Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab.

BACKGROUND: An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment. PATIENTS AND METHODS: All pts with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC) who received anti-PD1 nivolumab monotherapy in second-line setting or later were included in this French multicentric retrospective study. NLR values were prospectively collected prior to each nivolumab administration. Clinical characteristics were recorded. Associations between baseline NLR, NLR variations and survival outcomes were determined using Kaplan-Meier's method and multivariable Cox regression models. RESULTS: 161 pts (86 mRCC and 75 mNSCLC) were included with a median follow-up of 18 months. On the whole cohort, any NLR increase at week 6 was significantly associated with worse outcomes compared to NLR decrease, with a median PFS of 11 months vs 3.7 months (p < 0.0001), and a median OS of 28.5 months vs. 18 months (p = 0.013), respectively. In multivariate analysis, NLR increase was significantly associated with worse PFS (HR 2.2; p = 6.10-5) and OS (HR 2.1; p = 0.005). Consistent results were observed in each cohort when analyzed separately. CONCLUSION: Any NLR increase at week 6 was associated with worse PFS and OS outcomes. NLR variation is an inexpensive and dynamic marker easily obtained to monitor anti-PD1 efficacy.

Epidemiology of Lyme borreliosis through two surveillance systems: the national Sentinelles GP network and the national hospital discharge database, France, 2005 to 2016.

BACKGROUND: Lyme borreliosis (LB) is the most frequent vector-borne disease in France. Since 2009, surveillance of LB is conducted by a sentinel network of general practitioners (GPs). This system, in conjunction with the national hospitalisation database was used to estimate the incidence and describe the characteristics of LB in France. AIM: To describe the estimated incidence and trends in GP consultations and hospital admissions for LB in France and identify risk groups and high-incidence regions. RESULTS: From 2011 to 2016, the mean yearly incidence rate of LB cases was 53 per 100,000 inhabitants (95% CI: 41-65) ranging from 41 in 2011 to 84 per 100 000 in 2016. A mean of 799 cases per year were hospitalised with LB associated diagnoses 2005-16. The hospitalisation incidence rate (HIR) ranged from 1.1 cases per 100,000 inhabitants in 2005 to 1.5 in 2011 with no statistically significant trend. We observed seasonality with a peak during the summer, important inter-regional variations and a bimodal age distribution in LB incidence and HIR with higher incidence between 5 and 9 year olds and those aged 60 years. Erythema migrans affected 633/667 (95%) of the patients at primary care level. Among hospitalised cases, the most common manifestation was neuroborreliosis 4,906/9,594 (51%). CONCLUSION: Public health strategies should focus on high-incidence age groups and regions during the months with the highest incidences and should emphasise prevention measures such as regular tick checks after exposure and prompt removal to avoid infection.

Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives.

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials involves examination of i) technical performance to determine biomarker bias and reproducibility and ii) biological performance to interrogate a specific aspect of biology or to forecast outcome. Unfortunately, the variety of acquisition and analysis methodologies employed at different centres make ADC values non-comparable between them. This invalidates implementation in multicentre trials and limits utility of ADC as a biomarker. This article reviews the factors contributing to ADC variability in terms of data acquisition and analysis. Hardware and software considerations are discussed when implementing standardised protocols across multi-vendor platforms together with methods for quality assurance and quality control. Processes of data collection, archiving, curation, analysis, central reading and handling incidental findings are considered in the conduct of multicentre trials. Data protection and good clinical practice are essential prerequisites. Developing international consensus of procedures is critical to successful validation if ADC is to become a useful biomarker in oncology. KEY POINTS: • Standardised acquisition/analysis allows quantification of imaging biomarkers in multicentre trials. • Establishing "precision" of the measurement in the multicentre context is essential. • A repository with traceable data of known provenance promotes further research.

Road traffic accidents: a pictorial review.

Road traffic accidents are still a major cause of morbidity and mortality. With well-established whole-body CT protocols in trauma, radiologists are an integral part of trauma diagnosis and management teams. Five well-recognized traumatic syndromes (seat belt syndrome, handlebar syndrome, scapulothoracic dissociation, dashboard syndrome, and brake pedal injury) with their frequent associated complications should be diagnosed precociously according to the accident mechanism to avoid diagnostic delays and poor prognosis even if the circumstances seem minor.

[Self-injuring, a symptom retaining our attention]. / L'automutilation, ce symptôme qui retient notre attention.

Self-injuring is a process that usually occurs during adolescence; its prevalence has increased over recent years. Nowadays, nearly one out of six teenagers is concerned. The most frequent form is the «superficial¼ one and corresponds to the term NSSI (Non Suicidal Self Injury) recently mentioned in the third section of the DSM-5. More and more publicized, this practice may disturb. However, it reflects an underlying state of psychic suffering and should not be underestimated or dramatized. It has to be considered as a form of coping even if it is clearly damaging and, in some cases, may be connected to a higher suicidal risk. This article aims at raising the reader's attention to this expression of the patient's pain. A better approach of this symptom in its context enables to better understand its clinical significance and to adapt the therapeutical approach.

L'automutilation est un phénomène, habituellement rencontré durant l'adolescence, dont la prévalence a augmenté au cours des dernières années. Elle concerne aujourd'hui près d'un jeune sur six. La modalité dite «superficielle¼ est le plus fréquemment rencontrée et correspond au terme NSSI (Non Suicidal Self Injury) ou «lésions auto-infligées non suicidaires¼ récemment repris dans la section 3 du DSM-5. De plus en plus médiatisée, cette pratique interpelle. Elle reflète une souffrance psychique sous-jacente et ne doit être ni banalisée, ni dramatisée. Elle est à considérer comme un mode d'adaptation dommageable pouvant être associé à une augmentation du risque suicidaire. Le but de cet article est de sensibiliser le lecteur à cette forme d'expression de la souffrance chez un patient jeune. Mieux appréhender le geste dans son contexte permet d'en comprendre la valeur clinique et d'adapter la prise en charge.

External radiation dose and cancer mortality among French nuclear workers: considering potential confounding by internal radiation exposure.

OBJECTIVES: French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. METHODS: A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat à l'Energie Atomique), AREVA NC, or EDF (Electricité de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. RESULTS: For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. CONCLUSIONS: This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination.

Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.

OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology. METHODS: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured. RESULTS: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1). CONCLUSION: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness. KEY POINTS: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.

Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting.

Many drugs are available in renal cell carcinoma (RCC), yet clinicians are still looking for predictive biomarkers of disease recurrence or progression supporting more personalised treatments. An assessment of circulating biomarkers over time was carried out in this French, open-label, single-arm, multicentre trial conducted in 25 patients with either locally advanced (n = 14) or metastatic RCC (n = 11) who received everolimus (10 mg daily) for 6 weeks prior to nephrectomy (NEORAD, NCT01715935). Circulating biomarkers, including circulating tumour cells, haematopoietic and endothelial cells, plasma angiogenesis and inflammatory markers were quantified at baseline, upon everolimus and post-nephrectomy. We assessed tumour burden, objective response rate upon RECIST1.1, disease-free survival (DFS) and progression-free survival (PFS). The correlation between circulating biomarkers was evaluated with multiple factor analysis and biomarker association with DFS/PFS by Cox regression. No objective response rate was obtained before nephrectomy. Upon everolimus, neutrophils, platelets and sVEGFR2 significantly decreased. We did not find any association between circulating biomarkers and DFS/PFS, but patients with the highest tumour burden at baseline had significantly higher plasma levels of interleukin-6, an inflammatory circulating biomarker, and lower levels of sVEGFR2, related to angiogenesis. Further understanding of the link between these circulating biomarkers could help to optimise drug combinations in RCC.

First cases of Omicron in France are exhibiting mild symptoms, November 2021-January 2022.

OBJECTIVES: We aimed to investigate the first Omicron cases detected in France in order to assess case characteristics and provide supporting information on the possible impact of this variant on the healthcare system. METHODS: A standardized questionnaire was used to collect information from confirmed and probable Omicron cases. RESULTS: Median age of 468 investigated cases was 35 years, 376 were symptomatic (89%); 64% were vaccinated with two doses and 7% had received three doses. Loss of smell and taste were reported by 8.3% and 9% of cases, respectively. Seven cases were hospitalized, three of those were unvaccinated (including two with reported precondition). No admissions to intensive care and no deaths were reported. CONCLUSIONS: Our results confirm a mild clinical presentation among the first Omicron cases detected in France and highlight the importance for the national COVID-19 surveillance system to quickly detect and adapt to the emergence of a new variant.

[Epithelial ovarian cancers and minimally invasive cytoreductive surgery after neoadjuvant chemotherapy: A systematic review]. / Cancers épithéliaux de l'ovaire et chirurgie de cytoréduction par voie mini-invasive après chimiothérapie néoadjuvante : revue systématique de la littérature.

INTRODUCTION: Advanced epithelial ovarian cancer (EOC) is associated with high mortality and often managed first with neoadjuvant chemotherapy (NACT) followed by debulking surgery. Laparoscopic surgery with or without robotic assistance (Minimally Invasive Surgery (MIS)) may represent a beneficial option for these patients. The objective of this literature review is to clarify the place of MIS in the management of advanced EOC for selected patients. METHOD: Pubmed, Cochrane and Clinicaltrials.gov online databases were used for this review, to select English or French published articles. RESULTS: We selected 11 original articles published between 2015 and 2020, 6 of which compared MIS and laparotomy. Among these 11 studies, 8 were retrospective cohorts, 2 were phase II trials, and one was a case-control study. In total, there were 3721 patients, of which 854 (23%) were treated with MIS. The robotic assistance was used with 224 patients (26%) of those MIS patients. Looking specifically at MIS patients, the laparoconversion rate was 9.5%, the rate of complete resection (CC-0) was 83.4%. Finally, the MIS complication rate was 1% intraoperatively and 12% postoperatively. The rate of complete resection, postoperative complication, as well as overall survival (OS) were comparable between patients treated with MIS or laparotomy. One study found an improved disease-free survival (DFS) in MIS versus laparotomy (18 months versus 12 months; P=0.027). CONCLUSION: MIS seems feasible, effective, and reliable in comparison to laparotomy for the completion of cytoreductive surgery after NACT without compromising oncological safety. Prospective randomized controlled trials are needed to confirm the role of MIS in advanced EOC.

Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: In metastatic renal cell carcinoma (mRCC), antiangiogenic treatments rarely achieve a reduction of -30% in the sum of longest diameters (SLD) of target lesions required by RECIST for an 'objective response', although they objectively improve progression-free survival (PFS). We sought to determine a threshold for the computed tomography evaluation of these patients' best reflecting patient outcome. PATIENTS AND METHODS: In 334 mRCC patients treated with sunitinib, we tested thresholds from -45% to +10%. We classified patients as 'responders' when the best relative variation of the sum of longest diameters (DeltaSLD) reached the tested threshold and as 'nonresponders' otherwise. For each tested threshold, the median PFS of the two groups were compared. Receiver operating characteristic (ROC) analysis was also carried out among the 103 patients that progressed during follow-up. Finally, the 'optimal' threshold was retested on an independent cohort of 39 patients. RESULTS: The DeltaSLD threshold of -10% gave the most significant difference. It divided patients into 256 responders and 78 nonresponders (median PFS 11.1 and 5.6 months). The same -10% threshold was found using the ROC analysis. Results were confirmed on the external validation cohort. CONCLUSION: A variation of -10% in the SLD accurately and rapidly identifies mRCC patients benefiting from sunitinib.

[Diffusion-weighted MR imaging of the female pelvis]. / IRM de diffusion et pelvis féminin.

Due to technical advances (parallel imaging and new phased-array coils), diffusion-weighted MR imaging can be used to image the female pelvis. Diffusion-weighted (b=1000) images are now acquired as a complement to conventional sequences (T2W, dynamic T1W images after intravenous injection of gadolinium). Diffusion weighted imaging improves the detection of small uterine tumors and the visualization of small implants of peritoneal carcinomatosis, which could play a significant role for tumor staging. It is helpful for characterization of complex ovarian tumors: the absence of hyperintensity on b=1000 diffusion-weighted images has an excellent positive predictive value for a benign etiology. It could also be helpful to characterize endometrial lesions, to differentiate between endometrial polyp and carcinoma when hysteroscopy is not possible, and to differentiate uterine fibroid from sarcoma. Finally, diffusion-weighted imaging could be helpful to assess the response of uterine tumors to therapy and could confirm a good outcome following uterine artery embolization of uterine fibroids.

[Hemolytic uremic syndrome with an atypical presentation]. / Syndrome hémolytique et urémique: à propos d'une présentation atypique.

The hemolytic uremic syndrome (HUS) is rare and of guarded prognosis in adults. It expresses a renal thrombotic microangiopathy. We report the case of a young patient whose clinical presentation and exploration make a diagnosis of HUS likely. The atypical presentation provides an opportunity not only to discuss all diagnostic elements based on recent pathophysiological hypotheses, but also to highlight recommendations for the management of this severe disease.

Diffusion MRI: Technical principles and application to uterine cervical cancer.

Imaging is involved in the management of uterine cervical cancer with several objectives: 1/to assess local and lymph node extension of the initial disease; 2/evaluate treatment response to conservative therapy; 3/detect recurrences. Pelvic MRI is the first-line examination in all these indications. It is the key element for delineation after image fusion when the indication of chemoradiation therapy is made. It is also essential for guiding the placement of applicators and optimising the dosimetry of brachytherapy. The diffusion-weighted acquisition is a sequence sensitive to the motion of water molecules. It allows distinguishing water molecules with free diffusion from water molecules with diffusion restricted by obstacles such as cell membranes or the cytoskeleton. The diffusion is thus connected to the cellularity of the explored tissue, and the cancers, being hypercellular, will present a high signal. It thus provides additional information thanks to a high contrast between the tumour and the surrounding tissues, facilitating detection, evaluation of the volume and extent of the disease.

[Encapsulant peritonitis]. / Une péritonite encapsulante.

INTRODUCTION: Encapsulating peritonitis is a rare but severe chronic fibrotic condition related to the development of a white fibrous membrane surrounding the digestive tract. Idiopathic forms have been described, however the disease is most often secondary to peritoneal dialysis or more rarely to surgery. Treatment is difficult and not codified. CASE REPORT: We report here the observation of a 36-year-old patient whose diagnosis of encapsulating peritonitis was made after a long sub-occlusive history, eight years after a gastric ulcer perforation. DISCUSSION: We discuss the possible etiologies and we present a focus on this rare and little-known entity.

[Naftidrofuryl in arterial obstructive disease: A systematic revue of the literature]. / Naftidrofuryl dans l'artériopathie oblitérante des membres inférieurs : une revue systématique de la littérature.

INTRODUCTION: Arterial obstructive disease is a disease affecting 11 % of the general population. This prevalence is constantly increasing. Nafronyl is still prescribed despite a decreasing reimbursement rate since 2005. The objective of this study was to summarize data from the scientific literature on the efficacy and safety of nafronyl used for the treatment of peripheral arterial obstructive disease. METHOD: A systematic review was made on EMBASE, MEDLINE and the Cochrane Library. Randomized controlled trials, systematic reviews and meta-analyses comparing naftidrofuryl with placebo were included. The main outcome was an improvement in the maximum walking distance or pain free walking distance. The quality of the reviews was analysed using a standardised reading grid. Only the best study was retained. RESULTS: Among 193articles, one meta-analyses were selected. Naftidrofuryl improved the initial pain free walking distance by 60 % at six months, without a demonstrated increase in the risk of adverse reactions. CONCLUSION: The efficacy of naftidrofuryl over the maximum walking distance in peripheral arterial obstructive disease appears similar to physical exercise or simvastatin.

Three artificial intelligence data challenges based on CT and MRI.

PURPOSE: The second edition of the artificial intelligence (AI) data challenge was organized by the French Society of Radiology with the aim to: (i), work on relevant public health issues; (ii), build large, multicentre, high quality databases; and (iii), include three-dimensional (3D) information and prognostic questions. MATERIALS AND METHODS: Relevant clinical questions were proposed by French subspecialty colleges of radiology. Their feasibility was assessed by experts in the field of AI. A dedicated platform was set up for inclusion centers to safely upload their anonymized examinations in compliance with general data protection regulation. The quality of the database was checked by experts weekly with annotations performed by radiologists. Multidisciplinary teams competed between September 11th and October 13th 2019. RESULTS: Three questions were selected using different imaging and evaluation modalities, including: pulmonary nodule detection and classification from 3D computed tomography (CT), prediction of expanded disability status scale in multiple sclerosis using 3D magnetic resonance imaging (MRI) and segmentation of muscular surface for sarcopenia estimation from two-dimensional CT. A total of 4347 examinations were gathered of which only 6% were excluded. Three independent databases from 24 individual centers were created. A total of 143 participants were split into 20 multidisciplinary teams. CONCLUSION: Three data challenges with over 1200 general data protection regulation compliant CT or MRI examinations each were organized. Future challenges should be made with more complex situations combining histopathological or genetic information to resemble real life situations faced by radiologists in routine practice.

[Diagnostic value of imaging (ultrasonography, doppler, CT, MR, PET-CT) for the diagnosis of a suspicious ovarian mass and staging of ovarian, tubal or primary peritoneal cancer: Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Valeur diagnostique de l'imagerie (échographie, doppler, scanner, IRM et TEP-TDM) pour le diagnostic d'une masse ovarienne suspecte et le bilan d'extension d'un cancer de l'ovaire, des trompes ou péritonéal primitif. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

Transvaginal ultrasound is the first-line examination allowing characterizing 80 to 90% of adnexal masses (LP1). If performed by an expert, a subjective analysis is optimal. If performed by a non-expert, combining the use of Simple Rules with subjective analysis can achieve the diagnostic performance of an expert (LP1). Whichever the chosen model (subjective analysis by an expert or combination of the Simple Rules with a subjective analysis by a non-expert), a second-line examination will have to be proposed in the complex or indeterminate cases (about 20% of the masses) (grade A). The best-performing second-line test for characterization is pelvic MRI (LP1). If read by an expert, a pathological hypothesis can or should be suggested (grade D). In case of non-expert reading, the use of the ADNEXMR score allows a reliable assessment of the positive predictive value of malignancy to guide the patient towards the best management (gradeC). For preoperative assessment and evaluation of resectability of ovarian, fallopian tube or primary peritoneal cancer, it is recommended to perform a chest abdomen and pelvis CT with contrast agent injection (LP2, grade B). In the event of a contraindication to the injection of iodinated contrast agent (severe renal insufficiency, GFR <30mL/min), an abdomen and pelvis MRI completed with a non-injected chest CT may be proposed (LP3, grade C). By analogy, the same examinations are recommended to evaluate the disease after neo-adjuvant chemotherapy (LP3, Recommendation grade C). Further studies will be required to determine whether PET-CT provides better lymph node assessment before retroperitoneal and pelvic lymphadenectomy. PET-CT may be used to eliminate lymph node involvement in the absence of suspicious lymph nodes on morphological examination (LP3, grade C). The report should specify the localizations leading to a risk of incomplete cytoreductive surgery and lesions outside the field explored during surgery.