Anaemia in Hospitalized Cancer Patients: A Retrospective Study of Two Cohorts before and after the Guideline Update.

INTRODUCTION: The incidence of anaemia and its consequences are often underestimated during cancer management. We propose to evaluate the situation before and after the recommendations were updated in order to assess their impact on the day-to-day practice. METHODS: In this single-centre retrospective study, eligible patients were treated for cancer and warranted overnight hospitalization over two periods (n = 206 in 2011, n = 143 in 2018). The diagnosis of anaemia was defined by a haemoglobin level below 12 and 13 g/dL for women and men, respectively. RESULTS: The prevalence of anaemia was 26% in 2011 and 16% in 2018 (p < 0.001). Biological assessment had changed between the two periods, with more tests of iron metabolism and measurements of inflammatory parameters. Patients hospitalized in 2018 had more advanced cancer and more severe anaemia (8.2 g/dL [±1.07] in 2011 vs. 7.9 g/dL [±1.18] in 2018). Rate of transfusion therapy did not change, but patients with mild and moderate anaemia were transfused less in 2018 (57% in 2011 vs. 44% in 2018). Intravenous iron and erythropoiesis-stimulating agent were used more frequently in 2018 (1 and 5 and 13 and 23% in 2011 and 2018, respectively), mainly for mild anaemia and life-threatening anaemia, respectively. Overall survival was poor in both cohorts at 24 months (15.4% in 2011 and 6.5% in 2018, p = 0.048). CONCLUSION: Practices have changed in the diagnosis of anaemia and prescriptions for erythropoiesis-stimulating agents and intravenous iron have increased. Efforts must continue to explore the causes of anaemia, optimize patients' quality of life, and reduce transfusions.

In vivo MRS for the assessment of mouse colon using a dedicated endorectal coil: initial findings.

Inflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow-up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues. An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B1 magnetic field, and a dedicated ERC was used for signal reception. Colon-wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 µL to 2 µL while keeping acquisition times below 3 min. The acquired spectra show various biochemical contents such as α- and ß-methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon-wall complex exhibits both high lipid and high water contents. To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies.

Endoluminal high-resolution MR imaging protocol for colon walls analysis in a mouse model of colitis.

OBJECTIVE: An endoluminal magnetic resonance (MR) imaging protocol including the design of an endoluminal coil (EC) was defined for high-spatial-resolution MR imaging of mice gastrointestinal walls at 4.7 T. MATERIALS AND METHODS: A receive-only radiofrequency single-loop coil was developed for mice colon wall imaging. Combined with a specific protocol, the prototype was first characterized in vitro on phantoms and on vegetables. Signal-to-noise ratio (SNR) profiles were compared with a quadrature volume birdcage coil (QVBC). Endoluminal MR imaging protocol combined with the EC was assessed in vivo on mice. RESULTS: The SNR measured close to the coil is significantly higher (10 times and up to 3 mm of the EC center) than the SNR measured with the QVBC. The gain in SNR can be used to reduce the in-plane pixel size up to 39 × 39 µm(2) (234 µm slice thickness) without time penalty. The different colon wall layers can only be distinguished on images acquired with the EC. CONCLUSION: Dedicated EC provides suitable images for the assessment of mice colon wall layers. This proof of concept provides gains in spatial resolution and leads to adequate protocols for the assessment of human colorectal cancer, and can now be used as a new imaging tool for a better understanding of the pathology.

Hepatic lentiviral gene transfer prevents the long-term onset of hepatic tumours of glycogen storage disease type 1a in mice.

Glycogen storage disease type 1a (GSD1a) is a rare disease due to the deficiency in the glucose-6-phosphatase (G6Pase) catalytic subunit (encoded by G6pc), which is essential for endogenous glucose production. Despite strict diet control to maintain blood glucose, patients with GSD1a develop hepatomegaly, steatosis and then hepatocellular adenomas (HCA), which can undergo malignant transformation. Recently, gene therapy has attracted attention as a potential treatment for GSD1a. In order to maintain long-term transgene expression, we developed an HIV-based vector, which allowed us to specifically express the human G6PC cDNA in the liver. We analysed the efficiency of this lentiviral vector in the prevention of the development of the hepatic disease in an original GSD1a mouse model, which exhibits G6Pase deficiency exclusively in the liver (L-G6pc(-/-) mice). Recombinant lentivirus were injected in B6.G6pc(ex3lox/ex3lox). SA(creERT2/w) neonates and G6pc deletion was induced by tamoxifen treatment at weaning. Magnetic resonance imaging was then performed to follow up the development of hepatic tumours. Lentiviral gene therapy restored glucose-6 phosphatase activity sufficient to correct fasting hypoglycaemia during 9 months. Moreover, lentivirus-treated L-G6pc(-/-) mice presented normal hepatic triglyceride levels, whereas untreated mice developed steatosis. Glycogen stores were also decreased although liver weight remained high. Interestingly, lentivirus-treated L-G6pc(-/-) mice were protected against the development of hepatic tumours after 9 months of gene therapy while most of untreated L-G6pc(-/-) mice developed millimetric HCA. Thus the treatment of newborns by recombinant lentivirus appears as an attractive approach to protect the liver from the development of steatosis and hepatic tumours associated to GSD1a pathology.

Hyperpolarized 3He MR for sensitive imaging of ventilation function and treatment efficiency in young cystic fibrosis patients with normal lung function.

PURPOSE: To assess the sensitivity of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging for the detection of peripheral airway obstruction in younger cystic fibrosis (CF) patients showing normal spirometric results (mean forced expiratory volume in 1 second [FEV(1)], 112% +/- 14.5 [standard deviation]) and to observe the immediate effects of a single chest physical therapy (CPT) session, thereby comparing two image quantification techniques. MATERIALS AND METHODS: Ten pediatric CF patients (age range, 8-16 years) with normal spirometric results were included in this study after approval from the local research ethics committee. Spirometry followed by proton and hyperpolarized (3)He three-dimensional lung imaging were performed with a 1.5-T MR unit before and after 20 minutes of CPT. The number of ventilation defects per image (VDI) and the ventilated lung fraction (VF), defined as the ratio of ventilated lung volume divided by total lung volume, were quantified. RESULTS: Ventilation defects were found in all patients (mean VDI, 5.1 +/- 1.9; mean global VF, 78.5% +/- 12.3; and mean peripheral VF, 75.5% +/- 17.1) despite normal spirometric results. After CPT, disparate changes in the distribution of ventilation defects were observed but the average VDI and VF did not change significantly (mean VDI, 5.1 +/- 1.1; mean global VF, 83.5% +/- 12.2; and mean peripheral VF, 80.3% +/- 12.2). There was no correlation between FEV(1) and VDI (rho = -0.041, P = .863) or global VF (rho = -0.196, P = .408) values but peripheral VF and VDI were correlated (rho = -0.563, P = .011). CONCLUSION: Although spirometric results indicate normal lung function, the mean VDI in patients (5.1) found in this study is well above the VDI in healthy subjects (1.6) reported in the literature. A single CPT session induces disparate changes in the distribution and extent of ventilation defects.

Safety and tolerability of ultrasmall superparamagnetic iron oxide contrast agent: comprehensive analysis of a clinical development program.

BACKGROUND: Because of its cellular uptake pattern, ferumoxtran-10 may be potentially useful for the imaging of a variety of diseases (eg, atheroma, multiple sclerosis, stroke, renal graft rejection, glomerulonephritis and brain tumors, in addition to differentiation of metastatic and nonmetastatic lymph nodes). The aim of this article is to present a comprehensive review of the safety and tolerability of ferumoxtran-10 as reported during clinical development of the compound as an ultrasmall superparamagnetic iron oxide contrast agent for use in magnetic resonance imaging. MATERIALS AND METHODS: The safety profile of ferumoxtran-10 was assessed using pooled data from 37 phase I to III clinical studies in 1777 adults (1663 received the contrast agent [1527 patients and 136 healthy volunteers], 75 received placebo, and 39 patients were enrolled but did not receive study medication). RESULTS: At least one adverse event was reported in 23.2% of patients who received ferumoxtran-10. Adverse events were of mild-to-moderate severity in 86.3% of patients in the ferumoxtran-10 group. At least 1 event considered by the investigator to be related to study treatment was reported in 18.2% of patients in the ferumoxtran-10 group. The most commonly reported treatment-related adverse events were back pain, pruritus, headache, and urticaria. A total of 44 patients (2.6%) in the ferumoxtran-10 group reported 76 serious adverse event (SAE). Only 7 SAEs (0.42%) were considered to be treatment-related (anaphylactic shock, chest pain, dyspnea, skin rash, oxygen saturation decreased, and 2 cases of hypotension). There were 12 deaths, only one of which (anaphylactic shock) was considered to be related to ferumoxtran-10 which was administered by bolus injection of undiluted product, a mode of administration that is no longer recommended. Results in high-risk groups of patients including the elderly and those with hepatic, renal or cardiovascular disease seemed to show no cause for special clinical concern in these groups. CONCLUSIONS: Clinical experience to date therefore shows ferumoxtran-10 to be a well tolerated contrast agent.