RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis.

Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. Although these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as a candidate gene enriched in CTCs. Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 (also known as TAK1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes, and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.

Successful use of brachytherapy for a severe hidradenitis suppurativa variant.

Hidradenitis suppurativa is a member of the follicular occlusion tetrad, along with acne conglobata, dissecting cellulitis of the scalp and pilodinal sinus. These conditions share common pathophysiologic features, including follicle occlusion, bacterial overgrowth, severe suppurative inflammation, scarring, and sinus tract formation. Treatment of severe cases is challenging, and a novel treatment modality would be of significant value. We describe a 46-year-old man who presented with a 15-year history of suppurative and scarring nodules involving his groin, scalp, neck, face, and chest. Based on their distribution and morphology, these lesions were most characteristic of hidradenitis suppurativa, although he had features of acne conglobata and dissecting cellulitis as well. Over the years, he had been treated with several antimicrobial and immunomodulatory agents, the main conventional therapies for follicular occlusion syndromes, without much success. We then treated him with superficial brachytherapy to his right groin and occiput, which led to significant improvement. No toxic side effects were noted. This case demonstrates the successful application of superficial brachytherapy for the treatment of severe hidradenitis suppurativa, and possibly for other follicular occlusion syndromes.

Granulomatous reaction to liquid injectable silicone for gluteal enhancement: review of management options and success of doxycycline.

Liquid injectable silicone (LIS) for cosmetic purposes has been widely available and commonly used for almost half a century. An increase in buttock augmentation procedures because of patients wanting to emulate the look of some celebrities has recently highlighted cases in the media of unsafe administration of liquid silicone injections. Severe complications including death have been reported. In this article, we report a case in which liquid silicone was injected in the patient's gluteal tissue resulting in granulomatous reactions in the surrounding tissues. The patient responded well to doxycycline, presumably because of both its antimicrobial properties and immunomodulatory effects.

Combination Systemic Fluorouracil and Radiation for the Treatment of Recalcitrant Condyloma with Associated Squamous Cell Carcinoma in an Immunocompromised 15-Year-Old Girl.

Condylomata acuminata (CA), or anogenital warts, are typically benign lesions caused by human papillomavirus infection. Although they are rare, immunocompromised individuals are at a higher risk of CA undergoing transformation into invasive anal squamous cell carcinoma (SCC). These patients need aggressive evaluation and management. Treatment of CA is challenging, particularly for immunocompromised hosts, in whom warts are resistant to treatment and commonly recur. Currently, there is no gold standard treatment for CA, especially in children and immunodeficient individuals. We report the case of a 15-year-old immunocompromised girl with severe recalcitrant condyloma that resolved after a course of systemic 5-fluorouracil, mitomycin C, and radiation therapy for SCC.

In vitro analysis of interactions between Pseudomonas aeruginosa and Candida albicans treated with silver sulfadiazine in wound infections.

Background: Microorganisms tend to rely on close relationships with other species to survive. Consequently, biofilms formed by interactions of different species have been shown to delay the wound healing process. Studies suggest these mixed-population infections contribute to the development of drug resistance and inhibition of host immune response. Silver sulfadiazine (SSD) has been shown to effectively decrease the risk of infection in an open wound. Typically, these are bacterial wound infections; however, the role of fungal species needs further attention. Objectives: The purpose of this in vitro study was to determine the effect of SSD on interactions between Pseudomonas aeruginosa 09-009 (PA1) or P. aeruginosa 09-010 (PA2) and Candida albicans ATTC 64550 (CA). Methods: A mixture of 4 mL of tryptic soy broth (TSB) and 100 µL of CA and/or PA1 or PA2 (∼106 log cfu/mL) inoculums were deposited into either wells or vials. The wells or vials were then sonicated (50 W for 10 s) to separate microorganisms attached to the walls. After incubation, cell counts were performed at 24 and 48 h for each microorganism using specific media. Results: Our results show that without SSD treatment, P. aeruginosa exhibits an inhibitory effect on C. albicans. Treatment with SSD demonstrated significant reduction of P. aeruginosa; however, C. albicans persisted. This experiment demonstrates that SSD was effective in reducing the bioburden of both P. aeruginosa strains after 24 and 48 h; however, it was not as effective in reducing C. albicans. Conclusions: The data suggest that for polymicrobial mixed infections containing Pseudomonas spp. and C. albicans, treatment with SSD may be beneficial but does not provide adequate microorganism eradication. As such, added treatments that provide coverage for Candida infection are necessary. Additional in vivo studies are needed to obtain a better understanding of the complex interactions between these organisms.

Amplification-free digital gene expression profiling from minute cell quantities.

Generating reliable expression profiles from minute cell quantities is critical for scientific discovery and potential clinical applications. Here we present low-quantity digital gene expression (LQ-DGE), an amplification-free approach involving capture of poly(A)(+) RNAs from cellular lysates onto poly(dT)-coated sequencing surfaces, followed by on-surface reverse transcription and sequencing. We applied LQ-DGE to profile malignant and nonmalignant mouse and human cells, demonstrating its quantitative power and potential applicability to archival specimens.

Morphea with Oral Mucosa Involvement and Unilateral Nevoid Telangiectasia as an Early Presentation of Morphea: A Case Report and Review of the Literature.

Oral mucosal involvement in patients with morphea is quite rare. Unilateral nevoid telangiectasia is a rare vascular dermatosis characterized by unilateral telangiectasia distributed in a dermatomal pattern, especially on the upper trunk and extremities. We describe a case of a 10-year-old female patient that presents with morphea on her left chin and upper lip extending to the inner oral mucosa as well as a unilateral nevoid telangiectasia on her left cheek as an early presentation of localized scleroderma. This case is significant as it demonstrates a striking clinical presentation of morphea and an interesting early presentation of morphea as a unilateral nevoid telangiectasia that improved after treatment with oral methotrexate and prednisone.

Treatment of Dermatological Conditions Associated with HIV/AIDS: The Scarcity of Guidance on a Global Scale.

Background. Skin diseases associated with Human Immunodeficiency Virus (HIV) infection are associated with significant morbidity and mortality. In resource-limited settings, nondermatologists and lay health care providers on the front line of HIV care provide much of the treatment for these conditions. Objective. To evaluate guidelines for treatment of HIV-related skin conditions and assess their accessibility, comprehensiveness, and quality of evidence employed. Methods. A review was undertaken of all national and society guidelines which included treatment information on the ten highest burden HIV-related skin conditions. The search strategy included gray and peer-reviewed literature. Results. Of 430 potential guidelines, 86 met inclusion criteria, and only 2 were written specifically to address HIV-related skin diseases as a whole. Treatment information for HIV-related skin conditions was embedded within guidelines written for other purposes, primarily HIV/AIDs treatment guidelines (49%). Development of guidelines relied either partially or completely on expert opinion (62%). Only 16% of guidelines used gradation of evidence quality and these were primarily from high-income countries (p = 0.001). Limitations. Due to the nature of gray literature, not all guidelines may have been identified. Conclusion. This review highlights the need for evidence-based summary guidelines that address treatment for HIV-related skin conditions in an accessible format.

Vesiculobullous and hemorrhagic erythema migrans: uncommon variants of a common disease.

BACKGROUND: The diagnosis of Lyme disease relies on the accurate diagnosis of erythema chronicum migrans (ECM) because serologic tests, culture, and polymerase chain reactions are often inaccurate. Although ECM is classically associated with a targetoid rash, there are many variants of this lesion. These variants of ECM are often initially diagnosed as cellulitis or spider bite reactions and treated with oral antibiotics. Inappropriate treatment further delays the diagnosis of Lyme disease, leading to late complications. METHODS: We present four cases of vesiculobullous and hemorrhagic ECM, a less common variant of ECM. RESULTS: All four patients had a history of exposure to wooded areas in Massachusetts during the summer months. In these patients, ECM presented with central vesicles and bullae with hemorrhage, crusting, and in some cases necrosis. Serologic testing was positive in three of the four cases at presentation. In one case, microscopic examination of a skin biopsy showed epidermal spongiosis with parakeratosis, focal necrosis, papillary dermal edema, erythrocyte extravasation, and a superficial and deep perivascular lymphocytic infiltrate with neutrophils and eosinophils of the dermis. No fungal organisms or bacteria were identified. All four patients were treated with doxycycline with complete resolution of symptoms. CONCLUSIONS: It is important to recognize the vesiculobullous and hemorrhagic variants of ECM in order to minimize the provision of inappropriate antibiotic treatment for other diagnoses. Early diagnosis of ECM and the initiation of appropriate antibiotics may prevent late complications of Lyme disease.

Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers.

Satellite repeats in heterochromatin are transcribed into noncoding RNAs that have been linked to gene silencing and maintenance of chromosomal integrity. Using digital gene expression analysis, we showed that these transcripts are greatly overexpressed in mouse and human epithelial cancers. In 8 of 10 mouse pancreatic ductal adenocarcinomas (PDACs), pericentromeric satellites accounted for a mean 12% (range 1 to 50%) of all cellular transcripts, a mean 40-fold increase over that in normal tissue. In 15 of 15 human PDACs, alpha satellite transcripts were most abundant and HSATII transcripts were highly specific for cancer. Similar patterns were observed in cancers of the lung, kidney, ovary, colon, and prostate. Derepression of satellite transcripts correlated with overexpression of the long interspersed nuclear element 1 (LINE-1) retrotransposon and with aberrant expression of neuroendocrine-associated genes proximal to LINE-1 insertions. The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection.