Differentiation Between Invasive Adenocarcinoma and Focal Interstitial Fibrosis among Persistent Pulmonary Part-solid Nodules: With Emphasis on the CT Morphologic Analysis.

PURPOSE: Focal interstitial fibrosis (FIF) manifesting as a persistent part-solid nodule (PSN) has been mistakenly treated surgically due to similar imaging features to invasive adenocarcinoma (ADC). The purpose of this study was to observe predictive imaging features correlated with FIF through CT morphologic analysis. MATERIALS AND METHODS: From January 2009 to December 2020, 44 patients with surgically proven FIF in a single institution were enrolled and compared with 88 ADC patients through propensity score matching. Patient characteristics and CT morphologic analysis of persistent PSNs were used to identify predictive imaging features of FIF. Receiver operating characteristic (ROC) curve analysis was used to quantify the performance of imaging features. RESULTS: A total of 132 patients with 132 PSNs (44 FIF, 88 ADC; mean age, 67.7±7.58; 75 females) were involved in our analysis. Multivariable analysis demonstrated that preserved peritumoral vascular margin (preserved vascular margin), preserved secondary pulmonary lobule margin (preserved lobular margin), and lower coronal to axial ratio (C/A ratio; cutoff: 1.005) were significant independent predictors of FIF (P<0.05). ROC curve analysis to evaluate the predictive value of the logistic model based on the imaging features of FIF, and the AUC value was 0.881. CONCLUSION: CT imaging features of preserved vascular margin, preserved lobular margin, and lower C/A ratio (cutoff, <1.005) might be helpful imaging features in discriminating FIF over ADC among persistent PSN in clinical practice.

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. METHODS: This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. RESULTS: The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2 cc) compared to those without renal insufficiency (110.5 ± 93.2 cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3 cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4 cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (ß = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. CONCLUSION: Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

Tumor-infiltrating lymphocyte enrichment predicted by CT radiomics analysis is associated with clinical outcomes of non-small cell lung cancer patients receiving immune checkpoint inhibitors.

Background: Enrichment of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment (TME) is a reliable biomarker of immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Phenotyping through computed tomography (CT) radiomics has the overcome the limitations of tissue-based assessment, including for TIL analysis. Here, we assess TIL enrichment objectively using an artificial intelligence-powered TIL analysis in hematoxylin and eosin (H&E) image and analyze its association with quantitative radiomic features (RFs). Clinical significance of the selected RFs is then validated in the independent NSCLC patients who received ICI. Methods: In the training cohort containing both tumor tissue samples and corresponding CT images obtained within 1 month, we extracted 86 RFs from the CT images. The TIL enrichment score (TILes) was defined as the fraction of tissue area with high intra-tumoral or stromal TIL density divided by the whole TME area, as measured on an H&E slide. From the corresponding CT images, the least absolute shrinkage and selection operator model was then developed using features that were significantly associated with TIL enrichment. The CT model was applied to CT images from the validation cohort, which included NSCLC patients who received ICI monotherapy. Results: A total of 220 NSCLC samples were included in the training cohort. After filtering the RFs, two features, gray level variance (coefficient 1.71 x 10-3) and large area low gray level emphasis (coefficient -2.48 x 10-5), were included in the model. The two features were both computed from the size-zone matrix, which has strength in reflecting intralesional texture heterogeneity. In the validation cohort, the patients with high predicted TILes (≥ median) had significantly prolonged progression-free survival compared to those with low predicted TILes (median 4.0 months [95% CI 2.2-5.7] versus 2.1 months [95% CI 1.6-3.1], p = 0.002). Patients who experienced a response to ICI or stable disease with ICI had higher predicted TILes compared with the patients who experienced progressive disease as the best response (p = 0.001, p = 0.036, respectively). Predicted TILes was significantly associated with progression-free survival independent of PD-L1 status. Conclusions: In this CT radiomics model, predicted TILes was significantly associated with ICI outcomes in NSCLC patients. Analyzing TME through radiomics may overcome the limitations of tissue-based analysis and assist clinical decisions regarding ICI.

Effect of Perfluorobutane Microbubbles on Radiofrequency Ablation for Hepatocellular Carcinoma: Suppression of Steam Popping and Its Clinical Implication.

OBJECTIVE: To evaluate the effect of perfluorobutane microbubbles (Sonazoid®, GE Healthcare) on steam popping during radiofrequency (RF) ablation for treating hepatocellular carcinoma (HCC), and to assess whether popping affects treatment outcomes. MATERIALS AND METHODS: The institutional review board approved this retrospective study, which included 90 consecutive patients with single HCC, who received percutaneous RF ablation as the first-line treatment. The patients were divided into two groups, based on the presence or absence of the popping phenomenon, which was defined as an audible sound with a simultaneous sudden explosion within the ablation zone as detected via ultrasonography during the procedure. The factors contributing to the popping phenomenon were identified using multivariable logistic regression analysis. Local tumor progression (LTP) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with the log-rank test for performing comparisons between the two groups. RESULTS: The overall incidence of the popping phenomenon was 25.8% (24/93). Sonazoid® was used in 1 patient (4.2%) in the popping group (n = 24), while it was used in 15 patients (21.7%) in the non-popping group (n = 69). Multivariable analysis revealed that the use of Sonazoid® was the only significant factor for absence of the popping phenomenon (odds ratio = 0.10, p = 0.048). There were no significant differences in cumulative LTP and DFS between the two groups (p = 0.479 and p = 0.424, respectively). CONCLUSION: The use of Sonazoid® has a suppressive effect on the popping phenomenon during RF ablation in patients with HCC. However, the presence of the popping phenomenon may not affect clinical outcomes.

Surgically Resected Esophageal Squamous Cell Carcinoma: Patient Survival and Clinicopathological Prognostic Factors.

We aimed to report patients' survival after surgical resection of eSCC and to ascertain the clinical, imaging, and pathological factors related to patient prognosis. This retrospective study included 435 patients with eSCC of

Resected Pure Small Cell Lung Carcinomas and Combined Small Cell Lung Carcinomas: Histopathology Features, Imaging Features, and Prognoses.

OBJECTIVE: The objective of our study was to investigate histopathology features, imaging features, and prognoses of surgically resected pure small cell lung carcinomas (SCLCs) and combined SCLCs. MATERIALS AND METHODS: Forty-one patients with a pure SCLC or a combined SCLC underwent preoperative chest CT and 18F-FDG PET/CT and subsequent surgical resection. The clinicopathologic findings were noted by reviewing the electronic medical records. The imaging features of individual tumors were analyzed on chest CT and PET/CT scans. Each tumor was classified as being located centrally (at or in the segmental bronchus or proximal to the segmental bronchus) or peripherally (distal to the segmental bronchus). The maximum standardized uptake value (SUVmax) of each tumor was measured at PET. The 7th edition of the TNM staging system was adopted for staging. RESULTS: The study group was composed of 34 men and seven women with a mean age of 62.0 ± 10.2 (SD) years. Sixteen of 41 (39%) patients had pure SCLC, and the remaining patients had combined SCLC. The most common combined SCLC histologic subgroup was combined SCLC and large cell neuroendocrine carcinoma in 17 (41%) patients. The mean SUVmax of pure SCLCs was 5.6 ± 2.2 and was significantly lower than that of combined SCLCs (p < 0.01). Thirty-one patients (76%) had a peripheral tumor, and 10 (24%) had a central tumor. The overall survival (OS) of the 10 patients with a central tumor was 44.6 months, significantly shorter than the OS of the 31 patients with a peripheral tumor (179.2 months) (p = 0.017). The OS of 21 patients with stage I disease was significantly longer than the OS of patients with higher-stage cancer (p = 0.004). CONCLUSION: In our study group of patients with surgically resected SCLC, patients with a peripheral tumor (including a purely endobronchial tumor) or stage I disease showed a better prognosis than those with a central tumor or higher-stage disease.

Which definition of a central tumour is more predictive of occult mediastinal metastasis in nonsmall cell lung cancer patients with radiological N0 disease?

BACKGROUND: Guidelines recommend invasive mediastinal staging for centrally located tumours, even in radiological N0 nonsmall cell lung cancer (NSCLC). However, there is no uniform definition of a central tumour that is more predictive of occult mediastinal metastasis. METHODS: A total of 1337 consecutive patients with radiological N0 disease underwent invasive mediastinal staging. Tumours were categorised into central and peripheral by seven different definitions. RESULTS: About 7% (93 out of 1337) of patients had occult N2 disease, and they had significantly larger tumour size and more solid tumours on computed tomography. After adjustment for patient- and tumour-related characteristics, only the central tumour definition of the inner one-third of the hemithorax adopted by drawing concentric lines arising from the midline significantly predicted occult N2 disease (adjusted OR 2.13, 95% CI 1.17-3.87; p=0.013). This association was maintained after excluding patients with pure ground-glass nodules (adjusted OR 2.54, 95% CI 1.37-4.71; p=0.003) or only including those with solid tumours (adjusted OR 2.30, 95% CI 1.08-4.88; p=0.030). CONCLUSIONS: We suggest that a central tumour should be defined using the inner one-third of the hemithorax adopted by drawing concentric lines from the midline. This is particularly useful for predicting occult N2 disease in patients with NSCLC.

Surgically resected T1- and T2-stage esophageal squamous cell carcinoma: T and N staging performance of EUS and PET/CT.

This study aimed to evaluate the frequency of nodal metastases and to disclose the diagnostic performance of endoscopic ultrasonography (EUS) and PET/CT in T and N staging in surgically resected early-stage esophageal squamous cell carcinomas (eSCCs). Institutional review board approved this retrospective study with waiver of informed consent for reviewing medical record. We included 435 patients with an early T-stage (Tis or T1a [≤T1a], T1b and T2) eSCC. The rates of metastatic lymphadenopathy were calculated. Then, the performance of EUS and PET/CT in subdividing T and N stages was assessed. 131 ≤ T1a, 234 T1b, and 70 T2 eSCCs were identified. In discriminating ≤T1a from other cancers, the sensitivity, specificity, and accuracy of EUS were 60.3% (79/131), 80.3% (244/304), and 74.3% (323/435) respectively. With ROC curve analysis, cut-off value of SUVmax 3.05 at PET provided sensitivity 74.8% (98/131), specificity 70.1% (213/304), and accuracy 71.5% (311/435) for differentiating ≤T1a eSCCs from others. Ten (7.6%) of 131 ≤ T1a cancers had nodal metastasis. In discriminating N0 from node-positive disease, sensitivity, specificity, and accuracy of EUS were 89.6% (267/298), 41.6% (57/137), and 74.5% (324/435), respectively, whereas those of PET/CT were 88.9% (265/298), 38.7% (53/137), and 73.1% (318/435) respectively. In >70% of patients with ≤T1a eSCCs, the tumor stage can be discriminated from higher stage cancers by using EUS or PET/CT. Substantial percentage (7.6%) of ≤T1a eSCC patients have nodal metastases, which are missed in more than half of the patients in clinical staging.

Magnifying Endoscopy for Esophageal Ectopic Sebaceous Glands.

Ectopic sebaceous glands are found very rarely in the esophagus; heretofore, several cases have been reported. The sebaceous gland is originally a source of an endodermal origin; however, there have been controversies regarding whether the origin of the esophageal ectopic sebaceous gland is ectodermal or endodermal. Ectopic sebaceous glands of the esophagus usually do not cause symptoms; thus, they are often found incidentally on endoscopy for routine health screening. Endoscopic findings are characterized by single or multiple yellow patches or nodular lesions of various sizes, sometimes with small central openings. We report two cases of esophageal ectopic sebaceous glands found incidentally during endoscopy with magnifying endoscopic findings. The lesions were in the mid-esophagus and lower esophagus, respectively, and both endoscopic findings were similar as multiple yellowish patches or plaques. Magnifying endoscopy revealed the openings of the excretory ducts surrounded by circular microvessels in both cases.

JOURNAL CLUB: Doubling Time of Thymic Epithelial Tumors Correlates With World Health Organization Histopathologic Classification.

OBJECTIVE: Awareness of volume doubling times (VDTs) of different thymic epithelial tumors (TETs), including low- and high-grade thymomas and thymic carcinomas, is important for their management. The purpose of this study was to evaluate the VDTs of incidentally found TETs using 3D volumetry (3D-VDT) and longest diameter (LD-VDT). MATERIALS AND METHODS: This retrospective study included 50 patients (30 men, 20 women) who had histologically proven TETs and who underwent at least two serial CT studies at greater than 2-month intervals. TETs were classified into World Health Organization subtypes and further divided into low-grade (group A [A-B1]) and high-grade (group B [B2, B3]) thymoma and thymic carcinoma (group C). Tumor volumetry was performed by either manual segmentation (3D-VDT) or longest diameter measurement (LD-VDT). RESULTS: Groups A, B, and C accounted for 15, 26, and nine tumors. The median LDVDT in group A was 703.6 days (range, 286.7-1855.9 days); group B, 412.1 days (range, 130.9-716.9 days), and group C, 146.3 days (range, 68.9-448.3 days) (p < 0.01). The median 3D-VDTs were 1138.8 days (range, 350.1-3915.3 days), 711.0 days (range, 145.5-7209.5 days), and 203.1 days (range, 58.9-766.9 days) (p < 0.01). In ROC analysis, both LD-VDT (AUC, 0.873; p < 0.01; optimal cutoff value, 222.6 days; 90.2% sensitivity, 77.8% specificity) and 3DVDT (AUC, 0.859; p < 0.01; optimal cutoff value, 218.0 days; 92.7% sensitivity; 66.7% specificity) differentiated group C from groups A and B. CONCLUSION: VDTs differ among TETs according to tumor grade. Measurement of either LD-VDT or 3D-VDT is sensitive for differentiating carcinomas from thymomas (cutoff value, ≈ 220 days).

ZnO nanowire-based nonvolatile memory devices with Al2O3 layers as storage nodes.

Top-gate ZnO nanowire field-effect transistors (FETs) with Al2O3 gate dielectric layers as storage nodes were fabricated and their memory effects were characterized in this work. The Al2O3 layers deposited on the ZnO nanowire channels were utilized not only as gate dielectric ones but also as charge trapping ones. For a representative top-gate ZnO nanowire FET, its I(DS)-V(GS) characteristics for the double sweep of the gate voltages exhibit the counterclockwise hysteresis and the threshold voltage shift. The gate voltage in the pulse form was applied for 1 s, and the threshold voltage shift of I(DS)-V(GS) characteristics was extended from 0.3 to 0.8 V compared with that for the double sweep. In this ZnO nanowire FET, negative charge carriers originated from the gate electrode are stored in the Al2O3 layer for applied negative gate voltages, and they are extracted for applied positive gate voltages.

Silicon nanowire-based tunneling field-effect transistors on flexible plastic substrates.

A technique to implement silicon nanowire (SiNW)-based tunneling field-effect transistors (TFETs) on flexible plastic substrates is developed for the first time. The p-i-n configured Si NWs are obtained from an Si wafer using a conventional top-down CMOS-compatible technology, and they are then transferred onto the plastic substrate. Based on gate-controlled band-to-band tunneling (BTBT) as their working principle, the SiNW-based TFETs show normal p-channel switching behavior with a threshold voltage of -1.86 V and a subthreshold swing of 827 mV/dec. In addition, ambipolar conduction is observed due to the presence of the BTBT between the heavily doped p+ drain and n+ channel regions, indicating that our TFETs can operate in the n-channel mode as well. Furthermore, the BTBT generation rates for both the p-channel and n-channel operating modes are nearly independent of the bending state (strain = 0.8%) of the plastic substrate.

ZnO nanowire field-effect transistors with floating gate nodes of Au nanoparticles.

The memory characteristics of top-gate single ZnO nanowire-based field-effect transistors (FETs) with floating gate nodes consisting of Au nanoparticles on top of the nanowire channels were investigated in this study. Au nanoparticles, synthesized by a thermal deposition of Au thin film and by a subsequent thermal annealing procedure, were embedded in between Al2O3 tunneling and control gate layers deposited on ZnO nanowire channels. For a representative single ZnO nanowire-based FET with floating gate nodes consisting of Au nanoparticles embedded between Al2O3 layers, its drain current versus gate voltage (I(DS)-V(DS)) characteristics for a double sweep in the gate voltage range from -4 to 4 V exhibit a clockwise hysteresis loop with a threshold voltage shift of deltaV(th) = 1.6 V, resulting from the tunneling of the charge carriers from the ZnO nanowire channel into the Au nanoparticles. In addition, the charge storage characteristic of threshold voltage shift with the elapsed time observed in this FET is also discussed in this paper.

A 60-Hz sinusoidal magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species.

PURPOSE: To explore the effects of power frequency magnetic fields (MF) on cell growth in prostate cancer, DU145, PC3, and LNCaP cells were examined in vitro. MATERIALS AND METHODS: The cells were exposed to various intensities and durations of 60-Hz sinusoidal MF in combination with various serum concentrations in the media. To analyze MF effects on cell growth, cell counting, trypan blue exclusion assay, Western blot analysis, flow cytometry, enzyme-linked immunosorbent assay (ELISA), semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence microscopy, and spectrofluorometry were used. RESULTS: MF exposure induced significant cell growth inhibition and apoptosis in an intensity- and time-dependent manner, in which cell cycle arrest, cleaved Caspase-3, and reactive oxygen species (ROS) increased. Pretreatment with a Caspase-3 inhibitor or antioxidant, N-acetyl-L-cysteine (NAC), significantly attenuated MF-induced cell growth inhibition and cell death. Media replacement experiments failed to show any notable change in the MF effects. CONCLUSIONS: These results demonstrate 60-Hz sinusoidal MF-activated cell growth inhibition of prostate cancer in vitro. Apoptosis together with cell cycle arrest were the dominant causes of the MF-elicited cell growth inhibition, mediated by MF-induced ROS. These results suggest that a possibility of using 60-Hz MF in radiation therapy of prostate cancer could usefully be investigated.

NOT and NAND logic circuits composed of top-gate ZnO nanowire field-effect transistors with high-k Al(2)O(3) gate layers.

Electrical characteristics of NOT and NAND logic circuits fabricated using top-gate ZnO nanowire field-effect transistors (FETs) with high-k Al(2)O(3) gate layers were investigated in this study. To form a NOT logic circuit, two identical FETs whose I(on)/I(off) ratios were as high as ∼10(8) were connected in series in a single ZnO nanowire channel, sharing a common source electrode. Its voltage transfer characteristics exhibited an inverting operation and its logic swing was 98%. In addition, the characteristics of a NAND logic circuit composed of three top-gate FETs connected in series in a single nanowire channel are discussed in this paper.

ZnO nanowire-based nano-floating gate memory with Pt nanocrystals embedded in Al(2)O(3) gate oxides.

The memory characteristics of ZnO nanowire-based nano-floating gate memory (NFGM) with Pt nanocrystals acting as the floating gate nodes were investigated in this work. Pt nanocrystals were embedded between Al(2)O(3) tunneling and control oxide layers deposited on ZnO nanowire channels. For a representative ZnO nanowire-based NFGM with embedded Pt nanocrystals, a threshold voltage shift of 3.8 V was observed in its drain current versus gate voltage (I(DS)-V(GS)) measurements for a double sweep of the gate voltage, revealing that the deep effective potential wells built into the nanocrystals provide our NFGM with a large charge storage capacity. Details of the charge storage effect observed in this memory device are discussed in this paper.

Fabrication and device characterization of omega-shaped-gate ZnO nanowire field-effect transistors.

Omega-shaped-gate (OSG) nanowire-based field effect transistors (FETs) have attracted a great deal of attention recently, because theoretical simulations predicted that they should have a higher device performance than nanowire-based FETs with other gate geometries. OSG FETs with channels composed of ZnO nanowires were successfully fabricated in this study using photolithographic processes. In the OSG FETs fabricated on oxidized Si substrates, the channels composed of ZnO nanowires with diameters of about 110 nm are coated with Al(2)O(3) using atomic layer deposition, which surrounds the channels and acts as a gate dielectric. About 80% of the surfaces of the nanowires coated with Al(2)O(3) are covered with the gate metal to form OSG FETs. A representative OSG FET fabricated in this study exhibits a mobility of 30.2 cm(2)/ (V s), a peak transconductance of 0.4 muS (V(g) = -2.2 V), and an I(on)/I(off) ratio of 10(7). To the best of our knowledge, the value of the I(on)/I(off) ratio obtained from this OSG FET is higher than that of any of the previously reported nanowire-based FETs. Its mobility, peak transconductance, and I(on)/I(off) ratio are remarkably enhanced by 3.5, 32, and 10(6) times, respectively, compared with a back-gate FET with the same ZnO nanowire channel as utilized in the OSG FET.