A Novel Interpretable Radiomics Model to Distinguish Nodular Goiter From Malignant Thyroid Nodules.

OBJECTIVES: The purpose of this study is to inquire about the potential association between radiomics features and the pathological nature of thyroid nodules (TNs), and to propose an interpretable radiomics-based model for predicting the risk of malignant TN. METHODS: In this retrospective study, computed tomography (CT) imaging and pathological data from 141 patients with TN were collected. The data were randomly stratified into a training group (n = 112) and a validation group (n = 29) at a ratio of 4:1. A total of 1316 radiomics features were extracted by using the pyradiomics tool. The redundant features were removed through correlation testing, and the least absolute shrinkage and selection operator (LASSO) or the minimum redundancy maximum relevance standard was used to select features. Finally, 4 different machine learning models (RF Hybrid Feature, SVM Hybrid Feature, RF, and LASSO) were constructed. The performance of the 4 models was evaluated using the receiver operating characteristic curve. The calibration curve, decision curve analysis, and SHapley Additive exPlanations method were used to evaluate or explain the best radiomics machine learning model. RESULTS: The optimal radiomics model (RF Hybrid Feature model) demonstrated a relatively high degree of discrimination with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.70-0.97; P < 0.001) for the validation cohort. Compared with the commonly used LASSO model (AUC, 0.78; 95% CI, 0.60-0.91; P < 0.01), there is a significant improvement in AUC in the validation set, net reclassification improvement, 0.79 (95% CI, 0.13-1.46; P < 0.05), and integrated discrimination improvement, 0. 20 (95% CI, 0.10-0.30; P < 0.001). CONCLUSION: The interpretable radiomics model based on CT performs well in predicting benign and malignant TNs by using quantitative radiomics features of the unilateral total thyroid. In addition, the data preprocessing method incorporating different layers of features has achieved excellent experimental results. CLINICAL RELEVANCE STATEMENT: As the detection rate of TNs continues to increase, so does the diagnostic burden on radiologists. This study establishes a noninvasive, interpretable and accurate machine learning model to rapidly identify the nature of TN found in CT.

E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.

OBJECTIVE: The role E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) has not been studied in pancreatic cancer. METHOD: Pancreatic cancer cell lines and the normal pancreatic cells were tested in vitro studies and male athymic nude mice were tested in vivo studies. Measuring cell viability by Cell Counting Kit-8 assay (CCK8), 5-ethynyl-2'- deoxyuridine (Edu) staining, and colony formation assay. Wound healing assay was implemented for cell migration and Transwell assay was performed for cell invasion to evaluate the histological status by hematoxylin and eosin staining and to detect the protein ubiquitination by ubiquitination assay. The protein expression was determined by immunohistochemistry staining and western blotting, and mRNA expression was measured by quantitative reverse transcription polymerase chain reaction. RESULT: The expression of MARCH8 was increased whereas PTPN4 was decreased in pancreatic cancer cells. Overexpression of MARCH8 promoted the growth, migration, and invasion of cells, and knockdown of PTPN4 had the similar effects both in vitro and in vivo. MARCH8 promoted PTPN4 protein degradation through ubiquitination. Moreover, PTPN4 suppressed the transcription activities of STAT3 by impairing the level of pSTAT3 (705), while inhibition of PTPN4 activated phosphorylation of STAT3. CONCLUSIONS: MARCH8 promoted pancreatic cancer growth and invasion through mediating the degradation of PTPN4 and activated the phosphorylation of STAT3.

Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8+ T effector cells of liver malignancies based on single cell transcriptomics.

Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies. Methods: In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment. Results: There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway. Conclusion: This study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.

Clinical Outcomes and Predictors in Patients With Unresectable Colorectal Cancer Liver Metastases Following Salvage Percutaneous Radiofrequency Ablation: A Single Center Preliminary Experience.

PURPOSE: The purpose of this study was to investigate the clinical efficacy of salvage percutaneous radiofrequency ablation in patients with unresectable colorectal cancer liver metastases. METHODS: The cohort consisted of 81 patients with 126 colorectal cancer liver metastases who underwent radiofrequency ablation between January 2012 and September 2016. The clinical data and ablation data were retrospectively analyzed. The local tumor progression-free survival, overall survival, and prognostic factors were analyzed using the log-rank test and Cox regression model. RESULTS: The technique success rate was 99.21%. The primary efficacy rate was 100% at the 1-month follow-up. Minor complications were observed in 2 patients, which recovered within 1 week. The median local tumor progression-free survival time of all patients was 29.8 months. The absence of subsequent chemotherapy was an independent predictor of a shorter local tumor progression-free survival time (P < 0.001, hazard ratio: 2.823, 95% confidence interval: 1.603, 4.972). The median overall survival time was 26.8 months. A lesion size greater than 3 cm (P = 0.011, hazard ratio: 2.112, 95% confidence interval: 1.188, 3.754) and the presence of early local tumor progression (P = 0.011, hazard ratio: 2.352, 95% confidence interval: 1.217, 4.545) were related to a shorter survival time. CONCLUSIONS: Percutaneous radiofrequency ablation is safe in patients with colorectal cancer liver metastases refractory from chemotherapy. Subsequent chemotherapy is important to enhance local control. Small lesions and favorable early responses are related to prolonged overall survival.

CT-guided cryoablation for unresectable pelvic recurrent colorectal cancer: a retrospective study.

OBJECTIVE: The study aimed to investigate the efficacy of computed tomography (CT)-guided cryoablation debulking of unresectable pelvic recurrent colorectal cancer (CRC). PATIENTS AND METHODS: From January 2013 to April 2016, 30 patients (18 males and 12 females; aged 57.8±10.5 years) with unresectable pelvic recurrent CRC who had previously received radiotherapy or chemotherapy were included. A total of 35 tumors ranging from 1.2 to 6.3 cm underwent cryoablation. Tumor response was evaluated 1 month after cryoablation according to the Modified Response Evaluation Criteria in Solid Tumors. Logistic regression was used to analyze the risk factors for tumor response. Degree of pain palliation was also determined using the Numerical Rating Scale. Cox proportional hazard models were used to identify predictors of outcomes. RESULTS: Cryoablation was successfully performed in all patients. Complete response (CR) was achieved for 27 tumors in 23 patients and partial response was achieved for eight tumors in seven patients 1 month after cryoablation. The rate of CR was 77.14%, and tumor size was an independent risk factor for CR. Pain relief was satisfactory in 21 symptomatic patients (P<0.001), and the median duration of pain relief was 6.0 months (95% CI: 2.67-9.33). Serum carcinoembryonic antigen (CEA) was significantly decreased after cryoablation in 15 patients with elevated CEA (P=0.005). The median progression-free survival (PFS) was 10.0 months (95% CI: 4.43-15.67). Multivariate analysis revealed that tumor size (HR =3.089, P<0.001), sex (HR =0.089, P=0.002), and elevated CEA (HR =7.015, P=0.002) were independent predictors of PFS. CONCLUSION: CT-guided cryoablation is a safe and effective therapeutic option for pelvic recurrent CRC. Tumor size is an important predictor of poor outcomes.

Image-guidedcryoablation in unresectable or recurrent advanced colorectal cancer: a retrospective study.

Purpose: The present study retrospectively analyzed thesafety and efficacy of computed tomography (CT)-guided cryoablationin the treatment ofunresectable or recurrent advanced colorectal cancer, which did not respond well to or experienced progression with radiotherapy or chemotherapy. Materials and Methods: From January 2013 to April 2015, 31 lesions in 27 patients (16 males, 11 females; mean age of 57.2 years) with pelvic unresectableadvanced or recurrent colorectal cancer were included in the study. The tumor diameter was approximately 3.37 ±1.41 cm. The primary tumor included 25 rectal cancers, 1 sigmoid colon adenocarcinoma, and 1 ileocecal mucinous adenocarcinoma. Cryoablation was performed with 17-gauge cryoprobes and monitored by 64-slice spiral CT. Follow-up was carried out by contrast-enhanced magnetic resonance imaging (MRI). The treatment efficacy was evaluated by symptom palliation, decreased carcinoembryonic antigen (CEA) serum level, and tumor response. Results: The cryoablation procedure was well-tolerated in all patients without major complications or procedure-related mortality. Long-term complications included abscess formation (1 patient), skin frostbite and post-sacrum antrum formation (1 patient). Pain relief was satisfactory in patients with perineal pain (P<0.001), and the median time of pain relief was 3.0 months. Complete ablations were obtained in 22 lesions of 18 patients, while 9 lesions in 9 patients underwent incomplete ablation. The median time to local recurrence for lesions with complete ablations was 15.0 months, and that to the progression of tumors with incomplete ablation was 4.0 months. Conclusion: CT-guided cryoablation is a minimally invasive, safe, and effective therapeutic option for unresectableadvanced or recurrent colorectal cancer. The treatment is well-tolerated by patients, and pain relief is achieved rapidly.

CT-guided Hookwire localization before video-assisted thoracoscopic surgery for solitary ground-glass opacity dominant pulmonary nodules: radiologic-pathologic analysis.

The optimal screening or treatment strategies of solitary pulmonary nodules especially ground-glass opacities (GGOs) remain controversial. With CT-guided Hookwire localization, it is accurate to find the small lesions during video-assisted thoracoscopic surgery (VATS). In this study, we evaluate the efficiency and safety of CT-guided Hookwire localization of GGO-dominant (GGO component > 50%) pulmonary nodules before VATS and investigate the correlation between the radiologic features and pathology. From April 2008 to April 2014, a total of 273 patients with solitary GGO-dominant pulmonary nodules were included. Tumor size was 12.4 ± 5.7 mm in diameter, including 208 pulmonary adenocarcinomas and 65 benign nodules. Dislodgement occurred in six patients (2.20%) during surgery. Postoperative complications included asymptomatic needle track hemorrhage (27.1%), minimal pneumothorax (5.9%) and hemoptysis (0.4%). In 208 (76.2%) pulmonary adenocarcinomas, 82 nodules showed ≥90% GGO and 126 showed 50%≤GGO<90%, while 84 nodules staged as T1aN0M0, 96 staged as T1bN0M0, and 28 staged as T1cN0M0. The multivariable analysis demonstrated that 50%≤GGO<90% (HR=2.459, 95% CI: 1.246-4.853, P=0.010), speculation (HR=3.911, 95% CI: 1.966-7.663, P<0.001), lobulation (HR=4.582, 95% CI: 2.149-9.767, P<0.001) and vascular convergence (HR=4.096, 95% CI: 1.132-14.824, P=0.032) were the independent risk factors to identification of the malignant GGO-dominant pulmonary nodules. In conclusions,CT-guided Hookwire localizati for GGO-dominant pulmonary nodules before VATS is a safe and effective procedure for accurate diagnosis and resection of indeterminate solitary pulmonary nodules.

Clinical outcomes and prediction of survival following percutaneous biliary drainage for malignant obstructive jaundice.

The present study aimed to investigate the clinical outcomes of percutaneous transhepatic biliary drainage in patients with obstructive jaundice and identify potential predictors of patient survival. Clinical data from 102 patients (66 males and 36 females; median age, 63.50 years; range, 29-84 years) with a mean (± standard deviation) pre-drainage serum bilirubin level of 285.4 (±136.7 µmol/l), were retrospectively studied. Technical and clinical success, complications and survival time were recorded and their relationship with clinical factors, including age, obstruction level, liver metastases, serum bilirubin level and subsequent treatments following drainage, were analyzed by Fisher's exact test. Patient survival rate and other predictors were analyzed by Kaplan-Meier survival curves and Cox's proportional hazard model. The technical and clinical success rates were 100 and 76.5%, respectively. The presence of liver metastases was associated with reduced successful drainage. The overall complication rate was 7.8% and the overall median survival time was 185 days [95% confidence interval (CI), 159-211 days]. A log-rank test showed that age (χ2, 4.003; P=0.04), bilirubin levels following procedure (χ2, 5.139; P=0.02) and subsequent therapy (χ2, 15.459; P=0.00) affected survival time. However, Cox's regression analysis revealed no administration of additional treatments to be a risk factor of survival (odds ratio, 2.323; 95% CI, 1.465-3.685; P=0.000). Percutaneous transhepatic biliary drainage for malignant biliary obstruction was found to be a safe and effective method to relieve jaundice caused by progressive neoplasms. Subsequent radical therapy following drainage, including surgery, chemotherapy and other local treatment types, are likely to increase patient survival.

Endovascular treatment of posttraumatic carotid-cavernous fistulas and pseudoaneurysms with covered stents.

OBJECTIVE: The treatment of posttraumatic direct carotid-cavernous fistulas (TCCFs) with detachable balloons (DBs) is associated with relatively high recanalization rate. The aim of this study was to evaluate the feasibility of using covered stents in patients with posttraumatic carotid-cavernous fistulas (CCFs) and pseudoaneurysms. METHODS: Twelve patients with posttraumatic CCFs and 3 with pseudoaneurysms following detachable balloon deployment referred for treatment with covered stents were enrolled into this prospective study. Data on technical success, initial and final angiography results, mortality, morbidity, and the final clinical outcome, were retrospectively collected and analyzed at 1-, 3-, 6-, 12-months, and then annually. RESULTS: The navigation and deployment of the covered stents to the target CCF were technically successful in 14 of the 15 attempted stents, giving a successful technical rate of 93.3%. Angiography poststent placement showed complete occlusion in 11 patients with 11 CCFs, and incomplete occlusion in 3. Follow-up angiography revealed complete occlusion and no obvious in-stent stenosis in any patient. Clinical follow-up demonstrated full recovery in 13 patients, and an unchanged status in 1. CONCLUSION: These preliminary results indicate that the use of a covered stent is a feasible procedure for the treatment CCFs and pseudoaneurysms.

Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis.

AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS (1)H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm(3), the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. (1)H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiation- treated pancreatic tumor tissues were compared. RESULTS: Compared with (1)H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the (1)H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.

Safety and efficacy of splenic artery coil embolization for hypersplenism in liver cirrhosis.

BACKGROUND: Partial splenic artery embolization is an effective treatment for hypersplenism but often lacks long-term benefits. PURPOSE: To evaluate the long-term effects of coil embolization of the splenic artery in patients with liver cirrhosis and hypersplenism. MATERIAL AND METHODS: Forty-nine patients with liver cirrhosis and hypersplenism underwent coil embolization of the main splenic artery. The coils were deployed in the mid- or distal segment of the splenic artery to allow collateral blood flow to the spleen. The following data were collected from 2 weeks to 4 years after the embolization: technical success, length of hospital stay, white blood cell count, platelet count, splenic volume, and complication. RESULTS: The technical success rate of splenic artery coil embolization was 100%. The post embolization syndrome rate was 75% (36/49) with no incidence of major complications. The mean length of hospital stay was 9 days. After embolization, the patient's white blood and platelet counts increased significantly, peaked at 2 weeks, and gradually decreased during the 4-year follow-up period, but remained at significantly higher levels than pre-embolization levels. Follow-up CT scans demonstrated a gradual increase in the volume of the enhanced portions of the spleens with a decrease in the volume of unenhanced portion. No significant changes occurred in the red blood cell count and liver function after the embolization. CONCLUSION: Embolization of the mid-and distal main splenic artery with coils is a safe and effective treatment of hypersplenism in cirrhosis with long-term hematologic benefits.

Comparison of total splenic artery embolization and partial splenic embolization for hypersplenism.

AIM: To evaluate whether total splenic artery embolization (TSAE) for patients with hypersplenism delivers better long-term outcomes than partial splenic embolization (PSE). METHODS: Sixty-one patients with hypersplenism eligible for TSAE (n = 27, group A) or PSE (n = 34, group B) were enrolled into the trial, which included clinical and computed tomography follow-up. Data on technical success, length of hospital stay, white blood cell (WBC) and platelet (PLT) counts, splenic volume and complications were collected at 2 wk, 6 mo, and 1, 2, 3, 4 years postoperatively. RESULTS: Both TSAE and PSE were technically successful in all patients. Complications were significantly fewer (P = 0.001), and hospital stay significantly shorter (P = 0.007), in group A than in group B. Post-procedure WBC and PLT counts in group A were significantly higher than those in group B from 6 mo to 4 years (P = 0.001), and post-procedure residual splenic volume in group A was significantly less than that observed in group B at 1, 2, 3 and 4 years post-procedure (P = 0.001). No significant differences were observed in red blood cell counts and liver function parameters between the two groups following the procedure. CONCLUSION: Our results indicate that TSAE for patients with hypersplenism not only delivers a better long-term outcome, but is also associated with lower complication rates and a shorter hospital stay than PSE.

Total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism.

AIM: To study the safety and feasibility of total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis. METHODS: Fifteen consecutive patients with hypersplenism due to cirrhosis were enrolled in this study from January 2006 to June 2010. All patients underwent total embolization of the main splenic artery. Clinical symptoms, white blood cell (WBC) and platelet (PLT) counts, splenic volume, and complications of the patients were recorded. The patients were followed up for 1 and 6 mo, and 1, 2, 3 years, respectively, after operation. RESULTS: Total embolization of the main splenic artery was technically successful in all patients. Minor complications occurred in 13 patients after the procedure, but no major complications were found. The WBC and PLT counts were significantly higher and the residual splenic volume was significantly lower 1 and 6 mo, and 1, 2, 3 years after the procedure than before the procedure (P < 0.01). Moreover, the residual splenic volume increased very slowly with the time after embolization. All patients were alive during the follow-up period. CONCLUSION: Total embolization of the main splenic artery is a safe and feasible procedure and may serve as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.

Anticoagulation with warfarin for Budd-Chiari syndrome with chronic inferior vena cava thrombosis: an initial clinical experience.

BACKGROUND: To evaluate the initial clinical safety and feasibility of anticoagulation using warfarin for Budd-Chiari syndrome (BCS) with chronic inferior vena cava (IVC) thrombosis. METHODS: Between October 2005 and June 2009, a total of 16 consecutive BCS patients with chronic IVC thrombosis were treated with warfarin. Warfarin was administered orally at 2.5 mg/d for approximately 3-12 months. Transluminal balloon dilatation of the IVC with a 30-mm balloon catheter was applied for the patients with complete resolution of the thrombus. Data relating to the technical success, angiographic results, complications, and final clinical outcome were collected retrospectively and follow-ups were performed at 1, 3, 6, and 12 months after the stent placement, and annually thereafter. RESULTS: Warfarin was successfully used for anticoagulation in all patients without any complications. Patients were followed up as outpatients for 6.43 ± 2.19 months, and in 14 cases, complete disappearance of the thrombosis was achieved with successful treatment by balloon dilation. In two patients with partial resolution of the thrombosis, Z-stent placement was initiated to compress the thrombus to prevent migration of the thrombosis, followed by dilation of the IVC. During the follow-up for 20.94 ± 10.31 months after the procedure, all the IVC remained patent without complications or pulmonary embolus, and all patients were alive with resolution of symptoms at the time of this study. CONCLUSIONS: The use of warfarin for anticoagulation proved to be simple, safe, and feasible for BCS with chronic IVC thrombosis.

[Study of period and area factors of manganese exposure on the postnatal development of brain in rats].

OBJECTIVE: To investigate the effects of period and area factors of manganese exposure on the postnatal development of brain in rats. METHODS: A combination of GFAP cytoimmunochemistry and imaging analysis was used to determine the morphological changes of glial cells and the average proportional densities of GFAP-immunochemistry positive products of different brain areas in different Mn-exposured period. RESULTS: (1) In both one month's and two month's groups, no differences were found in the GFAP-immunochemistry extensities and the average proportional densities of GFAP reaction positive products between the Mn-exposured group and the control group in the somatic motor and sensory cortexes, but in the expyramid nuclei or areas, that were increased significantly than the the control group. (2) In three month's Mn-exposured groups, the GFAP-immunochemistry extensities and the average proportional densities of GFAP reaction positive products in all related areas of three groups were previously increased than that of the control group. CONCLUSION: In the interferential factors of manganese exposure on the postnatal brain development, both the Mn-exposure period and the areas were the important ones.