5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. A subset of gliomas, especially low-grade tumors, do not accumulate PpIX intracellularly or readily fluoresce upon 5-ALA administration, making gross total resection difficult to achieve in diffuse lesions. We review existing literature on 5-ALA metabolism and PpIX accumulation to explore potential mechanisms of 5-ALA-induced glioma tissue fluorescence. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment.
Chordomas and chondrosarcomas are rare but devastating neoplasms that are characterized by chemoradiation resistance. For both tumors, surgical resection is the cornerstone of management. Immunotherapy agents are increasingly improving outcomes in multiple cancer subtypes and are being explored in chordoma and chondrosarcoma alike. In chordoma, brachyury has been identified as a prominent biomarker and potential molecular immunotherapy target as well as PD-1 inhibition. While studies on immunotherapy in chondrosarcoma are sparse, there is emerging evidence and ongoing clinical trials for PD-1 as well as IDH inhibitors. This review highlights potential biomarkers and targets for immunotherapy in chordoma and chondrosarcoma, as well as current clinical evidence and ongoing trials.
The emergence of three-dimensional human organoids has opened the door for the development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. The mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource and time intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell–cell and cell–stroma interactions, the tumor microenvironment, and therapeutic responsiveness. PDO models and drug-screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant time frames and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.
Study Design: Cross-Sectional Study Objectives: Socioeconomic status (SES) is a fundamental root of health disparities, however, its effect on surgical outcomes is often difficult to capture in clinical research, especially in spine surgery. Here, we present a large single-center study assessing whether SES is associated with cause-specific surgical outcomes. Methods: Patients undergoing spine surgery between 2015 and 2019 were assigned income in accordance with the national distribution and divided into quartiles based on the ZIP code-level median household income. We performed univariate, chi-square, and Analysis of Variance (ANOVA) analysis assessing the independent association of SES, quantified by household income, to operative outcomes, and multiple metrics of opioid consumption. Results: 1199 patients were enrolled, and 1138 patients were included in the analysis. Low household income was associated with the greatest rates of 3-month opioid script renewal (OR:1.65, 95% CI:1.14-2.40). In addition, low-income was associated with higher rates of perioperative opioid consumption compared to higher income including increased mean total morphine milligram equivalent (MME) 252.25 (SD 901.32) vs 131.57 (SD 197.46) (P < .046), and inpatient IV patient-controlled analgesia (PCA) MME 121.11 (SD 142.14) vs 87.60 (SD 86.33) (P < .023). In addition, household income was independently associated with length of stay (LOS), and emergency room (ER) revisits with low-income patients demonstrating significantly longer postop LOS and increasing postoperative ER visits. Conclusions: Considering the comparable surgical management provided by the single institution, the associated differences in postoperative outcomes as defined by increased morbidities and opioid consumption can potentially be attributed to health disparities caused by SES.
Single-center retrospective study. The objective of this study was to evaluate the association of psoas muscle mass defined sarcopenia with perioperative outcomes in geriatric patients undergoing elective spine surgery. We included geriatric patients undergoing thoracolumbar spinal surgery. Total psoas surface area (TPA) was measured on preoperative axial computerized tomography or magnetic resonance imaging at the L3 vertebra and normalized to the L3 vertebral body area. Patients were divided into quartiles by normalized TPA, and the fourth quartile (Q4) was compared to quartiles 1–3 (Q1-3). Outcomes included perioperative transfusions, length of stay (LOS), delirium, pseudoarthrosis, readmission, discharge disposition, revision surgery, and mortality. Of the patients who met inclusion criteria (n = 196), the average age was 73.4 y, with 48 patients in Q4 and 148 patients in Q1-3. Q4 normalized TPA cut-off was <1.05. Differences in Q4 preoperative characteristics included significantly lower body mass index, baseline creatinine, and a greater proportion of females (Table 1). Q4 patients received significantly more postoperative red blood cell and platelet transfusions and had longer ICU LOS (P < .05; Table 2). There was no difference in intraoperative transfusion volumes, delirium, initiation of walking, discharge disposition, readmission, pseudoarthrosis, or revision surgery (Tables 2 and 3). Mortality during follow-up was higher in Q4 but was not statistically significant (P = .075). Preoperative TPA in geriatric patients undergoing elective spine surgery is associated with increased need for intensive care and postoperative blood transfusion. Preoperative normalized TPA is a convenient measurement and could be included in geriatric preoperative risk assessment algorithms.