Prolonged overall survival following metastasectomy in stage IV melanoma.

BACKGROUND/OBJECTIVES: Current literature supports mixed conclusions regarding the outcomes of metastasectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non-primary site surgery with overall survival (OS) in Stage IV melanoma. METHODS: The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n = 14 034). Patients were separated into 'metastasectomy' (n = 4214, 30.0%) and 'non-metastasectomy' (n = 9820, 70.0%) cohorts. Survival outcomes were analysed using Kaplan-Meier and Cox proportional hazards regressions. RESULTS: On univariate analysis, patients with Stage IV melanoma undergoing metastasectomy (median survival: 15.67 month) had greater overall survival compared with those not receiving non-primary surgery (median survival: 7.13 month; 5-year OS 13.2% vs. 5.6%, P < 0.001). M1a patients that underwent non-primary metastasectomy (median survival: 46.36 month) showed greater survival than those that did not (median survival: 15.31 month; P < 0.001). Metastasectomy was undertaken more frequently for cutaneous (M1a) metastasis compared with non-M1a metastasis (34.6% vs. 28.4%, P < 0.001). Of those receiving metastasectomy, 20.3% also received primary site resection, 33.6% radiation, 26.5% chemotherapy and 31.5% immunotherapy. Controlling for covariates on Cox proportional hazard analysis, all metastasectomy patients demonstrated longer survival [Hazard Ratio = 0.519, P < 0.001; CI 95% (0.495-0.545)] as well as when analysing solely M1a metastasectomy patients [Hazard Ratio = 0.546, P < 0.001; CI 95% (0.456-0.653)], lung (M1b) metastasectomy patients [Hazard Ratio = 0.389, P < 0.001; CI 95% (0.328-0.462)] and visceral (M1c) metastasectomy patients [Hazard Ratio = 0.474, P < 0.001; CI 95% (0.434-0.517)]. CONCLUSION: Metastasectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung and visceral organs.

Langerhans cell: exciting developments in health and disease.

Langerhans cells (LCs) have been the subject of much research since their discovery in 1868. LCs belong to the subset of leucocytes called dendritic cells. They are present in the epidermis and the pilosebaceous apparatus and monitor the cutaneous environment for changes in homeostasis. During embryogenesis, a wave of yolk sac macrophages seed the fetal skin. Then, fetal liver monocytes largely replace the yolk sac macrophages and comprise the majority of adult LCs. In the presence of skin irritation, LCs process antigen and travel to regional lymph nodes to present antigen to reactive T lymphocytes. Changes in LCs' surface markers during the journey occur under the influence of cytokines. The difference in expression of surface markers and the ability to resist radiation have allowed researchers to differentiate LCs from the murine Langerin-positive dermal dendritic cells. Exciting discoveries have been made recently regarding their role in inflammatory skin diseases, cancer and HIV. New research has shown that antibodies blocking CD1a appear to mitigate inflammation in contact hypersensitivity reactions and psoriasis. While it has been established that LCs have the potential to induce effector cells of the adaptive immune system to counter oncogenesis, recent studies have demonstrated that LCs coordinate with natural killer cells to impair development of squamous cell carcinoma caused by chemical carcinogens. However, LCs may also physiologically suppress T cells and permit keratinocyte transformation and tumorigenesis. Although long known to play a primary role in the progression of HIV infection, it is now understood that LCs also possess the ability to restrict the progression of the disease. There is a pressing need to discover more about how these cells affect various aspects of health and disease; new information gathered thus far seems promising and exciting.

Topical antiviral and antifungal medications in pregnancy: a review of safety profiles.

Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy. Docosanol, imiquimod and penciclovir are likely safe, but should be utilized as second-line agents. Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and terbinafine may be utilized after the above agents. Econazole should be avoided during the first trimester and used sparingly during 2nd and 3rd trimester. Ketoconazole and selenium sulphide are likely safe, but should be employed in limited areas for brief periods.

Bullous pemphigoid and its association with neurological diseases: a systematic review and meta-analysis.

Bullous pemphigoid (BP) is a chronic, autoimmune vesiculobullous disease that frequently occurs in the elderly population. Previous epidemiological studies have suggested an association between BP and neurological diseases; some studies, however, showed conflicting results. This study aimed to investigate if patients with BP have significantly higher risks for neurological disorders, compared to controls. A comprehensive search was performed using MEDLINE, EMBASE and Cochrane library databases. Case-control and cohort studies that assessed the relationship between BP and neurological diseases were included. DerSimonian and Laird random-effects models were utilized to calculate the pooled relative risks (RRs). Publication bias was evaluated qualitatively by constructing a funnel plot and quantitatively by conducting Egger's test. Fourteen studies, with 23 369 BP cases and 128 697 controls were included in this meta-analysis. Patients with BP were significantly more likely to have stroke (RR 2.68, 95% CI: 2.07-3.46), Parkinson's disease (PD; RR 3.42, 95% CI: 3.01-3.87), dementia (RR 4.46, 95% CI: 3.23-6.16), epilepsy (RR 2.98, 95% CI: 1.42-6.28), multiple sclerosis (RR 12.40, 95% CI: 6.64-23.17) and any aforementioned neurological disease (RR 4.93, 95% CI: 3.62-6.70), compared to controls. Moderate to high heterogeneity were observed for analyses of most neurological diseases, except for PD and multiple sclerosis. This study provided support for a significant association between BP and neurological diseases. Clinicians should be aware of this association and manage modifiable risk factors for neurological diseases accordingly.

Cutaneous leishmaniasis and rickettsial African tick-bite fever: a combination of exotic traveler's diseases in the same patient.

BACKGROUND: Cutaneous leishmaniasis and rickettsial African tick-bite fever are two zoonoses increasingly diagnosed in industrialized nations due to more international travel to endemic areas. METHODS: A 52-year-old American nurse was evaluated for a 0.5 cm well-demarcated, tender, shallow ulcer on her wrist, nonproductive cough, fever, chills, and night sweats, all of which began three weeks after travel to Botswana and a visit to a game reserve, where she reported being scratched on the ankle by a cheetah. RESULTS: This cutaneous finding was strongly suggestive of leishmaniasis, but the systemic symptoms were perplexing. Although excisional biopsy showed only nonspecific changes, a specimen sent to the United States Centers for Disease Control revealed leishmania promastigotes of L. tropica. Initial Rickettsia typhi titers and many other serologic tests were negative. However, four weeks after admission, R. typhi IgG titer was 1 : 64 and R. rickettsii IgG was 1 : 1024. CONCLUSION: Thus, our patient had two tropical diseases simultaneously.

Erythroderma: review of a potentially life-threatening dermatosis.

Erythroderma, or generalized exfoliative dermatitis, is a disease characterized by erythema and scaling of greater than 90% of the body's surface. The resultant dysmetabolism is potentially life threatening. A detailed history is to identify and treat the underlying cause of this dermatitis. We present two cases of erythroderma in African patients and review this important disease.

Presence and quantification of macrophages in squamous cell carcinoma of the cervix.

Cervical cancer is a major cause of morbidity and mortality in women. The presence of macrophages as well as other inflammatory cells has been noted in many of these tumors. Intratumoral macrophages/monocytes induce anergy to cytokine therapy and cause apoptosis in natural killer(NK) and T cells. The aim of this study was to better evaluate and quantify the presence of macrophages in these tumors. Twenty-four cases of squamous cell carcinoma of the cervix seen at our institution were evaluated. Sections were stained with CD68, a marker for macrophages. Staining was graded microscopically by two reviewers together on a scale of 0-4+, with 4+ representing the greatest number of positive cells. Image analysis was conducted to quantify the percent area stained in a given lesion. For each lesion, 10 fields were evaluated, and a mean percentage area stained was calculated. 4+ staining was observed in five cases, 3+ in zero cases, 2+ in three cases, 1+ in six cases, 1-2+ in one case, and nine cases were negative. Image analysis results correlated well with the light microscopic scoring. Presence of a prominent infiltrate of macrophages did not correlate with tumor grade or with histologic lymph node status, but showed a strong negative correlation with tumor stage. Some squamous cell carcinomas of the cervix show a prominent macrophage component in the tumor-associated inflammatory infiltrate. The presence of this prominent infiltration of macrophages did not correlate with tumor grade or lymph node status, but showed a strong negative correlation with tumor stage. The results suggest that immunotherapy may have a potential role in the treatment of cervical carcinoma. Computerized image analysis appears to be a valid measure to assess macrophage counts in such lesions.

The halting arrival of left-handed Z-DNA.

Forty-nine years ago Watson and Crick proposed a double-stranded (ds-) model for DNA. This double helix has become an icon of molecular biology. Twenty-six years later, Rich accidently discovered Z-DNA, an exotic left-handed nucleic acid. For many years thereafter, this left-handed DNA was thought to be an artifact. DNA is no longer looked upon as a static molecule but rather an extremely dynamic structure in which different conformations are in equilibrium with each other. Many researchers have spent the last two decades characterizing this novel left-handed DNA structure. Now many investigators are beginning to accept the possibility that this novel ds-DNA conformation may play a significant in vivo role within eukaryotic and prokaryotic cells. However, more research needs to be performed before it is absolutely accepted by all in the scientific community.

Erupción peculiar de la mama debidaa la fijación unilateral de un fármaco / Peculiar unilateral fiexed drug eruption of the breast

Antecedentes: La erupción debida a la fijación de un fármaco (EFF) es un trastorno cutáneo frecuente, que se desarrolla a las pocas horas de ingerir el fármaco agresor y recurre en la misma zona si hay una exposición posterior al mismo fármaco. Los antiinflamatorios no esteroideos (AINE) son fármacos que producen agresiones de este tipo habitualmente. Métodos: Una niña de catorce años se presentó en consulta inicialmente habiendo experimentado durante un año recurrencias de una placa rojiza-castaña alrededor de la areola derecha. La lesión se hizo prurítica, surgía durante las menstruaciones y desaparecía durante el resto del ciclo menstrual, con la excepción de una hiperpigmentación residual, que persistía. La paciente consumía naproxeno durante la menstruación para aliviar la dismenorrea. Resultados: Se hizo una biopsia de piel que demostró la presencia de ampollas locales y queratinocitos necróticos dispersos en la epidermis, degeneración hidrópica de la capa de células basales, incontinencia pigmentaria e infiltrado perivascular compuesto de linfocitos y eosinófilos. Estos cambios confirmaron el diagnóstico de erupción por fijación de fármaco. Conclusiones: La erupción debida a fijación de fármacos antiinflamatorios no esteroideos es frecuente. Sin embargo, la EFF debida a naproxeno, uno de estos AINE, se ha descrito muy pocas veces. Describimos un caso poco habitual de EFF, con recurrencia en todas las menstruaciones (AU)

Pyoderma vegetans.

BACKGROUND: Pyoderma vegetans is a rare condition that is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. The etiology of this disorder remains unknown. OBJECTIVES: We describe a 24-year-old woman with rapidly evolving pyoderma vegetans. Our patient had the unique additional findings of a highly elevated serum IgE level and a history of hidradenitis suppurativa. CONCLUSIONS: Pyoderma vegetans is diagnosed on clinical and histological criteria. Differentiation must be made from disorders such as pyoderma gangrenosum, Sweet's syndrome, and deep fungal infections. We illustrate a case of pyoderma vegetans and review the literature on this rare disorder. Clinical and histological criteria for diagnosis are presented, as well as differentiation from some mimicking disorders.

Comparison of apoptosis and terminal differentiation: the mammalian aging process.

Apoptosis is the ordered chain of events that lead to cell destruction. Terminal differentiation (denucleation) is the process in which cells lose their nuclei but remain functional. Our group examined cell death in three tissues using two different fixatives and a postfixation procedure, involving young (5 months) and old (2 years) guinea pigs. The data reveal that B-DNA and Z-DNA content decreases, whereas single-stranded (ss-) DNA increases, in older tissues undergoing apoptosis (skin and cornea) and terminal differentiation (ocular lens). We speculate that some of the factors that contribute to the aging process might also be responsible for the enhanced amount of damaged DNA in older tissues undergoing cell death. (J Histochem 49:929-930, 2001)

Cutaneous ciliated cyst with interspersed apocrine features presenting as a pilonidal cyst in a child.

We present a case of a cutaneous ciliated cyst that presented in a 13-year-old female. The lesion was felt to be a pilonidal cyst, based on its location and clinical appearance. This case is unusual because it is the youngest reported example of this very rare lesion. In addition, the admixture of apocrine and ciliated cells is extremely unusual. The histogenesis of cutaneous ciliated cysts is considered.

Pseudoporphyria: an atypical variant resembling toxic epidermal necrolysis.

BACKGROUND: Pseudoporphyria has been attributed to both medication usage and chronic hemodialysis. Histologically, it is identical to porphyria cutanea tarda. It is most commonly seen as localized bullae on sun-exposed skin, often on the dorsum of the hands and fingers. OBJECTIVES: We describe a 31-year-old man with rapidly evolving bullae which became denuded, clinically suggestive of toxic epidermal necrolysis. Pseudoporphyria was proven histologically. However, our patient's eruption was not localized as small bullae but was widespread, with large bullae evolving into large, cutaneous, denuded erosions. CONCLUSIONS: We describe a previously unreported, generalized variant of pseudoporphyria that resembles toxic epidermal necrolysis. We provide a review of pseudoporphyria and compare our variant to toxic epidermal necrolysis and mimicking disorders.