Traitements chirurgicaux des maladies fonctionnelles oesogastriques [Surgical treatment of gastroesophageal diseases].

Les pathologies fonctionnelles oesogastriques regroupent plusieurs maladies touchant la fonction digestive haute : la maladie de reflux, les hernies hiatales, l'oesophage court et l'achalasie. Leur mode de présentation est parfois similaire, mais leur traitement diffère sur de nombreux points. L'approche initiale passe souvent par une modification de l'hygiène de vie et une prise en charge médicale. Mais une prise en charge chirurgicale est parfois nécessaire. Une sélection très stricte des patients permet de garantir un bon résultat à long terme, tout en limitant le risque de complications. Elle repose sur un bilan fonctionnel précis et une prise en charge dans le cadre de discussions multidisciplinaires. Cette revue fait un point actuel sur la prise en charge générale, les bilans nécessaires et les traitements chirurgicaux disponibles. Gastroesophageal functional diseases comprise several pathologies impending upper gastrointestinal function: reflux disease, hiatal hernias, short esophagus and achalasia. Their presentation may be similar, but their treatment differs on many points. The initial approach consists of lifestyle changes and medical management. However, surgical treatment is sometimes necessary. Strict patient selection ensures good long-term results, while limiting the risk of complications. This selection is based on precise functional assessment and management in the context of multidisciplinary discussions. This article aims to discuss current aspects on general management, functional investigations and surgical treatments available.

Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases.

Dopamine (DA) plays a major role in motor and cognitive functions as well as in reward processing by regulating glutamatergic inputs. In particular in the striatum the release of DA rapidly influences synaptic transmission modulating both AMPA and NMDA receptors. Several neurodegenerative and neuropsychiatric disorders, including Parkinson, Huntington and addiction-related diseases, manifest a dysregulation of glutamate and DA signaling. Here, we will focus our attention on the mechanisms underlying the modulation of the glutamatergic transmission by DA in striatal circuits.

Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive regions of interest.

PURPOSE: Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. METHODS: Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. RESULTS: Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). CONCLUSION: In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted.

A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective.

OBJECTIVE: To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. METHODS AND MATERIALS: An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). RESULTS: With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. CONCLUSIONS: ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.

"Hit the primary": A paradigm shift in the treatment of metastatic prostate cancer?

Patients with metastatic prostate cancer (PC) represent a heterogeneous group with survival rates varying between 13 and 75 months. The current standard treatment in this setting is hormonal therapy, with or without docetaxel-based chemotherapy. In the era of individualized medicine, however, maximizing treatment options, especially in long-term surviving patients with limited disease burden, is of capital importance. Emerging data, mainly from retrospective surgical series, show survival benefits in men diagnosed with metastatic PC following definitive therapy for the prostate. Whether the irradiation of primary tumor in a metastatic disease might improve the therapeutic ratio in association with systemic treatments remains investigational. In this scenario, modern radiation therapy (RT) can play a significant role owing to its intrinsic capability to act as a more general immune response modifier, as well as to the potentially better toxicity profile compared to surgery. Preclinical data, clinical experience, and challenges in local treatment in de novo metastatic PC are reviewed and discussed.

Prostate cancer screening in Switzerland: 20-year trends and socioeconomic disparities.

BACKGROUND: Despite important controversy in its efficacy, prostate cancer (PCa) screening has become widespread. Important socioeconomic screening disparities have been reported. However, trends in PCa screening and social disparities have not been investigated in Switzerland, a high risk country for PCa. We used data from five waves (from 1992-2012) of the population-based Swiss Health Interview Survey to evaluate trends in PCa screening and its association with socioeconomic indicators. METHODS: We used multivariable Poisson regression to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and use of healthcare. RESULTS: The study included 12,034 men aged ≥50 years (mean age: 63.9). Between 1992 and 2012, ever use of PCa screening increased from 55.3% to 70.0% and its use within the last two years from 32.6% to 42.4% (p-value <0.05). Income, education, and occupational class were independently associated with PCa screening. PCa screening within the last two years was greater in men with the highest (>$6,000/month) vs. lowest income (≤$2,000) (46.5% vs. 38.7% in 2012, PR for overall period =1.29, 95%CI: 1.13-1.48). These socioeconomic disparities did not significantly change over time. CONCLUSIONS: This study shows that about half of Swiss men had performed at least one PCa screening. Men belonging to high socioeconomic status are clearly more frequently screened than those less favored. Given the uncertainty of the usefulness of PCa screening, men, including those with high socioeconomic status, should be clearly informed about benefits and harms of PCa screening, in particular, the adverse effect of over-diagnosis and of associated over-treatment.

Enhanced capture of healthcare-related harms and injuries in the 11th revision of the International Classification of Diseases (ICD-11).

The World Health Organization (WHO) plans to submit the 11th revision of the International Classification of Diseases (ICD) to the World Health Assembly in 2018. The WHO is working toward a revised classification system that has an enhanced ability to capture health concepts in a manner that reflects current scientific evidence and that is compatible with contemporary information systems. In this paper, we present recommendations made to the WHO by the ICD revision's Quality and Safety Topic Advisory Group (Q&S TAG) for a new conceptual approach to capturing healthcare-related harms and injuries in ICD-coded data. The Q&S TAG has grouped causes of healthcare-related harm and injuries into four categories that relate to the source of the event: (a) medications and substances, (b) procedures, (c) devices and (d) other aspects of care. Under the proposed multiple coding approach, one of these sources of harm must be coded as part of a cluster of three codes to depict, respectively, a healthcare activity as a 'source' of harm, a 'mode or mechanism' of harm and a consequence of the event summarized by these codes (i.e. injury or harm). Use of this framework depends on the implementation of a new and potentially powerful code-clustering mechanism in ICD-11. This new framework for coding healthcare-related harm has great potential to improve the clinical detail of adverse event descriptions, and the overall quality of coded health data.

Les maladies rénales chroniques ne sont pas toutes silencieuses [Chronic kidney diseases do not always pass unnoticed].

Kidney diseases are frequent, but most of the time, they develop unnoticed. This paucity of symptoms may lead to delayed diagnosis with important consequences on their outcome. Nevertheless, specific systemic signs such as skin lesions, joint pain or electrolytes disturbances may sometimes alert the clinician and direct the diagnosis to an underlying nephropathy. A high awareness of clinicians is warranted to recognize these red flags and diagnose these diseases early, as illustrated by two clinical cases discussed in this article.

Biopsies de la prostate en 2015: quelle biopsie pour quel patient [Prostate biopsy: which strategy for which patient?].

L'adoption de l'IRM dans le parcours diagnostique a déterminé la transition des biopsies aléatoires aux biopsies ciblées vers les lésions visibles à l'imagerie. L'utilisation de logiciels rendant possible la fusion d'images IRM et échographiques permet d'améliorer significativement la précision diagnostique de ces biopsies. De plus, pour déterminer l'éligibilité d'un patient à une thérapie focale, davantage de précision diagnostique est requise au niveau de toute la glande ; par conséquent, des biopsies avec une densité d'échantillonnage plus élevée par voie transpérinéale peuvent être proposées.Les nouvelles techniques de biopsie de la prostate permettent une prise en charge personnalisée grâce à une meilleure caractérisation de l'agressivité et de l'extension locale du cancer de la prostate. The adoption of multiparametric MRI within the diagnostic pathway has allowed urologists to move from random biopsy to targeted biopsy directed towards MR-visible lesions. The use of software for MR to TRUS fusion may enhance the diagnostic accuracy of targeted biopsy. To determine the eligibility for tissue-preserving approaches, further precision is required, and template prostate mapping biopsy may be offered. The employment of novel biopsy techniques provide better characterisation of the disease, and allows a tailored approach to a single subject.

Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants-including variants that do not reach genome-wide significance-often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).