Measuring Walking Speed Failed to Predict Early Death and Toxicity in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) Selected for Undergoing First-Line Systemic Treatment: An Observational Exploratory Study.

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8−12), and median WS 1.09 (IQR: 0.9−1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3−4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2−26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.

Vitamin B12 Deficiency Dysregulates m6A mRNA Methylation of Genes Involved in Neurological Functions.

INTRODUCTION: Vitamin B12 deficiency presents various neurological manifestations, such as cognitive dysfunction, mental retardation, or memory impairment. However, the involved molecular mechanisms remain to date unclear. Vitamin B12 is essential for synthesizing S-adenosyl methionine (SAM), the methyl group donor used for almost all transmethylation reactions. Here, we investigate the m6A methylation of mRNAs and their related gene expression in models of vitamin B12 deficiency. METHODS AND RESULTS: This study observes two cellular models deficient in vitamin B12 and hippocampi of mice knock-out for the CD320 receptor. The decrease in SAM levels resulting from vitamin B12 deficiency is associated with m6 A reduced levels in mRNAs. This is also potentially mediated by the overexpression of the eraser FTO. We further investigate mRNA methylation of some genes involved in neurological functions targeted by the m6A reader YTH proteins. We notably observe a m6A hypermethylation of Prkca mRNA and a consistently increased expression of PKCα, a kinase involved in brain development and neuroplasticity, in the two cellular models. CONCLUSION: Our data show that m6A methylation in mRNA could be one of the contributing mechanisms that underlie the neurological manifestations produced by vitamin B12 deficiency.

Impact of prophylactic cranial irradiation and hippocampal sparing on 18F-FDG brain metabolism in small cell lung cancer patients.

BACKGROUND AND PURPOSE: Prophylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC) patients improves survival. However, it is also associated with cognitive impairment, although the underlying mechanisms remain poorly understood. Our study aims to evaluate the impact of PCI and potential benefit of hippocampal sparing (HS) on brain metabolism assessed by 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). MATERIALS AND METHODS: We retrospectively included 22 SCLC patients. 50% had hippocampal-sparing (HS) PCI. 18F-FDG PET/CT was performed 144.5 ± 73 days before and 383 ± 451 days after PCI. Brain 18F-FDG PET scans were automatically segmented in 12 regions using Combined-AAL Atlas from MI-Neurology Software (Syngo.Via, Siemens Healthineers). For all atlas regions, we computed SUV Ratio using brainstem as a reference region (SUVR = SUVmean/Brainstem SUVmean) and compared SUVR before and after PCI, using a Wilcoxon test, with a level of significance of p < 0.05. RESULTS: We found significant decreases in 18F-FDG brain metabolism after PCI in the basal ganglia (p = 0.004), central regions (p = 0.001), cingulate cortex (p < 0.001), corpus striata (p = 0.003), frontal cortex (p < 0.001), parietal cortex (p = 0.001), the occipital cortex (p = 0.002), precuneus (p = 0.001), lateral temporal cortex (p = 0.001) and cerebellum (p < 0.001). Conversely, there were no significant changes in the mesial temporal cortex (MTC) which includes the hippocampi (p = 0.089). The subgroup who received standard PCI showed a significant decrease in metabolism of the hippocampi (p = 0.033). Contrastingly, the subgroup of patients who underwent HS-PCI showed no significant variation in metabolism of the hippocampi (p = 0.783). CONCLUSION: PCI induced a diffuse decrease in 18F-FDG brain metabolism. HS-PCI preserves metabolic activity of the hippocampi.

Bilateral Silicone Granulomas Mimicking Breast Cancer Recurrence on 18F-FDG PET/CT.

ABSTRACT: We report the case of a 45-year-old woman with a history of right breast reconstruction with silicone implant for breast cancer. An 18F-FDG PET/CT performed several years later revealed the presence of 18F-FDG-avid nodules at the periphery of the silicone implant, in the right internal mammary chain, and in the contralateral breast. Needle core biopsies were positive for bilateral silicone granulomas, without any sign of malignancy. This case displays intense 18F-FDG uptake in silicone granulomas affecting the contralateral breast after implant reconstruction.

Monte Carlo 90Y PET/CT dosimetry of unexpected focal radiation-induced lung damage after hepatic radioembolisation.

Transarterial radioembolization (TARE) with 90Y-loaded microspheres is an established therapeutic option for inoperable hepatic tumors. Increasing knowledge regarding TARE hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE. A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-volume-histograms were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume. Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 ml) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 Gy to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume. This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those considered for single administration or cumulative lung dose delivered during TARE.

Transarterial Radioembolization for the Treatment of Advanced Hepatocellular Carcinoma Invading the Right Atrium.

Hepatocellular carcinoma (HCC) has the tendency to invade the portal and/or hepatic venous system. The invasion of the right atrium is uncommonly observed and constitutes a treatment challenge. We report the case of a patient with HCC invading the right atrium treated with 90Yttrium-transarterial radioembolization (90Y-TARE). Following the treatment, organizing pneumonia secondary to nivolumab occurred, raising the question of an interaction between 90Y-TARE and nivolumab.

Increased 18F-FDG signal recovery from small physiological structures in digital PET/CT and application to the pituitary gland.

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in 18F-FDG imaging. We compared the physiological 18F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2-20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0-5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher 18F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new "higher" SUV of the normal 18F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis.

Detection Rate of Culprit Tumors Causing Osteomalacia Using Somatostatin Receptor PET/CT: Systematic Review and Meta-Analysis.

BACKGROUND: Tumor-induced or oncogenic osteomalacia (TIO) is a rare paraneoplastic syndrome in which osteomalacia is a consequence of fibroblast growth factor 23 (FGF23) secretion by a mesenchymal tumor. The localization of the culprit lesion in patients with TIO is often challenging. Several studies have evaluated the detection rate (DR) of these tumors using somatostatin receptor positron emission tomography (SSTR-PET/CT). We aimed to summarize literature findings on this topic providing pooled estimates of DR. METHODS: A comprehensive literature search by screening PubMed, Embase and Cochrane library electronic databases through August 2019 was performed. The pooled DR of culprit tumors using SSTR-PET/CT in patients with TIO was calculated using a random-effects statistical model. RESULTS: Fourteen studies on the use of SSTR-PET/CT in detecting the culprit tumor in patients with TIO were included in the qualitative analysis. The pooled DR of SSTR-PET/CT on a per-patient-based analysis calculated using eleven studies (166 patients) was 87.6% (95% confidence interval (95% CI) 80.2-95.1%). Statistical heterogeneity among studies was detected (I-square = 63%), likely due to the use of different radiolabeled somatostatin analogues, as demonstrated by a subgroup analysis. CONCLUSIONS: Despite limited literature data due to the rarity of the disease, SSTR-PET/CT demonstrated a very high DR of culprit tumors in patients with TIO and it could be used as first-line imaging method for this indication.

First experience of durable cytoreduction in chronic lymphoid leukemia with 177Lu-DOTATATE.

This is the first described case of effective and durable cytoreduction after PRRT with 177Lu-DOTATATE in a 75-year-old female, with B cell chronic lymphoid leukemia, and well-differentiated metastatic neuroendocrine tumor.

Galactocele, Pitfall for the Evaluation by 18F-FDG PET/CT.

A high F-FDG uptake was found in mammary lesions in a 36-year-old woman who underwent a PET/CT scan for initial staging of diffuse large B-cell lymphoma. The patient has given birth 2 months ago and was breastfeeding. Ultrasound-guided fine-needle aspiration of 1 lesion yielded creamy liquid consistent with milk and confirmed the diagnosis of galactocele.

Pre-treatment magnetic resonance-based texture features as potential imaging biomarkers for predicting event free survival in anal cancer treated by chemoradiotherapy.

AIM: To assess regular MRI findings and tumour texture features on pre-CRT imaging as potential predictive factors of event-free survival (disease progression or death) after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) without metastasis. MATERIALS AND METHODS: We retrospectively included 28 patients treated by CRT for pathologically proven ASCC with a pre-CRT MRI. Texture analysis was carried out with axial T2W images by delineating a 3D region of interest around the entire tumour volume. First-order analysis by quantification of the histogram was carried out. Second-order statistical texture features were derived from the calculation of the grey-level co-occurrence matrix using a distance of 1 (d1), 2 (d2) and 5 (d5) pixels. Prognostic factors were assessed by Cox regression and performance of the model by the Harrell C-index. RESULTS: Eight tumour progressions led to six tumour-specific deaths. After adjusting for age, gender and tumour grade, skewness (HR = 0.131, 95% CI = 0-0.447, p = 0.005) and cluster shade_d1 (HR = 0.601, 95% CI = 0-0.861, p = 0.027) were associated with event occurrence. The corresponding Harrell C-indices were 0.846, 95% CI = 0.697-0.993, and 0.851, 95% CI = 0.708-0.994. CONCLUSION: ASCC MR texture analysis provides prognostic factors of event occurrence and requires additional studies to assess its potential in an "individual dose" strategy for ASCC chemoradiation therapy. KEY POINTS: • MR texture features help to identify tumours with high progression risk. • Texture feature maps help to identify intra-tumoral heterogeneity. • Texture features are a better prognostic factor than regular MR findings.

FDG PET/CT in Pediatric Neurolymphomatosis.

An 8-year-old girl presented with back and leg pain and left arm and leg paresis. Lumbar puncture was suggestive of lymphocytic meningitis without identified organism. A second lumbar puncture demonstrated a large number of lymphoid B cells, with positive immunohistochemical staining for CD20 and CD25, proving the diagnosis of neurolymphomatosis. Brain and spine MRI demonstrated involvement of cervical and lumbosacral nerve roots. FDG PET/CT showed multiple bone metastases in addition to nerve involvement. Postchemotherapy FDG PET/CT demonstrated complete metabolic response.

18F-FDG Imaging of Chronic Inflammation Associated With Promontofixation of the Uterus.

A high F-FDG uptake was found in a mesh of promontofixation in a 74-year-old woman who underwent a PET/CT scan for initial staging of cervical cancer. The patient underwent a laparoscopic treatment for a prolapsed uterus 7 years before. Promontofixation can be associated with complications due to chronic inflammation. F-FDG-PET may diagnose chronic inflammation of the mesh.

Three-Dimensional Measurement of Hepatocellular Carcinoma Ablation Zones and Margins for Predicting Local Tumor Progression.

PURPOSE: To propose a postprocessing technique that measures tumor surface with insufficient ablative margins (≤ 5 mm) on magnetic resonance (MR) imaging to predict local tumor progression (LTP) following radiofrequency (RF) ablation. MATERIALS AND METHODS: A diagnostic method is proposed based on measurement of tumor surface with a margin ≤ 5 mm on MR imaging. The postprocessing technique includes fully automatic registration of pre- and post-RF ablation MR imaging, a semiautomatic segmentation of pre-RF ablation tumor and post-RF ablation volume, and a subsequent calculation of the three-dimensional exposed tumor surface area. The ability to use this surface margin ≤ 5 mm to predict local recurrence at 2 years was then tested on 16 patients with cirrhosis who were treated by RF ablation with a margin ≤ 5 mm in 2012: eight with LTP matched according to tumor size and number and α-fetoprotein level versus eight without local recurrence. RESULTS: The error of estimated tumor surface with a margin ≤ 5 mm was less than 12%. Results of a log-rank test showed that patients with a tumor surface area > 425 mm(2) had a 2-year LTP rate of 77.5%, compared with 25% for patients with a tumor surface area ≤ 425 mm(2) (P = .018). CONCLUSIONS: This proof-of-concept study proposes an accurate and reliable postprocessing technique to estimate tumor surface with insufficient ablative margins, and underscores the potential usefulness of tumor surface with a margin ≤ 5 mm to stratify patients with HCC treated by RF ablation according to their risk of LTP.

Benign cystic mesothelioma: false-positive iodine accumulation in a patient with oncocytic follicular thyroid carcinoma.

Whole-body (131I) scintigraphy (WBS) is used to detect residual or metastatic tissue during treatment of differentiated thyroid carcinoma in combination with thyroglobulin (Tg) and ultrasonography of the neck. It is a highly sensitive method, but there is a high rate of false positives. We report the case of a 52-year-old woman with false-positive iodine accumulation in a benign cystic mesothelioma discovered during treatment for a oncocytic follicular thyroid carcinoma (stage pT2 pNx Mx). This lesion was detected by WBS and confirmed by surgery and histopathologic analysis.

Predomínio da gestão e violência simbólica / Management predominance and symbolic violence

Após duas décadas de forte ascensão do neoliberalismo, a degradação das condições de trabalho foi denunciada por numerosos observadores: alguns falam de "violência no trabalho", acentuando as dimensões socioeconômicas que estruturam os universos profissionais. Este artigo se inscreve nesta perspectiva e considera particularmente o papel que a dinâmica de gestionarização desempenha no exercício da violência no trabalho. O artigo se apoia sobre duas situações emblemáticas: o trabalho nas centrais de teleatendimento e a implementação de um dispositivo de gestão "total", o Balanced Scorecard, em uma multinacional. Mostra que as violências ligadas ao fato gestionário manifestam-se em três níveis articulados. No primeiro nível, esta violência resulta das transformações macropolíticas que tornam incontornáveis a introdução e a renovação dos dispositivos de gestão. No segundo nível, a violência se exerce em torno da implementção de dispositivos de gestão. Enfim, no terceiro nível, violência simbólica, que dá suporte às práticas de diferentes categorias de ator, manifesta-se. A imbricação entre estes níveis leva uma maioria de atores a adotar uma atitude de resignação diante da impossibilidade de se emancipar da gestão. Esta constatação pemite focar melhor o lugar e o modo de ação para enfrentar a violência no trabalho.

After two decades of dramatic ascension of neoliberalism, several observers have denounced the degradation of work conditions: some of them mention "violence at work", highlighting the social-economic dimensions that shape professional universes. This article is included in this perspective and particularly considers the role of "managerialism dynamics" in the use of violence at work. It stands on two emblematic situations: work in call centers, and the implementation of a "total" management device called Balanced Scorecard, in a multinational company. The paper shows that violences linked to a "managerial fact" are revealed in three different articulated levels. In the first one, violence results from macro-political transformations that make introduction and renewing of the management devices implausible. In the second level, violence takes place as a result of the implementation of management devices. Finally in the third level, symbolic violence, which supports practices of different categories of actors, is revealed. The overlapping between these levels makes most actors adopt an attitude of resignation due to their impossibility to get free from management. This evidence leads to a better focusing on the place and on the way of acting to face violence at work.

Sealing pseudo-aneurysms of the femoral artery with saline injection: a new technique.

AIMS: Pseudo-aneurysm (PA) of the femoral artery is the most frequent complication after diagnostic or therapeutic catheterisation. PA may manifest with large and painful haematoma or compression of the adjacent nerve and vein. Among several therapeutic approaches, compression by injection of saline around the neck is a recent and promising method. To explore compression with saline as an alternative treatment for iatrogenic femoral artery PA was the aim of this study. METHODS AND RESULTS: From December 2009 to January 2011, all consecutive patients with symptomatic PA were included in this study. After ultrasonic assessment, the PA neck was occluded by injection of a saline/lidocaïne (0.2%) mixture in the soft tissue at its vicinity, followed by a short echo-guided compression. Outcome was assessed at one and 30 days by duplex sonography. Eleven patients with PA requiring immediate treatment were included. All patients had at least one PA cavity. Moreover, four patients had multiple pulsatile cavities and seven patients had large thigh or abdominal haematoma, with either active bleeding, compression of adjacent organ or hypotension. Three patients had very short PA neck. The mean injected volume was 47±11 ml. The mean compression time until the PA was closed was 6±3 minutes. At one and 30 days, all PA remained occluded without any complication related to the procedure. CONCLUSIONS: Saline injection to seal PA is feasible, safe and very effective. The technique is rapid and well tolerated, and allows, after limited training, the closure of very large PA, even in case of emergency. This new technique is more comfortable for the patient and the operator, and surely more economical than thrombin injection or surgical arterial suture.

[Aortic calcification and the risk of osteoporotic fractures]. / Calcification des grandes artères et risque de fracture ostéoporotique.

Osteoporosis and atherosclerosis seem to be epidemiologically correlated. Several medical conditions are risk factors for both osteoporosis and atheromatosis (i.e. age, diabetes, end stage renal disease, sedentarity, smoking), but a common pathogenic link may be present beyond this. The burden of cardiovascular events and of osteoporotic fracture is considerable for the health care system in term of costs and resources. However, both diseases are rarely managed together. This article is a review of the recent studies in this new field.