Dilemma of clinically node-negative head and neck melanoma: outcome of "watch and wait" policy, elective lymph node dissection, and sentinel node biopsy--a systematic review

The management of patients with clinically node-negative melanoma of the head and neck remains controversial. This is a systematic review of management strategies for stage I head and neck melanoma. Subgroup analysis of 1 randomized controlled trial (RCT) and most available cohort studies do not reveal a significant impact of elective neck dissection on survival. For 1.2- to 3.5-mm-thick melanoma at all anatomical sites, 1 RCT does not show an overall significant melanoma-specific survival benefit of sentinel node biopsy, but subgroup analysis suggests a survival benefit for lymph node-positive patients, confirming findings from 3 retrospective series. Sentinel node biopsy in the head and neck region can be technically demanding, with lower identification rates and higher false-negative rates. There is no conclusive survival advantage of either elective neck dissection or sentinel node biopsy in patients with clinically node-negative head and neck melanoma of intermediate thickness.     

The contribution of reactive oxygen species and p38 mitogen-activated protein kinase to myofilament oxidation and progression of heart failure in rabbits

Background and purpose:

The formation of reactive oxygen species (ROS) is increased in heart failure (HF). However, the causal and mechanistic relationship of ROS formation with contractile dysfunction is not clear in detail. Therefore, ROS formation, myofibrillar protein oxidation and p38 MAP kinase activation were related to contractile function in failing rabbit hearts.

Experimental approach and key results:

Three weeks of rapid left ventricular (LV) pacing reduced LV shortening fraction (SF, echocardiography) from 32 ± 1% to 13 ± 1%. ROS formation, as assessed by dihydroethidine staining, increased by 36 ± 8% and was associated with increased tropomyosin oxidation, as reflected by dimer formation (dimer to monomer ratio increased 2.28 ± 0.66-fold in HF vs. sham, P < 0.05). Apoptosis (TdT-mediated dUTP nick end labelling staining) increased more than 12-fold after 3 weeks of pacing when a significant increase in the phosphorylation of p38 MAP kinase and HSP27 was detected (Western blotting). Vitamins C and E abolished the increases in ROS formation and tropomyosin oxidation along with an improvement of LVSF (19 ± 1%, P < 0.05 vs. untreated HF) and prevention of apoptosis, but without modifying p38 MAP kinase activation. Inhibition of p38 MAP kinase by SB281832 counteracted ROS formation, tropomyosin oxidation and contractile failure, without affecting apoptosis.

Conclusions and implications:

Thus, p38 MAP kinase activation appears to be upstream rather than downstream of ROS, which impacts on LV function through myofibrillar oxidation. p38 MAP kinase inhibition is a potential target to prevent or treat HF.     

Regional lymph nodes at a distance

In 3 patients, two men aged 22 years and 38 years with melanoma, and one woman aged 46 years with breast cancer, local tumour growth recurred following regional lymph node dissection. All three developed metastasis in new distant regional basins, which were once more dissected. The first melanoma patient died from haematogenous metastasis, 2 years after the excision of his primary melanoma. The other melanoma patient was alive, without evidence of disease, 8 years after the treatment of his primary tumour. The breast cancer patient, who underwent contralateral axillary lymph node dissection, was also alive, without evidence of disease, 27 years after the treatment of her primary tumour. Diversion of lymphatic flow as a result of regional lymph node dissection for cancer may lead to metastasis to a distant lymph node basin if tumour growth recurs in the original area. Knowledge of this usually unknown phenomenon is important since metastasis to these new regional basins can still be treated curatively, in the form of another lymph node dissection. These distant lymph node basins must therefore be carefully checked during follow-up monitoring.     

What is a sentinel node and what is a false-negative sentinel node?

Morton's original definition of a sentinel node as the first lymph node to receive afferent lymphatic drainage from a primary tumor reflects the concept of stepwise spread of cancer through the lymphatic system. Several new definitions have been developed, based on surgical anatomy and on the technique that is used to find the node. The various definitions of a sentinel node are critically analyzed. Breast cancer surgeons use three different definitions of a false-negative sentinel node biopsy. The best definition appears to be based on the assumption that the procedure is truly positive if either the sentinel node or a suspicious node that is not radioactive or blue contains metastatic disease.     

Immune response in demodicosis

BACKGROUND: Demodex folliculorum and Demodex brevis are obligatory parasites in the hair follicles and in the pilosebaceous glands. Although most people are infested with these mites, only a small number develop the clinical symptoms of demodicosis. The objective of this study was to determine the distinguishing features of the immune response to the infestation of the skin by Demodex mites. METHODS: Twenty-nine patients with human demodicosis and 13 age- and sex-matched healthy subjects participated in the study. The presence of mites was determined by microscopic inspection of secretion from sebum glands. The immune response was evaluated in the peripheral blood by identifying membrane markers of different immune cells using monoclonal antibodies, while the concentration of immunoglobulin (Ig)A, IgM and IgG was calculated by simple radial immunodiffusion using anti-IgA, anti-IgM and anti-IgG. The level of circulating immune complexes and total haemolytic complement, as well as the preparatory and digestive function of neutrophils, and the functional activity of leucocytes were also studied. RESULTS: The absolute number of CD95+ was higher in patients with demodicosis. The absolute number of CD3+, CD4+, CD8+ and CD16+ cells, the ratio CD3+/CD20+ and the functional activity of leucocytes were significantly lower in individuals infested with Demodex mites. No significant differences were found in the percentage and absolute number of CD20+ cells, the ratio of CD4+/CD8+ T-cell subpopulations, circulating immune complexes, level of serum complement activity (CH(50)), activity and index of phagocytosis and the levels of IgA, IgM and IgG antibodies between individuals infested with Demodex mites and the control group. CONCLUSION: The readiness of lymphocytes to undergo apoptosis increases in parallel to the increasing density of the mites. This could be the result of local immunosuppression caused by the mites, which allows them to survive in the host skin.