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• V-Q difference shows classical and reversed mismatches simultaneously. • Saving the ratio with very large values is avoided by using the V-Q difference. • The scaled V-Q difference represents change in lung function. • No masking of artifacts is needed for the scaled V-Q difference images. • Functional difference images could improve the diagnostic value of VQ SPECT. Ventilation Perfusion SPECT is important in the diagnostics of e.g. pulmonary embolism and chronic obstructive pulmonary disease. Classical and reverse mismatched defects can be identified by utilizing the ventilation-perfusion ratio. Unfortunately, this ratio is only linear in the ventilation, the scale is not symmetrical regarding classical and reversed mismatches and small perfusion values give rise to artifacts. The ventilation-perfusion (VQ) difference is developed as an alternative. For both VQ-ratio and VQ-difference a scaling factor for the perfusion is computed, so that voxels with matched ventilation and perfusion (on average) yield zero signal. The relative VQ-difference is calculated by scaling with the summed VQ-signal in each voxel. The scaled VQ-difference is calculated by scaling with the global maximum of this sum. The relative and scaled differences have a scale from −1 (perfusion only) to + 1 (ventilation only). Image quality of relative VQ-difference and VQ-ratio images is hampered by artifacts from areas with both low perfusion and low ventilation. Ratio and differences have been investigated in ten patients and are shown for three patients (one without defects). Clinical thresholds for the difference images are derived resulting in color maps of relevant (reversed) mismatches with a (reciprocal) ratio larger than two. The relative ventilation-perfusion difference is a methodological improvement on the ventilation-perfusion ratio, because it has a symmetrical scale and is bound on a closed domain. A better diagnostic value is expected by utilizing the scaled difference, which represents functional difference instead of relative difference. [ABSTRACT FROM AUTHOR]

Lymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer. Consecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III. 31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p = 0.032) with a mean of 24 LN (range: 12–33 LN in levels Ib-III compared to 18 LN (range: 10–36 LN) in the control group, respectively. NIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics. [ABSTRACT FROM AUTHOR]

Ventilation-perfusion scintigraphy is a functional imaging biomarker that has the potential of captivating the heterogeneity of chronic obstructive pulmonary disease (COPD). It specifically images the distribution of ventilation and perfusion within the lungs, which is a critical pathophysiological component of COPD. The extent of ventilation defects and ventilation inhomogeneity, as well as the ventilation-perfusion ratio distribution thus correlate with severity of disease. Furthermore, specific scintigraphic patterns, such as the "stripe sign" may detect centrilobular emphysematous lesions with a higher sensitivity than other imaging techniques. Although ventilation-perfusion scintigraphy may conceivably detect COPD before any specific changes can be detected by spirometry or high-resolution CT, it is currently mostly used in the workup of lung volume reduction treatment, and for diagnosing various complications and comorbidities of COPD when combined with low-dose CT. [ABSTRACT FROM AUTHOR]

Summary: There is an increasing amount of evidence on the usability of PET in response evaluation of non-small cell lung cancer. However, data on SCLC is scarce and mainly retrospective. This prospective study assesses the use of PET (positron emission tomography) and PET/CT in response evaluation of patients with small cell lung cancer (SCLC). Methods: Assignment of early and final response was compared between PET, PET/CT, and CT in 20 patients with SCLC. Final response as assigned by CT (RECIST) served as reference. Results: At response evaluation after one cycle of chemotherapy major disagreement (responder versus non-responder) between PET and CT in predicting final response was seen in 1 of 12 patients. At final response evaluation major disagreement between PET, PET/CT and CT was seen in 2 of 19 patients (11%). All measurements of FDG-uptake were significantly correlated to size and changes in size as measured by CT. A significant difference in relative change in tumour FDG-uptake and volume was found between responding and non-responding patients. No significant difference was found between a visual and semi-quantitative analysis of PET. Conclusion: Response evaluation of SCLC by PET/CT is feasible, but it is uncertain whether it adds further information to evaluation by RECIST, thus further studies and standardization of methods are needed. [Copyright &y& Elsevier]

Purpose Assessment of the state of the lungs by ventilation perfusion (V/Q) Single Photon Emission Computed Tomography combined with Computed Tomography (SPECT/CT) has proved its value as a clinical tool. Physicians study both ventilation and perfusion images, but also the ratio image of these two. However, the interpretation of these images is qualitative. For the ventilation images quantitative measures were investigated in the case of Krypton-81 m and Technegas (Tc-99 m labelled graphite particles). Krypton is a gaseous ventilation tracer and distributes similarly to air. However, it is not widely available and relatively expensive. Technegas is cheaper and has wider availability, but is an aerosol, which may result in hot spots in obstructed airways. Methods Dual-isotope ventilation SPECT/CT with both Technegas(140 keV) and Krypton(190 keV) simultaneously was obtained for 11 patients with medium and low energy general purpose collimators including a follow-up. This resulted in 38 ventilation studies in total. Reconstruction was performed with and without attenuation and scatter correction. The penetration index and the heterogeneity index (with and without band filtering for relevant clinical sizes) were calculated for the right and left lung. Scatterplots of the intensities of the Krypton and Technegas images were made and statistical outliers were detected. Results Significant lower penetration indexes for Technegas were found for the medium energy collimators, but were not seen for the low energy collimators. The higher heterogeneity indexes for Technegas were significant in all cases except for the uncorrected medium energy collimators data. Band filtering of the heterogeneity index improved the statistical significance of the differences. The scatterplots showed that all patients suffered from Technegas-outliers in one or both lungs, indicating the presence of hot spots. The visually identified hot spots could be mapped to the outliers seen in the scatterplots. Conclusions The applied quantitative analysis revealed that there are significant differences between Krypton and Technegas as a ventilation tracer for patients with severe COPD. The penetration index may have limited clinical relevance, since it does not capture complicated activity distributions. However, the heterogeneity index with band filtering is potentially a useful quantitative clinical measure. [ABSTRACT FROM AUTHOR]

Pharmacologic stress testing with adenosine in heart transplant recipients implies a high risk of atrioventricular block. Dipyridamole is preferable as a coronary vasodilator. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To assess the expected costs and outcomes of alternative strategies for staging of lung cancer to inform a Danish National Health Service perspective about the most cost-effective strategy. Methods: A decision tree was specified for patients with a confirmed diagnosis of non–small-cell lung cancer. Six strategies were defined from relevant combinations of mediastinoscopy, endoscopic or endobronchial ultrasound with needle aspiration, and combined positron emission tomography-computed tomography with F18-fluorodeoxyglucose. Patients without distant metastases and central or contralateral nodal involvement (N2/N3) were considered to be candidates for surgical resection. Diagnostic accuracies were informed from literature reviews, prevalence and survival from the Danish Lung Cancer Registry, and procedure costs from national average tariffs. All parameters were specified probabilistically to determine the joint decision uncertainty. The cost-effectiveness analysis was based on the net present value of expected costs and life years accrued over a time horizon of 5 years. Results: At threshold values of around €30,000 for cost-effectiveness, it was found to be cost-effective to send all patients to positron emission tomography-computed tomography with confirmation of positive findings on nodal involvement by endobronchial ultrasound. This result appeared robust in deterministic sensitivity analysis. The expected value of perfect information was estimated at €52 per patient, indicating that further research might be worthwhile. Conclusions: The policy recommendation is to make combined positron emission tomography-computed tomography and endobronchial ultrasound available for supplemental staging of patients with non–small-cell lung cancer. The effects of alternative strategies on patients’ quality of life, however, should be examined in future studies. [Copyright &y& Elsevier]

Background: Because bronchiolitis obliterans syndrome (BOS) is defined and graded according to the decline in forced expiratory volume in 1 second (FEV1) relative to a maximal baseline value obtained post-transplantation, the criteria discriminates against recipients with lower maximal baseline values (i.e., constitutes a statistical bias). This study describes the effect of transplant procedure on the development of BOS, adjusting for the absolute value of post-transplant baseline FEV1. Methods: All patients receiving a cadaveric lung transplant from 1992 to 2004 were included in the study (n = 389). Exclusion criteria were patients surviving <3 months (n = 39) and missing spirometry measurements (n = 4). Results: Baseline FEV1 was strongly associated with the freedom from BOS Grade 1, and longer-duration BOS-free survival in univariate and multivariate survival analyses. After adjusting for baseline FEV1, and recipient–donor gender, bilateral lung transplantation (BLT) was associated with an increase in the cause-specific risk of BOS Grade 1 (hazard ratio [HR] 2.0, confidence interval [CI] 1.2 to 3.1, p = 0.004), and an increase in the cause-specific risk of death/re-transplantation or BOS Grade 1 as a combined end-point (HR 2.3, CI 1.5 to 3.4, p < 0.0001) compared with single-lung transplantation (SLT). In the competing risk regression model adjusting for recipient–donor gender and transplant procedure, only baseline FEV1 remained independently associated with the cumulative incidence of BOS Grade 1 (p < 0.05); however, BLT recipients were more likely to have death/re-transplantation unrelated to BOS than SLT recipients. Conclusions: The absolute value of baseline lung function appears to be an important confounder in the analyses of BOS, and should be considered in future risk factor analyses. [Copyright &y& Elsevier]

Background: The objectives of this study were to describe the natural history of bronchiolitis obliterans syndrome (BOS) in a large consecutive series of patients from a national center in accordance with the most recent grading criteria, and to examine the prognosis with respect to onset and severity of BOS. Methods: All patients receiving a cadaveric lung transplant between 1992 and 2004 were included in the study (n = 389). Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and lack of available lung function measurements (n = 4). Results: The 1-, 3-, 5- and 10-year actuarial survival rates for the entire series were 81%, 67%, 60% and 36%, respectively. The 1-, 3-, 5- and 10-year actuarial freedom from BOS Grade ≥1 was 81%, 53%, 38% and 15%, respectively. A Cox regression model with BOS grade as a time-dependent covariate was performed in a sub-group of patients surviving at least 3 years (n = 237). Both progression from BOS Grade 1 to 2 and from BOS Grade 2 to 3 were associated with a significant increase in mortality: hazard ratio (HR) = 3.1 (confidence interval [CI] 1.2 to 7.9) and HR = 2.9 (CI 1.6 to 5.3), respectively. The addition of a non–time-dependent covariate to signify early (within 18 months of transplantation) or late (after 18 months) development of BOS was not significant (p = 0.5). Conclusions: The development and progression of chronic allograft rejection after lung transplantation (BOS Grades 2 and 3) is associated with a 3-fold increase in the risk of death at each stage, irrespective of whether BOS developed early or late. [Copyright &y& Elsevier]

Establishment of baseline values for forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), or total lung capacity (TLC) is required when diagnosing and phenotyping chronic lung allograft dysfunction after lung transplant. It is generally accepted that the baseline (peak) values of these parameters occur simultaneously, but this assumption has not been substantiated for TLC. All lung function measurements in all double lung transplant recipients from a single center in the period from 1992-2014 were included. Time to baseline FEV 1 was assessed according to standards from the International Society for Heart and Lung Transplantation, and time to peak FVC, TLC, and diffusion capacity for carbon monoxide were evaluated. A total of 288 double lung transplants surviving more than 3 months after transplant were included. Baseline FEV 1 occurred at a median of 0.77 years post transplant and was statistically different from median times to the peak FVC (1.02 years), to peak TLC (1.37 years), and to peak diffusion capacity for carbon monoxide 1.04 years post transplant (all log-rank P <.001). At the time of baseline FEV1, FVC, and TLC were at a mean of 96% and 95% of their peak values, respectively. The peak lung function is reached at different time points for different parameters post transplant with FEV 1 baseline occurring first. For most patients values of FVC and TLC obtained at time for baseline FEV 1 is a good estimate of peak values, but in a small percentage of patients this procedure may jeopardize phenotyping of chronic lung allograft dysfunction based solely on lung function parameters. [ABSTRACT FROM AUTHOR]

Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV 1 ), FEV 1 /forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases. [ABSTRACT FROM AUTHOR]

Background: The prevalence, prognostic importance, and factors that predict the presence and degree of pulmonary hypertension (PH) diagnosed with right heart catheterization (RHC) in patients with end-stage chronic obstructive pulmonary disease (COPD) remain unclear. Methods: This retrospective study included 409 patients (61% women) with COPD/emphysema or α-1-antitrypsin deficiency who underwent lung transplant evaluation during 1991 to 2010. We analyzed the occurrence and degree of PH and compared demographics, oxygenation, lung function, hemodynamics, functional capacity, and survival in patients with and without PH. Prediction of PH was assessed using univariate and multivariate regression analysis. Results: The mean age at evaluation was 54 ± 7 years. All patients were in New York Heart Association functional class III-IV, with forced expiratory volume in 1 second of 23% ± 7% and total lung capacity of 126% ± 21% of predicted. PH was present in 146 (36%). The analysis excluded 53 (13%) with pulmonary venous hypertension (PVH). The distribution of the mean pulmonary artery pressure (mPAP) in patients with or without PH showed a unimodal normally distributed population, with a mean of 23.8 ± 6.0 mm Hg. Predictors of PH were partial pressures of oxygen and carbon dioxide. The 5-year survival rate was 37% in COPD patients with PH vs 63% in patients without PH (p = 0.016). Survival after lung transplantation did not differ (p = 0.37). Conclusions: RHC verified PH in 36% of COPD patients. Hypoxemia and hypercapnia were associated with mPAP. PH is associated with worse survival in COPD, but PH does not influence the prognosis after lung transplantation. [ABSTRACT FROM AUTHOR]

Background: Post-transplant baseline forced expiratory volume in 1 second (FEV1) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV1. Methods: A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4). Results: The first maximum FEV1 occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV1 was a significant confounder in all survival and competing risk analyses of BOS (p < 0.05). Conclusion: Despite early diagnosis and prompt treatment, acute cellular rejection remains an independent risk factor for the development of BOS after adjusting for the confounding of post-transplant baseline FEV1. [Copyright &y& Elsevier]

Positron-emission tomography (PET) with 18-fluorodeoxyglucose has a role in the diagnosis and staging of lung cancer, but is also appealing for assessment of prognosis and treatment. A systematic search of the published work shows good evidence that [18F]FDG uptake on PET has independent prognostic value in newly diagnosed non-small-cell lung cancer. PET is a sensitive method of measuring the biological effects of anticancer therapy, but until better standardisation and large-scale experience is available, it should only be used for additional assessments of early response in clinical trials. Further studies are needed to define the role of [18F]FDG-PET in restaging after induction therapy in multimodality approaches for locally advanced lung cancer. The assessment of prognosis by [18F]FDG-PET is less substantiated in treated lung cancer than in newly diagnosed patients. Good prospective evidence documents the effectiveness of [18F]FDG-PET over CT in the correct identification of recurrent lung cancer. [Copyright &y& Elsevier]