Functional changes induced by extrusion during cocoa alkalization.

Polyphenols, a group of secondary metabolites, have well-known relevant effects on human health. During traditional alkalization, this content dramatically lowers. We aimed to evaluate an alternative alkalization method based on extrusion on cocoa functional characteristics. The results showed that the antioxidant capacity and total phenolic values increased as alkali concentration and temperature did, and these values doubled under less extreme conditions. Comparing the functional properties between extruded and traditionally produced powders revealed that catechin, epicatechin and dimers B1 and B2 contents were 43%, 33%, 54% and 34% lower in the extruded samples, respectively. However, this reduction was partially balanced by increased clovamide content up to 50%. Thus the total phenol content and antioxidant capacity of the extruded samples were statistically above those of the commercial one. Hence extrusion alkalization should be considered a new processing alternative to avoid markedly reducing functional properties.

Chronic administration of minoxidil protects elastic fibers and stimulates their neosynthesis with improvement of the aorta mechanics in mice.

Arterial wall elastic fibers, made of 90% elastin, are arranged into elastic lamellae which are responsible for the resilience and elastic properties of the large arteries (aorta and its proximal branches). Elastin is synthesized only in early life and adolescence mainly by the vascular smooth muscles cells (VSMC) through the cross-linking of its soluble precursor, tropoelastin. In normal aging, the elastic fibers become fragmented and the mechanical load is transferred to collagen fibers, which are 100-1000 times stiffer than elastic fibers. Minoxidil, an ATP-dependent K+ channel opener, has been shown to stimulate elastin expression in vitro, and in vivo in the aorta of male aged mice and young adult hypertensive rats. Here, we have studied the effect of a 3-month chronic oral treatment with minoxidil (120 mg/L in drinking water) on the abdominal aorta structure and function in adult (6-month-old) and aged (24-month-old) male and female mice. Our results show that minoxidil treatment preserves elastic lamellae integrity at both ages, which is accompanied by the formation of newly synthesized elastic fibers in aged mice. This leads to a generally decreased pulse pressure and a significant improvement of the arterial biomechanical properties in female mice, which present an increased distensibility and a decreased rigidity of the aorta. Our studies show that minoxidil treatment reversed some of the major adverse effects of arterial aging in mice and could be an interesting anti-arterial aging agent, also potentially usable for female-targeted therapies.

Metabolic comorbidities and hypertension in psoriasis patients in France. Comparisons with French national databases.

INTRODUCTION: Several studies have shown a high prevalence of cardiovascular and metabolic comorbidities in psoriasis. Our study aimed to evaluate the association of psoriasis with key comorbidities such as smoking, obesity, hypertension, dyslipidaemia and diabetes comparatively with French national data. MATERIAL AND METHODS: This multicentre noninterventional observational study of adults with psoriasis was conducted in 29 dermatology centres in France. A total of 2210 patients were included. The prevalence of comorbidities in psoriatic patients was compared to data from the French national databanks "ObEpi 2012" (obesity, hypertension, dyslipidaemia and diabetes) and "Baromètre Santé 2010" (smoking). RESULTS: We reported a higher prevalence of all metabolic comorbidities and high blood pressure in psoriatic patients. Smoking: 32.5% were active smokers; the age of onset and the prevalence of familial psoriasis were significantly lower in the smoking group but the severity of psoriasis was significantly higher. The frequency of smoking was higher than in the general population, particularly among young female patients. Obesity: 24% of patients with psoriasis were obese. Multivariate analysis showed obesity to be significantly associated with other comorbidities, severity of psoriasis and psoriatic arthritis. The incidence of obesity was higher than in general population, occurring chiefly in subjects aged over 45 years. HYPERTENSION: 26% of patients with psoriasis had hypertension. The age of onset of psoriasis and the prevalence of psoriatic arthritis were significantly higher in the hypertension group, although there was less familial psoriasis. The incidence of hypertension was higher than in general population. Dyslipidaemia: 27.5% of patients with psoriasis had dyslipidaemia. The age of onset in the dyslipidaemia group was higher although there was less familial psoriasis. The incidence of dyslipidaemia was higher than in general population. Diabetes: 11.0% of patients with psoriasis had diabetes. The age of onset of psoriasis was significantly higher in the diabetes group although there was less familial psoriasis. The incidence of diabetes was higher than in general population particularly after the age of 35 years. CONCLUSION: These results confirmed that psoriasis is associated with significant metabolic comorbidities and hypertension compared to the general population in France, with certain epidemiological differences for each.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

Psoriasis in the elderly: epidemiological and clinical aspects, and evaluation of patients with very late onset psoriasis.

BACKGROUND: Age of the patients and age of onset of psoriasis may have an impact on the disease. There is little information about psoriasis in elderly patients. OBJECTIVE: We evaluated epidemiological, clinical aspects, comorbidities and treatments of psoriasis in the elderly (>70 years) patients, and in patients with very late onset psoriasis (onset ≥ 70 years). METHODS: This observational multicentre non-interventional study of adults with psoriasis was conducted in 29 departments of dermatology in France. A total of 2210 adults with psoriasis were included. RESULTS: A total of 212 (9.5%) patients were elderly. This group had a higher frequency of females (P = 0.005), a later onset of the disease (P < 0.0001), a lower frequency of familial (P < 0.0001) and plaque psoriasis (P < 0.0001), but higher frequency of guttate and inverse psoriasis (P ≤ 0.005). Hypertension, diabetes, dyslipidaemia, and major cardiovascular events (MACE) were more frequent in this group (P < 0.0001), but not tobacco (P < 0.0001). Systemic and biological therapies were used less frequently in the elderly group (P < 0.0001). Fifty-eight (2.7%) patients had late onset psoriasis. Patients with very late onset psoriasis were more frequently women (P = 0.02) and older (P < 0.0001), among elderly group. They had significantly less frequently familial (P < 0.0001) and plaque psoriasis (P < 0.0001), and were less often on systemic treatment including biological. Frequencies of comorbidities were not statically different but patients with 'early' onset psoriasis have a tendency (P < 0.5) to have higher frequencies of obesity, diabetes, dyslipidaemia, hypertension and MACE. CONCLUSION: This study highlights phenotypic features of psoriasis in elderly and in very late onset psoriasis. The management of these fragile patients remains poorly codified and needs further investigation.

[High-resolution ultrasonography for differential diagnosis between nodular basal carcinoma and sebaceous hyperplasia of the face: A pilot study]. / Échographie cutanée haute résolution dans le diagnostic différentiel entre carcinome basocellulaire nodulaire et hyperplasie sébacée du visage: une étude pilote.

BACKGROUND: Clinical differential diagnosis between incipient nodular basal carcinoma (NBC) and sebaceous hyperplasia (SH) of the face is difficult in some cases. A comparative histological analysis of these two entities led us to the hypothesis that 20MHz high-resolution ultrasonography (HRUS) may enable differentiation between NBC and SH. PATIENTS AND METHODS: Seventy-seven facial tumours requiring histological confirmation to distinguish between NBC and SH were scanned using HRUS before excision. No other imaging technique was used. The ultrasound scans were submitted to two blinded reviewers who were asked to classify the ultrasound pictures of the tumours as either hypoechoic or isoechoic/hyperechoic. Hypoechogenicity was defined as a diagnostic criterion for NBC. RESULTS: Reviewer response reproducibility for 2 images of the same tumour was 90%. Both reviewers agreed regarding the echogenicity classification of an image in 87.4% of cases. The sensitivity of the procedure was 90.9% for detection of NBC and 89.4% for detection of malignant lesions. Specificity was 69.6% for detection of basal cell carcinomas and 78.8% for detection of malignant lesions. DISCUSSION: HRUS is a non-invasive examination technique with excellent sensitivity for the detection of NBC in differential diagnosis with SH. Hypoechogenicity is not specific to NBC. The sensitivity of HRUS in our study suffered as a result of ultrasonography difficulties regarding unexpected differential diagnoses of NBC as well as tumour localisation in seborrhoeic areas.

Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group.

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.

Quality of life and side effects in patients with actinic keratosis treated with ingenol mebutate: a pilot study.

INTRODUCTION: Actinic keratosis (AK) lesions are in situ squamous cell carcinoma. These lesions have a low risk of progressing to invasive disease but significant impact on patients' quality of life (QoL). The aim of this study was to assess QoL and side effects in patients with AK receiving treatment with ingenol mebutate. MATERIAL AND METHODS: This was a prospective, non-randomized pilot study carried out in Spain. The target population was adults with a clinical diagnosis of AK affecting any part of the body. Outcomes were assessed on the basis of a QoL questionnaire (Skindex-29), local skin response, the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), and clinical response. RESULTS: A total of 19 patients were studied. Most of the participants were men (89.5%) and mean age was 76.2 years. After treatment with ingenol mebutate, significant improvement was observed in the Skindex-29 subscales relating to symptom severity (P=.041), the patients' emotional state (P=.026), and in the overall score (P=.014). Erythema, crusting, and flaking or scaling were the local skin responses with highest median score (2.0 in all 3 cases). Imiquimod 5% and ingenol mebutate achieved higher median scores for effectiveness and global satisfaction than any other previous treatments (as measured by TSQM 1.4). In the patients' assessment of convenience, ingenol mebutate had a higher median score than previous treatments. Over half of the patients (52.6%) had an improvement of at least 75% at month 3. CONCLUSIONS: QoL in patients with AK improves after treatment with ingenol mebutate. The presence of side effects did not affect QoL or patient satisfaction with treatment.

[Fungal infections and ureteral material: How to manage?]. / Infections fongiques et matériel urétéral: quelle prise en charge?

INTRODUCTION: Urinary tract infections due to Candida species are mostly encountered in hospital environment. The management of candiduria on ureteral catheter is not consensual. The objective of our work was to make a review of medical literature related to definition, physiopathology, management and prevention of candiduria on ureteral catheter. MATERIAL AND METHODS: The research was made on Medline using the following keywords: Candida; fungal; urinary tract infection; ureteral stent; ureteric stent; double-J pigtail. RESULTS: The threshold defining candiduria is 10(5) CFU/mL. Candiduria corresponds to many different clinical presentations from colonization to candidemia. Species found are mostly Candida albicans (19-72%) and Candida glabrata (15.6-49.4%). The colonization of ureteral stent due to Candida is of 10% and comes with candiduria in 40% of the cases, due to the presence of biofilm. Prevention of infections on ureteral stents requires a regular change of material every 3-6 months depending on the patients risk groups. In case of symptomatic candiduria on ureteral stent, an anti-fungal therapy should be initiated 48 hours to 3 weeks before the change of the stent, in order to get a sterilization of urines and prevent the recolonization of the stent. Fluconazole is the drug of choice to use. CONCLUSION: Colonization of ureteral stents due to Candida is common and can be responsible of symptomatic infection. Anti-fungal therapy should be introduced before the change of the stent but a consensual duration of treatment before surgery is not found in the literature.

[Treatment of angiolymphoid hyperplasia with eosinophilia (ALHE) using topical tacrolimus: Two cases]. / Traitement de l'hyperplasie angiolymphoïde avec éosinophilie (HALE) par le tacrolimus topique : deux observations.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease, currently considered a benign vascular proliferation of unknown etiology, and whose treatment is still unclear and challenging. PATIENTS AND METHODS: Two women in their thirties consulted for itchy lesions of the right ear. Both presented with a reddish bleeding papulonodular infiltration of the auricle, with a nodule at the entrance to the external auditory canal in the first patient. Laboratory tests showed no abnormalities and in particular no hypereosinophilia or elevated serum immunoglobulin E. In both cases, histology of lesional skin showed vascular proliferation with thick-walled vessels lined by plump endothelial cells, protruding into the lumen, together with a mixed dermal inflammatory infiltrate consisting primarily of eosinophils and lymphocytes. A diagnosis of ALHE was made in both patients based on clinical and histological features. MRA revealed no underlying vascular malformation in both cases. Patients started treatment with 0.1% tacrolimus ointment twice daily. The pruritic sensation and bleeding had completely subsided within two weeks and the reddish infiltration and nodules had practically disappeared after two months of topical tacrolimus. Continuous application resulted in no recurrence at 6 months of follow-up. DISCUSSION: Treatment of ALHE is still poorly standardized due to doubts concerning the pathophysiology of this rare condition and the small number of available studies. Topical tacrolimus was originally developed for the treatment of moderate to severe atopic dermatitis because of its anti-inflammatory and immunomodulatory properties. Recent studies suggest that this drug may be effective in treating other forms of inflammatory dermatosis. Our two observations suggest that tacrolimus ointment also represents potentially valuable treatment in AHLE.

[Aquagenic palmar keratoderma in a patient heterozygous for the mutation c.3197G>C in the CFTR gene]. / Kératodermie aquagénique palmaire chez une patiente hétérozygote pour la mutation c.3197G>C du gène CFTR.

BACKGROUND: Aquagenic palmar keratoderma is an entity recently described in the literature by English and McCollough in 1996. It is a rare condition affecting young women and is of unknown incidence. It causes a wrinkled and oedematous appearance in the skin of the hands that may be seen a few minutes after immersion in water. This condition may be associated with a heterozygous mutation in CFTR, the gene involved in cystic fibrosis. We report the first case of aquagenic keratoderma associated with a new mutation in the CFTR gene. PATIENTS AND METHODS: An 18-year-old patient with no particular history was referred for a painful rash on both palms occurring whenever she showered, and which had been ongoing for several months. The clinical examination was normal except for an appearance of moderate palmar hyperhidrosis. Following a test in which both hands were immersed in cold water for 5minutes, the patient presented itching, burning and pain localized to the hands. The palms were wrinkled and oedematous with white, translucent and confluent papules. A clinical diagnosis of aquagenic palmar keratoderma was made. Since this condition may be associated with mutations in the CFTR gene, a genetic study was performed for this patient and revealed the presence of a new mutation in the CFTR gene for cystic fibrosis in the heterozygous state inherited from her mother: c.3197G>C or p.Arg1066.Pro and a heterozygous polypyrimidic 5T variant inherited from her father. DISCUSSION: We report a new case of aquagenic palmar keratoderma in a patient heterozygous for a new mutation of the gene involved in cystic fibrosis. Several studies have shown association of aquagenic keratoderma with the CFTR gene for heterozygotes (carriers without cystic fibrosis), for patients with cystic fibrosis and for a patient presenting CFTRopathy with pancreatic insufficiency.

[Hypocomplementaemic urticarial vasculitis with bullous lesions and pericardial involvement]. / Vascularite urticarienne hypocomplémentémique avec lésions bulleuses et péricardite spécifique.

BACKGROUND: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare disease involving urticarial cutaneous vasculitis, hypocomplementaemia and systemic manifestations. Pericardial involvement occurs in very rare cases. We report a case of HUVS associated with specific pericarditis and bullous lesions. PATIENTS AND METHODS: A 63-year-old woman consulted for chronic urticaria that had appeared ten months earlier. Her skin lesions were associated with weight loss of 10 kg, deterioration of respiratory function and abdominal pain. Leukocytoclastic vasculitis was seen in the skin biopsy sample. Hypocomplementaemia and anti C1q antibodies were present and a diagnosis of HUVS was made. During hospitalisation, extensive compressive pericardial effusion was identified, and histological examination of the biopsy revealed specific pericardial lymphocytic vasculitis. During follow-up, four episodes of infectious pneumonitis were noted. Bullous skin lesions were also observed. DISCUSSION: HUVS is a disease caused by an antibody against C1q complement responsible for urticarial lesions and vasculitis antibodies. To our knowledge, there have been only five reports in the literature of pericardial injury associated with HUVS. In our case, histological examination of the pericardium demonstrated lymphocytic vasculitis.

Cutaneous melanoma in patients treated with tumour necrosis factor inhibitors: a retrospective series of 15 patients.

BACKGROUND: Several case reports suggested that tumour necrosis factor-α (TNF) inhibitors might increase the incidence and/or alter the natural course of melanoma towards a more aggressive behaviour. OBJECTIVE: Our objective was to point if history of melanoma in patients exposed to TNF inhibitors could present with a particular pattern at diagnosis or during follow-up. METHODS: We performed a retrospective multicentre study settled in the West part of France to collect and analyse all cases of patients with melanoma who received anti-TNF therapy. RESULTS: Fifteen cases were included. First, 10 patients (mean age: 55.6 years; sex ratio: 1) had a melanoma diagnosed after TNF inhibitors initiation. The mean duration between initiation of treatment and melanoma was 48.7 months. Two patients died of metastatic disease. Second, four patients had a past history of melanoma before anti-TNF therapy (mean duration of treatment: 10.8 months). None experienced a progression of melanoma disease. Last, one woman had a past history of melanoma before and then developed a second melanoma when exposed to biotherapy. CONCLUSION: Our case series does not reveal a distinct profile of melanoma in the patients exposed to TNF inhibitors. Additional prospective trials including larger number of patient are needed to demonstrate the possible link between biological therapy with TNF inhibitors and development of melanoma.

Evaluation of risk factors for body weight increment in psoriatic patients on infliximab: a multicentre, cross-sectional study.

BACKGROUND: A significant weight gain has been reported in patients with psoriasis treated with anti-tumour necrosis factor-alpha agents. Among these patients, there are contradictory results about risk factors for weight gain. OBJECTIVE: Assessing risk factors for weight increment in psoriatic patients on infliximab (IFX). METHODS: This study was a 4-month, non-interventional, cross-sectional, multicentre study on adults with psoriasis performed in 19 French dermatological centres. All the patients who received IFX for at least 1 year were prospectively included, with retrospective analysis of data. Impact of sex, age, severity of the disease, cardiovascular and metabolic comorbidities, and previous and simultaneous systemic treatments on weight changes, was analysed. Weight gain was defined as an increment of more than 2% of baseline weight. RESULTS: Overall, 191 psoriatic patients (males: 68.6%; mean age: 46.9 years) were included. Mean weight gain was 1.6 kg (2.1%) after 1 year of IFX. Half (48.2%) suffered from a weight gain, and 9.9% from a weight increment of 10% or more. Baseline weight and Body Mass Index, and cardiovascular and metabolic comorbidities did not influence weight. Men (P=0.007) and patients with severe psoriasis (BSA, P=0.005) had a tendency to put on weight. Patients with a hospital dietary follow-up (P=0.01; OR=0.36 [0.16-0.79]) and patients on methotrexate (P=0.03; OR=0.41 [0.18-0.93]) during IFX treatment are thinner, in a multivariate analysis. CONCLUSION: Severe weight increment is frequent on IFX treatment, mainly in men, and patients with severe psoriasis. Dietary follow-up or simultaneous use of methotrexate could limit this weight increment.

Childhood-onset psoriasis: association with future cardiovascular and metabolic comorbidities.

BACKGROUND: Psoriasis is associated with higher prevalences of cardiovascular and metabolic comorbidities in adults but the relationship of age at onset and those prevalences is unknown. OBJECTIVE: To evaluate whether the childhood onset of psoriasis (COP) is correlated with the frequency of cardiovascular and metabolic comorbidities in adulthood. METHODS: This noninterventional, cross-sectional, multicentre study of adults with psoriasis was conducted in 29 dermatology centres in France. Data on sex, age at onset of psoriasis and its clinical characteristics, and cardiovascular risk factors, including weight, body mass index, waist circumference, dyslipidaemia, diabetes, hypertension, smoking, and personal/familial major adverse cardiovascular events (MACE) were systematically recorded. RESULTS: Two thousand two hundred and one patients with psoriasis (male: 56%; mean age: 49 years; 25% with COP) were included consecutively in the study. Univariate analysis showed that COP was associated with lower frequencies of obesity, high waist circumference, diabetes, dyslipidaemia, hypertension, familial cardiovascular disease, MACE and metabolic syndrome, but more frequent active smoking. Multivariate analysis retained age as being associated with frequency of cardiovascular and metabolic comorbidities, and sex with smoking, but not age at the onset of psoriasis. Psoriasis severity was associated with higher frequencies of obesity and psoriatic arthritis. CONCLUSION: Our results showed that COP does not seem to be an additional risk factor for higher frequencies of cardiovascular and metabolic comorbidities during adulthood.

[Atypical eruptive collagenoma: two cases]. / Collagénomes éruptifs atypiques: deux cas.

BACKGROUND: Eruptive collagenoma is a rare cutaneous lesion seen in young adults. It consists of asymptomatic, flesh-coloured papules that are usually localised on the trunk and the root of the upper limbs. Herein we report two cases on account of the atypical topography of the lesions and the advanced age of the patients. CASE REPORTS: Case n 1: a 69-year-old man consulted for firm, whitish papules on the wrists, elbows, popliteal fossae and groin without associated signs, and which first appeared several years earlier. The standard laboratory assessment and ocular fundus test were normal. Case no 2: a 69-year-old woman had very firm, flesh-coloured papules on the trunk and the root of the limbs, which appeared after the age of 40. The results of ocular fundus, cardiovascular investigation and laboratory examinations were normal. The histology of papules was similar in both cases and revealed a nodular zone in the reticular dermis, comprising disorganized collagen bundles and excessive quantities of elastic fibres, without elastorrhexis. This histology was consistent with collagenoma. DISCUSSION: We report two singular cases that were atypical in terms of patient age and localisation in the flexion folds. Histological analysis of a papule enables a diagnosis of collagenoma to be made. Such analysis usually reveals a hamartoma in which the amount of collagen is increased, with variable quantities of elastic tissue, though often decreased. The principal differential diagnoses are elastoma and pseudoxanthoma elasticum.

Adjuvant prophylactic regional radiotherapy versus observation in stage I Merkel cell carcinoma: a multicentric prospective randomized study.

BACKGROUND: The treatment of stage I Merkel cell carcinoma (MCC) usually includes wide local excision (WLE) combined with irradiation of the tumor bed (ITB). No randomized study has ever been conducted in MCC. The purpose of this study was to assess the efficacy and safety of prophylactic adjuvant radiotherapy on the regional nodes. PATIENTS AND METHODS: In this randomized open controlled study, patients for a stage I MCC treated by WLE and ITB were randomly assigned to regional adjuvant radiotherapy versus observation. Overall survival (OS) and probability of regional recurrence (PRR) were primary end points. Progression-free survival (PFS) and tolerance of irradiation were secondary end points. RESULTS: Eighty-three patients were included before premature interruption of the trial, due to a drop in the recruitment mainly due to the introduction of the sentinel node dissection in the management of MCC. No significant improvement in OS (P = 0.989) or PFS (P = 0.4) could be demonstrated after regional irradiation, which, however, significantly reduced the PRR (P = 0.007) with 16.7% regional recurrence rate in the observation arm versus 0% in the treatment arm. The treatment was well tolerated. CONCLUSION: The adjuvant regional irradiation significantly decreased the PRR in MCC, but benefit in survival could not be demonstrated.

APOA5 gene expression in the human intestinal tissue and its response to in vitro exposure to fatty acid and fibrate.

BACKGROUND AND AIMS: APOA5, a key gene regulating triglyceride (TG) levels, is reported to be expressed exclusively in the liver where it may regulate TG-rich particle synthesis and secretion. Since the same lipoprotein processing occurs in the intestine, we have postulated that this organ would also express APOA5. METHODS AND RESULTS: We have detected the APOA5 gene expression in C57BL/6J mouse and in human small intestine samples. In humans, it is expressed mainly in the duodenum and colon, with messenger RNA (mRNA) levels four orders of magnitude lower than in the liver, and the protein product being one-sixth of the liver equivalent. Subsequently, we carried out in vitro experiments in TC-7/CaCo(2) human intestinal cells to analyse the expression of APOA5, APOC3, APOB and MTP genes after the incubation with long- and short-chain fatty acids, and a peroxisome proliferator-activated receptor alpha (PPARα) agonist (Wy 14643, a fibrate therapeutic agent). In the TC-7 cell line, APOA5 expression was significantly upregulated by saturated fatty acids. The short-chain fatty acid butyrate increased APOA5 expression almost fourfold while APOB was downregulated by increasing butyrate concentrations. When TC-7 cells were incubated with PPARα agonist, the APOA5 expression was increased by 60%, while the expression of APOB, MTP and APOC3 was decreased by 50%, 30% and 45%, respectively. CONCLUSION: Our results demonstrate that APOA5 is expressed in the intestine, albeit at a much lower concentration than in the liver. While it remains to be determined whether intestinal apo A-V is functional, our in vitro experiments show that its expression is modifiable by dietary and pharmacological stimuli.

[Original treatment of constitutional painful callosities by surgical excision, collagen/elastin matrix (MatriDerm(®)) and split thickness skin graft secured by negative wound therapy]. / Traitement original des callosités plantaires douloureuses constitutionnelles par exérèse, matrice de collagène et d'élastine (MatriDerm(®)) et greffe de peau mince en un temps, associée à une thérapie par pression négative.

Constitutional painful callosities is an unusual pathology, integrated in the frame of "palmoplantar keratodermia" (PPK). Lesions are located at areas of support of the sole. These lesions are painful and disable the normal walking. Treatments are suspensive and painkillers. We report our experience of a single surgical treatment: surgical excision, split thickness skin graft applied on a dermal substitute and secured by negative wound therapy. A 28-year-old patient, affected by this disease, has a desire of pregnancy but her treatment is highly teratogen. A year post-op, wounds were healed. The walk was possible with a relief of the pain, without any ulcerations. The surgical treatment by excision and graft or flaps was previously reported for PPK. The use of dermal substitute was never described for this indication. Dermal substitute compensate the thickness of the soft tissue defect and give an accurate quality of elasticity in this localisation .The negative wound therapy enhances the quality and shortens the length of graft taking, and the adhesion of the dermal substitute on his bed.