ASO Visual Abstract: Association of Obesity with Worse Operative and Oncologic Outcomes Among Patients Undergoing Gastric Cancer Resection

Annals of Surgical Oncology -     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Exploratory assessment of treatment‐dependent random‐effects distribution using gradient functions

In analyzing repeated measurements from randomized controlled trials with mixed‐effects models, it is important to carefully examine the conventional normality assumption regarding the random‐effects distribution and its dependence on treatment allocation in order to avoid biased estimation and correctly interpret the estimated random‐effects distribution. In this article, we propose the use of a gradient function method in modeling with the different random‐effects distributions depending on the treatment allocation. This method can be effective for considering in advance whether a proper fit requires a model that allows dependence of the random‐effects distribution on covariates, or for finding the subpopulations in the random effects.     

Interleukin-3-dependent potentiation of IgE responsiveness in mouse basophils

Basophils produce interleukins (IL)-4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL-4 in response to IL-3 but not to high-affinity Fc receptor (FcεRI) cross-linking (CL), yet both required the immunoreceptor tyrosine-based activation motif (ITAM) containing adaptor Fc receptor γ-chain (FcRγ), while basophils activated in vitro by IL-3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection with Trichinella spiralis or administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL-3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation-associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP-12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL-3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL-4 production and the other to render basophils competent to respond to stimuli dependent on ITAM-containing adaptors DAP12 and FcRγ for IL-4 production.     

Suppression of electroencephalogram Δ power density during non-rapid eye movement sleep as a result of a prolonged cognitive task prior to sleep onset

The effects of a prolonged cognitive task prior to sleep onset on subsequent sleep patterns were examined in 14 healthy subjects who were randomly assigned to two conditions. Those assigned to a working condition were asked to engage in a prolonged cognitive task until close to bedtime (0200 hours), whereas those assigned to a relaxing condition were instructed to perform the same task during the daytime and then to stay awake in a relaxed state until the same bedtime as the work group. Visual scoring of sleep stages showed no significant differences in the amounts of stage 4 and slow wave sleep (stage 3+4) between the two conditions. Power spectrum analysis of sleep electroencephalogram (EEG) revealed that the EEG (0.5–4.0 Hz) power density in the first non-rapid eye movement (REM)-REM sleep cycle was significantly lower following the prolonged cognitive task prior to sleep onset than following the relaxed wakefulness and that the decreased EEG power density in the first sleep cycle was not compensated for during the later part of the sleep. These findings would indicate that the prolonged cognitive task prior to sleep onset may suppress EEG power density during subsequent sleep, suggesting that such a task may interfere with the development of deep non-REM sleep.     

Evaluation of a screening program on reduction of gastric cancer mortality in Japan: preliminary results from a cohort study.

BACKGROUND: Systematic population-based screening for gastric cancer is widely spread in Japan. However, the case-control study method has been the main method used to evaluate the effectiveness of the screen ing to reduce gastric cancer mortality in Japan. METHODS: This article presents a population-based cohort study. A questionnaire about lifestyles and dietary habits was distributed to 36,990 residents in a city of Japan. The response rate to the questionnaire was 92.0%. After ineligible responders had been excluded, 24,134 subjects were classified into screened and un screened groups according to their self-reports of participation in the screening the previous year. We followed them up for 40 months and linked resident death records in the city. We compared mortality from gastric cancer and all other causes between the groups by us ing the Cox proportional hazard model. RESULTS: The follow-up period was 78,156.6 person-years from September 1992 to December 1995. The multivariate relative risks for gastric cancer death of the screened group in comparison with the unscreened group were 0.72 (95% CI 0.31-1.66) among males and 1.46 (95% CI 0.43-4.90) among females. CONCLUSION: Although our data are preliminary, we were unable to demonstrate a large contribution of the present screening program to decreasing gastric cancer mortality. Further follow-up is needed to in crease the precision.     

Overtime, psychosocial working conditions, and occurrence of non- insulin dependent diabetes mellitus in Japanese men

OBJECTIVES: To ascertain the effects of overtime and psychosocial job conditions on the occurrence of non-insulin dependent diabetes mellitus (NIDDM) in Japan. DESIGN: An eight year prospective cohort study. SETTING: An electrical company in Japan. PARTICIPANTS: In 1984, a mailed questionnaire was sent to industrial workers of an electrical company in Japan. After excluding those who had a history of diabetes mellitus or other chronic diseases, 2597 male respondents were prospectively followed up for the succeeding eight years. Data from 2194 (84%) who were completely followed up were analysed. The occurrence of NIDDM during the follow up period was assessed according to the WHO criteria on the basis of an annual screening programme. MAIN RESULTS: The age adjusted incidence of NIDDM was significantly higher in those who worked overtime more than 50 hours per month than in those who worked 25 hours or less per month (p < 0.05). It was significantly higher in those who worked with new technology at baseline than in those who did not (p < 0.05). Cox's proportional hazard model indicated that those who worked overtime more than 50 hours per month had 3.7 times higher risk of NIDDM after controlling for known risk factors (p < 0.01) and those who worked with new technology had 2.4 times higher risk of NIDDM (p < 0.05). CONCLUSIONS: It is suggested that longer overtime and use of new technology are risk factors of NIDDM in Japanese men.     

Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat

The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats were compared with those in young rats. The incorporation of [3H]glucosamine and [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa from 7-week-old rats. In contrast, tetragastrin could not enhance mucin biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced stimulation of corpus mucin biosynthesis observed in middle-aged rats was essentially the same as that seen in young rats. Nitric oxide (NO) synthase activity of the corpus was significantly reduced in the middle-aged rats compared to the young rats. NO synthase-immunoreactivity was observed at surface mucous cells in the corpus mucosa of young, but not of middle-aged, rats. These results suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis through the age-related loss of NO synthase function in the surface mucous cell layer of rat stomach.