Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study.

BACKGROUND: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS). METHODS: In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed. RESULTS: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%). CONCLUSION: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov reference NCT00563953.

The place of Surgical Schools: Their role in training surgeons.

Surgical Schools have appeared on university campuses as technical learning platforms only fairly recently. They define and assess progressive educational programs in each of the specialties. The students must learn both technical and non-technical acts. The teaching is intended primarily for students during their initial training but also can serve for continuing education in the context of learning new techniques. These technical platforms are expensive, and consideration must be given to pooling of resources at the regional or national levels for the most sophisticated among them. The teaching is carried out with a set of synthetic or organic simulators. In accordance with European regulations, the use of animal models should be kept to a minimum. The use of human anatomical specimens is very useful for certain specialties and justifies the participation of anatomy and pathology laboratories in the training of young surgeons. Certification of these technical simulation platforms should be obtained. Funding for initial surgical training on these high-tech platforms has yet to be resolved.

Dietary methionine deficiency reduces laying performances of female common ducks and impacts traits of interest of their mule ducklings.

The effects of maternal nutrition on offspring phenotypes have been mainly documented over the past years in mammals, and are now studied in poultry as well. In the present study, we investigated the effects of a reduced level of dietary Methionine (Met) on laying performances of common laying ducks and their impacts on the phenotype of their mule ducklings. A total of 60 female laying ducks were divided into 2 dietary treatments at 10 wk of age. The restricted group received Met-restricted diets (R group) containing 0.25% of Met whereas the control group received control diets (C group) containing 0.40% of Met that meets Met requirements. The restriction was applied during the growing and laying periods, from 10 to 51 wk of age and a particular focus was put on female breeder traits that might be affected by the Met restriction. Plasma parameters of hepatic and lipid metabolisms were recorded in ducklings. Total weight (P < 0.001), albumen weight (P < 0.001) and albumen percentage of dry matter (P < 0.01) were decreased for eggs laid by female breeders from the R group. Both male and female ducklings from the R group of female breeders showed a reduced BW at hatching (P < 0.001) and a tendency to an increased proportional liver weight (P = 0.07). Finally, the maternal low dietary Met level modified plasma parameters in newborn ducklings regardless of sex: alkaline phosphatase (ALP) and alanine transaminase (ALT) activities were reduced (P = 0.07 and P = 0.002, respectively), levels of glucose (P = 0.03) and triglycerides (P = 0.01) were higher whereas level of free fatty acids decreased (P = 0.01). It was concluded that feeding female laying ducks with a restricted dietary Met content during the growing and laying periods has a negative effect on egg weight and composition. The ducklings that were restricted in nutrients during their early development, have a reduced BW, and altered lipid and hepatic metabolisms.

Do teenagers return to normal physical activity levels after limb fractures? A longitudinal, accelerometry-based, activity monitoring study.

PURPOSE: This study aimed to elucidate whether levels of physical activity (PA) return to normal after bone healing or whether long-term behavioural changes in PA are to be expected in children and teenagers who have sustained limb fractures. METHODS: In all, 100 children and teenagers with a first episode of limb fracture and 100 sex- and age-matched healthy controls (CTRL) were recruited for a prospective study. PA in limb fracture patients was assessed at 18-month follow-up using accelerometer measurements, and values were compared with those of CTRL. Time spent in PA at different levels of intensity was determined for each participant and expressed in minutes and as a percentage of total validly measured time. RESULTS: Mean levels of PA at different levels of intensity by previously injured children and teenagers were similar than CTRL (42 sets of paired data). However, time spent in moderate-to-vigorous PA (MVPA) was lower than 60 minutes among limb-fracture patients at 18-month follow-up. CONCLUSION: The amount of skeletal loading in children and teenagers returns to normal values by 18 months after limb fracture. Even if time spent in MVPA is not significantly lower in children and teenagers with limb fractures, it no longer reached the international recommendations for school-aged children (MVPA > 60 minutes), which may be interpreted as a lifestyle modification or a behavioural change to avoid new trauma. LEVEL OF EVIDENCE: II.

Sarcoma de Kaposi palpebral bilateral en un paciente virus de la inmunodeficiencia humana negativo / Bilateral eyelid Kaposi's sarcoma in an HIV-negative patient

CASO CLÍNICO: Un varón de 70 años, procedente de Sicilia, acude con una masa palpebral bilateral con afectación tarsal conjuntival, que resultó ser un sarcoma de Kaposi al examen histológico. Se demostró afectación cutánea y pulmonar por el sarcoma de Kaposi. El paciente no tenía un diagnóstico previo de infección por el virus de la inmunodeficiencia humana. Este caso fue tratado con éxito tras 5 ciclos de quimioterapia con doxorrubicina liposomal, con resolución de las lesiones palpebrales, cutáneas y pulmonares. Conclusiones: La localización en el párpado es una posible manifestación inicial, aunque rara, del sarcoma de Kaposi en personas de edad avanzada negativos para el virus de la inmunodeficiencia humana. La doxorrubicina liposomal es un tratamiento seguro y efectivo

CASE REPORT: We report a case of 70-year-old male from Sicily, who presented with a bilateral eyelid mass involving the tarsal conjunctiva, found to be Kaposi's sarcoma on histologic examination. Cutaneous and pulmonary Kaposi's sarcoma involvement was documented. The patient had no prior diagnosis of human immunodeficiency virus infection. This case was managed successfully after the completion of five cycles of chemotherapy with liposomal doxorubicin, and his eyelid, skin and pulmonary lesions disappeared. CONCLUSIONS: Location in the eyelid is a possible, though rare, initial solitary manifestation of Kaposi's sarcoma in elderly HIV-negative patients. Liposomal doxorubicin is a safe and effective treatment

Bilateral eyelid Kaposi's sarcoma in an HIV-negative patient. / Sarcoma de Kaposi palpebral bilateral en un paciente virus de la inmunodeficiencia humana negativo.

CASE REPORT: We report a case of 70-year-old male from Sicily, who presented with a bilateral eyelid mass involving the tarsal conjunctiva, found to be Kaposi's sarcoma on histologic examination. Cutaneous and pulmonary Kaposi's sarcoma involvement was documented. The patient had no prior diagnosis of human immunodeficiency virus infection. This case was managed successfully after the completion of five cycles of chemotherapy with liposomal doxorubicin, and his eyelid, skin and pulmonary lesions disappeared. CONCLUSIONS: Location in the eyelid is a possible, though rare, initial solitary manifestation of Kaposi's sarcoma in elderly HIV-negative patients. Liposomal doxorubicin is a safe and effective treatment.

Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii, which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1ß (IL-1ß) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls (P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients (P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT (P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1ß gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT (P = 0.0494). The IL-10, IFN-γ, and IL-1ß polymorphisms influence the development of OT in the Colombian population.

Knowledge, attitudes, representations and declared practices of nurses and physicians about obesity in a university hospital: training is essential.

In the context of a worldwide obesity epidemic, healthcare providers play a key role in obesity management. Knowledge of current guidelines and attitudes to prevent stigmatization are especially important. This study aimed to assess knowledge, attitudes, beliefs, perception of opportunity for intervention, declared practices and need for training and material of nurses and physicians about obesity in a Swiss University Hospital. A total of 834 physicians and nurses filled an online survey. The questionnaire was based on literature, exploratory interviews and expert committee review. It was pre-tested with 15 physicians and nurses. Participants declared a low level of negative attitudes towards individuals living with obesity. However, the results highlighted a lack of knowledge to diagnose obesity in adults and children, as well as confidence and training to care of patients with obesity. One-third of providers did not know how to calculate body mass index. Half of providers felt it was part of their role to take care of patients with obesity, even if 55% of them had the feeling that they did not have adequate training. Nurses and physicians working in a university hospital showed a low level of negative attitudes but a lack of knowledge and skills on obesity management. Training should be improved in this population to insure adequate and coherent messages and equal access to evidence-based treatment for patients living with obesity.

Dysexecutive syndrome in amnesic mild cognitive impairment: a multicenter study.

BACKGROUND: Executive functions (EF) in Alzheimer's disease (AD), classically related to the prefrontal cortex, have been forgotten in mild stages, given more importance to temporal lobe associated disorders, such as memory. The study of disexecutive syndrome (DS) has been relegated to advanced stages of the disease. Our goal is to demonstrate that EF are already present in amnesic mild cognitive impairment (aMCI). Furthermore, we are interested in knowing whether poor scores in EF tests are related to the progression to AD or another kind of dementia. METHODS: We studied patients with aMCI (n = 81) and healthy controls (n = 142) from neurological departments of several centers of Basque Country with a cross-sectional design. Patients underwent a complete neuropsychological evaluation, neuroimaging testing APOE genotype and 3 year of prospective follow-up. RESULTS: In the first visit, patients with aMCI showed more alterations in tests that evaluate EF such as Stroop, trail-making and categorical verbal fluency. More alterations were also found in NPI scale (P <0.05). Stroop and Trail-Making test were not associated with the future development of AD, but fluency (p = 0.01) and apathy (p = 0.031) did. No patient developed a different kind of dementia different from AD. CONCLUSIONS: DS is a broad concept not confined to frontal lobes, and can be found in early stages of aMCI. DS impacts negatively on patient autonomy and may have prognostic value.

[The W-shaped ileal neobladder: Long term functional outcomes and health-related quality of life]. / La néovessie iléale en W : résultats fonctionnels et qualité de vie à long terme.

PURPOSE: To evaluate functional outcomes and patients' health-related quality of life over ten years after a W-shaped ileal neobladder urinary diversion. PATIENTS AND METHODS: From 1994 to 2004, 87 patients with bladder cancer underwent a cystoprostatectomy with a W-shaped ileal neobladder. Among them, 31 patients (35.6%) were evaluated. The average follow-up was 158months, average age was 72years. We assessed functional outcomes (use of protections, USP score, uroflowmetry, postvoid residual volume), overall health-related quality of life (SF-36 score), and specific urinary-related quality of life (Ditrovie scale). RESULTS: Daytime continence was satisfactory in 29 patients (96.8%). Night-time continence was satisfactory in 27 patients (87.1%). Mean daytime continence, hyperactivity and dysuria scores of the USP were respectively 1.5/9, 3.2/21 and 2/9. Mean value of the maximum flow rate was 18mL/s for an average voiding volume of 324mL and an average postvoid residual volume of 70mL. The 8 dimensions of the SF-36 were all comparable with the French population's values. According to the Ditrovie scale whose average value was 1.83, the health-related quality of life was unchanged or little changed by urinary disorders in 28 patients (90.3%). CONCLUSIONS: Our results suggest that voiding status and health-related quality of life remain satisfactory over ten years after an orthotopic ileal neobladder derivation. LEVEL OF EVIDENCE: 5.

Effects of oil and oil burn residues on seabird feathers.

It is well known, that in case of oil spill, seabirds are among the groups of animals most vulnerable. Even small amounts of oil can have lethal effects by destroying the waterproofing of their plumage, leading to loss of insulation and buoyancy. In the Arctic these impacts are intensified. To protect seabirds, a rapid removal of oil is crucial and in situ burning could be an efficient method. In the present work exposure effects of oil and burn residue in different doses was studied on seabird feathers from legally hunted Common eider (Somateria mollissima) by examining changes in total weight of the feather and damages on the microstructure (Amalgamation Index) of the feathers before and after exposure. The results of the experiments indicate that burn residues from in situ burning of an oil spill have similar or larger fouling and damaging effects on seabird feathers, as compared to fresh oil.

[Cryotherapy percutaneous for renal tumors: Our center's beginning experience]. / Cryothérapie pour les tumeurs rénales: le début d'expérience de notre centre.

OBJECTIVE: To evaluate oncologic and functional outcomes after percutaneous cryoablation (PCA) for renal masses based on our single center experience. PATIENTS AND METHODS: We retrospectively identified 26 patients who underwent PCA for 28 tumors between November 2006 and June 2011. Patient's demographics and baseline clinical characteristics, tumor features, perioperative information, and postoperative outcomes we rerecorded. A biopsy was performed systematically before each procedure. Control imaging was obtained at 1, 3, 6 and 12 months, and yearly thereafter. Oncological outcomes were determined by radiographic evidence of tumor recurrence, which was defined by contrast enhancement at the cryoablation site on control imaging at M3. RESULTS: Patients had mean age of 70.1 years, mean Charlson comorbidity index (CCI) and body mass index) were 6 and 29 kg/m(2) respectively. There were 11 kidney transplants, including 4 solitary. Mean tumor size was 29.5mm and was represented mainly by clear cell renal cell carcinomas (16/28), endophytic (17/28) and midkidney (14/28) (±9.8). Twenty-five cryoablations were performed percutaneously by two lumbotomy. Mean clearance preoperative MDRD was 66,1 mL/min. Mean length of stay was 3.3 days (±2.2). Intraoperative complications consisted of 2 pneumothorax and 6 minor complications postoperative (Clavien≤2). There were no major complications. Mean follow-up was 27.5 months (±15.7), MDRD clearance distance was 61.9 mL/min. Overall survival and disease-specific survival was 100%, while the recurrence-free survival was 78.6% (5 recurrences and 1 failure treatment). CONCLUSION: The percutaneous cryoablation provides a safe and oncologically to extirpative surgery for renal masses in patients with significant medical comorbidities. LEVEL OF EVIDENCE: 5.

[Urological complications after kidney transplantation from extended criteria donors: Ureteroneocystostomy versus pyelo-ureterostomy]. / Complications urologiques après transplantation de reins issus de donneurs à critères étendus : anastomoses urétéro-vésicales versus anastomoses pyélo-urétérales.

INTRODUCTION: The use of transplants from extended criteria donors increases the number of urological complications after renal transplantation. Two different anastomosis techniques used to restore urinary continuity are compared in this study. PATIENTS AND METHODS: Retrospective study, bi-center over a period of 5 years. One hundred and seventy six patients operated at Hospices Civils de Lyon benefited from ureteroneocystostomy according to De Campos-Freire (group 1) and 167 patients operated at the Necker Hospital in Paris had a pyelo-ureterostomy (group 2). The various urological complications (fistulas, strictures, seromas, haematomas and vesico-ureteric reflux) and their care were compared. Risk factors were sought. RESULTS: The waiting time before transplantation was longer in group 2 than in group 1 (51 and 33.84 months) as the percentage of anuric patients (52.9 % against 32.9 %) (P<0.001). The cold ischemic time was shorter in group 1 (939.3minutes on average against 1325.3minutes for group 2) (P<0.001). A double J stent was put in place in 97.6 % of cases in group 2 against 84.2 % for group 1 (P<0.001). We did not find any significant difference in the occurrence of stenosis and fistulas (major complications) between the 2 groups. There were more minor complications (hematoma, seroma and vesico-ureteric reflux) in group 1 (P=0.033). There was a difference in the treatment of these complications, especially stenosis (P=0.024) with a significantly more conservative approach in group 2. Multivariate analysis found anuria, sex of recipients and donor age as independent risk factors in the onset of complications and the double J stent as a protective factor. CONCLUSION: This study does not demonstrate the superiority of a urinary anastomosis technique. The establishment of a double J stent reduces the risk of complications. Analysis of risk factors allows to propose a decision tree to guide the surgical strategy, particularly in the population of anuric recipients. LEVEL OF EVIDENCE: 5.

[Effectiveness of flexible ureteroscopy versus extracorporeal shock wave lithotripsy for kidney stones treatment]. / Efficacité de l'urétéroscopie souple versus lithotritie extracorporelle dans le traitement des calculs du rein.

Primary endpoint was to objective a better effectiveness of flexible ureteroscopy (fURS) compared to extracorporeal shock wave lithotripsy (ESWL) 3 months after treatment of a unique kidney stone from 5 to 20mm. Secondary endpoints were to evaluate effectiveness in subgroup and tolerance. We conducted a prospective comparative randomised trial between May 2012 and February 2014. A computerised tomography was done before treatment and another 3 months after treatment. Of the 30 randomised patients, 8 dropped out from the study and 4 were lost to follow-up. Median time of follow-up was 3.82 months. In per-protocol analysis, success rate was 60% for fURS group versus 28.6% for ESWL group (P=0.29). In intention to treat analysis, success rate was 77.8% in fURS group versus 53.8% in ESWL group (P=0.38). In ESWL group, 5 patients (41.7%) needed a second treatment versus none in fURS group but it was not significant. During follow-up, 1 patient in each group presented a complication. Results of this feasibility study did not allowed to conclude on superiority of a technic. A multicenter study with more important enrollment is necessary considering economic side and tolerance of these treatments.

[Impact of neoadjuvant chemotherapy on therapeutic management of muscle-invasive bladder cancer]. / Impact de la chimiothérapie néoadjuvante sur la prise en charge des tumeurs de vessie infiltrant le muscle.

OBJECTIVE: Assess the toxicity of neoadjuvant chemotherapy (NAC), its impact on surgical schedule and postoperative morbidity of cystectomy for muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Retrospective multicentric study of 78 patients who underwent a cystectomy from January 2009 to March 2012 for MIBC. The following criteria have been studied: toxicity of NC (WHO classification), precystectomy interval, postoperative morbidity (Clavien), duration of stay, downsizing on CT-scan before cystectomy, and free of cancer pathology (pT0). RESULTS: Seventy-eight patients had been included, thirty-nine had a NAC. Thirty-three percent had a incomplete chemotherapy because of toxicity. Forty-eight percent had a significant toxicity and grade ≥ 3 toxicity was 33%. Median time between diagnosis and cystectomy was 12.6 weeks (0.7-38), 18 weeks with NAC (group 1) versus eight weeks without NAC (group 2) (P=0.01). In case of toxicity, the delay was 3.5 weeks longer (P=0.12). After cystectomy, 60% of patients had at least one postoperative complication; including 23% had major morbidity. NAC did not increase neither postoperative morbidity (P=0.15) nor duration of stay (18 vs 20 days; P=0.2). Radiological response rate to NC was 38%. pT0 rate was 79 vs 7.7%. The increase of precystectomy interval after NC did not worsen the pathological stage (P=0.5). CONCLUSION: NC had a high toxicity, but without impact on postoperative morbidity, and precystectomy interval did not have any impact on the prognosis. LEVEL OF EVIDENCE: 5.

[Management of rectourethral fistulas with the York Mason procedure: surgical techniques and outcomes]. / Traitement des fistules uréthro-rectales par voie trans-anorectale de York Mason: technique et résultats.

OBJECTIVE: To report our experience for the management of urethro-rectal fistula by the York Mason technique. PATIENTS AND METHODS: We retrospectively analyzed the data of patients treated surgically for FUR by the technique of York Mason, between 2000 and 2012. RESULTS: Seventeen patients were included in the study. All patients had a bowel diversion before surgery. We observed four recurrences of FUR (23.5%). Recurrences occurred in a radiation field for two patients and in a oncologic recurrence for 1 patient. The fourth recurrence was treated by a second procedure of York Mason successfully. CONCLUSION: In our study, the York Mason technique was safe and reproducible for the treatment of FUR. The main factor of failure was a history of pelvic radiotherapy.