Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVE: We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B). METHODS: From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 < 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; n = 53) groups. RESULTS: The 3 groups were comparable according to patient characteristics (except for back pain (P < .01) and CA 19-9 (P < .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P < .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P < .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P < .001), respectively. CONCLUSIONS: The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.

Performance of the Iris iQ(R)200 Elite analyser in the cell counting of serous effusion fluids and cerebrospinal drainage fluids.

AIMS: Evaluation of the Iris iQ(®)200 Elite analyser, initially designed for urinary cell counting, for the analysis of biological fluids (serous effusion fluids and cerebrospinal drainage fluids) and comparison of its performance with that of the manual microscopic method. METHODS: Routine samples (ascite fluids, pleural fluids and cerebrospinal fluids) were evaluated in terms of red blood cells and nucleated elements using the iQ(®)200 analyser and the manual method. The authors compared the reliability, repeatability and speed of the two techniques. In addition, the authors assessed the contribution of two different sample dilution processes to the improvement of iQ(®)200 analyser cytological results. RESULTS: Very good agreements were found between the two methods and between the two sample dilution processes. Regarding the repeatability, the coefficients of variation obtained with the iQ200 were slightly higher than those obtained by the manual method. Besides, the difference in the speed of the two methods was not significantly different for series with <10 samples. CONCLUSIONS: The Iris iQ(®)200 Elite analyser has allowed us to obtain reliable results, equivalent to that of the manual method, for cell enumeration in biological fluids. Although the speed of this instrument needs to be improved for larger series of samples, it enables standardised and objective cytological results to be obtained and represents an alternative to the usual manual microscopic method. Moreover, automation of such analyses permits saving of technician time.

Proteomic data in meningiomas: post-proteomic analysis can reveal novel pathophysiological pathways.

Meningiomas account for approximately 20% of adult primary intracranial tumours. WHO I meningiomas are the most common and are generally benign, but can progress, recur or transform to WHO II or WHO III grades over many years. A systematic review of multiple independent shotgun proteomic analyses of meningioma was performed to provide insight into underlying disease pathways. Shotgun proteomics has been conducted in seven meningioma related studies but there is considerable variation in aims, methodology, statistical power and the use of control tissue between these studies. Fifteen proteins which are different between WHO I and WHO II meningiomas and nine proteins which are different between WHO II and WHO III meningiomas have been described but without a view of their biological significance. Network analysis of proteins different between WHO I and WHO II meningiomas provided a coherent hypothesis for the involvement of these proteins in meningioma. Western blot analyses of meningioma tissue provided a measure of support for a core component in the network (involving VDAC2, APOA1 and HNF4α) but highlighted intrinsic difficulty of proteomic and biochemical analysis of meningiomas (as a consequence of gross alterations in tissue composition). Systematic review of shotgun proteomics and network analysis provides insight into meningioma pathophysiology despite the many barriers and difficulties that are inherent to this type of study.

NR2D-containing NMDA receptors mediate tissue plasminogen activator-promoted neuronal excitotoxicity.

Although the molecular bases of its actions remain debated, tissue-type plasminogen activator (tPA) is a paradoxical brain protease, as it favours some learning/memory processes, but increases excitotoxic neuronal death. Here, we show that, in cultured cortical neurons, tPA selectively promotes NR2D-containing N-methyl-D-aspartate receptor (NMDAR)-dependent activation. We show that tPA-mediated signalling and neurotoxicity through the NMDAR are blocked by co-application of an NR2D antagonist (phenanthrene derivative (2S(*), 3R(*))-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid, PPDA) or knockdown of neuronal NR2D expression. In sharp contrast with cortical neurons, hippocampal neurons do not exhibit NR2D both in vitro and in vivo and are consequently resistant to tPA-promoted NMDAR-mediated neurotoxicity. Moreover, we have shown that activation of synaptic NMDAR prevents further tPA-dependent NMDAR-mediated neurotoxicity and sensitivity to PPDA. This study shows that the earlier described pro-neurotoxic effect of tPA is mediated by NR2D-containing NMDAR-dependent extracellular signal-regulated kinase activation, a deleterious effect prevented by synaptic pre-activation.

HtrA1-dependent proteolysis of TGF-beta controls both neuronal maturation and developmental survival.

Transforming growth factor-beta (TGF-beta) signalling controls a number of cerebral functions and dysfunctions including synaptogenesis, amyloid-beta accumulation, apoptosis and excitotoxicity. Using cultured cortical neurons prepared from either wild type or transgenic mice overexpressing a TGF-beta-responsive luciferase reporter gene (SBE-Luc), we demonstrated a progressive loss of TGF-beta signalling during neuronal maturation and survival. Moreover, we showed that neurons exhibit increasing amounts of the serine protease HtrA1 (high temperature responsive antigen 1) and corresponding cleavage products during both in vitro neuronal maturation and brain development. In parallel of its ability to promote degradation of TGF-beta1, we demonstrated that blockage of the proteolytic activity of HtrA1 leads to a restoration of TGF-beta signalling, subsequent overexpression of the serpin type -1 plasminogen activator inhibitor (PAI-1) and neuronal death. Altogether, we propose that the balance between HtrA1 and TGF-beta could be one of the critical events controlling both neuronal maturation and developmental survival.

[Magnetic resonance imaging applications in obstetrics]. / Applications de l'imagerie par résonance magnétique en obstétrique.

PURPOSE: To review the main indications and results of magnetic resonance imaging in the pregnant women. MATERIAL AND METHOD: We reviewed MRI practice during the pregnancy based on our own experience in a prenatal diagnostic center and data in the literature. Rapid improvement in MRI technology has allowed more extensive use, giving a good contrast-to-noise ratio and multiplanar imaging. RESULTS: Although ultrasound provides primary screening information, final diagnosis may require further investigations. MRI, to be performed in the second and third trimester, is the non-invasive second line tool of choice in this context. The most widespread indications are for brain disease: search for a cause of ventriculomegaly or biometric abnormality, confirmation of a malformative or acquired lesion. Progressively, indications were widened to head and neck, thorax, abdomen and pelvis areas. Moreover, systematic indications include previous fetal pathology or the pregnancy context. Other MRI indications have been suggested: placental malposition, pelvimetry and maternal genito-urinary tract. CONCLUSION: MRI is becoming the natural and necessary second line imaging technique, with increasing indications. It must be kept in mind however that all pathological conditions cannot be depicted by these morphological studies.

[MRI in gynecology]. / IRM en gynécologie.

OBJECTIVES: To review the complementary role and contribution of magnetic resonance imaging (MRI) in gynecology diseases. RESULTS: Tissue characterization can be obtained with T2, T1 weighted images before and after contrast medium injection and T1 fat sat sequences. Localization of the lesion and relationships with adjacent structures are facilitated by multiplanar imaging. Endometrium and ovarian follicles display high signal intensity, visualizing the normal uterine and ovarian components. The relative high signal intensity of uterine tumors facilitates evaluation of extension. Uterine leiomyoma diagnosis is supported by its low signal intensity, allowing localization, size, and number assessment, and to distinguish adenomyoma. In doubtful malformation cases, MRI may be contributive. Ovarian mass characterization can be done with MRI, particularly for dermoid cyst and endometrioma. In this case, deep endometriosis can be associated and be extensive. Recent technical advances enable fast imaging, which can be useful for pelvic floor assessment with dynamic evaluation. CONCLUSION: MRI is becoming the complementary reference imaging tool for us. Its increasing indications are: gynecologic cancer, pelvis endometriosis, pelvis floor, indeterminate pelvis mass and fibroleiomyoma.

[Cerebral fetal MRI and ventriculomegaly]. / IRM cérébrale foetale et ventriculomégalie.

OBJECTIVE: To evaluate MRI usefulness in diagnosis and management of fetuses with cerebral ventriculomegaly at US. PATIENTS AND METHODS: Sonography depicted cerebral ventriculomegaly in 61 fetuses. Management included MRI in all cases and infectious screening, and karyotype in 51 cases. Final diagnosis was supported by fetal autopsy (n=24), postnatal follow-up>6 months (n=19), infectious screening or karyotype (n=8), and MR imaging when diagnosis was obvious (n=16). RESULTS: MRI was more informative than ultrasonography in 32.8% of cases with identification of the etiology in 21.3% of cases. In 45% MRI and sonography were considered to be normal. In the remaining cases, MRI confirmed the ultrasound diagnosis of cerebral malformation. Ultrasonography never depicted more anomalies than MR imaging. The 2 false negatives were gyration disorders but MR imaging was performed too early. CONCLUSION: US is the imaging modality of choice in the evaluation of fetal anomalies but MRI has to be systematically performed in case of cerebral ventriculomegaly because MRI demonstrates its usefulness in patient counseling, even if there are a few false negative results.

[Urethral duplication type II in a male child: a case report]. / Duplication de l'urètre de type II chez le garçon: A propos d'un cas.

Urethral duplication is a rare congenital anomaly, most common in male. The clinical presentation varies because of the various anatomical variant. A case of complete duplication with an accessory channel arising from a diverticulum, in a male child is reported. The clinical presentation, the imaging findings, and the management are described.

[Power Doppler sonography and acute pyelonephritis in children: comparison with Tc-DMSA scintigraphy]. / Echographie doppler énergie et pyélonéphrite aiguë de l'enfant: comparaison avec la scintigraphie au DMSA-Tc.

UNLABELLED: Acute pyelonephritis is a common infection in children. The clinical and biological diagnosis is still sometimes difficult. For most authors, Technecium 99m dimercaptosuccinic acid scintigraphy is considered as the gold standard tool for diagnosis but it is invasive and expensive. The aim of our study was to compare the sensitivity and the specificity of B-mode sonography and power doppler to DMSA-Tc scintigraphy in acute pyelonephritis. PATIENTS AND METHODS: Forty-nine children were enrolled in this study with suspicion of pyelonephritis. All infants underwent doppler sonography and scintigraphy within 48 hours after their hospitalization. Doppler sonography criteria were increased kidney size, thickness of sinus wall, vascular defect, and various echogenicity of the kidneys (focal or diffuse hyperechogenicity or focal hypoechogenicity). RESULTS: Among 28 children with a positive scintigraphy, 15 had a positive doppler sonography (sensitivity 54%) and 13 had a negative doppler sonography. Among 21 children with a negative scintigraphy, 20 had a negative doppler sonography (specificity 95%) and one had a positive doppler sonography. CONCLUSION: In clinically suspected acute pyelonephritis, doppler sonography has a high specificity. A positive doppler sonography should avoid the use of scintigraphy.

[Imaging of the female pelvis in adolescence]. / Imagerie du pelvis féminin à l'adolescence.

The aim of this chapter is to familiarize the radiologists with the evolutive morphological features of the female genital apparatus, as it can be seen during the puberty, and to view the pathologies panel which may occur in ths period of life. This chapter is going to illustrate the morphological sonographic modifications from the childhood to the adolescence, emphasing the signs of pubertal maturation (uterus and ovaries shape, size and vascularization). Through clinical signs (delayed sexual maturation, primary or secondary amenorrhea, menstrual dysfunction, acute, cyclic, chronic pelvic pain and pelvic mass) the different pathologies are viewed, illustrating the important role of ultrasonography, but not an exclusive role.

[Imaging of the endometrium]. / Imagerie de l'endomètre.

During genital activity, physiological and pathological modifications can be observed; Pre- and postmenopausal menometror-rhagia are the principle clinical signs of various endometrial pathologies: benign (polyp, atrophy or endometrial hypertrophy), malignant (cervical or endometrial carcinoma) or neighboring pathologies (myometrium or ovary). The value and methods of various imaging techniques (B-mode and Doppler abdominal and endovaginal ultrasonography, hysterosonography, computed tomography, MR imaging and hysteroscopy) are described together with symptomatological features permitting identification of the endometrial pathology.

Biogenesis of endoplasmic reticulum proteins involved in Ca2+ signalling during megakaryocytic differentiation: an in vitro study.

The endoplasmic reticulum (ER) plays a key role in Ca(2+) signalling through Ca(2+) release via inositol 1,4,5-trisphosphate receptors (InsP(3)-Rs) and Ca(2+) uptake by sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs). Here, we investigated the organization of platelet ER and its biogenesis during megakaryocytopoiesis. First, erythro/megakaryoblastic MEG 01, UT7, M-O7e and CHRF 288-11 cell lines, platelets and thrombopoietin-induced UT7-Mpl cells were selected for the study of SERCA2b and SERCA3 proteins by Western blotting using the antibodies IID8 and PL/IM430, respectively. As judged by platelet glycoprotein IIIa (GPIIIa) expression, an increase in SERCA3 proteins was observed while that of SERCA2b remained unchanged throughout maturation. Second, these studies were extended to the newly described alternatively spliced SERCA3a-c RNAs and InsP(3)-Rs using the in vitro model of PMA-induced differentiation of MEG 01 cells. Time-course and dose-response studies showed a maximal approx. 4-fold up-regulation of SERCA3 proteins using 10(-8) M PMA for 3 days, which paralleled induction of GPIIIa expression. SERCA3 induction was found to occur at the level of mRNA. The modulation of the different SERCA3 species (i.e. 3a, 3b and 3c) was isoform-specific: while SERCA3a was slightly increased, an approx. 3-fold induction of SERCA3b, and a 4-fold induction of SERCA3c, was observed after 24 h of PMA treatment. Isoform-specific Western blotting and/or reverse transcriptase PCR studies showed that InsP(3)-R types I, II and III are expressed in MEG 01 cells, as well as in platelets. Study of the expression of these InsP(3)-R types in PMA-induced MEG 01 cells revealed that: (i) InsP(3)-RI protein and mRNA showed no changes; (ii) InsP(3)-RII mRNA was up-regulated and peaked at hour 48 and (iii) InsP(3)-RIII mRNA and protein showed a transitory maximal 3- and 2.3-fold increase at hours 6 and 30, respectively. Upon PMA treatment of CHRF 288-11 cells, in which GPIIIa is not induced upon treatment, a similar pattern of regulation of InsP(3)-R types II and III was seen, but a distinct pattern of SERCA3 regulation was observed. These results suggest a profound reorganization of ER-protein patterns during megakaryocytopoiesis and underline the role of SERCA3 gene regulation in the control of Ca(2+)-dependent platelet functions.

Lineage-specific modulation of calcium pump expression during myeloid differentiation.

Calcium is accumulated from the cytosol into the endoplasmic reticulum by sarco-endoplasmic reticulum calcium transport ATPase (SERCA) enzymes. Because calcium stored in the endoplasmic reticulum is essential for cell growth, differentiation, calcium signaling, and apoptosis and because different SERCA enzymes possess distinct functional characteristics, in the present report we explored SERCA expression during in vitro differentiation of the human myeloid/promyelocytic cell lines HL-60 and NB4 and of freshly isolated acute promyelocytic leukemia cells. Two SERCA species have been found to be coexpressed in these cells: SERCA 2b and another isoform, SERCAPLIM, which is recognized by the PLIM430 monoclonal antibody. Induction of differentiation along the neutrophil granulocytic lineage by all-trans retinoic acid or cyclic AMP analogs led to an increased expression of SERCAPLIM, whereas the expression of the SERCA 2b isoform was decreased. The modulation of SERCA expression was manifest also on the mRNA level. Experiments with retinoic acid receptor isoform-specific retinoids indicated that SERCA expression is modulated by retinoic acid receptor alpha-dependent signaling. SERCA expression of retinoic acid-resistant cell variants was refractory to treatment. Differentiation along the monocyte/macrophage lineage by phorbol ester resulted in an increased expression of both SERCA isoforms. In addition, when cells were treated by phorbol ester in the presence of the glucocorticoid dexamethasone, a known inhibitor of monocyte differentiation, a selective blockage of the induction of SERCAPLIM was observed. Altered SERCA expression modified the functional characteristics of calcium transport into the endoplasmic reticulum. These observations show for the first time that the modulation of calcium pump expression is an integral component of the differentiation program of myeloid precursors and indicate that a lineage-specific remodelling of the endoplasmic reticulum occurs during cell maturation. In addition, these data show that SERCA isoforms may serve as useful markers for the study of myeloid differentiation.

Platelet sarco/endoplasmic reticulum Ca2+ATPase isoform 3b and Rap 1b: interrelation and regulation in physiopathology.

Platelet Ca2+ signalling involves intracellular Ca2+ pools, whose content is controlled by sarco/endoplasmic reticulum Ca2+ATPases (SERCAs). Among these, a key role is played by the inositol trisphosphate-sensitive Ca2+ pool, associated with the SERCA 3b isoform. We have investigated the control of this Ca2+ pool through the cAMP-dependent phosphorylation of the GTP-binding protein, Rap (Ras-proximate) 1b. We first looked for this Ca2+ pool target of regulation by studying the expression of the different SERCA and Rap 1 proteins in human platelets and various cell lines, by Western blotting and reverse transcription-PCR. Since co-expression of Rap 1b and SERCA 3b was obtained, we looked for their protein-protein interaction as a function of the cAMP-dependent phosphorylation of Rap 1b. Co-immunoprecipitations of SERCA 3b and Rap 1b proteins were found in the absence of phosphorylation, induced by the catalytic subunit of the cAMP-dependent protein kinase (csPKA). In contrast, upon pre-treatment of platelet membranes with csPKA, the SERCA 3b dissociated from the Rap 1b protein, in agreement with a role of its phosphorylated state in their interaction. Finally, we looked for adaptation of this complex in a platelet pathological model of hypertension. We investigated the expression of both proteins, as well as the cAMP-dependent phosphorylation of Rap 1b and SERCA 3b activity in platelets from control normotensive Wistar-Kyoto rats and from spontaneously hypertensive rats (SHRs). A decrease in SERCA 3b activity was associated with a decrease in Rap 1b endogenous phosphorylation in SHR platelets, consistent with a functional role in the regulation of the SERCA 3b-associated Ca2+ pool.

Expression of two isoforms of the third sarco/endoplasmic reticulum Ca2+ ATPase (SERCA3) in platelets. Possible recognition of the SERCA3b isoform by the PL/IM430 monoclonal antibody.

Human platelets express several sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) isoenzymes: SERCA2b of 100 kDa apparent molecular mass and two distinct enzymes of 97 kDa, one of them identified as being the SERCA3a isoform. The molecular identity of the third enzyme specifically recognized by the PL/IM430 monoclonal antibody has remained elusive. First, the study of the 3'-end part of platelet SERCA3 mRNA, by means of RT-PCR amplification using sets of primers covering the N-3 to N (ultimate) exons of the human SERCA3 sequence, revealed the presence of two distinct mRNA sequences, SERCA3a and a longer variant. Second, this additional sequence was identified as SERCA3b and found to refer to the insertion of a new exon of 73 bp, located at bp 349 from the beginning of the intronic sequence, linking the penultimate (N-1) exon to the last exon (N) of the human SERCA3 gene. Third, a relationship between the expression of this SERCA3b mRNA and the PL/ IM430 recognizable SERCA protein was observed. SERCA3b mRNA was found to be absent in epithelial HeLa cells not recognized by the PL/IM430 antibody and the expression of this SERCA3b RNA species correlated with that of the SERCA protein recognized by PL/IM430 which was down-modulated in the platelet precursor megakaryocytic CHRF 288-11 cell line as well as upon in vitro lymphocyte activation. Taken together, these results strongly support the notion of the presence of the SERCA3b protein in human cells by showing SERCA3b mRNA in platelets and the fact that the protein corresponding to this mRNA species is very likely the 97 kDa protein recognized by the PL/IM430 antibody.

Modulation of endoplasmic reticulum calcium pump expression during T lymphocyte activation.

Calcium mobilization from intracellular storage organelles is a key component of the second messenger system inducing cell activation. Calcium transport ATPases associated with intracellular calcium storage organelles play a major role in controlling this process by accumulating calcium from the cytosol into intracellular calcium pools. In this study the modulation of the expression of the sarco-endoplasmic reticulum calcium transport ATPase (SERCA) isoenzymes has been studied in lymphocytes undergoing phorbol myristate acetate and ionomycin-induced activation. In several T lymphocyte cell lines a combined treatment by the two drugs resulted in an approximately 90% decrease of the expression of the calcium pump isoform recognized by the PLIM430 isoform-specific antibody, whereas the expression of the SERCA 2b isoform was increased approximately 2-fold. Phorbol ester or ionomycin applied separately was ineffective. In Jurkat T cells the down-modulation of expression of the SERCA isoform recognized by the PLIM430 antibody appeared concomitantly with the induction of interleukin-2 expression and could be inhibited by the immunosuppressant drug cyclosporine-A. These data indicate that T cell activation induces a selective and cyclosporine-A-sensitive modulation of the expression of the SERCA calcium pump isoforms. This reflects a profound reorganization of the calcium homeostasis of T cells undergoing activation and may open new avenues in the understanding of the plasticity of the calcium homeostasis of differentiating cells and in the pharmacological modulation of lymphocyte function.

Prostaglandin E2 level in tissue surrounding aseptic failed total hips. Effects of materials.

Production of inflammatory mediators (IM) by cells and specifically macrophages around loosened implants may be responsible for their loosening. Our hypothesis was that different materials give rise to different amounts of these IM. It is thought that alumina/alumina for total hip replacement (THR), which has been used for 15 years in our orthopedic department, may produce less IM than other systems. We initiated a clinical prospective study to measure the level of prostaglandin E2 (PGE2) in tissue surrounding loosened prostheses to quantify PGE2 production regarding the types of material involved in the friction couple, i.e., alumina/alumina versus metal/polyethylene, and the type of fixation, i.e., cemented versus cementless. A total of 29 THR revisions were performed in 28 patients. Four implant groups were identified: alumina/alumina cemented, alumina/alumina cementless, metal/polyethylene cemented, and metal/polyethylene cementless. For each revision, tissues surrounding the failed implants were harvested and processed, and the PGE2 was measured in a blind manner using an immunoassay technique. As the measuring technique was difficult, at least three determinations for each sample were necessary. Some samples were excluded from the analysis for various reasons, for example, second or further revisions involving many different materials in the past, conjunction of metallic and alumina debris and samples taken from non-loosened components. Finally, 15 samples were considered adequate for inclusion in this study. Two groups were analyzed and compared: the alumina/alumina couple and the metal/polyethylene couple. Tissue surrounding the first group demonstrated a PGE2 level of 69 +/- 56 fmol/mg wet weight compared to 202 +/- 156 fmol/mg for the second.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intradural metastases of visceral cancers. MRI aspects. Apropos of 2 cases]. / Métastases intradurales des cancers viscéraux. Aspects IRM. A propos de 2 cas.

The authors report two cases of intradural metastasis: a man with bronchopulmonary cancer suffering from left L5 sciatic pain and a woman with breast cancer whose examination shows motor weakness of both legs. CT was negative in the first case. Gadolinium injection on T1 sequence shows in the first case small nodular lesions along the roots of cauda equina and in the second case linear enhancements around the spine, at different levels. These aspects are the most frequently reported. MRI is an innocuous and the most sensitive technic for such lesions. An early diagnosis improves the functional prognosis. Despite of radiotherapy and chemotherapy, vital prognosis remains bad because of widespread of the intradural lesions and their frequent association with cerebral metastasis.