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STUDY DESIGN: A laboratory study comparing polyether ether ketone (PEEK)-zeolite and PEEK spinal implants in an ovine model. OBJECTIVE: This study challenges a conventional spinal implant material, PEEK, to PEEK-zeolite using a nonplated cervical ovine model. SUMMARY OF BACKGROUND DATA: Although widely used for spinal implants due to its material properties, PEEK is hydrophobic, resulting in poor osseointegration, and elicits a mild nonspecific foreign body response. Zeolites are negatively charged aluminosilicate materials that are hypothesized to reduce this pro-inflammatory response when used as a compounding material with PEEK. MATERIALS AND METHODS: Fourteen skeletally mature sheep were, each, implanted with one PEEK-zeolite interbody device and one PEEK interbody device. Both devices were packed with autograft and allograft material and randomly assigned to one of 2 cervical disc levels. The study involved 2 survival time points (12 and 26 weeks) and biomechanical, radiographic, and immunologic endpoints. One sheep expired from complications not related to the device or procedure. A biomechanical evaluation was based on measures of segmental flexibility, using 6 degrees of freedom pneumatic spine tester. Radiographic evaluation was performed using microcomputed tomography scans in a blinded manner by 3 physicians. Levels of the pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha at the implant, were quantified using immunohistochemistry. RESULTS: PEEK-zeolite and PEEK exhibited an equivalent range of motion in flexion extension, lateral bending, and axial torsion. A motion was significantly reduced for implanted devices at both time points as compared with native segments. Radiographic assessments of fusion and bone formation were similar for both devices. PEEK-zeolite exhibited lower levels of IL-1ß ( P = 0.0003) and IL-6 ( P = 0.03). CONCLUSION: PEEK-zeolite interbody fusion devices provide initial fixation substantially equivalent to PEEK implants but exhibit a reduced pro-inflammatory response. PEEK-zeolite devices may reduce the chronic inflammation and fibrosis previously observed with PEEK devices.

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BACKGROUND: Magnetic sphincter augmentation (MSA) is a promising surgical treatment for patients with GERD. The aim of this study was to evaluate the outcomes of MSA in a large cohort of patients with GERD and to determine the factors predicting a favorable outcome. METHODS: This was a retrospective review of prospectively collected data of 553 patients who underwent MSA at our institution in a 5-year period. Preoperative clinical, endoscopic, manometric, and pH data were used in a univariate analysis. This was followed by a regression multivariable analysis to determine the factors predicting a favorable outcome. Favorable outcome was defined as freedom from proton pump inhibitors and ≥50% improvement in Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) total score. RESULTS: At a mean (SD) follow-up of 10.3 (10.6) months after MSA, 92.7% of the patients were free of proton pump inhibitor use and 84% reported at least 50% improvement in their GERD-HRQL total score. The GERD-HRQL total score was improved from a mean (SD) baseline value of 33.8 (18.7) to 7.2 (9.0) (p < 0.001) and 76.1% of the patients had normalization of their esophageal acid exposure. Independent predictors of a favorable outcome after MSA included age younger than 45 years (odds ratio [OR] 4.2; 95% CI, 1.1 to 15.2; p = 0.0305), male sex (OR 2.5; 95% CI, 1.1 to 5.7; p = 0.0301), GERD-HRQL total score >15 (OR 7.5; 95% CI, 3.3 to 16.8; p < 0.0001), and abnormal DeMeester score (OR, 2.6; 95% CI, 1.1 to 5.7; p = 0.0225). CONCLUSIONS: In this largest single-institution series, we demonstrate that MSA implantation is associated with very good clinical and objective outcomes. Age younger than 45 years, male sex, GERD-HRQL total score >15, and abnormal DeMeester score are the 4 preoperative factors predicting a favorable outcome and can be used in patient counseling and MSA use.

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OBJECTIVE: To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. BACKGROUND: EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. METHODS: In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. RESULTS: In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (control = 9.4%), increase in 9.1% (control = 37.5%), and stable disease in 54.5% (control = 43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90ß, and CDK4, and upregulation of Hsp72. CONCLUSIONS: AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.

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