Paul Legmann’s research while affiliated with Hôpital Cochin (Hôpitaux Universitaires Paris Centre) and other places

PurposeTo determine efficacy and safety of thermal ablation (TA) for the local treatment of lung metastases of thyroid cancer.Methods We retrospectively studied 47 patients from 10 centers treated by TA (radiofrequency, microwaves, and cryoablation) over 10 years. The endpoints were overall survival (OS), local efficacy, complications (CTCAE classification), and factors associated with survival. OS curves after first TA were built using the Kaplan–Meier method and compared with the log-rank test.ResultsA total of 107 lung metastases during 75 sessions were treated by radiofrequency (n = 56), microwaves (n = 9), and cryoablation (n = 10). Median follow-up time after TA was 5.2 years (0.2–13.3). OS was 93% at 2 years (95% confidence interval (CI): 86–94) and 79% at 3 years (95% CI: 66–91). On univariate and multivariate analysis with a Cox model, histology was the only significant factor for OS. OS at 3 years was 94% for follicular, oncocytic, or papillary follicular variant carcinomas, compared to 59% for papillary, medullary, insular or anaplastic carcinomas (P = 0.0001). The local control rate was 98.1% at 1 year and 94.8% at 2, 3, 4, and 5 years. Morbidity was low with no major complications (grade 4 and 5 CTCAE) and no complications in 29 of 75 sessions (38.7%).ConclusionsTA is a useful, safe and effective option for local treatment of lung metastases from thyroid carcinoma. Prolonged OS was obtained, especially for lung metastases from follicular, oncocytic, or papillary follicular variant carcinomas. Achieving disease control with TA delays the need for systemic treatment.

Objective Myocardial involvement may occur during systemic sclerosis (SSc) and can lead to impaired myocardial contraction and/or arrhythmia. Cardiac magnetic resonance imaging (MRI) is used for noninvasive characterization of the myocardium. The aim of this study was to evaluate the utility of cardiac MRI with intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and longitudinal relaxation time (T1) sequence mapping for assessment of myocardial microvascular and interstitium impairment in SSc. Methods In this single‐center prospective cohort study, 40 consecutive patients with SSc and 20 healthy controls were assessed by cardiac MRI with IVIM DWI and T1 mapping sequences on a 3T scanning system. Images were analyzed independently by 2 assessors, and Bland‐Altman plots were used to assess interreader concordance and reproducibility. Characteristics of the patients were compared according to quartiles of T1 and perfusion fraction (f‐coefficient) values, using exact Cochran‐Ermitage trend tests for qualitative variables and analysis of variance for quantitative variables. Kaplan‐Meier cardiac events–free survival curves were plotted and compared with a log‐rank test for trend. Results T1 values were higher in SSc patients than in healthy controls, and were higher in the diffuse cutaneous SSc (dcSSc) subset (P = 0.02). Higher T1 values were associated with the immunologic pattern seen in patients with the dcSSc form (P = 0.0001), a higher modified Rodnan skin thickness score (MRSS) (P = 0.003), and a higher frequency of interstitial lung disease (P = 0.03). Moreover, higher T1 values were correlated with higher MRSS scores (r = +0.32, P = 0.04) and reduced forced vital capacity (r = −0.34, P = 0.048), and tended to be correlated with reduced total lung capacity (r = −0.30, P = 0.07). Lower f‐coefficient values, as a measure of decreased tissue perfusion, were associated with less frequent use of vasodilators (P = 0.02 for angiotensin‐converting enzyme inhibitors and P = 0.06 for calcium‐channel blockers) and more frequent use of glucocorticoids (P = 0.02). The f‐coefficients were inversely correlated with the T1 values (r = −0.31, P = 0.02). Furthermore, higher T1 values were associated with higher incidence of cardiac events (log‐rank test for trend P = 0.03). Conclusion Increased T1 values, potentially suggesting microscopic fibrosis, were observed more frequently in patients with dcSSc, and higher T1 values were associated with interstitial lung disease and more frequent cardiac events during follow‐up. The results of this study show that cardiac MRI with T1 mapping sequences and IVIM DWI may be useful in assessing myocardial involvement in patients with SSc.

Purpose: This study aimed to report the magnetic resonance imaging (MRI) features of acinar cell carcinoma (ACC) of the pancreas including diffusion-weighted MRI findings. Materials and methods: The MRI examinations of five patients (3 men, 2 women; median age, 61years) with histopathologically proven ACC of the pancreas were retrospectively reviewed. MR images were analyzed qualitatively (location, shape, homogeneity, signal intensity, vascular involvement and extrapancreatic extent of ACC) and quantitatively (tumor size, apparent diffusion coefficient [ADC] and normalized ADC of ACC). Results: All ACC were visible on MRI, presenting as an oval pancreatic mass (5/5; 100%), with moderate and heterogeneous enhancement (5/5; 100%), with a median transverse diameter of 43mm (Q1, 35; Q3, 82mm; range: 30-91mm). Tumor capsule was visible in 4/5 ACC (80%) and Wirsung duct enlargement in 2/5 ACC (40%). On diffusion-weighted MRI, all ACC (5/5; 100%) were hyperintense on the 3 b value images. Median ADC value of ACC was 1.061×10-3mm2/s (Q1, 0.870×10-3mm2/s; Q3, 1.138×10-3mm2/s; range: 0.834-1.195×10-3mm2/s). Median normalized ADC ratio of ACC was 1.127 (Q1, 1.071; Q3, 1.237; range: 1.054-1.244). Conclusions: On MRI, ACC of the pancreas presents as a large, oval pancreatic mass with moderate and heterogeneous enhancement after intravenous administration of a gadolinium chelate, with restricted diffusion and a median ADC value of 1.061×10-3mm2/s on diffusion-weighted MRI. Further studies however are needed to confirm our findings obtained in a limited number of patients.

Introduction Des études ont montré l’atteinte possible du myocarde au cours de la sclérodermie systémique (ScS), entraînant une insuffisance cardiaque. Nous avons montré précédemment que l’imagerie par résonance magnétique (IRM) cardiaque avec séquences en mapping T1 pouvait détecter la fibrose myocardique microscopique chez 50 % des patients atteints de ScS, en particulier chez ceux présentant des formes cutanées diffuses. Cependant, aucune donnée prospective n’est encore disponible pour analyser l’impact pronostique de cette fibrose sur le pronostic cardiaque chez les patients atteints de ScS. Patients et méthodes Nous avons mené une étude prospective monocentrique de patients consécutifs atteints de ScS répondant aux critères ACR/EULAR. Des séquences d’IRM cardiaque en mapping T1 et en diffusion ont été réalisées chez tous les patients. Les séquences mapping T1 évaluent l’infiltration myocardique du collagène, définissant la fibrose microscopique. Les patients ont été suivis prospectivement pour détecter la survenue d’événements cardiovasculaires et évaluer la diminution de la fraction d’éjection ventriculaire gauche en échographie cardiaque. Résultats Quarante patients, 35 femmes et 5 hommes, d’âge moyen de 54,7 ± 14,6 ans, ont été inclus. À l’inclusion, les patients présentaient des formes cutanées diffuses dans 19 cas, des formes cutanées limitées dans 16 cas et une sclérodermie limitée dans 5 cas. Le délai médian entre le diagnostic de la maladie et l’IRM cardiaque était de 77 mois (1–302). Une fibrose myocardique microscopique était observée chez 21 patients (53 %) atteints de ScS. Après un suivi médian de 38,2 mois (EIQ 19,4–41,0), 10 patients (25 %) ont présenté des événements cardiovasculaires : hospitalisation pour trouble du rythme cardiaque dans 7 cas, insuffisance cardiaque dans 2 cas (décès dans un cas) et angine instable dans un cas. La présence d’une fibrose myocardique microscopique à l’inclusion était significativement associée à une survie sans événements cardiovasculaires plus faible (p = 0,02). Le hazard ratio (intervalle de confiance à 95 %) pour la survenue d’événements cardiovasculaires incidents chez les patients atteints de fibrose myocardique microscopique était de 4,47 (1,27–15,8) par rapport à ceux sans fibrose microscopique. En revanche, aucune différence dans la diminution de la FEVG cours du suivi n’a été mis en évidence entre les patients avec et sans fibrose myocardique microscopique (de 62,03,2 et 62,94,7 % à l’inclusion à 59,010,8 et 59, 45,3 % à 36 mois, respectivement). Conclusion Cette étude montre une association significative entre la fibrose myocardique microscopique évaluée sur l’IRM cardiaque et la survenue d’événements cardiovasculaires dans la sclérodermie systémique. En revanche, aucun impact sur le déclin de la FEVG n’était observé au cours du suivi. L’impact pronostique de la fibrose myocardique microscopique doit être évaluée dans des études plus larges, en particulier chez les patients présentant des formes cutanées diffuses.

Objectives: To develop an automated density-based computed tomography (CT) score evaluating high-attenuating lung structural abnormalities in patients with cystic fibrosis (CF). Methods: Seventy adult CF patients were evaluated. The development cohort comprised 17 patients treated with ivacaftor, with 45 pre-therapeutic and follow-up chest CT scans. Another cohort of 53 patients not treated with ivacaftor was used for validation. CT-density scores were calculated using fixed and adapted thresholds based on histogram characteristics, such as the mode and standard deviation. Visual CF-CT score was also calculated. Correlations between the CT scores and forced expiratory volume in 1 s (FEV1% pred), and between their changes over time were assessed. Results: On cross-sectional evaluation, the correlation coefficients between FEV1%pred and the automated scores were slightly lower to that of the visual score in the development and validation cohorts (R = up to -0.68 and -0.61, versus R = -0.72 and R = -0.64, respectively). Conversely, the correlation to FEV1%pred tended to be higher for automated scores (R = up to -0.61) than for visual score (R = -0.49) on longitudinal follow-up. Automated scores based on Mode + 3 SD and Mode +300 HU showed the highest cross-sectional (R = -0.59 to -0.68) and longitudinal (R = -0.51 to -0.61) correlation coefficients to FEV1%pred. Conclusions: The developed CT-density score reliably quantifies high-attenuating lung structural abnormalities in CF. Key points: • Automated CT score shows moderate to good cross-sectional correlations with FEV 1 %pred . • CT score has potential to be integrated into the standard reporting workflow.

Purpose: To compare inter-reader concordance and accuracy of qualitative diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for the diagnosis of peripheral zone prostate cancer. Materials and methods: Two radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74 patients (64.3±5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men). A standardised ADCmean and nine ADC-derived parameters were measured, including ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror-ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were the reference for tumours and benign foci, respectively. Inter-reader agreement was assessed by the Cohen-kappa-coefficient and the intraclass correlation coefficient (ICC). Univariate-multivariate regressions determined the most predictive factor for cancer. Results: Fifty lesions were malignant. Inter-reader concordance was fair for qualitative assessment, but excellent for quantitative assessment for all quantitative variables. At univariate analysis, ADCmean, WP-ADCratio and WL-ADCmean performed equally, but significantly better than the mirror-ADCratio (p<0.001). At multivariate analysis, the only independent variable significantly associated with malignancy was the whole-prostate-ADCratio. At a cut-off value of 0.68, sensitivity was 94-90 % and specificity was 60-38 % for readers 1 and 2, respectively. Conclusion: The whole-prostate-ADCratio improved the qualitative inter-reader concordance and characterisation of focal PZ-lesions. Key points: • Inter-reader concordance of DW PI-RADSv2.0 score for PZ lesions was only fair. • Using a standardised ADCmean measurement and derived DW-quantitative parameters, concordance was excellent. • The whole-prostate ADCratio performed significantly better than the mirror-ADCratio for cancer detection. • At a cut-off of 0.68, sensitivity values of WP-ADCratio were 94-90 %. • The whole-prostate ADCratio may circumvent variations of ADC metrics across centres.

Contexte Le syndrome de Nelson associe classiquement un macroadénome corticotrope et une ACTH élevée après surrénalectomie bilatérale. En 2007, le concept de progression tumorale corticotrope était proposé comme plus adapté à la pratique clinique moderne. Comme les progressions rapides sont bien plus problématiques que les progressions lentes, nous proposons d’affiner ce concept en considérant la vitesse de progression tumorale corticotrope (VPC). Objectif Décrire la VPC et identifier les facteurs associés. Méthodes Quatre-vingt-dix-neuf patients avec maladie de Cushing suivis à Cochin, ayant subi une surrénalectomie entre 1991 et 2016 sont inclus. Les données cliniques et biologiques (tests au ddAVP, au CRH, au freinage fort) ont été colligées, ainsi que l’histologie hypophysaire. Les IRM hypophysaires ont été relues. La VPC a été mesurée, exprimée en mm/an. Le suivi moyen était de 8 ans. Résultats La VPC maximale par patient varie entre 0 et 40,7 mm/an. La VPC maximale est observée entre 0,13 et 14,4 années après surrénalectomie. La VPC maximale est corrélée à l’ACTH dans l’année suivant la SBT (p = 0,02). Pendant le suivi, la VPC est corrélée au pic d’ACTH après ddAVP (p = 0,003). L’apoplexie, le syndrome caverneux et les troubles du champ visuel sont associées aux VPC les plus élevées (p < 0,05). La grossesse n’est pas associée à une VPC plus élevée. Enfin, la VPC n’est pas plus élevée après surrénalectomie qu’avant, suggérant que la surrénalectomie n’accélère pas la croissance tumorale corticotrope. Discussion La VPC est probablement la mesure la plus adaptée pour le suivi des adénomes corticotropes après surrénalectomie.

Purpose: We aimed to identify modifiable and nonmodifiable risk factors for hemoptysis complicating computed tomography (CT)-guided transthoracic needle biopsy. Methods: All procedures performed in our institution from November 2013 to May 2015 were reviewed. Hemoptysis was classified as mild if limited to hemoptoic sputum and abundant otherwise. Presence of intra-alveolar hemorrhage on postbiopsy CT images was also evaluated. Patient- and lesion-related variables were considered nonmodifiable, while procedure-related variables were considered modifiable. Results: A total of 249 procedures were evaluated. Hemoptysis and alveolar hemorrhage occurred in 18% and 58% of procedures, respectively, and were abundant or significant in 8% and 17% of procedures, respectively. Concordance between the occurrence of significant alveolar hemorrhage (grade ≥2) and hemoptysis was poor (κ=0.28; 95% CI [0.16-0.40]). In multivariate analysis, female gender (P = 0.008), a longer transpulmonary needle path (P = 0.014), and smaller lesion size (P = 0.044) were independent risk factors for hemoptysis. Transpulmonary needle-path length was the only risk factor for abundant hemoptysis with borderline statistical significance (P = 0.049). Conclusion: The transpulmonary needle path should be as short as possible to reduce the risk of abundant hemoptysis during CT-guided transthoracic needle biopsy.

New European guidelines for the management of adrenal incidentalomas were recently released. One of the most novel recommendations is to stop following patients when they present a typical, small and non-secreting adenoma. We report here the case of a 71-year-old man with such an adenoma, who developed an adrenocortical carcinoma (ACC) fourteen years later, with subsequent metastases and death. Clinically he had a normal blood pressure and no sign of hormonal hypersecretion. The hormonal work-up showed no hormone excess: urinary free cortisol level was normal, the diurnal cortisol rhythm was respected and urinary catecholamine metabolites levels were normal. Computed tomography (CT) scan showed a homogeneous lesion, with a low density. The lesion remained unchanged during the five years of follow-up. Eight years after the last CT, a large right heterogeneous adrenal mass was incidentally discovered during an ultrasound examination. On CT-scan it was a 6 cm heterogeneous tumor. On hormonal work-up there was no secretion. The patient was operated of an adrenalectomy and the histology described an ACC with a Weiss score at 8, with no benign contingent. To our knowledge this is the first case of an ACC occurring in a patient with prior adrenal imaging showing a typical benign adenoma.

Objectives.: Specific cardiac involvement in granulomatosis with polyangiitis (GPA) is probably underestimated since many of these conditions are subclinical. The objective of this study was to assess the prevalence and patterns of cardiac abnormalities detected by cardiac MRI (CMRI) in patients with GPA. Methods.: Thirty-one consecutive patients with newly diagnosed or relapsing GPA underwent CMRI to assess morphological, functional, perfusion at rest and delayed enhancement abnormalities. Results.: At least one abnormality was observed on CMRI for 19 of 31 patients (61%). Four patients (13%) had an impaired left ventricle ejection fraction (LVEF). LV regional wall motion abnormalities were found in 11 patients (35%). Late gadolinium enhancement (LGE) was detected in 10 of 31 patients (32%). LGE was mostly nodular ( n = 9). Myocardial early contrast enhancement was detected in 5 of the 31 patients (16%), which was systematically associated with LGE in the same territory. CMRI detected pericarditis in eight patients (26%). GPA with <18 months duration was associated with a higher LVEF ( P = 0.03), fewer CMRI abnormalities ( P = 0.04) and less LV hypokinesia ( P = 0.04) than GPA with a longer duration. Patients with recent-onset GPA had a higher LVEF ( P = 0.01) and less LV hypokinesia ( P = 0.006) than patients experiencing a relapse ( P = 0.02). Conclusion.: CMR is an accurate technique for detecting heart involvement in GPA. This unique non-invasive technique may provide information with important clinical implications for the accurate early assessment of cardiac lesions in GPA patients and for detecting cumulative, irreversible damage. It may also have prognostic implications.