The impact of interval between primary cytoreductive surgery with bowel resection and initiation of adjuvant chemotherapy on survival of women with advanced ovarian cancer: a multicenter cohort study.

OBJECTIVE: Our aim was to determine if the time interval between bowel resection and initiation of adjuvant chemotherapy impacts survival in advanced ovarian cancers. METHODS: This was a retrospective cohort study using data from two cancer centers, Princess Margaret Cancer Centre in Toronto, Ontario, Canada and Samsung Comprehensive Cancer Center in Seoul, South Korea. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer that underwent large bowel resection during primary cytoreductive surgery (PCS) were included. RESULTS: Ninety-one women were eligible of which the majority (90.1%) were diagnosed with high-grade serous cancer. The median interval from PCS to chemotherapy for all patients was 21 days (7-86 days). Patients were stratified into 3 groups: 1) Interval ≤14 days, 32 (35.2%) patients; 2) Interval between 15-28 days, 27 (29.6%) patients; and 3) Interval between 29-90 days, 32 (35.2%) patients. Surgical procedures and postoperative outcomes were similar between groups. Multivariate analysis indicated that PCS to chemotherapy interval of 2-4 weeks, younger age, and completion of 4 or more adjuvant chemotherapy cycles were independent prognostic factors of favorable overall survival. CONCLUSION: Initiation of adjuvant chemotherapy between 2 to 4 weeks after PCS with bowel resection may improve survival outcomes in women with advanced ovarian cancer by maximizing the benefit of PCS plus adjuvant chemotherapy.

Assessing fluorescence detection and effective photothermal therapy of near-infrared polymer nanoparticles using alginate tissue phantoms.

OBJECTIVE: Photothermal therapy (PTT) uses light absorbing materials to generate heat for treatment of diseases, like cancer. The advantages of using PTT components that absorb in the near-infrared (NIR) include reduced tissue auto-fluorescence and higher penetration depths. However, NIR laser light can still be scattered and absorbed by biological tissues, thus decreasing the amount of the energy reaching the PTT agents. We have developed two distinct formulations of NIR-absorbing nanoparticles, one which can be utilized for PTT only, and another for both PTT and fluorescence imaging of colorectal cancer. In this work, the fluorescence detection limit and the PTT heating potential of the two nanoparticle types were determined using alginate tissue phantoms. The objective of this study was to determine the PTT efficiency and theranostic potential of the nanoparticles by irradiating 3D collagen tumor spheroids, containing nanoparticles and CT26 mouse colorectal cancer cells, through increasing tissue phantom thicknesses and then quantifying cell death. Materials and Methods Our lab has previously developed nanoparticles based on the semiconducting, conjugated polymer poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). We have also made a hybrid nanoparticle that heats and fluoresces by combining PCPDTBSe polymer with the fluorescent poly[(9,9-dihexylfluorene)-co-2,1,3-benzothiadiazole-co-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PFBTDBT10) polymer to yield nanoparticles termed Hybrid Donor-Acceptor Polymer Particles (H-DAPPs). H-DAPPs and PCPDTBSe nanoparticles were added to three-dimensional collagen gel tumor spheroids in order to represent nanoparticles in a tumor. Alginate tissue phantoms, comprised of an optical scattering agent (Intralipid) and an optical absorbing material (hemoglobin) in order to mirror biological tissue scattering effects, were used to simulate increasing tissue thickness between the nanoparticles and the PTT energy source. RESULTS: Fluorescence from the H-DAPPs was detectable through 6 mm of tissue phantoms. It was found that less than 10% of the laser energy could penetrate through 9 mm of tissue phantoms and only 60% of the laser energy passed through the 1.5 mm phantoms, regardless of laser power. PTT experiments, using 800 nm light at 2.2 W/cm2 for 60 s through tissue phantoms to stimulate nanoparticle-doped tumor spheroids, showed 55% cell death through 3 mm of tissue phantoms using H-DAPPs. Results from using the PCPDTBSe nanoparticles showed 72% cell death through 3 mm and over 50% cell death through 6 mm of tissue phantoms. CONCLUSION: The results of this work validated the heating potential and fluorescence detection limitations of two theranostic polymer nanoparticles by utilizing alginate tissue phantoms and 3D tumor spheroids. H-DAPPs and PCPDTBSe polymer nanoparticles can be utilized as effective PTT agents by exploiting their absorption of NIR light and H-DAPPs have advantageous fluorescence for imaging colorectal cancer. The data generated from this study design can allow for other NIR absorbing and fluorescing nanoparticle formulations to be evaluated prior to in vivo experimentation. Lasers Surg. Med. 50:1040-1049, 2018. © 2018 Wiley Periodicals, Inc.

Effects of filtering visual short wavelengths during nocturnal shiftwork on sleep and performance.

Circadian phase resetting is sensitive to visual short wavelengths (450-480 nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480 nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age ± SD: 31.3 ± 4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2 h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p < 0.01) and sleep efficiency (p = 0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p = 0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40 min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p < 0.05) and middle (p < 0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p < 0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers.

Tumor progression in the LPB-Tag transgenic model of prostate cancer is altered by vitamin D receptor and serum testosterone status.

Previous studies have suggested that 1,25 dihydroxyvitamin D(3) (1,25(OH)2D3) induces cell cycle arrest and/or apoptosis in prostate cancer cells in vitro, suggesting that vitamin D may be a useful adjuvant therapy for prostate cancer and a chemopreventive agent. Most epidemiological data however shows a weak link between serum 25(OH)D3 and risk of prostate cancer. To explore this dichotomy we have compared tumor progression in the LPB-Tag model of prostate in VDR knock out (VDRKO) and wild type (VDRWT) mice. On the C57BL/6 background LPB-Tag tumors progress significantly more rapidly in the VDRKO mice. VDRKO tumors show significantly higher levels of cell proliferation than VDRWT tumors. In mice supplemented with testosterone to restore the serum levels to the normal range, these differences in tumor progression, and proliferation are abrogated, suggesting that there is considerable cross-talk between the androgen receptor (AR) and the vitamin D axis which is reflected in significant changes in steady state mRNA levels of the AR, PCNA, cdk2 survivin and IGFR1 and 2 genes. These alterations may explain the differences between the in vitro data and the epidemiological studies.

The effect of acupuncture utilization on healthcare utilization.

OBJECTIVE: To determine whether acupuncture is a complement to or substitute for various medical services. DATA SOURCE: This study used managed care claims data from a midsize metropolitan insurance company from 2002. Zip code level data from the 2000 US Census was also incorporated. The original dataset contained medical and drug claims data for every eligible acupuncture user (n = 1688) and every 18th eligible nonacupuncture user (n = 16,282) covered by the data provider. STUDY DESIGN: Simultaneous equations models with an exclusion restriction were used in this cross-sectional study. The influence of acupuncture utilization was assessed independently on each conventional service of interest, controlling for numerous clinical and demographic characteristics. Bivariate probit models were estimated using distance to the nearest acupuncturist as the exclusion restriction. RESULTS: Acupuncture was a statistically significant (P < 0.05) substitute for primary care, all outpatient services, pathology services, all surgery, and gastrointestinal medications. Acupuncture seemed to complement numerous therapies, particularly chiropractic and physical therapy; however, acupuncture did not statistically significantly complement any therapies after controlling for unobservable characteristics that influence the use of acupuncture and/or conventional medicine. CONCLUSIONS: Acupuncture is an economic substitute for some medical services and pharmaceuticals, a finding of some importance to insurers, healthcare practitioners, and policy makers. The fact that acupuncture has an effect on other medical services needs to be explored more fully with an emphasis on how this substitution impacts patient health.