ABSTRACT
PURPOSE: To predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC) patients receiving bacillus Calmette-Guérin (BCG), we evaluated circulating basophils as a biomarker that could be detected from the complete blood count. PATIENTS AND METHODS: We use a pooled cohort of patients from the Centre Hospitalier Universitaire de Québec-Université Laval (2016-2020) and the Vancouver General Hospital (2010-2018) where a complete blood count was available before transurethral resection of bladder tumor (TURBT) of a high-grade NMIBC and subsequent BCG. Descriptive statistics described the cohort based on the dichotomous presence or absence of basophils on the complete blood count. Kaplan-Meier estimates and a log-rank test compared recurrence-free survival (RFS) and progression-free survival (PFS), with multivariable cox regression analysis used to estimate proportional hazard ratios. RESULTS: The study cohort included 261 patients, with a median follow-up of 31.5 months (interquartile range 18.1-45.0 months). The median age was 74.0 years and 16.8% were female. Circulating basophils were detectable in 49 (18.9%) patients. Both RFS and PFS were significantly lower in patients with detectable basophils. Multivariable analysis demonstrated detectable basophils were an independent predictor of both recurrence (HR = 1.85; 95% confidence interval [CI] 1.20-2.85; P = .01) and progression (HR = 2.29; 95% CI 1.14-4.60; P = .02). CONCLUSION: Our results confirm that baseline levels of circulating basophils are an immunological biomarker to predict recurrence and progression of NMIBC.
Subject(s)
Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Humans , Female , Aged , Male , BCG Vaccine/therapeutic use , Prognosis , Basophils/pathology , Disease Progression , Neoplasm Recurrence, Local , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/pathology , Biomarkers , Neoplasm Invasiveness , Retrospective Studies , Administration, IntravesicalABSTRACT
We tested the hypothesis that intermittent hypoxia elicits plasticity in respiratory chemoreflexes in bullfrog tadpoles. Metamorphic tadpoles (Taylor-Kollros stages XVI-XX) were subjected to intermittent hypoxia (PW(O(2))=45 Torr; 12 h/day) or constant normoxia (PW(O(2))=156 Torr) for 2 weeks before ventilatory responses to hypoxia and hypercarbia were measured. Buccal pressure changes were used to quantify the frequency and amplitude of movements associated with gill and lung ventilation. Morphometric assessment showed that intermittent hypoxia delayed development in comparison with controls. Oxygen consumption was enhanced in tadpoles subjected to intermittent hypoxia; however, this increase was not sufficient to affect basal ventilatory activity or the hypoxic ventilatory response. During acute hypercarbic exposure, tadpoles subjected to intermittent hypoxia showed (1) a greater decrease in gill ventilation frequency and (2) a greater increase in lung ventilation frequency than tadpoles maintained under control conditions. We conclude that intermittent hypoxia augments the responsiveness to hypercarbia, thereby promoting lung ventilation when animals face this stimulus. This manifestation of respiratory plasticity may reflect uncoupling between physiological and morphological development in the bi-modally breathing bullfrog tadpole.
