Clinical and histological features of head and neck melanoma: a population-based study in France.

BACKGROUND: Head and neck melanomas (HNMs) account for an increasing proportion of melanomas and have a poor prognosis. OBJECTIVES: To compare the clinical and histological characteristics of HNMs with those of melanomas at other sites (MOS), and to identify pertinent clinicopathological subgroups of HNM. METHODS: A retrospective population-based study of incident in situ and invasive melanomas in the period 2004-2011 was performed. RESULTS: HNMs represented 26·7% of 1548 melanomas, corresponding to a density ratio of 3·7 between HNMs and MOS. HNMs occurred later than MOS (71·2 vs. 58·4 years; P < 0·01), included a higher proportion of in situ cases (49·6% vs. 13·5%; P < 0·01) and were mainly lentigo malignant melanomas (73·0% vs. 2·6%; P < 0·01). Invasive HNMs included a higher proportion of thick (> 2 mm) tumours [33·7% vs. 24·1% (P = 0·01); mean Breslow thickness: 2·18 vs. 1·77 mm (P = 0·03)] and nodular melanomas (20·1% vs. 12%; P < 0·01). HNMs in the peripheral area of the head and neck differed from those of central location by a younger age of onset (65·2 vs. 72·4 years; P < 0·01), male predominance (64·4% vs. 33·8%; P < 0·01), and higher proportions of invasive (67·2% vs. 42%; P < 0·01) and nodular (15·1% vs. 7·5%; P = 0·01) melanomas. CONCLUSIONS: HNMs highly differ from MOS, and are clinically and histologically heterogeneous, possibly as a consequence of different patterns of sun exposure. These data could help to improve primary and secondary prevention messages for patients and doctors.

Comparison of anatomical locations of cutaneous melanoma in men and women: a population-based study in France.

BACKGROUND: Identification of differences in melanoma location between the sexes could lead to sex-specific preventive measures. OBJECTIVES: To compare precise melanoma location and side in men and women. METHODS: The location of 1542 incident melanomas diagnosed during the period 2004-2011 in the French Champagne-Ardenne region (1·3 million inhabitants) was recorded using a regional registry and questionnaires sent to physicians. Men and women were compared for frequency of tumours on the head and neck; trunk; upper limb; lower limb; hand and foot. For each location, more precise sublocations were recorded. The laterality (right vs. left) was studied for head/neck and limb tumours. RESULTS: Melanomas predominated on the lower limb in women (32·2% vs. 9·3% in men; P < 0·01) and on the trunk in men (41·8% vs. 14·9%; P < 0·01), while the proportion of upper limb and head/neck tumours was similar in both sexes. Hand and foot melanomas predominated in women (10·3% vs. 6·3%; P < 0·01), with a sex-related distribution between sublocations. Within the head and neck location, 75·1% of tumours in women were located in the central area vs. 53·7% in the peripheral area in men (P < 0·01). Head and neck melanomas were more frequently right-sided in women and left-sided in men (P = 0·04), with the left/right ratio reaching 1·58 in men vs. 0·61 in women for peripheral tumours (P < 0·01). No difference in laterality was observed for other locations. CONCLUSIONS: Sex differences in occupational and leisure time ultraviolet exposure, clothing (including shoes), hairstyle, and side and photo exposure in cars could explain these results. General preventive messages could be completed by sex-specific advice for melanoma prevention.

Diagnosis and management of melanoma with regional lymph node metastases: a population-based study in France.

BACKGROUND: Stage III melanoma represents a borderline situation regarding the potential curability of this potentially aggressive cancer and consequently, regional lymph node metastases (RLNM) are a major challenge for melanoma management. OBJECTIVE: To describe the management of melanoma with RLNM as practised in France in 2008 and compare results with previous data from 2004, considering that new French recommendations were published in 2005. METHODS: Retrospective population-based study in five regions of France totalling 8.3 million inhabitants, targeting all incident cases of RLNM diagnosed in 2008. Questionnaires were mailed to physicians to identify cases and collect data, with verification by cancer registries for cases diagnosed concomitantly with the primary tumour using sentinel lymph node biopsies (SLNB). RESULTS: Data were collected for 101 patients in 2008, and compared to 89 cases treated in 2004. Palpation by a dermatologist was the most common circumstance of diagnosis of RLNM in 2008 (36%), followed by SLNB (29%), self-palpation by the patient (16%) and lymph node ultrasonography (6%), without significant modification from 2004. After lymphadenectomy an adjuvant therapy was proposed in 62% of cases, mainly consisting in high-dose interferon (HD-IFN) (80%). Overall, HD-IFN was proposed in 49% of cases, but effectively started in only 40% of cases after being proposed, and prematurely withdrawn in 28%, showing major changes as compared with 2004 (33%, 77% and 67%, respectively, P < 0.05). Adjuvant chemotherapy was not proposed to any patients in 2008, compared to 29% in 2004. Surveillance procedures included medical imaging less often in 2008 (76%) than in 2004 (92%) (P = 0.004), but more often included FDG-PET (23% vs. 12%, P = 0.09). CONCLUSION: Overall, actual practice was in accordance with French recommendations. The main developments from 2004 to 2008 were the disappearance of adjuvant chemotherapies and a more accurate selection of patients for adjuvant interferon.

Clinical and pathological characteristics of melanoma: a population-based study in a French regional population.

BACKGROUND: Although incidence and mortality data are numerous, population-based studies including clinical and pathological characteristics of melanoma are rare. OBJECTIVES: To describe the characteristics of melanoma in a rural French region during 2004-2008 and to identify differences according to age, gender and geographical areas. METHODS: Pathology reports of cutaneous melanomas diagnosed in residents from the Champagne-Ardenne region during 2004-2008 were anonymously collected from pathology laboratories. Demographic, clinical and pathological data were extracted and analysed by experts, including dermatologists, pathologists and epidemiologists. RESULTS: One hundred and seventy-seven in situ melanomas were diagnosed in 177 patients (female/male ratio : 1.72). Patients with head and neck in situ melanomas were older than patients with melanomas in other locations (72 vs. 54 years; P < 0.0001). Six hundred and sixty-one invasive melanomas were diagnosed (female/male ratio : 1.26), corresponding to an annual incidence rate of 6.3/100,000. Male patients had thicker and more frequently ulcerated tumours. The location widely varied between genders, involving the trunk in 47% of male patients and the lower limb in 48% of female patients. Older patients had thicker and more advanced melanomas, with a more frequent head and neck location. Nodular, acral lentiginous and unclassified melanomas were much thicker than superficial spreading and lentigo maligna melanomas (4.37 vs. 1.33 mm, P < 0.0001). Primary melanomas of advanced stages were more frequent in one of the four districts of the study area. Overall, the mean Breslow thickness (2.02 mm) was much higher than that previously observed in other regions of north-eastern France (1.59 mm). CONCLUSIONS: Information and screening campaigns should particularly target rural areas, males, older people and focus on nodular, acrolentiginous and unclassified subtypes.

Aneurysm Characteristics, Study Population, and Endovascular Techniques for the Treatment of Intracranial Aneurysms in a Large, Prospective, Multicenter Cohort: Results of the Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm Study.

BACKGROUND AND PURPOSE: The Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm (ARETA) prospective study aims to determine factors predicting recurrence after endovascular treatment for intracranial aneurysms. In this publication, we review endovascular techniques and present the study population. Characteristics of treated and untreated unruptured aneurysms were analyzed. MATERIALS AND METHODS: Sixteen neurointerventional departments prospectively enrolled patients treated for ruptured and unruptured intracranial aneurysms between December 2013 and May 2015. Patient demographics, aneurysm characteristics, and endovascular techniques were recorded. RESULTS: A total of 1289 patients with 1761 intracranial aneurysms, 835 (47.4%) ruptured, were enrolled. Of these, 1359 intracranial aneurysms were treated by endovascular means. Ruptured intracranial aneurysms were treated by coiling and balloon-assisted coiling in 97.8% of cases. In unruptured intracranial aneurysms, the rates of flow diversion, flow disruption, and stent-assisted coiling were 11.6%, 6.9%, and 7.8%, respectively. Rupture status and aneurysm location, neck diameter, and sac size significantly influenced the chosen technique. Treated unruptured intracranial aneurysms, compared with untreated counterparts, had larger aneurysm sacs (7.6 ± 4.0 versus 3.4 ± 2.0 mm; P < 0.001) and neck dimensions (4.1 ± 2.2 versus 2.4 ± 1.3 mm; P < 0.001) and more frequently an irregular form (84.6% versus 44.4%; P < 0.001). Also, its location influenced whether an unruptured intracranial aneurysm was treated. CONCLUSIONS: Our study provides an overview of current neurointerventional practice in the ARETA cohort. The technique choice was influenced by aneurysm morphology, location, and rupture status. Flow diversion, flow disruption, and stent-assisted coiling were commonly used in unruptured intracranial aneurysms, while most ruptured intracranial aneurysms were treated with coiling and balloon-assisted coiling.

Production of lactones and peroxisomal beta-oxidation in yeasts.

Among aroma compounds interesting for the food industry, lactones may be produced by biotechnological means using yeasts. These microorganisms are able to synthesize lactones de novo or by biotransformation of fatty acids with higher yields. Obtained lactone concentrations are compatible with industrial production, although detailed metabolic pathways have not been completely elucidated. The biotransformation of ricinoleic acid into gamma-decalactone is taken here as an example to better understand the uptake of hydroxy fatty acids by yeasts and the different pathways of fatty acid degradation. The localization of ricinoleic acid beta-oxidation in peroxisomes is demonstrated. Then the regulation of the biotransformation is described, particularly the induction of peroxisome proliferation and peroxisomal beta-oxidation and its regulation at the genome level. The nature of the biotransformation product is then discussed (4-hydroxydecanoic acid or gamma-decalactone), because the localization and the mechanisms of the lactonization are still not properly known. Lactone production may also be limited by the degradation of this aroma compound by the yeasts which produced it. Thus, different possible ways of modification and degradation of gamma-decalactone are described.

Peroxisomal beta-oxidation activities and gamma-decalactone production by the yeast Yarrowia lipolytica.

gamma-Decalactone is a peachy aroma compound resulting from the peroxisomal beta-oxidation of ricinoleic acid by yeasts. The expression levels of acyl-CoA oxidase (gene deletion) and 3-ketoacyl-CoA thiolase activities (gene amplification on replicative plasmids) were modified in the yeast Yarrowia lipolytica. The effects of these modifications on beta-oxidation were measured. Overexpression of thiolase activity did not have any effect on the overall beta-oxidation activity. The disruption of one of the acyl-CoA oxidase genes resulted in an enhanced activity. The enhancement led to an increase of overall beta-oxidation activity but reduced the gamma-decalactone production rates. This seemed to indicate a non-rate-limiting role for beta-oxidation in the biotransformation of ricinoleic acid to gamma-decalactone by the yeast Yarrowia lipolytica. All strains produced and then consumed gamma-decalactone. We checked the ability of the different strains to consume gamma-decalactone in a medium containing the lactone as sole carbon source. The consumption of the strain overexpressing acyl-CoA oxidase activity was higher than that of the wild-type strain. We concluded that peroxisomal beta-oxidation is certainly involved in gamma-decalactone catabolism by the yeast Y. lipolytica. The observed production rates probably depend on an equilibrium between production and consumption of the lactone.

Secretion of active beta-lactamase to the medium mediated by the Escherichia coli haemolysin transport pathway.

An in frame gene fusion containing the coding region for mature beta-lactamase and the 3'-end of hylA encoding the haemolysin secretion signal, was constructed under the control of a lac promoter. The resulting 53 kDa hybrid protein was specifically secreted to the external medium in the presence of the haemolysin translocator proteins, HlyB and HlyD. The specific activity of the beta-lactamase portion of the secreted protein (measured by the hydrolysis of penicillin G), approximately 1 U/microgram protein, was close to that of authentic, purified TEM-beta-lactamase. This is an important example of a hybrid protein that is enzymatically active, and secreted via the haemolysin pathway. Previous studies have indicated that haemolysin is secreted directly into the medium, bypassing the periplasm, to which beta-lactamase is normally targeted. This study indicated, therefore, that normal folding of an active beta-lactamase, can occur, at least when fused to the HlyA C-terminus, without the necessity of entering the periplasm. Despite the secretion of approximately 5 micrograms/ml levels of the active beta-lactamase fusion into the medium, there was maximally only a 50% detectable increase in the LD50 for resistance to ampicillin at the individual cell level. This result suggests that, normally, resistance to ampicillin requires a high concentration of the enzyme close to killing targets, i.e. in the periplasm, in order to achieve significant levels of protection.

Cloning and characterization of the peroxisomal acyl CoA oxidase ACO3 gene from the alkane-utilizing yeast Yarrowia lipolytica.

The ACO3 gene, which encodes one of the acyl-CoA oxidase isoenzymes, was isolated from the alkane-utilizing yeast Yarrowia lipolytica as a 10 kb genomic fragment. It was sequenced and found to encode a 701-amino acid protein very similar to other ACOs, 67.5% identical to Y. lipolytica Aco1p and about 40% identical to S. cerevisiae Pox1p. Haploid strains with a disrupted allele were able to grow on fatty acids. The levels of acyl-CoA oxidase activity in the ACO3 deleted strain, in an ACO1 deleted strain and in the wild-type strain, suggested that ACO3 encodes a short chain acyl-CoA oxidase isoenzyme. This narrow substrate spectrum was confirmed by expression of Aco3p in E. coli.