[Hypnotherapy in psycho-oncology : clinical benefits and future prospects]. / Hypnothérapie en psycho-oncologie : bénéfices cliniques et perspectives d'avenir.

After a cancer diagnosis, emotional distress is common. We currently have many conventional treatments such as radiotherapy, surgery, chemotherapy, targeted therapies and immunotherapy to fight cancer. However, these treatments are associated with significant adverse effects, which may themselves be the cause of psychic suffering. Hypnosis has been shown to be effective in relieving some of these symptoms, but its practice is still limited in oncology. This is as much related to ignorance about the discipline as to a lack of large randomized prospective studies. This article provides an overview of hypnotherapy and its benefits in the field of psycho-oncology and discusses the prospects for the future.

Pour lutter contre le cancer, nous disposons à l'heure actuelle de nombreux traitements tels que la chirurgie, la radiothérapie, la chimiothérapie, mais également les thérapies ciblées et l'immunothérapie. La détresse émotionnelle pouvant accompagner le diagnostic peut parfois s'aggraver en raison des effets indésirables des traitements entrepris. Il est démontré que l'hypnose médicale est efficace pour soulager certains des symptômes présentés, pourtant sa pratique en oncologie reste limitée, probablement en raison de la méconnaissance de cet outil et d'un manque de grandes études prospectives randomisées. Cet article se propose de faire un état des lieux de l'hypnothérapie et de ses bénéfices dans le domaine de la psycho-oncologie et identifie les perspectives d'avenir.

Sex-dependent factors encoded in the immune compartment dictate relapsing or progressive phenotype in demyelinating disease.

TCR1640 mice, which have a T cell receptor (TCR) directed against MOG92-106, spontaneously develop experimental autoimmune encephalomyelitis. Female mice mostly develop a relapsing-remitting (RR) course and have a higher incidence of disease, while males most frequently suffer from progressive disease, reflecting the unresolved clinical sex discrepancies seen in multiple sclerosis. Herein, we performed adoptive transfers of male and female TCR1640 immune cells into WT animals to investigate if disease course is dependent on the sex of the donor immune cells or on the sex of the recipient animal. We found that transfer of female TCR1640 immune cells led to a RR disease while transfer of male TCR1640 immune cells led to a progressive course, independent of the sex of the recipient. In addition, regulatory and pathogenic T cell infiltration after transfer was also immune cell sex intrinsic. We performed genetic profiling of the donor immune cells and found significant differences between the transcriptomic profiles of male and female TCR1640 immune cells, interestingly, within genes related to immune regulation of T lymphocytes. These results suggest that differences in gene expression profiles related to regulation of T cell immunity seen in male and female neuroinflammatory disease drive relapsing versus progressive disease course.

Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis.

Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls. Passive EAE transfer experiments suggested that the pathophysiology observed in active EAE was linked to the absence of ALCAM on BBB-ECs. In addition, phenotypic characterization of unimmunized ALCAM KO mice revealed a reduced expression of BBB junctional proteins. Further in vivo, in vitro, and molecular analysis confirmed that ALCAM is associated with tight junction molecule assembly at the BBB, explaining the increased permeability of CNS blood vessels in ALCAM KO animals. Collectively, our data point to a biologically important function of ALCAM in maintaining BBB integrity.

Melanoma cell adhesion molecule-positive CD8 T lymphocytes mediate central nervous system inflammation.

OBJECTIVE: Although Tc17 lymphocytes are enriched in the central nervous system (CNS) of multiple sclerosis (MS) subjects and of experimental autoimmune encephalomyelitis (EAE) animals, limited information is available about their recruitment into the CNS and their role in neuroinflammation. Identification of adhesion molecules used by autoaggressive CD8(+) T lymphocytes to enter the CNS would allow further characterization of this pathogenic subset and could provide new therapeutic targets in MS. We propose that melanoma cell adhesion molecule (MCAM) is a surface marker and adhesion molecule used by pathogenic CD8(+) T lymphocytes to access the CNS. METHODS: Frequency, phenotype, and function of MCAM(+) CD8(+) T lymphocytes was characterized using a combination of ex vivo, in vitro, in situ, and in vivo approaches in humans and mice, including healthy controls, MS subjects, and EAE animals. RESULTS: Herein, we report that MCAM is expressed by human effector CD8(+) T lymphocytes and it is strikingly upregulated during MS relapses. We further demonstrate that MCAM(+) CD8(+) T lymphocytes express more interleukin 17, interferon γ, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor than MCAM(-) lymphocytes, and exhibit an enhanced killing capacity toward oligodendrocytes. MCAM blockade restricts the transmigration of CD8(+) T lymphocytes across human blood-brain barrier endothelial cells in vitro, and blocking or depleting MCAM in vivo reduces chronic neurological deficits in active, transfer, and spontaneous progressive EAE models. INTERPRETATION: Our data demonstrate that MCAM identifies encephalitogenic CD8(+) T lymphocytes, suggesting that MCAM could represent a biomarker of MS disease activity and a valid target for the treatment of neuroinflammatory conditions.

Netrin 1 regulates blood-brain barrier function and neuroinflammation.

Blood-brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses the blood-brain barrier is compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine barrier properties during homeostasis and increases with inflammation. Netrin 1 supports blood-brain barrier integrity by upregulating endothelial junctional protein expression, while netrin 1 knockout mice display disorganized tight junction protein expression and barrier breakdown. Upon inflammatory conditions, blood-brain barrier endothelial cells significantly upregulated netrin 1 levels in vitro and in situ, which prevented junctional breach and endothelial cell activation. Finally, netrin 1 treatment during experimental autoimmune encephalomyelitis significantly reduced blood-brain barrier disruption and decreased clinical and pathological indices of disease severity. Our results demonstrate that netrin 1 is an important regulator of blood-brain barrier maintenance that protects the central nervous system against inflammatory conditions such as multiple sclerosis and experimental autoimmune encephalomyelitis.

Focal disturbances in the blood-brain barrier are associated with formation of neuroinflammatory lesions.

Early changes in the normal appearing white matter of multiple sclerosis (MS) patients precede the appearance of gadolinium-enhancing lesions. Although these findings suggest blood-brain barrier (BBB) breakdown as an important feature in MS pathogenesis, limited information is available on the BBB alterations during lesion genesis. Here, we perform a longitudinal characterization of the vascular, neuropathological and immunological changes before lesion formation in mice developing spontaneous relapsing-remitting experimental autoimmune encephalomyelitis (sRR-EAE). We found a significant upregulation of Th1 and Th17 cytokines in the periphery of sRR-EAE mice before any evident neuropathology. In the CNS, BBB and astroglial activations were the first pathological changes occurring after 45days of age and were followed by immune cell infiltration by day 50. These pathological alterations subsequently led to perivascular demyelination and disease onset. In MS, (p)reactive lesions mirrored the changes seen in early sRR-EAE by displaying considerable BBB disruption, perivascular astrogliosis, redistribution of junctional proteins and increased expression of endothelial cell adhesion molecules. Our findings suggest that BBB breach occurs before significant immune cell infiltration and demyelination. In addition, peripheral immune activation during sRR-EAE precedes CNS pathology, suggesting that outside in signaling mechanisms play a role in the development of neuroinflammatory lesions.

Preoperative imaging in the planning of deep inferior epigastric artery perforator flap surgery.

Breast reconstruction with adipocutaneous free flap from the abdominal wall combines the benefits of abdominoplasty to those of a prosthesis-free breast reconstruction. The deep inferior epigastric artery perforator (DIEP) flap is supplied by intramuscular perforators from the deep inferior epigastric artery (DIEA). It consists of the dissection of perforating branches of the DIEA within the rectus abdominis muscle, thus sparing both muscle and fascia. Preoperative imaging in the planning of DIEP flap surgery has been shown to facilitate faster and safer surgery. This review article aims to discuss advantages and drawbacks of current imaging modalities for mapping the course of perforating vessels in the planning of DIEP flap surgery, and to present state-of-the-art imaging techniques.

Toxic megacolon in patients with severe acute colitis: computed tomographic features.

OBJECTIVE: The objective of the study was to evaluate computed tomography (CT) in the differential diagnosis of patients with toxic megacolon (TM) complicating severe acute colitis (SAC) and patients with SAC but no TM. MATERIALS AND METHODS: We identified 16 patients who presented clinically complicated SAC and CT examination before surgery. The CT scans of these patients were retrospectively evaluated in consensus by two abdominal radiologists blinded to the clinical and pathological results for CT findings of SAC, i.e., diffuse colonic wall thickening, submucosal edema, pericolonic fat stranding and ascites, and CT findings of TM reported in the literature, i.e., segmental colonic wall thinning, air-filled colonic distension over 6 cm with abnormal haustral pattern, nodular pseudopolyps and associated small bowel distension. Fisher's Exact Test was used for all statistical analyses. RESULTS: Segmental colonic wall thinning with abnormal haustral pattern was noted in TM only (P=.001). As compared to patients with SAC but no TM as a complication, patients with TM showed statistically more frequent air-filled colonic distension over 6 cm (P=.001) and nodular pseudopolyps (P=.001). Diffuse colonic wall thickening (P=.036) and submucosal edema (P=.036) were more present in cases of uncomplicated SAC. Pericolonic fat stranding (P=.12), ascites (P=.6), and small bowel and gastric distension (P=1) were not distinctive criteria. CONCLUSION: Computed tomography is useful in distinguishing patients with TM from patients with SAC but no TM as a complication. The association of air-filled colonic distension >6 cm, abnormal haustral pattern and segmental colonic parietal thinning seems pathognomonic of TM and should lead to rapid surgery.