Tracking the vector acceleration with a hybrid quantum accelerometer triad.

Robust and accurate acceleration tracking remains a challenge in many fields. For geophysics and economic geology, precise gravity mapping requires onboard sensors combined with accurate positioning and navigation systems. Cold atom-based quantum inertial sensors can potentially provide these high-precision instruments. However, current scalar instruments require precise alignment with vector quantities. Here, we present the first hybrid three-axis accelerometer exploiting the quantum advantage to measure the full acceleration vector by combining three orthogonal atom interferometer measurements with a classical navigation-grade accelerometer triad. Its ultralow bias permits tracking the acceleration vector over long time scales, yielding a 50-fold improvement in stability (6 × 10-8 g) over our classical accelerometers. We record the acceleration vector at a high data rate (1 kHz), with absolute magnitude accuracy below 10 µg, and pointing accuracy of 4 µrad. This paves the way toward future strapdown applications with quantum sensors and highlights their potential as future inertial navigation units.

Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications.

Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to a reconsideration of MPM molecular classifications. We show that each tumor can be decomposed as a combination of epithelioid-like and sarcomatoid-like components whose proportions are highly associated with the prognosis. Moreover, we show that this more subtle way of characterizing MPM heterogeneity provides a better understanding of the underlying oncogenic pathways and the related epigenetic regulation and immune and stromal contexts. We discuss the implications of these findings for guiding therapeutic strategies, particularly immunotherapies and targeted therapies.

Non-islet-cell tumour hypoglycaemia (NICTH): About a series of 6 cases.

The purpose of this study was to analyse the characteristics of 6 patients managed in a university hospital between 1996 and 2016 for non-islet cell tumor hypoglycemia (NICTH), a form of hypoglycaemia due to the paraneoplastic secretion of IGF-2 or its related substances. RESULTS: Three of these 6 patients (50%), aged over 69 years, including 2 with acromegaloid phenotype, presented with a pleural solitary fibrous tumor (SFT), with median diameter 20 cm (interquartile range, 12.5-20.5) with a low median SUV (3.3 g/mL (QR, 2-7.5)) on 18F-FDG PET. The other 3 patients presented respectively neuroendocrine carcinoma (NEC) of the palate (70-year-old woman), retroperitoneal myxofibrosarcoma (66-year-old man) and meningeal hemangiopericytoma (36-year-old woman). All 3 were inoperable and did not respond to any therapy other than glucose solution. Corticosteroid therapy was effective in the 3 SFTs and the NEC. One of the SFTs recurred 10 years later with asymptomatic hypoglycemia, which resolved after reintervention. Median (IQR) blood glucose levels of the 6 patients was 0.4g/L (QR, 0.31-0.41), with hypoinsulinemia at 0.7mIU/L (QR 0.7-2.0), undetectable GH, low IGF-1, normal IGF-2 level in 5/6 cases, a high IGF-2:IGF-1 ratio at 26.9 (QR, 20.8-37.8), hypokalemia and hypomagnesemia. CONCLUSION: NICTH is a rare syndrome, which should be considered in the presence of hypoinsulinemic hypoglycemia with low GH and IGF-1, and a IGF-2:IGF-1 ratio>10. Corticosteroid therapy was effective in elderly subjects, particularly with solitary fibrous tumor, which was generally operable. Hemangiopericytoma and myxofibrosarcoma had poor prognosis in younger patients.

Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.

Compared characteristics of current vs. past smokers at the time of diagnosis of a first-time lung or head and neck cancer: a cross-sectional study.

BACKGROUND: Active smoking at the time of diagnosis of a first head & neck (H&N) or lung cancer is associated with a worse cancer outcome and increased mortality. However, the compared characteristics of active vs. former smokers at cancer diagnosis are poorly known. METHODS: In 371 subjects with a first H&N or lung cancer, we assessed: 1) socio-demographic features; 2) lifelong types of smoking; 3) alcohol use disorder identification test (AUDIT); 4) cannabis abuse screening test (CAST); and 5) Mini International Neuropsychiatric Interview (MINI). Using a multivariable regression model, we compared the profile of current smokers and past smokers. RESULTS: Current smokers more frequently exhibited H&N cancer (OR 3.91; 95% CI [2.00-6.51]; p <  0.0001) and ever smoking of hand-rolled cigarettes (OR 2.2; 95% CI [1.25-3.88]; p = 0.007). Among subjects with lung cancer (n = 177), current smoking was primarily associated with ever smoking of hand-rolled cigarettes (OR 2.88; 95% CI [1.32-6.30]; p = 0.008) and negatively associated with age (OR 0.92; 95% CI [0.89-0.96]; p <  0.001). Among subjects with H&N cancer (n = 163), current smokers exhibited a significantly greater AUDIT score (OR = 1.08; 95% CI [1.01-1.16]; p = 0.03). CONCLUSION: At the time of diagnosis of the first lung or H&N cancer, current smoking is highly associated with previous type of smoking and alcohol drinking patterns. TRIAL REGISTRATION: NCT01647425 ; Registration date: July 23, 2012.

Repeated Resections of Hepatic and Pulmonary Metastases from Colorectal Cancer Provide Long-Term Survival.

BACKGROUND: Liver and lungs are the two most frequent sites of metastatic spread of colorectal cancer (CRC). Complete resection of liver and/or lung metastases is the only chance of cure, and several studies have reported an improved survival after an aggressive treatment. Nevertheless, CRC liver metastases (CLM) have been recognized as a pejorative factor for patients undergoing pulmonary metastasectomy. We report our experience with patients successively operated on for CRC hepatic and pulmonary metastasis (CPM) and seek to identify prognostic factors. METHODS: All consecutive patients who had resection of CPM and CLM between 2001 and 2014 were enrolled in the study. Clinicopathological and survival data were retrospectively analysed. RESULTS: Forty-six patients underwent resections of both CLM and CPM. Hepatic resection preceded pulmonary resection in most cases (91.3%). The median intervals between the resection of the primary tumour and the hepatic recurrence and between hepatic and pulmonary recurrences were 12 months [0-72] and 21.5 months [1-84], respectively. The mortality rate following CPM resection was 4.3%. After a median follow-up of 41.5 months [0-126], 35 patients recurred of whom 14 (40%) and 11(31.4%) could benefit from repeated resection of recurrent CLM and CPM, respectively. The median and 5-year overall survivals (OS) were 53 months and 49%, respectively. No prognostic factor was identified. CONCLUSION: An aggressive management of CLM and CPM, including repeated resections, may provide a long-term survival comparable to survival of patients with unique metastasectomy. The absence of prognostic factor may reflect the highly selected pattern of the eligible patients.

Exhaustive preoperative staging increases survival in resected adrenal oligometastatic non-small-cell lung cancer: a multicentre study.

OBJECTIVES: Adrenal oligometastatic non-small-cell lung cancer is rare, and surgical management remains controversial. METHODS: We performed a multicentre, retrospective study from January 2004 to December 2014. The main objective was to evaluate survival in patients who had undergone adrenalectomy after resection of primary lung cancer. Secondary objectives were to determine prognostic, survival and recurrence factors. RESULTS: Fifty-nine patients were included. Forty-six patients (78%) were men. The median age was 58 years [39-75 years]. Twenty-six cases (44%) showed synchronous presentation, and 33 cases (56%) had a metachronous presentation. The median time to onset of metastasis was 18.3 months [6-105 months]. The 5-year overall survival rate was 59%; the median survival time was 77 months [0.6-123 months]. A recurrence was observed in 70% of the population. Mediastinal lymph node invasion (P = 0.035) is a detrimental prognostic factor of survival. CONCLUSIONS: After exhaustive staging, patients with adrenal oligometastatic non-small-cell lung cancer benefit from bifocal surgery.

High-MET status in non-small cell lung tumors correlates with receptor phosphorylation but not with the serum level of soluble form.

OBJECTIVES: The receptor tyrosine kinase MET is essential to embryonic development and organ regeneration. Its deregulation is associated with tumorigenesis. While MET gene amplification and mutations leading to MET self-activation concern only a few patients, a high MET level has been found in about half of the non-small cell lung cancers (NSCLCs) tested. How this affects MET activation in tumors is unclear. Also uncertain is the prognostic value, in cancer, of a phenomenon well described in cell models: MET shedding, i.e. its cleavage by membrane proteases leading to release of a soluble fragment into the medium. MATERIALS AND METHODS: A prospective cohort of 39 NSCLC patients was constituted at diagnosis or soon after. Normal tissues, tumor tissues, and blood samples were obtained. This allowed, for the same patient, synchronous determination of (i) the MET level in the tumor, (ii) receptor phosphorylation, and (iii) the concentration of soluble MET fragment (sMET) in the serum. RESULTS: After confirming the adequacy of an ELISA for measuring the serum level of sMET, we found no correlation between this level and the concentration of MET in tumors, as evaluated by immunohistochemistry and western blotting. Nevertheless, all but one tumor displaying a high MET level also displayed receptor phosphorylation, restricted to a small number of tumor cells. CONCLUSION: Our results thus demonstrate that the serum level of sMET is not indicative of the amount of MET present in the tumor cells and cannot be used as a biomarker for therapeutic purposes. However, MET scoring of tumor biopsies could be a first step prior to determination of MET receptor activation in high-MET tumors.

Conservatively treated extended tracheal necrosis complicating pharyngolaryngectomy.

Tracheal necrosis is a rare life-threatening phenomenon that most often occurs after thyroid operations or prolonged intubation. Conservative treatment can be one choice in extensive tracheal necrosis. We report the case of a 59-year-old man, with tracheal necrosis that developed after pharyngolaryngectomy, that we treated conservatively using hyperbaric oxygen therapy and antibiotic therapy. The follow-up was assured by tracheobronchoscopy. A year after his discharge, the trachea was totally healed.

Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?

In the surgical multimodal management of malignant pleural mesothelioma, it seems crucial to proceed with an efficient local adjuvant treatment to kill residual tumor cells. Intrapleural photodynamic therapy has recently emerged as a potential candidate in this goal. In this review, we analyzed and classified 16 articles in which patients with malignant pleural mesothelioma received intrapleural photodynamic therapy after maximal surgical resection. The toxicity, effect on survival, and development of the technique were assessed. After two decades of clinical studies, intrapleural photodynamic therapy after surgical resection became a safe treatment that significantly improved the survival of patients.

Asymptomatic pelvic metastasis from thymic carcinoma: a case report.

Thymic epithelial tumors are rare and often occur somewhere local. Metastatic sites of thymic carcinomas (Masaoka-Koga stage IVb) are mostly seen in the lung, liver and brain. We report a 64-year-old female with an initial diagnosis of thymoma B3 who first showed thoracic recurrences and then an asymptomatic isolated pelvic metastasis from her thymic carcinoma.

Thoracic epidural anaesthesia for awake thoracic surgery in severely dyspnoeic patients excluded from general anaesthesia.

OBJECTIVES: General anaesthesia (GA) carries high risks of ventilator dependency with increased morbidity and mortality in patients with severe respiratory disease. It also presents an ethical dilemma if surgery remains the only treatment option for patients with advanced terminal chronic respiratory disease. Thoracic epidural anaesthesia for awake thoracic surgery (TEATS) in high-risk patients with dyspnoea at rest could avoid ventilator dependency and speed up recovery even in patients with severe dyspnoea. This retrospective observational study analysed indications, management and outcome of patients contraindicated to GA undergoing awake thoracic surgery with thoracic epidural anaesthesia. METHODS: From 716 patients requiring thoracic surgery, nine were contraindicated to GA. Eight patients [American Society of Anesthesiologists (ASA) 4] had a maximum grade four of the modified Medical Research Council dyspnea scale (MMRC). Two patients (ASA 3, grade 1 MMRC and ASA 4, grade 4 MMRC) refused GA. RESULTS: Patients (female : male ratio 1.25 : 1, age 19-76 years) had the following chronic respiratory diseases: pulmonary fibrosis (n = 2), pulmonary metastases (n = 3), chronic obstructive pulmonary disease (n = 1), alveolitis (n = 1) and myopathy (n = 2). Surgical indications were: thoracotomy (n = 6) for pleurectomy to treat recurring pneumothorax (n = 3), pleurostomy (n = 1), emphysema surgery (n = 1), lung biopsy (n = 1) and thoracoscopy (n = 3) for pleural/lung biopsy (n = 2), pneumothorax (n = 1). Lidocaine 20 mg/ml or ropivacaine 7.5 mg/ml was titrated to achieve an anaesthesia level T2-T12. No patient required GA [time of surgery: 46-128 min, mean = 76 min, standard deviation (SD) = 23 min]. Seven patients had light sedation with TCI propofol, remifentanyl or both and remained responsive. Fifty percent of patients received phenylephrine or ephedrine to maintain arterial pressure. Two patients went into hypercapnia, which was reversed with assisted mask ventilation. One patient suffered acute respiratory distress 7 days postoperatively and died of intestinal bleeding on Day 25. There were no postoperative complications in other patients. Excluding Patient 9 always remaining in a medical intensive care unit (ICU), the mean postoperative ICU stay in thoracic surgery was 4.4 days (SD 5.2). Hospital discharge was between 5 and 40 days after surgery. CONCLUSIONS: TEATS with/without sedation was an alternative to GA for thoracotomy/thoracoscopy in severely dyspnoeic patients (MMRC grade 4, ASA 4) without postoperative sequelae.

Lymph node involvement and metastatic lymph node ratio influence the survival of malignant pleural mesothelioma: a French multicenter retrospective study.

Malignant pleural mesothelioma (MPM) is a rare tumor with disastrous evolution. The prognostic value of nodal involvement is still debated. We analyzed the impact of nodal involvement on overall survival (OS) in patients treated by multimodal therapy including extra pleural pneumonectomy (EPP). We evaluated the role, as a prognostic factor, of the metastatic lymph node ratio (LNR), corresponding to the number of involved nodes out of the total number of removed nodes. In this retrospective multicentric study, we reviewed the data of 99 MPM patients. Information regarding lymph node involvement was assessed from the final pathology reports. N1-N3 patients were pooled as N+ group. The OS, calculated by the Kaplan-Meier method, was compared using the log-rank test. A multivariate Cox proportional hazards model was used to identify independent prognostic factors. For the whole cohort, median OS was 18.3 months and 5-year survival was 17.5%. N+ status reduced significantly the median survival (22.4 months for N0 patients vs 12.7 months for N+ patients, P=0.002). A lower metastatic LNR (≤13%) was associated with a significantly improved median survival (19.9 vs. 11.7 months, P=0.01). OS was not related to the number of involved or total removed lymph nodes. In multivariate analysis, only adjuvant radiotherapy (P=0.001) was identified as an independent positive prognostic factor. Metastatic LNR is a more reliable prognostic factor than the number of involved lymph nodes or the total number of removed nodes. However, it could not be identified as an independent prognostic factor.

National perioperative outcomes of pulmonary lobectomy for cancer: the influence of nutritional status.

OBJECTIVES: Nutritional assessment is not included yet as a major recommendation in lung cancer guidelines. The purpose of this study was thus to assess the influence on surgical outcome of the nutritional status of patients with primary lung cancer undergoing lobectomy. METHODS: We queried Epithor, the national clinical database of the French Society of Thoracic and Cardiovascular Surgery, and identified a retrospective cohort of 19 635 patients having undergone lobectomy for a primary lung cancer in the years 2005-11. Their nutritional status was categorized according to the WHO definition: underweight (BMI < 18.5): 857 patients (4.4%), normal (18.5 ≤ BMI < 25): 9391 patients (47.8%), overweight (25 ≤ BMI < 30): 6721 patients (34.2%), obese (BMI ≥ 30): 2666 patients (13.6%). Operative mortality, pulmonary, cardiovascular, infectious and surgical complications rates were collected and analysed for these various BMI groups. RESULTS: In the normal-weight category, operative mortality, pulmonary, surgical, cardiovascular and infectious complications rates were 2.7, 14.6, 13.8, 5.5 and 4.1%, respectively. When compared with that of normal BMI patients, adjusted operative mortality was significantly lower in overweight (2.3%; odd ratio (OR): 0.72 [95% confidence interval (CI): 0.59-0.89]; P = 0.002) and obese patients (1.9%, OR: 0.54 [95% CI: 0.40-0.74]; P < 0.001), and significantly higher in underweight patients (4.1%, OR: 1.89 [95% CI: 1.30-2.75]; P = 0.001). Underweight patients experienced significantly more pulmonary (21.1%; P < 0.001), surgical (23.2%; P < 0.001) and infectious (5.1%; P = 0.05) complications (P < 0.0001). Among surgical complications, prolonged air leaks (17.6%; P < 0.001) and bronchial stump dehiscence (1.5%; P = 0.001) were significantly more frequent in underweight patients than in normal BMI patients. Obesity was not associated with increased incidence of postoperative complications, except for arrhythmia (5.6%; P < 0.05), deep venous thrombosis and pulmonary embolism (1.5%; P = 0.005). Moreover, a statistical protective effect of obesity was observed regarding surgical complications (7.1%; P < 0.001). CONCLUSIONS: Despite having an increased risk of some postoperative cardiovascular complications, obese patients should undergo surgical standard of care therapy for appropriately stage-specific lung cancer. In underweight patients, in addition to preoperative rehabilitation including a nutritional program, attention should be given to aggressive prophylactic respiratory therapy in the perioperative period, and specific intraoperative actions to prevent prolonged air leaks and bronchial stump dehiscence.

Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid.

BACKGROUND: Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). MPE animal models and immunotherapy trials in MPM patients previously suggested defects of the cellular immunity in MPE. However only few observational studies of the immune response were done in MPM patients, using questionable control groups (transudate…). METHODS: We compared T cell populations evaluated by flow cytometry from blood and pleural effusion of untreated patients with MPM (n = 58), pleural metastasis of adenocarcinoma (n = 30) or with benign pleural lesions associated with asbestos exposure (n = 23). Blood and pleural fluid were also obtained from healthy subjects, providing normal values for T cell populations. RESULTS: Blood CD4+ or CD8+ T cells percentages were similar in all groups of patients or healthy subjects. Whereas pleural fluid from healthy controls contained mainly CD8+ T cells, benign or malignant pleural effusions included mainly CD4+ T cells. Effector memory T cells were the main T cell subpopulation in pleural fluid from healthy subjects. In contrast, there was a striking and selective recruitment of central memory CD4+ T cells in MPE, but not of effector cells CD8+ T cells or NK cells in the pleural fluid as one would expect in order to obtain an efficient immune response. CONCLUSIONS: Comparing for the first time MPE to pleural fluid from healthy subjects, we found a local defect in recruiting effector CD8+ T cells, which may be involved in the escape of tumor cells from immune response. Further studies are needed to characterize which subtypes of effector CD8+ T cells are involved, opening prospects for cell therapy in MPE and MPM.

Relevance of an extensive follow-up after surgery for nonsmall cell lung cancer.

There are no international guidelines for an appropriate and cost-effective follow-up for resected nonsmall cell lung cancer (NSCLC). We retrospectively reviewed the outcome of NSCLC patients after curative surgery. Follow-up included physical examination and chest radiography every 3 months, and chest computed tomography (CT) scan, bronchoscopy, abdominal ultrasound, brain CT scan and bone scan every 6 months for 3 years, then every year over the following 2 years. Prognostic factors and costs were analysed. Median overall survival following surgery for NSCLC in 162 patients was 38.5 months. Recurrence occurred in 85 (52.5%) patients including 41 (48%) symptomatic subjects. Disease-free survival was similar between patients with asymptomatic recurrence versus symptomatic patients (11.4 versus 12 months; p=0.41). Recurrence was detected by physical examination or chest radiography in 47 (55.3%) patients. Curative-intent therapy was provided in 18 (41%) out of 44 patients with asymptomatic recurrence and in four (10%) out of 41 symptomatic cases (p=0.001). Median overall survival from time of recurrence was higher in asymptomatic patients than in symptomatic patients (15.5 versus 7.2 months; p=0.001). The cost per year of life gained was USD32 700 (€22 397). An extensive follow-up, with acceptable cost, may improve the outcome of patients with resected NSCLC through detection of asymptomatic recurrences; however, validation by prospective studies is required.

Open window thoracostomy and thoracoplasty to manage 90 postpneumonectomy empyemas.

BACKGROUND: Postpneumonectomy empyema (PPE) is a serious complication. The treatment options are similar to the management of any abscess, with drainage, ideally open, often of critical importance. After infection control, many techniques for space obliteration have been described. This study summarizes a 10-year experience in the management of PPE in our center. METHODS: From 2000 to 2010, 90 patients (83 men) with PPE were treated. Median follow-up was 5.3 years. Once the diagnosis of empyema was confirmed, chest drainage was performed through open window thoracostomy (OWT), with ensuing extramusculoperiosteal thoracoplasties if healthy tissue was present. RESULTS: Pneumonectomy was performed in 72 patients with lung cancer. Mortality after PPE was 2.2%. OWT achieved infection control in 89 patients. Seven OWT spontaneously healed, and 24 were never closed. The remaining 59 patients with OWT underwent thoracoplasty. Mortality after thoracoplasty was 5%. Empyema recurred in 3 patients. Overall success rate of PPE control after pleural obliteration was 91.5%. CONCLUSIONS: Thoracoplasty is a reliable filling procedure. It has a significantly higher success rate and a lower mortality rate than the other techniques. We believe that this procedure has a part to play in the future management of PPE.

Primary pulmonary myoepithelial carcinoma.

Primary salivary gland-type tumors of the lung are rare neoplasms. The pulmonary myoepithelial carcinoma belongs to this group. Since it was first described in 1998, we have identified only seven actual cases reported in the literature so far. We describe the case of a non-smoker 60-year-old Caucasian female, who was referred to our institution for the treatment of three peripheral nodules. Her medical history revealed that a wedge resection, for pulmonary myoepithelial carcinoma, was performed in another center 15 months previously. After resection of the current nodules, the histological findings showed three myoepithelial carcinomas of the lung. There was no vascular or lymphatic invasion. The hilar and mediastinal lymph nodes were negatives. The patient is doing well without any sign of recurrence. Herein we shall discuss the case of a primary pulmonary myoepithelial carcinoma in a female and propose a brief review of the literature.