SEOM/SERAM consensus statement on radiological diagnosis, response assessment and follow-up in colorectal cancer

Colorectal cancer (CRC) is one of the world’s most common cancers, and has one of the highest mortality rates. The last few decades have seen great progress in preventing, diagnosing and treating this disease, providing undeniable impact on patients’ prognosis and quality of life. At all these stages of CRC management, imaging techniques play an essential role. This article reviews some important issues concerning the use of various radiological techniques in the screening, diagnosis, staging, assessment of treatment response, and follow-up of patients with CRC. It also includes a number of practical recommendations on indications for use, technical requirements, minimum information required in the radiology report, evaluation criteria for the response to various drugs, and the recommended frequency at which different examinations should be performed. This consensus statement is the result of cooperation between the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Radiology (SERAM) (AU)

No disponible

SEOM/SERAM consensus statement on radiological diagnosis, response assessment and follow-up in colorectal cancer.

Colorectal cancer (CRC) is one of the world's most common cancers, and has one of the highest mortality rates. The last few decades have seen great progress in preventing, diagnosing and treating this disease, providing undeniable impact on patients' prognosis and quality of life. At all these stages of CRC management, imaging techniques play an essential role. This article reviews some important issues concerning the use of various radiological techniques in the screening, diagnosis, staging, assessment of treatment response, and follow-up of patients with CRC. It also includes a number of practical recommendations on indications for use, technical requirements, minimum information required in the radiology report, evaluation criteria for the response to various drugs, and the recommended frequency at which different examinations should be performed. This consensus statement is the result of cooperation between the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Radiology (SERAM).

NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis.

Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.

LRP5/canonical Wnt signalling and healing of ischemic myocardium.

LRP5 (low-density lipoprotein receptor-related protein 5) activates canonical Wnt signalling. LRP5 plays multiple roles including regulation of lipoprotein and cholesterol homeostasis as well as innate immunity cell function. However, it is not known whether LRP5 has a role in the myocardium. The aim of this study was to investigate LRP5 and Wnt signalling in myocardial remodelling after acute myocardial infarction (MI). Wnt protein levels were determined in a hypercholesterolemic porcine model of MI, in Lrp5 -/- C57Bl6 mice, in cultured cardiomyocytes and in human explanted hearts with previous MI episodes. 21 days post-MI, there was upregulation of LRP5 in the ischemic myocardium of hypercholesterolemic pigs as well as an upregulated expression of proteins of the Wnt pathway. We demonstrate via overexpression and silencing experiments that LRP5 induces Wnt pathway activation in isolated cardiomyocytes. Hypoxia and lipid-loading induced the expression of Wnt proteins, whereas this effect is blocked in LRP5-silenced cardiomyocytes. To characterize the function of the LRP5-Wnt axis upregulation in the heart, we induced MI in wild-type and Lrp5 -/- mice. Lrp5 -/- mice had significantly larger infarcts than Wt mice, indicating a protective role of LRP5 in injured myocardium. The LRP5 upregulation in post-MI hearts seen in pigs and mice was also evident in human hearts as dyslipidemic patients with previous episodes of ischemia have higher expression of LRP5 and Wnt-signalling genes than non-ischemic dilated hearts. We demonstrate an upregulation of LRP5 and the Wnt signalling pathway that it is a prosurvival healing response of cardiomyocytes upon injury.

Update on PET/CT colonography in the diagnosis of colorectal cancer / Actualización sobre la utilidad de la PET/TC colonografía en el diagnóstico del cáncer colorrectal

No disponible

LRP5 associates with specific subsets of macrophages: Molecular and functional effects.

Innate and acquired immunity is involved in the progression of atherosclerosis. The molecular mechanisms ruling monocyte to macrophage (Mø) differentiation are not yet fully understood. Different subtypes of plaque macrophages that have differentiated from monocytes recruited from circulating blood, have been characterized based on surface epitopes. We have recently shown that LRP5, a member of the LDL receptor superfamily supporting Wnt signalling, has an important role in monocyte to macrophage differentiation. The aim of this study was to investigate whether the CD16- and CD16+ macrophage subsets found in human atherosclerotic plaques have a differential LRP5 expression/function and Wnt signalling potential. We show for the first time that LRP5 expression is significantly higher in human CD16+Mø derived from CD14(+)CD16(+) monocytes than in CD16-Mø macrophages derived from CD14(+)CD16(-) monocytes. LRP5 is not found in human healthy vessel or arterial intimal thickening but is found in advanced human atherosclerotic lesions co-localizing only with the CD16+Mø macrophage subset. LRP5 expressing macrophages infiltrate the deep layers of atherosclerotic plaques towards the intima-media boundaries showing increased migratory activity and higher phagocytic activity. The equivalent for human patrolling CD14(+)CD16(+) monocytes in mice, CD115(+)GR1(low) monocytes, also show an increased expression of LRP5. In summary, classical CD14(+)CD16(-)monocytes that differentiate into CD16-Mø do not express LRP5. Instead, human monocytes expressing LRP5 differentiate into CD16+Mø antiinflammatory macrophages. These antiinflammatory macrophages are found in advanced atherosclerotic human plaques. Thus LRP5 is a signature of the anti-inflammatory defensive phenotype of macrophages.

Choroid Plexus Neoplasms: Toward a Distinction between Carcinoma and Papilloma Using Arterial Spin-Labeling.

Pediatric choroid plexus papillomas and carcinomas are highly vascularized neoplasms, which are difficult to distinguish with conventional imaging. We aimed to analyze the diagnostic accuracy of PWI, by using both pseudocontinuous arterial spin-labeling and DSC-PWI. We reviewed the PWI of 13 children with choroid plexus neoplasms (7 papillomas and 6 carcinomas). We quantified CBF, relative CBF, and relative CBV in each lesion and compared papillomas and carcinomas. Relative CBF values by using arterial spin-labeling were significantly higher for carcinomas (P = .028). The median value of relative CBF was 1.7 (range, 1.4-1.9) for carcinomas and 0.4 (range, 0.3-0.6) for papillomas. The CBF median value was 115 mL/min/100 g (range, 90-140 mL/min/100 g) for carcinomas and 41 mL/min/100 g (range, 10-73 mL/min/100 g) for papillomas (P = .056). Measures with DSC-PWI were more variable and not significantly different (P = .393). Arterial spin-labeling is a promising technique to differentiate choroid plexus carcinomas and papillomas.

Activation of the Prostaglandin E2 receptor EP2 prevents house dust mite-induced airway hyperresponsiveness and inflammation by restraining mast cells' activity.

BACKGROUND: Prostaglandin E2 (PGE2 ) has been proposed to exert antiasthmatic effects in patients, to prevent antigen-induced airway pathology in murine models, and to inhibit mast cells (MC) activity in vitro. OBJECTIVE: To assess in a murine model whether the protective effect of PGE2 may be a consequence of its ability to activate the E-prostanoid (EP)2 receptor on airway MC. METHODS: Either BALB/c or C57BL/6 mice were exposed intranasally (i.n.) to house dust mite (HDM) aeroallergens. Both strains were given PGE2 locally (0.3 mg/kg), but only BALB/c mice were administered butaprost (EP2 agonist: 0.3 mg/kg), or AH6809 (EP2 antagonist; 2.5 mg/kg) combined with the MC stabilizer sodium cromoglycate (SCG: 25 mg/kg). Airway hyperresponsiveness (AHR) and inflammation, along with lung MC activity, were evaluated. In addition, butaprost's effect was assessed in MC-mediated passive cutaneous anaphylaxis (PCA) in mice challenged with 2,4-dinitrophenol (DNP). RESULTS: Selective EP2 agonism attenuated aeroallergen-caused AHR and inflammation in HDM-exposed BALB/c mice, and this correlated with a reduced lung MC activity. Accordingly, the blockade of endogenous PGE2 by means of AH6809 worsened airway responsiveness in sensitive BALB/c mice, and such worsening was reversed by SCG. The relevance of MC to PGE2 -EP2 driven protection was further highlighted in MC-dependent PCA, where butaprost fully prevented MC-induced ear swelling. Unlike in BALB/c mice, PGE2 did not protect the airways of HDM-sensitized C57BL/6 animals, a strain in which we showed MC to be irrelevant to aeroallergen-driven AHR and inflammation. CONCLUSIONS & CLINICAL RELEVANCE: The beneficial effect of both exogenous and endogenous PGE2 in aeroallergen-sensitized mice may be attributable to the activation of the EP2 receptor, which in turn acts as a restrainer of airway MC activity. This opens a path towards the identification of therapeutic targets against asthma along the 'EP2 -MC-airway' axis.

Novel CK2α and CK2ß subunits in maize reveal functional diversification in subcellular localization and interaction capacity.

In plants, CK2α/ß subunits are encoded by multigenic families. They assemble as heterotetrameric holoenzymes or remain as individual subunits and are usually located in distinct cell compartments. Here we revise the number of maize CK2α/ß genes, bringing them up to a total of eight (four CK2α catalytic and four CK2ß regulatory subunits). We characterize CK2ß4, which presents nuclear localization and interacts with CK2α1, CK2α3, CK2ß1, and CK2ß3. We also describe two CK2α isoforms (CK2α2 and CK2α4) containing N-terminal extensions that correspond to putative cTPs (chloroplast transit peptides). These cTPs are functional and responsible for the subcellular localization of CK2α2 and CK2α4 in chloroplasts. Phylogenetic analysis of the CK2α gene family, further supported by the gene structure and architecture of conserved protein domains, reveals the evolutionary expansion and diversification of this family. The subcellular localization of all four CK2α isoforms was found to be altered when were co-expressed with CK2ß, thereby pointing to the latter as regulators of CK2α localization.

[Macrophage activation syndrome and autoimmunity due to visceral leishmaniasis]. / Syndrome d'activation macrophagique et auto-immunité cortico-sensible révélateurs d'une leishmaniose viscérale.

Hemophagocytic syndromes are a heterogeneous group of diseases characterized by an excessive immune response, mediated by activated cytotoxic T cells and macrophages. Among hemophagocytic syndromes, genetic and secondary forms can be distinguished. We report on the case of a male newborn who presented with macrophage activation syndrome associated with lymphoproliferation with favorable outcome under prednisone and cyclosporin. Hemopathy, infection, or genetic lymphohistiocytosis were initially ruled out. Severe autoimmunity was suspected because of positive antinuclear antibodies and Farr test associated with anemia and a positive Coombs test as well as cytolytic hepatitis with anti-liver, kidney microsome (LKM) antibodies. Treatment was therefore intensified by adding mycophenolate mofetil. This led to an unexpected deterioration of general health and lab exam results with recurrence of fever and inflammation. The initial investigations were revisited and completed by a liver biopsy, which revealed the presence of numerous leishmania parasites at the amastigote stage, enabling the diagnosis of visceral leishmaniasis. The patient's condition dramatically improved under liposomal amphotericin B treatment. Our observation shows that visceral leishmaniasis can present as lupus-like syndrome with lymphoproliferation. Moreover, the lack of leishmania on marrow aspiration cannot rule out the diagnosis of visceral leishmaniasis. Detection of leishmania by serological or molecular tests is mandatory in case of hepatosplenomegaly with hemophagocytic syndrome together with autoantibodies, in order to avoid useless and life-threatening exposure to immunosuppressive treatments.

Cholesterol modulates LRP5 expression in the vessel wall.

OBJECTIVE: Macrophages are key players in atherosclerotic lesion formation and progression. We have recently demonstrated that lipid-loaded macrophages show activation of the canonical Wnt signaling pathway. METHODS: To test the in vivo role of the canonical Wnt pathway in atherosclerosis we used mice deficient in the Wnt signaling receptor LRP5 (LRP5(-/-)) fed a hypercholesterolemic diet (HC) to induce atherosclerosis. These dietary groups were further subdivided into two subgroups receiving their respective diets supplemented with 2% plant sterol esters (PSE). All mice remained on their assigned diets until age 18 weeks. RESULTS: HC WT mice had mildly increased non-HDL cholesterol levels, developed aortic atherosclerotic lesions and showed upregulated expression levels of aortic Lrp5. HC LRP5(-/-) mice develop larger aortic atherosclerotic lesions than WT mice indicating that LRP5 has a protective function in atherosclerosis progression. The oral administration of PSE, a dietary cholesterol-lowering agent, had an effect in the expression levels of the Wnt signaling receptor and in atherosclerosis progression. We found that PSE reduced serum total cholesterol levels, abolished HC-induced LRP5 overexpression and reduced aortic atherosclerotic plaques. CONCLUSION: The proatherogenic effects of the excess of plasma lipids are in part mediated by modulation of LRP5 in the aorta. LRP5 and canonical Wnt signaling exert a protective defense mechanism against hyperlipidemia and atherosclerosis lesion progression.

[Hoigne syndrome following an intravenous injection of ceftriaxone: a case report]. / Un cas de syndrome de Hoigné lors d'une injection intraveineuse de ceftriaxone.

INTRODUCTION: Hoigne's syndrome is characterized by the development of acute clinical manifestations which are mainly psycho-sensorial. Classically, these features immediately follow the injection of procaine penicillin G. CASE REPORT: We report a 59-year-old man who presented with psycho-organic manifestations that occurred just after the intravenous injection of ceftriaxone; to our knowledge, this is the first case of Hoigne's syndrome reported after an injection of this antibiotic. CONCLUSION: The pathophysiologic basis of this syndrome is still unknown. It is important to keep in mind its clinical characteristics, which may mimic immuno-allergic symptoms. It should be differentiated from anaphylactic manifestations because Hoigne's syndrome allows the continuation of the treatment.

[Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases]. / Variabilité phénotypique et corrélations génotype-phénotype des dystrophinopathies : contribution des banques de données.

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum. We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials.

Circulating biomarkers.

Cardiovascular diseases (CVD) remain a leading cause of death worldwide. In the past years new biomarkers have drawn the clinician's attention for their use in primary prevention and in the identification of individuals at cardiovascular risk. Biomarkers also provide information on the progression and possible recurrence of cardiovascular events, and include inflammatory markers (C-reactive protein and interleukin-18), endothelial dysfunction markers (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), neurohormonal markers (brain natriuretic peptide and copeptine), ischemia biomarkers (apolipoprotein J) and necrosis markers (troponins). Although biomarkers provide utility for predicting cardiovascular risk, the identification and characterization of new biomarkers to achieve increasing diagnosis and prognostic efficiency in CVD prevention is of high clinical interest. In this review we will discuss on recently discovered biomarkers and their clinical applications.

[Recurrent Guillain-Barré syndrome after surgery]. / Syndrome de Guillain-Barré postopératoire récurrent.

INTRODUCTION: Recurrent Guillain-Barré syndrome is a very rare entity. Few cases have been reported. CASE REPORT: We report two patients who have developed a recurrent Guillain-Barré syndrome where one or even two episodes occurred after the same type of surgery, a hip prosthesis replacement. DISCUSSION: Occurrence of Guillain-Barré syndrome after surgery has mainly been reported in relation to epidural anesthesia and less frequently general anesthesia. Although underlying pathogenic mechanisms remain unknown, a molecular mimicry phenomenon has been proposed.

Pathogenesis of Eimeria praecox in chickens: virulence of field strains compared with laboratory strains of E. praecox and Eimeria acervulina.

The pathogenesis in chickens of the apicomplexan Eimeria praecox was compared with that of Eimeria acervulina, using intestinal lesions, mucosal integrity, body weight gain (BWG) and the feed conversion ratio (FCR) as criteria. Characteristics of each species were described by combinations of polymerase chain reaction assays and classic parasitological signs. There were considerable overlaps in lengths, breadths, shape indices and volumes of the oocysts of each species. Both species caused statistically significant reductions in BWG at the lowest inocula tested (500,000 sporulated oocysts per bird of E. praecox and 250,000 of E. acervulina). E. praecox was observed for the first time to cause actual body weight loss and marked increases in FCR, as did E. acervulina. E. acervulina caused gross, white pathognomonic lesions, but E. praecox caused micro-lesions, visible in fresh tissue only with a dissecting microscope. Occasionally, lesions of the Houghton strain of E. acervulina were observed to be rounded, rather than typically "ladder-like". Both species caused villous erosion and atrophy. No mortality occurred in birds receiving up to 1 million sporulated oocysts of either species. Using BWG and FCR as criteria, the virulence of recent field strains of E. praecox from Wales (Tynygongl) and the USA (Raleigh) was compared with English laboratory strains of E. praecox (Houghton) and E. acervulina (Houghton). E. praecox (Tynygongl) was markedly more virulent than E. acervulina (Houghton), which was more virulent than E. praecox (Raleigh) and E. praecox (Houghton).