Whole Process of Standardization of Diffusion-Weighted Imaging: Phantom Validation and Clinical Application According to the QIBA Profile.

Background: To use the apparent diffusion coefficient (ADC) as reliable biomarkers, validation of MRI equipment performance and clinical acquisition protocols should be performed prior to application in patients. This study aims to validate various MRI equipment and clinical brain protocols for diffusion weighted imaging (DWI) using commercial phantom, and confirm the validated protocols in patients' images. Methods: The performance of four different scanners and clinical brain protocols were validated using a Quantitative Imaging Biomarker Alliance (QIBA) diffusion phantom and cloud-based analysis tool. We evaluated the performance metrics regarding accuracy and repeatability of ADC measurement using QIBA profile. The validated clinical brain protocols were applied to 17 patients, and image quality and repeatability of ADC were assessed. Results: The MRI equipment performance of all four MRI scanners demonstrated high accuracy in ADC measurement (ADC bias, -2.3% to -0.4%), excellent linear correlation to the reference ADC value (slope, 0.9 to 1.0; R2, 0.999-1.000), and high short-term repeatability [within-subject-coefficient-of-variation (wCV), 0% to 0.3%]. The clinical protocols were also validated by fulfilling QIBA claims with high accuracy (ADC bias, -3.1% to -0.7%) and robust repeatability (wCV, 0% to 0.1%). Brain DWI acquired using the validated clinical protocols showed ideal image quality (mean score ≥ 2.9) and good repeatability (wCV, 1.8-2.2). Conclusions: The whole process of standardization of DWI demonstrated the robustness of ADC with high accuracy and repeatability across diverse MRI equipment and clinical protocols in accordance with the QIBA claims.

Automated segmentation of the fractured vertebrae on CT and its applicability in a radiomics model to predict fracture malignancy.

Although CT radiomics has shown promising results in the evaluation of vertebral fractures, the need for manual segmentation of fractured vertebrae limited the routine clinical implementation of radiomics. Therefore, automated segmentation of fractured vertebrae is needed for successful clinical use of radiomics. In this study, we aimed to develop and validate an automated algorithm for segmentation of fractured vertebral bodies on CT, and to evaluate the applicability of the algorithm in a radiomics prediction model to differentiate benign and malignant fractures. A convolutional neural network was trained to perform automated segmentation of fractured vertebral bodies using 341 vertebrae with benign or malignant fractures from 158 patients, and was validated on independent test sets (internal test, 86 vertebrae [59 patients]; external test, 102 vertebrae [59 patients]). Then, a radiomics model predicting fracture malignancy on CT was constructed, and the prediction performance was compared between automated and human expert segmentations. The algorithm achieved good agreement with human expert segmentation at testing (Dice similarity coefficient, 0.93-0.94; cross-sectional area error, 2.66-2.97%; average surface distance, 0.40-0.54 mm). The radiomics model demonstrated good performance in the training set (AUC, 0.93). In the test sets, automated and human expert segmentations showed comparable prediction performances (AUC, internal test, 0.80 vs 0.87, p = 0.044; external test, 0.83 vs 0.80, p = 0.37). In summary, we developed and validated an automated segmentation algorithm that showed comparable performance to human expert segmentation in a CT radiomics model to predict fracture malignancy, which may enable more practical clinical utilization of radiomics.

Prediction of the Acuity of Vertebral Compression Fractures on CT Using Radiologic and Radiomic Features.

RATIONALE AND OBJECTIVES: To develop and validate prediction models to differentiate acute and chronic vertebral compression fractures based on radiologic and radiomic features on CT. MATERIALS AND METHODS: This study included acute and chronic compression fractures in patients who underwent both spine CT and MRI examinations. For each fractured vertebra, three CT findings ([1] cortical disruption, [2] hypoattenuating cleft or sclerotic line, and [3] relative bone marrow attenuation) were assessed by two radiologists. A radiomic score was built from 280 radiomic features extracted from non-contrast-enhanced CT images. Weighted multivariable logistic regression analysis was performed to build a radiologic model based on CT findings and an integrated model combining the radiomic score and CT findings. Model performance was evaluated and compared. Models were externally validated using an independent test cohort. RESULTS: A total to 238 fractures (159 acute and 79 chronic) in 122 patients and 58 fractures (39 acute and 19 chronic) in 32 patients were included in the training and test cohorts, respectively. The AUC of the radiomic score was 0.95 in the training and 0.93 in the test cohorts. The AUC of the radiologic model was 0.89 in the training and 0.83 in the test cohorts. The discriminatory performance of the integrated model was significantly higher than the radiologic model in both the training (AUC, 0.97; p<0.01) and the test (AUC, 0.95; p=0.01) cohorts. CONCLUSION: Combining radiomics with radiologic findings significantly improved the performance of CT in determining the acuity of vertebral compression fractures.

Incidence of Immune-Mediated Pseudoprogression of Lymphoma Treated with Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis.

We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords "lymphoma," "immunotherapy," and "pseudoprogression." Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran's Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06-0.17). There was no publication bias in Begg's test (p = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08-0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs.

Photothermal therapy via a gold nanoparticle-coated stent for treating stent-induced granulation tissue formation in the rat esophagus.

Minimally invasive therapies using stent technology are currently limited by stent-induced granulation tissue formation adjacent to the stent. The effectiveness of photothermal therapy (PTT) using a gold nanoparticle (AuNP)-coated stent for treating stent-induced granulation tissue formation in the rat esophagus was investigated. All experiments were approved by the animal research committee of our institution. An AuNP-coated, self-expandable metallic stent (SEMS) was produced to conduct PTT under near-infrared laser irradiation. Forty rats were randomly divided into four groups (10 rats each). The animals in group A (non-coated SEMS) and group B (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) were sacrificed 4 weeks after stent placement. The rats in group C (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) and group D (AuNP-coated SEMS with local heating at 65 °C at 4 and 8 weeks) were sacrificed 8 weeks after stent placement. The effectiveness of local heating was assessed by histopathology. All procedures were successful in all of the animals. Seven rats were excluded because of stent migration (n = 2) and death (n = 5). Granulation tissue formation-related variables were significantly higher in group A than in groups B-D (all p < 0.05). Heat-shock protein 70 (HSP70) and TUNEL expression were significantly lower in group A than in groups B-D (all p < 0.05). Granulation tissue formation-related variables were significantly higher in group C than in groups B and D (all p < 0.05). PTT using AuNP-coated SEMS successfully treated granulation tissue formation after stent placement in the rat esophagus.

CDISC-compliant clinical trial imaging management system with automatic verification and data Transformation: Focusing on tumor response assessment data in clinical trials.

OBJECTIVE: Major issues in imaging data management of tumor response assessment in clinical trials include high human errors in data input and unstandardized data structures, warranting a new breakthrough IT solution. Thus, we aim to develop a Clinical Data Interchange Standards Consortium (CDISC)-compliant clinical trial imaging management system (CTIMS) with automatic verification and transformation modules for implementing the CDISC Study Data Tabulation Model (SDTM) in the tumor response assessment dataset of clinical trials. MATERIALS AND METHODS: In accordance with various CDISC standards guides and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, the overall system architecture of CDISC-compliant CTIMS was designed. Modules for standard-compliant electronic case report form (eCRF) to verify data conformance and transform into SDTM data format were developed by experts in diverse fields such as medical informatics, medical, and clinical trial. External validation of the CDISC-compliant CTIMS was performed by comparing it with our previous CTIMS based on real-world data and CDISC validation rules by Pinnacle 21 Community Software. RESULTS: The architecture of CDISC-compliant CTIMS included the standard-compliant eCRF module of RECIST, the automatic verification module of the input data, and the SDTM transformation module from the eCRF input data to the SDTM datasets based on CDISC Define-XML. This new system was incorporated into our previous CTIMS. External validation demonstrated that all 176 human input errors occurred in the previous CTIMS filtered by a new system yielding zero error and CDISC-compliant dataset. The verified eCRF input data were automatically transformed into the SDTM dataset, which satisfied the CDISC validation rules by Pinnacle 21 Community Software. CONCLUSIONS: To assure data consistency and high quality of the tumor response assessment data, our new CTIMS can minimize human input error by using standard-compliant eCRF with an automatic verification module and automatically transform the datasets into CDISC SDTM format.

Combined radiomics-clinical model to predict malignancy of vertebral compression fractures on CT.

OBJECTIVES: To develop and validate a combined radiomics-clinical model to predict malignancy of vertebral compression fractures on CT. METHODS: One hundred sixty-five patients with vertebral compression fractures were allocated to training (n = 110 [62 acute benign and 48 malignant fractures]) and validation (n = 55 [30 acute benign and 25 malignant fractures]) cohorts. Radiomics features (n = 144) were extracted from non-contrast-enhanced CT images. Radiomics score was constructed by applying least absolute shrinkage and selection operator regression to reproducible features. A combined radiomics-clinical model was constructed by integrating significant clinical parameters with radiomics score using multivariate logistic regression analysis. Model performance was quantified in terms of discrimination and calibration. The model was internally validated on the independent data set. RESULTS: The combined radiomics-clinical model, composed of two significant clinical predictors (age and history of malignancy) and the radiomics score, showed good calibration (Hosmer-Lemeshow test, p > 0.05) and discrimination in both training (AUC, 0.970) and validation (AUC, 0.948) cohorts. Discrimination performance of the combined model was higher than that of either the radiomics score (AUC, 0.941 in training cohort and 0.852 in validation cohort) or the clinical predictor model (AUC, 0.924 in training cohort and 0.849 in validation cohort). The model stratified patients into groups with low and high risk of malignant fracture with an accuracy of 98.2% in the training cohort and 90.9% in the validation cohort. CONCLUSIONS: The combined radiomics-clinical model integrating clinical parameters with radiomics score could predict malignancy in vertebral compression fractures on CT with high discriminatory ability. KEY POINTS: • A combined radiomics-clinical model was constructed to predict malignancy of vertebral compression fractures on CT by combining clinical parameters and radiomics features. • The model showed good calibration and discrimination in both training and validation cohorts. • The model showed high accuracy in the stratification of patients into groups with low and high risk of malignant vertebral compression fractures.

Test-retest repeatability of ultrasonographic shear wave elastography in a rat liver fibrosis model: toward a quantitative biomarker for preclinical trials.

PURPOSE: This study evaluated the test-retest repeatability and measurement variability of ultrasonographic shear wave elastography (SWE) for liver stiffness in a rat liver fibrosis model. METHODS: In 31 Sprague-Dawley rats divided into three groups (high-dose, low-dose, and control), liver fibrosis was induced by intraperitoneal administration of thioacetamide for 8 weeks. A dedicated radiographer performed SWE to measure liver stiffness in kilopascals in two sessions at a 3-day interval. We calculated correlations between liver stiffness and histopathologic results, measurement variability in each session using coefficients of variation (CoVs) and interquartile/median (IQR/M), and test-retest repeatability between both sessions using the repeatability coefficient. RESULTS: Different levels of liver fibrosis in each group were successfully induced in the animal model. The mean liver stiffness values were 8.88±1.48 kPa in the control group, 11.62±1.70 kPa in the low-dose group, and 11.91±1.73 kPa in the high-dose group. The correlation between collagen areas and liver stiffness values was moderate (r=0.6). In all groups, the second session yielded lower CoVs (i.e., more reliable results) for liver stiffness than the first session, suggesting a training effect for the operator. The mean IQR/M values were also lower in the second session than in the first session, which had four outliers (0.21 vs. 0.12, P<0.001). The test-retest repeatability coefficient was 3.75 kPa and decreased to 2.82 kPa after removing the four outliers. CONCLUSION: The use of ultrasonographic SWE was confirmed to be feasible and repeatable for evaluating liver fibrosis in preclinical trials. Operator training might reduce variability in liver stiffness measurements.

Temporary percutaneous radiologic gastrojejunostomy with single gastropexy.

BACKGROUND: Although the effectiveness of percutaneous radiologic gastrojejunostomy (PRGJ) has been reported, a detailed description of the indications and clinical effectiveness of temporary PRGJ is still limited. PURPOSE: To evaluate the clinical effectiveness and technical feasibility of temporary PRGJ using the modified Chiba-needle technique with single gastropexy. MATERIAL AND METHODS: Temporary PRGJ using the modified Chiba-needle technique with single gastropexy was performed in 27 consecutive patients (19 men, 8 women; mean age = 61 years; age range = 32-77 years) for esophageal perforation (n = 18) or postoperative gastroparesis (n = 9). Outcomes analyzed included the technical and clinical success, procedure-related complications, and the tube indwelling period. RESULTS: Technical and clinical success was achieved in all 27 patients. All the tubes were electively removed 19-364 days (mean indwelling period = 104 days) after confirmation of the possibility of oral intake. Asymptomatic pneumoperitoneum occurred in 2/27 (7.4%) patients as minor complications and was resolved spontaneously by the time of the one-week follow-up. There were no major complications. During the follow-up period, a total of 11 tube changes were performed in seven patients for an elective tube change within a six-month interval (n = 5) or because of tube occlusion (n = 6). CONCLUSION: Temporary PRGJ using the modified Chiba-needle technique with a single gastropexy was clinically effective and technically feasible in patients with esophageal perforation or gastroparesis. It can provide adequate enteral nutrition during its temporary placement.

Percutaneous antegrade removal of foreign bodies in the urinary tract: a 20-year, single-center experience.

BACKGROUND: While removing urinary tract foreign bodies is mostly performed through retrograde cystoscopy, antegrade removal using interventional procedures is reported less frequently. PURPOSE: To evaluate the safety and effectiveness of percutaneous antegrade removal of urinary tract foreign bodies. MATERIAL AND METHODS: A total of 14 consecutive patients (age range 9-80 years) who percutaneous antegrade removal of urinary tract foreign bodies between January 2001 and March 2020 were reviewed. Detailed removal procedures and complications were reviewed retrospectively. RESULTS: Types of foreign bodies were sheared percutaneous nephrostomy (PCN) catheters (n = 5), sheared double J stents (n = 3), migrated ureteral catheters (n = 3), embolization coils (n = 2), and a 0.018-inch guide wire (n = 1). The mean and median indwelling times (range 0-306 days) of the foreign bodies were 58.3 and 1.5 days, respectively. Computed tomography (CT) scans were conducted in six patients, and the extent and nature of the foreign bodies were well-visualized on CT scans. The removal access was new PCN access (n = 8), the tract missing PCN catheter (n = 3), pre-existing PCN access (n = 2), and percutaneous dissection (n = 1). The removal success rate was 92.9% (13/14) with either a simple (n = 8) or modified (n = 4; combination of a snare and guide wire is used) snare technique or a direct forceps grasp (n = 1). The mean procedure time for successful cases was 14.2 min (range 7-25 min). Procedure-related hematoma with (n = 2) or without (n = 1) renal pelvis injury occurred in three patients, which were all self-limited within one week. CONCLUSION: Percutaneous antegrade removal is safe and effective for urinary tract foreign bodies.

Tract ablation after radiofrequency ablation to prevent viable tumor cell adhesion to the needle electrode.

PURPOSE: To evaluate whether the additive needle tract ablation (TA) can reduce adherent cells on the needle tract after radiofrequency ablation (RFA) in a preclinical HCC mouse model. METHODS: Hep3B-Luc cells were engrafted in the Balb/c-nude mice. Nineteen mice were randomly assigned into three groups: the needle only group (needle placement only without performing RFA), the RFA only group (needle placement with active RFA treatment), and the RFA-TA group (needle placement with active RFA treatment and additive tract ablation). The 17-gauge needle with a 10-mm active tip was used. After RFA and TA, the viability of adherent tumor cells on the RFA needle was evaluated with bioluminescence imaging (BLI) and live-cell counting. RESULTS: We observed that RFA-TA group had the lowest BLI values compared with other groups (needle only group, 11.2 ± 6.4 million; RFA only group, 13.6 ± 9.1 million; RFA-TA group, 1.11 ± 0.8 million, p = 0.001). Live cell counting with acridine orange/propidium iodide staining also confirmed that the counted viable cell numbers in RFA-TA group were lowest compared to the other groups (needle only group, 14.8 ± 4.5; RFA only group, 643.8 ± 131.9; RFA-TA group, 1.5 ± 0.9, p < 0.001). CONCLUSIONS: The additive tract ablation can significantly reduce the number of viable tumor cells adherent to the RFA needle, which can prevent needle tract seeding after RFA procedure.

Defense Mechanisms and Psychological Characteristics According to Suicide Attempts in Patients with Borderline Personality Disorder.

OBJECTIVE: There have been many biological studies on suicide behaviors of borderline personality disorder (BPD), however few studies have sought to psychoanalytic characteristics including defense mechanisms. Therefore, we investigated psychological, symptomatic, and personality characteristics including defense mechanisms in suicide attempters and non-suicide attempters among patients with BPD. METHODS: We enrolled 125 patients with BPD. Forty-two patients with a history of one or more suicide attempts formed the suicide attempters group and 83 patients with no such history formed the non-suicide attempters group. We collated the differences in clinical and psychological characteristics between the two groups by using the Symptom Checklist-90-Revised (SCL-90-R), the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the Personality Disorder Questionnaire-4+ (PDQ-4+), and the Defense Style Questionnaire (DSQ). RESULTS: The suicide attempters group scored higher on the hostility subscale of SCL-90-R. The suicide attempters group also scored higher on the Infrequency, Back Infrequency, Lie, Masculinity-femininity, Paranoia, Psychasthenia, and Schizophrenia scales of the MMPI-2. The incidence of paranoid and antisocial personality disorders, as assessed by the PDQ-4+, was significantly different in both groups. Maladaptive, self-sacrificing defense style, splitting and affiliation on the DSQ were also higher for the suicide attempters group. In the results of the logistic regression analysis, gender, the F(B) and L scales on the MMPI-2, and 'splitting of other's image' defense mechanism on the DSQ were the factors that significantly influenced to suicide attempts. CONCLUSION: These findings suggest that impulsive psychiatric features and maladaptive defense style may be related to suicidal risk in patients with BPD. Therefore, our findings may help clinicians in estimating the risk of suicide in patients with BPD.

Gadoxetate-enhanced dynamic contrast-enhanced MRI for evaluation of liver function and liver fibrosis in preclinical trials.

BACKGROUND: To facilitate translational drug development for liver fibrosis, preclinical trials need to be run in parallel with clinical research. Liver function estimation by gadoxetate-enhanced dynamic contrast-enhanced MRI (DCE-MRI) is being established in clinical research, but still rarely used in preclinical trials. We aimed to evaluate feasibility of DCE-MRI indices as translatable biomarkers in a liver fibrosis animal model. METHODS: Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (200 mg, 150 mg, and saline for the high-dose, low-dose, and control groups, respectively). Subsequently, DCE-MRI was performed to measure: relative liver enhancement at 3-min (RLE-3), RLE-15, initial area-under-the-curve until 3-min (iAUC-3), iAUC-15, and maximum-enhancement (Emax). The correlation coefficients between these MRI indices and the histologic collagen area, indocyanine green retention at 15-min (ICG-R15), and shear wave elastography (SWE) were calculated. Diagnostic performance to diagnose liver fibrosis was also evaluated by receiver-operating-characteristic (ROC) analysis. RESULTS: Animal model was successful in that the collagen area of the liver was the largest in the high-dose group, followed by the low-dose group and control group. The correlation between the DCE-MRI indices and collagen area was high for iAUC-15, Emax, iAUC-3, and RLE-3 but moderate for RLE-15 (r, - 0.81, - 0.81, - 0.78, - 0.80, and - 0.51, respectively). The DCE-MRI indices showed moderate correlation with ICG-R15: the highest for iAUC-15, followed by iAUC-3, RLE-3, Emax, and RLE-15 (r, - 0.65, - 0.63, - 0.62, - 0.58, and - 0.56, respectively). The correlation coefficients between DCE-MRI indices and SWE ranged from - 0.59 to - 0.28. The diagnostic accuracy of RLE-3, iAUC-3, iAUC-15, and Emax was 100% (AUROC 1.000), whereas those of RLE-15 and SWE were relatively low (AUROC 0.777, 0.848, respectively). CONCLUSION: Among the gadoxetate-enhanced DCE-MRI indices, iAUC-15 and iAUC-3 might be bidirectional translatable biomarkers between preclinical and clinical research for evaluating histopathologic liver fibrosis and physiologic liver functions in a non-invasive manner.

Balloon-Expandable Biodegradable Stents Versus Self-Expandable Metallic Stents: A Comparison Study of Stent-Induced Tissue Hyperplasia in the Rat Urethra.

PURPOSE: To compare the degrees of stent-induced tissue hyperplasia of balloon-expandable, biodegradable stents (BEBSs) with those of self-expandable metallic stents (SEMSs) in a rat urethral model. MATERIALS AND METHODS: A total of 20 rats were randomized into two groups. The BEBS group (n = 10) received a poly-l-lactic acid (PLLA) biodegradable stent. The SEMS group (n = 10) received a nitinol bare stent. All rats were killed eight weeks after stent placement. The degree of stent-induced tissue hyperplasia was assessed by comparing the results of retrograde urethrography and histologic examination between the two groups. RESULTS: Stent placement was technically successful in all rats. Two rats in the BEBS group were excluded due to procedure-related death. The mean luminal diameter of stented urethra on urethrograms was not significantly different at 4 and 8 weeks between the two groups. On histologic analysis, the percentage of granulation tissue area (p < 0.001) and the thickness of papillary projection (p < 0.001) were significantly higher in the BEBS group compared with the SEMS group. The inflammatory cell infiltration showed a clear tendency to significance (p = 0.050). There were no statistical differences in the number of epithelial layers and the thickness of submucosal fibrosis between the two groups. CONCLUSION: Formation of stent-induced tissue hyperplasia was significantly evident in the rat urethra with similar degrees between the BEBS and the SEMS. The BEBS was associated with a thicker papillary projection and larger granulation tissue area resulting from higher inflammation compared with the SEMS.

In Vivo Fluorescence Microendoscopic Monitoring of Stent-Induced Fibroblast Cell Proliferation in an Esophageal Mouse Model.

PURPOSE: To evaluate the feasibility of self-expanding metal stent (SEMS) placement and fluorescence microendoscopic monitoring for determination of fibroblast cell proliferation after stent placement in an esophageal mouse model. MATERIALS AND METHODS: Twenty fibroblast-specific protein (FSP)-1 green fluorescent protein (GFP) transgenic mice were analyzed. Ten mice (Group A) underwent SEMS placement, and fluoroscopic and fluorescence microendoscopic images were obtained biweekly until 8 weeks thereafter. Ten healthy mice (Group B) were used for control esophageal values. RESULTS: SEMS placement was technically successful in all mice. The relative average number of fibroblast GFP cells and the intensities of GFP signals in Group A were significantly higher than in Group B after stent placement. The proliferative cellular response, including granulation tissue, epithelial layer, submucosal fibrosis, and connective tissue, was increased in Group A. FSP-1-positive cells were more prominent in Group A than in Group B. CONCLUSIONS: SEMS placement was feasible and safe in an esophageal mouse model, and proliferative cellular response caused by fibroblast cell proliferation after stent placement was longitudinally monitored using a noninvasive fluorescence microendoscopic technique. The results have implications for the understanding of proliferative cellular response after stent placement in real-life patients and provide initial insights into new clinical therapeutic strategies for restenosis.

Evaluation of drug mechanism and efficacy of a novel anti-angiogenic agent, TTAC-0001, using multi-modality bioimaging in a mouse breast cancer orthotopic model.

PURPOSE: Targeting of vascular endothelial growth factor receptors (VEGFRs) has potential anti-angiogenic effects because VEGFR-2 is the major signaling regulator of VEGF/VEGFR pathways. We aimed to elucidate the drug mechanism and anti-tumor efficacy of TTAC-0001, a novel, fully human anti-VEGFR-2/KDR monoclonal antibody, in mouse orthotopic breast cancer model using multi-modal bioimaging. MATERIALS AND METHODS: We used orthotopic xenograft tumor model in which human breast cancer cells (MDA-MB-231) were injected into the right mammary fat pad of Balb/c nude mice. We investigated its biodistribution using serial fluorescence imaging after injecting fluorescent-labelled-drug and mode of action using Matrigel plug angiogenesis assays. The anti-tumor efficacy of drug was assessed using ultrasonography and bioluminescence imaging. Histopathologic analyses, including hematoxylin and eosin staining and immunohistochemistry with anti-CD31 and anti-Ki-67 antibodies, were performed. Each experiment had four groups: control, bevacizumab 10 mg/kg (BVZ-10 group), TTAC-0001 2 mg/kg (TTAC-2 group), and TTAC-0001 10 mg/kg (TTAC-10 group). RESULTS: The TTAC-10 group showed good tumor targeting that lasted for at least 6 days and had a good anti-angiogenic effect with decreased hemoglobin content and fewer CD31-positive cells in the Matrigel plug. Compared with BVZ-10 and TTAC-2 groups, the TTAC-10 group showed the strongest anti-tumor efficacy, inhibiting tumor growth as detected by ultrasonography and bioluminescence imaging. The TTAC-10 group also showed the lowest viable tumor and micro-vessel areas and the lowest Ki-67 index in histopathologic analyses. CONCLUSION: We firstly demonstrated that TTAC-0001 effectively inhibited tumor growth and neovascularization in mouse orthotopic breast cancer model. It may provide a future treatment option for breast cancer.

Radiation-induced esophageal strictures treated with fluoroscopic balloon dilation: clinical outcomes and factors influencing recurrence in 62 patients.

Background Balloon dilation is safe and effective for the treatment of radiation-induced esophageal stricture (RIES), with favorable short-term and mid-term outcomes; however, few reports of long-term outcomes exist. Few studies have evaluated factors associated with recurrence after balloon dilation. Purpose To evaluate the long-term outcome of balloon dilation in patients with RIES and to identify factors associated with stricture recurrence. Material and Methods The medical records of 62 consecutive patients who had undergone fluoroscopic balloon dilation for RIES at our institution between December 1998 and June 2016 were reviewed. Results One hundred and twenty balloon dilation sessions were performed in 62 patients (mean = 1.9 sessions per patient). Clinical success was achieved in 53 (86%) patients after single (n = 37) or multiple (n = 16) dilation sessions. Complications occurred in 27% of the dilation sessions. The primary patency rates at one, two, three, and five years were 60%, 56%, 52%, and 52%, respectively. Secondary patency rates at one, two, three, and five years were 87%, 85%, 85%, and 80%, respectively. Multivariate logistic regression analysis identified an interval from radiation therapy (RT) to stricture of ≥6 months (hazard ratio [HR] = 0.205; P < 0.001), strictures located at the cervical esophagus (HR = 5.846; P < 0.001), and stricture length of ≥2 cm (HR = 2.923; P = 0.006) as significant predictors of recurrence. Conclusion Despite the high incidence of ruptures and recurrences, fluoroscopic balloon dilation is valuable as an initial therapeutic option for patients with RIES.

Direct Synthesis of Carbon Nanotube Field Emitters on Metal Substrate for Open-Type X-ray Source in Medical Imaging.

We report the design, fabrication and characterization of a carbon nanotube enabled open-type X-ray system for medical imaging. We directly grew the carbon nanotubes used as electron emitter for electron gun on a non-polished raw metallic rectangular-rounded substrate with an area of 0.1377 cm² through a plasma enhanced chemical vapor deposition system. The stable field emission properties with triode electrodes after electrical aging treatment showed an anode emission current of 0.63 mA at a gate field of 7.51 V/µm. The 4.5-inch cubic shape open type X-ray system was developed consisting of an X-ray aperture, a vacuum part, an anode high voltage part, and a field emission electron gun including three electrodes with focusing, gate and cathode electrodes. Using this system, we obtained high-resolution X-ray images accelerated at 42-70 kV voltage by digital switching control between emitter and ground electrode.

Fluoroscopic-guided stent placement in failed tentative endoscopic approaches to malignant gastroduodenal obstructions.

Background Fluoroscopic or endoscopic placement of metallic stents is used as a safe, non-surgical, palliative treatment option for malignant gastroduodenal obstructions. However, endoscopic stent placement is not always feasible, due to the tight or tortuous stricture of the obstructed area and insufficient visualization of the stomach due to remnant food material. Purpose To assess the technical feasibility and clinical outcomes of fluoroscopic-guided stent placement in malignant gastroduodenal obstructions following the technical failure of endoscopic stent placement. Material and Methods In all, 19 patients (14 men, 5 women; age range, 36-85 years) were referred due to technical failures of tentative endoscopic stent placement. Indications were failure to pass the guide wire through the obstruction (n = 13), failure to reach the stricture lesion due to short endoscope (n = 5), and acute angulation of the stricture lesion (n = 1). Data were retrospectively collected regarding the technical and clinical success of the fluoroscopy, the dysphagia score before and after stent placement, and major complications and their management. Results Fluoroscopic stent placement was technically successful in 15/19 patients (79%). Failures were due to complete obstruction (n = 3) and acute angulation of the stricture lesion (n = 1). Clinical success was achieved in all 15 patients with successful stent placement. The dysphagia score significantly improved after stent placement ( P < 0.001). Complications occurred in 4/15 patients (27%), including tumor overgrowth (n = 2), stent collapse (n = 1), and jaundice (n = 1). Conclusion Fluoroscopic stent placement in malignant gastroduodenal obstructions following a technical failure of endoscopic stent placement is technically feasible and has an acceptable clinical outcome.