A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma

BACKGROUND: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC). METHODS: In this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate. RESULTS: Eighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22–69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %). CONCLUSIONS: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Educomunicação, Transformação Social e Desenvolvimento Sustentável

Esta publicação apresenta os principais trabalhos dos GTs do II Congresso Internacional de Comunicação e Educação nos temas Transformação social, com os artigos que abordam principalmente Educomunicação e/ou Mídia-Educação, no contexto de políticas de diversidade, inclusão e equidade; e, em Desenvolvimento Sustentável os artigos que abordam os avanços da relação comunicação/educação no contexto da educação ambiental e desenvolvimento sustentável

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Role of Combined-Modality Therapy in the Management of Locally Advanced Rectal Cancer

The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU–based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation

Molecular basis and management of gastrointestinal stromal tumors

Molecularly targeted agents have dramatically impacted the management of several cancers. Targeting KIT has led to a new treatment paradigm in gastrointestinal stromal tumors (GISTs). KIT is a cell surface receptor with tyrosine kinases that, upon binding of its ligand, stem cell factor, activates various signaling pathways. Imatinib and sunitinib, both tyrosine kinase inhibitors directed to KIT, were approved for first- and second-line treatment of metastatic and unresectable GISTs. In this article, we will review the molecular pathogenesis of GISTs followed by a discussion of imatinib and sunitinib’s role in the treatment of GISTs. Finally, we will introduce novel therapeutic options for imatinib- and sunitinib-resistant GISTs

Depressive symptoms among caregivers of colorectal cancer patients during the first year since diagnosis: a longitudinal investigation

Objective Few studies have examined prospectively and longitudinally depressive symptoms of family caregivers who provide care to colorectal cancer patients, and fewer have addressed ethnic minorities in this regard. This study investigated the relations of social support and caregiving stress with caregivers' depressive symptoms during the first year since the relative's diagnosis, as well as the role of ethnicity in such relations. Methods Seventy‐nine caregivers provided complete data at 2 months (T1), 6 months (T2), and 12 months (T3) after their relative's cancer diagnosis. Demographics and caregiving experiences were measured at T1. Depressive symptoms were assessed at T1 through T3. Results Greater caregiving stress and lack of social support were significant predictors of greater depressive symptoms. The adverse effect of caregiving stress was more pronounced among African American caregivers, whereas the beneficial effect of social support was more pronounced among White caregivers. Conclusions The findings highlight the importance of both caregiving stress and lack of social support early in caregivership. Findings also suggest that caregivers may benefit from programs tailored for their ethnicity. Copyright © 2011 John Wiley & Sons, Ltd