A novel clip-on device for electromagnetic tracking in endobronchial ultrasound bronchoscopy.

INTRODUCTION: The established method for assessment of mediastinal and hilar lymph nodes is endobronchial ultrasound bronchoscopy (EBUS) with needle aspirations. Previously, we presented an electromagnetic navigation platform for this purpose. There were several issues with the permanent electromagnetic tracking (EMT) sensor attachment on the tip of the experimental EBUS bronchoscope. The purpose was to develop a device for on-site attachment of the EMT sensor. MATERIAL AND METHODS: A clip-on EMT sensor attachment device was 3D-printed in Ultem™ and attached to an EBUS bronchoscope. A specially designed ultrasound probe calibration adapter was developed for on-site and quick probe calibration. Navigation accuracy was studied using a wire cross water phantom and clinical feasibility was tested in a healthy volunteer. RESULTS: The device attached to the EBUS bronchoscope increased its diameter from 6.9 mm to 9.5 mm. Average preclinical navigation accuracy was 3.9 mm after adapter calibration. The maneuvering of the bronchoscope examining a healthy volunteer was adequate without harming the respiratory epithelium, and the device stayed firmly attached. CONCLUSION: Development, calibration and testing of a clip-on EMT sensor attachment device for EBUS bronchoscopy was successfully demonstrated. Acceptable accuracy results were obtained, and the device is ready to be tested in patient studies.

Reasons for prolonged time for diagnostic workup for stage I-II lung cancer and estimated effect of applying an optimized pathway for diagnostic procedures.

BACKGROUND: Minimizing the time until start of cancer treatment is a political goal. In Norway, the target time for lung cancer is 42 days. The aim of this study was to identify reasons for delays and estimate the effect on the timelines when applying an optimal diagnostic pathway. METHODS: Retrospective review of medical records of lung cancer patients, with stage I-II at baseline CT, receiving curative treatment (n = 100) at a regional cancer center in Norway. RESULTS: Only 40% started treatment within 42 days. The most important delays were late referral to PET CT (n = 27) and exercise test (n = 16); repeated diagnostic procedures because bronchoscopy failed (n = 15); and need for further investigations after PET CT (n = 11). The time from referral to PET CT until the final report was 20.5 days in median. Applying current waiting time for PET CT (≤7 days), 48% would have started treatment within 42 days (p = 0.254). "Optimal pathway" was defined as 1) referral to PET CT and exercise test immediately after the CT scan and hospital visit, 2) tumor board discussion to decide diagnostic strategy and treatment, 3) referral to surgery or curative radiotherapy, 4) tissue sampling while waiting to start treatment. Applying the optimal pathway, current waiting time for PET CT and observed waiting times for the other procedures, 80% of patients could have started treatment within 42 days (p < 0.001), and the number of tissue sampling procedures could have been reduced from 112 to 92 (- 16%). CONCLUSION: Changing the sequence of investigations would significantly reduce the time until start of treatment in curative lung cancer patients at our hospital and reduce the resources needed.

Pulmonologist evaluation on new CT visualization for guidance to lung lesions during bronchoscopy.

OBJECTIVE: Endoluminal visualization in virtual and video bronchoscopy lacks information about the surrounding structures, and the traditional 2 D axial, coronal and sagittal CT views can be difficult to interpret. To address this challenge, we previously introduced a novel visualization technique, Anchored to Centerline Curved Surface, for navigated bronchoscopy. The current study compares the ACCuSurf to the standard ACS CT views as planning and guiding tools in a phantom study. MATERIAL AND METHODS: Bronchoscope operators navigated in physical phantom guided by virtual realistic image data constructed by fusion of CT dataset of phantom and anonymized patient CT data. We marked four different target positions within the virtual image data and gave 12 pulmonologists the task to navigate, with either ACCuSurf or ACS as guidance, to the corresponding targets in the physical phantom. RESULTS: Using ACCuSurf reduced the planning time and increased the grade of successful navigation significantly compared to ACS. CONCLUSION: The phantom setup with virtual patient image data proved realistic according to the pulmonologists. ACCuSurf proved superior to ACS regarding planning time and navigation success grading. Improvements on visualisation or display techniques may consequently improve both planning and navigated bronchoscopy and thus contribute to more precise lung diagnostics.

A new visualization method for navigated bronchoscopy.

OBJECTIVE: In flexible endoscopy techniques, such as bronchoscopy, there is often a challenge visualizing the path from start to target based on preoperative data and accessing these during the procedure. An example of this is visualizing only the inside of central airways in bronchoscopy. Virtual bronchoscopy (VB) does not meet the pulmonologist's need to detect, define and sample the frequent targets outside the bronchial wall. Our aim was to develop and study a new visualization technique for navigated bronchoscopy. MATERIAL AND METHODS: We extracted the shortest possible path from the top of the trachea to the target along the airway centerline and a corresponding auxiliary route in the opposite lung. A surface structure between the centerlines was developed and displayed. The new technique was tested on non-selective CT data from eight patients using artificial lung targets. RESULTS: The new display technique anchored to centerline curved surface (ACCuSurf) made it easy to detect and interpret anatomical features, targets and neighboring anatomy outside the airways, in all eight patients. CONCLUSIONS: ACCuSurf can simplify planning and performing navigated bronchoscopy, meets the challenge of improving orientation and register the direction of the moving endoscope, thus creating an optimal visualization for navigated bronchoscopy.

Measurement of health-related quality of life during chemotherapy - the importance of timing.

BACKGROUND: Side effects of chemotherapy may occur at different time-points in the treatment cycle, and the exact assessment time relative to chemotherapy may affect HRQoL scores. The current study examined the variation of HRQoL during chemotherapy cycles, and whether differences in HRQoL scores varied at selected time-points between patients allocated to two different chemotherapy regimens. MATERIAL AND METHODS: Patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) were randomly assigned to receive three cycles of carboplatin plus vinorelbine (VC) or gemcitabine (GC) every 3 weeks. HRQoL was reported on the EORTC QLQ-C30 and LC13 on days 1, 4, 8, 11 and 15 of every cycle. Global health status, nausea/vomiting, fatigue and dyspnea (LC13) were defined as the HRQoL scales of primary interest. RESULTS: Fifty-two patients were enrolled. Variation of mean scores of global health status, nausea/vomiting and fatigue showed a consistent pattern during chemotherapy. Day 4 appeared to be the time-point when chemotherapy influenced HRQoL the most. The differences in mean HRQoL scores between the two treatment arms varied at the different time-points, especially for nausea/vomiting. CONCLUSION: There was a clinically relevant variation of HRQoL during chemotherapy cycles, with increased symptom burden the first week following treatment. Our results suggest that timing of HRQoL assessment can influence the chances of detecting differences between the treatment regimens.

Medical complexity and time to lung cancer treatment - a three-year retrospective chart review.

BACKGROUND: The time from a referral for suspected lung cancer is received at a hospital until treatment start has been defined as a quality indicator. Current Norwegian recommendation is that ≥70% should start surgery or radiotherapy within 42 calendar days and systemic therapy within 35 days. However, delays can occur due to medical complexity. The aim of this study was to quantify the proportion of patients who started treatment within the recommended timeframes; and to assess the proportion of non-complex patients for which there were no good reasons for delays. METHODS: We performed a retrospective chart review of all patients diagnosed with lung cancer at a university hospital during 2011-2013. We defined "non-complex" patients as those who underwent ≤1 tissue diagnostic procedure and had no delays due to comorbidity, intercurrent disease or complications to diagnostic procedures ("Medical delays") of more than three days. RESULTS: Four hundred forty-nine cases were analyzed; 142 (32%) had >1 tissue diagnostic procedures; 67 (15%) had medical delays >3 days; 262 (58%) were non-complex and 363 (81%) received treatment for lung cancer. Median number of days until surgery or radiotherapy was 48 (overall) and 41 (non-complex patients). The proportions who started surgery or radiotherapy within 42 days were 41% (overall) and 56% (non-complex). Corresponding numbers for systemic therapy were 29 days (overall) and 25 days (non-complex), and 64% (overall) and 80% (non-complex). CONCLUSION: Fewer lung cancer patients than desired started treatment within the recommended timeframes. Even among the least complex patients, too few patients received timely treatment. The reasons need to be identified and understood, and changes in the organization appear to be necessary in order to offer timely treatment to more patients.

Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer.

BACKGROUND: Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy. PATIENTS AND METHODS: In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy. RESULTS: In total 35 patients, 48% women, mean age 67 years (range 56-86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% -7.3--1.9; p<0.002), corresponding to a 1.4 kg loss of whole body muscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p=0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p=0.073). Stage of disease (p=0.003), treatment regimen (p=0.023), response to chemotherapy (p=0.007) and SMCA change (p=0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses. CONCLUSION: Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor.

Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer.

BACKGROUND: On the basis of our own experience and literature search, we hypothesised that a canine olfactory test may be useful for detecting lung cancer in an unselected population of patients suspected to have lung cancer. MATERIAL AND METHODS: We conducted a prospective study of 93 patients consecutively admitted to hospital with suspected lung cancer. Exhaled breath and urine were sampled before the patients underwent bronchoscopy. The canine olfactory test was performed in a double-blinded manner. Sensitivity and specificity were outcome measures. RESULTS: With 99% sensitivity, the olfactory test demonstrated that dogs have the ability to distinguish cancer patients from healthy individuals. With an intensified training procedure, the exhaled breath and urine tests showed sensitivity rates of 56-76% and specificity rates of 8.3-33.3%, respectively, in our heterogeneous study population. CONCLUSION: Although the olfactory test appears to be a promising tool for the detection of cancer, the main challenge is to determine whether the test can sufficiently discriminate between patients at risk, patients with benign disease, and patients with malignant disease. We need to gain a deeper understanding of this test and further refine it before applying it as a screening tool for lung cancer in clinical settings.

[Occupational lung cancer in Sør-Trøndelag county]. / Arbeidsbetinget lungekreft i Sør-Trøndelag.

BACKGROUND: Lung cancer can be caused by occupational exposure. This is not always recognised or reported, and not all patients receive the benefits to which they are entitled. MATERIAL AND METHOD: We collected occupational case histories for patients from Sør-Trøndelag county with a first-time diagnosis of lung cancer. The number of reported cases of occupationally related lung cancer was collected from the Norwegian Labour Inspection Authority, and information on approval of occupational illness was collected from the Norwegian Labour and Welfare Authority (NAV). RESULTS: 105 patients with lung cancer took part in the study, 73 men and 32 women. Among the men, altogether 12 cases (16%) were assessed as likely and 16 (22%) as possibly occupationally related. Among the women, none of the cases were assessed as occupationally related. The reporting frequency from the health regions to the Norwegian Labour Inspection Authority varied from 1.7% to 5.1%. Altogether 9 out of 11 likely cases and 5 out of 12 possible cases of occupationally related lung cancer were granted injury compensation by the Norwegian Labour and Welfare Authority. INTERPRETATION: In this study, we found that approximately 20% of the cases of lung cancer in men are occupationally related, and that the underreporting of occupationally related lung cancer appears to be considerable. The obligation of doctors to report to the Norwegian Labour Inspection Authority should be made better known. Most likely, more patients would have had their lung cancer verified as an occupational illness and could have received injury compensation if they had been aware of the opportunity to apply for this.

Accuracy of electromagnetic tracking with a prototype field generator in an interventional OR setting.

PURPOSE: The authors have studied the accuracy and robustness of a prototype electromagnetic window field generator (WFG) in an interventional radiology suite with a robotic C-arm. The overall purpose is the development of guidance systems combining real-time imaging with tracking of flexible instruments for bronchoscopy, laparoscopic ultrasound, endoluminal surgery, endovascular therapy, and spinal surgery. METHODS: The WFG has a torus shape, which facilitates x-ray imaging through its centre. The authors compared the performance of the WFG to that of a standard field generator (SFG) under the influence of the C-arm. Both accuracy and robustness measurements were performed with the C-arm in different positions and poses. RESULTS: The system was deemed robust for both field generators, but the accuracy was notably influenced as the C-arm was moved into the electromagnetic field. The SFG provided a smaller root-mean-square position error but was more influenced by the C-arm than the WFG. The WFG also produced smaller maximum and variance of the error. CONCLUSIONS: Electromagnetic (EM) tracking with the new WFG during C-arm based fluoroscopy guidance seems to be a step forward, and with a correction scheme implemented it should be feasible.

A novel research platform for electromagnetic navigated bronchoscopy using cone beam CT imaging and an animal model.

Electromagnetic guided bronchoscopy is a new field of research, essential for the development of advanced investigation of the airways and lung tissue. Consecutive problem-based solutions and refinements are urgent requisites to achieve improvements. For that purpose, our intention is to build a complete research platform for electromagnetic guided bronchoscopy. The experimental interventional electromagnetic field tracking system in conjunction with a C-arm cone beam CT unit is presented in this paper. The animal model and the navigation platform performed well and the aims were achieved; the 3D localization of foreign bodies and their navigated and tracked removal, assessment of tracking accuracy that showed a high level of precision, and assessment of image quality. The platform may prove to be a suitable platform for further research and development and a full-fledged electromagnetic guided bronchoscopy navigation system. The inclusion of the C-arm cone beam CT unit in the experimental setup adds a number of new possibilities for diagnostic procedures and accuracy measurements. Among other future challenges that need to be solved are the interaction between the C-arm and the electromagnetic navigation field, as we demonstrate in this feasibility study.

Associations Between Time to Treatment Start and Survival in Patients With Lung Cancer.

BACKGROUND: Time-to-treatment is defined as a quality indicator for cancer care but is not well documented. We investigated whether meeting Norwegian timeframes of 35/42 days from referral until start of chemotherapy or surgery/radiotherapy for lung cancer was associated with survival. PATIENTS AND METHODS: The medical records of 439 lung cancer patients at a regional cancer center were reviewed and categorized according to treatment: (i) surgery; ii) radical radiotherapy; iii) stereotactic radiotherapy; iv) palliative treatment, no cancer symptoms; v) palliative treatment with severe cancer symptoms). RESULTS: Proportions receiving timely treatment varied significantly at 39%, 48%, 10%, 44% and 89%, respectively (p<0.001). Overall, those starting treatment on time had the shortest median overall survival (10.6 vs. 22.6 months; p<0.001). This was also the case for palliative (5.3 vs. 11.4 months) (p<0.001) but not for curative treatment (not reached vs. 38.3 months) (p=0.038). CONCLUSION: Timely treatment is not necessarily associated with improved survival.

A prospective phase II study: high-dose pemetrexed as second-line chemotherapy in small-cell lung cancer.

PURPOSE: To investigate the efficacy and tolerability of high-dose pemetrexed as second-line chemotherapy in small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with verified SCLC who had received one prior chemotherapy regimen, aged 18-75 years, WHO Performance Status 0-2, no clinical signs of brain metastases and measurable disease were eligible. Patients received pemetrexed 900 mg/m(2) IV every 3 weeks. Four courses were planned for all patients. Patients with relapse later than 3 months since last course of first-line chemotherapy were defined as "sensitive", those with relapse within 3 months as "refractory". Toxicity was graded using the CTCAE v3.0. RESULTS: 36 patients were accrued, 34 received study treatment. Median age was 61 (range 43-74), 18 (53%) males and 16 (47%) females. Mean number of courses administered was 2.5. One patient (3%) had partial response, three (9%) had stable disease and 29 (85%) progressed. One patient (3%) was not evaluable for response. Median TTP (n=33) was 7.7 weeks ("sensitive": 8.4 weeks, "refractory": 5.1 weeks). Median OS (n=34) was 17.6 weeks ("sensitive": 22.6 weeks, "refractory": 15.3 weeks). Of grade 3-4 haematological toxicity, anemia was observed in 2 (6%) patients, leukopenia in 6 (18%), granulocytopenia in 9 (27%) and thrombocytopenia in 3 (9%). Febrile neutropenia occurred in 6 (18%) patients. There were no treatment related deaths. CONCLUSION: High-dose pemetrexed monotherapy to patients with recurrent SCLC yielded moderate toxicity, but limited treatment efficacy.

Using the CustusX toolkit to create an image guided bronchoscopy application: Fraxinus.

PURPOSE: The aim of this paper is to show how a specialized planning and guidance application called Fraxinus, can be built on top of the CustusX platform (www.custusx.org), which is an open source image-guided intervention software platform. Fraxinus has been customized to meet the clinical needs in navigated bronchoscopy. METHODS: The application requirements for Fraxinus were defined in close collaboration between research scientists, software developers and clinicians (pulmonologists), and built on top of CustusX. Its superbuild system downloads specific versions of the required libraries and builds them for the application in question, including the selected plugins. New functionality is easily added through the plugin framework. The build process enables the creation of specialized applications, adding additional documentation and custom configurations. The toolkit's libraries offer building blocks for image-guided applications. An iterative development process was applied, where the clinicians would test and provide feedback during the entire process. RESULTS: Fraxinus has been developed and is released as an open source planning and guidance application built on top of CustusX. It is highly specialized for bronchoscopy. The proposed workflow is adapted to the different steps in this procedure. The user interface of CustusX has been modified to enhance information, quality assurance and user friendliness with the intention to increase the overall yield for the patient. As the workflow of the procedure is relatively constant, some actions are predicted and automatically performed by the application, according to the requirements from the clinicians. CONCLUSIONS: The CustusX platform facilitates development of new and specialized applications. The toolkit supports the process and makes important extension and injection points available for customization.

Learning endobronchial ultrasound transbronchial needle aspiration - a 6-year experience at a single institution.

INTRODUCTION: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has become an important diagnostic tool for the pulmonologist. Learning this procedure and maintaining technical skills requires continuous practice and evaluation. OBJECTIVES: The aims of the study were a retrospective evaluation of the diagnostic quality of the EBUS-technique and the learning profile of the endoscopy team during the first years (2007-2013) of experience in an unselected population. METHODS: EBUS-TBNA procedures were analysed for clinical data, including results from surgery or clinical/radiological follow-up for at least 6 months. Rapid on-site cytological evaluation (ROSE) was introduced on regular basis the forth year. RESULTS: A total of 711 EBUS-TBNA from 635 patients were included. The percentage of representative EBUS-TBNA initially decreased the first years (minimum 60,9%), before increased to a final result of 82,4%. There was a lower proportion of representative EBUS-TBNA in the benign group (76,8%) vs the malignant group (85,8%). A significant increase in the proportion of representative EBUS-TBNA was seen after ROSE had been introduced. The major indications were diagnosing/staging of lung cancer (54%) and mediastinal lymphadenopathy of unknown cause (25,7%). The sensitivity detecting malignancy was 94,9%, negative predictive value 81,2% and diagnostic accuracy 95,8%. During the study period the percentage of re-examinations with EBUS-TBNA declined from 18,0% to 8,2%. CONCLUSION: After an initial run-in period with declining results, the overall diagnostic yield of EBUS-TBNA increased and reached acceptable levels. These results underline the importance of continuously evaluation of our own results when new methods are implemented in clinical practice.

A multimodal image guiding system for Navigated Ultrasound Bronchoscopy (EBUS): A human feasibility study.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is the endoscopic method of choice for confirming lung cancer metastasis to mediastinal lymph nodes. Precision is crucial for correct staging and clinical decision-making. Navigation and multimodal imaging can potentially improve EBUS-TBNA efficiency. AIMS: To demonstrate the feasibility of a multimodal image guiding system using electromagnetic navigation for ultrasound bronchoschopy in humans. METHODS: Four patients referred for lung cancer diagnosis and staging with EBUS-TBNA were enrolled in the study. Target lymph nodes were predefined from the preoperative computed tomography (CT) images. A prototype convex probe ultrasound bronchoscope with an attached sensor for position tracking was used for EBUS-TBNA. Electromagnetic tracking of the ultrasound bronchoscope and ultrasound images allowed fusion of preoperative CT and intraoperative ultrasound in the navigation software. Navigated EBUS-TBNA was used to guide target lymph node localization and sampling. Navigation system accuracy was calculated, measured by the deviation between lymph node position in ultrasound and CT in three planes. Procedure time, diagnostic yield and adverse events were recorded. RESULTS: Preoperative CT and real-time ultrasound images were successfully fused and displayed in the navigation software during the procedures. Overall navigation accuracy (11 measurements) was 10.0 ± 3.8 mm, maximum 17.6 mm, minimum 4.5 mm. An adequate sample was obtained in 6/6 (100%) of targeted lymph nodes. No adverse events were registered. CONCLUSIONS: Electromagnetic navigated EBUS-TBNA was feasible, safe and easy in this human pilot study. The clinical usefulness was clearly demonstrated. Fusion of real-time ultrasound, preoperative CT and electromagnetic navigational bronchoscopy provided a controlled guiding to level of target, intraoperative overview and procedure documentation.

Intraoperative localized constrained registration in navigated bronchoscopy.

PURPOSE: One of the major challenges in electromagnetic navigated bronchoscopy is the navigation accuracy. An initial rigid image-to-patient registration may not be optimal for the entire lung volume, as the lung tissue anatomy is likely to have shifted since the time of computer tomography (CT) acquisition. The accuracy of the initial rigid registration will also be affected throughout the procedure by breathing, coughing, patient movement and tissue displacements due to pressure from bronchoscopy tools. A method to minimize the negative impact from these factors by updating the registration locally during the procedure is needed and suggested in this paper. METHODS: The intraoperative local registration method updates the initial registration by optimization in an area of special interest, for example, close to a biopsy position. The local registration was developed through an adaptation of a previously published registration method used for the initial registration of CT to the patient anatomy. The method was tested in an experimental breathing phantom setup, where respiratory movements were induced by a robotic arm. Deformations were also applied to the phantom to see if the local registration could compensate for these. RESULTS: The local registration was successfully applied in all 15 repetitions, five in each of the three parts of the airway phantom. The mean registration accuracy was improved from 11.8-19.4 mm to 4.0-6.7 mm, varying to some degree in the different segments of the airway model. CONCLUSIONS: A local registration method, to update and improve the initial image-to patient registration during navigated bronchoscopy, was developed. The method was successfully tested in a breathing phantom setup. Further development is needed to make the method more automatic. It must also be verified in human studies.

Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling.

The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung cancer patients, were cachexia is prevalent, there was a significant correlation between elevated IL-6 expression in the tumor and poor prognosis of the patients. We found evidence for an autophagy-inducing bioactivity in serum from cancer patients and that this is clearly associated with weight loss. Importantly, the autophagy-inducing bioactivity was reduced by interference with IL-6 trans-signaling. Together, our findings suggest that IL-6 trans-signaling may be targeted in cancer cachexia.

Heparin resistance and increased platelet activation in coronary surgery patients treated with enoxaparin preoperatively.

OBJECTIVE: Patients with unstable coronary disease have changes in the hemostatic system. These patients are often treated with low molecular weight heparin. In patients who are accepted for coronary artery bypass grafting, treatment with low molecular weight heparin is frequently continued until surgery. We hypothesized that in coronary artery bypass grafting, the hypercoagulable state seen in unstable patients persists into the intra- and postoperative phase despite preoperative treatment with low molecular weight heparin. The aim of this study was to explore and describe the perioperative hemostatic process in patients with unstable coronary artery disease undergoing coronary artery bypass grafting. METHODS: Thirty-two patients with unstable coronary disease treated preoperatively with enoxaparin, and 32 stable control patients not treated with enoxaparin, were included. All patients were taking low dose aspirin until the day before surgery. Before cardiopulmonary bypass, all patients were given tranexamic acid as a bolus injection. Blood samples for analysis of platelet counts, international normalized ratio, activated partial thromboplastin time, fibrinogen, protein S, protein C, prothrombin fragment 1 + 2, thrombin-antithrombin complex, antithrombin, plasmin-antiplasmin complex, D-dimer, neutrophil-activating peptide 2, platelet-monocyte complexes, and heparin concentrations were drawn preoperatively, after 30 min on cardiopulmonary bypass, and 30 min, 3 h, and 20 h postoperatively. Heparin was given during cardiopulmonary bypass to maintain an activated clotting time above 480 s. RESULTS: Patients in the enoxaparin group needed more heparin to maintain an activated clotting time above 480 s, and had higher heparin concentrations and lower antithrombin values compared with control patients. Neutrophil-activating peptide 2 concentrations were higher in the enoxaparin group. CONCLUSIONS: Patients treated with enoxaparin before coronary artery bypass grafting showed signs of heparin resistance intraoperatively. Enoxaparin-treated patients also had increased perioperative platelet activation. Reasons for the observed difference in platelet activation remain unclear.

A novel platform for electromagnetic navigated ultrasound bronchoscopy (EBUS).

PURPOSE: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes is essential for lung cancer staging and distinction between curative and palliative treatment. Precise sampling is crucial. Navigation and multimodal imaging may improve the efficiency of EBUS-TBNA. We demonstrate a novel EBUS-TBNA navigation system in a dedicated airway phantom. METHODS: Using a convex probe EBUS bronchoscope (CP-EBUS) with an integrated sensor for electromagnetic (EM) position tracking, we performed navigated CP-EBUS in a phantom. Preoperative computed tomography (CT) and real-time ultrasound (US) images were integrated into a navigation platform for EM navigated bronchoscopy. The coordinates of targets in CT and US volumes were registered in the navigation system, and the position deviation was calculated. RESULTS: The system visualized all tumor models and displayed their fused CT and US images in correct positions in the navigation system. Navigating the EBUS bronchoscope was fast and easy. Mean error observed between US and CT positions for 11 target lesions (37 measurements) was [Formula: see text] mm, maximum error was 5.9 mm. CONCLUSION: The feasibility of our novel navigated CP-EBUS system was successfully demonstrated. An EBUS navigation system is needed to meet future requirements of precise mediastinal lymph node mapping, and provides new opportunities for procedure documentation in EBUS-TBNA.