Preoperative bevacizumab does not increase complications following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Preoperative bevacizumab has been reported to increase postoperative complication risk following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We sought to review our experience with preoperative bevacizumab in patients undergoing CRS/HIPEC for peritoneal surface malignancy. METHODS: This is a retrospective review of patients who received neoadjuvant systemic therapy with or without bevacizumab prior to CRS/HIPEC at a high-volume academic center from 2007-2018. RESULTS: Of 499 patients, a total of 88 patients received neoadjuvant chemotherapy alone (n = 34) or in combination with bevacizumab (n = 54) within 3 months prior to CRS/HIPEC. No differences existed in 60-day major morbidity (17.6 vs. 16.7%, p = 0.81) or 60-day mortality (0 vs. 0%) between the two cohorts, and neoadjuvant bevacizumab was not associated with increased odds of overall complications (OR 0.86, 95% CI 0.35-2.09, p = 0.73) or major morbidity (OR 0.86, 95% CI 0.24-3.00, p = 0.81). Stratifying patients by primary tumor origin and post-operative complications did not reveal any significant differences between the two treatment groups. In addition, progression-free survival (PFS) and overall survival (OS) were similar in both cohorts. CONCLUSIONS: Preoperative bevacizumab is not associated with increased morbidity or mortality following CRS/HIPEC. Neoadjuvant therapy employing this biologic agent is safe and should not be a deterrent for aggressive cytoreduction with curative intent.

Silver-Catalyzed, N-Formylation of Amines Using Glycol Ethers.

A silver-catalyzed protocol was found to afford the N-formylation of amines in moderate-to-good yields. Ethylene glycol-derived, oligomeric ethers were found to function as the formylating agent, with 1,4-dioxane affording the best results. This reaction does not require the use of stoichiometric activating reagents, and avoids the use of explosive reagents or toxic gases, such as CO, as the C1 synthon. Mechanistic studies indicate a single-electron transfer-based pathway. This work highlights the ability of silver to participate in unexpected reaction pathways.

The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies.

Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior in vitro efficacy to treatment based upon the NF2 genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth in vivo. Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies. SIGNIFICANCE: Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas.This article is highlighted in the In This Issue feature, p. 1611.

Quad S2-Alar-Iliac Screw Fixation via Navigated Spinal Robotics With Software Planning: 2-Dimensional Operative Video.

The use of robotic guidance for spinal instrumentation has become promising for its ability to offer the advantages of precision, accuracy, and reproducibility. However, utilization and adoption of robotic platforms for spine surgery remain limited especially in comparison to other surgical fields. We present here a case of a 71-yr-old man with a prior T4-pelvis long-segment fusion who presented with distal sacro-iliac instrumentation loosening with pseudarthrosis. He subsequently underwent construct revision with quad (bilateral dual) S2-alar-iliac screw fixation with navigated spinal robotic assistance (Mazor X Stealth Edition, Medtronic Sofamor Danek, Medtronic Inc, Dublin, Ireland). To our knowledge, this is the first video demonstrating the preoperative software planning and intraoperative workflow for placing quad S2-alar-iliac screws with navigated spinal robotic guidance using the Mazor X Stealth Edition. There is no identifying information in this video. Patient consent was obtained for the surgical procedure and for publishing of the material included in the video.