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21 Background: Studies have shown that Black patients receiving chemoradiation (CRT) for locally advanced rectal cancer (LARC) have achieved clinical outcomes less satisfactory than those achieved by other racial groups, but the source of this disparity is poorly understood. This study investigated the demographic, geographic, socioeconomic, and clinical factors that underlie this disparity. Methods: We interrogated the National Cancer Database from 2004-2017 to identify patients with T3-T4 or N > 0 LARC treated with CRT prior to surgery. Response to CRT was determined by the rates of pathologic complete response (pCR) and tumor downstaging after treatment. Univariate analysis (UVA) was performed with chi-square and Fisher’s exact tests. Multivariate analysis (MVA) was then used to identify independent factors associated with improved pCR. Results: A total of 37,783 patient records were reviewed for the study (7.8% Black, 86.0% White, 6.1% Other). Black patients were younger (p < 0.0001), more often female (p < 0.0001), and more likely to live in metropolitan areas (p < 0.0001). LARC in Black patients was diagnosed at a higher clinical stage (p = 0.0007) and was more often treated with abdominoperineal resection in preference to low anterior resection (p < 0.0001). Black patients were more often uninsured or covered by Medicaid (p < 0.0001) and less often covered by commercial insurance (p < .0001). UVA demonstrated that Black patients achieved pCR and tumor downstaging at lower rates than White patients (11.6% vs 14.5%; 46.9% vs 51.8%, both p < 0.0001). On MVA, Black race (OR 0.8015, 95%CI 0.7101-0.9047), a rural location (OR 0.8211, 95% CI 0.7082-0.952), absence of commercial medical insurance (Medicaid OR 0.8394 95% CI 0.7456-0.9449; Medicare OR 0.8989 95% CI 0.8226-0.9823; No Insurance OR 0.6107 95% CI 0.5103-0.7309), and higher tumor grade and stage remained independent risk factors for a lower pCR. Additional significant unfavorable prognostic factors for pCR included younger age, male sex, lower hospital treatment volume, and higher tumor grade or stage. Similarly, Black race, lower hospital treatment volume, absence of commercial medical insurance, and higher grade or stage were significant unfavorable prognostic factors for downstaging. Neither lower income nor fewer years of education was associated with pCR or tumor downstaging. Conclusions: The results confirm a lower rate of response to CRT in Black patients with LARC. The identification of race as an independent risk factor after adjustment for sociodemographic, geographic, and clinical factors suggests that other unknown variables–including genetic differences unaddressed in this study–must be pursued comprehensively in future studies. The more advanced stage of rectal cancers in Black patients suggests that critical evaluation of current cancer screening methods may play a role in this effort.

11007 Background: We aimed to evaluate the outcomes and generalizability of a distance learning curriculum on intensity modulated radiotherapy (IMRT), a course developed for radiotherapy clinics across Africa and Latin America (LATAM) at no cost, as measured by a knowledge-based multiple-choice exam, learner self-evaluation, and open-ended feedback. Methods: Following needs identification studies, a curriculum entitled “IMRT 2.0” was created for an audience that included medical physicists, radiation oncologists, radiation therapists, and trainees. Volunteer educators delivered 27 hour-long sessions 1-2 times weekly for four months using video conferencing to African and LATAM programs in English and Spanish, respectively. Recordings and educational materials were shared following each session. Pre- and post-course multiple choice examinations were administered to LATAM participants, and pre- and post-course Likert scale self-evaluation and open-ended feedback were collected for both programs. Paired sample t-tests and chi-squared tests were performed for all available paired quantitative and categorical data, respectively. Pearson correlation coefficient, multivariate linear regression, and spline regression models were used to explore impact of course attendance on outcomes. Results: 25 centers across Africa (12 + 1 sister institution in Pakistan) and LATAM (12) were recruited, the majority (92%) of which were recently transitioning or planning to transition to IMRT, yielding a total of 332 enrolled participants. 27 sessions were delivered with a mean of 44 (std dev 22.5) and 85 (std dev 25.4) participants per session for the African and LATAM programs, respectively. Paired pre- and post-course data demonstrated significant improvement in both knowledge (n = 51, p

Video-assisted thoracic surgery (VATS) has been widely adopted in early-stage lung cancer as an oncologically sound and minimally invasive approach with certain proven short-term advantages over open thoracotomy especially in terms of postoperative morbidity. Nevertheless, VATS is associated with visual and mechanical limitations, many of which were overcome with the introduction of robotic surgical techniques. Robotic-assisted thoracic surgery (RATS) can approximate the visual perspective of open surgery, while utilizing instruments that mimic the maneuverability of the human wrist and provide magnified three-dimensional imaging. The added cost in addition to the effort required of surgeons to master RATS may be ultimately compensated by enhanced surgical efficiency, access to rapidly developing technical innovations, and the potential for improved patient outcomes.

This work is devoted to investigate the ecoservice role of soil saprophages in the formation of sustainable man-made ecosystems under forest plantations. The investigation allowed effect of earthworm casting activities on soil buffering against solution with different pH levels and copper compounds to be detected within the territory remediated after coal mining (Western Donbass, Ukraine). Assays of pH-buffering capacity and copper immobilization/mobilization performed on earthworm casts and artificial remediated soil. Ecosystem effectiveness of soil saprophages (earthworms, Lumbricidae) was shown to be effected on increase of acid-alkaline (pH-buffering) buffering capacity in remediated soil. The study results prove that acid-alkaline buffering capacity of earthworm casts was significantly higher than that of remediated soil and subsoil by 17.9% and 20.8%, respectively. Effectiveness of copper immobilization reflecting degree of soil stability to copper contamination was increased from 23.1% to 39.2%, respectively. Thus, earthworm ecoservice activity had positive changes on environmental conditions of remediated soil and naturalization of artificial edaphotopes within remediated lands in Steppe zone. Environmental quality of remediated soil enriched in earthworm casts was confirmed to be improved.

About 75% of lung cancer patients are not surgical candidates, either due to advanced disease or medical comorbidities. Furthermore, conventional treatments that can be offered to these patients are beneficial only to a small percentage of them. Thermal ablation is a minimally invasive treatment that is commonly used in this group of patients, and which has shown promising results. Currently, the most widely used ablation techniques in the treatment of lung malignancies are radiofrequency ablation (RFA), microwave ablation, and cryoablation. Although the most studied technique is RFA, recent studies with microwave ablation and cryoablation have shown some advantages over RFA. This article reviews the application of thermal ablation in the thorax, including patient selection, basic aspects of procedure technique, imaging follow-up, treatment outcomes, and comparison of ablation techniques.

806 Background: Microsatellite instability (MSI) is a marker for hypermutability due to impaired DNA mismatch repair and has been shown to be a favorable prognostic marker in colon cancer. We examined the role of MSI in locally advanced rectal cancer (LARC) as a predictive marker for response to neoadjuvant chemoradiation (CRT). Methods: We identified T3-T4 or ≥ N1 rectal cancer with reported MSI status in the National Cancer Data Base from 2007 – 2012. Patients were eligible if they were treated with CRT followed by surgical resection. Squamous cell and carcinoid histologies were excluded. The primary outcome was neoadjuvant rectal (NAR) score, categorized as low ( < 8), intermediate (8-16), and high ( > 16), representing a good, intermediate, and poor response to CRT, respectively. The secondary outcomes were complete pathologic response (ypCR) rate and overall survival (OS). Chi-square, Fisher’s exact, and independent sample t-tests were used to compare MSI status. Multivariable logistic regression models were used to examine factors associated with increasing level of NAR score and ypCR. OS was examined using multivariable Cox proportional hazards models. Results: A total of 1849 patients were eligible for the study and were classified as MSI-high (n = 52) or MSI-low/stable (n = 1797). Patients in the MSI-high group were younger (median age 50.5 vs 57.0, p = 0.005) and had higher rates of mucinous and signet ring histology (p < 0.001), clinical T4 disease (p = 0.001), and clinically positive lymph nodes (p = 0.049). The two groups did not differ in gender, race, grade, or resection margin status. While clinical T and N stage, histology, LVI, tumor grade, and PNI were correlated with the NAR score groups, MSI-high status was not significantly associated with a higher NAR score group on multivariable analysis (OR 1.168, 95% CI 0.673 – 2.028). The MSI-high group also did not differ significantly from MSI-low/stable group in ypCR rate (OR 0.748, 95% CI 0.179 – 3.115) or OS (HR 1.727, 95% CI 0.864 – 3.453) on multivariable analysis. Conclusions: MSI status in LARC was not associated with NAR score, ypCR rate, or OS. Our results do not support the use of MSI status as a predictive marker for response to CRT in LARC.

The word "Hydroxypropyl" is misspelled in the article title. The correct title is: Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropyl-β-Cyclodextrin. The correct citation is: Shulman M, Cohen M, Soto-Gutierrez A, Yagi H, Wang H, et al. (2011) Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropyl-β-Cyclodextrin. PLoS ONE 6(4): e18033. doi:10.1371/journal.pone.0018033 Hydroxypropyl is also misspelled in the fifth sentence of the abstract. The fifth sentence should read: Hydroxypropyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold.

The liver is the largest internal organ in mammals, serving a wide spectrum of vital functions. Loss of liver function due to drug toxicity or viral infection is a major cause of death in the United States. The development of Bioartificial Liver (BAL) devices and the demand for pharmaceutical and cosmetic toxicity screening require the development of long-term hepatocyte culture techniques. However, primary hepatocytes rapidly lose their cuboidal morphology and liver-specific functions over a few days in culture. Accumulation of stress fibers, loss of metabolic function, and cell death are known phenomena. In recent years, several techniques were developed that can support high levels of liver-specific gene expression, metabolic and synthetic function for several weeks in culture. These include the collagen double-gel configuration, hepatocyte spheroids, coculture with endothelial cells, and micropatterned cocultures with 3T3-J2 fibroblasts. This chapter covers the current status of hepatocyte culture techniques, including: hepatocyte isolation, media formulation, oxygen supply, heterotypic cell-cell interactions, and basic functional assays.

The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection., National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (K01DK080241), Harvard Clinical Nutrition Research Center (P30-DK040561), European Research Council (Starting Grant (TMIHCV 242699)), Massachusetts General Hospital (BioMEMS Resource Center (P41 EB-002503)), Alexander Silberman Institute of Life Sciences

GLUT2 is a facilitative glucose transporter, expressed in polarized epithelial cells of the liver, intestine, kidney and pancreas, where it plays a critical role in glucose homeostasis. Together with SGLT1/2, it mediates glucose absorption in metabolic epithelial tissues, where it can be translocated apically upon high glucose exposure. To track the subcellular localization and dynamics of GLUT2, we created an mCherry–hGLUT2 fusion protein and expressed it in multicellular kidney cysts, a major site of glucose reabsorption. Live imaging of GLUT2 enabled us to avoid the artefactual localization of GLUT2 in fixed cells and to confirm the apical GLUT2 model. Live cell imaging showed a rapid 15 ± 3 min PKC-dependent basal-to-apical translocation of GLUT2 in response to glucose stimulation and a fourfold slower basolateral translocation under starvation. These results mark the physiological importance of responding quickly to rising glucose levels. Importantly, we show that phloretin, an apple polyphenol, inhibits GLUT2 translocation in both directions, suggesting that it exerts its effect by PKC inhibition. Subcellular localization studies demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, and that it is at least partly recovered in Rab11A-positive recycling endosome. Our work illuminates GLUT2 dynamics, providing a platform for drug development for diabetes and hyperglycaemia.