Identification of Differential Patterns of Oxidative Biomarkers in Prostate Cancer Progression.

INTRODUCTION: Oxidative stress has been found to be associated with the progression of prostate cancer (PCa); however, human studies which identify differential roles of each oxidation pathway in PCa progression are lacking. We aimed to identify which oxidative stress markers, specifically lipid and global oxidation and glycation, are associated with PCa progression. PATIENTS AND METHODS: We recruited 3 groups of patients from a urologic clinic at the University of Cincinnati Medical Center: men with PCa who had undergone prostatectomy, men with PCa under watchful waiting, and men with benign prostatic hyperplasia (BPH). We used the most commonly used lipid oxidation marker, F2-isoprostanes; global oxidation markers, fluorescent oxidation products (FlOPs); and the commonly used marker for advanced glycation end products, carboxymethyllysine. These biomarkers were measured in plasma samples at baseline entry. Plasma prostate-specific antigen (PSA) was measured at enrollment and follow-up visits. RESULTS: Compared with men with BPH, men with PCa who had undergone prostatectomy had 26% (P = .01) higher levels of F2-isoprostanes and 20% (P = .08) higher levels of carboxymethyllysine. All the oxidation markers were similar when comparing men under watchful waiting with men with BPH. When examining the associations between baseline oxidation markers and follow-up PSAs, we found that different oxidation markers had differential patterns associated with PSA elevation. F2-isoprostanes were positively associated with PSA elevation among men with PCa; FlOP_320 was positively associated with PSA elevation among both men with PCa and men with BPH, whereas among men with PCa under watchful waiting, FlOP_360 and FlOP_400 had opposite trends of associations with PSA elevation. CONCLUSIONS: Our study suggested that high levels of lipid oxidation were associated with PCa progression, whereas different global oxidation markers had different patterns associated with PCa progression. Large-scale clinical studies are needed to confirm our associations. Our study provides a comprehensive view of the relationship between biomarkers and PCa progression.

Pulsed and CW adjustable 1942 nm single-mode all-fiber Tm-doped fiber laser system for surgical laser soft tissue ablation applications.

A surgical laser soft tissue ablation system based on an adjustable 1942 nm single-mode all-fiber Tm-doped fiber laser operating in pulsed or CW mode with nitrogen assistance is demonstrated. Ex vivo ablation on soft tissue targets such as muscle (chicken breast) and spinal cord (porcine) with intact dura are performed at different ablation conditions to examine the relationship between the system parameters and ablation outcomes. The maximum laser average power is 14.4 W, and its maximum peak power is 133.1 W with 21.3 µJ pulse energy. The maximum CW power density is 2.33 × 106 W/cm2 and the maximum pulsed peak power density is 2.16 × 107 W/cm2. The system parameters examined include the average laser power in CW or pulsed operation mode, gain-switching frequency, total ablation exposure time, and the input gas flow rate. The ablation effects were measured by microscopy and optical coherence tomography (OCT) to evaluate the ablation depth, superficial heat-affected zone diameter (HAZD) and charring diameter (CD). Our results conclude that the system parameters can be tailored to meet different clinical requirements such as ablation for soft tissue cutting or thermal coagulation for future applications of hemostasis.

Impact of Afirma gene expression classifier on cytopathology diagnosis and rate of thyroidectomy.

BACKGROUND: The Afirma gene expression classifier (GEC) assesses malignancy risk in patients with indeterminate thyroid nodules. Afirma putatively reduces costs by classifying certain nodules as benign and thereby avoiding unnecessary surgery. Prior studies have evaluated its impact exclusively on GEC-tested nodules. The objective of the current study was to analyze the effect of Afirma on 1) cytopathology diagnosis, 2) the rate of surgery, and 3) the rate of malignancy on all indeterminate nodules at a high-volume thyroid center. METHODS: A retrospective cohort analysis of indeterminate (Bethesda III/IV) thyroid nodules from 2012 through 2014 was performed. Cases were evaluated from January 2012 to July 2013 (pre-Afirma), and from July 2013 to December 2014 (post-Afirma). RESULTS: Of 4292 fine-needle aspirations (FNAs) performed, 13.2% were classified as indeterminate. The GEC was used in 45.3% of post-Afirma cases, with the GEC-Benign call rate at 37.1%. In comparing pre-Afirma and post-Afirma cohorts, a significant increase in Bethesda III (10.7% vs 13.4%; P<.005) and Bethesda IV (1.8% vs 2.9%; P<.01) rates were observed. Conversely, the incidence of Bethesda II was found to be significantly decreased (74.6% vs 68.8%; P<.001). The rate of surgery did not change significantly between pre-Afirma and post-Afirma cohorts (37.7% vs 45.1%; P = .11), nor did the malignancy rate (25.3% vs 36.0%; P = .12). CONCLUSIONS: The incidence of indeterminate FNA diagnoses significantly increased after Afirma became routinely available, whereas the incidence of benign diagnoses significantly decreased. These data suggest that Afirma may shift FNA interpretation toward Bethesda III/IV, in which molecular testing is used. Moreover, the institutional rates of surgery and malignancy did not appear to change, raising uncertainty regarding the benefits of molecular assay risk stratification. Afirma may produce unintended collateral effects, increasing the number of indeterminate FNA diagnoses while not affecting the institutional thyroidectomy rate or malignancy yield. Cancer Cytopathol 2016;124:722-8. © 2016 American Cancer Society.

30 Years of Neurosurgical Robots: Review and Trends for Manipulators and Associated Navigational Systems.

This review provides an examination of contemporary neurosurgical robots and the developments that led to them. Improvements in localization, microsurgery and minimally invasive surgery have made robotic neurosurgery viable, as seen by the success of platforms such as the CyberKnife and neuromate. Neurosurgical robots can now perform specific surgical tasks such as skull-base drilling and craniotomies, as well as pedicle screw and cochlear electrode insertions. Growth trends in neurosurgical robotics are likely to continue but may be tempered by concerns over recent surgical robot recalls, commercially-driven surgeon training, and studies that show operational costs for surgical robotic procedures are often higher than traditional surgical methods. We point out that addressing performance issues related to navigation-related registration is an active area of research and will aid in improving overall robot neurosurgery performance and associated costs.

Development of an integrated optical coherence tomography-gas nozzle system for surgical laser ablation applications: preliminary findings of in situ spinal cord deformation due to gas flow effects.

Gas assisted laser machining of materials is a common practice in the manufacturing industry. Advantages in using gas assistance include reducing the likelihood of flare-ups in flammable materials and clearing away ablated material in the cutting path. Current surgical procedures and research do not take advantage of this and in the case for resecting osseous tissue, gas assisted ablation can help minimize charring and clear away debris from the surgical site. In the context of neurosurgery, the objective is to cut through osseous tissue without damaging the underlying neural structures. Different inert gas flow rates used in laser machining could cause deformations in compliant materials. Complications may arise during surgical procedures if the dura and spinal cord are damaged by these deformations. We present preliminary spinal deformation findings for various gas flow rates by using optical coherence tomography to measure the depression depth at the site of gas delivery.

Use of evidence-based guidelines reduces radioactive iodine treatment in patients with low-risk differentiated thyroid cancer.

OBJECTIVE: The goal was to determine if there was a relation between the introduction of evidence-based radioactive iodine (RAI) treatment guidelines for differentiated thyroid cancer (DTC) at Cedars-Sinai Medical Center (CSMC) and subsequent RAI use. In addition, we compared RAI treatment rates for DTC at CSMC to data from the National Cancer Database (NCDB) to see if the trends in RAI use at CSMC differed from the national trends. METHODS: RAI data from the CSMC Thyroid Cancer Center were reviewed to determine if RAI treatment was given appropriately. Kaplan-Meier curves were used to estimate disease-free survival for patients who received or did not receive treatment. RAI data from the NCDB were also used to compare how CSMC treatment rates compare nationally. RESULTS: There were 444 CSMC patients identified with DTC between 2009 and 2012. Approximately 95% of the patients had papillary thyroid cancer (n=423) with 65% in the stage I risk group (n=290). Kaplan-Meier curves for stages I-III show that those who did not receive RAI treatment had 100% disease-free survival, which was better than those who had received RAI. However, given that the total population in both stages II and III is quite small, having received RAI ablation was not found to be statistically significant. Stage I patients who received RAI had a significantly increased incidence of recurrent disease. The NCDB RAI rates for all DTC stages in each year have consistently been over 50% with an overall treatment rate of 57%. There were significant differences in the treatment rates between CSMC and NCDB, with a decrease in the use of RAI in low-risk patients with stage I tumors at CSMC following institution of the guidelines. CONCLUSION: Prudent use of RAI treatment should be considered for low-risk patients. Ablation rates have been decreasing steadily at CSMC, particularly among low-risk patients, with the adoption of more stringent RAI treatment guidelines. It is apparent from our data that physician practices can change with the implementation and dissemination of evidence-based guidelines for the treatment of DTC with RAI.

Comparison with published systems of a new staging system for papillary and follicular thyroid carcinoma.

BACKGROUND: Several staging systems exist to estimate the prognosis for patients with thyroid carcinoma. Our goal was to develop a new staging system to predict cancer-specific survival (CSS) and evaluate it against published systems. METHODS: The Cedars-Sinai Medical Center (CSMC)'s staging system was derived using data from an adjusted analysis of 1622 patients with differentiated thyroid carcinomas (DTCs) from the CSMC Thyroid Cancer Center. Mean follow-up time was 11.8 years. There were 1180 female and 442 male patients with a mean age of 46. Staging systems reviewed include University of Alabama (Birmingham) and M.D. Anderson Cancer Center (UAB-MDACC); the Tumor-Node-Metastasis (TNM) 5th and 7th editions; Memorial Sloan-Kettering (MSK); the National Thyroid Cancer Treatment Cooperative Study (NTCTCS); Ohio State; Clinical Class; Metastases, Age, Completeness of resection, Invasion, and tumor Size (MACIS); Noguchi; and the Yildirim model for predicting outcomes. The proportion of variance explained (PVE) and the C-index were computed to rank and compare each staging system's ability to predict CSS with this patient population. RESULTS: Adjusted hazard ratios revealed that age at surgery of >45 years, the presence of distant metastases, capsular invasion, and vascular invasion were the most significant predictors of CSS in this patient population. The final CSMC risk score consists of low-, moderate-, and high-risk groups. Among the well-differentiated thyroid carcinoma staging systems, the CSMC and NTCTCS ranked highest with PVE values of 5% and 4.3%, respectively, while the NTCTCS and CSMC staging systems were reversed using the C-index (0.77 and 0.76, respectively). CONCLUSION: The PVE and C-index values were relatively low across all applicable staging systems and varied in each study reviewed. This suggests that no one staging system has been shown to be superior to another across different patient populations with DTC. In the future, additional factors, such as biological markers, added to the clinical and pathological characteristics may lead to the development of superior staging systems.