Citations

Abstract BACKGROUND: Patients with pleomorphic xanthoastrocytoma (PXA) routinely undergo multiple procedures to ensure recurrence-free survival and are resultantly at increased risk of experiencing perioperative complications (regional, medical, and/or neurological), a combination of which has not been recorded in previous studies. OBJECTIVE: To determine perioperative outcomes in a cohort of patients (adult and pediatric) with intracranial PXA. METHODS: We retrospectively identified 39 patients who underwent surgery at our institution for intracranial PXA between 1994 and 2011. Demographic factors were recorded along with Karnofsky Performance Status (KPS), complications, and mortality. RESULTS: Mean patient age was 31 years at the most recent surgery. A majority of patients (24; 62%) had multiple surgeries with a mean of 2 operations per patient. Eleven PXAs (28%) were malignant (grade III or IV). Perioperative complications included permanent neurological worsening in 4 patients (10%), regional complications in 4 (10%), and medical complications in 3 (8%). Preoperative KPS was ≥70 in 34 of 38 patients (89%). Long-term postoperative KPS was ≥70 in 36 of 37 patients (97%), suggesting good functional outcomes. There was no perioperative mortality, but 7 patients (18%) died of tumor progression. Patients with malignant PXAs trended toward higher risk of regional complications (3 of 11 patients [27%]; P = .06), received adjuvant therapy more often (10 of 11 patients [91%]; P < .001), had higher mortality from tumor progression (7 of 11 patients [64%]; P < .001), and were significantly larger (mean, 6.05 ± 0.73 cm standard error of the mean; n = 7; P < .01). CONCLUSION: Both pediatric and adult PXAs may be resected with good functional outcomes. Perioperative neurological complications are relatively common, but do not affect long-term functional outcome or mortality. Malignant PXAs are higher risk for perioperative complications and, ultimately, death from tumor progression, despite increased use of adjuvant radiation and chemotherapy.

Study Design. Prospective cohort study. Objective. To characterize the accuracy of patient recollection of preoperative symptoms after lumbar spine surgery. Summary of Background Data. Although patient-reported outcomes have become important in the evaluation of spine surgery patients, the accuracy of patient recall remains unknown. Methods. Patients undergoing lumbar decompression with or without fusion were enrolled. Back and leg Numeric Pain Scores and Oswestry Disability Indices were recorded preoperatively. Patients were asked to recall their preoperative status at a minimum of 1 year after surgery. Actual and recalled scores were compared using paired t tests and relations were quantified using Pearson correlation coefficients. Multivariable linear regression was used to identify factors that affected recollection. Results. Sixty-two patients with a mean age of 66.1 years were included. Compared to their preoperative scores, patients showed significant improvement in back pain (mean difference [MD] = −3.2, 95% CI −4.0 to −2.4), leg pain (MD −3.3, 95% CI −4.3 to −2.2), and disability (MD −25.0%, 95% CI −28.7 to −19.6). Patient recollection of preoperative status was significantly more severe than actual for back pain (MD +2.3, 95% CI 1.5–3.2), leg pain (MD +1.8, 95% CI 0.9–2.7), and disability (MD +9.6%, 95% CI 5.6–14.0). No significant correlation between actual and recalled scores with regards to back (r = 0.18) or leg (r = 0.24) pain and only moderate correlation with disability (r = 0.44) were seen. This was maintained across age, sex, and time between date of surgery and recollection. More than 40% of patients switched their predominant symptom from back pain to leg pain or leg pain to back pain on recall. Conclusion. Relying on patient recollection does not provide an accurate measure of preoperative status after lumbar spine surgery. Recall bias indicates the importance of obtaining true baseline scores and patient-reported outcomes prospectively and not retrospectively. Level of Evidence: 2

Significance Ubiquitin-specific protease 6 (USP6) is a deubiquitylase that is overexpressed by chromosome translocation in two human neoplasms, aneurysmal bone cyst and nodular fasciitis. The relevant substrates of this ubiquitin-specific protease are not clear. Here, we identify the Wnt receptor Frizzled (Fzd) as a key target of the USP6 oncogene. Increased expression of USP6 increases the membrane abundance of Fzd, and hence increases cellular sensitivity to Wnts. USP6 opposes the activity of the ubiquitin ligase and tumor suppressor ring finger protein 43 (RNF43). This study identifies a new mechanism for pathological Wnt pathway activation in human disease and suggests a new approach to regulate Wnt activity therapeutically.

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is lethal cancer whose primary tumor is characterized by dense composition of cancer cells, stromal cells, and extracellular matrix (ECM) composed largely of collagen. Within the PDAC tumor microenvironment, activated pancreatic stellate cells (PSC) are the dominant stromal cell type and responsible for collagen deposition. Lumican is a secreted proteoglycan that regulates collagen fibril assembly. We have previously identified that the presence of lumican in the ECM surrounding PDAC cells is associated with improved patient outcome after multimodal therapy and surgical removal of localized PDAC. Experimental Design: Lumican expression in PDAC from 27 patients was determined by IHC and quantitatively analyzed for colocalization with PSCs. In vitro studies examined the molecular mechanisms of lumican transcription and secretion from PSCs (HPSCs and HPaSteC), and cell adhesion and migration assays examined the effect of lumican on PSCs in a collagen-rich environment. Results: Here we identify PSCs as a significant source of extracellular lumican production through quantitative IHC analysis. We demonstrate that the cytokine, TGF-β, negatively regulates lumican gene transcription within HPSCs through its canonical signaling pathway and binding of SMAD4 to novel SBEs identified within the promoter region. In addition, we found that the ability of HPSCs to produce and secrete extracellular lumican significantly enhances HPSCs adhesion and mobility on collagen. Conclusions: Our results demonstrate that activated pancreatic stellate cells within PDAC secrete lumican under the negative control of TGF-β; once secreted, the extracellular lumican enhances stellate cell adhesion and mobility in a collagen-rich environment. Clin Cancer Res; 22(19); 4934–46. ©2016 AACR.

Abstract Alzheimer's disease research has often focused on the molecular brain changes that promote memory loss and other dementia‐related cognitive impairments. Many studies, for example, have used positron emission tomography (PET) imaging to measure brain levels of the beta‐amyloid protein, a key molecular suspect in Alzheimer's. In recent years, PET scans have become more prominent in clinical settings. Clinicians may use a positive PET scan—that is, a significant presence of beta‐amyloid plaques in the brain—to help determine a diagnosis of Alzheimer's disease. Yet, because beta‐amyloid PET remains a fairly new diagnostic tool, physicians and patients still have many basic questions about how and why it is used. This article addresses some of those questions. It explains what PET scans actually show, how they are employed in research and clinical trials, and when they should and should not be used to help diagnose Alzheimer's in everyday patients. The article also discusses whether cognitively healthy people should request PET scans to assess their risk for developing dementia. Information in the text will be updated in future years, as diagnostic imaging techniques for Alzheimer's disease continue to evolve.

AbstractSVC obstruction is a rare acute complication after bicaval cardiac transplantation and can be catastrophic for the patient. Herein, we report the case of a child who developed SVC thrombosis causing acute SVC syndrome nine days after heart transplantation. Thrombolysis was successfully performed using the AngioJet™ system and subsequent balloon angioplasty with re‐establishment of flow. This procedure allowed for revascularization without repeat sternotomy or stent implantation. The patient is well without recurrence at last follow‐up.