Actualities in the anaesthetic management of pheochromocytoma/ paraganglioma.

The anaesthetic management of pheochromocytoma is complicated and challenging. However, preoperative pharmacologic preparation, modern anaesthetic techniques and drugs associated with advanced monitoring in conjunction with the evolution of surgical techniques (open laparotomy to laparoscopic surgery and robotic approaches in the present day) improved significantly perioperative outcome, and intraoperative and postoperative hemodynamic stability. Although there are not randomised clinical trials to suggest one approach over another and there is a high international variability amongst intraoperative anaesthetic techniques, most management principles are still universal.

The HealtheSteps™ lifestyle prescription program to improve physical activity and modifiable risk factors for chronic disease: a pragmatic randomized controlled trial.

BACKGROUND: Our objective was to determine the influence of the HealtheSteps™ lifestyle prescription program on physical activity and modifiable risk factors for chronic disease in individuals at risk. METHODS: One hundred eighteen participants were recruited from 5 sites in Southwestern Ontario, Canada and randomized to either the intervention (HealtheSteps™ program, n = 59) or a wait-list control group (n = 59). The study comprised three phases: an Active Phase (0 to 6 months) consisted of bi-monthly in-person lifestyle coaching with access to a suite of eHealth technology supports (Heathesteps app, telephone coaching and a private HealtheSteps™ social network) followed by a Minimally-Supported Phase I (6 to 12 months), in which in-person coaching was removed, but participants still had access to the full suite of eHealth technology supports. In the final stage, Minimally-Supported Phase II (12 to 18 months), access to the eHealth technology supports was restricted to the HealtheSteps™ app. Assessments were conducted at baseline, 6, 12 and 18 months. The study primary outcome was the 6-month change in average number of steps per day. Secondary outcomes included: self-reported physical activity and sedentary time; self-reported eating habits; weight and body composition measures; blood pressure and health-related quality of life. Data from all participants were analyzed using an intent-to-treat approach. We applied mixed effects models for repeated measurements and adjusted for age, sex, and site in the statistical analyses. RESULTS: Participants in HealtheSteps™ increased step counts (between-group [95% confidence interval]: 3132 [1969 to 4294], p < 0.001), decreased their sitting time (- 0.08 [- 0.16 to - 0.006], p = 0.03), and improved their overall healthful eating (- 1.5 [- 2.42 to - 0.58], p = 0.002) to a greater extent compared to control at 6 months. Furthermore, exploratory results showed that these individuals maintained these outcomes 12 months later, after a minimally-supported phase; and retained improvements in sedentary time and improved healthful eating after 18 months. No differences in self-reported physical activity, health-related quality of life, weight, waist circumference or blood pressure were observed between groups at 6 months. CONCLUSIONS: Our findings suggest that HealtheSteps™ is effective at increasing physical activity (i.e., step counts per day), decreasing weekday sitting time, and improving healthful eating in adults at increased risk for chronic disease after 6 months; however, we did not see change in other risk factors. Nonetheless, the maintenance of these behaviours with minimal support after 12 and even 18 months indicates the promise of HealtheSteps™ for long-term sustainability. TRIAL REGISTRATION: The trial was registered on April 6, 2015 with ClinicalTrials.gov (identifier: NCT02413385 ).

Impact of locoregional irradiation in patients with upfront metastatic head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the frequency of use, modalities and potential interest of locoregional irradiation (LRT) in patients with upfront metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective multicentric study. Were included all patients presenting an upfront metastatic HNSCC treated by platin-5FU- cetuximab based regimen, from 2008 to 2016. Patients with past history of cervical irradiation or HNSCC within the 5 years before metastasis diagnosis were excluded. RESULTS: 65 patients were included. 25 patients (38%) presented a response or stable disease with chemotherapy. Forty-one patients (63%) underwent a locoregional irradiation: 5 patients before chemotherapy (upfront RT), 13 patients with stable disease or response after chemotherapy (consolidation RT), and 23 patients with progressive disease. Median overall survival (OS) was 11.6 months, median progression free survival was 7.9 months. OS was significantly improved for patients who underwent LRT (median OS 16.1 vs 7.5 months, p < 0.01). Among patients who received LRT, OS trended to be better if LRT was performed as consolidation RT compared to upfront RT (median OS of 22.1 vs 15.5 months, p = 0.11). Among patients with stable disease or response after chemotherapy, there was a non-significant better OS for the 13 patients treated by LRT (median OS 22.1 vs 11.8 months, p = 0.21)). Radical dose was not associated with better locoregional control compared to palliative dose (p = 0.37). CONCLUSION: LRT is frequently performed during management of upfront metastatic HNSCC and associated with better OS. Non-progressive disease after firs-line chemotherapy seems a good way to select patients who would benefit from radical LRT.

Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.

BACKGROUND: Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. CLINICALTRIALSGOV: NCT00450892.

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.

Histopathological and immunohistochemical features of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have become a model of targeted therapy in oncology. The diagnosis of GISTs relies on histological arguments - proliferation of spindle cells, seldom of epithelioid cells or both spindle and epithelioid cells - and on immunohistochemical arguments - expression of CD117 usually associated with CD34 expression. The evaluation of the prognosis is essential and based on a simple algorithm using two prognostic parameters, tumor size and mitotic index. The aim of this paper is a complex histopathological assessment, using both classic and modern (immunohistochemistry) techniques, of the GISTs comprised in the study. GISTs occur mainly in older adults (median age 60-69 years), anywhere along the gastrointestinal tract but also retroperitoneal. Most of them were nodular (75%), tumor necrosis and mucosal ulceration being the most frequent encountered secondary alterations; these modifications proved to be significantly correlated with large tumor size and high malignancy. Immunohistochemical evaluation revealed that 77 (97%) cases of GISTs presented a positive reaction for CD117, 50 (63%) cases were positive for CD34, 19 (24%) were positive for SMA and only 10 (13%) were positive for S100. Immunohistochemical evaluation remains an important tool of pathology in the diagnosis of GISTs, in the differential diagnosis from other gastrointestinal mesenchymal tumors and represents the gold standard for diagnosis of these tumors and an eligibility criterion for imatinib therapy.

Predictive preoperatory variables of the prostate tumor volume.

Prostate cancer (PCa) is the second most frequent malignant tumor in men worldwide and the most common form of cancer in men over 50-year-old. The adequate preoperative estimation of tumor volume in order to identify small tumors that lack a short-term aggressive behavior and do not necessitate a forthwith-radical prostatectomy (RP) is the subject of various recent studies and numerous debates. In this study, that included 128 cases, we attempted to evaluate some of the common preoperative variables (patient's age, total prostate volume determined on ultrasound examination, serum PSA, the number of positive biopsies and tumor size, the percentage of tumor length and the Gleason score) that could predict the tumor volume on the final RP. Based on these correlations, we develop a scoring system that combines only the Gleason score, the number of positive biopsies and the percentage of tumor length and that has been statistically proved to be correlated and predictive for the tumor volume. Our study brings additional and practical information about a true and effective prospective evaluation of the volume of the PCa.

Music acupuncture stimulation method.

Harmonic Medicine is the model using the theory that the body rhythms synchronize to an outer rhythm applied for therapeutic purpose, can restores the energy balance in acupuncture channels and organs and the condition of well-being. The purpose of this scientific work was to demonstrate the role played by harmonic sounds in the stimulation of the Lung (LU) Meridian (Shoutaiyin Feijing) and of the Kidney (KI) Meridian (Zushaoyin Shenjing). It was used an original method that included: measurement and electronic sound stimulation of the Meridian Entry Point, measurement of Meridian Exit Point, computer data processing, bio feed-back adjustment of the music stimulation parameters. After data processing, it was found that the sound stimulation of the Lung Meridian Frequency is optimal between 122 Hz and 128 Hz, with an average of 124 Hz (87% of the subjects) and for Kidney Meridian from 118 Hz to 121 Hz, with an average of 120 Hz (67% of the subjects). The acupuncture stimulation was more intense for female subjects (> 7%) than for the male ones. We preliminarily consider that an informational resonance phenomenon can be developed between the acupuncture music stimulation frequency and the cellular dipole frequency, being a really "resonant frequency signature" of an acupoint. The harmonic generation and the electronic excitation or low-excitation status of an acupuncture point may be considered as a resonance mechanism. By this kind of acupunctural stimulation, a symphony may act and play a healer role.