Trends in Detection of Adenoma and Sessile Serrated Lesions Over a Decade in a Community-Based Healthcare System.

INTRODUCTION: Adenoma detection rate (ADR) is an accepted benchmark for screening colonoscopy. Factors driving ADR and its relationship with sessile serrated lesions detection rate (SSLDR) over time remain unclear. We aim to explore patient, physician, and procedural influences on ADR and SSLDR trends. METHODS: Using a large healthcare system in northern California from January 2010 to December 2020, a total of 146,818 screening colonoscopies performed by 33 endoscopists were included. ADR and SSLDR were calculated over time using natural language processing. Logistic regression was used to calculate the odd ratios of patient demographics, physician attributes, and procedural details over time. RESULTS: Between 2010 and 2020, ADR rose from 19.4% to 44.4%, whereas SSLDR increased from 1.6% to 11.6%. ADR increased by 2.7% per year (95% confidence interval 1.9%-3.4%), and SSLDR increased by 1.0% per year (95% confidence interval 0.8%-1.2%). Higher ADR was associated with older age, male sex, higher body mass index, current smoker, higher comorbidities, and high-risk colonoscopy. By contrast, SSLDR was associated with younger age, female sex, white race, and fewer comorbidities. Patient and procedure characteristics did not significantly change over time ( P -interaction >0.05). Longer years in practice and male physician were associated with lower ADR and SSLDR in 2010, but significantly attenuated over time ( P -interaction <0.05). DISCUSSION: Both ADR and SSLDR have increased over time. Patient and procedure factors did not significantly change over time. Male endoscopist and longer years in practice had lower initial ADR and SSLDR, but significantly lessened over time.

Change in stage after neoadjuvant chemoradiation is associated with survival in patients with esophageal cancer.

BACKGROUND: The aim of this study was to determine if change in stage after neoadjuvant chemoradiation (CRT) was associated with improved survival in esophageal cancer using a national database. METHODS: Using the National Cancer Database, patients with non-metastatic, resectable esophageal cancer who received neoadjuvant CRT and surgery were identified. Comparing clinical to the pathologic stage, change in stage was classified as pathologic complete response (pCR), downstaged, same-staged, or upstaged. Univariable and multivariable Cox regression models were used to identify factors associated with survival. RESULTS: A total of 7745 patients were identified. The median overall survival (OS) was 34.9 months. Median OS was 60.3 months if pCR, 39.1 months if downstaged, 28.3 months if same-staged, and 23.4 months if upstaged (p < 0.0001). On multivariable analysis, pCR was associated with improved OS compared to the other groups (downstaged: hazard ratio [HR]: 1.32 [95% confidence interval [CI]: 1.18-1.46]; same-staged: HR: 1.89 [95% CI: 1.68-2.13]; upstaged: HR: 2.54 [95% CI: 2.25-2.86]; all p < 0.0001). CONCLUSIONS: In this large database study, change in stage after neoadjuvant CRT was strongly associated with survival for patients with non-metastatic, resectable esophageal cancer. There was a significant stepwise decline in survival, in descending order of pCR, downstaged tumor, same-staged tumor, and upstaged tumor.

A Platform for Spatiotemporal "Matrix" Stimulation in Brain Networks Reveals Novel Forms of Circuit Plasticity.

Here we demonstrate a facile method by which to deliver complex spatiotemporal stimulation to neural networks in fast patterns, to trigger interesting forms of circuit-level plasticity in cortical areas. We present a complete platform by which patterns of electricity can be arbitrarily defined and distributed across a brain circuit, either simultaneously, asynchronously, or in complex patterns that can be easily designed and orchestrated with precise timing. Interfacing with acute slices of mouse cortex, we show that our system can be used to activate neurons at many locations and drive synaptic transmission in distributed patterns, and that this elicits new forms of plasticity that may not be observable via traditional methods, including interesting measurements of associational and sequence plasticity. Finally, we introduce an automated "network assay" for imaging activation and plasticity across a circuit. Spatiotemporal stimulation opens the door for high-throughput explorations of plasticity at the circuit level, and may provide a basis for new types of adaptive neural prosthetics.

A Prospective Trial to Compare Deep Inspiratory Breath Hold With Prone Breast Irradiation.

PURPOSE: To compare heart and lung doses for adjuvant whole breast irradiation (WBI) between radiation plans generated supine with deep inspiratory breath hold (S-DIBH) and prone with free-breathing (P-FB) and examine the effect of breast volume (BV) on dosimetric parameters. METHODS AND MATERIALS: Patients with left breast ductal carcinoma in situ or invasive cancer receiving adjuvant WBI were enrolled on a single-institutional prospective protocol. Patients were simulated S-DIBH and P-FB; plans were generated using both scans. Wilcoxon signed-rank and rank-sum tests were used to compare intrapatient differences between plans for the entire cohort and within BV groups defined by tertiles. RESULTS: Forty patients were enrolled. Thirty-four patients are included in the analysis owing to patient withdrawal or inability to hold breath. With WBI dose of 4005 to 4256 cGy, mean heart dose (MHD) was 80 cGy in S-DIBH and 77 cGy in P-FB (P = .08). Mean ipsilateral lung dose (MLD) was 453 cGy in S-DIBH and 45 cGy in P-FB (P < .0001). Mean and max left anterior descending artery doses were 251 cGy and 551 cGy in S-DIBH, respectively (P = .1), and 324 cGy and 993 cGy in P-FB, respectively (P = .3). Hot spot and separation were 109% and 22 cm in S-DIBH, respectively, and 107% and 16 cm in P-FB, respectively (P < .0001). For patients with smallest BV, S-DIBH improved MHD and left anterior descending artery doses; for those with largest BV, P-FB improved cardiac dosimetry. With increasing BV, there was an increasing advantage of P-FB for MHD (P = .05), and max (P = .03) and mean (P = .02) left anterior descending artery doses, and the reduction in MLD, hot spot, and separation with P-FB increased (P < .05). CONCLUSIONS: MHD did not differ between P-FB and S-DIBH, whereas MLD was significantly lower with P-FB. Analysis according to breast volume revealed improved cardiac dosimetry with S-DIBH for women with smallest BV and improved cardiac dosimetry with P-FB for women with larger BV, thereby providing a dosimetric rationale for using breast size to help determine the optimal positioning for WBI.

Radiation effect on late cardiopulmonary toxicity: An analysis comparing supine DIBH versus prone techniques for breast treatment.

Two commonly used whole breast irradiation (WBI) techniques, deep inspiration breath hold (DIBH) and prone positioning, are compared with regard to dosimetry and estimated late cardiac morbidity and secondary lung cancer mortality using published models. Forty patients with left-sided DCIS or breast cancer who underwent lumpectomy and required adjuvant WBI were enrolled on a prospective trial comparing supine DIBH (S-DIBH) with prone free breathing (P-FB) planning. Patients underwent CT simulation in both positions; two plans were generated for each patient. Comparative dosimetry was available for 34 patients. Mean cardiac and lung doses were calculated. Risk of death from ischemic heart disease (IHD), risk of at least one acute coronary event (ACE), and lung cancer mortality were estimated from published data. Difference between S-DIBH and P-FB plans was compared using paired two-tailed t test. Estimated mean risk of death from IHD by age 80 was 0.1% (range 0.0%-0.2%) for both plans (P = 1.0). Mean risk of at least one ACE was 0.3% (range 0.1%-0.6%) for both plans (P = .6). Mean lung cancer mortality risk was 1.4% (range 0.5%-15.4%) for S-DIBH and 1.0% (range 0.4%-9.8%) for P-FB (P = .008). Excess lung cancer mortality due to radiation was 0.5% (range 0.1%-6.0%) with S-DIBH and 0.0% (range 0.0%-0.4%) with P-FB (P = .008). Both S-DIBH and P-FB provide excellent cardiac sparing. Prone positioning results in lower lung dose than S-DIBH and leads to an absolute decrease of 0.5% in excess lung cancer mortality for patients receiving WBI.

Effects of ß-Adrenergic Antagonists on Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Locally advanced non-small cell lung cancer (NSCLC) is highly resistant to chemoradiotherapy, and many cancer patients experience chronic stress. Studies that suggest stimulation of ß-adrenergic receptors (ß-AR) promotes tumor invasion and therapy resistance. We investigated whether ß-AR inhibition with beta-blockers acts as a chemotherapy and radiation sensitizer in vitro and in patients treated with chemoradiation for locally advanced NSCLC. METHODS: We investigated the effects of the non-selective beta-blocker propranolol on two human lung adenocarcinoma cell lines (PC9, A549) treated with radiation or cisplatin. We retrospectively evaluated 77 patients with Stage IIIA NSCLC who received induction chemoradiation followed by surgery. Pathological and imaging response, metastatic rate, and survival were analyzed using SPSS v22.0 and PrismGraphpad6. RESULTS: Propranolol combined with radiation or cisplatin decreased clonogenic survival of PC9 and A549 cells in vitro (p < 0.05). Furthermore, propranolol decreased expression of phospho-protein kinase A (p-PKA), a ß-adrenergic pathway downstream activation target, in both cell lines compared to irradiation or cisplatin alone (p < 0.05). In patients treated for Stage IIIA NSCLC, 16 took beta-blockers, and 61 did not. Beta-blockade is associated with a trend to improved overall survival (OS) at 1 year (81.3% vs 57.4%, p = 0.08) and distant metastasis-free survival (DMFS) (2.6 years vs. 1.3 years, p = 0.16). Although beta-blocker use was associated with decreased distant metastases (risk ratio (RR) 0.19; p = 0.03), it did not affect primary tumor pathological response (p = 0.40) or imaging response (p = 0.36). CONCLUSIONS: ß-AR blockade enhanced radiation and cisplatin sensitivity of human lung cancer cells in vitro. Use of beta-blockers is associated with decreased distant metastases and potentially improved OS and DMFS. Additional studies are warranted to evaluate the role of beta-blockers as a chemoradiation sensitizer in locally advanced NSCLC.

Stereotactic body radiation therapy with higher biologically effective dose is associated with improved survival in stage II non-small cell lung cancer.

OBJECTIVES: The role of stereotactic body radiation therapy (SBRT) in treating stage II non-small cell lung cancer (NSCLC) remains unclear. This study evaluates SBRT dose prescription patterns and survival outcomes in Stage II NSCLC using the National Cancer Database (NCDB). MATERIALS AND METHODS: Patients diagnosed with Stage II NSCLC and treated with SBRT between 2004-2013 were identified in NCDB. The biologically effective dose with α/ß = 10 Gy (BED10) was calculated. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox regression models. RESULTS: Of 56,543 patients with Stage II NSCLC, 451 (0.8%) received SBRT. There were 360 patients (79.8%) with node-negative and 91 patients (20.2%) with node-positive disease. The most common prescriptions were 10 Gy x 5 (35.9%) and 12 Gy x 4 (19.3%). The mean and median BED10 were 114.9 Gy and 105.6 Gy, respectively. With median follow-up of 19.3 months, overall median survival was 23.7 months. Median survival was 22.4 months for those treated with BED10 < 114.9 Gy versus 31.5 months for BED10 ≥ 114.9 Gy (p = 0.036). On multivariate analysis, BED10 as a continuous variable (hazard ratio [HR] 0.991, p = 0.009) and ≥ 114.9 Gy (HR 0.63, p = 0.015) were associated with improved survival in node-negative patients. BED10 as a continuous variable (HR 0.997, p = 0.465) and ≥ 114.9 Gy (HR 0.81, p = 0.546) were not significant factors for predicting survival in node-positive patients. CONCLUSION: SBRT is infrequently utilized to treat Stage II NSCLC in the United States. Treatment with higher BED10 was associated with improved survival, and the benefit was limited to patients with node-negative disease.

Definitive treatment patterns and survival in stage II non-small cell lung cancer.

OBJECTIVES: This study delineated definitive treatment patterns for Stage II non-small cell lung cancer (NSCLC) in the United States and evaluated survival by treatment approach. MATERIALS AND METHODS: Patients with clinically-staged Stage II NSCLC treated with surgery-based therapy, chemoradiation, conventionally-fractionated radiation (CFR), or stereotactic body radiotherapy (SBRT) were identified using the National Cancer Database (NCDB). Median survival was estimated using Kaplan-Meier analysis. Crude and adjusted hazard ratios (HR) and 95% confidence intervals were computed using Cox regression modeling. RESULTS: Between 2004-2012, 19,749 patients met study criteria: 13,382 (67.8%) underwent surgery-based treatment, 4,310 (21.8%) received chemoradiation, 1,606 (8.1%) received CFR, and 451 (2.3%) received SBRT. Surgery and SBRT utilization increased over time while CFR and chemoradiation decreased (all p ≤ 0.002). Patients receiving radiation-based treatments were older, with more comorbidities, and higher T/N stage (all p < 0.0001). With median follow-up of 25.2 months, median survival was 51.6, 23.3, 15.4, and 23.7 months for surgery-based treatment, chemoradiation, CFR, and SBRT, respectively (p < 0.0001). On multivariate analysis, chemoradiation (HR 1.67 [1.59-1.75], p < 0.0001), CFR (HR 2.38 [2.22-2.55], p < 0.0001), and SBRT (HR 1.76 [1.53-2.01], p < 0.0001) were associated with decreased survival versus surgery-based treatment. CFR was associated with decreased survival versus chemoradiation (HR 1.52 [1.41-1.63], p < 0.0001) and SBRT (HR 1.39 [1.19-1.61], p < 0.0001). SBRT was associated with similar survival versus chemoradiation (HR 1.10 [0.95-1.27], p = 0.212). CONCLUSION: NCDB data demonstrate increasing use of surgery-based treatments and SBRT for Stage II NSCLC over time. Radiation-based therapies were associated with decreased survival compared to surgery. CFR was associated with decreased survival compared to chemoradiation and SBRT.

Effect of Massed Versus Interleaved Teaching Method on Performance of Students in Radiology.

PURPOSE: Radiology instruction is based on the principle that grouped (or massed) repetition of an intellectual activity leads to expertise. The aim of this study was to test the hypothesis that the spaced (or interleaved) method of teaching chest x-ray interpretation is more effective than the massed method. METHODS: After institutional review board approval was obtained, 40 first- and second-year medical students were randomized into two groups matched by age, gender, and education experience. Both groups saw six examples of 12 common chest radiographic patterns, one grouped, the other scrambled randomly without repeating strings. After a distraction, participants took a multiple-choice test consisting of two cases in each radiographic pattern, one previously shown, one new. Results were analyzed using two-tailed Student's t test of proportion. RESULTS: Comparing interleaved and massed groups, the average overall score was 57% versus 43% (P = .03), the recollection score was 61% versus 47% (P = .03), and the induction score was 53% versus 40% (P = 0.10), respectively. Comparing second- and first-year students, average scores were 67% and 39%, respectively (P < .01). First-year students in the interleaved and massed groups scored 55% and 36% (P = .02) in recall and 40% and 28% (P = .10) in induction. Second-year students in the interleaved and massed groups scored 71% and 63% (P = .36) in recall and 74% and 59% (P = .03) in induction. CONCLUSIONS: The interleaved method of instruction leads to better results than the massed method across all levels of education. A higher level of medical education improves performance independent of method of instruction.

Higher locoregional recurrence rate for triple-negative breast cancer following neoadjuvant chemotherapy, surgery and radiotherapy.

BACKGROUND: Breast cancer subtype, determined by expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2, is predictive for prognosis. The importance of subtype to locoregional recurrence (LRR) following neoadjuvant chemotherapy (NAC) is unknown, particularly after adjuvant radiotherapy (RT). METHODS: We retrospectively identified 160-breast cancer patients registered at Columbia University Medical Center from 1999 to 2012 treated with NAC, surgery and adjuvant RT. RESULTS: Patients were grouped by receptor status: hormone receptor positive (HR+) [(ER or PR+)/HER2-; n = 75], HER2+ (n = 46), or triple-negative (TNBC) [ER (-) PR (-) HER2 (-); n = 36]. The median follow-up was 28 months. 92.0% received an anthracycline-taxane based NAC and 80.4% of HER2+ patients received trastuzumab. All underwent surgical resection followed by RT. 15.6% had a pathologic complete response (pCR): 26% of HER2+, 5% of HR+, and 25% of TN. The actuarial rate of DM was 13.8% for the entire cohort, with equivalent rates by subtypes in non-pCR patients. The overall rate of LRR was 8%. However, the LRR rate was significantly higher for TNBC patients (22.2%) than HER2+ (5.6%) (p = 0.025) or HR+ (3.0%) (p = 0.037) in non-pCR group. In the pCR group, two patients had recurrence; one LRR and one a DM, both had TNBC. All LRR occurred in or near the radiation field. CONCLUSIONS: TNBC patients with < pCR to NAC have a significantly higher LRR rate as compared to other subtypes even with surgery and adjuvant RT. Our data support a need to further intensify local therapy in TNBC patients.

Two-way communication with neural networks in vivo using focused light.

Neuronal networks process information in a distributed, spatially heterogeneous manner that transcends the layout of electrodes. In contrast, directed and steerable light offers the potential to engage specific cells on demand. We present a unified framework for adapting microscopes to use light for simultaneous in vivo stimulation and recording of cells at fine spatiotemporal resolutions. We use straightforward optics to lock onto networks in vivo, to steer light to activate circuit elements and to simultaneously record from other cells. We then actualize this 'free' augmentation on both an 'open' two-photon microscope and a leading commercial one. By following this protocol, setup of the system takes a few days, and the result is a noninvasive interface to brain dynamics based on directed light, at a network resolution that was not previously possible and which will further improve with the rapid advance in development of optical reporters and effectors. This protocol is for physiologists who are competent with computers and wish to extend hardware and software to interface more fluidly with neuronal networks.

Curcumin inhibits aggregation of alpha-synuclein.

Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid and prevent further oligomerization of Abeta monomers onto growing amyloid beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson's disease (PD) and AD, we investigated the effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant alpha-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.