No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report.

BACKGROUND: Sentinel lymph node biopsy (SLNB) was developed in the hope that it would improve outcomes for patients with melanoma. SLNB is an area of discussion and controversy in melanoma medicine. The final trial results of the Multicenter Selective Lymphadenectomy Trial (MSLT-I) have now been published and the authors suggest their long-term results 'clearly validate the use of sentinel-node biopsy in patients with intermediate-thickness or thick primary melanomas'. An accompanying editorial states that MSLT-I is a practice-changing trial. CONCLUSIONS: However, critical appraisal of MSLT-I data does not support the claims of the final report. On the contrary, MSLT-I failed to demonstrate that there is a significant treatment-related difference in the 10-year melanoma-specific survival rate in the overall study population. Furthermore, there was no improvement in overall or melanoma-specific survival of the intermediate-thickness group (1·2-3·5 mm). Completion lymphadenectomy can result in complications in about a third of patients, with a rate of clinically significant lymphoedema following axillary or groin dissection of 5-10%. Unnecessary lymphadenectomy can therefore have a major effect on patient quality of life. The evidence provided by Morton et al. does not support the claim that sentinel lymph node biopsy followed by lymphadenectomy in patients with positive sentinel nodes should be the standard of care in patients with melanoma. Readers are encouraged to check with registration sites to make sure declared primary outcomes are fairly reported. Post-hoc analyses are at best exploratory and cannot be used to form the principal conclusions of a trial.

IL-22 defines a novel immune pathway of antifungal resistance.

The role of IL-17 and Th17 cells in immunity vs. pathology associated with the human commensal Candida albicans remains controversial. Both positive and negative effects on immune resistance have been attributed to IL-17/Th17 in experimental candidiasis. In this study, we provide evidence that IL-22, which is also produced by Th17 cells, has a critical, first-line defense in candidiasis by controlling the growth of infecting yeasts as well as by contributing to the host's epithelial integrity in the absence of acquired Th1-type immunity. The two pathways are reciprocally regulated, and IL-22 is upregulated under Th1 deficiency conditions and vice versa. Whereas both IL-17A and F are dispensable for antifungal resistance, IL-22 mediates protection in IL-17RA-deficient mice, in which IL-17A contributes to disease susceptibility. Thus, our findings suggest that protective immunity to candidiasis is made up of a staged response involving an early, IL-22-dominated response followed by Th1/Treg reactivity that will prevent fungal dissemination and supply memory.

Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis.

Innate responses combine with adaptive immunity to generate the most effective form of anti-Aspergillus immune resistance. Although some degree of inflammation is required for protection, progressive inflammation may worsen disease and ultimately prevents pathogen eradication. To define molecular pathways leading to or diverting from pathogenic inflammation in infection, we resorted to dendritic cells (DCs), known to activate distinct signaling pathways in response to pathogens. We found that distinct intracellular pathways mediated the sensing of conidia and hyphae by lung DCs in vitro, which translate in vivo in the activation of protective Th1/Treg responses by conidia or inflammatory Th2/Th17 responses by hyphae. In vivo targeting inflammatory (PI3K/Akt/mTOR) or anti-inflammatory (STAT3/IDO) DC pathways by intranasally delivered small interfering RNA (siRNA) accordingly modified inflammation and immunity to infection. Thus, the screening of signaling pathways in DCs through a systems biology approach may be exploited for the development of siRNA therapeutics to attenuate inflammation in respiratory fungal infections and diseases.

Systemic treatment of severe psoriasis.

Severe psoriasis presents a difficult therapeutic challenge. Some modalities such as synthetic retinoids, phototherapy and methotrexate have been available for many years and need reappraisal, cyclosporin has only recently become available and requires careful administration. In this article we focus on the therapeutic modalities available to the dermatologist in Australia.

Flesh-coloured micropapules on the face and upper trunk.

The following case report is of a 49 year old man who presented with a 20 year history of small asymptomatic flesh coloured firm papules which were concentrated on his face, neck and upper trunk. The diagnosis of multiple fibrofolliculomas of the familial type was reached.

Spotted cicatricial alopecia in dark skin. A dermoscopic clue to fibrous tracts.

Study of areas of cicatricial alopecia in a 42 year old black woman by dermoscopy with oil revealed uniform pale dots associated with a radiating pigment network. Scalp biopsy showed a cicatricial alopecia with lichen planopilaris and multiple fibrous tracts. The pale dots appear to correspond to focal decrease in epidermal melanin pigment overlying the site of the fibrous tracts and may provide a dermoscopic clue in analysing the cicatricial alopecias.

Pilomatrix carcinoma of the scalp.

A matrical carcinoma (pilomatrix carcinoma) of the scalp is described--the first reported case in this site. This malignant hair follicle tumour must be distinguished histologically from benign pilomatricoma and proliferating trichilemmal tumour, which can have similar features.

The eye and the hand: a clinical review.

The visual system is highly susceptible to involvement in many systemic disorders. Disorders of tissues common to the eye and the hand, such as vascular, connective and neural, may have striking clinical signs in both. Thus signs in the hand may provide useful diagnostic clues in the assessment of disorders of the visual system. The hand may even be causative in traumatic or infective eye diseases. This review provides a schema for a suitable hand examination and documents the eye and hand features of various common and uncommon disorders. The importance to the ophthalmologist of a careful hand examination is emphasised.

Lichen nitidus confined to one palm.

Lichen nitidus is an unusual dermatosis which tends to involve the trunk, penis and forearms of children and young adults. It is usually bilaterally symmetrical. We report a case of unilateral palmar lichen nitidus in an elderly man.