Objectives
To determine the accuracy of CT-guided percutaneous transthoracic needle lung biopsy (PTNB) for the diagnosis of malignancy and the associated complication rates in patients with ...idiopathic pulmonary fibrosis (IPF).
Methods
This retrospective study included 91 CT-guided PTNBs performed in 80 patients with IPF from April 2003 through December 2016. Data regarding patients, target lesions, procedures, complications, and pathological reports were collected, and the final diagnosis was made. The diagnostic accuracy, sensitivity, specificity, percentage of nondiagnostic results, and complication rates were determined. Multivariable logistic regression analyses were performed to identify risk factors for nondiagnostic results and major complications.
Results
Three biopsies (technical failure
n
= 2 and undetermined final diagnosis
n
= 1) were excluded from the diagnostic accuracy calculation. The diagnostic accuracy, sensitivity, and specificity were 89% (78/88), 90% (62/69), and 84% (16/19), respectively. The percentage of nondiagnostic results was 34% (30/88). Lesion size ≤ 3 cm (odds ratio OR, 8.8; 95% confidence interval CI, 2.5–31.2;
p
= 0.001) and needle tip placement outside the target lesion (OR, 13.7; 95% CI, 1.4–132.2;
p
= 0.02) were risk factors for nondiagnostic results. The overall and major complication rates were 51% (46/91) and 12% (11/91), respectively. The presence of honeycombing along the path of the needle (OR, 11.2; 95% CI, 1.4–89.1;
p
= 0.02) was an independent risk factor for major complications.
Conclusions
CT-guided PTNB shows a relatively reasonable accuracy in diagnosing malignancy in patients with IPF. The complication rate may be high, especially when the needle passes through honeycomb lesions.
Key Points
• In patients with idiopathic pulmonary fibrosis (IPF), CT-guided percutaneous transthoracic needle lung biopsy (PTNB) showed a relatively reasonable accuracy for the diagnosis of malignancy.
• Target lesion size ≤ 3 cm and biopsy needle tip placement outside the target lesion were risk factors for nondiagnostic results of CT-guided PTNB.
• The complication rate may be high, especially in cases where the biopsy needle passes through honeycomb lesions.
Abstract
Background
Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an ...abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification.
Methods
Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes.
Results
The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial.
Conclusions
Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.
There is increasing demand for reconstruction of glottal insufficiency. Several injection materials have been examined for this purpose, but all had limitations, such as poor long-term durability, ...migration from the injection site, inflammation, granuloma formation, and interference with vocal fold vibration due to viscoelastic mismatch. Here, we developed a novel injection material, consisting of polycaprolactone (PCL) microspheres, which exhibits better viscoelasticity than conventional materials, and Pluronic F127 carrier, which decreases the migration of the injection materials. The material was injected into rabbits with glottal insufficiency and compared with the FDA-approved injection material, calcium hydroxylapatite (CaHA). Endoscopic and histological examinations indicated that PCL/Pluronic F127 remained at the injection site with no inflammatory response or granuloma formation, whereas CaHA leaked out and migrated from the injection site. Therefore, vocal fold augmentation was almost completely retained during the 12-month follow-up period in this study. Moreover, induced phonation and high-speed recording of vocal fold vibration showed decreased vocal fold gap area in the PCL/Pluronic F127 group. Our newly developed injection material, PCL/Pluronic F127, permits efficient augmentation of paralyzed vocal fold without complications, a concept that can be applied clinically, as demonstrated by the successful long-term follow-up.
The mechanical properties and biodegradability of retted kenaf and modified starch composites fabricated by adding enzyme-retted kenaf as a filler and poly(vinyl alcohol) (PVA), poly(ethylene ...glycol), or glycerol as a plasticizer are compared with those of the NaOH-retted counterparts fabricated under identical conditions. In the case of enzyme retting, the composite treated with the PVA plasticizer was deemed the most appropriate for achieving optimal tensile strength, flexural strength, and flexural modulus. Further, the retting treatment, the length of the kenaf fiber, the type of treatment (single- or double-sided), and the adhesion force at the interface significantly affect the mechanical properties of the composites. According to the aerobic biodegradability assessment in natural reclamation conditions, the modified starch composite fabricated using 50-mm-long enzyme-retted kenaf fibers as the filler and double-side treated with PVA plasticizer showed a biodegradation rate of 80% or higher after 80 days.
Gefitinib was compared with pemetrexed as second-line therapy in a clinically selected population previously treated with platinum-based chemotherapy.
A phase 3 trial of gefitinib (250 mg/day) versus ...pemetrexed (500 mg/m(2) on day 1, every 3 weeks) was conducted in patients who had never smoked and who had advanced pulmonary adenocarcinoma treated with 1 previous platinum-based regimen. The primary endpoint was progression-free survival (PFS).
A total of 135 patients were analyzed. The gefitinib group had significantly longer PFS compared with the pemetrexed group, with a median PFS time of 9.0 versus 3.0 months (P = .0006). The objective response rates were 58.8% and 22.4% for gefitinib and pemetrexed, respectively (P < .001). However, there was no statistically significant difference in overall survival between the 2 groups (22.2 vs 18.9 months; P = .37). The difference of PFS was increased in a subgroup analysis of 33 patients with activating epidermal growth factor receptor mutation (15.7 vs 2.9 months; hazard ratio, 0.3; 95% confidence interval, 0.13-0.72; P = .005), with numerical superiority of gefitinib in the 38 patients testing negative for epidermal growth factor receptor mutation (5.9 vs 2.7 months; P = .099). Both regimens were well tolerated. There were no significantly different changes in quality of life between the 2 groups, except that symptom scores for dyspnea and diarrhea favored the gefitinib and pemetrexed arms, respectively.
Gefitinib showed superior efficacy to pemetrexed as second-line therapy in Korean never-smokers with pulmonary adenocarcinoma.
Pathogenic variants in genes related to channelopathy and cardiomyopathy are the most common cause of sudden unexplained cardiac death. However, few reports have investigated the frequency and/or ...spectrum of pathogenic variants in these genes in Korean sudden cardiac arrest survivors. This study aimed to investigate the causative genetic variants of cardiac-associated genes in Korean sudden cardiac arrest survivors. We performed exome sequencing followed by filtering and validation of variants in 100 genes related to channelopathy and cardiomyopathy in 19 Korean patients who survived sudden cardiac arrest. Five of the 19 patients (26.3%) had either a pathogenic variant or a likely pathogenic variant in MYBPC3 (n=1), MYH7 (n=1), RYR2 (n=2), or TNNT2 (n=1). All five variants were missense variants that have been reported previously in patients with channelopathies or cardiomyopathies. Furthermore, an additional 12 patients (63.2%) had more than one variant of uncertain significance. In conclusion, pathogenic or likely pathogenic variants in genes related to channelopathy and cardiomyopathy are not uncommon in Korean sudden cardiac arrest survivors and cardiomyopathy-related genes should be included in the molecular diagnosis of sudden cardiac arrest in Korea.
The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict, partly owing to its heterogeneity. Composite physiologic index (CPI) and gender-age-physiology (GAP) models are ...easy-to-use predictors of IPF progression. This study aimed to compare the predictive values of these two models. From 2003 to 2007, the Korean Interstitial Lung Disease (ILD) Study Group surveyed ILD patients using the 2002 ATS/ERS criteria. A total of 832 patients with IPF were enrolled in this study. CPI was calculated as follows: 91.0 - (0.65 × %DL
) - 0.53 × %FVC + 0.34 × %FEV
. GAP stage was calculated based on gender (0-1 points), age (0-2 points), and two physiologic lung function parameters (0-5 points). The two models had similar significant predictive values for patients with IPF (p < 0.001). The area under the curve (AUC) was higher for CPI than GAP for prediction of 1-, 2-, and 3-year mortality in this study. The AUC was higher for surgically diagnosed IPF patients than for clinically diagnosed patients. However, neither CPI nor GAP yielded good predictions of outcomes; the AUC was approximately 0.61~0.65. Although both CPI and GAP stage are significantly useful predictors for IPF, they have limited capability to accurately predict outcomes.
Pancreatic cancer (PC; pancreatic ductal adenocarcinoma) is characterized by significant morbidity and mortality worldwide. Although carbohydrate antigen (CA) 19-9 has been known as a PC biomarker, ...it is not commonly used for general screening because of its low sensitivity and specificity. Therefore, there is an urgent need to develop a new biomarker for PC diagnosis in the earlier stage of cancer. To search for a novel serologic PC biomarker, we carried out an integrated proteomic analysis for a total of 185 pooled or individual plasma from healthy donors and patients with five disease groups including chronic pancreatitis (CP), PC, and other cancers (e.g., hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer) and identified complement factor b (CFB) as a candidate serologic biomarker for PC diagnosis. Immunoblot analysis of CFB revealed more than two times higher expression in plasma samples from PC patients compared with plasma from individuals without PC. Immunoprecipitation coupled to mass spectrometry analysis confirmed both molecular identity and higher expression of CFB in PC samples. CFB showed distinctly higher specificity than CA 19-9 for PC against other types of digestive cancers and in discriminating PC patients from non-PC patients (p < 0.0001). In receiver operator characteristic curve analysis, CFB showed an area under curve of 0.958 (95% CI: 0.956 to 0.959) compared with 0.833 (95% CI: 0.829 to 0.837) for CA 19-9. Furthermore, the Y-index of CFB was much higher than that of CA 19-9 (71.0 vs 50.4), suggesting that CFB outperforms CA 19-9 in discriminating PC from CP and other gastrointestinal cancers. This was further supported by immunoprecipitation and qRT-PCR assays showing higher expression of CFB in PC cell lines than in normal cell lines. A combination of CFB and CA 19-9 showed markedly improved sensitivity (90.1 vs 73.1%) over that of CFB alone in the diagnosis of PC against non-PC, with similar specificity (97.2 vs 97.9%). Thus, our results identify CFB as a novel serologic PC biomarker candidate and warrant further investigation into a large-scale validation and its role in molecular mechanism of pancreatic carcinogenesis.
The interest in vascular substitutes has recently increased. We evaluated the feasibility of using a homologous parietal peritoneum as a vascular substitute for venous reconstruction during abdominal ...surgery.
The inferior vena cava was replaced with a homologous parietal peritoneum after cross-linking with glutaraldehyde in 36 rabbits. At 7, 14, and 28 days, the patency rate, outer and inner graft diameters, histology, and immunohistochemistry were evaluated.
Both the 7- and 14-day groups maintained vascular patency. Vascular patency was maintained in 3 rabbits in the 28-day group. The inner diameters of the anastomotic sites were 6.23 ± 0.18, 5.64 ± 0.16, and 2.34 ± 0.21 mm in the 7-day, 14-day, and 28-day groups, respectively. The midpoint inner diameters of the homologous parietal peritoneum grafts were 624 ± 0.46, 5.74 ± 0.26, and 2.14 ± 0.28 mm in each group, respectively. Endothelial cell proliferation on the homologous parietal peritoneum graft surfaces in all groups was based on the histological findings from the first group. Multiple neovascularizations of the homologous parietal peritoneum graft were found in the 14- and 28-day groups, indicating neo-media formation. Acute inflammation appeared to progress to the entire layer of the homologous parietal peritoneum graft without an intraluminal thrombus, but the graft was patent in the 14-day group. In the 28-day group, 6 rabbits showed near-total occlusion and a thrombus formed in the homologous parietal peritoneum graft at the anastomosis site with severe stricture; however, the rabbits were alive and had collateral vessel formation.
Using homologous parietal peritoneum is feasible for venous reconstruction in abdominal surgery.
Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of ...systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.
We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.
This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.
These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
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