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This article examines why Asia-Pacific middle powers cooperate with each other on security issues. The article challenges the assumption that middle powers are primarily influenced by great-power s...

Background An association between melanoma and Parkinson disease (PD) has been hinted at in the neurology and oncology literature since the 1970s after the initiation of levodopa (L-DOPA) therapy for PD. Given that L-DOPA is a substrate in melanin synthesis, there existed a concern that this therapy might cause melanoma. Objective The objective was to research possible etiological links to explain the connection between PD and melanoma. Methods A PubMed and Google Scholar literature search was performed using access provided by the University of Minnesota biomedical library. Results Patients with PD have an overall decreased risk of cancer diagnoses. However, breast cancer and melanoma have an uncharacteristically high rate of co-occurrence with PD. Family history of melanoma and lighter hair and skin color confer a higher risk of developing PD, and having a first-degree relative with either disease conveys a significantly increased risk of developing the other. Other possible connections that have been explored include pigmentation genes in neural-derived cells, pesticides, MC1R polymorphisms, and abnormal cellular autophagy. Conclusion Although a link between PD and melanoma exists, the etiology of this link continues to be elusive. Both PD and melanoma are likely multifactorial diseases involving genetic and environmental risk factors.

There are limited published data comparing wide local excision (WLE) with Mohs micrographic surgery (MMS) for the treatment of melanoma.To describe a novel treatment algorithm for the surgical management of head and neck melanoma and compare rates of local recurrence for tumors treated with either MMS using immunohistochemistry or WLE.A 10-year retrospective chart review including all in situ and invasive melanomas of the head and neck treated at one institution from January 2004 to June 2013.Among 388 patients with melanoma, MMS was associated with decreased rates of local recurrence (p = .0012). However, patient and tumor characteristics varied significantly, and WLE subgroup was largely composed of higher stage and risk tumors. Subgroup analysis found that patients with in situ or thin invasive tumors (0.8 mm) treated with MMS had improved local recurrence outcomes (p = .0049), despite more frequent tumor location on high risk anatomic sites (e.g., central face). In addition, MMS was associated with a favorable delay in time to local recurrence among in situ tumors (HR = 31.8; p = .0148).These findings further support the use of MMS for treatment of melanoma of the head and neck and help to validate our proposed clinical decision tree.

Background Mohs micrographic surgery (MMS) is gaining acceptance as a treatment for lentigo maligna (LM) and lentigo maligna melanoma (LMM), especially with the use of melanocyte-staining immunohistochemical (IHC) stains. In 2006, we reported our 4-year experience with Mel-5 immunostaining, with only one recurrence noted in 200 patients after a mean follow-up of 38.4 months.1 Objectives We present an update regarding our 13-year experience with the use of Mel-5. Methods and Materials Patients with primary or recurrent LM or LMM (n = 260) underwent MMS with Mel-5; 174 were followed up to evaluate for recurrence, with a mean follow-up of 34 months. The 200 patients described in the initial case series from 1999 to 2003 were also followed. Results Of the 460 patients treated from January 1999 to December 2011, five recurrences were noted in four patients; one in the initial case series and four in this new, updated series, including one re-recurrence from the initial series. One melanoma-related death occurred in a patient intermittently lost to follow-up. Conclusion MMS with Mel-5 immunostaining continues to yield excellent results in the treatment of LM and LMM.

Skin cancers are the most common malignancies in solid organ transplant recipients (SOTR). A case-observational, retrospective study was performed to determine the efficacy of low-dose capecitabine in the secondary prevention of skin cancers in SOTRs treated at a single institution. SOTRs with recurrent squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC) were given low-dose capecitabine 1 g/m(2) daily, days 1-14 of a 21-d treatment cycle. Skin surveillance was performed by dermatologists every 1-3 months. Cumulative incidence rates of SCC, BCC, and actinic keratosis (AK) before and after treatment were scored and statistically compared for each patient using a non-parametric Wilcoxon signed rank test. Fifteen patients (13 men and two women) with a median age of 57 yr (range 40-73) were treated. Incidence rates as measured by mean number of events per month declined by 0.33 for SCC, 0.04 for BCC, and 2.45 for AK (p < 0.05). The most common grade 3 and 4 toxicities included fatigue (40.0%), hand-foot syndrome (20.0%), and diarrhea (20.0%). The discontinuation rate at one yr was approximately 33.3%. We conclude that oral capecitabine significantly decreases the incidence rates of recurrent SCC, BCC, and AK in SOTRs and is associated with manageable toxicity.

Introduction Hyaluronan (HA) and its biosynthetic enzymes hyaluronan synthases (HAS2 and HAS3) mediate Matrigel invasion by SW620 colon carcinoma cells. Because matrix metalloproteinases (MMPs) have been implicated in cancer invasion, we hypothesized that changes in HAS expression would alter MMP expression and activity in these cells. Methods To determine whether an MMP was involved in invasion, Matrigel invasion assays with SW620 cells were performed in the presence or absence of the MMP inhibitors GM6001 or TIMP2. HAS isozymes were inhibited by stably transfecting SW620 cells with vectors that contained antisense HAS2 and/or -3 cDNA; transfection with an empty vector served as a control. MMP-7 transcription was assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-7 protein was detected by enzyme-linked immunosorbent assay (ELISA) and enzymatic activity compared using zymography. Results GM6001 and TIMP2 decreased Matrigel invasion, which confirms that an MMP played a key role in this process. MMP-7 expression was then detected in SW620 cells. Finally, MMP-7 expression, protein, and enzymatic activity were significantly lower in antisense HAS tranfectants than in SW620 or vector control cells. Conclusion We have demonstrated previously that inhibition of HAS expression and HA production in SW620 colon carcinoma cells inhibits Matrigel invasion. In the studies presented here, we have demonstrated that SW620 cells express high levels of MMP-7 and that inhibition of HAS isozymes dramatically decreases MMP-7 expression, protein, and enzymatic activity. Taken together, these findings suggest that HAS and HA may mediate cellular invasion via changes in MMP-7 expression.

Background: Plaque-type syringoma is a rare variant of syringoma. This benign neoplasm may be easily misdiagnosed as microcystic adnexal carcinoma (MAC), potentially resulting in unnecessary surgery with disfiguring consequences. Methods: We report two cases of plaque-type syringoma that were initially diagnosed as MAC. Microscopically, these lesions were composed of nests of cuboidal cells arrayed within sclerotic collagen in the upper dermis. The deep reticular dermis was spared. No perineural involvement was observed. Results and Conclusions: Our cases are discussed in the context of histopathologic diagnosis. Detailed histopathologic findings of syringoma, as well as other considerations in the differential diagnosis, are reviewed. We also include a review of all cases of plaque-type syringoma published to date.

In black-spot poison ivy dermatitis, a black lacquerlike substance forms on the skin when poison ivy resin is exposed to air. Although the Toxicodendron group of plants is estimated to be the most common cause of allergic contact dermatitis in the United States, black-spot poison ivy dermatitis is relatively rare.

Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL12 is a chemokine that promotes lymphocyte invasion and migration into tissues; however, the mechanism for this process remains incompletely understood. In this study, we show that CXCL12 significantly enhanced CD16(+)CD56(+) human peripheral NK-cell invasion into type I collagen by the catalytic activity of matrix metalloproteinase-1 (MMP-1). Confocal immunofluorescence and co-immunoprecipitation studies suggest that MMP-1 colocalized with alpha(2)beta(1) integrin on CXCL-12-stimulated NK-cell surface. The binding of pro-MMP-1 with alpha(2)beta(1) integrin required activation of G(i)-coupled pathway. However, the production of MMP-1 from CXCL12-stimulated NK cells was mediated by p38 and mitogen-activated or extracellular signal-regulation protein kinase kinase 1/2 in a manner independent of the G(i)-coupled pathway. These results suggest that CXCL12/CXCR4 interaction transduces the two signaling pathways to promote NK-cell invasion, which stimulates pericellular degradation of extracellular matrix proteins by membrane-associated MMP-1. The mechanisms would thus play a role in facilitating lymphocyte trafficking and accumulation in tissues during physiological and pathological processes.

BACKGROUND Mohs micrographic surgery (MMS) continues to become a more common and accepted treatment for lentigo maligna (LM) and lentigo maligna melanoma (LMM). The primary difficulty encountered lies in the accurate identification of atypical single melanocytes to determine tumor-free margins. Numerous methods have been used to better visualize single melanocytes, with varying results. We present our experience using Mel-5 immunostaining in MMS of LM and LMM. METHODS Two hundred patients with primary or recurrent LM or LMM were treated using MMS from 1999 to 2003 at the University of Minnesota. The initial clinical margins were determined by Wood's light examination, and an initial debulk specimen was taken and sent for formalin fixation and later reviewed by a dermatopathologist. The first Mohs layer was then taken, and staining with hemotoxylin and eosin as well as Mel-5 immunostaining was performed. All patients were followed up to evaluate for recurrence, with a mean follow-up time of 38.4 months. RESULTS Of the 200 patients treated, only one recurrence was noted. This patient had been treated with excision followed by radiation before MMS. Use of Mel-5 immunostaining added approximately 40 minutes to each stage. Use of the Autostainer Immunostaining System (DAKO, Carpenterina, CA, USA) shortened the added time to 20 minutes. CONCLUSIONS MMS with Mel-5 immunostaining yielded excellent results in the treatment of LM and LMM, with only one recurrence noted in 200 patients. When an automated immunostainer was used, minimal time was added to each Mohs stage.

BACKGROUND Dermatofibroma (DF) is one of the most basic and common dermatologic diseases treated by practicing dermatologists on a daily basis. Although benign, it can be pruritic or tender. Furthermore, it is difficult to treat effectively with optimal cosmetic outcomes. OBJECTIVE We report a safe, effective, and cosmetically superior method of treating DF with the 600 nm pulsed dye laser (PDL). METHODS We used a 600 nm PDL to treat 20 lesions from 18 Caucasian patients. The laser parameter was set at a fluence of 7 J/cm2, a spot size of 7 mm and a pulse duration of 1.5 ms. Each lesion was treated three times at a 6- to 8-week interval. For each treatment, the lesion was double pulsed with a 20 to 30% overlap. Clinical improvement was graded by a single examiner in evaluating three clinical parameters: color, size/volume, and symptoms. For each parameter, improvement was ranked as no improvement, partial improvement, and complete response. RESULTS All 18 patients (17 women) completed the study. For the volume/size parameter, 15 of 20 lesions (75%) showed complete response. For improvement in color, 12 of 20 patients (60%) showed complete response. Only six lesions were symptomatic (i.e., tender and irritating), and all six lesions showed complete resolution of symptoms after the PDL treatments. After each treatment, all patients experienced blistering, crusting, and purpura that usually resolved after 10 days. CONCLUSIONS We have demonstrated for the first time that PDL (600 nm and 1.5 ms pulse duration) is an effective and safe treatment of DF. It may provide superior cosmetic outcomes compared with other modalities such as surgical excision.

Importance Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population–based incidence in the United States. Objective To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

There is some debate regarding the rate of progression of actinic keratosis (AK) into squamous cell carcinoma (SCC).1-4 However, it is clear that treatment for AK lesions is warranted. Results from numerous studies with aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) for the treatment of AKs, SCC, and Bowen's disease show high rates of clearance for these lesions. MAL/PDT provides similar efficacy to ALA/PDT with the benefits of shorter incubation times according to the approved FDA labeling, greater selectivity, reduced pain during and immediately following therapy, and fewer systemic side effects. Cosmetic outcomes are better with PDT than with cryosurgery or excisional surgery. A number of case reports show efficacy with ALA/PDT and MAL/PDT for acne, photorejuvenation, and other off-label indications. Side effects with PDT tend to be mild to moderate and transient in nature. Overall, ALA/PDT and MAL/PDT are effective for a variety of skin diseases and conditions. MAL/PDT provides some advantages over ALA/PDT.

Solidorgan transplant recipients (SOTRs) are at greater risk of nonmelanoma skin cancer (NMSC) than the general population, in large part because of their immunosuppression. Select individual SOTRs demonstrate a rate of tumor development at the upper end of their cohort. Capecitabine, a prodrug converted in the body to 5-fluorouracil (5-FU), may alter the risk for development of NMSC in an individual SOTR with a high rate of tumor development.To report observations of a series of 10 SOTRs treated with capecitabine as adjuvant prevention for high-incidence NMSC.Ten SOTRs were administered cycles of low-dose oral capecitabine (0.5-1.5 g/m(2) per day) for days 1 to 14 of a 21-day treatment cycle. Measurements (skin screenings, laboratory and toxicity monitoring) were performed every 1 to 3 months. Incidence rates of squamous cell carcinoma (SCC) before and during treatment were determined and compared using the Wilcoxon signed-rank test.The average incidence rate (mean ± SD) of SCC before treatment (0.56 ± 0.28 SCCs/month, range 0.17-1.17 SCCs/month) declined to 0.16 ± 0.11 SCCs/month (range 0-0.33 SCCs/month) during the first 12 months of treatment (mean reduction 68 ± 30.0%, range 0-100%, p .005). Reduction in actinic keratosis was observed. Common side effects included fatigue, nausea, hand-and-foot syndrome, gout, and poor renal function. Seven of 10 participants required dose adjustment, and two of these were discontinued from the study drug because of side effects.Case series design, small observational population.SOTRs experienced a clinically and statistically significant decline in incident SCCs during treatment with low-dose oral capecitabine, with varying degrees of side effects. Larger randomized trials will determine the dose and efficacy of capecitabine for adjuvant treatment of NMSC in SOTRs.

Non-melanoma skin cancer (NMSC) is traditionally treated with surgical excision. Non-surgical methods such as cryotherapy and topical chemotherapeutics, amongst other treatments, are other options. Actinic keratosis (AKs) are considered precancerous lesions that eventually may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) offers an effective treatment for AKs, and is also effective for superficial basal cell carcinoma (BCC). Nodular BCC and Bowen’s disease (SCC in situ) have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes. Methylaminolevulinate (MAL) PDT is a more effective treatment option than 5-aminolevulinic acid (ALA) PDT for nodular BCC. Several studies have shown that PDT results in superior cosmetic outcomes compared to surgical treatment. PDT is overall well-tolerated, with pain being the most common side effect.

Background: There is an increased risk of new basal cell carcinomas (BCCs) developing in a person who has had a BCC. Objective: This study attempts to define the magnitude of this increased risk. Methods: The charts of 260 white patients with a histologically proven BCC were reviewed for the occurrence of new BCCs. The cumulative 5-year incidence (modified life-table method) for new BCCs developing in these patients was compared with the 5-year incidence in the general white population of the United States. Results: Of the 260 patients, new BCCs developed in 137 within an average of 38.3 months, a 5-year cumulative rate of one or more new BCCs of 45.2%. The yearly risk for new BCCs developing in the study population remained high during the 5-year interval. In the general white population of the United States, the maximal 5-year incidence was calculated to be 5% (p Conclusion: Patients with a history of BCC require life-long follow-up because of the high probability of new BCCs developing.

Skin cancers are the most common malignancies in solid organ transplant recipients (SOTR). A case-observational, retrospective study was performed to determine the efficacy of low-dose capecitabine in the secondary prevention of skin cancers in SOTRs treated at a single institution. SOTRs with recurrent squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC) were given low-dose capecitabine 1 g/m(2) daily, days 1-14 of a 21-d treatment cycle. Skin surveillance was performed by dermatologists every 1-3 months. Cumulative incidence rates of SCC, BCC, and actinic keratosis (AK) before and after treatment were scored and statistically compared for each patient using a non-parametric Wilcoxon signed rank test. Fifteen patients (13 men and two women) with a median age of 57 yr (range 40-73) were treated. Incidence rates as measured by mean number of events per month declined by 0.33 for SCC, 0.04 for BCC, and 2.45 for AK (p0.05). The most common grade 3 and 4 toxicities included fatigue (40.0%), hand-foot syndrome (20.0%), and diarrhea (20.0%). The discontinuation rate at one yr was approximately 33.3%. We conclude that oral capecitabine significantly decreases the incidence rates of recurrent SCC, BCC, and AK in SOTRs and is associated with manageable toxicity.

Toxic shock syndrome toxin (TSST) 1 was purified from ovine (TSST-ovine) and bovine (TSST-bovine) mastitis-associated Staphylococcus aureus. These toxins were previously reported to have molecular weights identical to that of human TSST-1. However, TSST-ovine was reported as having an isoelectric point (pI) of 8.5, whereas TSST-bovine has the same pI (7.2) as TSST-1. Nucleotide sequence analysis revealed that TSST-bovine was identical to TSST-1 and that TSST-ovine had 14 nucleotide differences that changed 9 amino acid residues. Only 1 nucleotide difference, at position 514, was predicted to cause an amino acid charge difference, as glutamic acid at position 132 of TSST-1 was changed to lysine in TSST-ovine. Like TSST-1, TSST-ovine was mitogenic, but unlike TSST-1, it was not pyrogenic, was unable to enhance endotoxic shock, and was unable to induce TSS in a rabbit model. Also, TSST-ovine was less reactive to certain monoclonal antibodies raised against TSST-1.

Squamous cell carcinomas (SCCs) produce significant morbidity in solid organ transplant recipients (SOTRs), particularly in patients who develop multiple tumors. Topical photodynamic therapy (PDT) has been shown to decrease the number of keratotic lesions in SOTRs, but the duration of the beneficial effect is limited. The aim of this study was to evaluate the potential benefit of cyclic PDT in the prevention of new SCCs in SOTRs.Twelve high-risk SOTRs received cyclic PDT treatments at 4- to 8-week intervals for 2 years. The development of new SCCs (invasive and in situ) performed 12 and 24 months after the start of cyclic PDT were compared with the number of SCCs developed during the year before initiation of cyclic PDT.The median reduction in the 12- and 24-month post-treatment counts from the 1-month pretreatment counts was 79.0% (73.3-81.8%) and 95.0% (87.5-100.0%), respectively. Treatments were well tolerated.Cyclic PDT with 5-aminolevulinic acid may reduce the incidence of SCC in SOTRs. Additional studies with larger numbers of patients and optimized protocols are necessary to further explore the potential benefits of cyclic PDT in the prevention of skin cancer in this high-risk patient population.

Accurate diagnosis and management of pigmented lesions is critical because of the morbidity and mortality associated with melanoma.We sought to compare accuracy of store-and-forward teledermatology for pigmented neoplasms with standard, in-person clinic dermatology.We conducted a repeated measures equivalence trial involving veterans with pigmented skin neoplasms. Each lesion was evaluated by a clinic dermatologist and a teledermatologist; both generated a primary diagnosis, up to two differential diagnoses, and a management plan. The primary outcome was aggregated diagnostic accuracy (match of any chosen diagnosis with histopathology). We also compared the severity of inappropriately managed lesions and, for teledermatology, evaluated the incremental change in accuracy when polarized light dermatoscopy or contact immersion dermatoscopy images were viewed.We enrolled 542 patients with pigmented lesions, most were male (96%) and Caucasian (97%). The aggregated diagnostic accuracy rates for teledermatology (macro images, polarized light dermatoscopy, and contact immersion dermatoscopy) were not equivalent (95% confidence interval for difference within +/-10%) and were inferior (95% confidence interval lower bound10%) to clinic dermatology. In general, the addition of dermatoscopic images did not significantly change teledermatology diagnostic accuracy rates. In contrast to diagnostic accuracy, rates of appropriate management plans for teledermatology were superior and/or equivalent to clinic dermatology (all image types: all lesions, and benign lesions). However, for the subgroup of malignant lesions (n = 124), the rate of appropriate management was significantly worse for teledermatology than for clinic dermatology (all image types). Up to 7 of 36 index melanomas would have been mismanaged via teledermatology.Nondiverse study population and relatively small number of melanomas were limitations.In general, the diagnostic accuracy of teledermatology was inferior whereas management was equivalent to clinic dermatology. However, for the important subgroup of malignant pigmented lesions, both diagnostic and management accuracy of teledermatology was generally inferior to clinic dermatology and up to 7 of 36 index melanomas would have been mismanaged via teledermatology. Teledermatology and teledermatoscopy should be used with caution for patients with suspected malignant pigmented lesions.

Studies of teledermatology utilizing the standard reference of histopathology are lacking.To compare accuracy of store-and-forward teledermatology for non-pigmented neoplasms with in-person dermatology.This study was a repeated-measures equivalence trial involving veterans with non-pigmented skin neoplasms. Each lesion was evaluated by an in-person dermatologist and a teledermatologist; both generated a primary diagnosis, up to two differential diagnoses, and management plan. The primary outcome was aggregated diagnostic accuracy (percent correct matches of any chosen diagnosis with histopathology). Secondary outcomes included management plan accuracy (percent correct matches with expert panel management plan). Additional analyses included evaluation of the incremental effect of using polarized light dermatoscopy in addition to standard macro images, and evaluating benign and malignant lesion subgroups separately.Most of the 728 participants were male (97.8%) and Caucasian (98.9%). The aggregated diagnostic accuracy (primary outcome) of teledermatology (macro images) was not equivalent (95% confidence interval [CI] for difference within +/-10%) and was inferior (95% CI lower bound10%) to in-person dermatology for all lesions and the subgroups of benign and malignant lesions. However, management plan accuracy was equivalent. Teledermatology aggregated diagnostic accuracy using polarized light dermatoscopy was significantly better than for macro images alone (P = .0017). The addition of polarized light dermatoscopy showed the same pattern for malignant lesions, but not for benign lesions. Most interestingly, for malignant lesions, the addition of polarized light dermatoscopy yielded equivalent aggregated diagnostic accuracy rates.Non-diverse study population.Using macro images, the diagnostic accuracy of teledermatology was inferior to in-person dermatology, but accuracy of management plans was equivalent. The addition of polarized light dermatoscopy yielded significantly better aggregated diagnostic accuracy, but management plan accuracy was not significantly improved. For the important subgroup of malignant lesions, the addition of polarized light dermatoscopy yielded equivalent diagnostic accuracy between teledermatologists and clinic dermatologists.

In black-spot poison ivy dermatitis, a black lacquerlike substance forms on the skin when poison ivy resin is exposed to air. Although the Toxicodendron group of plants is estimated to be the most common cause of allergic contact dermatitis in the United States, black-spot poison ivy dermatitis is relatively rare.

Hyaluronan mediates growth of SW620 colon cancer cells. Because hyaluronan is the active ingredient in Seprafilm, we hypothesized that Seprafilm would affect intraperitoneal tumor growth in a mouse model of peritoneal seeding.Immunodeficient mice underwent laparotomy and intraperitoneal inoculation of 10(5) SW620 cells. Seprafilm (n = 22), Vicryl mesh (foreign body control; n = 24), or no material (sham; n = 19) was placed under the incision. Mice were killed after four weeks and tumors were dissected, counted, and weighed.Ninety-five percent of mice in the sham group and 96 percent in the Vicryl group developed intraperitoneal tumors. In contrast, only 64 percent of mice in the Seprafilm group developed tumors (P = 0.024), and these tumors were smaller than those in the sham group; (Seprafilm = 42 +/- 9 mg vs. sham = 82 +/- 17 mg; P = 0.05). In contrast, tumors in the Vicryl group were dramatically larger (349 +/- 49 mg; P0.001 vs. sham or Seprafilm).Despite previous data that suggested that hyaluronan increases colon cancer cell growth, we found that Seprafilm decreased tumor formation and tended to decrease size in this model. In contrast, Vicryl mesh increased tumor formation and size. Our results suggest that Seprafilm does not promote intraperitoneal tumor growth, especially compared with Vicryl mesh.

BACKGROUND. Parathyroid cancer is a rare cause of hyperparathyroidism. The objectives of this study were to determine the patterns of disease, treatment trends, and outcomes among patients with parathyroid cancer by using a population-based data source. METHODS. Surveillance, Epidemiology, and End Results (SEER) cancer registry data were used to identify patients who were diagnosed with parathyroid cancer from 1988 through 2003. To assess whether the incidence rate, treatment, tumor size, and cancer stage changed over time, the Cochrane-Armitage trend test was used, and Cox proportional-hazards modeling was used to identify the factors associated with an improved overall survival rate. RESULTS. From 1988 through 2003, 224 patients with parathyroid cancer were reported in the SEER data. Over that 16-year study period, the incidence of parathyroid cancer increased by 60% (1988–1991, 3.58 per 10,000,000 population; 2000–2003, 5.73 per 10,000,000 population). Most patients (96%) underwent surgery (parathyroidectomy, 78.6% of patients; en bloc resection, 12.5% of patients; other, 4.9% of patients). The rate of surgical treatment increased significantly during the study period. The 10-year all-cause mortality rate was 33.2%, and the 10-year cancer-related mortality rate was 12.4%. Patient age (P < .0001), sex (P ¼ .0106), the presence of distant metastases at diagnosis (P ¼ .0004), and the year of diagnosis (P ¼ .0287) were associated significantly with the overall survival rate. Tumor size, lymph node status, and type of surgery were not associated significantly with the overall survival rate. CONCLUSIONS. Although parathyroid cancer is rare, the incidence increased significantly in the United States from 1988 through 2003. Young age, female gender, recent year of diagnosis, and absence of distant metastases were associated significantly with an improved survival rate. Cancer 2007;109:1736–41. � 2007 American Cancer Society.

We previously reported that CS (chondroitin sulfate) GAG (glycosaminoglycan), expressed on MCSP (melanoma-specific CS proteoglycan), is important for regulating MT3-MMP [membrane-type 3 MMP (matrix metalloproteinase)]-mediated human melanoma invasion and gelatinolytic activity in vitro. In the present study, we sought to determine if CS can directly enhance MT3-MMP-mediated activation of pro-MMP-2. Co-immunoprecipitation studies suggest that MCSP forms a complex with MT3-MMP and MMP-2 on melanoma cell surface. When melanoma cells were treated with βDX (p-nitro-β-D-xylopyranoside) to inhibit coupling of CS on the core protein, both active form and proform of MMP-2 were no longer co-immunoprecipitated with either MCSP or MT3-MMP, suggesting a model in which CS directly binds to MMP-2 and presents the gelatinase to MT3-MMP to be activated. By using recombinant proteins, we determined that MT3-MMP directly activates pro-MMP-2 and that this activation requires the interaction of the C-terminal domain of pro-MMP-2 with MT3-MMP. Activation of pro-MMP-2 by suboptimal concentrations of MT3-MMP is also significantly enhanced in the presence of excess C4S (chondroitin 4-sulfate), whereas C6S (chondroitin 6-sulfate) or low-molecular-mass hyaluronan was ineffective. Affinity chromatography studies using CS isolated from aggrecan indicate that the catalytic domain of MT3-MMP and the C-terminal domain of MMP-2 directly bind to the GAG. Thus the direct binding of pro-MMP-2 with CS through the C-domain would present the catalytic domain of pro-MMP-2 to MT3-MMP, which facilitates the generation of the active form of MMP-2. These results suggest that C4S, which is expressed on tumour cell surface, can function to bind to pro-MMP-2 and facilitate its activation by MT3-MMP-expressing tumour cells to enhance invasion and metastasis.

The results from four phase III, randomized, vehicle-controlled studies showed that imiquimod 5% cream (imiquimod) was safe and effective in the treatment of actinic keratosis (AK). Patients applied imiquimod or vehicle cream to AK lesions on the face or balding scalp, dosing three times per week or two times per week for 16 weeks.To obtain long-term safety follow-up data and estimate AK recurrence in patients who completely cleared their AK lesions in the treatment area at the 8-week post-treatment visit in the phase III studies.One hundred forty-six patients from 30 study centers in the United States were evaluated for clinical evidence of AK, and safety data were collected.After a median follow-up period of 16 months, 24.7% (19 of 77) of the patients administered imiquimod three times per week and 42.6% (23 of 54) of the patients administered imiquimod two times per week had a recurrence of AK (the appearance of at least one AK lesion) in the original treatment area. The median number of AK lesions present was one lesion for both patients receiving imiquimod three times and those receiving imiquimod two times per week compared with a median of six lesions at baseline in the combined three times per week and two times per week phase III studies. There were no long-term safety issues, and the skin quality seen in the imiquimod-treated patients at the end of the phase III studies was maintained.One and a half years following treatment, imiquimod continued to provide a long-term clinical benefit in a majority of patients who experienced complete clearance of their AK lesions.

Background The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. Objective Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. Methods A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. Results The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (≥75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. Conclusion Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

Skin cancers are the most common types of all cancers, and the most commonly occurring skin cancers are basal cell carcinoma, squamous cell carcinoma, and malignant melanoma, in that order. This article discusses the clinical presentations and subtypes of these 3 types of cancer and the current state of treatments for them. Also discussed are precursor lesions to these malignancies, including actinic keratosis, a squamous cell carcinoma precursor, and atypical or dysplastic nevus, a potential precursor of malignant melanoma.

Background Efficient treatment of patients with multiple synchronous nonmelanomaskin cancers represents a therapeutic challenge. Objective To study the safety and efficacy of photodynamic therapy (PDT) withverteporfin and red light in the treatment of multiple nonmelanoma skin cancers. Design Open-label, randomized, multicenter, dose-ranging phase 2 study conductedat 4 North American university-based dermatology clinics. Patients Fifty-four patients with 421 multiple nonmelanoma skin cancers includingsuperficial and nodular basal cell carcinoma and squamous cell carcinoma insitu (Bowen disease). Methods A single intravenous infusion of 14 mg/m 2 of verteporfinfollowed 1 to 3 hours later by exposure of tumors to 60, 120, or 180 J/cm 2 of red light (688 ± 10 nm) from a light-emitting diode panel. Main Outcome Measures Pathologic response of treated sites was assessed at 6 months. Clinicaland cosmetic responses were assessed and graded at 6 weeks, 3 months, and6 months after verteporfin PDT, with optional follow-up visits at 12, 18,and 24 months. Results The histopathologic response, defined as absence of tumor on biopsyspecimens 6 months after verteporfin PDT, ranged from 69% at 60 J/cm 2 to 93% at 180 J/cm 2 . At 24 months of follow-up (276 tumorsin 31 patients), the clinical complete response rate ranged from 51% at 60J/cm 2 to 95% at 180 J/cm 2 . No significant systemic adverseevents were observed; most events occurred at the treated tumor sites andincluded events such as pain. Overall, 65% (95% confidence interval, 58%-71%)of tumors were judged to have good to excellent cosmesis at 24 months. Conclusion A single course of verteporfin PDT showed treatment benefit for patientswith multiple nonmelanoma skin cancers.

Background: A novel electrosurgical technology that uses a bipolar electrode-tipped stylet to deliver relatively low-radiofrequency energy through an electrically conductive medium has been developed. Objective: To evaluate the efficacy and safety of the radiofrequency resurfacing system for the treatment of facial wrinkles. Design: Multicenter, prospective, noncomparative study with longitudinal follow-up. Setting: Four US academic dermatologic surgery clinics. Patients: Ninety-five patients with mild to severe photodamage (Fitzpatrick classes I-III) involving periorbital (75 treatment sites) and perioral (50 sites) facial skin. Intervention: Radiofrequency resurfacing with the use of 2 to 3 passes at 125 or 139 V. Main Outcome Measures: Wrinkle and cosmetic improvements evaluated by patients, investigators, and, by means of photographs, an independent panel of 5 evaluators. Results: All evaluators determined a positive mean improvement in wrinkles for both periorbital and perioral anatomic sites, with greater improvement for patients with more severe wrinkles at baseline. An increased number of passes and higher voltage settings had a positive impact on wrinkle improvement. Transient postinflammatory hyperpigmentation occurred in 26% of periorbital and 4% of perioral sites. Hypertrophic scars occurred in 3.8% of treatment sites, with all but 1 scar resolving by 6 months. For the most part, healing was rapid, pain was minimal, and erythema largely resolved within 2 months. Other untoward effects were relatively few and shortlived. Conclusions: At the study settings used, radiofrequency resurfacing is an effective modality in the treatment of periorbital and perioral wrinkles in patients with Fitzpatrick class I, II, and III photodamage. There is less severe postoperative morbidity than seen with carbon dioxide or coagulating erbium:YAG lasers. The potential risks are similar to those seen with other resurfacing modalities.

Cutaneous lasers, including argon, Q-switched Nd:YAG, Q-switched ruby, Q-switched alexandrite, and short pulsed dye lasers, have been used to treat solar lentigines and other benign melanocytic lesions. However, the effects of these lasers at standard fluences on atypical melanocytic lesions have not been examined. We describe two patients in whom the Q-switched ruby laser failed to successfully treat clinically atypical-appearing solar lentigines. In both, clinically atypical-appearing melanocytic lesions were treated with excellent initial cosmetic results. In the first patient, the pigmentation returned several months after treatment and continued to increase in size and color. A biopsy specimen 30 months after Q-switched ruby laser therapy revealed a lentigo maligna melanoma. In the second patient, the lesion recurred 6 months after Q-switched ruby laser therapy, and a biopsy specimen 1 year after treatment showed an early lentigo maligna. Thus Q-switched ruby lasers and other cutaneous lasers capable of targeting melanin may be inadequate to eliminate lentigo maligna and other atypical melanocytic lesions completely. These cases emphasize the importance of careful clinical assessment before any laser surgery and the need to advise patients to return for evaluation should pigmentation return.

In staphylococcal toxic shock syndrome, hypotension and shock due to capillary leak may rapidly lead to death of the host. To investigate its pathogenesis, the cytotoxic effects of toxic shock syndrome toxin 1 (TSST-1) on porcine aortic endothelial cells (PAEC) were examined in vitro. TSST-1 killed PAEC (as measured by 51Cr release) in a dose- and time-dependent fashion and was blocked by anti-TSST-1 antibodies. Receptor-mediated endocytosis may be critical for the cytotoxic effects of TSST-1, as killing was inhibited by cold (4 degrees C) and by addition of chloroquine and methylamine. Furthermore, calcium and oxygen appeared necessary for TSST-1 effects on PAEC. Membrane receptor binding studies indicated PAEC bind TSST-1 with high affinity (Kd = 5.7 x 10(-7) M) and had 2.2 x 10(4) receptors/cell. Last, as measured by 125I-labeled albumin flux in a transendothelial permeability model, TSST-1 enhanced the permeability of PAEC monolayers in a dose- and time-dependent manner.

Toxic shock syndrome toxin 1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPE A) belong to a family of pyrogenic toxins produced by Staphylococcus aureus and Streptococcus pyogenes, respectively. Both toxins are responsible for causing toxic shock syndrome (TSS) and related illnesses, clinically characterized by multiorgan involvement. The most severe TSS symptom is acute hypotension and shock after the initial febrile response. In this study, we examined possible mechanisms of shock development in TSS, particularly the role of T-cell proliferation, endotoxin enhancement by toxins, and capillary leakage. American Dutch belted rabbits, with subcutaneously implanted miniosmotic pumps filled with either TSST-1 or SPE A, served as the animal model. For both TSST-1 and SPE A-treated rabbits, administration of cyclosporin A prevented toxin-induced T-cell proliferation but failed to protect the rabbits. Polymyxin B treatment of rabbits, to neutralize endogenous endotoxin, partially protected rabbits from challenge with either exotoxin; two of six rabbits survived on day 2 when treated with only TSST-1, whereas six of six animals survived after challenge with TSST-1 and polymyxin B. Similarly, with SPE A-treated rabbits, only 1 of 10 animals without polymyxin B treatment survived on day 8, but 4 of 6 rabbits survived on day 8 when given polymyxin B. Fluid replacement was successful in preventing lethality. Twelve of 14 rabbits survived when given TSST-1 with fluid, and all rabbits treated with SPE A and fluid survived. Finally, by using miniosmotic pumps, staphylococcal exfoliative toxin A and concanavalin A were administered to rabbits in an attempt to induce lethality. These two T-cell mitogens caused T-cell proliferation but failed to induce lethality in rabbits. The data suggest that toxin interactions causing vascular leakage and to some extent endotoxin enhancement are of major importance in development of hypotension and shock in TSS. It appears that T-cell proliferation may not contribute significantly to the induction of shock and death.

Streptococcal pyrogenic exotoxins (SPEs) A, B, and C, like other members of the pyrogenic toxin family, are able to cause toxic shock-like syndromes. One of the major properties of these toxins is the ability to induce T-cell proliferation. Characterization of T cell mitogenicity associated with SPEs A, B, and C was undertaken. SPEs A, B, and C were mitogenic for C57BL10/SnJ and BALB/cWAT T cells, with activities differing in intensity depending on the mouse strain and toxin employed. SPE-induced, T-cell-proliferative activity was dependent on class II major histocompatibility complex molecules expressed on antigen-presenting cells. The abilities of SPEs A, B, and C to preferentially stimulate murine cells with certain T-cell receptor V beta s were investigated by fluorescence-activated cell sorter analysis. SPE A preferentially activated T cells expressing V beta 8 but not V beta 3, 6, or 11, while SPEs B and C preferentially stimulated T cells which did not express any of the tested V beta s.

Many bacteria require a complex set of host-parasite interactions in order to cause disease. Perhaps the most straightforward of these interactions is elaboration by the microbe of toxins which induce disease manifestations. In this example the pathogen must only be able to survive and multiply within the host for a sufficient period of time to make the toxin. Toxin-host cell receptor interactions then determine the extent of host tissue damage.

The inflammatory stage of acne vulgaris is mediated by neutrophils. Histologic study shows that masses of neutrophils congregate within the intact or ruptured comedo. 1 Chemoattractants, cytokines, and complement activation are important in neutrophilic migration. In addition, colony-stimulating factors (CSFs) may serve as important cytokines in neutrophil-mediated processes by promoting the proliferation, maturation, and function of neutrophils. 2 We report the exacerbation of acne after administration of recombinant human granulocyte colony-stimulating factor (G-CSF). This is the first report of GCSF causing exacerbation of acne.

Introduction and objectives: Photodynamic therapy (PDT) with verteporfin may be particularly well suited for patients with multiple low risk non-melanoma skin cancers (NMSC) while providing good cosmetic outcomes as compared to standard treatments. The objectives of this study were to prospectively assess the tumor responses and cosmetic outcomes of verteporfin-treated NMSC. Patients and methods: This was a phase 11, open-label, light-dose ranging, multicenter study of 54 patients with multiple NMSC. A total of 421 biopsy-proven tumors that were either basal cell carcinomas or in situ squamous cell carcinomas underwent PDT with intravenous verteporfin 14 mg/m2 followed by exposure to red light from LED diode arrays (658-718 nm FWHM) at fluences of 60, 120, or 180 J/cm2. Each patient was randomly assigned to receive one of the three light doses to all their tumors. Treated tumors underwent follow up biopsies at 6 months after the initial PDT session to determine the pathologic complete response rate. In addition, the treated tumors were assessed clinically for up to 24 months. The cosmetic outcome of each treated tumor site was assessed by the investigators based on color, profile, and surface texture. Results: The pathologic complete response rates at 6 months were 69, 79, and 93% for the 60, 120 and 180 J/cm2 light fluences, respectively. The clinical complete response rates by tumor at 6 months were 78, 89 and 98% at 60, 120 and 180 J/cm2, respectively, while at 24 months, the corresponding rates were 51, 79, and 95%. The cosmetic outcome by tumor at 24 months judged by the investigator to have achieved at least a satisfactory or higher outcome was 92, 76, and 86% at 60, 120 and 180 J/cm2, respectively. Conclusions: PDT of NMSC with verteporfin provides effective tumor clearing that is dose-dependent with satisfactory to excellent outcomes in the majority of patients.