[French ccAFU guidelines - update 2020-2022: prostate cancer]. / Recommandations françaises du Comité de cancérologie de l'AFU ­ actualisation 2020­2022 : cancer de la prostate.

OBJECTIVE: - The purpose of the guidelines national committee ccAFU was to propose updated french guidelines for prostate cancer. METHODS: - A Medline search was achieved between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of prostate cancer (PCA), and to evaluate the different references specifying their levels of evidence. RESULTS: - The guidelines outline the genetics, epidemiology and diagnosis of prostate cancer, as well as the concepts of screening and early detection. MRI, the gold standard imaging test for localized cancer, is indicated before prostate biopsies are performed. The therapeutic methods are detailed and indicated according to the clinical situation. Active surveillance is a reference therapeutic option for low-risk tumours with a low evolutionary risk. Early salvage radiotherapy is indicated in case of biological recurrence after radical prostatectomy. Androgen deprivation therapy (ADT) remains the backbone therapy in the metastatic stage. Docetaxel in combination with ADT improves overall first-line survival in synchronous metastatic prostate cancer. In this situation, the combination of ADT with abiraterone is also a standard of care regardless of tumor volume. Recent data indicate that ADT should be indicated with a new generation of hormone therapy (Apalutamide or Enzalutamide) in metastatic synchronous or metachronous patients, regardless of tumour volume. Local treatment of prostate cancer with radiotherapy improves survival in synchronous oligometastatic patients. Targeted treatment of metastases is being evaluated. In patients with castration-resistant prostate cancer (CRPC), new therapies that have emerged in recent years help to better control tumor progression and improve survival. CONCLUSION: - These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.

[Comparison of the prognostic value of different clinical, angiographic and scintigraphic scores in stable coronary patients after acute coronary syndrome]. / Étude et comparaison de la valeur pronostique de différents scores clinique, coronarographique et scintigraphique chez le patient coronarien stable après un syndrome coronarien aigu.

INTRODUCTION: To date, there is no consensus regarding the follow-up of asymptomatic coronary patients with an intermediate risk of events. Indeed, most of cardiovascular events (CVE) occur in asymptomatic patients, hence the clinician's interest in establishing risk stratification scores. In asymptomatic patient, the risk assessment after acute coronary syndrome (ACS) can currently be based on 3 types of score: clinical with, for example, the REACH score; angiographic with the residual SYNTAX score; imaging with different scintigraphic scores. These scores differ widely in terms of evaluation criteria and period of analysis. The aim of our study was therefore, in stable and asymptomatic coronary patients after ACS, to compare these different predictive scores; to establish that the combination of these scores makes it possible to optimize the risk assessment during the follow-up. METHODS: Our retrospective study included 236 revascularized patients after ACS. Three different risk scores were collected: 1) the residual SYNTAX score, calculated at the time of revascularization; 2) the scintigraphic risk score described by Sharir et al., performed 3 to 12 months after the event and taking into account the extent of ischemia (SDS) and the poststress left ventricular ejection fraction (LVEF). Patients with LVEF <50% and/or moderate to severe ischemic disease (SDS≥2) were considered with an intermediate or high scintigraphic risk; 3) the REACH clinical score calculated on the day of the scintigraphic examination. After the myocardial scintigraphic exam, patients had a 1-year follow-up and CVE were recorded. Continuous data were analyzed either by Student's t-test or non-parametric Mann-Whitney test. The dichotomous data were compared either by the χ2 test or by Fisher's exact test. RESULTS: Forty-eight patients (20.1%) had a CVE during the 1-year follow-up. Thirty patients (13.8%) had a high residual SYNTAX score (≥8) without any correlation observed between the residual SYNTAX score and CVE (P=0.359). 148 patients (57.7%) had a high REACH clinical score (≥11) with no significant correlation observed with CVE (P=0.079). Lastly, 34 patients (14.4%) had an intermediate or high scintigraphic score, this imaging score being strongly correlated with a greater number of CVE (P<0.001). Multivariate analysis revealed 3 independent factors associated with CVE: a scintigraphic score> 2 (OR [(95% CI): 5.530 [2.426-12.605] P<0.001); Peripheral Arterial Obstructive Disease (PAOD) (OR [95% CI]: 8.531 [2.540-28.660] P<0.001); diabetes (OR [95% CI]: 2.86 [1.262-6.517] P=0,012). CONCLUSION: The combination of the scintigraphic score with two clinical factors, such as PAOD and diabetes, provides optimal prognostic value in the evaluation of asymptomatic and stable patients after ACS. Our study therefore highlights the importance of optimizing evaluation strategies in the follow-up of these patients who remain at risk of post-revascularization CVE.

Radiolabeled F(ab')2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models

Purpose: This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111In and 177Lu, respectively. Methods: We designed F(ab′)2-fragments of cetuximab radiolabeled with 111In and 177Lu. 111In-F(ab′)2-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111In-F(ab′)2-cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177Lu-F(ab′)2-cetuximab was evaluated in SWISS nude mice bearing A431 tumors. Results: Radiolabeling procedure did not change F(ab′)2-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111In-DOTAGA-F(ab′)2-cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab′)2-cetuximab. SPECT imaging of 111In-DOTAGA-F(ab′)2-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177Lu-DOTAGA-F(ab′)2-cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. Conclusions: 111In-DOTAGA-F(ab′)2-cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177Lu-DOTAGA-F(ab′)2-cetuximab is an interesting theranostic tool allowing therapy and imaging

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Radiolabeled F(ab')2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models.

PURPOSE: This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111In and 177Lu, respectively. METHODS: We designed F(ab')2-fragments of cetuximab radiolabeled with 111In and 177Lu. 111In-F(ab')2-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111In-F(ab')2-cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177Lu-F(ab')2-cetuximab was evaluated in SWISS nude mice bearing A431 tumors. RESULTS: Radiolabeling procedure did not change F(ab')2-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111In-DOTAGA-F(ab')2-cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab')2-cetuximab. SPECT imaging of 111In-DOTAGA-F(ab')2-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177Lu-DOTAGA-F(ab')2-cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. CONCLUSIONS: 111In-DOTAGA-F(ab')2-cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177Lu-DOTAGA-F(ab')2-cetuximab is an interesting theranostic tool allowing therapy and imaging.

Chikungunya outbreak in Montpellier, France, September to October 2014.

In October 2014, an outbreak of 12 autochthonous chikungunya cases, 11 confirmed and 1 probable, was detected in a district of Montpellier, a town in the south of France colonised by the vector Aedes albopictus since 2010. A case returning from Cameroon living in the affected district was identified as the primary case. The epidemiological investigations and the repeated vector control treatments performed in the area and around places frequented by cases helped to contain the outbreak. In 2014, the chikungunya and dengue surveillance system in mainland France was challenged by numerous imported cases due to the chikungunya epidemic ongoing in the Caribbean Islands. This first significant outbreak of chikungunya in Europe since the 2007 Italian epidemic, however, was due to an East Central South African (ECSA) strain, imported by a traveller returning from West Africa. Important lessons were learned from this episode, which reminds us that the threat of a chikungunya epidemic in southern Europe is real.

The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic.

BACKGROUND: Psoriasis has been linked to metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Data suggest that the prevalence of NAFLD is increased in patients with psoriasis. The aim of this study was to determine the prevalence and severity of NAFLD in this patient population. AIM: To determine the prevalence of both NAFLD and non-alcoholic steatohepatitis (NASH) in patients with psoriasis. METHODS: Patients between the ages of 18 and 70 years with a diagnosis of psoriasis or psoriatic arthritis and followed by either the Dermatology or Rheumatology Division within the Department of Medicine at San Antonio Military Medical Center were considered for enrollment. Each patient completed a questionnaire, underwent a thorough skin evaluation, and had a right upper quadrant ultrasound and fasting blood work. If the liver enzymes were elevated or fatty liver detected on imaging, percutaneous liver biopsy was recommended. RESULTS: One hundred and twenty-nine patients were enrolled and 103 completed all necessary studies. The participants were predominantly middle aged (52.7 ± 12) and overweight or obese (average BMI 30.1 ± 5.9, range: 19.8-52.5 kg/m(2)). 53% (n = 54) were male while 15% (n = 15) of participants identified themselves as being a diabetic. The overall prevalence of NAFLD was 47%. The overall prevalence of NASH was 22% in those who underwent biopsy. CONCLUSIONS: Non-alcoholic fatty liver disease is very common among our cohort of patients with psoriasis, occurring in roughly 47% of patients. The more progressive form of the disease, NASH, is found in approximately one in five patients. Health care providers should be mindful of this association given the high prevalence of both NAFLD and NASH in this cohort of patients.

[Multimodality MRI and PET for restaging prostate cancer after biochemical failure of the treatment]. / Quelle imagerie pour la prise en charge de la rechute biochimique du cancer de la prostate : TEP ou IRM ?

Major improvements in the field of radiotherapy planning such as stereotactic radiation therapy, have recently been performed, aiming to the development of personalized therapeutic strategies in patients with biochemical failure of prostate cancer. However, this needs an early and accurate location of sites of recurrence. Development of multimodality magnetic resonance imaging (MRI) and positron emission tomography (PET) permits to consider this objective. Thus, it is worthwhile to apprehend the respective performance of these imaging techniques in order to rationalize their use. We propose a review of the recent literature organized by technique and by location, regarding the performance of multimodality MRI and PET for restaging of patients with biochemical failure of prostate cancer initially treated with curative intent.

Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how?

Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.

Large number of imported chikungunya cases in mainland France, 2014: a challenge for surveillance and response.

During the summer of 2014, all the pre-requisites for autochthonous transmission of chikungunya virus are present in southern France: a competent vector, Aedes albopictus, and a large number of travellers returning from the French Caribbean islands where an outbreak is occurring. We describe the system implemented for the surveillance of chikungunya and dengue in mainland France. From 2 May to 4 July 2014, there were 126 laboratory-confirmed imported chikungunya cases in mainland France.

Predictors of post-stress LVEF drop 6 months after reperfused myocardial infarction: a gated myocardial perfusion SPECT study.

OBJECTIVE: To identify the predictive factors of myocardial stunning as assessed by the drop in post-stress Left Ventricular Ejection Fraction (LVEF) in patients with a recent history of myocardial infarction (MI). METHODS: We prospectively included 215 consecutive patients admitted for acute MI who underwent percutaneous coronary intervention with a greater than or equal to grade-3 TIMI flow in the culprit vessel. Six months after discharge, a post-stress/rest 99mTc-sestamibi gated SPECT was performed. The perfusion score was evaluated visually using a 17-segment model. The LVEF drop was considered significant if the post-stress LVEF was ≥ 5% below the rest LVEF (QGS® software). RESULTS: A post-stress LVEF drop was observed in 51 (24%) patients. Patients with an LVEF drop were more likely than patients with a stable post-stress LVEF to have diabetes (22% vs. 10%, p = 0.048), significant ischemia (SDS > 2) (51% vs. 28% p = 0.003) and higher rest LVEF [62% (56-69) vs. 56% (49-63) p < 0.001]. In contrast, summed rest score, related to infarct size, did not differ between the groups. Multivariate logistic regression analysis identified SDS > 2 (OR 3.78, 95% CI 1.8-7.92, p < 0.001), diabetes (OR 3.35, 95% CI 1.33-8.49; p = 0.011) and rest LVEF (OR 1.08, 95% CI 1.04-1.12, p < 0.001) as independent explanatory variables of an LVEF drop. CONCLUSION: In patients with recent MI and post-procedural grade-3 TIMI flow, ischemia and diabetes were independent predictive factors of myocardial stunning. The higher incidence of reversible perfusion abnormalities validates the model of myocardial stunning in the post-MI period, and excludes the potential involvement of myocardial necrosis.

Changes in 18F-FDG tumor metabolism after a first course of neoadjuvant chemotherapy in breast cancer: influence of tumor subtypes.

BACKGROUND: The aim of this study is to evaluate the impact of the different breast cancer subtypes on the tumor (18)F-FDG uptake at baseline and on its changes after the first course of neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: One hundred and fifteen women with newly diagnosed, large or locally advanced breast cancer undergoing NAC were included. Estrogen receptor (ER), progesterone receptor (PR) and HER2 status were used to define three major tumor subtypes: triple negative (TN) (ER-/PR-/HER2-), luminal (ER+ and/or PR+; HER2-) and HER2 positive (HER2+). Using Fluorine-18 fluorodeoxyglucose positron emission tomography, the tumoral standard uptake value (SUV) maximal index was measured at baseline and just before the second course of NAC. RESULTS: TN tumors presented the highest baseline SUV (11.3 ± 8.5; P < 0.0001). The decrease of SUV after the first course of NAC (ΔSUV) was significantly higher in TN and HER2-positive subtypes (-45% ± 25% and -57% ± 30%, respectively) than in luminal one (-19% ± 35%; P < 0.0001). ΔSUV was a predictive factor of the pathological complete response only in HER2-positive tumors (cut-off = -75%; P < 0.03) with an accuracy of 76%. CONCLUSION: The baseline (18)F-FDG tumoral uptake but also its early response to NAC is different according to the immunohistological subtypes of breast cancer.

Comparison of PEDOT films obtained via three different routes through spectroelectrochemistry and the differential cyclic voltabsorptometry method (DCVA).

The performance of different poly(3,4-ethylenedioxythiophene) (PEDOT) films was compared by electrochemical, spectroelectrochemical, and time-derivative measurements of absorbance versus potential (linear potential-scan voltabsorptometry) for an overall spectroelectrochemical characterization of the electrochromic properties in ionic liquids such as 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMITFSI). The time-derivative signals were monitored at different wavelengths, and information obtained therefrom was complementary to that obtained from conventional cyclic voltammetry. PEDOT films prepared via in situ chemical oxidative polymerization appeared to be much more efficient than electropolymerized and PEDOT-poly(styrenesulfonate) (PSS) reference films, in terms of both contrast ratio and coloration efficiency, which was the case even for PEDOT films deposited on less conductive flexible plastic substrates.

Unacceptably high mortality related to measles epidemics in Niger, Nigeria, and Chad.

BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality-reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality-reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy.

[Impact of a new cognitive remediation strategy on interpersonal problem solving skills and social autonomy in schizophrenia]. / Impact de la remédiation cognitive dans la schizophrénie sur les stratégies de résolution de problèmes et l'autonomie sociale: utilisation du logiciel REHACOM.

INTRODUCTION: Despite recent developments, the impact of pharmacotherapy on social autonomy and interpersonal problem solving skills in patients with schizophrenia remains limited, with consequences in terms of socio-professional functioning. Indeed, independently of the positive, negative and/or disorganization symptoms, functional deficits in patients with schizophrenia rely mainly on various cognitive impairments. OBJECTIVES: To determine the impact of a new Cognitive Remediation Strategy on interpersonal problem solving skills, social autonomy and symptoms in patients with schizophrenia. METHODS: Thirty patients with schizophrenia were enrolled in a program consisting of 14 training sessions of 4 cognitive functions (attention/concentration, topological memory, logical reasoning, executive functions) using the REHACOM software. Measurements of attention (Continuous Performance Test, CPT), memory (Rivermead Behavioural Memory Test, RBMT) and executive functions (Wisconsin Card Sorting Test, WCST) as well as interpersonal problem solving skills (Assessment of Interpersonal Problem-Solving Skills, AIPSS) and social autonomy (Social Autonomy Scale, EAS) and finally schizophrenia symptoms (Positive And Negative Syndrom Scale, PANSS) were undertaken at the beginning and the end of the 14 remediation meetings. RESULTS: Cognitive functions, interpersonal problems solving skills, social autonomy and symptoms were significantly improved by the Cognitive Remediation Strategy. CONCLUSION: Our results confirm the therapeutic impact of a Cognitive Remediation Strategy among 30 schizophrenic patients stabilised on clinical, therapeutic and functional levels. The question of the long-term maintenance of such improvements still requires further investigation.

[The therapeutic impact of PET-FDG scanning in broncho-pulmonary cancer]. / Impact thérapeutique de l'imagerie TEP-FDG en carcinologie bronchopulmonaire.

BACKGROUND: Because of the expected high performances of scintigraphic scans with [18F]-fluorodeoxyglucose (FDG) not only in diagnostics and but also in therapeutic impact, especially in thoracic oncology, there are a lot of French nuclear medicine departments which will soon be equipped with a positron emission tomograph (PET). MATERIAL AND METHODS: The Nuclear Medicine Department of the Hôpital d'Instructions des Armées du Val-de-Grâce, Paris, led a retrospective study among physicians interested in 338 FDG-PET exams performed between may 2000 and march 2002 in order to compare its own results with international literature concerning four indications for lung cancer: pulmonary nodule or mass malignancy diagnostic, lung carcinoma extension evaluation, therapeutic efficiency, recurrence suspicion. RESULTS: There seems to be no divergence, regarding limitation induced by the not exhaustive analysis of the retrospective study: more than every two FDG-PET exam highly influenced the effective therapy. CONCLUSION: That is why clinical FDG-PET has to be widely developed to investigate lung cancer.