Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function.

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Clinical application of next-generation sequencing for the management of desmoid tumors: A case report and literature review.

RATIONALE: Desmoid tumors are rare myofibroblastic neoplasms characterized by local invasiveness and high rates of recurrence, and sometimes mimic local recurrence of previously resected malignancies. Previous studies have suggested that molecular profiling may be useful for the diagnosis of the tumors and risk stratification. However, the clinical utility of next-generation sequencing (NGS) for the management of desmoid tumors has not been established. PATIENT CONCERNS: A 42-year-old man visited our clinic for routine follow-up 1 year after left upper lobe lingular segmentectomy for lung adenocarcinoma. DIAGNOSES: Chest computed tomography showed a pleural mass adherent to the thoracotomy site. Positron emission tomography revealed mildly increased metabolism with a maximal standardized uptake value of 2.7 within the tumor, suggesting local recurrence of the previous neoplasm. Exploratory thoracotomy and en bloc resection of the tumor revealed spindle cells in a massive collagenous tissue consistent with a desmoid tumor. INTERVENTIONS: NGS was performed to confirm the diagnosis and to identify any genetic alterations that might be relevant to the prognosis of this tumor. The tumor harbored an S45F mutation in CTNNB1, which has been correlated with a high recurrence rate. Therefore, we performed adjuvant radiotherapy on the resection bed at a dose of 56 Gy. OUTCOMES: The patients experienced no postoperative or radiotherapy-related complications. Periodic follow-up examinations using computed tomography were performed every 3 months, and no evidence of recurrence of either tumor was observed during the 38 months after the last surgery. LESSONS: To the best of our knowledge, this is the first case reporting the clinical application of NGS and aggressive treatment based on the genotyping results for the management of a desmoid tumor. Our case highlights the need to consider desmoid tumors among the differential diagnoses when a pleural mass is encountered at a previous thoracotomy site. More importantly, molecular profiling using NGS can be useful for the establishment of a treatment strategy for this tumor, although further investigations are required.

Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study.

OBJECTIVES: We aimed to compare the antiviral effect of hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) in patients with COVID-19. METHODS: Nationwide retrospective case-control study was conducted to compare the effect of HCQ and LPV/r on viral shedding duration among patients with mild-to-moderate COVID-19 using the reimbursement data of National Health Insurance Service. After propensity score matching (PSM), multivariate analysis was conducted to determine statistically significant risk factors associated with prolonged viral shedding. RESULTS: Overall, 4197 patients with mild-to-moderate COVID-19 were included. Patients were categorized into three groups: LPV/r (n = 1268), HCQ (n = 801), and standard care without HCQ or LPV/r (controls, n = 2128). The median viral shedding duration was 23 (IQR 17-32), 23 (IQR 16-32), and 18 (IQR 12-25) days in the LPV/r, HCQ, and control groups, respectively. Even after PSM, the viral shedding duration was not significantly different between LPV/r and HCQ groups: 23 (IQR, 17-32) days versus 23 (IQR, 16-32) days. On multivariate analysis, old age, malignancy, steroid use, and concomitant pneumonia were statistically significant risk factors for prolonged viral shedding. CONCLUSION: The viral shedding duration was similar between HCQ and LPV/r treatment groups. There was no benefit in improving viral clearance compared to the control group.

Case report of tracheobronchial injuries after acid ingestion: CT findings with serial follow-up: Airway complication after acid ingestion.

RATIONALE: Tracheobronchial injury from acid ingestion is a less reported clinical presentation than injury of the gastrointestinal tract, but it can occur due to direct exposure from acid aspiration and cause fatal complications. PATIENT CONCERNS: A 43-year-old man presented to the emergency department after ingesting nitric acid complaining of chest pain and dyspnea. DIAGNOSES: The initial chest computed tomography (CT) images revealed an acute lung injury related to acid aspiration. The follow-up chest CT showed acute and late tracheobronchial injures. INTERVENTIONS: Bronchoscopy showed deep caustic airway injuries consisting of hemorrhage, sloughing of the mucosa, and ulceration of the trachea and left-side bronchial tree. OUTCOMES: Progressive narrowing of the left main bronchus with total collapse of the left lung occurred as a late complication of acid ingestion. LESSONS: Tracheobronchial injury should be considered in cases of aspiration pneumonia after acid ingestion; chest CT can be used to detect and assess acute and late complications of tracheobronchial injuries.

Primary Resistance to Immune Checkpoint Blockade in an STK11/TP53/KRAS-Mutant Lung Adenocarcinoma with High PD-L1 Expression.

Several studies have shown that STK11 and TP53 mutations have different effects on the susceptibility to immune checkpoint blockade in KRAS-mutant non-small cell lung cancer (NSCLC). However, the impact of STK11/TP53 co-mutations on treatment outcomes in the same clinical setting has never been reported. We recently encountered a case of a 70-year-old man who was diagnosed with advanced lung adenocarcinoma with high-programmed death-ligand 1 (PD-L1) expression. He received pembrolizumab monotherapy as a frontline treatment; however, the tumor did not respond to this therapy and showed deleterious outcome. Next-generation sequencing revealed that the tumor harbored a rare STK11/TP53/KRAS triple mutation. Our case suggests that these compound mutations may constitute a distinct, aggressive subset that is resistant to immunotherapy even when the tumor strongly expresses PD-L1. In addition, this report highlights the importance of using molecular profiling to detect co-mutations that can be associated with primary resistance or disease progression to improve survival even in the immunotherapy setting.

Measurement accuracy of lung nodule volumetry in a phantom study: Effect of axial-volume scan and iterative reconstruction algorithm.

An axial-volume scan with adaptive statistical iterative reconstruction-V (ASIR-V) is newly developed. Our goal was to identify the influence of axial-volume scan and ASIR-V on accuracy of automated nodule volumetry.An "adult' chest phantom containing various nodules was scanned using both helical and axial-volume modes at different dose settings using 256-slice CT. All CT scans were reconstructed using 30% and 50% blending of ASIR-V and filtered back projection. Automated nodule volumetry was performed using commercial software. The image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were measured.The axial-volume scan reduced radiation dose by 19.7% compared with helical scan at all radiation dose settings without affecting the accuracy of nodule volumetric measurement (P = .375). Image noise, CNR, and SNR were not significantly different between two scan modes (all, P > .05).The use of axial-volume scan with ASIR-V achieved effective radiation dose reduction while preserving the accuracy of nodule volumetry.

Combined CT texture analysis and nodal axial ratio for detection of nodal metastasis in esophageal cancer.

OBJECTIVE: To assess the accuracy of a combination of CT texture analysis (CTTA) and nodal axial ratio to detect metastatic lymph nodes (LNs) in esophageal squamous cell carcinoma (ESCC). METHODS: The contrast-enhanced chest CT images of 78 LNs (40 metastasis, 38 benign) from 38 patients with ESCC were retrospectively analyzed. Nodal axial ratios (short-axis/long-axis diameter) were calculated. CCTA parameters (kurtosis, entropy, skewness) were extracted using commercial software (TexRAD) with fine, medium, and coarse spatial filters. Combinations of significant texture features and nodal axial ratios were entered as predictors in logistic regression models to differentiate metastatic from benign LNs, and the performance of the logistic regression models was analyzed using the area under the receiver operating characteristic curve (AUROC). RESULTS: The mean axial ratio of metastatic LNs was significantly higher than that of benign LNs (0.81 ± 0.2 vs 0.71 ± 0.1, p = 0.005; sensitivity 82.5%, specificity 47.4%); namely, significantly more round than benign. The mean values of the entropy (all filters) and kurtosis (fine and medium) of metastatic LNs were significantly higher than those of benign LNs (all, p < 0.05). Medium entropy showed the best performance in the AUROC analysis with 0.802 (p < 0.001; sensitivity 85.0%, specificity 63.2%). A binary logistic regression analysis combining the nodal axial ratio, fine entropy, and fine kurtosis identified metastatic LNs with 87.5% sensitivity and 65.8% specificity (AUROC = 0.855, p < 0.001). CONCLUSION: The combination of CTTA features and the axial ratio of LNs has the potential to differentiate metastatic from benign LNs and improves the sensitivity for detection of LN metastases in ESCC. ADVANCES IN KNOWLEDGE: The combination of CTTA and nodal axial ratio has improved CT sensitivity (up to 87.5%) for the diagnosis of metastatic LNs in esophageal cancer.

Coronary artery calcium severity grading on non-ECG-gated low-dose chest computed tomography: a multiple-observer study in a nationwide lung cancer screening registry.

OBJECTIVES: To identify the optimal method for evaluation of coronary artery calcium (CAC) severity on non-electrocardiogram-gated low-dose chest computed tomography (LDCT) in a nationwide lung cancer screening registry. METHODS: A total of 256 subjects were retrospectively enrolled from participants of the Korean Lung Cancer Screening (K-LUCAS) project (an LDCT lung cancer screening registry for high-risk individuals). Four board-certified cardiothoracic radiologists independently assessed CAC severity using four different scoring methods (visual assessment, artery-based grading, segment-involvement grading, and segment-based grading) and classified severity for each case using all four methods as none, mild, moderate, or severe. Agreements between the four observers for CAC category classification and between the four different scoring methods for the same observer were assessed by Fleiss kappa statistics. Evaluation time for CAC grading was compared between observers and between grading methods. RESULTS: Interobserver agreement was moderate for visual assessment (Fleiss kappa 0.451) and substantial for the other three methods (Fleiss kappa 0.673-0.704). Agreement between the four grading methods for the same observer was substantial for three observers (Fleiss kappa 0.610-0.705) and moderate for one (Fleiss kappa 0.578). Mean evaluation time differed significantly between methods (visual assessment, 14.3 ± 11.8 s; artery-based grading, 17.6 ± 22.3 s, segment-involvement grading, 19.2 ± 6.8 s; segment-based grading, 34.2 ± 37.4 s; p < 0.01). CONCLUSION: Artery-based grading could be appropriate with substantial interobserver agreement and an acceptable mean evaluation time. KEY POINTS: • CAC severity grading methods on LDCT show moderate to substantial agreements between grading methods and observers. • Artery-based grading could be appropriate with substantial interobserver agreement and a mean evaluation time of 17.6 s. • Visual assessment is disadvantaged by high interobserver variability despite having the shortest evaluation time.

Clinical Utility of Quantitative CT Analysis for Fissure Completeness in Bronchoscopic Lung Volume Reduction: Comparison between CT and Chartis™.

OBJECTIVE: The absence of collateral ventilation (CV) is crucial for effective bronchoscopic lung volume reduction (BLVR) with an endobronchial valve. Here, we assessed whether CT can predict the Chartis™ results. MATERIALS AND METHODS: This study included 69 patients (mean age: 70.9 ± 6.6 years; 66 [95.7%] males) who had undergone CT to assess BLVR eligibility. The Chartis™ system (Pulmonox Inc.) was used to check CV. Experienced thoracic radiologists independently determined the completeness of fissures on volumetric CT images. RESULTS: The comparison between the visual and quantitative analyses revealed that 5% defect criterion showed good agreement. The Chartis™ assessment was performed for 129 lobes; 11 (19.6%) of 56 lobes with complete fissures on CT showed positive CV, while this rate was significantly higher (40 of 49 lobes, i.e., 81.6%) for lobes with incomplete fissures. The size of the fissure defect did not affect the rate of CV. Of the patients who underwent BLVR, 22 of 24 patients (91.7%) with complete fissures and three of four patients with incomplete fissures (75%) achieved target lobe volume reduction (TLVR). CONCLUSION: The quantitative analysis of fissure shows that incomplete fissures increased the probability of CV on Chartis™, while the defect size did not affect the overall rates. TLVR could be achieved even in some patients with relatively large fissure defect, if they showed negative CV on Chartis™.

Quantitative computed tomography texture analysis: can it improve diagnostic accuracy to differentiate malignant lymph nodes?

BACKGROUND AND OBJECTIVE: Mediastinal lymph node (LN) staging in individuals with non-small-cell lung cancer plays an important role in staging and treatment planning. This study aimed to assess the accuracy of computed tomography (CT) texture analysis (CTTA) in differentiating benign and malignant mediastinal LNs. METHODS: Pathologically confirmed malignant and benign mediastinal LN samples, obtained using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), were retrospectively reviewed, in addition to chest CT and 18-fluorodeoxyglucose (FDG) uptake positron emission tomography (PET) data. For each LN, CTTA was performed using "AVIEW" software (Coreline Soft, Republic of Korea) by drawing a region of interest. RESULTS: A total of 132 LNs from 80 patients were included and classified into two groups according to pathology results: malignant (n = 61) and benign (n = 71). In EBUS, size > 1 cm, round shape, heterogeneous echogenicity, and presence of coagulation necrosis sign were more prevalent in malignant than in benign LNs; length was the only feature that distinguished the two groups. Among CTTA features, compactness and normalized standard deviation (SD) showed differences between the two groups. The ability to distinguish malignant LNs was higher using high standard uptake value (SUV) on FDG PET/CT (SUVmax ≥ 5) and normalized SD on CTTA (area under the receiver operating characteristic curve 0.739 versus 0.742, respectively); however, normalized SD demonstrated very low sensitivity despite high specificity. CONCLUSIONS: CTTA may be helpful in distinguishing between benign and malignant LNs; however, the diagnostic value was not high. Therefore, integrated evaluation with other imaging modalities is needed.

Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A.

Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8+ T cells and the innate-like cytolytic activity of CD8+ T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8+ T cells, a result with implications for acute viral diseases.

Comparative Evaluation of the Loop-Mediated Isothermal Amplification Assay for Detecting Pulmonary Tuberculosis.

BACKGROUND: Early detection of tuberculosis (TB) is challenging in resource-poor settings because of limited accessibility to molecular diagnostics. The aim of this study was to evaluate the performance of the loop-mediated isothermal amplification kit (TB-LAMP) for TB diagnosis compared with conventional and molecular tests. METHODS: A total of 290 consecutive sputum samples were collected from May till September, 2015. All samples were processed using the N-Acetyl-L-cysteine (NALC) NaOH method and tested by smear microscopy, solid and liquid culture, real-time PCR, and TB-LAMP. RESULTS: The sensitivity of TB-LAMP for smear-positive and smear-negative samples with culture positivity was 92.0% and 58.8%, respectively. TB-LAMP was positive in 14.9% of TB culture-negative samples; however, all those samples were also positive by real-time PCR. In addition, none of the samples positive for nontuberculous mycobacteria by culture were positive by TB-LAMP. The overall agreement between TB-LAMP and real-time PCR was good; however, the concordance rate was significantly lower for real-time PCR positive samples with Ct values of 30-35. CONCLUSIONS: TB-LAMP could replace smear microscopy and increase TB diagnostic capacity when Xpert MTB/RIF is not feasible because of poor infrastructure.

Comparison and Combination of Strain and Shear Wave Elastography of Breast Masses for Differentiation of Benign and Malignant Lesions by Quantitative Assessment: Preliminary Study.

OBJECTIVES: To compare the diagnostic performance of strain and shear wave elastography of breast masses for quantitative assessment in differentiating benign and malignant lesions and to evaluate the diagnostic accuracy of combined strain and shear wave elastography. METHODS: Between January and February 2016, 37 women with 45 breast masses underwent both strain and shear wave ultrasound (US) elastographic examinations. The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) final assessment on B-mode US imaging was assessed. We calculated strain ratios for strain elastography and the mean elasticity value and elasticity ratio of the lesion to fat for shear wave elastography. Diagnostic performances were compared by using the area under the receiver operating characteristic curve (AUC). RESULTS: The 37 women had a mean age of 47.4 years (range, 20-79 years). Of the 45 lesions, 20 were malignant, and 25 were benign. The AUCs for elasticity values on strain and shear wave elastography showed no significant differences (strain ratio, 0.929; mean elasticity, 0.898; and elasticity ratio, 0.868; P > .05). After selectively downgrading BI-RADS category 4a lesions based on strain and shear wave elastographic cutoffs, the AUCs for the combined sets of B-mode US and elastography were improved (B-mode + strain, 0.940; B-mode + shear wave; 0.964; and B-mode, 0.724; P < .001). Combined strain and shear wave elastography showed significantly higher diagnostic accuracy than each individual elastographic modality (P = .031). CONCLUSIONS: These preliminary results showed that strain and shear wave elastography had similar diagnostic performance. The addition of strain and shear wave elastography to B-mode US improved diagnostic performance. The combination of strain and shear wave elastography results in a higher diagnostic yield than each individual elastographic modality.

Improvement in Ventilation-Perfusion Mismatch after Bronchoscopic Lung Volume Reduction: Quantitative Image Analysis.

Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases ventilation and therefore improves ventilation-perfusion (V/Q) mismatch. Materials and Methods All patients provided written informed consent to be included in this study, which was approved by the Institutional Review Board (2013-0368) of Asan Medical Center. The physiologic changes that occurred after BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced perfusion dual-energy computed tomography (CT). Patients with severe emphysema plus hyperinflation who did not respond to usual treatments were eligible. Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of life assessment, and dual-energy CT were performed at baseline and 3 months after BLVR. The effect of BLVR was assessed with repeated-measures analysis of variance. Results Twenty-one patients were enrolled in this study (median age, 68 years; mean forced expiratory volume in 1 second [FEV1], 0.75 L ± 0.29). After BLVR, FEV1 (P < .001) and 6MWD (P = .002) improved significantly. Despite the reduction in lung volume (-0.39 L ± 0.44), both ventilation per voxel (P < .001) and total ventilation (P = .01) improved after BLVR. However, neither perfusion per voxel (P = .16) nor total perfusion changed significantly (P = .49). Patients with lung volume reduction of 50% or greater had significantly better improvement in FEV1 (P = .02) and ventilation per voxel (P = .03) than patients with lung volume reduction of less than 50%. V/Q mismatch also improved after BLVR (P = .005), mainly owing to the improvement in ventilation. Conclusion The dual-energy CT analyses showed that BLVR improved ventilation and V/Q mismatch. This increased lung efficiency may be the primary mechanism of improvement after BLVR, despite the reduction in lung volume. © RSNA, 2017 Online supplemental material is available for this article.

Preoperative Axillary Lymph Node Evaluation in Breast Cancer: Current Issues and Literature Review.

Axillary lymph node (ALN) status is an important prognostic factor for overall breast cancer survival. In current clinical practice, ALN status is evaluated before surgery via multimodal imaging and physical examination. Mammography is typically suboptimal for complete ALN evaluation. Currently, ultrasonography is widely used to evaluate ALN status; nonetheless, results may vary according to operator. Ultrasonography is the primary imaging modality for evaluating ALN status. Other imaging modalities including contrast-enhanced magnetic resonance imaging, computed tomography, and positron emission tomography/computed tomography can play additional roles in axillary nodal staging.The purpose of this article is (1) to review the strengths and weaknesses of current imaging modalities for nodal staging in breast cancer patients and (2) to discuss updated guidelines for ALN management with regard to preoperative ALN imaging.

Incidentally Found Postoperative Spindle Cell Nodule of the Breast 6 Months After Ultrasound-Guided Vacuum-Assisted Excision.

Postoperative spindle cell nodule (PSCN) is a very rare pathologic complication that can occur in association with a recent core needle biopsy, surgery, or trauma. Cases of PSCN have been reported in the lower genitourinary tract, endometrium, and thyroid but are rare in the breast. Herein, we report an ultrasound-guided biopsy-proven PSCN after ultrasound-guided vacuum-assisted excision in the breast.

Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

RATIONALE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. PATIENT CONCERNS: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. DIAGNOSES: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. INTERVENTIONS: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. OUTCOMES: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. LESSONS: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical suspicion of a possible connective tissue disorder when we encounter cases with atypical presentation and/or unique chest radiologic findings especially in young patients.

Comparisons of clinical outcomes in patients with and without a preoperative tissue diagnosis in the persistent malignant-looking, ground-glass-opacity nodules.

To evaluate the clinical usefulness of surgical resection of persistent malignant-looking ground-glass-opacity nodules (GGN) without a preoperative tissue diagnosis.From September 1998 to November 2011, we retrospectively enrolled 288 patients (126 men, 162 women; mean age, 59.3 years) with lung adenocarcinoma proven by surgery and which appeared as GGN on chest computed tomography (CT, ground-glass-opacity [GGO] proportion >20%). We divided the study subjects into 2 groups: patients with a preoperative tissue diagnosis (PTD group, n = 207) and patients without a preoperative tissue diagnosis (No-PTD group, n = 81). In patients with GGN having GGO ≥ 90% (n = 140), we divided them into 2 groups: PTD group (n = 83) and No-PTD group (n = 57). The clinical and surgical outcomes were compared between the 2 groups.In 204 patients who underwent lobectomy for stage Ia lung cancer, there was no significantly different recurrence-free survival between the 2 groups (P = 0.721). A significantly lower percentage of No-PTD group waited >14 days for surgery (77.8% vs 87.9%, P = 0.030) and were hospitalized for >7 days (56.8% vs 89.9%, P < 0.001). They showed a shorter mean surgery time (136.9 vs 155.0 minutes, P = 0.019). In patients with GGN having GGO ≥ 90%, the results were the same as those of all of the study subjects.No-PTD group can gain benefits perioperatively, showing no different recurrence-free survival with PTD group in stage Ia lung cancer.

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B.

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

Instability of Plasma and Serum Progastrin-Releasing Peptide During Repeated Freezing and Thawing.

OBJECTIVES: Progastrin-releasing peptide (proGRP) is a promising biomarker for small cell lung cancer. However, not much is known about how sample processing and storage conditions affect the stability of proGRP. Here, we examined the effects of repeated freeze-thaw cycles on the stability of proGRP in plasma and serum. METHODS: Concentrations of proGRP were measured in plasma and serum samples exposed to two, three, or four freeze-thaw cycles and these were compared with values of corresponding samples exposed to one cycle (baseline). We also performed the area under the receiver-operating-characteristic curve (AUC) analysis to determine whether the differences of proGRP concentrations between each paired plasma and serum sample (ΔproGRP) can be used for identifying the samples that have been exposed to multiple freeze-thaw cycles. RESULTS: Concentrations of proGRP gradually decreased in both plasma and serum samples with increasing numbers of freeze-thaw cycles. Reduction rates of proGRP concentrations were greater in serum than in plasma samples and serum proGRP levels declined with statistical significance (p < 0.001) up to 10.1% after four freeze-thaw cycles. The ΔproGRP measurement showed fair accuracy (AUC = 0.741) for identifying samples that had been through four freeze-thaw cycles. The sensitivity was 82.8% and specificity was 62.1% at an optimal cut-off point of > 4.9. CONCLUSION: Our study shows that the stability of circulating proGRP is affected in both plasma and serum samples by repeated freezing and thawing. We also show that ΔproGRP could be used for identifying paired plasma and serum samples subjected to multiple freeze-thaw cycles.