Decrease of pro-angiogenic monocytes predicts clinical response to anti-angiogenic treatment in patients with metastatic renal cell carcinoma

The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1+ CD14 and Tie2+ CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell carcinoma (mRCC) patients were treated with two anti-angiogenic drugs, either sunitinib or pazopanib. Blood samples from 86 patients were collected prospectively at baseline (T1), and at 10 weeks (T2) and 20 weeks (T3) after starting anti-angiogenic therapy. Various subpopulations of myeloid cells (monocytes, VEGFR-1+ CD14 and Tie2+ CD14 cells) decreased during treatment. When patients were divided into two subgroups with a decrease (defined as a >20% reduction from baseline value) (group 1) or not (group 2) at T3 for VEGFR-1+ CD14 cells, group 1 patients presented a median PFS and OS of 24 months and 37 months, respectively, compared with a median PFS of 9 months (p = 0.032) and a median OS of 16 months (p = 0.033) in group 2 patients. The reduction in Tie2+ CD14 at T3 predicted a benefit in OS at 18 months after therapy (p = 0.04). In conclusion, in this prospective clinical trial, a significant decrease in subpopulations of pro-angiogenic monocytes was associated with clinical response to anti-angiogenic drugs in patients with mRCC

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Assessment of team training in management of adverse acute events occurring during cardiopulmonary bypass procedure: a pilot study based on an animal simulation model (Fouilloux, Team training in cardiac surgery)

Successful cardiac surgery is highly dependent upon effective and efficient teamwork. Practical training and development will further enhance the team ability to react to a series of low-frequency occurring adverse events during cardiopulmonary bypass (CPB). One of our specialized educational programs focuses on training the whole team. This training is based on an original animal simulation model. The objective of this pilot study was to assess our method of training and learning in an attempt to optimize and improve team management and functioning. Methods: Four members of the same cardiac surgery team joined our program. They performed a common procedure, with a cardiopulmonary bypass (CPB) circuit set up to produce several adverse incidents. Events management was ana¬lyzed and debriefed in technical and non-technical perspectives. Results: Management of the adverse events was significantly improved. Discussion and debriefing time was fundamental in identifying the most appropriate management for each event. Rescue procedures were assimilated and team training was found to be effective, with the time reduced by up to 50% for 3 events and by up to 70% for air embolism. Conclusion: Our pilot program is an innovative, low-cost tool for the improvement of the management of adverse events occurring during CPB. It includes the different components of surgical education and training. Such an educational tool might be relevant for training. To confirm those encouraging results, it should be assessed in a larger surgical team panel. Further investigations are required for assessing efficiency in real conditions

A novel pleural-bladder pump for the management of recurrent malignant pleural effusions: a feasibility animal study

International audienceRecurrent malignant pleural effusions (MPE) are common and associated with significant morbidity in cancer patients. A new pump connecting the pleural cavity and the bladder may have application for the management of recurrent MPE. In a pre-clinical study, we investigated the utility of this pump in healthy pigs. Methods: A novel pump system (Pleurapump® system) was inserted into four pigs under general anaesthesia. A tunnelled-pleural catheter was connected to a subcutaneously implanted pump while the urinary bladder was connected by percutaneous technique. Animals were ventilated mechanically and pump functioning was tested using a range of ventilation parameters and spontaneous breathing. Fluid was added to the pleural space to mimic pleural effusion and to assess the effectiveness of the pump at removing fluid to the bladder. Results: The 'pleurapump' system successfully transported fluid from the pleural cavity to the bladder. Pressure variations caused by respiration and variations in the amount of fluid in the pleural cavity had no impact on the pumping. Pumping stopped when the pleural cavity was drained. Conclusion: This pump can be implanted into pigs and successfully removed fluid from the pleural cavity to the bladder and may represent a new treatment for management of recurrent MPE. Evaluation in humans is planned

Efficacy of endoscopic gastrojejunal bypass in obese Yucatan pigs: a comparative animal study

Abstract Background Natural orifice transluminal endoscopy surgery (NOTES) gastrojejunal anastomosis (GJA) with duodenal exclusion (DE) could be used as a less invasive alternative to surgical gastric bypass. The aim of this study was to compare the efficacy and safety of both methods for bariatric purpose. Methods This was a prospective, experimental and comparative study on 27 obese living pigs, comparing 4 groups: GJA alone (group 1, G1), GJA + DE (group 2, G2), surgical gastric bypass (group 3, G3), control group (group 4, G4). GJA was endoscopically performed, using NOTES technic and LAMS, while DE was performed surgically for limb length selection. Animals were followed for 3 months. Primary outcome included technical success and weight change, while secondary endpoints included the rate of perioperative mortality and morbidity, histological anastomosis analysis and biological analysis. Results Technical success was 100% in each intervention group. No death related to endoscopic procedures occurred in the endoscopic groups, while early mortality (< 1 month) was 57,1% in the surgical group, all due to anastomotic dehiscence. At 3 months, compared to baseline, mean weight change was + 3,1% in G1 (p = 0,46); -14,9% in G2 (p = 0,17); +5,6% in G3 (p = 0,38) and + 25% in G4 (p = 0,029). Histopathological analysis of endoscopic GJA showed complete fusion of different layers without leak or abscess. Conclusions Endoscopic GJA with DE provides the efficacy of bypass on weight control in an animal model. Next steps consist of the development of devices to perform exclusively endoscopically limb length selection and DE

Evaluation of feasibility, efficiency and safety of a pure NOTES gastrojejunal bypass with gastric outlet obstruction, in an in vivo porcine model

Introduction: Natural orifice transluminal endoscopic surgery (NOTES) gastrojejunal anastomosis (GJA) is a less invasive surgery for bariatric procedures and gastric outlet obstruction. The aim of this study was to evaluate the feasibility, efficacy, and safety of a pure NOTES gastrojejunal bypass using an in vivo porcine model. Material and methods: A prospective study was performed on nine swine. A double-channel scope was used. The intervention steps were: (i) gastric incision; (ii) peritoneal access; (iii) jejunal loop selection and mobilization into the stomach; (iv) stoma creation within the gastric wall and incision; (v) anastomosis suture and pylorus closure using a T-tag prototype. The animals were assessed clinically for 3 weeks including the weight gain. The patency of the GJA was assessed at necropsy and a histological analysis was performed. Results: We successfully performed all the procedures with a mean (standard deviation [SD]) operative time of 108 (26) minutes. We used a mean of 5.55 (1.30) stitches. There were no intraprocedural adverse events. Five animals survived up till euthanasia at 3 weeks (65 %). These showed a significant difference in weight curves of a loss of 3.2 kg compared with gain of 5.2 kg in a control group. Four pigs died from anastomotic dehiscence complicated by peritonitis. Conclusion: Gastrojejunal bypass with a pure NOTES approach is feasible. This procedure is effective, resulting in a patent anastomosis and a significant weight loss. However, the anastomotic dehiscence is a major concern because of its mortality rate, and further studies including improvement of the suturing device and the technique are needed

Implementation of a surgical simulation care pathway approach to training in emergency abdominal surgery

Background Simulation-based care pathway approach (CPA) training is a novel approach in surgical education. The objective of the present study was to determine whether CPA was feasible for training surgical residents and could improve efficiency in patients’ management. A common disease was chosen: acute appendicitis. Methods All five junior residents of our department were trained in CPA: preoperative CPA consisted in virtual patients (VPs) presenting with acute right iliac fossa pain; intraoperative CPA involved a virtual competency-based curriculum for laparoscopic appendectomy (LAPP); finally, post-operative VP were reviewed after LAPP. Thirty-eight patients undergoing appendectomy were prospectively included before (n = 21) and after (n = 17) the training. All demographic and perioperative data were prospectively collected from their medical records, and time taken from admission to management was measured. Results All residents had performed less than 10 LAPP as primary operator. Pre- and intraoperative data were comparable between pretraining and post-training patients. Times to liquid and solid diet were significantly reduced after training [7 h (2–20) vs. 4 (4–6); P = 0.004, and 17 h (4–48) vs. 6 (4–24); P = 0.005] without changing post-operative morbidity [4 (19%) vs. 0 (0); P = 0.11] and length of stay [48 h (30–264) vs. 44 (21–145); P = 0.22]. Conclusions CPA training is feasible in abdominal surgery. In the current study, it improved patients’ management in terms of earlier oral intake