Au cœur de la cardiomyopathie diabétique

Le diabète de type 2 (DT2) est un facteur de risque indépendant de l’insuffisance cardiaque. Ces anomalies sont cependant associées à une lipotoxicité et à une glucotoxicité cardiaques. Pourtant, les mécanismes exacts de ces toxicités cardiaques demeurent inconnus. Récemment, le phénotype cardiaque d’un modèle unique de DT2, les souris lipodystrophiques invalidées pour le gène codant la seipine (SKO), a révélé l’importance de la glucotoxicité dans le développement des anomalies cardiaques. En effet, les souris SKO présentent une cardiomyopathie associée à une surcharge en glucose, qui est corrigée par l’utilisation d’un agent hypoglycémiant, un inhibiteur du co-transporteur sodium-glucose de type 2 (SGLT2). Dans ce modèle, la glucotoxicité peut ainsi, à elle seule, générer les dysfonctions cardiaques associées au diabète

18F-FDOPA PET Compared With 123I-Metaiodobenzylguanidine Scintigraphy and 18F-FDG PET in Secreting Sporadic Pheochromocytoma

International audienceWe report the case of a 23-year-old man presenting a right hypersecreting pheochromocytoma, falsely negative on 18 F-FDG PET/CT and on 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy but strongly positive on 18 F-FDOPA PET/CT. Functional imaging has a key role in diagnosis and prognosis of pheochromocytomas, but choosing the most relevant modality remains difficult. Despite its high specificity, 123 I-MIBG has a limited sensitivity. 18 F-FDG can be used, but it is an unspecific tracer, and 18 F-FDG uptake in brown adipose tissue can hinder the analysis. However, 18 F-FDOPA shows very high sensitivity and specificity in pheochromocyto-mas with fewer drug interferences than 123 I-MIBG

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

International audienceThe STK11/LKB1 gene codes for liver kinase B1 (STK11/LKB1), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for STK11/LKB1 involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of STK11/LKB1 leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of STK11/LKB1 is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8+ T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of STK11/LKB1 and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of STK11/LKB1 alterations on the immune system and response or resistance to immune checkpoint inhibitors

Carcinoembryonic Antigen Increase in a Patient with Colon Cancer Who Have Achieved Complete Remission and Negative 18F-FDG PET/CT: Don’t Forget the Thyroid!

International audienceSerum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18Ffluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations

Meningiomas and cyproterone acetate: a retrospective, monocentric cohort of 388 patients treated by surgery or radiotherapy for intracranial meningioma

International audiencePurpose Meningiomas are the most common intracranial tumors, accounting for 20-30% of central nervous system tumors. Recently, the European Medicines Agency issued an alert on cyproterone acetate (CPA) based on the results of a study that found an increased risk of meningioma 7 to 20 times higher when a patient is on CPA. The primary objective of this study was to determine the prevalence of CPA exposure in patients who had one or more intracranial meningiomas treated surgically or with radiation therapy. The secondary objectives were to establish a description of the patients who had intracranial meningioma in Nantes and to establish whether there was a difference in the intrinsic and tumoral characteristics of patients exposed to CPA compared with patients who had no hormonal exposure and patients who had been exposed to other hormones. Methods Monocentric, retrospective study including all patients treated by surgery or radiotherapy for intracranial meningioma from 2014 to 2017 excluding those with a history of exposure to ionizing radiation or neurofibromatosis type 2. Results 388 patients were included, 277 were treated by surgery and 111 by radiotherapy. 3.9% of the patients had a history or current use of CPA, 16.2% were taking other hormonal treatment. Compared with the group without hormonal exposure, the CPA-exposed group had significantly an earlier onset of meningiomas at 48.9 vs. 61.9 years (p = 0.0005) and had more multiple meningiomas, 26.7% vs. 6.1% (p = 0.0115). Conclusions In our study, patients with a history or current use of CPA had significantly more meningiomas and were significantly younger at the onset

Prospective Multicentric Assessment of ⁶⁸Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET

The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs