Operative treatment of anterior thoracic spinal cord herniation:three new cases and an individual patient data meta-analysis of 126 case reports

OBJECTIVE: Anterior thoracic spinal cord herniation is a rare cause of progressive myelopathy. Much has been speculated about the best operative treatment. However, no evidence in favor of any of the promoted techniques is available to date. Therefore, we decided to analyze treatment procedures and treatment outcomes of anterior thoracic spinal cord herniation to identify those factors that determine postoperative outcome. METHODS: An individual patient data meta-analysis was conducted, focusing on age, gender, vertebral segment of herniation, preoperative neurological status, operative interval, operative findings, operative techniques, intraoperative neurophysiological monitoring, postoperative imaging, neurological outcome and follow-up. Three cases from our own institution were added to the material collected. Bivariate analysis tests and multivariate logistic regression tests were used so as to define which variables were associated with outcome after surgical treatment of anterior thoracic spinal cord herniation. RESULTS: Brown-Séquard syndrome and release of the herniated spinal cord appeared to be strong independent factors, associated with favorable postoperative outcome. Widening of the dura defect is associated with the highest prevalence of postoperative motor function improvement when compared with the application of an anterior dura patch (P < 0.036). CONCLUSION: Most patients with anterior thoracic spinal cord herniation require operative treatment because of progressive myelopathy. Patients with Brown-Séquard syndrome have a better prognosis with respect to postoperative motor function improvement. In this review, spinal cord release and subsequent widening of the dura defect were associated with the highest prevalence of motor function improvement. D-wave recording can be a very useful tool for the surgeon during operative treatment of this disorder

Characteristics of Patients Who Survived < 3 Months or > 2 Years After Surgery for Spinal Metastases: Can We Avoid Inappropriate Patient Selection?

PURPOSE: Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is < 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. PATIENTS AND METHODS: A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS]), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. RESULTS: In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. CONCLUSION: Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival

Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their potential to reduce radiation toxicity. A number of different types of stem cells are being investigated for their potential to treat a variety of disorders. Their current status, localization, characterization, isolation, and potential in stem cell-based therapies are addressed. Although clinical adult stem cell research is still at an early stage, preclinical experiments show the potential these therapies may have. Based on the major advances made in this field, stem cell-based therapy has great potential to allow prevention or treatment of normal tissue damage after radiotherapy. Semin Radiat Oncol 19:112-121 (C) 2009 Elsevier Inc. All rights reserved.</p

Fingolimod: therapeutic mechanisms and ocular adverse effects.

Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, discontinuation of fingolimod alone may not be sufficient and intra-vitreal therapy may be required. We also propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity

Mesenchymal stem cell-derived HGF attenuates radiation-induced senescence in salivary glands via compensatory proliferation

BACKGROUND &amp; AIM: Irradiation of the salivary glands during head and neck cancer treatment induces cellular senescence in response to DNA damage and contributes to radiation-induced hyposalivation by affecting the salivary gland stem/progenitor cell (SGSC) niche. Cellular senescence, such as that induced by radiation, is a state of cell-cycle arrest, accompanied by an altered pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP) with potential detrimental effects on the surrounding microenvironment. We hypothesized that the pro-regenerative properties of mesenchymal stem cells (MSCs) may attenuate cellular senescence post-irradiation. Therefore, here we evaluated the effects of adipose-derived MSCs (ADSCs) on the radiation-induced response of salivary gland organoids (SGOs).METHODS: Proteomic analyses to identify soluble mediators released by ADSCs co-cultured with SGOS revealed secretion of hepatocyte growth factor (HGF) in ADSCs, suggesting a possible role in the stem cell crosstalk. Next, the effect of recombinant HGF in the culture media of ex vivo grown salivary gland cells was tested in 2D monolayers and 3D organoid models.RESULTS: Treatment with HGF robustly increased salivary gland cell proliferation. Importantly, HGF supplementation post-irradiation enhanced proliferation at lower doses of radiation (0, 3, 7 Gy), but not at higher doses (10, 14 Gy) where most cells stained positive for senescence-associated beta-galactosidase. Furthermore, HGF had no effect on the senescence-associated secretory phenotype (SASP) of irradiated SGOs, suggesting there may be compensatory proliferation by cell-division competent cells instead of a reversal of cellular senescence after irradiation.CONCLUSION: ADSCs may positively influence radiation recovery through HGF secretion and can promote the ex vivo expansion of salivary gland stem/progenitor cells to enhance the effects of co-transplanted SGSC.</p