ZEB1 loss increases glioma stem cell tumorigenicity and resistance to chemoradiation.

OBJECTIVE: Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas. METHODS: The authors explored resistance to therapy in the context of ZEB1 loss and overexpression in glioma stem cells (GSCs) and in patient data. RESULTS: Patients with ZEB1 loss had a shorter survival time than patients with wild-type ZEB1 in both the high- and low-MGMT groups. Consistent with the clinical data, mice implanted with ZEB1 knockdown GSCs showed shortened survival compared with mice inoculated with nonsilencing control (NS) short-hairpin RNA (shRNA) GSC glioblastoma. ZEB1-deleted GSCs demonstrated increased tumorigenicity with regard to proliferation and invasion. Importantly, GSCs that lose ZEB1 expression develop enhanced resistance to chemotherapy, radiotherapy, and combined chemoradiation. ZEB1 loss may lead to increased HER3 expression through the HER3/Akt pathway associated with this chemoresistance. Conversely, overexpression of ZEB1 in GSCs that are ZEB1 null leads to increased sensitivity to chemoradiation. CONCLUSIONS: The study results indicate that ZEB1 loss in cancer stem cells confers resistance to chemoradiation and uncovers a potentially targetable cell surface receptor in these resistant cells.

Vision Outcomes in Early versus Late Surgical Intervention of Pituitary Apoplexy: Meta-Analysis.

BACKGROUND: Pituitary apoplexy (PA) is defined by hemorrhage and necrosis of the pituitary gland, often acute in onset, and frequently in the setting of an existing pituitary adenoma. Our objective was to conduct a meta-analysis of the available literature on vision outcomes following surgical intervention for PA on the basis of the timing from apoplexy to surgery (ATS). METHODS: A thorough literature search of the published English-language literature was performed in PubMed, Ovid, and Cochrane databases using the key words ("pituitary apoplexy") and ("surgery" or "vision") from database inception to August 2018 was conducted. The primary outcome variable evaluated using a binary random-effects model was vision recovery outcomes (metric: odds ratio). RESULTS: Of 234 articles found, 12 articles containing 200 patients met our eligibility criteria. The mean age was 46.1, with a male-to-female ratio of 2.9:1. A total of 86% of PA patients presented with visual deficits (ATS <7 days in 93 and >7 days in 79 patients). In patients with an ATS <7 days, 97.8% experienced visual recovery, compared with 84.8% with an ATS >7 days (odds ratio 2.6 [95% CI 0.94-7.31]; P value = 0.07). CONCLUSIONS: Despite readily accepted guidelines provided by the United Kingdom advocating for early surgical intervention in PA, the rates of vision outcomes we report demonstrate >80% recovery for patients in both the early and late surgical intervention group. As such, conservative management may be warranted for early stabilization before surgical intervention in PA patients with respect to vision outcomes.

Gastrointestinal cancer surgery in patients with a prior ventriculoperitoneal shunt: the department of veterans affairs experience.

BACKGROUND: The estimated prevalence of hydrocephalus in all age groups is between 1% and 1.5%. Placement of a ventriculoperitoneal (VP) shunt in such patients offers them relatively normal lives. There are minimal data concerning the risk of postoperative complications in patients with shunts who undergo subsequent major visceral operations. We hypothesized that healthy adults who had VP shunts placed for acquired conditions and later underwent surgery for gastric or colon cancer would frequently have dense, shunt-related adhesions and high rates of adverse outcomes, particularly infection. METHODS: We assumed that all veterans were healthy on entry into military service. We searched national Department of Veterans Affairs databases from October 1994 through September 2003 to identify all Department of Veterans Affairs patients with shunts for acquired conditions and a curative-intent operation for stomach or colon cancer. We conducted chart reviews to determine their clinical courses. RESULTS: Five patients had codes for VP shunt, gastric cancer, and gastrectomy; 3 met our inclusion criteria. Fourteen had codes for VP shunt, colon cancer, and colectomy; 4 met our criteria. One of the evaluable gastrectomy patients had dense, shunt-related adhesions. None of the colectomy patients had notable adhesions. There were no postoperative complications in any of the seven patients. CONCLUSION: We believe this is the first report analyzing the clinical course of adults with VP shunts who later had major abdominal cancer surgery. The presence of a shunt was associated with dense adhesions in 1 (14%) of the 7 patients in this series, but not with an increased risk of postoperative complications.