International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease.

The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.

Diagnostic value of lipopolysaccharide-binding protein and procalcitonin for sepsis diagnosis in forensic pathology.

The aims of this study were twofold. The first was to investigate the diagnostic performance of two biochemical markers, procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP), considering each individually and then combined, for the postmortem diagnosis of sepsis. We also tested the usefulness of pericardial fluid for postmortem LBP determination. Two study groups were formed, a sepsis-related fatalities group of 12 cases and a control group of 30 cases. Postmortem native CT scans, autopsy, histology, neuropathology, and toxicology as well as other postmortem biochemical investigations were performed in all cases. Microbiological investigations were also carried out in the septic group. Postmortem serum PCT and LBP levels differed between the two groups. Both biomarkers, individually considered, allowed septic states to be diagnosed, whereas increases in both postmortem serum PCT and LBP levels were only observed in cases of sepsis. Similarly, normal PCT and LBP values in postmortem serum were identified only in non-septic cases. Pericardial fluid LBP levels do not correlate with the presence of underlying septic states. No relationship was observed between postmortem serum and pericardial fluid LBP levels in either septic or non-septic groups, or between pericardial fluid PCT and LBP levels.

Cellular pathology of hilar neurons in Ammon's horn sclerosis.

In addition to functionally affected neuronal signaling pathways, altered axonal, dendritic, and synaptic morphology may contribute to hippocampal hyperexcitability in chronic mesial temporal lobe epilepsies (MTLE). The sclerotic hippocampus in Ammon's horn sclerosis (AHS)-associated MTLE, which shows segmental neuronal cell loss, axonal reorganization, and astrogliosis, would appear particularly susceptible to such changes. To characterize the cellular hippocampal pathology in MTLE, we have analyzed hilar neurons in surgical hippocampus specimens from patients with MTLE. Anatomically well-preserved hippocampal specimens from patients with AHS (n = 44) and from patients with focal temporal lesions (non-AHS; n = 20) were studied using confocal laser scanning microscopy (CFLSM) and electron microscopy (EM). Hippocampal samples from three tumor patients without chronic epilepsies and autopsy samples were used as controls. Using intracellular Lucifer Yellow injection and CFLSM, spiny pyramidal, multipolar, and mossy cells as well as non-spiny multipolar neurons have been identified as major hilar cell types in controls and lesion-associated MTLE specimens. In contrast, none of the hilar neurons from AHS specimens displayed a morphology reminiscent of mossy cells. In AHS, a major portion of the pyramidal and multipolar neurons showed extensive dendritic ramification and periodic nodular swellings of dendritic shafts. EM analysis confirmed the altered cellular morphology, with an accumulation of cytoskeletal filaments and increased numbers of mitochondria as the most prominent findings. To characterize cytoskeletal alterations in hilar neurons further, immunohistochemical reactions for neurofilament proteins (NFP), microtubule-associated proteins, and tau were performed. This analysis specifically identified large and atypical hilar neurons with an accumulation of low weight NFP. Our data demonstrate striking structural alterations in hilar neurons of patients with AHS compared with controls and non-sclerotic MTLE specimens. Such changes may develop during cellular reorganization in the epileptogenic hippocampus and are likely to contribute to the pathogenesis or maintenance of temporal lobe epilepsy.

Atlas iconographique tomodensitométrique des pathologies bénignes de l'amiante [Computed tomographic atlas of benign asbestos related pathology].

The demonstration by computed tomography of abnormalities related to asbestos is essential for the recognition of industrial disease, the compensation of which has considerable economic consequences. The use of compute tomography, the most reliable technique for the detection of pleuro-parenchymatous abnormalities related to asbestos exposure, has increased considerably in France since the publication of the results of a consensus conference in Paris in 1999. Since that time, developments in technology have noticeably modified the protocols of investigation and increased the sensitivity of the detection of pleural and interstitial parenchymatous abnormalities and of nodules. The technical recommendations and those for the interpretation of pleural and parenchymatous abnormalities need to be well known. They are presented in the form of an atlas that gives detailed criteria for asbestosis, pleural plaques and pleural fibrosis. The diagnosis of pleural plaques depends on the combination of clear limits at the pleural and pulmonary interface, typical topography and multiple, bilateral localization. In the context of asbestos exposure the plaques are characteristic of this exposure, unlike diffuse pleural thickening, crow's feet images, parenchymatous bands and entrapped atalectasis. The writing of the radiological report would be most appropriate on this basis.

Language and syntactic impairment following stroke in late bilingual aphasics.

PURPOSE: Bilingual aphasia generally affects both languages. However, the age of acquisition of the second language (L2) seems to play a role in the anatomo-functional correlation of the syntactical/grammatical processes, thus potentially influencing the L2 syntactic impairment following a stroke. The present study aims to analyze the influence of late age of acquisition of the L2 on syntactic impairment in bilingual aphasic patients. METHODS: Twelve late bilingual participants (speaking French as L2 and either English, German, Italian or Spanish as L1) with stroke-induced aphasia participated in the study. The MAST or BAT aphasia batteries were used to evaluate overall aphasia score. An auditory syntactic judgement task was developed and used to test participants syntactic performance. RESULTS: The overall aphasia scores did not differ between L1 and L2. In a multiple case analysis, only one patient had lower scores in L2. However, four patients presented significantly lower performances in syntactic processing in the late L2 than in their native language (L1). In these four patients the infarct was localized, either exclusively or at least partially, in the pre-rolandic region. CONCLUSION: This pilot study suggests that, in late bilingual aphasics, syntactic judgment abilities may be more severely impaired in L2, and that this syntactic deficit is most likely to occur following anterior lesions.

Usefulness of postmortem biochemistry in forensic pathology: illustrative case reports.

The aim of this work is to present some practical, postmortem biochemistry applications to illustrate the usefulness of this discipline and reassert the importance of carrying out biochemical investigations as an integral part of the autopsy process. Five case reports are presented pertaining to diabetic ketoacidosis in an adult who was not known to suffer from diabetes and in presence of multiple psychotropic substances; fatal flecainide intoxication in a poor metabolizer also presenting an impaired renal function; diabetic ketoacidosis showing severe postmortem changes; primary aldosteronism presented with intracranial hemorrhage and hypothermia showing severe postmortem changes. The cases herein presented can be considered representative examples of the importance of postmortem biochemistry investigations, which may provide significant information useful in determining the cause of death in routine forensic casework or contribute to understanding the pathophysiological mechanisms involved in the death process.

Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives.

Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8-10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted.

Counsellor behaviours and patient language during brief motivational interventions: a sequential analysis of speech

AIMS: To investigate empirically the hypothesized relationship between counsellor motivational interviewing (MI) skills and patient change talk (CT) by analysing the articulation between counsellor behaviours and patient language during brief motivational interventions (BMI) addressing at-risk alcohol consumption. DESIGN: Sequential analysis of psycholinguistic codes obtained by two independent raters using the Motivational Interviewing Skill Code (MISC), version 2.0. SETTING: Secondary analysis of data from a randomized controlled trial evaluating the effectiveness of BMI in an emergency department. PARTICIPANTS: A total of 97 patients tape-recorded when receiving BMI. MEASUREMENTS: MISC variables were categorized into three counsellor behaviours (MI-consistent, MI-inconsistent and 'other') and three kinds of patient language (CT, counter-CT (CCT) and utterances not linked with the alcohol topic). Observed transition frequencies, conditional probabilities and significance levels based on odds ratios were computed using sequential analysis software. FINDINGS: MI-consistent behaviours were the only counsellor behaviours that were significantly more likely to be followed by patient CT. Those behaviours were significantly more likely to be followed by patient change exploration (CT and CCT) while MI-inconsistent behaviours and 'other' counsellor behaviours were significantly more likely to be followed by utterances not linked with the alcohol topic and significantly less likely to be followed by CT. MI-consistent behaviours were more likely after change exploration, whereas 'other' counsellor behaviours were more likely only after utterances not linked with the alcohol topic. CONCLUSIONS: Findings lend support to the hypothesized relationship between MI-consistent behaviours and CT, highlight the importance of patient influence on counsellor behaviour and emphasize the usefulness of MI techniques and spirit during brief interventions targeting change enhancement.

Microvascular pathology in late-life depression.

Since the era of Gaupp who introduced the concept of atheroscletic depressive disorder, the concept of late-life depression has been correlated with cerebrovascular comorbidities, microvascular lesions, frontal cortical and subcortical gray and white matter hyperintensities. The predominant neuropsychological deficits concern the domains of planning, organization and abstraction, with executive dysfunction being the predominant finding. MRI studies reveal a higher prevalence of white matter lesions in elderly patients with depression. Molecular mechanisms underlying the disease still remain unclear. Hyperhomocysteinemia has been associated with depression through its toxicity to neurons and blood vessels. Endothelial dysfunction is another possible mechanism referring to the loss of vasodilatation capacity. Inflammatory phenomena, such as increased peripheral leucocytes, elevated CRP and cytokine levels, could play a role in endothelial dysfunction. In this review we will briefly combine findings from neurobiological, epidemiological, structural and post-mortem data. A more complex model in late-life depression combining different modalities could be an elucidating approach to the disease's etiopathogeny in the future.