Prognostic value of bone marrow tracer uptake pattern in baseline PET scans in hodgkin lymphoma: Results from an international collaborative study

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of Different patterns of bone marrow (BM)18F-FDG uptake in HL. Methods: One hundred eighty newly Diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycinvinblastine-dacarbazine (ABVD) courses with18F-FDG PET, enrolled in 2 international stuDies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD 4-6 cycles and involved-field raDiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET1), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (.liver) Diffuse uptake (dPET1) and 89 (48.4%) showed no or faint (#liver) BM uptake (nPET1). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET1, in 1 of 53 (1.9%) for dPET1, and in 5 of 89 (5.6%) for nPET1. dPET1 was correlated with younger age, higher frequency of bulky Disease, lower hemoglobin levels, higher leukocyte counts, and similar Diffuse uptake in the spleen. Patients with pure dPET1 had a 3-y progression-free survival identical to patients without any18F-FDG uptake (82.9% and 82.2%, respectively, P 5 0.918). However, patients with fPET1 (either unifocal or multifocal) had a 3-y progressionfree survival significantly inferior to patients with dPET1 and nPET1 (66.7% and 82.5%, respectively, P 5 0.03). The k values for interobserver agreement were 0.84 for focal uptake and 0.78 for Diffuse uptake. Conclusion: We confirmed that18F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal18F-FDG BM uptake should be considered as a harbinger of HL

ATP-sensitive potassium channels (K ) in retina: a key role for ATP delayed ischemic tolerance

International audienceThe objectives of the present study were to determine the localization of K channels in normal retina and to evaluate their potential ATP roles in ischemic preconditioning (IPC) in a rat model of ischemia induced by increased intraocular pressure (IOP). Brown Norway rats were subjected to sublethal 3-, lethal 20-and 40-min ischemia and the functional recovery was evaluated using electroretinography. The time interval between ischemic insults ranged from 1 to 72 h. The effects of K channel blockade on IPC protection were studied by ATP treatment with 0.01% glipizide. IPC was mimicked by injection of K channel openers of 0.01% (2)cromakalim or 0.01% P1060 72 h ATP before 20-min ischemia. Co-expression of K channel subunits Kir6.2 / SUR1 was observed in the retinal pigment epithelium, inner ATP segments of photoreceptors, outer plexiform and ganglion cell layers and at the border of the inner nuclear layer. In contrast to a 20-or 40-min ischemia, a 3-min ischemia induced no alteration of the electroretinogram (ERG) and constituted the preconditioning stimulus. An ischemic challenge of 40 min in preconditioned rats induced impairment of retinal function. However, animals preconditioned 24, 48 and 72 h before 20-min ischemia had a significant improvement of the ERG. (2)Cromakalim and P1060 mimicked the effect of IPC. Glipizide significantly suppressed the protective effects of preconditioning. In conclusion, activation of K channels plays an important role in the ATP mechanism of preconditioning by enhancing the resistance of the retina against a severe ischemic insult