A Study of the Correlation of Perfusion Parameters in High-Resolution GRASP MRI With Microvascular Density in Lung Cancer.

BACKGROUND: The histological count of microvascular density (MVD) is the current clinical standard for assessing tumor angiogenesis. Although it is hypothesized that perfusion MRI can be a noninvasive alternative to MVD, there have been few studies to validate their correlations, particularly in lung cancer. PURPOSE: To investigate the correlation between MVD and perfusion parameters obtained from high-resolution GRASP (Golden-angle RAdial Sparse Parallel) dynamic contrast-enhanced (DCE)-MRI in a cohort of lung cancer patients, and to validate that GRASP MRI can serve as a free-breathing, noninvasive imaging approach for studying tumor angiogenesis. STUDY TYPE: Prospective. POPULATION: Twenty-five lung cancer patients (16 male, 9 female, mean age = 57.3 ± 11.7 years). FIELD STRENGTH/SEQUENCE: 3T MRI; a prototype golden-angle stack-of-stars sequence. ASSESSMENT: Contrast-enhanced MR data were acquired during free breathing and were reconstructed using GRASP with a temporal resolution of ∼3 sec/phase. For all data, perfusion analysis was performed using a standard Tofts model to generate the volume transfer coefficient (Ktrans ) and the interstitial volume (Ve ). The MVD of corresponding tumor specimens, obtained from Computed Tomography-guided biopsies, were counted with CD34 staining. STATISTICAL TESTS: Pearson correlation analysis; one-way analysis of variance analysis; least significant difference-t method of multiple comparisons. RESULTS: The correlation coefficient was 0.983 and 0.972 for the measurement and remeasurement of Ktrans and Ve . The mean values of Ktrans , Ve , and MVD were 0.33 ± 0.22 min-1 , 0.25 ± 0.12, and 49.68 ± 27.08 vessels/0.723 mm2 , respectively, in all patients (n = 25); 0.36 ± 0.26 min-1 , 0.27 ± 0.13, and 49.09 ± 29.84 vessels/0.723 mm2 , respectively, in adenocarcinoma (n = 15); 0.34 ± 0.17 min-1 , 0.26 ± 0.12, and 53.85 ± 23.53 vessels/0.723 mm2 , respectively, in squamous cell carcinoma (n = 8); and 0.13 ± 0.15 min-1 , 0.14 ± 0.06, and 37.20 ± 28.28 vessels/0.723 mm2 , respectively, in small-cell carcinoma (n = 2). There was a positive relationship between the Ktrans and MVD in all patients (r = 0.738, P < 0.001). DATA CONCLUSION: High spatiotemporal resolution DCE-MRI using GRASP is a promising noninvasive alternative to the histological count of MVD for assessing tumor angiogenesis in lung cancer. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1186-1194.

Free-breathing dynamic contrast-enhanced MRI for assessment of pulmonary lesions using golden-angle radial sparse parallel imaging.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown to be a promising technique for assessing lung lesions. However, DCE-MRI often suffers from motion artifacts and insufficient imaging speed. Therefore, highly accelerated free-breathing DCE-MRI is of clinical interest for lung exams. PURPOSE: To test the performance of rapid free-breathing DCE-MRI for simultaneous qualitative and quantitative assessment of pulmonary lesions using Golden-angle RAdial Sparse Parallel (GRASP) imaging. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (17 males, mean age = 55.1 ± 14.4) with known pulmonary lesions. FIELD STRENGTH/SEQUENCE: 3T MR scanner; a prototype fat-saturated, T1 -weighted stack-of-stars golden-angle radial sequence for data acquisition and a Cartesian breath-hold volumetric-interpolated examination (BH-VIBE) sequence for comparison. ASSESSMENT: After a dual-mode GRASP reconstruction, one with 3-second temporal resolution (3s-GRASP) and the other with 15-second temporal resolution (15s-GRASP), all GRASP and BH-VIBE images were pooled together for blind assessment by two experienced radiologists, who independently scored the overall image quality, lesion delineation, overall artifact level, and diagnostic confidence of each case. Perfusion analysis was performed for the 3s-GRASP images using a Tofts model to generate the volume transfer coefficient (Ktrans ) and interstitial volume (Ve ). STATISTICAL TESTS: Nonparametric paired two-tailed Wilcoxon signed-rank test; Cohen's kappa; unpaired Student's t-test. RESULTS: 15s-GRASP achieved comparable image quality with conventional BH-VIBE (P > 0.05), except for the higher overall artifact level in the precontrast phase (P = 0.018). The Ktrans and Ve in inflammation were higher than those in malignant lesions (Ktrans : 0.78 ± 0.52 min-1 vs. 0.37 ± 0.22 min-1 , P = 0.020; Ve : 0.36 ± 0.16 vs. 0.26 ± 0.1, P = 0.177). Also, the Ktrans and Ve in malignant lesions were also higher than those in benign lesions (Ktrans : 0.37 ± 0.22 min-1 vs. 0.04 ± 0.04 min-1 , P = 0.001; Ve : 0.26 ± 0.12 vs. 0.10 ± 0.00, P = 0.063). DATA CONCLUSION: This feasibility study demonstrated the performance of high spatiotemporal resolution free-breathing DCE-MRI of the lung using GRASP for qualitative and quantitative assessment of pulmonary lesions. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:459-468.

Aberrant interhemispheric homotopic functional and structural connectivity in amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is an idiopathic and fatal neurodegenerative disease of the human motor system. While microstructural alterations in corpus callosum (CC) have been identified as a consistent feature of ALS, studies directly examining interhemispheric neural connectivity are still lacking. To shed more light on the pathophysiology of ALS, the present study aims to examine alterations of interhemispheric structural and functional connectivity in individuals with ALS. METHODS: Diffusion tensor imaging (DTI) and resting-state functional MRI (rfMRI) data were acquired from 38 individuals with ALS and 35 gender-matched and age-matched control subjects. Indices of interhemispheric functional and structural neural connection were derived with analyses of voxel mirrored homotopic connectivity (VMHC) and probabilistic fibre tracking. RESULTS: The rfMRI has revealed extensive reductions of VMHC associated with ALS in brain regions of the precentral and postcentral gyrus, the paracentral lobule, the superior temporal gyrus, the middle cingulate gyrus, the putamen and the superior parietal lobules. With DTI, the analysis has also revealed reductions of interhemispheric structural connectivity through the CC subregions II, III and V in patients with ALS. Additionally, interhemispheric functional connectivity of the bilateral precentral gyri positively correlated with fractional anisotropy values of the CC subregion III, which structurally connects the bilateral motor cortices. CONCLUSIONS: The present data provided direct evidence confirming and extending the view of impaired interhemispheric neural communications mediated by CC, providing a new perspective for examinations and understanding the pathophysiology of ALS.

Incidence and risk factors for pulmonary hemorrhage after percutaneous CT-guided pulmonary nodule biopsy: an observational study.

To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage.

Pneumothorax after percutaneous CT-guided lung nodule biopsy: a prospective, multicenter study.

Background: Pneumothorax is a common complication induced by computed tomography (CT)-guided percutaneous needle biopsy, with a frequency of 17-40.4%. It remains debatable how to predict and prevent the occurrence of post-biopsy pneumothorax. In a real-world setting, we investigated the characteristics associated with pneumothorax in primary lung nodule biopsy. Methods: This clinical registry cohort study recorded patients with newly diagnosed pulmonary nodules from 10 medical centers from April 2021 to April 2022, and the data were input into the electronic data capture (EDC) system. The eligibility criteria for participants included being within the age range of 18 to 80 years and expressing a willingness to undergo percutaneous puncture biopsy, among other requirements. Conversely, the exclusion criteria included an inability to cooperate throughout the biopsy process and the emergence of new health issues during the study duration resulting in attendance delays, among other factors. This study collected data from 924 patients, out of which 593 were included after exclusion. The essential characteristics, imaging features of pulmonary nodules, and technical factors associated with percutaneous biopsy were recorded. T-tests or one-way analysis of variance (ANOVA) were performed for continuous variables and Pearson's χ2 test, likelihood ratio, or Fisher's exact test were applied for categorical variables for comparison as appropriate, followed by multivariate logistic regression. Results: The overall incidence of pneumothorax was 13.0% (77/593), among which timely pneumothorax was 10.3% (61/593), delayed pneumothorax was 2.7% (16/593), and the rate of chest tube placement was 3.4% (20/593). There was no significant difference in the incidence of pneumothorax in a needle size range of 16-19 G (P=0.129), but the incidence of pneumothorax was lower with 17 G needles than with 18 G. An increased morbidity of pneumothorax was correlated with age (P=0.003), emphysema (P=0.006), and operation time (P=0.002). There was no significant increase in the incidence of pneumothorax between 1 or 2 passes through the pleura (P=0.062). However, multiple pleural passes (3 times) increased the chances of pneumothorax significantly (P=0.022). These risk factors have a certain clinical value in predicting the incidence of post-biopsy pneumothorax, and the area under the curve (AUC) was 0.749. Conclusions: The most common post-biopsy complication, pneumothorax, was managed conservatively in most cases. A maximum of two pleural passes does not increase the incidence of pneumothorax, and the 17 G needle is more suitable for percutaneous biopsy of pulmonary nodules in the real world.

Effects of iodine-125 seed brachytherapy on patients with heterochronous pulmonary metastasis from hepatocellular carcinoma: A propensity score matching study.

Purpose: To investigate the effects of iodine-125 seed brachytherapy (ISB) on the overall survival (OS) of patients with heterochronous pulmonary metastasis (HPM) secondary to hepatocellular carcinoma (HCC). Materials and Methods: The clinical and imaging data of 123 patients with HPM secondary to HCC treated at a single center from July 2012 to July 2020 were analyzed retrospectively. The patients were divided into ISB and non-ISB groups based on ISB treatment. Propensity score matching yielded 46 pairs of patients. A total of 191 lesions were treated, and the data were evaluated for 6 months after ISB. The OS rates of the two groups were compared using the Kaplan-Meier method. Independent prognostic factors were determined using a Cox proportional hazards regression model. Results: The percentages of lung lesions in complete remission, partial remission, disease stable, and disease progression stages were 49.2%, 32.8%, 9.6%, and 8.4%, respectively. The disease control rate was 91.6%. The median follow-up time from the initial diagnosis was 47 months and 33 months for the ISB and non-ISB groups, respectively. Patients in the ISB group had a longer OS than those in the non-ISB group (1-year: 95.7% vs. 80.3%; 3-year: 62.9% vs. 45.7%; 5-year: 37% vs. 20.9%; P < 0.05). Multivariate analysis demonstrated that ISB treatment, tumor differentiation, vascular invasion, and Child - Pugh score were independent prognostic factors for survival. Conclusion: ISB improves local control and OS rates of HPM secondary to HCC; thus, it is an effective and feasible option for patients with HPM secondary to HCC.

Hounsfield Units as an Independent Predictor of Failed Percutaneous Drainage of Spinal Tuberculosis Paraspinal Abscess Under Computed Tomography Guidance.

OBJECTIVE: To investigate the value of Hounsfield units (HUs) as an independent predictor of failed percutaneous drainage of spinal tuberculosis paraspinal abscess under computed tomography (CT) guidance. METHODS: A retrospective analysis was conducted on 61 patients who underwent CT-guided percutaneous drainage for spinal tuberculosis paraspinal abscess between October 2017 and October 2020. Preoperative CT scans were used to measure the HUs of the abscess. Patients were categorized into successful drainage (n = 49) and failed drainage (n = 12) groups. Statistical analysis involved independent sample t-tests and chi-square tests to compare between the 2 groups. Binary logistic regression was performed to identify independent predictive factors for drainage failure. Receiver operating characteristic (ROC) curves were employed to ascertain risk factor thresholds and diagnostic performance. RESULTS: Among the patients, 49 experienced successful drainage while 12 faced drainage failure. The mean HUs of abscesses in the failed drainage group were significantly higher than those in the successful drainage group (p < 0.001). ROC analysis revealed an area under the curve of 0.897 (95% confidence interval, 0.808-0.986) for predicting drainage failure based on HUs. The optimal HU cutoff value for predicting drainage failure was 22.3, with a sensitivity of 91.7% and specificity of 69.4%. CONCLUSION: HUs are an independent predictor of failed percutaneous drainage of spinal tuberculosis paraspinal abscess under CT guidance. The HU value of 22.3 can be used as an initial screening threshold for predicting the success or failure of drainage.

125I Radioactive Particles Drive Protective Autophagy in Hepatocellular Carcinoma by Upregulating ATG9B.

Background and Aims: 125I radioactive particles implantation have demonstrated efficacy in eradicating hepatocellular carcinoma (HCC). However, progressive resistance of HCC to 125I radioactive particles has limited its wide clinical application. Methods: We investigated the cellular responses to 125I radioactive particles treatment and autophagy-related 9B (ATG9B) silencing in HCC cell lines and Hep3B xenografted tumor model using Cell Counting Kit-8 reagent, western blotting, immunofluorescence, flow cytometry, transmission electron microscopy and immunohistochemistry. Results: In this study, we demonstrated that 125I radioactive particles induced cell apoptosis and protective autophagy of HCC in vitro and in vivo. Inhibition of autophagy enhanced the radiosensitivity of HCC to 125I radioactive particles. Moreover, 125I radioactive particles induced autophagy by upregulating ATG9B, with increased expression level of LC3B and decreased expression level of p62. Furthermore, ATG9B silencing downregulated LC3B expression and upregulated p62 expression and enhanced radiosensitivity of HCC to 125I radioactive particles in vitro and in vivo. Conclusions: Inhibition of ATG9B enhanced the antitumor effects of 125I particle radiation against HCC in vitro and in vivo. Our findings suggest that 125I particle radiation plus chloroquine or/and the ATG9B inhibitor may be a novel therapeutic strategy for HCC.

Stereotactic ablative brachytherapy with or without assistance of 3D-printing templates for inoperable locally recurrent or oligometastatic soft-tissue sarcoma: a multicenter real-world study.

The management of inoperable locally recurrent or oligometastatic soft-tissue sarcoma (STS) remains a clinical challenge. This study aimed to explore the long-term outcomes of stereotactic ablative brachytherapy (SABT) for these patients. Patients diagnosed with inoperable locally recurrent or oligometastatic STS from eight hospitals between 2006 and 2021 underwent iodine-125 (I-125) seed SABT, either with or without the assistance of three-dimensional (3D)-printing templates. The analysis concentrated on several key parameters, including objective response rate (ORR), disease control rate (DCR), local control time (LCT), overall survival (OS), adverse events (AEs), pain relief rate, and performance improvement rate. The ORR and DCR reached 78.3% and 95.0%, respectively. The results of multivariate logistic regression analysis indicated that a smaller tumor volume and a higher treatment dose were significantly associated with complete response (P < 0.001; P=0.036). The 1-, 3-, and 5-year LCT rates were 73.2%, 40.6%, and 37.9%, respectively. The 1-, 3-, and 5-year OS rates reached 83.1%, 50.5%, and 36.1%, respectively. Multivariate analysis revealed that a higher dose, a smaller tumor volume, and utilization of 3D-printing templates were significantly positive prognostic factors of LCT (P=0.006; P=0.007; P=0.034). Moreover, the tumor locations of trunk wall and extremities and lower tumor grade (G1/2) were significantly positive prognostic factors of survival (P=0.008; P=0.002). Pain relief rate was 88.0%, and the performance improvement rate was 46.7%. The AEs were predominantly of grade ≤ 2 and were well-tolerated. SABT seems to be an efficacious and safe alternative therapy for inoperable locally recurrent or oligometastatic STS.

Clinical outcomes of radioactive seed brachytherapy and microwave ablation in inoperable stage I non-small cell lung cancer.

This study assessed the efficacy and safety of radioactive iodine-125 seed ablation brachytherapy (RSABT) in comparison to microwave ablation therapy (MWAT) for treating inoperable stage I non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of data from stage I NSCLC patients who underwent CT-guided RSABT or MWAT. The primary outcomes measured were progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. Of the patients included in the study, 71 underwent RSABT and 105 received MWAT. The median follow-up time for these groups was 47.4 months and 60 months, respectively. The PFS rates at 1-year, 3-year, and 5-year for the RSABT group were 87.3%, 72.6%, and 65.8%, while for the MWAT group, they were 89.5%, 69.3%, and 43.7%, respectively (P = 0.011). The OS rates at 1-year, 3-year, and 5-year for the RSABT group were 97.2%, 78.1%, and 66.1%, and for the MWAT group, they were 99%, 75.8%, and 55%, respectively (P = 0.112). Upon multivariate analysis, the treatment modality was identified as an independent predictor of PFS (P = 0.008). Additionally, both sex and T stage were found to be independent predictors of both PFS and OS (P < 0.05). Adverse events, such as pneumothorax, occurred in 50% of the MWAT group and 39% of the RSABT group (P = 0.313). The incidence of pleural effusion was 44% in the MWAT group compared to 14% in the RSABT group (P < 0.001). Needle bleeding was observed in 32% of the RSABT group and 5% of the MWAT group (P < 0.001). We conclude RSABT demonstrates promising efficacy and safety in the treatment of stage I NSCLC. However, further studies are essential to validate these preliminary findings.

Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis.

Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2+ACE2+ small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2+ACE2+ cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27+ memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2+ACE2+ small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2+ACE2+ cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.

Pulmonary sclerosing hemangioma: report of two cases.

Pulmonary sclerosing hemangioma (PSH) is a rare benign tumor of the lungs. These tumors are composed of cuboidal surface cells and polygonal stromal cells and show four histological manifestations: hemorrhagic, papillary, solid, and sclerotic. PSH predominantly affects asymptomatic middle-aged women. The tumor often occurs at the intralobar site, and less commonly in the bronchus and mediastinum. PSH is easy to be misdiagnosed preoperatively. In this study, we present in detail the treatment procedures followed for two atypical cases of PSH. Case 1 was a 62-year-old woman bearing a tumor for 15 years. The tumor lesion was found to be located in the oblique fissure of the left lung. PSH was confirmed by surgical resection and postoperative pathological diagnosis. There was no sign of recurrence and metastasis 1.5 years after surgery. Case 2 was a 54-year-old woman diagnosed with bilateral multiple nodules by physical examination. This patient was diagnosed with definite PSH through computed tomography-guided percutaneous lung biopsy. Surgical resection was not performed. The patient also showed no sign of enlarged tumor and metastasis after 2 years of follow-up. Although PSH can be cured by surgical resection, the findings in our cases indicate that surgical resection need not be considered the preferred course of treatment. If PSH is diagnosed before surgery, the patients may survive while bearing the tumor.

Clinical Outcome of CT-Guided Iodine-125 Radioactive Seed Implantation for Intrahepatic Recurrent Hepatocellular Carcinoma: A Retrospective, Multicenter Study.

The efficacy and safety of CT-Guided Iodine-125 Radioactive Seed Implantation (RSI) for the treatment of intrahepatic recurrent hepatocellular carcinoma (rHCC) were analyzed in this multicenter retrospective study. We reviewed the medical records of patients with rHCC treated with I-125 seed implantation at four different hospitals in China from December 2011 and January 2021. The local progression-free survival (LPFS),liver PFS, and overall survival (OS) were calculated, and the short-term efficacy and treatment-related toxicities were evaluated. A total of 82 patients were enrolled; the median follow-up time was 46 months (range, 3-80 months). The 1-, 3- and 5-year LPFS rates were 63.8%, 27.1%, and 7.9%, respectively, and the corresponding OS rates were 74.8%, 32.9%, and 12.6%, respectively. Univariate analysis showed that factors influencing LPFS included the maximum lesion diameter, Barcelona Clinic Liver Cancer (BCLC) stage, interval between treatment and recurrence, and D90. Multivariate analyses revealed that the BCLC stage, interval between treatment and recurrence, and D90 were independent factors influencing LPFS, whereas BCLC stage, D90, and short-term efficacy were independent factors influencing OS. In summary, I-125 seed implantation is a safe and effective treatment for rHCC. The BCLC stage, interval, and D90 were found to influence the local control. A larger, prospective study is required to confirm the dose-response curve for Iodine-125 RSI of rHCC.

Iodine-125 Seeds Inhibit Carcinogenesis of Hepatocellular Carcinoma Cells by Suppressing Epithelial-Mesenchymal Transition via TGF-ß1/Smad Signaling.

To investigate the radioactive iodine-125 (I-125) seed on migrating and invading of hepatocellular carcinoma (HCC) cells and its mechanism, the irradiation of PLC and Huh7 cells was carried out with I-125 seeds in vitro. Cell counting kit 8 assay was employed to measure cell viability. Cell migration was evaluated by using wound-healing assay. Cell invasion was detected by Transwell assay; RT-PCR and Western blot were used for the detection of the mRNA and proteins of TGF-ß1 signaling pathway-related genes. The viability of PLC and Huh7 cells declined in a dose-dependent manner with increasing irradiation from 0 Gy, 2 Gy, 4 Gy, and 6 Gy, to 8 Gy, respectively. The IC50 of PLC and Huh7 cells were 6.20 Gy and 5.39 Gy, respectively, after 24 h of irradiation. Migration and invasion abilities of I-125 group cells were greatly weakened (P < 0.05) comparing with the control group. According to the outcomes of RT-PCR and WB, I-125 seed irradiation significantly inhibited the mRNA and protein expression of N-cadherin, vimentin, TGF-ß1, p-Smad2/3, and Snail. But the mRNA and protein expressions of E-cadherin were enhanced. Rescue experiment demonstrates that TGF-ß1 activator could reverse the inhibitory effects of I-125 on invasion and migration of cells. The results of in vivo experiments further verified that the I-125 seeds can inhibit the proliferation and TGF-ß1 of xenographed PLC cells. In conclusion, I-125 seeds restrain the invasion and migration of HCC cells by suppressing epithelial to mesenchymal transition, which may associate with the inhibition of the TGF-ß1 signaling.

Safety and efficacy of stereotactic ablative brachytherapy as a salvage therapy for recurrent chest wall cancer: A retrospective, multicenter study.

Purpose: To evaluate the safety and efficacy of stereotactic ablative brachytherapy (SABT) as a salvage therapy for patients with recurrent chest wall cancer (rCWC) who have previously received external beam radiotherapy (EBRT) or surgery. Materials and methods: Between November 2013 and October 2020, a total of 130 patients (including 75 men with a median age of 63 years) with rCWC treated with SABT were enrolled in this multicenter retrospective study. There were 97 cases of non-small-cell lung carcinoma, 24 cases of breast cancer, and 9 cases of thymic cancer. Of the patients included, 102 patients previously received surgery and 58 patients received EBRT, with systemic treatment progressing after recurrence. None of them were suitable or refused to undergo salvage EBRT or surgery again. Results: During the 22 (4-70)-month median patient follow-up, 59 patients died. The local control (LC) rates at 6, 12, 24, and 36 months were 88.3%, 74.3%, 50.4%, and 36.7%, respectively. The 1-, 2- and 3-year survival rates were 85%, 56%, and 42%, respectively. The median overall survival was 26 months (95% CI, 18.9-33.1 months). The pain relief rate was 81%, and the median to remission time was 10 days. Univariate and multivariate analyses showed that independent prognostic factors for LC included tumor size and postoperative D90. On the other hand, independent prognostic factors for survival include the Karnofsky performance status (KPS) score, tumor size, and D90 19 patients (14.6%) developed grade I/II skin reaction complications. No grade III or severer complications occurred. Conclusion: SABT is safe and effective as a salvage therapy for rCWC following EBRT/surgery. For patients with a KPS score greater than 80, prescribed dose greater than 130 Gy, and tumor size less than 4 cm may bring better results.

Recurrence and disease-free survival outcomes after computed tomography-guided needle biopsy in stage IA non-small cell lung cancer patients in China: a propensity score matching analysis.

BACKGROUND: Whether preoperative biopsy before radical resection can lead to recurrence and impact patient survival in non-small cell lung cancer (NSCLC) remains controversial. In this study, we carried out a retrospective analysis to determine whether preoperative biopsy can cause disease recurrence and influence disease-free survival (DFS) in patients with stage IA NSCLC. METHODS: Patients diagnosed with stage IA NSCLC (solid nodule) between January 2010 and December 2014 were identified from the databases of 7 Chinese medical centers and divided into two groups: a preoperative computed tomography (CT)-guided needle biopsy (CTNB) plus radical resection group, and a non-CTNB group. The propensity score matching (PSM) method was adopted to balance the observed covariates, and Kaplan-Meier estimates were used for survival analysis. Cox regression was used in a single-factor analysis to identify the factors affecting DFS in stage IA NSCLC. RESULTS: After initial screening, 730 patients were enrolled in this study, with 186 and 544 patients in the CTNB group and the non-CTNB group, respectively. After PSM, 186 patients were eventually included in each group. No significant differences in basic clinical features were identified between the two groups (P>0.05). The rates of recurrence were 17.2% and 14.0% in the CTNB and non-CTNB groups (χ2=0.735, P=0.391), respectively. No notable differences in DFS (χ2=1.895, P=0.173) or overall survival (OS, χ2=1.785, P=0.182) were observed. Lung adenocarcinoma [hazard ratio (HR), 0.167, P=0.001] and lesion size (>2 cm) (HR, 2.712, P=0.000) were identified as risk factors for DFS in stage IA NSCLC. CONCLUSIONS: CTNB does not increase the incidence of recurrence in stage IA NSCLC or affect patient survival; therefore, it is not a risk factor for DFS. Lung adenocarcinoma and lesion size are risk factors for DFS.

LncRNA CRNDE Promotes ATG4B-Mediated Autophagy and Alleviates the Sensitivity of Sorafenib in Hepatocellular Carcinoma Cells.

Autophagy is closely related to the growth and drug resistance of cancer cells, and autophagy related 4B (ATG4B) performs a crucial role in the process of autophagy. The long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) promotes the progression of hepatocellular carcinoma (HCC), but it is unclear whether the tumor-promoting effect of CRNDE is associated with the regulation of ATG4B and autophagy. Herein, we for the first time demonstrated that CRNDE triggered autophagy via upregulating ATG4B in HCC cells. Mechanistically, CRNDE enhanced the stability of ATG4B mRNA by sequestrating miR-543, leading to the elevation of ATG4B and autophagy in HCC cells. Moreover, sorafenib induced CRNDE and ATG4B as well as autophagy in HCC cells. Knockdown of CRNDE sensitized HCC cells to sorafenib in vitro and in vivo. Collectively, these results reveal that CRNDE drives ATG4B-mediated autophagy, which attenuates the sensitivity of sorafenib in HCC cells, suggesting that the pathway CRNDE/ATG4B/autophagy may be a novel target to develop sensitizing measures of sorafenib in HCC treatment.

Clinical Outcome of CT-Guided Stereotactic Ablative Brachytherapy for Unresectable Early Non-Small Cell Lung Cancer: A Retrospective, Multicenter Study.

OBJECTIVE: To analyze the efficacy and safety of low dose rate stereotactic ablative brachytherapy (L-SABT) for treatment of unresectable early-stage non-small cell lung cancer (NSCLC). METHODS: Data of patients with early-stage NSCLC who received CT-guided L-SABT (radioactive I-125 seeds implantation) at eight different centers from December 2010 to August 2020 were retrospectively analyzed. Treatment efficacy and complications were evaluated. RESULTS: A total of 99 patients were included in this study. Median follow-up duration was 46.3 months (6.1-119.3 months). The 1-year, 3-year, and 5-year local control rates were 89.1%, 77.5%, and 75.7%, respectively. The 1-year, 3-year, and 5-year overall survival rates were 96.7%, 70.1%, and 54.4%, respectively. Treatment failure occurred in 38.4% of patients. Local/regional recurrence, distant metastasis, and recurrence combined with metastasis accounted for 15.1%, 12.1%, and 11.1%, respectively. Pneumothorax occurred in 47 patients (47.5%) with 19 cases (19.2%) needing closed drainage. The only radiation-related adverse reaction was two cases of grade 2 radiation pneumonia. KPS 80-100, T1, the lesion was located in the left lobe, GTV D90 ≥150 Gy and the distance between the lesion and chest wall was < 1 cm, were associated with better local control (all P < 0.05); on multivariate analysis KPS, GTV D90, and the distance between the lesion and chest wall were independent prognostic factors for local control (all P < 0.05). KPS 80-100, T1, GTV D90 ≥150 Gy, and the distance between the lesion and chest wall was < 1 cm were also associated with better survival (all P < 0.05); on multivariate analysis KPS, T stage, and GTV D90 were independent prognostic factors for survival (all P < 0.05). The incidence of pneumothorax in patients with lesions <1 cm and ≥1cm from the chest wall was 33.3% and 56.7%, respectively, and the differences were statistically significant (P = 0.026). CONCLUSION: L-SABT showed acceptable efficacy in the treatment of unresectable early-stage NSCLC. But the incidence of pneumothorax is high. For patients with T1 stage and lesions <1 cm from the chest wall, it may have better efficacy. Prescription dose greater than 150 Gy may bring better results.

Chinese expert consensus of image-guided irreversible electroporation for pancreatic cancer.

Pancreatic cancer (PC) is a lethal disease with extremely high mortality. Although surgical resection is the optimal therapeutic approach for PC, about 30%-40% of those patients are not candidates for surgical resection when diagnosed. Chemotherapy and radiotherapy also could not claim a desirable effect on PC. The application of interventional radiology approaches is limited by unavoidable damage to the surrounding vessels or organs. By the superiority of mechanism and technology, IRE could ablate the tumor by creating irreversible pores on the membrane of PC cells with other tissues like vessels and pancreatic ducts untouched. This consensus gathers the theoretical basis and clinical experience from multiple Chinese medical centers, to provide the application principles and experience from Chinese experts in the IRE field.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.