Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial.

BACKGROUND: Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. METHODS: We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. RESULTS: CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001). CONCLUSION: The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial.

BACKGROUND: We compared the health-related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I-III esophageal cancer. METHODS: A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5-fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5-fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. RESULTS: There was no significant difference in the functional assessment of cancer therapy-esophageal (FACT-E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre-treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT-E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-OG25), and EuroQol 5-D-3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30-day mortalities and 2% vs. 10% 90-day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5-year: 35% vs. 32%, p = 0.409) or disease-free survival (DFS) (5-year: 31% vs. 30%, p = 0.710). CONCLUSION: Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed.

Development of an In Situ Thoracic Surgery Crisis Simulation Focused on Nontechnical Skill Training.

BACKGROUND: Our vision was to develop an inexpensive training simulation in a functional operating room (in situ) that included surgical trainees and nursing and anesthesia staff to focus on effective interprofessional communication and teamwork skills. METHODS: The simulation scenario revolved around an airway obstruction by residual tumor after pneumonectomy. This model included our thoracic operating room with patient status displayed by an open access vital sign simulator and a reversibly modified Laerdal airway mannequin (Shavanger, Norway). The simulation scenario was run seven times. Simulations were video recorded and scored with the use of Non-Technical Skills for Surgeons (NOTSS) and TeamSTEPPS2. Latent safety threats (LSTs) and feedback were obtained during the debriefing after the simulation. Feedback was captured with the Method Material Member Overall (MMMO) questionnaire. RESULTS: Several LSTs were identified, which included missing and redundant equipment and knowledge gaps in participants' roles. Consultant surgeons received a higher overall score than thoracic surgery fellows on both NOTSS (3.8 versus 3.3) and TeamSTEPPS2 (4.1 versus 3.2) evaluations, suggesting that the scenario effectively differentiated learners from experts with regards to nontechnical skills. The MMMO overall simulation experience score was 4.7 of 5, confirming a high-fidelity model and useful experiential learning model. At the Canadian Thoracic Bootcamp, the MMMO overall experience score was 4.8 of 5, further supporting this simulation as a robust model. CONCLUSIONS: An inexpensive in situ intraoperative crisis simulation model for thoracic surgical emergencies was created, implemented, and demonstrated to be effective as a proof of concept at identifying latent threats to patient safety and differentiating the nontechnical skills of trainees and consultant surgeons.

RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy.

BACKGROUND AND OBJECTIVES: Pneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy. METHODS: Retrospective cohort study of consecutive pneumonectomies undertaken at a tertiary hospital (2003-2013). Multivariable logistic regression was performed to adjust for confounding factors. RESULTS: ARDS and respiratory failure occurred in 12.4% (n = 20) and 19.2% (n = 31) of 161 pneumonectomy patients, respectively, and were more likely to occur in transfused patients (P = 0.03, P < 0.001). pRBCs, FFP and platelets were transfused in 27% (n = 43), 6% (n = 9), and 2% (n = 3), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBC use was the only independent predictor of ARDS with odds ratio (OR) = 1.23 (95%CI:1.08-1.39, P = 0.002) and OR = 2.45 (95%CI:1.10-5.49, P = 0.03), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBCs were the only independent predictor of respiratory failure with OR = 1.37 (95%CI:1.16-1.60, P < 0.001) and OR = 3.17 (95%CI:1.25-8.02, P = 0.02), respectively. CONCLUSIONS: Peri-operative pRBC use appears to be an independent risk factor for ARDS and respiratory failure after pneumonectomy. There is a significant dose-response relationship. Platelets and FFP did not appear to increase ARDS risk but this may be due to low utilization.

Short report: interim safety results for a phase II trial measuring the integration of stereotactic ablative radiotherapy (SABR) plus surgery for early stage non-small cell lung cancer (MISSILE-NSCLC).

A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR) before surgery improves oncologic outcomes in patients with stage I non-small cell lung cancer (NSCLC). We report a mandated interim safety analysis for the first 10 patients who completed protocol treatment. Operable patients with biopsy-proven T1-2 N0 NSCLC were eligible. SABR was delivered using a risk-adapted fractionation (54Gy/3 fractions, 55/5 or 60/8). Surgical resection was planned 10 weeks later at a high-volume center (>200 lung cancer resections annually). Patients were imaged with dynamic positron emission tomography-computed tomography scans using 18F-fludeoxyglucose (18F-FDG-PET CT) and dynamic contrast-enhanced CT before SABR and again before surgery. Toxicity was recorded using CTCAE version 4.0. Twelve patients were enrolled between 09/2014 and 09/2015. Two did not undergo surgery, due to patient or surgeon preference; neither patient has developed toxicity or recurrence. For the 10 patients completing both treatments, median age was 70 (range: 54-76), 60% had T1 disease, and 60% had adenocarcinoma. Median FEV1 was 73% predicted (range: 54-87%). Median time to surgery post-SABR was 10.1 weeks (range: 9.3-15.6 weeks). Surgery consisted of lobectomy (n = 8) or wedge resection (n = 2). Median follow-up post-SABR was 6.3 months. After combined treatment, the rate of acute grade 3-4 toxicity was 10%. There was no post-operative mortality at 90 days. The small sample size included herein precludes any definitive conclusions regarding overall toxicity rates until larger datasets are available. However, these data may inform others who are designing or conducting similar trials. TRIAL REGISTRATION: NCT02136355 . Registered 8 May 2014.

Bidirectional Control of Generalized Epilepsy Networks via Rapid Real-Time Switching of Firing Mode.

Thalamic relay neurons have well-characterized dual firing modes: bursting and tonic spiking. Studies in brain slices have led to a model in which rhythmic synchronized spiking (phasic firing) in a population of relay neurons leads to hyper-synchronous oscillatory cortico-thalamo-cortical rhythms that result in absence seizures. This model suggests that blocking thalamocortical phasic firing would treat absence seizures. However, recent in vivo studies in anesthetized animals have questioned this simple model. Here we resolve this issue by developing a real-time, mode-switching approach to drive thalamocortical neurons into or out of a phasic firing mode in two freely behaving genetic rodent models of absence epilepsy. Toggling between phasic and tonic firing in thalamocortical neurons launched and aborted absence seizures, respectively. Thus, a synchronous thalamocortical phasic firing state is required for absence seizures, and switching to tonic firing rapidly halts absences. This approach should be useful for modulating other networks that have mode-dependent behaviors.

Identifying Primary Spontaneous Pneumothorax from Administrative Databases: A Validation Study.

Introduction. Primary spontaneous pneumothorax (PSP) is a disorder commonly encountered in healthy young individuals. There is no differentiation between PSP and secondary pneumothorax (SP) in the current version of the International Classification of Diseases (ICD-10). This complicates the conduct of epidemiological studies on the subject. Objective. To validate the accuracy of an algorithm that identifies cases of PSP from administrative databases. Methods. The charts of 150 patients who consulted the emergency room (ER) with a recorded main diagnosis of pneumothorax were reviewed to define the type of pneumothorax that occurred. The corresponding hospital administrative data collected during previous hospitalizations and ER visits were processed through the proposed algorithm. The results were compared over two different age groups. Results. There were 144 cases of pneumothorax correctly coded (96%). The results obtained from the PSP algorithm demonstrated a significantly higher sensitivity (97% versus 81%, p = 0.038) and positive predictive value (87% versus 46%, p < 0.001) in patients under 40 years of age than in older patients. Conclusions. The proposed algorithm is adequate to identify cases of PSP from administrative databases in the age group classically associated with the disease. This makes possible its utilization in large population-based studies.

Is it safe to wait? The effect of surgical wait time on survival in patients with non-small cell lung cancer.

BACKGROUND: The effect of surgical wait times on survival in patients with non-small cell lung cancer (NSCLC) remains largely unknown. Our objective was to determine the effect of surgical wait time on survival and incidence of upstaging in patients with stage I and II NSCLC. METHODS: All patients with clinical stage I and II NSCLC who underwent surgical resection in a single centre between January 2010 and December 2011 were reviewed. Analysis was stratified based on preoperative clinical stage. We assessed the effect of wait time on survival using a Cox proportional hazard model with wait time in months as a categorical variable. Incidence of upstaging at least 1 stage was assessed using logistic regression. RESULTS: We identified 222 patients: 180 were stage I and 42 were stage II. For stage I, wait times up to 4 months had no significant effect on survival or incidence of upstaging. For stage II, patients waiting between 2 and 3 months had significantly decreased survival (hazard ratio 3.6, p = 0.036) and increased incidence of upstaging (odds ratio 2.0, p = 0.020) than those waiting 0 to 1 month. For those waiting between 1 and 2 months, there was no significant difference in survival or upstaging. CONCLUSION: We did not identify an effect of wait time up to 4 months on survival or upstaging for patients with stage I NSCLC. For patients with stage II disease, wait times greater than 2 months adversely affected survival and upstaging.

CONTEXTE: En chirurgie, l'effet des temps d'attente sur la survie des patients atteints d'un cancer du poumon non à petites cellules (CPNPC) demeure pour une bonne part inconnu. Notre objectif était de déterminer l'effet des temps d'attente sur la survie et sur l'incidence de la restadification à un niveau plus élevé chez les patients atteints d'un CPNPC de stade I et II. MÉTHODES: Tous les patients présentant un CPNPC clinique de stade I et II ayant subi une résection chirurgicale dans un seul centre entre janvier 2010 et décembre 2011 ont été passés en revue. L'analyse a été stratifiée selon le stade clinique préopératoire. Nous avons évalué l'effet des temps d'attente sur la survie à l'aide d'un modèle de risques proportionnels de Cox, les temps d'attente en mois ayant servi de variable catégorielle. L'incidence de la restadification à la hausse d'au moins un stade a été évaluée par régression logistique. RÉSULTATS: Nous avons recensé 222 patients : 180 de stade I et 42 de stade II. Pour le stade I, les temps d'attente allant jusqu'à 4 mois n'ont eu aucun effet significatif sur la survie ou sur l'incidence de la restadification. Pour les stades II, les patients ayant attendu de 2 à trois 3 mois ont présenté une réduction significative de la survie (risque relatif 3,6, p = 0,036) et une incidence accrue de restadification (rapport des cotes 2,0, p = 0,02) comparativement à ceux qui avaient attendu 1 mois et moins. Chez les patients ayant attendu 1 ou 2 mois, on n'a noté aucune différence significative sur la survie ou la restadification. CONCLUSION: Nous n'avons observé aucun effet d'une attente allant jusqu'à 4 mois sur la survie ou la restadification chez les patients atteints d'un CPNPC de stade I. Pour les patients atteints d'une maladie de stade II, les temps d'attente de plus de 2 mois ont eu un impact négatif sur la survie et la restadification.

Repair of complete longitudinal esophageal rupture with preservation of esophageal motility.

There is no consensus on the ideal treatment for esophageal perforation and on the maximal extent of esophageal disruption amenable to primary repair. The effect of extensive esophageal injury on postoperative esophageal motility is also unknown. We report the case of a longitudinal iatrogenic esophageal laceration extending from the hypopharynx to the cardia in a morbidly obese patient treated with primary repair. The patient exhibited no postoperative esophageal leak or stricture and maintained a preserved esophageal peristalsis on manometry at 3 months. An extensively lacerated esophagus can be repaired primarily while maintaining a normal postoperative function.

Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597.

PURPOSE: Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. PATIENTS AND METHODS: Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 µg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. RESULTS: The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. CONCLUSION: Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

Feasibility and effectiveness of a home-based exercise training program before lung resection surgery.

BACKGROUND: Patients with lung cancer often experience a reduction in exercise tolerance, muscle weakness and decreased quality of life. Although the effectiveness of pulmonary rehabilitation programs is well recognized in other forms of cancers and in many pulmonary diseases, few researchers have studied its impact in patients with lung cancer, particularly in those awaiting lung resection surgery (LRS). OBJECTIVES: To investigate the feasibility of a short, home-based exercise training program (HBETP) with patients under investigation for non-small cell lung cancer and potential candidates for LRS, and to determine the effectiveness of this program on exercise tolerance, skeletal muscle strength and quality of life. METHODS: Sixteen patients with lung cancer awaiting LRS participated in a four-week HBETP including moderate aerobic activities (walking and cycling) and muscle training performed three times weekly. Before and after the intervention, a cardiopulmonary exercise test, a 6 min walk test and the assessment of muscle strength and quality of life were performed. RESULTS: Thirteen patients completed the four-week HBETP and all the patients completed >75% of the prescribed exercise sessions. The duration of the cycle endurance test (264±79 s versus 421±241 s; P<0.05) and the 6 min walk test distance (540±98 m versus 568±101 m; P<0.05) were significantly improved. Moreover, the strength of the deltoid, triceps and hamstrings were significantly improved (∆ post-pre training 1.82±2.83 kg, 1.32±1.75 kg and 3.41±3.7 kg; P<0.05, respectively). CONCLUSION: In patients with lung cancer awaiting LRS, HBETP was feasible and improved exercise tolerance and muscle strength. This may be clinically relevant because poor exercise capacity and muscle weakness are predictors of postoperative complications.

Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury.

Cerebrocortical injuries such as stroke are a major source of disability. Maladaptive consequences can result from post-injury local reorganization of cortical circuits. For example, epilepsy is a common sequela of cortical stroke, but the mechanisms responsible for seizures following cortical injuries remain unknown. In addition to local reorganization, long-range, extra-cortical connections might be critical for seizure maintenance. In rats, we found that the thalamus, a structure that is remote from, but connected to, the injured cortex, was required to maintain cortical seizures. Thalamocortical neurons connected to the injured epileptic cortex underwent changes in HCN channel expression and became hyperexcitable. Targeting these neurons with a closed-loop optogenetic strategy revealed that reducing their activity in real-time was sufficient to immediately interrupt electrographic and behavioral seizures. This approach is of therapeutic interest for intractable epilepsy, as it spares cortical function between seizures, in contrast with existing treatments, such as surgical lesioning or drugs.

Surgical site infections following transcatheter apical aortic valve implantation: incidence and management.

OBJECTIVE: The present study was undertaken to examine the incidence and management of surgical site infection (SSI) in patients submitted to transapical transcatheter aortic valve implantation (TA-TAVI). METHODS: From April 2007 to December 2011, 154 patients underwent TA-TAVI with an Edwards Sapien bioprosthesis (ES) at the Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ) as part of a multidisciplinary program to prospectively evaluate percutaneous aortic valve implantation. Patient demographics, perioperative variables, and postoperative complications were recorded in a prospective registry. RESULTS: Five (3.2%) patients in the cohort presented with an SSI during the study period. The infections were all hospital-acquired (HAI) and were considered as organ/space SSI's based on Center for Disease Control criteria (CDC). Within the first few weeks of the initial procedure, these patients presented with an abscess or chronic draining sinus in the left thoracotomy incision and were re-operated. The infection spread to the apex of the left ventricle in all cases where pledgeted mattress sutures could be seen during debridement. Patients received multiple antibiotic regimens without success until the wound was surgically debrided and covered with viable tissue. The greater omentum was used in three patients and the pectoralis major muscle in the other two. None of the patients died or had a recurrent infection. Three of the patients were infected with Staphylococcus epidermidis, one with Staphylococcus aureus, and one with Enterobacter cloacae. Patients with surgical site infections were significantly more obese with higher BMI (31.4±3.1 vs 26.2±4.4 p=0.0099) than the other patients in the cohort. CONCLUSIONS: While TA-TAVI is a minimally invasive technique, SSIs, which are associated with obesity, remain a concern. Debridement and rib resection followed by wound coverage with the greater omentum and/or the pectoralis major muscle were used successfully in these patients.

Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis.

OBJECTIVES: To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. METHODS: We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. RESULTS: Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). CONCLUSIONS: Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

Anatomy and physiology of the thoracic lymphatic system.

The thoracic lymphatic system is one of the most complex and poorly understood systems of the human body, and much is still to be learned, especially in lymphatic physiology. Knowledge of the normal anatomy of this system as well as of its variations is nevertheless important for thoracic surgeons investigating and treating patients with lung or esophageal neoplasms.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo.

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

Prophylactic irradiation of intervention sites in malignant pleural mesothelioma.

BACKGROUND AND PURPOSE: To assess the effectiveness of prophylactic irradiation of intervention track (PIT) to prevent tumor seeding in patients with malignant pleural mesothelioma. MATERIALS AND METHODS: A retrospective review was conducted of 171 patients with a histological diagnosis of pleural mesothelioma with some undergoing prophylactic irradiation of intervention sites. RESULTS: Forty-eight patients (28%) received PIT. A majority of patients were followed until death. Thoracoscopy (88%) was the procedure most often performed. Thirty-three percent of patients received chemotherapy. The median dose of PIT was 21 Gy in 3 fractions with electrons or 6 MV photons. The local progression free survival (LPFS) at the intervention site was significantly higher in the PIT group and was not influenced by chemotherapy. At 6 months, LPFS for the intervention sites was 91% with PIT and 74% without PIT (p=0.002). During the follow-up, 6 patients (13%) in the PIT group had tumor invasion of the subcutaneous tissue compared to 40 patients (33%) in the group without PIT (p=0.008). CONCLUSIONS: This study suggests that PIT in mesothelioma reduces the incidence of procedure tract metastasis. Finally, chemotherapy does not seem to have an influence on the incidence of tract metastasis.

Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD.

BACKGROUND: Factors involved in the regulation of muscle mass in chronic obstructive pulmonary disease (COPD) are still poorly understood. Comparing the signalisation involved in muscle mass regulation between two muscles with different levels of activation within the same subjects is an interesting strategy to tease out the impact of local (muscle activity) versus systemic factors in the regulation of muscle mass. A study was undertaken to measure and compare the protein levels of p-AKT, AKT, Atrogin-1, p-p70S6K, p-4E-BP1, p-GSK3ß as well as the mRNA expression of Atrogin-1, MuRF1 and FoxO-1 in the quadriceps and the diaphragm of 12 patients with COPD and 7 controls with normal lung function. METHODS: Diaphragm biopsies were obtained during thoracic surgery and quadriceps samples were obtained from needle biopsies. Protein content and mRNA expression were measured by western blot and quantitative PCR, respectively. RESULTS: Increased mRNA expressions of Atrogin-1, MuRF1 and FoxO-1 were found in the quadriceps compared with the diaphragm only in patients with COPD. The quadriceps/diaphragm ratio for MuRF1 was higher in COPD. The protein level of p-p70S6K was decreased in the quadriceps compared with the diaphragm in patients with COPD. The quadriceps/diaphragm ratios of p-p70S6K and p-GSK3ß were lower in patients with COPD than in controls. CONCLUSIONS: These results indicate a greater susceptibility to a catabolic/anabolic imbalance favouring muscle atrophy in the quadriceps compared with the diaphragm in patients with COPD. The balance between the atrophy and hypertrophy signalling is inhomogeneous between respiratory and lower limb muscles, suggesting that local factors are likely to be involved in the regulation of muscle mass in COPD.

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics.

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.