Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Psychometric Properties of the Patient Health Questionnaire-9 in Patients With Breast Cancer.

OBJECTIVE: Due to the high frequency of depressive symptoms associated with breast cancer, it is crucial to screen for depression in breast cancer patients. While numerous screening tools are available for depression in this population, there is a need for a brief and convenient tool to enhance clinical use. This study aims to investigate the psychometric properties of the Patient Health Questionnaire-9 (PHQ-9) in patients with breast cancer. METHODS: Patients with breast cancer (n=327) who visited the Breast Cancer Clinic were included in this study. The reliability of the PHQ-9 was analyzed by Cronbach's α, and the construct validity of the PHQ-9 was explored by factor analysis. The concurrent validity of the PHQ-9 was evaluated by Pearson correlation analysis with the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS). RESULTS: The values of Cronbach's α ranged from 0.800 to 0.879 was acceptable. The exploratory factor analysis revealed that the one-factor model and two-factor model of the PHQ-9 explained 46% and 57% of the variance, respectively. The PHQ-9 were significantly correlated with those of HADS (r=0.702, p<0.001) and PSS (r=0.466, p<0.001). Consequently, the PHQ-9 demonstrated acceptable reliability and validity in breast cancer patients. CONCLUSION: The findings of this study indicate that the PHQ-9 exhibits acceptable reliability and validity in patients with breast cancer. The convenience of this brief self-report questionnaire suggests its potential as a reliable and valid tool for assessing depression in breast cancer clinics.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Bioaccumulation of Lead, Cadmium, and Arsenic in a Mining Area and Its Associated Health Effects.

Soil contamination is associated with a high potential for health issues. This study aimed to investigate the bioaccumulation of heavy metals and its associated health impact among residents near a mining area. We performed environmental monitoring by analyzing lead (Pb), cadmium (Cd), and arsenic (As) levels in soil and rice samples, as well as biomonitoring by analyzing blood and urine samples from 58 residents living near the mine. Additionally, concentration trends were investigated among 26 participants in a 2013 study. The Cd and As levels in the soil samples and Cd levels in the rice samples exceeded the criteria for concern. The geometric mean blood Cd level (2.12 µg/L) was two times higher than that in the general population aged > 40 years. The blood Cd level showed decreasing trends from the previous measurements of 4.56-2.25 µg/L, but was still higher than that in the general population. The blood and urine Cd levels were higher in those with a low estimated glomerular filtration rate (eGFR) than in those with normal eGFR. In conclusion, heavy metals from mining areas can accumulate in soil and rice, adversely impacting human health. Continuous environmental monitoring and biomonitoring are required to ensure the safety of residents.

Percutaneous Cementoplasty for the Pelvis in Bone Metastasis: 12-Year Experience.

BACKGROUND: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

Preparation and Drug Release Behavior of Nifedipine-Loaded Poly(lactic acid)/Polyethylene Glycol Microcapsules.

Nifedipine (NF)-loaded poly(lactic acid) (PLA) and PLA/polyethylene glycol (PLA/PEG) microcapsules are synthesized using a high-speed agitator and a syringe pump with an oil-in-water emulsion-solvent evaporation technique to evaluate the effect of PLA/PEG ratio on morphology and drug release behavior of the capsules. Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimeter (DSC), and X-ray diffraction (XRD) results indicate that PEG reacts successfully with PLA due to the ether bond between PEG and PLA. The drug release rate of PLA and PLA/PEG capsules increases dramatically from 0 to 5 min and then reaches a plateau within 15 to 20 min. Due to the high specific surface area, the amount of NF released is raised by reducing the PLA concentration from 5 wt% to 2 wt%. Unlike PLA capsules, the drug release rate of PLA/PEG capsules increases due to the size effect by varying the PLA/PEG ratio from 10/0 to 6/4. Larger PLA/PEG capsules are attributed to higher amounts of encapsulated NF. The capsules show no evidence of cytotoxicity, suggesting that the PLA and PLA/PEG drug carriers are clinically safe.

Ceritinib-Induced Organizing Pneumonia in Lung Cancer: A Retrospective Analysis.

BACKGROUND: Ceritinib is a potent selective ALK inhibitor with a manageable safety profile. In anecdotal reports, ceritinib was associated with organizing pneumonia (OP), which could be confused with disease progression. OBJECTIVE: We aimed to delineate the characteristics of OP that occurs during treatment with ceritinib, and evaluate its clinical implications. PATIENTS AND METHODS: We retrospectively analyzed 44 lung cancer patients whose tumors harbored ALK or ROS1 fusions and who had received ceritinib. OP diagnosis was based on radiographic and clinical features. Four OP cases were pathologically confirmed. RESULTS: Among 44 patients, 22 OP events occurred in 16 (36.4%) patients. The median time to the first event was 17.2 weeks (range 6.7-68.7 weeks). All events were grade 1 or 2. Radiographic features were categorized into four patterns: nodular (54.6%), consolidation (27.3%), parenchymal band (4.5%), and ground-glass opacity (GGO) (13.6%). OP improved in 20 events with drug interruption or corticosteroids. The median duration of OP was 11.3 weeks (range 2-24 weeks). Tumor response rate was 75% in OP-positive and 42.9% in OP-negative groups. The median progression-free survival was 16.7 months [95% confidence interval (CI) 10.1-not applicable (NA)] in OP-positive and 5.4 months (95% CI 3.6-8.4) in OP-negative patients (P = 0.004). The median overall survival was 46.2 months (95% CI 38.1-NA) in OP-positive and 10.5 months (95% CI 6.2-18.9) in OP-negative patients (P < 0.001). CONCLUSION: OP occurs frequently during ceritinib treatment and must be distinguished from disease progression. OP could be reversible without fatal complications and its occurrence is associated with better survival outcomes.

Initial M Staging of Rectal Cancer: FDG PET/MRI with a Hepatocyte-specific Contrast Agent versus Contrast-enhanced CT.

BackgroundThe performance of PET/MRI in the determination of distant metastases (M stage) in rectal cancer relative to the current practice with contrast material-enhanced CT is largely unknown.PurposeTo compare the staging of clinical M stage rectal cancer with fluorine 18 fluorodeoxyglucose (FDG) PET/MRI (including dedicated liver and rectal MRI) to that of chest and abdominopelvic CT and dedicated rectal MRI.Materials and MethodsFrom January 2016 to August 2017, patients with newly diagnosed advanced mid to low rectal cancers were recruited for this prospective study (clinicaltrials.gov identifier: NCT0265170). Participants underwent both FDG PET/MRI with dedicated liver and rectal MRI and chest and abdominopelvic CT (the standard-of-care protocol) within 3 weeks of each other. Thereafter, M stage assessment performance was determined by using findings from 6-month clinical follow-up or biopsy as the reference standard. Performance was compared between protocols. Agreement in M stage classification was also assessed. Nonparametric statistical analyses were performed, and P < .05 indicated a significance difference.ResultsSeventy-one participants (28 women; mean age ± standard deviation, 61 years ± 9; age range, 39-79 years) were enrolled. The M stage could not be determined with the standard-of-care protocol in 22 of the 71 participants (31%; 95% confidence interval [CI]: 20.5%, 43.1%) because of indeterminate lesions. However, among these participants, PET/MRI correctly helped identify all 14 (100%; 95% CI: 76.8%, 100%) without metastases and seven of eight (88%; 95% CI: 47.4%, 99.7%) who were later confirmed to have metastases. PET/MRI showed high specificity for ruling out metastatic disease compared with the standard-of-care protocol (98% [54 of 55 participants] vs 72% [40 of 55 participants], respectively; P < .001), without increasing the number of participants with missed metastasis (6% [one of 16 participants] vs 6% [one of 16 participants]; P > .99).ConclusionPET/MRI with dedicated rectal and liver MRI can facilitate the staging work-up of newly diagnosed advanced rectal cancers by helping assess indeterminate lesions, metastases, and incidental findings better than contrast-enhanced CT, obviating for additional imaging work-up.© RSNA, 2019Online supplemental material is available for this article.Clinical trial registration no. NCT02651701.

Characterization of Tendon-Specific Markers in Various Human Tissues, Tenocytes and Mesenchymal Stem Cells.

Background: Unlike bone, cartilage, or muscle, tendon-specific markers are not well established. The purpose of the study was to investigate expression pattern and level of 6 well-known tendon-specific markers, in various human musculoskeletal tissues, tenocytes, and mesenchymal stem cells (MSCs). Methods: Musculoskeletal tissue samples of tendon, bone, cartilage, nerve, muscle, and fat were obtained from patients undergoing orthopedic surgery. Tenocytes, MSCs from bone marrow, adipose tissue, and umbilical cord were isolated from each tissue and cultured. Six tendon-specific markers, scleraxis (Scx), tenomodulin (TNMD), thrombospondin-4 (TSP-4), tenascin-C (TNC), type I collagen (Col I), and type III collagen (Col III) were investigated in tendon tissue, tenocytes, and MSCs. Results: mRNA levels of 6 tendon-specific markers were significantly higher in tendon tissue that in other connective tissues levels of Scx, TNMD, TSP-4, and Col III immediately decreased after plating tenocytes in culture dishes whereas those of TNC and Col I did not. In comparison with tendon tissue, mRNA levels pattern of Scx, TNMD, and TSP-4 in tenocytes were significantly higher than that in MSCs, but lower than in tendon tissue whereas expression pattern of TNC, Col I and III showed different pattern with each other. Conclusion: This study demonstrated that 6 commonly used tendon-specific markers were mainly expressed in tendon tissue, but that expression level and pattern of the tendon-specific markers with respect to kinds of tissues, culture duration of tenocytes and sources of MSCs.

Cone-Beam CT Virtual Navigation-Guided Percutaneous Needle Biopsy of Suspicious Pleural Metastasis: A Pilot Study.

Objective: To evaluate the diagnostic performance of cone-beam computed tomography (CBCT) virtual navigation-guided percutaneous pleural biopsy for suspected malignant pleural disease. Materials and Methods: This study enrolled 59 patients (31 males and 28 females; mean age, 63.4 years) with suspected malignant pleural disease diagnosed with CBCT from December 2010 to December 2016. Sixty-three CBCT-guided biopsies were performed using a coaxial system with 18- or 20-gauge cutting needles. Procedural details, diagnostic performance, radiation exposure, and complication rates were investigated. Results: The mean diameter perpendicular to the pleura of 51 focal and 12 diffuse pleural lesions was 1.53 ± 0.76 cm. The mean distance from the skin to the target was 3.40 ± 1.51 cm. Mean numbers of CT acquisitions and biopsies were 3.21 ± 0.57 and 3.05 ± 1.54. Total procedure time and coaxial introducer indwelling time were 11.87 ± 5.59 min and 8.78 ± 4.95 min, respectively. The mean dose area product was 12013.61 ± 7969.59 mGym2. There were 48 malignant, 10 benign, and 5 indeterminate lesions. Sensitivity, specificity, and diagnostic accuracy were 93.8% (45/48), 100% (10/10), and 94.8% (55/58), respectively. Positive and negative predictive values for malignancy were 100% (45/45) and 76.9% (10/13), respectively. Four patients (6.8%) with benign pathology during initial biopsy but still showing a high suspicion of malignancy underwent repeat biopsy and three of them were finally diagnosed with malignant pleural disease. There were three cases of minimal pneumothorax and no grave procedure-related complications. Conclusion: Cone-beam computed tomography-guided biopsy is an accurate and safe diagnostic technique for suspected malignant pleural lesion with reasonable radiation exposure and procedure time.

Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical centre.

OBJECTIVES: To validate the performances of two prediction models (Brock and Lee models) for the differentiation of minimally invasive adenocarcinoma (MIA) and invasive pulmonary adenocarcinoma (IPA) from preinvasive lesions among subsolid nodules (SSNs). DESIGN: A retrospective cohort study. SETTING: A tertiary university hospital in South Korea. PARTICIPANTS: 410 patients with 410 incidentally detected SSNs who underwent surgical resection for the pulmonary adenocarcinoma spectrum between 2011 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Using clinical and radiological variables, the predicted probability of MIA/IPA was calculated from pre-existing logistic models (Brock and Lee models). Areas under the receiver operating characteristic curve (AUCs) were calculated and compared between models. Performance metrics including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were also obtained. RESULTS: For pure ground-glass nodules (n=101), the AUC of the Brock model in differentiating MIA/IPA (59/101) from preinvasive lesions (42/101) was 0.671. Sensitivity, specificity, accuracy, PPV and NPV based on the optimal cut-off value were 64.4%, 64.3%, 64.4%, 71.7% and 56.3%, respectively. Sensitivity, specificity, accuracy, PPV and NPV according to the Lee criteria were 76.3%, 42.9%, 62.4%, 65.2% and 56.3%, respectively. AUC was not obtained for the Lee model as a single cut-off of nodule size (≥10 mm) was suggested by this model for the assessment of pure ground-glass nodules. For part-solid nodules (n=309; 26 preinvasive lesions and 283 MIA/IPAs), the AUC was 0.746 for the Brock model and 0.771 for the Lee model (p=0.574). Sensitivity, specificity, accuracy, PPV and NPV were 82.3%, 53.8%, 79.9%, 95.1% and 21.9%, respectively, for the Brock model and 77.0%, 69.2%, 76.4%, 96.5% and 21.7%, respectively, for the Lee model. CONCLUSIONS: The performance of prediction models for the incidentally detected SSNs in differentiating MIA/IPA from preinvasive lesions might be suboptimal. Thus, an alternative risk calculation model is required for the incidentally detected SSNs.

Cone beam computed tomography virtual navigation-guided transthoracic biopsy of small (≤ 1 cm) pulmonary nodules: impact of nodule visibility during real-time fluoroscopy.

OBJECTIVE: To evaluate the impact of nodule visibility during real-time fluoroscopy and other biopsy-related variables on the diagnostic accuracy and complication rates of cone beam CT (CBCT) virtual navigation (VN)-guided percutaneous transthoracic needle biopsies (PTNBs) of small (≤1 cm) pulmonary nodules. METHODS: Patients (99 males and 114 females; age, 62.1 ± 11.1 years) who underwent CBCT VN-guided biopsies for lung nodules ≤ 1 cm were retrospectively reviewed. The visibility of target nodules was assessed on the captured fluoroscopy images. Diagnostic accuracies were calculated and logistic regression analyses were performed to determine independent influencing factors for the correct diagnosis and complications (pneumothoraxes and hemoptysis) in CBCT VN-guided PTNBs, respectively. RESULTS: Among 213 nodules, 63 (29.6%) were invisible on real-time fluoroscopy during VN. The diagnostic accuracy of CBCT VN-guided PTNBs for the invisible nodules was 76.7%, while for the visible nodules was 89.1% (p = 0.042). In the logistic regression analysis, the visibility of a target nodule (odds ratio = 2.49, p = 0.047) was the only independent influencing factor for a correct diagnosis. As regards complication rates, nodule visibility was not a significant factor for the occurrence of a pneumothorax or hemoptysis. CONCLUSION: Although nodule visibility on real-time fluoroscopy was an affecting factor for the correct diagnosis, CBCT VN-guided PTNB was feasible for the invisible nodules with diagnostic accuracy of 76.7%. Advance in knowledge: CBCT VN-guided PTNB can be tried safely for the subcentimeter-sized pulmonary nodules regardless of their fluoroscopic visibility.

Risk factors for haemoptysis after percutaneous transthoracic needle biopsies in 4,172 cases: Focusing on the effects of enlarged main pulmonary artery diameter.

OBJECTIVES: To evaluate the risk factors for haemoptysis after cone-beam computed tomography (CBCT)-guided percutaneous transthoracic needle biopsy (PTNB), particularly on whether the enlargement of main pulmonary artery diameter (mPAD) is a risk factor for PTNB-related haemoptysis. METHODS: 4,172 cases of CBCT-guided PTNBs in 3,840 patients were retrospectively included in this study. Various data including mPAD measured on preprocedural CT images were evaluated using logistic regression analyses to determine significant risk factors for both haemoptysis and severe haemoptysis, designated as when blood transfusion, vascular embolisation or cardiopulmonary resuscitation were required to manage patients with haemoptysis. RESULTS: Haemoptysis occurred in 5.78 % (241/4172) of all PTNB procedures, while severe haemoptysis occurred in 0.18 % (7/4172). Female sex, history of antiplatelet or anticoagulative drugs, prolonged activated partial thromboplastin time, subsolid nodules, cavitary nodules and long pleura-to-target distance were revealed to be independent risk factors for haemoptysis, while mPAD enlargement (> 29.5 mm) was not. Regarding severe haemoptysis, however, mPAD enlargement was demonstrated to be an independent risk factor along with the presence of subsolid and cavitary target nodules. CONCLUSION: mPAD enlargement was not a significant risk factor for PTNB-related haemoptysis; however, it was a significant risk factor for severe haemoptysis. KEY POINTS: • mPAD enlargement was a significant risk factor for severe PTNB-related haemoptysis. • mPAD can be useful in screening high-risk patients for severe haemoptysis. • Subsolid or cavitary nodule was another significant risk factor for severe haemoptysis.

Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

OBJECTIVES: To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. METHODS: From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. RESULTS: Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. CONCLUSION: PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. KEY POINTS: • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

Influence of fissure integrity on quantitative CT and emphysema distribution in emphysema-type COPD using a dedicated COPD software.

OBJECTIVES: Fissure integrity (FI) plays a key role in selecting patients for interventional emphysema therapy. We investigated its interference with automated lobar segmentation in quantitative computed tomography (CT) and emphysema distribution. METHODS: CT was available for 50 patients with chronic obstructive pulmonary disease (COPD). Lobe segmentation was performed fully automated by software and corrected manually. FI was evaluated visually using a %-scale. The influence of FI on emphysema ratio (ER=percentage of lung volume with density values<-950 HU), mean lung density (MLD), emphysema and total volume of adjacent lobes was analyzed. Lobe-based results were compared with respect to FI. RESULTS: Differences in ER in adjacent lobes for complete vs. incomplete fissures were 12.4% for the right horizontal, 0.2% and 3% for the right oblique and 4.4% for the left oblique fissure (all p>0.05). Results for emphysema comparing automated vs. manually corrected segmentation exceeded clinically acceptable values, but were not significantly affected by FI (p>0.05). The widest limits of agreement for ER and MLD were noted in the right middle lobe ([-14, 17.4%], [-22.4, 32.4 Hounsfield Units]). CONCLUSIONS: Automated lobe segmentation and emphysema distribution are not significantly affected by FI. Manual correction of automated lobar segmentation is still recommended in severe emphysema.

The Impact of Iterative Reconstruction in Low-Dose Computed Tomography on the Evaluation of Diffuse Interstitial Lung Disease.

OBJECTIVE: To evaluate the impact of iterative reconstruction (IR) on the assessment of diffuse interstitial lung disease (DILD) using CT. MATERIALS AND METHODS: An American College of Radiology (ACR) phantom (module 4 to assess spatial resolution) was scanned with 10-100 effective mAs at 120 kVp. The images were reconstructed using filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), with blending ratios of 0%, 30%, 70% and 100%, and model-based iterative reconstruction (MBIR), and their spatial resolution was objectively assessed by the line pair structure method. The patient study was based on retrospective interpretation of prospectively acquired data, and it was approved by the institutional review board. Chest CT scans of 23 patients (mean age 64 years) were performed at 120 kVp using 1) standard dose protocol applying 142-275 mA with dose modulation (high-resolution computed tomography [HRCT]) and 2) low-dose protocol applying 20 mA (low dose CT, LDCT). HRCT images were reconstructed with FBP, and LDCT images were reconstructed using FBP, ASIR, and MBIR. Matching images were randomized and independently reviewed by chest radiologists. Subjective assessment of disease presence and radiological diagnosis was made on a 10-point scale. In addition, semi-quantitative results were compared for the extent of abnormalities estimated to the nearest 5% of parenchymal involvement. RESULTS: In the phantom study, ASIR was comparable to FBP in terms of spatial resolution. However, for MBIR, the spatial resolution was greatly decreased under 10 mA. In the patient study, the detection of the presence of disease was not significantly different. The values for area under the curve for detection of DILD by HRCT, FBP, ASIR, and MBIR were as follows: 0.978, 0.979, 0.972, and 0.963. LDCT images reconstructed with FBP, ASIR, and MBIR tended to underestimate reticular or honeycombing opacities (-2.8%, -4.1%, and -5.3%, respectively) and overestimate ground glass opacities (+4.6%, +8.9%, and +8.5%, respectively) compared to the HRCT images. However, the reconstruction methods did not differ with respect to radiologic diagnosis. CONCLUSION: The diagnostic performance of LDCT with MBIR was similar to that of HRCT in typical DILD cases. However, caution should be exercised when comparing disease extent, especially in follow-up studies with IR.

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema.

BACKGROUND: Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. METHODS: Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). FINDING: Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). INTERPRETATION: Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy.

Predictors of clinical outcome in emphysema patients with atelectasis following endoscopic valve therapy: A retrospective study.

BACKGROUND AND OBJECTIVE: The aim of endoscopic valve therapy in patients with emphysema is complete lobar atelectasis of the most emphysematous lobe. However, even after the radiological advent of atelectasis, great variability in clinical outcomes can be observed. METHODS: The baseline clinical measures (vital capacity (VC), forced expiratory flow in 1 s (FEV1 ), residual volume (RV) and 6-min walk test (6-MWT)) and computed tomography variables (low attenuation volume (LAV) of the target lobe, LAV% of the target and the ipsilateral untreated lobe and LAV of the target lobe to LAV of the target lung and to LAV of the total lung) of 77 patients with complete atelectasis following valve therapy were retrospectively examined to determine their impact on patient´s outcome (changes in VC, FEV1 , RV and 6-MWT from baseline to the time of atelectasis). RESULTS: Low attenuation volume of the target lobe to LAV of the target lung predicts a significant FEV1 improvement in patients with complete lobar atelectasis following valve therapy. A 10% difference in that computed tomography predictor was associated with a 82-mL improvement in FEV1 (P = 0.006). Lower 6-MWT scores, low VC and high RV at baseline were significantly associated with greater improvement in the respective parameter (all P < 0.001). CONCLUSION: Low attenuation volume of the target lobe to LAV of the target lung and baseline clinical measures seem to significantly predict clinical outcomes in patients with complete lobar atelectasis following valve treatment.

Fully Automated Pulmonary Lobar Segmentation: Influence of Different Prototype Software Programs onto Quantitative Evaluation of Chronic Obstructive Lung Disease.

OBJECTIVES: Surgical or bronchoscopic lung volume reduction (BLVR) techniques can be beneficial for heterogeneous emphysema. Post-processing software tools for lobar emphysema quantification are useful for patient and target lobe selection, treatment planning and post-interventional follow-up. We aimed to evaluate the inter-software variability of emphysema quantification using fully automated lobar segmentation prototypes. MATERIAL AND METHODS: 66 patients with moderate to severe COPD who underwent CT for planning of BLVR were included. Emphysema quantification was performed using 2 modified versions of in-house software (without and with prototype advanced lung vessel segmentation; programs 1 [YACTA v.2.3.0.2] and 2 [YACTA v.2.4.3.1]), as well as 1 commercial program 3 [Pulmo3D VA30A_HF2] and 1 pre-commercial prototype 4 [CT COPD ISP ver7.0]). The following parameters were computed for each segmented anatomical lung lobe and the whole lung: lobar volume (LV), mean lobar density (MLD), 15th percentile of lobar density (15th), emphysema volume (EV) and emphysema index (EI). Bland-Altman analysis (limits of agreement, LoA) and linear random effects models were used for comparison between the software. RESULTS: Segmentation using programs 1, 3 and 4 was unsuccessful in 1 (1%), 7 (10%) and 5 (7%) patients, respectively. Program 2 could analyze all datasets. The 53 patients with successful segmentation by all 4 programs were included for further analysis. For LV, program 1 and 4 showed the largest mean difference of 72 ml and the widest LoA of [-356, 499 ml] (p<0.05). Program 3 and 4 showed the largest mean difference of 4% and the widest LoA of [-7, 14%] for EI (p<0.001). CONCLUSIONS: Only a single software program was able to successfully analyze all scheduled data-sets. Although mean bias of LV and EV were relatively low in lobar quantification, ranges of disagreement were substantial in both of them. For longitudinal emphysema monitoring, not only scanning protocol but also quantification software needs to be kept constant.

Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery.

PURPOSE: To assess the impact of imaging, surgical, histopathologic and patient-related factors on the risks of recurrence and overall survival (OS) in stage IIIA-N2 non-small cell lung cancer (NSCLC) patients undergoing definitive resection after neoadjuvant concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively examined 104 consecutive patients with stage IIIA-N2 NSCLC who received neoadjuvant CCRT followed by surgery between 2008 and 2011. While reviewing the clinical and surgical data, we also assessed histopathologic and imaging (CT and PET/CT) factors. Disease-free survival (DFS) and OS were estimated with predictors for recurrence and survival. RESULTS: The 3-year OS for patients with and without recurrence was 37.1 and 63.3 %, respectively (p < 0.001). Size decrease of target lesion(s) ≥36 % on post-neoadjuvant CCRT CT (p = 0.048) and viable tumor size on surgical specimen <9.4 mm (p = 0.035) were related to longer OS. Regarding shorter DFS, tumor size on post-neoadjuvant CCRT CT (p = 0.046), SUV(max) of the primary tumor (p = 0.011), male gender (p = 0.023), total tumor size on surgical specimen (p = 0.041) and viable tumor size on surgical specimen (p = 0.043) were the significant predictors. CONCLUSIONS: OS is prolonged with greater extent of size decrease of target lesion(s) on post-neoadjuvant CCRT CT and smaller viable tumor size on surgical specimen. Larger tumor size on post-neoadjuvant CCRT CT, higher SUV(max), male gender, larger total tumor size and larger viable tumor size on surgical specimen may herald the higher probability of recurrence and the necessity of more attention.