The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma – a retrospective analysis of 392 cases

Twenty per cent of sentinel lymph node (SLN)-positive melanoma patients have positive non-SLN lymph nodes in completion lymph node dissection (CLND). We investigated SLN tumour load, non-sentinel positivity and disease-free survival (DFS) to assess whether certain patients could be spared CLND. Sentinel lymph node biopsy was performed on 392 patients between 1999 and 2005. Median observation period was 38.8 months. Sentinel lymph node tumour load did not predict non-SLN positivity: 30.8% of patients with SLN macrometastases (⩾2 mm) and 16.4% with micrometastases (⩽2 mm) had non-SLN positivity (P=0.09). Tumour recurrences after positive SLNs were more than twice as frequent for SLN macrometastases (51.3%) than for micrometastases (24.6%) (P=0.005). For patients with SLN micrometastases, the DFS analysis was worse (P=0.003) when comparing those with positive non-SLNs (60% recurrences) to those without (17.6% recurrences). This difference did not translate into significant differences in DFS: patients with SLN micrometastasis, either with (P=0.022) or without additional positive non-SLNs (P<0.0001), fared worse than patients with tumour-free SLNs. The 2-mm cutoff for SLN tumour load accurately predicts differences in DFS. Non-SLN positivity in CLND, however, cannot be predicted. Therefore, contrary to other studies, no recommendations concerning discontinuation of CLND based on SLN tumour load can be deduced

Prognostic Value of [18F]-Fluoro-Deoxy-Glucose PET/CT, S100 or MIA for Assessment of Cancer-Associated Mortality in Patients with High Risk Melanoma

PURPOSE: To assess the prognostic value of FDG PET/CT compared to the tumor markers S100B and melanoma inhibitory activity (MIA) in patients with high risk melanoma. METHODS: Retrospective study in 125 consecutive patients with high risk melanoma that underwent FDG PET/CT for re-staging. Diagnostic accuracy and prognostic value was determined for FDG PET/CT as well as for S100B and MIA. As standard of reference, cytological, histological, PET/CT or MRI follow-up findings as well as clinical follow-up were used. RESULTS: Of 125 patients, FDG PET/CT was positive in 62 patients. 37 (29.6%) patients had elevated S100B (>100 pg/ml) and 24 (20.2%) had elevated MIA (>10 pg/ml) values. Overall specificities for FDG PET/CT, S100B and MIA were 96.8% (95% CI, 89.1% to 99.1%), 85.7% (75.0% to 92.3%), and 95.2% (86.9% to 98.4%), corresponding sensitivities were 96.8% (89.0% to 99.1%), 45.2% (33.4% to 55.5%), and 36.1% (25.2% to 48.6%), respectively. The negative predictive values (NPV) for PET/CT, S100B, and MIA were 96.8% (89.1% to 99.1%), 61.4% (50.9% to 70.9%), and 60.6% (50.8% to 69.7%). The positive predictive values (PPV) were 96.7% (89.0% to 99.1%), 75.7% (59.9% to 86.6%), and 88.0% (70.0% to 95.8%). Patients with elevated S100B- or MIA values or PET/CT positive findings showed a significantly (p<0.001 each, univariate Cox regression models) higher risk of melanoma associated death which was increased 4.2-, 6.5- or 17.2-fold, respectively. CONCLUSION: PET/CT has a higher prognostic power in the assessment of cancer-associated mortality in melanoma patients compared with S100 and MIA

Mortality and morbidity among people living close to incinerators: a cohort study based on dispersion modeling for exposure assessment

<p>Abstract</p> <p>Background</p> <p>Several studies have been conducted on the possible health effects for people living close to incinerators and well-conducted reviews are available. Nevertheless, several uncertainties limit the overall interpretation of the findings. We evaluated the health effects of emissions from two incinerators in a pilot cohort study.</p> <p>Methods</p> <p>The study area was defined as the 3.5 km radius around two incinerators located near Forlì (Italy). People who were residents in 1/1/1990, or subsequently became residents up to 31/12/2003, were enrolled in a longitudinal study (31,347 individuals). All the addresses were geocoded. Follow-up continued until 31/12/2003 by linking the mortality register, cancer registry and hospital admissions databases. Atmospheric Dispersion Model System (ADMS) software was used for exposure assessment; modelled concentration maps of heavy metals (annual average) were considered the indicators of exposure to atmospheric pollution from the incinerators, while concentration maps of nitrogen dioxide (NO₂) were considered for exposure to other pollution sources. Age and area-based socioeconomic status adjusted rate ratios and 95% Confidence Intervals were estimated with Poisson regression, using the lowest exposure category to heavy metals as reference.</p> <p>Results</p> <p>The mortality and morbidity experience of the whole cohort did not differ from the regional population. In the internal analysis, no association between pollution exposure from the incinerators and all-cause and cause-specific mortality outcomes was observed in men, with the exception of colon cancer. Exposure to the incinerators was associated with cancer mortality among women, in particular for all cancer sites (RR for the highest exposure level = 1.47, 95% CI: 1.09, 1.99), stomach, colon, liver and breast cancer. No clear trend was detected for cancer incidence. No association was found for hospitalizations related to major diseases. NO₂levels, as a proxy from other pollution sources (traffic in particular), did not exert an important confounding role.</p> <p>Conclusions</p> <p>No increased risk of mortality and morbidity was found in the entire area. The internal analysis of the cohort based on dispersion modeling found excesses of mortality for some cancer types in the highest exposure categories, especially in women. The interpretation of the findings is limited given the pilot nature of the study.</p

Systematic review of epidemiological studies on health effects associated with management of solid waste

Background: Management of solid waste (mainly landfills and incineration) releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Our aim was to systematically review the available epidemiological literature on the health effects in the vicinity of landfills and incinerators and among workers at waste processing plants to derive usable excess risk estimates for health impact assessment.Methods: We examined the published, peer-reviewed literature addressing health effects of waste management between 1983 and 2008. For each paper, we examined the study design and assessed potential biases in the effect estimates. We evaluated the overall evidence and graded the associated uncertainties.Results: In most cases the overall evidence was inadequate to establish a relationship between a specific waste process and health effects; the evidence from occupational studies was not sufficient to make an overall assessment. For community studies, at least for some processes, there was limited evidence of a causal relationship and a few studies were selected for a quantitative evaluation. In particular, for populations living within two kilometres of landfills there was limited evidence of congenital anomalies and low birth weight with excess risk of 2 percent and 6 percent, respectively. The excess risk tended to be higher when sites dealing with toxic wastes were considered. For populations living within three kilometres of old incinerators, there was limited evidence of an increased risk of cancer, with an estimated excess risk of 3.5 percent. The confidence in the evaluation and in the estimated excess risk tended to be higher for specific cancer forms such as non-Hodgkin's lymphoma and soft tissue sarcoma than for other cancers.Conclusions: The studies we have reviewed suffer from many limitations due to poor exposure assessment, ecological level of analysis, and lack of information on relevant confounders. With a moderate level confidence, however, we have derived some effect estimates that could be used for health impact assessment of old landfill and incineration plants. The uncertainties surrounding these numbers should be considered carefully when health effects are estimated. It is clear that future research into the health risks of waste management needs to overcome current limitations

Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment

Toll-like receptors (TLRs) play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection or tissue injury. Recent findings show that functional TLRs are expressed not only on immune cells but also on cancer cells. TLRs play an active role in carcinogenesis and tumor progression during chronic inflammation that involves the tumor microenvironment. Damage-associated molecular patterns (DAMPs) derived from injured normal epithelial cells and necrotic cancer cells appear to be present at significant levels in the tumor microenvironment, and their stimulation of specific TLRs can foster chronic inflammation. This review discusses how carcinogenesis, cancer progression, and site-specific metastasis are related to interactions between cancer cells, immune cells, and DAMPs through TLR activation in the tumor microenvironment

An Overview of Three Promising Mechanical, Optical, and Biochemical Engineering Approaches to Improve Selective Photothermolysis of Refractory Port Wine Stains

During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion)