1.Monitoring real time polymorphic transformation of sulfanilamide by diffuse reflectance visible spectroscopy$
Ehiwe O. Tracy ; Alexander D. Bruce ; Mitchell C. John ; Snowden J. Martin ; Waters J. Laura
Journal of Pharmaceutical Analysis 2016;6(3):179-183
This study investigated the development of a novel approach to surface characterization of drug poly-morphism and the extension of the capabilities of this method to perform ‘real time’ in situ measure-ments. This was achieved using diffuse reflectance visible (DRV) spectroscopy and dye deposition, using the pH sensitive dye, thymol blue (TB). Two polymorphs, SFN-β and SFN-γ, of the drug substance sul-fanilamide (SFN) were examined. The interaction of adsorbed dye with polymorphs showed different behavior, and thus reported different DRV spectra. Consideration of the acid/base properties of the morphological forms of the drug molecule provided a rationalization of the mechanism of differential coloration by indicator dyes. The kinetics of the polymorphic transformation of SFN polymorphs was monitored using treatment with TB dye and DRV spectroscopy. The thermally-induced transformation fitted a first-order solid-state kinetic model (R2 ? 0.992), giving a rate constant of 2.43 ? 10 ? 2 s ? 1.
2.Preoperative Therapy Regimen Influences the Incidence and Implication of Nodal Downstaging in Patients with Gastric Cancer
Alexander P. STARK ; Mariela M. BLUM ; Yi-Ju CHIANG ; Prajnan DAS ; Bruce D. MINSKY ; Jeannelyn S. ESTRELLA ; Jaffer A. AJANI ; Brian D. BADGWELL ; Paul MANSFIELD ; Naruhiko IKOMA
Journal of Gastric Cancer 2020;20(3):313-327
Purpose:
Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen.
Materials and Methods:
Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and nodepositive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC.
Results:
Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P<0.001). In the matched cohort of cN+ patients, more recent diagnosis (2010–2015 vs. 2004–2009) (odds ratio [OR], 2.57; P<0.001) and NACR (OR, 2.02; P<0.001) were independently associated with nodal downstaging. The 5-year OS rate of downstaged N0 patients was significantly lower after NACR (46.4%) than after NAC (57.7%) (P=0.003).
Conclusions
Downstaged N0 patients have the same prognosis as natural N0 patients.Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.