucosal injection of triamcinolone acetonide around Skene's glands to decrease inflammation and scarring. It is a simple office procedure, while all other therapeutic modalities are surgical.     

Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis

BACKGROUND: Squamous cell carcinoma (SCC) with histologically contiguous actinic keratosis has long been thought of as a tumor with minimal risk for metastasis. The objective of this study was to determine if contiguous actinic keratosis is present in the original tumors of metastatic cutaneous SCC and to describe the histologic features of these tumors. METHODS: The primary lesions of 22 patients with metastatic cutaneous SCC were examined using light microscopy. RESULTS: Contiguous actinic keratosis was present histologically in 44% of the original lesions of cutaneous SCC that metastasized. The average tumor thickness was 6.6 mm. Greater than 66% of the tumors were well or moderately differentiated. The skin adjacent to the tumors showed solar degeneration in almost all instances. CONCLUSIONS: The histologic presence of contiguous actinic keratosis is not a useful predictor of the metastatic behavior of cutaneous SCC. Increased tumor thickness and depth of invasion are the most consistent histopathologic features of cutaneous SCC that metastasize.     

The new fluor-hydroxy pulse peel. A combination of 5-fluorouracil and glycolic acid

BACKGROUND: Chemical peels have become an increasingly popular method to treat a myriad of benign skin disorders. Individually, glycolic acid (GA) and 5-fluorouracil (5-FU) have been proven efficacious in the treatment of actinically damaged skin. However, to our knowledge the literature lacks a study examining the synergistic effects of these two agents in the treatment of actinic keratoses (AKs) and solar damage. OBJECTIVE: The aim of the study was to determine if a combination of 5-FU and 70% GA, when delivered in pulse doses, would have greater efficacy than using GA alone in destroying precancerous AKs and improving the cosmetic appearance of the skin. METHODS: A prospective randomized controlled study was designed with 18 subjects who had clinically apparent facial AKs. Each patient was treated with the combination of 5-FU and GA to one half of the face, while GA alone was applied to the other half, in a randomized fashion. A before-treatment count of the number of AKs present on each half of the face was recorded and pretreatment photographs were taken. The solutions were applied weekly to all patients for an 8-week period. A posttreatment count of AKs on each half of the face along with posttreatment photographs followed at 6 months. RESULTS: The combination of 5-FU and GA cleared 91.94% of AKs at a 6-month follow-up period as compared with 19.67% clearing by GA alone. There were no significant side effects reported with the combination peel. CONCLUSION: The fluor-hydroxy pulse peel applied in a pulse dose regimen not only provides cosmetic improvement, but more importantly, has a therapeutic effect on ablating premalignant AKs. This therapeutic effect occurs without the usual morbidity associated with using 5-FU alone in a nonpulsed dosage. Additionally, it is evident that the superficial peeling induced by alpha hydroxy acids may improve cosmesis of actinically damaged skin, but the GA alone cannot destroy a significant number of AKs.     

Successful treatment with fluconazole of protothecosis developing at the site of an intralesional corticosteroid injection

We report a case of cutaneous protothecosis treated successfully with oral fluconazole. Fluconazole appears to be an effective alternative to conventional drugs for the treatment of cutaneous protothecosis. Cutaneous protothecosis is an uncommon infection due to achlorophyllic, saprophytic, algae-like unicellular organisms of the genus Prototheca that occurs mainly in immunocompromised patients. To date there is no standard treatment regimen. Surgical excision, oral ketoconazole, intravenous amphotericin B alone or in combination with oral tetracycline have been reported to be effective in the management of protothecosis. We report a 55-year-old immunocompetent woman with cutaneous protothecosis which developed at the site of intralesional triamcinolone acetonide injection, who was successfully treated with oral fluconazole.     

Screening for cutaneous carcinoma]

Skin carcinoma is the most frequent of all cancers. The main risk factor is represented by solar exposition and, so, individuals with special risk are xeroderma pigmento sum (enzymatic defect of DNA repair), light phototype person, sun-seekers, outdoor-workers and patients treated with high doses of PUVA. X-rays, mineral oils, tar and arsenic are also known skin carcinogens. HPV can also participate to skin carcinogenis alone or associated with UV particularly in immunosupressed sujets. Subjects with predisposition for skin carcinoma can be pointed out and cautioned. Detection of preepitheliomatous lesions is easy; actinic keratosis are the main signs.     

Adjuvant therapy of colorectal carcinoma--1998 status]

Colorectal cancer is the second leading cause of cancer death in western countries. The prognosis is strongly correlated to the TNM-staging system and patients with stage T3-4 and/or node positive disease are at high risk for locoregional or distant relapse. It is now widely accepted that patients with node positive colon cancer should be offered postoperative adjuvant chemotherapy. Evidence is accumulating that six months' adjuvant fluorouracil plus leucovorin is equivalent to twelve months' fluorouracil and levamisole, which reduces cancer related deaths by more than 30%. Other adjuvant treatment approaches are perioperative regional chemotherapy or monoclonal antibody treatment, and the results of trials comparing these different treatment options alone or in combination are eagerly awaited. In rectal cancer, the risk of locoregional recurrence can be more than 50% and this event is associated with a deterimental effect on quality of life. The technique of mesorectal excision and the use of radiotherapy, alone or in combination with chemotherapy, have evolved as the most important measures for prevention of locoregional recurrence. In addition, chemotherapy has proven to be effective in reducing metastatic relapse and prolonging survival. The timing of radiotherapy (pre- versus postoperative) and the optimal combination of chemotherapy with radiation are presently important research issues in resected rectal cancer. In both colon and rectal cancer, a common theme emerging from the experience of the last few decades is that administration of dose-intensive fluorouracil is key for the success of adjuvant treatment.     

Ovine cutaneous squamous cell carcinoma: immunohistochemical expression of CD3, CD4, CD8 and MHC class II antigens in the associated inflammatory infiltrate

The immunohistochemical expression of CD3, CD4, CD8 and MHC class II antigens in the cellular inflammatory infiltrate associated with early and advanced ovine squamous cell carcinomas (OSCC), as well as actinic keratosis was analyzed. The majority of the peritumoral and intratumoral lymphocytes reacted with the anti-human CD3 polyclonal antibody. The number of CD8+ T lymphocytes increased in advanced OSCC compared with that of actinic keratosis and early OSCC, whereas the number of CD4+ lymphocytes was similar in early and advanced OSCC. Tumor cells were unreactive with the anti-MHC class II antibody, but the majority of the mononuclear cellular infiltrate expressed this antigen in early and advanced tumors.     

Treatment of persistent glaucoma secondary to periocular corticosteroids

PURPOSE: To describe two patients with uveitis who developed increased intraocular pressure that was unresponsive to maximum medical therapy eight and 13 months after periocular injection of triamcinolone acetonide. METHODS: Excised periocular tissue was analyzed for corticosteroid activity by gas chromatography and mass spectrometry. RESULTS: Excision of the periocular tissue, which contained visible triamcinolone acetonide, resulted in a normal intraocular pressure within 14 days in both patients. Analysis of the excised tissue disclosed residual corticosteroid in one of the two patients. CONCLUSION: Removal of periocular tissue containing injected corticosteroids may facilitate the management of patients developing increased intraocular pressure unresponsive to maximum medical therapy.     

Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer

BACKGROUND: Cardiotoxicity related to the widely used cytotoxic compound 5-fluorouracil (5-FU) is rare compared with the frequency observed with the use of anthracyclines. More effective protocols incorporating active biomodulatory compounds like folinic acid (FA) or combination chemotherapy change type and severity of toxicity as well. The objective of the current study was to assess cardiotoxicity of the combination 5-FU and folinic acid. METHODS: The authors' multicenter experience with 390 patients treated for advanced gastrointestinal cancer with intermediate-dose folinic acid and 5-FU was reviewed. RESULTS: The overall risk of cardiotoxicity was 3%, which is not significantly higher than that reported with 5-FU alone. Eight of 53 patients with a history of cardiac disease reported cardiac symptoms (15.1%), compared with 5 of 337 patients (1.5%) with a no history of cardiac disease. Median time to symptoms was 3 days (range, 2-6). Nine patients had symptoms resembling myocardial ischemia, one patient died due to assumed myocardial infarction related closely to fluorouracil treatment, four patients had supraventricular arrhythmia, and one patient had congestive heart failure. A history of cardiac disease was the only risk factor associated with cardiotoxicity. Relapses were frequent on reinstitution of therapy despite cardiac symptoms in the preceding cycle. Therapeutically or prophylactically administered nitrates had no significant effect. CONCLUSION: Physicians should be aware of the cardiotoxic properties of active fluorouracil treatment. The combination of 5-FU and leucovorin does not differ from single-agent therapy in frequency or type of cardiotoxicity. Close monitoring of patients is mandatory, especially for those patients at high risk for cardiac side effects. Treatment should be discontinued if coronary symptoms develop, because neither effective treatment nor prophylaxis exists for such symptoms.     

Skin problems of aging

It is not practical to treat diffuse areas of sun damage with liquid nitrogen. Patients with actinic keratoses require painstaking instruction and numerous visits to guide them through a course of 5-fluorouracil (5-Fu) therapy. While basal cell carcinoma rarely metastasizes, its potential for localized destruction and its tendency to recur after therapy should not be underestimated. In certain locations, the tumor does not have a benign clinical course.     

Management of nasopharyngeal and oropharyngeal stenosis in children

Nasopharyngeal stenosis and oropharyngeal stenosis are rare and challenging problems in the pediatric population. The most common etiology is currently the surgical trauma associated with adenotonsillectomy. Stenosis can vary from a thin band to a complete obstructing cicatrix. Presenting symptoms range from mild hyponasal speech to severe airway obstruction. We present a series of eight children with varying degrees of stenosis and associated symptoms. Choice of treatment varied with the severity of disease. In our series, successful interventions included triamcinolone acetonide injection, lysis of adhesions, rotational and advancement mucosal flaps, and jejunal free flap. Preoperative evaluation and individualized surgical repair are essential for successful treatment.     

Drug-induced acrosyndromes

Photodynamic therapy (PDT) is an experimental, noninvasive treatment of different malignant tumors. The principle is that applied photosensitizing substance selectively accumulate in neoplastic cells. Exposure to visible light then leads to the destruction of the tumor tissue. Following intravenous or oral administration of the photosensitizer (PS) generalised skin photosensitivity is the major side effect. Topical application of the PS under occlusive foil a novel method. Topical PDT (TPDT) is most investigated with 5-Aminolevulinic acid (ALA) as PS. ALA is a precursor of endogenous porphyrins in the biosynthetic pathway for heme. This new modality is increasingly and successfully used to treat precancerous and cancerous epithelial skin tumors, like actinic keratoses, basal-cell carcinoma, squamous-cell carcinoma and Bowen disease. An other approach of ALA-TPDT are nontumoral applications, especially psoriasis. ALA-TPDT is well tolerated by patients and makes excellent cosmetic results. It is an alternative treatment for various superficial skin tumors.     

Time trend of female breast carcinoma in situ by race and histology in Connecticut, USA

BACKGROUND: Surgical procedures used to remove genital warts (cryotherapy, electrodesiccation) are painful. Attempts to reduce the discomfort of surgery by prior lidocaine infiltration anesthesia are compromised by the pain of the infiltration. OBJECTIVE: Our purpose was to determine the efficacy of topically applied lidocaine/prilocaine cream to reduce the pain of lidocaine infiltration and the pain associated with cryotherapy to remove genital warts. METHODS: Men, scheduled for removal of genital warts by cryotherapy, were randomly selected to receive one of three treatments: (1) lidocaine/prilocaine cream application, (2) 1% lidocaine infiltration, and (3) lidocaine/prilocaine cream application followed by infiltration of 1% lidocaine. RESULTS: Application of lidocaine/prilocaine cream for 15 minutes markedly reduced the pain of lidocaine infiltration. The combination of lidocaine/prilocaine cream followed by infiltration of 1% lidocaine gave greater pain relief from the cryotherapy than did either anesthetic alone. CONCLUSION: The application of lidocaine/prilocaine cream as an adjunct to lidocaine infiltration reduced the pain of infiltration and the pain associated with cryotherapy for the removal of genital warts.     

Weight loss in the clinical setting: applications for cardiac rehabilitation

A 57-year-old man developed oligoarthritis of the right sacroiliac joint, knee and elbow in the wake of Clostridium difficile pseudomembranous colitis. He was HLA B27-positive and had a history of Reiter's syndrome. His joint manifestations resolved after a course of nonsteroidal antiinflammatory drug therapy and injection of the right knee with triamcinolone acetonide. Clostridium difficile should be recognized as a rare cause of reactive arthritis.     

Detection of human papillomavirus DNA in nongenital seborrhoeic keratoses

The histological similarities of seborrhoeic keratoses and common warts led to the investigation of the possible occurrence of human papillomavirus DNA (HPV-DNA) in a large number of nongenital seborrhoeic keratoses using the in situ hybridization technique. All specimens derived from normal skin (n = 173) were negative for the applied HPV-DNA probe, whereas the HPV genome was detected in 34 of 173 seborrhoeic keratosis specimens (19.65%). Of 34 HPV-positive specimens, 15 contained types 6/11 and 14 types 31/33/35, and 5 showed no positive reaction to the applied types. These results suggest that a considerable percentage of nongenital seborrhoeic keratoses may be related to an HPV infection.     

Absence of human herpesvirus 8 and Epstein-Barr virus genome sequences in cutaneous epithelial neoplasms arising in immunosuppressed organ-transplant patients

Recent studies have implicated herpesvirus 8 and Epstein-Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre-malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein-Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein-Barr virus likely do not play an etiologic role in cutaneous epithelial oncogenesis in immunocompromised patients.     

Nodular superficial pigmented basal cell epitheliomas

Eradication of multiple nodules, papules, and plaques of pigmented basal cell epitheliomas of the back of one patient was achieved by nine months of daily treatment with 5% fluorouracil cream. Such topical chemotherapy offers the physician an alternative to surgery and radiation in treating patients who have widespread nodular superficial epitheliomas. The need for a prolonged period of treatment and follow-up is emphasized.