Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

<p>Abstract</p> <p>Background</p> <p>Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.</p> <p>Methods</p> <p>This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/²/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.</p> <p>Results</p> <p>Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (<it>DPYD</it>) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).</p> <p>Conclusion</p> <p>Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.</p

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Facteurs pronostiques du survie à long terme des cancers du colon opérés stade II de l UICC (Dukes B) (à propos d une série prospective de 362 cas)

Les patients présentant un cancer du colon stade B de la classification de Dukes représentent un groupe hétérogène avec un taux de survie à 5 ans oscillant entre 60 et 80%. Le traitement de référence de ces patients est la résection chirurgicale complète avec curage mésentérique correspondant. L intérêt d une chimiothérapie adjuvante est encore controversé et non recommandé en routine. Cependant il semble exister un sous-groupe de patients à haut risque de récidive et de moins bonne survie à long terme, lesquels pourraient bénéficier d un traitement adjuvant ou une inclusion dans des protocoles de recherche clinique. Notre étude a permis de mettre en évidence 6 facteurs pronostiques indépendants associés à une moins bonne survie à long terme : l âge supérieur à 65 ans lors du diagnostic, le nombre de ganglions prélevés inférieur à 8, l envahissement périnerveux, l envahissement veineux, l envahissement lymphatique et le stade tumoral T4. La présence d un ou plusieurs de ces facteurs permet d identifier des patients avec une moins bonne survie à long terme auxquels il semble licite de proposer un traitement adjuvant.ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Motivations et freins des médecins généralistes du Maine-et-Loire à participer au dépistage de masse du cancer colorectal

Objectifs : préciser les motivations et les freins des médecins généralistes du Maine et Loire à participer au dépistage de masse du cancer colorectal, et rechercher d'éventuels facteurs déterminant une meilleure participation, avant le lancement de la campagne. Méthode : une enquête postale a été réalisée auprès de 400 médecins généralistes. Résultats : quarante-cinq pour cent des médecins ont répondu. La majorité des médecins (88%) déclaraient participer aux campagnes de dépistage de masse en cours. Trente-neuf pour cent des médecins étaient convaincus par l'efficacité du dépistage de masse du cancer colorectal par la recherche de sang occulte dans les selles. Quatre-vingt-sept pour cent des médecins souhaitaient une formation spécifique, majoritairement les médecins sceptiques sur l'efficacité du dépistage. Les facteurs les plus incitatifs à leur participation étaient : le bénéfice pour le patient, le rôle préventif et l'efficacité du test. La rémunération n était pas un facteur déterminant pour leur adhésion. Les principaux freins cités étaient la charge administrative, les faux négatifs et les faux positifs. Conclusion : cette enquête a montré l'intérêt des médecins généralistes pour le dépistage de masse du cancer colorectal. Les médecins les moins convaincus par l'efficacité du dépistage semblent plus réfractaires en raison de la performance du test lui-même et d'un manque d'information plutôt que freinés par le temps passé ou l'absence de rémunération. La formation des médecins généralistes au dépistage devrait contribuer à améliorer la motivation des médecins.ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Colorectal cancer screening: Physicians’ knowledge of risk assessment and guidelines, practice, and description of barriers and facilitators

BACKGROUND: Physician nonadherence to colorectal cancer (CRC) screening recommendations contributes to underuse of screening

Efficacy of 12 weeks oral beta‐alanine supplementation in patients with chronic obstructive pulmonary disease: a double‐blind, randomized, placebo‐controlled trial

International audienceBackground: Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD.Methods: In this double-blind, randomized, placebo (PL)-controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV1 % predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co-primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed.Results: Beta-alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49-4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO2 peak: +0.5 [-0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [-1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [-179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1-quartile 3); 100 (98-100)%) and PL (98 (96-100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes.Conclusions: Beta-alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed