Contribution of the cadaveric recirculation system in the anatomical study of lymphatic drainage of the ovary: applications in the management of ovarian cancer.

PURPOSE: The present knowledge about lymphatic drainage of the ovary is based on carcinological studies, but it has only rarely been studied under physiological conditions. However, it is one of the preferential routes of dissemination in ovarian cancer, and understanding it is therefore vital for optimal carcinological management.Our purpose was to evaluate the feasibility of an innovative technique to study the lymphatic drainage territories of the ovary using a recirculation module on the cadaveric model. METHODS: We injected patent blue into the cortex of twenty "revascularised" cadaver ovaries with the Simlife recirculation model. We observed the migration of the dye live and described the drainage territories of each ovary. RESULTS: We observed a staining of the lymphatic vessels and migration of the dye in all the subjects, systematically ipsilateral to the injected ovary. We identified a staining of the lumbo-aortic territory in 65% of cases, with a preferential lateral-caval involvement (60%) for the right ovary and lateral-aortic territory (40%) for the left ovary. A common iliac involvement was observed in only 10% of cases. In 57% of cases, the staining of the lumbo-aortic territory was associated with a staining of the suspensory ligament. The pelvic territory was involved in 50% of cases, with an external iliac staining in 25% of cases and internal in 20%. CONCLUSION: Our study provides for a better understanding of lymphatic drainage of the ovary using a new detection method, and allows the possibility of improving the teaching for operators with a realistic model. Continuation of this work could lead to considering more targeted and thus less morbid lymph node sampling for lymph node staging in early-stage ovarian cancer.

PET-MRI for evaluation of response to radiochemotherapy in patients with locally advanced cervical cancer.

OBJECTIVE: We aimed to analyze the diagnostic test accuracy of positron emission tomography and a magnetic resonance imaging scan (PET-MRI) fusion in evaluating tumor response after radiochemotherapy in patients with locally advanced cervical cancer. METHODS: Patients treated at two institutes between January 2008 and December 2016 were studied retrospectively. Re-evaluation by positron emission tomography (PET) and magnetic resonance imaging (MRI) was performed in a non-concurrent way 4-8 weeks after treatment. A nuclear medicine doctor and a radiologist (subsequently referred as "radiologists"), both experts in gynecological oncology, re-examined the post-treatment MRI and positron emission tomography-computed tomography (PET-CT) separately, and then performed a fusion of these examinations. In this study we describe this "a posteriori fusion methodology", with two levels, enabling limitation of anatomical shifts. The gold standard was anatomical pathology analysis of the surgical specimen, since all patients underwent surgery following this radiological re-evaluation. The radiologists' degree of certainty in their diagnoses, and the impact of fusion on their diagnostic confidence were assessed by the radiologists, using two Likert judgment scales. They also adjudicated on possible changes of interpretation after the fusion. RESULTS: Thirty-one patients were included. The PET-MRI fusion has a sensitivity of 79% and a specificity of 90%. The positive predictive value (PPV) was 94%, and the negative predictive value (NPV) was 69%. In 45% of cases (n=13), radiologists reported an improvement in their degree of certainty in their diagnosis using a Likert judgment scale, due to inspecting the PET and MRI fused. A change in interpretation of tumor response was observed using a Likert judgment scale in 31% of cases. CONCLUSION: PET-MRI fusion improves the radiologist's own diagnostic confidence in assessing response to concurrent radiochemotherapy in locally advanced cervical cancer. More studies using a latest generation hybrid system will be necessary to further compare to MRI and PET-CT.

Prevention of hypothermia in trauma victims - the HYPOTRAUM 2 study.

INTRODUCTION: Hypothermia is common in trauma patients. It contributes to increasing mortality rate. Hypothermia is multifactorial, favoured by exposure to cold, severity of the patient's state and interventions such as infusion of fluids at room temperature. AIM: To demonstrate that specific management of hypothermia (or of the risk of hypothermia) increases the number of trauma patients arriving at the hospital with a temperature >35°C. DESIGN: This is a prospective, multicentre, open-label, pragmatic, cluster randomized clinical trial of an expected 1,200 trauma patients included by 12 out-of-hospital mobile intensive care units (MICU). Trauma patients are included in a prehospital setting if they present at least one of the following criteria known to be associated with an increased incidence of hypothermia: ambient temperature <18°C, Glasgow coma scale <15, systolic arterial blood pressure <100 mm Hg or body temperature <35°C. Patients are randomized, by cluster, to receive a conventional management or 'interventional' nursing management associating: continuous epitympanic temperature monitoring, early installation in the heated ambulance (temperature target >30°C controlled by infrared thermometer), protection by a survival blanket, and use of heated solutes (temperature objective >35°C controlled by infrared thermometer). The primary end point is the prevalence of hypothermia on arrival at the hospital. The hypothesis tested is a reduction from 20% to 13% in the prevalence of hypothermia. Secondary end points are to evaluate the interaction between the effectiveness of the measures taken and: (1) the severity of the patients assessed by the Revised Trauma Score; (2) the meteorological conditions when they are managed; (3) the time of care; and (4) therapeutic interventions. DISCUSSION: This trial will assess the effectiveness of an invasive, out-of-hospital, temperature management on the onset of hypothermia in moderate to severe trauma patients. IMPACT: Specific management of hypothermia is expected to decrease hypothermia in trauma patients.

Body Mass Index as a Major Risk Factor for Severe Breast Cancer-Related Lymphedema.

Background: A few studies have examined the characteristics of severe breast cancer-related lymphedema (BCRL). This study aims at analyzing the factors associated with severe lymphedema (LE) across a specific population of patients with BCRL. Methods and Results: Seventy-four patients with BCRL were included and cared for in the Lymphology Unit of Toulouse University Hospital between 2015 and 2016. Characteristics of patients and factors related to severe BCRL were retrospectively assessed. The median age at time of LE was 56 years (30-82). Thirty-five patients (47.3%) had a mastectomy and 72 (97.3%) an axillary lymphadenectomy. Among patients treated with radiation therapy (n = 72), 76.3% received lymphatic nodes irradiation. Fifty-five patients (74.3%) received chemotherapy and 52 (70.3%) a hormonal suppression therapy. A high proportion of patients had severe (>400 mL, 64.9%) and premature LE, with a median time of 13 months since onset of surgery (0.1-400.2). Weight gain between surgery and LE management was more prevalent in obese patients (p = 0.0164). Body mass index (BMI) at BCRL diagnosis was the only risk factor associated with severe LE (p = 0.0132). There was no significant association between LE severity and treatments received for breast cancer. Conclusions: Our study did not show any influence of tumor characteristics and cancer-related treatments on the severity of BCRL. Only BMI at BCRL diagnosis appears as a factor related to severe LE. These results highlight the importance of an education care unit promoting personalized nutritional lifestyle and encouraging physical activity early in the management of breast cancer.

Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis.

Cytotoxic therapy for breast cancer inhibits the growth of primary tumors, but promotes metastasis to the sentinel lymph nodes through the lymphatic system. However, the effect of first-line chemotherapy on the lymphatic endothelium has been poorly investigated. In this study, we determined that paclitaxel, the anti-cancer drug approved for the treatment of metastatic or locally advanced breast cancer, induces lymphatic endothelial cell (LEC) autophagy to increase metastases. While paclitaxel treatment was largely efficacious in inhibiting LEC adhesion, it had no effect on cell survival. Paclitaxel inhibited LEC migration and branch point formation by inducing an autophagy mechanism independent of Akt phosphorylation. In vivo, paclitaxel mediated a higher permeability of lymphatic endothelium to tumor cells and this effect was reversed by chloroquine, an autophagy-lysosome inhibitor. Despite a strong effect on reducing tumor size, paclitaxel significantly increased metastasis to the sentinel lymph nodes. This effect was restricted to a lymphatic dissemination, as chemotherapy did not affect the blood endothelium. Taken together, our findings suggest that the lymphatic system resists to chemotherapy through an autophagy mechanism to promote malignant progression and metastatic lesions. This study paves the way for new combinative therapies aimed at reducing the number of metastases.

Compliance with a morphine protocol and effect on pain relief in out-of-hospital patients.

This study was carried out to evaluate the compliance with a morphine protocol and its effects on pain relief in pre-hospital care. In this prospective study, pain intensity was evaluated by the Visual Analog Scale (VAS) from the beginning and every 5 min until hospital arrival (Tend). Group 1: No major deviation from the protocol (intravenous morphine as a first bolus of 0.05 mg/kg followed by repeated boluses every 5 min until VAS < or = 30 mm). Group 2: Major deviation from the protocol. There were 216 patients included. The mean dose of morphine was 9.0 +/- 5.7 mg. The morphine protocol was respected in 123 patients (57%). The mean VAS score was significantly better at Tend in Group 1 vs. Group 2 (27.8 +/- 21.1 mm vs. 37.8 +/- 22.1 mm, respectively), the degree of pain relief was significantly better (73% vs. 53%, respectively) and the initiation time for pain relief was significantly shorter in Group 1 vs. Group 2 (10 min [5-15] vs. 15 min [10-26], respectively). Satisfaction was significantly better in patients expressing pain relief than in unrelieved patients (94% vs. 61%, respectively). Out-of-hospital pain management using morphine depends on careful attention to dosage and the time interval between re-injections. Emergency teams may employ these data to improve the quality of pain relief in the field.

Correlation of arterial PCO2 and PETCO2 in prehospital controlled ventilation.

INTRODUCTION: This study was carried out to estimate the relationship between arterial PCO2 (PaCO2) and end-tidal carbon dioxide (PETCO2) during prehospital controlled ventilation and also to evaluate variation of the gradient between PCO2 and PETCO2 during prehospital transport. METHODS: Measurements of PETCO2 from capnography values and PaCO2 from arterial blood gases were registered at the beginning (T(0)) and at the end (T(end)) of out-of-hospital management. For all patients requiring invasive ventilation, the gradient between PCO2 and PETCO2 was calculated for T(0) and T(end), the PaCO2-PETCO2 variation between T(end) and T(0) was also calculated. RESULTS: One hundred patients were included in this study (mean age, 58.4 +/- 16.4 years; 57 were male). There was no variation of the mean gradient (DeltaPaCO2-PETCO2 ) during transport (8.64 +/- 13.5 mm Hg at T(0) and 7.26 +/- 12.94 mm Hg at T(end)). Thirty-six percent of patients (n = 36) had a gradient above +10 mm Hg, and for 6% of patients (n = 4) the gradient was lower than -10 mm Hg. The PaCO2-PETCO2 gradient was not significantly different according to the pathology, but was significantly higher in hypercapnic patients compared with hypocapnic or normocapnic patients. In patients with severe head injury, the capnia was normalized in 80% of patients at the end of the transport according to the last blood gas result. In this subgroup the DeltaPaCO2-PETCO2 (T(end) - T(0)) gradient was stable between T(0) and T(end) except in 20% of the patients for whom the DeltaPaCO2-PETCO2 was lower than -10 mm Hg. Fifty-four percent of critical care physicians had modified the respiratory setting after the first arterial blood gas results. CONCLUSIONS: The PaCO2 cannot be estimated by the PETCO2 in the prehospital setting. There is wide variation in the gradient between PCO2 and PETCO2 depending on patient condition, and over time, the relationship does not remain constant and thus cannot be useful in prehospital ventilation management.

Epidemiology of adverse effects of prehospital sedation analgesia.

The aim of this study was to introduce a continuous monitoring of side effects related to sedation-analgesia in the field. A document was completed by physicians on board the ambulances for all prehospital interventions and checked daily by the medical staff. A total of 3605 interventions were evaluated over a 12-month period. Six hundred four patients undertook analgesia and/or sedation: group 1 (spontaneously breathing patients) n = 289 and group 2 (intubated-ventilated patients) n = 315. Sixty-four percent of patients received intravenous opioids in group 1. The anesthetic technique used for intubation was the rapid sequence induction in 70% of patients. Side effects were observed in 5.5% in group 1 (nausea: 2%, hypotension: 1%, hypoxemia: 1%) and 22% of patients in group 2 (hypotension-arrhythmia: 12%, cardiac arrest: 2%, difficult intubation: 5%, hypoxemia: 1%, pulmonary aspiration: 1%, laryngospasm/bronchospasm: 2%). No death was related to these medications. A close monitoring of side effects related to sedation-analgesia must be included in a quality program to improve patient safety in the field.