Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

Background In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. Methods/design This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. Discussion In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial. Trial registration Clinical trial identifier BACCHUS: NCT0165042

Hand and ultrasonic instrumentation in the treatment of chronic periodontitis after supragingival plaque control Instrumentação manual e ultra-sônica no tratamento da periodontite crônica após controle de placa supragengival

This study compared the clinical effects of hand or ultrasonic scaling and root planing on the treatment of chronic periodontitis. After supragingival plaque control, twenty patients were examined by a blinded and calibrated examiner for probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BOP). Experimental teeth were allocated to the following subgingival treatment groups according to PPD: 1) hand instrumentation; 2) hand instrumentation with irrigation; 3) ultrasonic instrumentation; 4) ultrasonic followed by hand instrumentation. Time used in the procedures was recorded. Follow-up examinations were performed at 30 and 90 days after treatment. Each patient's individual BOP, PPD and CAL means were analyzed with repeated-measures ANOVA. Differences in the instrumentation time were analyzed with 1-way ANOVA. Significance level was established at 5%. All treatments produced significant changes in the clinical parameters. BOP reduced, in proximal surfaces, from 67.21-79.17% at baseline to 45.75-51.54% at 90 days. Significant reductions were also found for PPD and CAL in all groups, both in proximal and free surfaces. Reductions in mean PPD at 90 days ranged from 0.92 to 1.14 mm for the free surfaces and from 1.01 to 1.35 mm for proximal surfaces, whereas reductions in CAL ranged from 0.43 to 0.82 mm and from 0.60 to 0.73 mm for free and proximal surfaces, respectively. Mean instrumentation time ranged from 4.77 to 5.30 minutes. No statistically significant differences were found among the four study groups. It can be concluded that the four methods of subgingival instrumentation were equally efficacious in the improvement of the studied clinical parameters.<br>Este estudo comparou, clinicamente, o efeito de raspagem e alisamento radicular por instrumentações manual e ultra-sônica no tratamento da periodontite crônica, após o controle de placa supragengival em 20 pacientes. Os parâmetros clínicos profundidade de sondagem (PS), nível de inserção clínica (NIC) e sangramento à sondagem (SS) foram avaliados por um examinador calibrado e cego. Os dentes experimentais foram alocados para uma das seguintes abordagens subgengivais, de acordo com a profundidade de sondagem: 1) manual, 2) manual associada à irrigação, 3) ultra-sônica, 4) ultra-sônica previamente à manual. O tempo usado nos procedimentos foi registrado. Avaliações foram feitas 30 e 90 dias após os tratamentos. Médias individuais de SS, PS e NIC foram analisadas pelo teste ANOVA de medidas repetidas (p < 0,05). Diferenças no tempo de instrumentação foram analisadas por meio do teste ANOVA para um critério de classificação (p < 0,05). Os resultados revelaram que os tratamentos produziram alterações significativas nos parâmetros clínicos sem diferenças estatisticamente significantes entre os quatro grupos. Observaram-se reduções no SS, que, nas faces proximais, variou de 67,21 a 79,17%, no início, para 45,75 a 51,54% no final. Também foram observadas reduções significativas na PS e no NIC em todos os grupos, tanto para faces livres quanto proximais: as médias da PS aos 90 dias reduziram entre 0,92 e 1,14 mm nas faces livres e entre 1,01 e 1,35 mm nas proximais, enquanto para NIC as reduções foram de 0,43 a 0,82 mm e 0,60 a 0,73 mm, para as faces livres e proximais respectivamente. A média do tempo operatório variou de 4,77 a 5,30 minutos. Pôde-se concluir que as quatro modalidades terapêuticas de instrumentação subgengival foram igualmente eficazes na melhora dos parâmetros clínicos estudados