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International audience; Importance: Because inadvertent damage of parathyroid glands can lead to postoperative hypocalcemia, their identification and preservation, which can be challenging, are pivotal during total thyroidectomy.Objective: To determine if intraoperative imaging systems using near-infrared autofluorescence (NIRAF) light to identify parathyroid glands could improve parathyroid preservation and reduce postoperative hypocalcemia.Design, setting, and participants: This randomized clinical trial was conducted from September 2016 to October 2018, with a 6-month follow-up at 3 referral hospitals in France. Adult patients who met eligibility criteria and underwent total thyroidectomy were randomized. The exclusion criteria were preexisting parathyroid diseases.Interventions: Use of intraoperative NIRAF imaging system during total thyroidectomy.Main outcomes and measures: The primary outcome was the rate of postoperative hypocalcemia (a corrected calcium

International audience; PURPOSE: We describe and validate a novel hybrid nonlinear vessel registration algorithm for intra-operative updating of preoperative magnetic resonance (MR) images using Doppler ultrasound (US) images acquired on the dura for the correction of brain-shift and registration inaccuracies. We also introduce an US vessel appearance simulator that generates vessel images similar in appearance to that acquired with US from MR angiography data. METHODS: Our registration uses the minimum amount of preprocessing to extract vessels from the raw volumetric images. This prevents the removal of important registration information and minimizes the introduction of artifacts that may affect robustness, while reducing the amount of extraneous information in the image to be processed, thus improving the convergence speed of the algorithm. We then completed 3 rounds of validation for our vessel registration method for robustness and accuracy using (i) a large number of synthetic trials generated with our US vessel simulator, (ii) US images acquired from a real physical phantom made from polyvinyl alcohol cryogel, and (iii) real clinical data gathered intra-operatively from 3 patients. RESULTS: Resulting target registration errors (TRE) of less than 2.5 mm are achieved in more than 90 % of the synthetic trials when the initial TREs are less than 20 mm. TREs of less than 2 mm were achieved when the technique was applied to the physical phantom, and TREs of less than 3 mm were achieved on clinical data. CONCLUSIONS: These test trials show that the proposed algorithm is not only accurate but also highly robust to noise and missing vessel segments when working with US images acquired in a wide range of real-world conditions.

International audience; BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.

International audience; Ovarian cancer is the leading cause of gynecological cancer-related death in Western countries. The present treatment standards for ovarian cancer are based on the association of debulking surgery with platinum-based chemotherapy. Another strategy that could be further investigated is intraperitoneal chemotherapy (IP). We previously described that the 2-h administration of intraoperative IP cisplatin did not reach satisfactory concentrations. In the present study, we present the results of a pharmacokinetic analysis performed after two consecutive 1-h IP 30 mg/l cisplatin administrations. Twenty-seven patients with advanced epithelial cancer classified FIGO stage IIIC were included in the study. Blood and IP samples were taken over a 24-h period, during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentration levels were analyzed. Biological and clinical toxicities were also recorded. With this strategy, IP Pt concentrations stayed above the target concentration (10 mg/l) for a satisfactory length of time. The serum Pt concentrations were higher than those observed with the "one-bath" protocol and they induced the occurrence of recoverable renal toxicities (3 grade 1, 7 grade 2 and 4 grade 3). The best predictive parameter for renal failure was the total Pt 24-h Area Under the Curve (AUC) with a threshold value of 25 mg h/l RR = 0.31 (95% CI 0.13 - 0.49, P < 0.01). Administration of an increased amount of cisplatin is feasible and a satisfactory level of IP Pt concentrations is obtained. However, this improvement is associated with an increase in serum Pt levels and resulting renal toxicities. An attractive solution would be to decrease Pt transfer from peritoneum to bloodstream. A phase 1 study using intraoperative IP epinephrine in order to decrease this transfer is presently being carried out.

The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated 'eloquent' areas and (ii) that a lesion within the eloquent area gives rise to major irrevocable deficits. However, in sharp contrast with these observations, it was recently found that patients with low-grade gliomas were able to undergo massive cerebral resections without detectable functional consequence. In this paper, we tackle this puzzling observation and address the idea that brain plasticity cannot be fully understood and fruitfully studied without considering the temporal pattern of the injury inflicted to the brain. To achieve this goal, we first review experimental evidence showing that functional recovery is considerably better in the context of slow-growing injuries than after acute lesions. Both human and animal data are considered. In a second step, we emphasize that slow and acute lesions involve very different patterns of reorganization. In agreement with this idea, we show that the recruitment of remote brain areas in the ipsi- and contralesional hemispheres is much more efficient in slow growing than acute lesions. Finally in a last section, we briefly discuss the main implications of these results.

Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by the left ILF, joining the posterior occipitotemporal regions to the temporal pole, then relayed by the uncinate fasciculus connecting the anterior temporal pole to the frontobasal areas. Nevertheless, this hypothesis was solely based on neurofunctional imaging, allowing a cortical mapping but with no anatomofunctional information regarding the white matter. Here, we report a series of 12 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the left temporal lobe. Before and during resection, we used the method of intraoperative direct electrostimulation, enabling us to perform accurate and reliable anatomofunctional correlations both at cortical and subcortical levels. In order to map the ILF. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where language disturbances were elicited by stimulations, both at cortical and subcortical levels. Our goal was to study the potential existence of parallel and distributed language networks crossing the left dominant temporal lobe, subserved by distinct subcortical pathways--namely the inferior occipitofrontal fasciculus and the ILF. Intraoperative stimulation of the anterior and middle temporal cortex elicited anomia in four patients. At the subcortical level, semantic paraphasia were induced in seven patients during stimulation of the inferior occipitofrontal fasciculus, and phonological paraphasia was generated in seven patients by stimulating the arcuate fasciculus. Interestingly, subcortical stimulation never elicited any language disturbances when performed at the level of the ILF. In addition, following a transient postoperative language deficit, all patients recovered, despite the resection of at least one part of the ILF, as confirmed by control MRI. On the basis of these results, we suggest that the "semantic ventral stream" could be constituted by at least two parallel pathways within the left dominant temporal lobe: (i) a direct pathway, the inferior occipitofrontal fasciculus, that connects the posterior temporal areas and the orbitofrontal region, crucial for language semantic processing, since it elicits semantic paraphasia when stimulated; (ii) and also possibly an indirect pathway subserved by the ILF, not indispensable for language, since it can be compensated both during stimulation and after resection.