Multimodal Theranostic Nanoparticles for Necrosis Targeting, Fluorescence/SPECT Imaging, and Radiotherapy of Residual Tumors after Hepatocellular Carcinoma Ablation.

Thermal ablation has been commonly used as an effective treatment for hepatocellular carcinoma; however, peri-necrotic tumor residues after ablation play a significant role in tumor recurrence and poor prognosis. Therefore, developing agents that can effectively target and eliminate residual tumors is critically needed. Necrosis targeting strategies have potential implications for evaluating tumor necrosis areas and treating the surrounding residual tumors. To address this issue, we have developed a biodegradable nanoparticle with necrosis avidity that is compatible with fluorescence imaging, single photon emission computed tomography (SPECT) imaging, and necrosis targeted radiotherapy. The nanoparticles were synthesized using iodine-131-labeled hypericin (131I-Hyp) as the core and amphiphilic copolymer poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as the shell. The developed nanoparticle, PNP@(131I-Hyp), has a uniform spherical morphology with a size of 33.07 ± 3.94 and 45.93 ± 0.58 nm determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light-scattering analysis (polydispersity index = 0.19 ± 0.01), respectively, and having a good stability and blood compatibility in vitro. In mouse subcutaneous ablated-residual tumor models, fluorescence and SPECT imaging demonstrated that PNP@(131I-Hyp) prominently accumulated in the tumor and was retained for as long as 168 h following intravenous injection. Moreover, ex vivo analyses showed that PNP@(131I-Hyp) mainly gathered in the necrotic zones of subcutaneous tumors and inhibited residual tumors by radiotherapy. In addition, histological examination of harvested organs and hematological analysis demonstrated that intravenous injection of 5 mCi/kg nanoparticles caused no gross abnormalities. This multifunctional nanoparticle, therefore, has necrosis imaging and targeted therapeutic effects on residual tumors after thermal ablation of hepatocellular carcinoma, showing potential for clinical application.

Nomogram-based development and evaluation for predictions of 30-day and 1-year survival in patients with spontaneously ruptured hepatocellular carcinoma.

BACKGROUND: Accurately predicting the prognosis of patients with spontaneously ruptured hepatocellular carcinoma (HCC) is crucial for effective clinical management. The aim of the present study was to establish and evaluate prediction models for 30-day and 1-year survival in patients with spontaneously ruptured HCC. METHODS: A total of 118 patients with spontaneous rupture HCC were enrolled. Univariate and multivariate analyses were performed using logistic-regression model and Cox proportional-hazard model. The identified indicators were used to establish prediction models, the performance of which we compared with those of commonly used liver disease scoring models. The survival possibilities of different risk categories were calculated using the newly developed models. RESULTS: Largest tumor size (LTS), serum albumin (ALB), total bilirubin (TBil), and serum creatinine were identified as independent predictors, which were used to establish a 30-day survival prediction model. LTS, BCLC staging, ALB, TBil, hepatectomy at rupture, and TACE during follow-up were identified as independent predictors of 1-year survival model. The 30-day survival model had sensitivity of 79.3%, specificity of 87.1%, and an AUC of 0.879, exhibiting better predictive performance than scores for Chronic Liver Failure Consortium Acute Decompensation score (CLIF-C ADs) and Model for End-stage Liver Disease (MELD). The 1-year survival model had sensitivity of 66.7%, specificity of 94.6%, and an AUC of 0.835, showing better predictive performance than Albumin-Bilirubin (ALBI), Child-Pugh, CLIF-C ADs, and MELD. After stratification, survival possibilities were 90.9 and 21.1% in low- and high-risk groups within 30 days, respectively, and 43.90, 4.35%, and 0 in low-, intermediate-, and high-risk groups at 1 year, respectively. CONCLUSIONS: The established models exhibited good performance in predicting both 30-day and 1-year survival in patients with spontaneously ruptured HCC.

Invasive treatment of persistent postoperative chylothorax secondary to thoracic duct variation injury: Two case reports and literature review.

RATIONALE: Postoperative chylothorax is a rare complication after pulmonary resection. Thoracic duct variations may play a key role in postoperative chylothorax occurrence and make treatment difficult. No studies in the literature have reported the successful treatment of chylothorax second to thoracic duct variation by lipiodol-based lymphangiography. PATIENT CONCERNS: A 63-year-old male and a 28-year-old female with primary lung adenocarcinoma were treated by video-assisted thoracoscopic cancer resection, and suffered postoperative chylothorax. Conservative treatment was ineffective, including nil per os, persistent thoracic drainage, fatty food restriction, and somatostatin administration. DIAGNOSIS: Postoperative chylothorax. INTERVENTIONS: Patients received lipiodol-based lymphangiography under fluoroscopic guidance. Iatrogenic injuries were identified at thoracic duct variations, including an additional channel in case 1 and the lymphatic plexus instead of the thoracic duct in case 2. OUTCOMES: Thoracic duct variations were identified by lipiodol-based lymphangiography, and postoperative chylothorax was successfully treated by lipiodol embolizing effect. LESSONS: Thoracic duct variations should be considered after the failure of conservative treatment for postoperative chylothorax secondary to pulmonary resection. Lipiodol-based lymphangiography is valuable for identifying the thoracic duct variations and embolizing chylous leakage.

Using stacked deep learning models based on PET/CT images and clinical data to predict EGFR mutations in lung cancer.

Purpose: To determine whether stacked deep learning models based on PET/CT images and clinical data can help to predict epidermal growth factor receptor (EGFR) mutations in lung cancer. Methods: We analyzed data from two public datasets of patients who underwent 18F-FDG PET/CT. Three PET deep learning ResNet models and one CT deep learning ResNet model were trained as low-level predictors based on PET and CT images, respectively. A high-level Support Vector Machine model (Stack PET/CT and Clinical model) was trained using the prediction results of the low-level predictors and clinical data. The clinical data included sex, age, smoking history, SUVmax and SUVmean of the lesion. Fivefold cross-validation was used in this study to validate the prediction performance of the models. The predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves. The area under the curve (AUC) was calculated. Results: One hundred forty-seven patients were included in this study. Among them, 37/147 cases were EGFR mutations, and 110/147 cases were EGFR wild-type. The ROC analysis showed that the Stack PET/CT & Clinical model had the best performance (AUC = 0.85 ± 0.09), with 0.76, 0.85 and 0.83 in sensitivity, specificity and accuracy, respectively. Three ResNet PET models had relatively higher AUCs (0.82 ± 0.07, 0.80 ± 0.08 and 0.79 ± 0.07) and outperformed the CT model (AUC = 0.58 ± 0.12). Conclusion: Using stack generalization, the deep learning model was able to efficiently combine the anatomic and biological imaging information gathered from PET/CT images with clinical data. This stacked deep learning model showed a strong ability to predict EGFR mutations with high accuracy.

Prognosis factors of predicting survival in spontaneously ruptured hepatocellular carcinoma.

AIM: To investigate predictors affecting survival in patients with spontaneously ruptured hepatocellular carcinoma (srHCC). METHODS: One-hundred-and-twenty-seven patients experiencing srHCC between January 2010 and December 2020 were enrolled. The clinical features, treatments, and outcomes were reviewed. Statistics included univariate analysis, Kaplan-Meier analysis, multivariate analysis using Cox proportional hazards model and logistic regression model, and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 127 srHCC patients, 24, 42, and 61 patients received conservative treatment, surgical treatment, and transarterial chemoembolization/embolization (TACE/TAE) treatment at HCC rupture, respectively. The largest tumor size [hazard ratio (HR) 1.127; p < 0.001], Barcelona-Clinic Liver Cancer (BCLC) stage (HR 2.184, p = 0.023), international normalized ratio (INR; HR 3.895; p = 0.012), total bilirubin level (TBil; HR 1.014; p = 0.014), TACE after rupture (compared with conservative treatment) (HR 0.549; p = 0.029), TACE/TAE and surgery at rupture, and albumin level (HR 0.949; p = 0.017) were independent predictors affecting overall survival. A survival predictive model for HCC rupture (SPHR) using these predictors was created. ROC analysis showed that the area under the curve (AUC) of the SPHR model for 30 day survival was 0.925, and the AUCs of the model for end-stage liver disease (MELD) score and Child-Pugh score for 30 day survival were 0.767 and 0.757, respectively. CONCLUSION: The largest tumor size, advanced BCLC stage, higher INR and TBil, lower albumin, and conservative treatment were negative independent predictors for overall survival. The SPHR model may be more suitable than the MELD score and Child-Pugh score for predicting 30 day survival in srHCC.

Factors affecting hemostasis in the control of iatrogenic renal hemorrhage.

PURPOSE: To investigate factors affecting hemostasis in iatrogenic renal hemorrhage. METHODS: Seventy-three patients with iatrogenic renal hemorrhage experiencing selective renal artery angiography between Jan 2015 and Dec 2020 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. Factors affecting hemostasis were analyzed by univariate and multivariate models using linear regression techniques. The optimum values of the independent factors to predict postangiographic hemostasis were conducted by receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 73 iatrogenic renal hemorrhage patients, 47 (64.4%) patients had positive angiographic findings and received therapeutic embolization. Of the patients with negative angiographic findings, 20 (76.9%) and 6 (23.1%) received conservative therapy and prophylactic embolization, respectively. The red blood cell (RBC) count (OR = 0.61, P = 0.04), the hematuria time before angiography (OR = - 0.19, P < 0.01) and treatment modality were independent factors affecting hemostasis time. The ROC curve analysis showed that the RBC count of 3.5 × 109/L and the hematuria time before angiography of 7 days were the optimum indicators. Therapeutic embolization and prophylactic embolization were protective factors affecting hemostasis time compared with conservative treatment (OR = - 1.59, P = 0.02; OR = - 3.31, P < 0.01). CONCLUSIONS: The hematuria time before selective renal artery angiography, the RBC count, and embolization treatment are associated with rapid hemostasis. Embolization is an effective strategy for iatrogenic renal hemorrhage, and also enables rapid hemostasis in patients with negative angiographic findings.

A novel multimodal nanoplatform for targeting tumor necrosis.

Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)-block-poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, ex vivo and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.

Elevated procalcitonin levels in primary hepatic neuroendocrine carcinoma: Case report and literature review.

RATIONALE: Procalcitonin (PCT) has been identified as a tumor biomarker in medullary thyroid carcinoma. Other neuroendocrine carcinomas with elevated PCT levels are relatively rare, and are mainly reported in the lung, digestive tract, and pancreas. No studies in the literature have reported a case of primary hepatic carcinoma complicated with unexpectedly elevated PCT levels. PATIENT CONCERNS: A 78-year-old man with persistent fatigue and mild fever was complicated with an extremely high PCT level. Radiological examination revealed a single hypodense lesion in the left lobe of the liver with a "rapid enhancement and rapid washout" pattern. Pathological analysis showed a poorly differentiated neuroendocrine carcinoma (grade 3) with multiple genetic mutations. DIAGNOSIS: Primary hepatic neuroendocrine carcinoma. INTERVENTIONS: The patient received antibiotic therapy and subsequent transcatheter hepatic arterial chemoembolization; a PCT assessment and computed tomography were performed during the follow-up. OUTCOMES: The PCT level did not decline after antibiotic therapy but greatly declined in response to effective transcatheter hepatic arterial chemoembolization. The patient survived and is still being followed up. LESSONS: An extremely elevated PCT level may raise a suspicion of a neuroendocrine carcinoma and plays an indicative role as a biomarker during therapy.

Biodegradable Hypericin-Containing Nanoparticles for Necrosis Targeting and Fluorescence Imaging.

Necrosis targeting and imaging has significant implications for evaluating tumor growth, therapeutic response, and delivery of therapeutics to perinecrotic tumor zones. Hypericin is a hydrophobic molecule with high necrosis affinity and fluorescence imaging properties. To date, the safe and effective delivery of hypericin to areas of necrosis in vivo remains a challenge because of its incompatible biophysical properties. To address this issue, we have developed a biodegradable nanoparticle (Hyp-NP) for delivery of hypericin to tumors for necrosis targeting and fluorescence imaging. The nanoparticle was developed using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) and hypericin by a modified solvent evaporation technique. The size of Hyp-NP was 19.0 ± 1.8 nm from cryo-TEM and 37.3 ± 0.7 nm from dynamic light-scattering analysis with a polydispersity index of 0.15 ± 0.01. The encapsulation efficiency of hypericin was 95.05% w/w by UV-vis absorption. After storage for 30 days, 91.4% hypericin was retained in Hyp-NP with nearly no change in hydrodynamic size, representing nanoparticle stability. In an ovarian cancer cell line, Hyp-NP demonstrated cellular internalization with intracellular cytoplasmic localization and preserved fluorescence and necrosis affinity. In a mouse subcutaneous tumor model, tumor accumulation was noted at 8 h postinjection, with near-complete clearance at 96 h postinjection. Hyp-NP was shown to be tightly localized within necrotic tumor zones. Histological analysis of harvested organs demonstrated no gross abnormalities, and in vitro, no hemolysis was observed. This proof-of-concept study demonstrates the potential clinical applications of Hyp-NP for necrosis targeting.

Delivery of Arsenic Trioxide by Multifunction Nanoparticles To Improve the Treatment of Hepatocellular Carcinoma.

Arsenic trioxide (ATO) is effective in the treatment of hematological malignancies and solid tumors. However, its toxicity and side effects are severe, posing an obstacle in its clinical application. A controlled-release ATO carrier with mitochondrial targeting was constructed in this study. The safety and efficacy in vitro were investigated using a hemolysis test, cytotoxicity, proliferation, migration, apoptosis, and other changes in cell behavior. The safety and efficacy were further evaluated in vivo by hematoxylin-eosin staining, terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling staining, and blood testing in tumor-bearing mice. Immunohistochemically and western blotting experiments were conducted to explore the mechanism of combination therapy of material-based chemotherapy and microwave hyperthermia in vitro. We demonstrated that the nano-zirconia (ZrO2) loading platform may be used to administer the ATO, with local precision-controlled release and mitochondrial targeting. Furthermore, we showed the safety of this approach for delivering high doses of ATO. In addition, we explored this new method in combination with in vitro microwave heat therapy, providing a potentially novel intravenous approach to chemotherapy. We described a new non-invasive treatment that improved the efficacy of ATO chemotherapy against hepatocellular carcinoma through nano-ZrO2 carriers.

Transarterial Delivery of a Biodegradable Single-Agent Theranostic Nanoprobe for Liver Tumor Imaging and Combinatorial Phototherapy.

PURPOSE: To assess selective accumulation of biodegradable nanoparticles within hepatic tumors after transarterial delivery for in vivo localization and combinatorial phototherapy. MATERIALS AND METHODS: A VX2 hepatic tumor model was used in New Zealand white rabbits. Transarterial delivery of silicon naphthalocyanine biodegradable nanoparticles was performed using a microcatheter via the proper hepatic artery. Tumors were exposed via laparotomy, and nanoparticles were observed by near-infrared (NIR) fluorescence imaging. For phototherapy, a handheld NIR laser (785 nm) at 0.6 W/cm2 was used to expose tumor or background liver, and tissue temperatures were assessed with a fiberoptic temperature probe. Intratumoral reactive oxygen species formation was assessed using a fluorophore (2',7'-dichlorodihydrofluorescein diacetate). RESULTS: Nanoparticles selectively accumulated within viable tumor by NIR fluorescence. Necrotic portions of tumor did not accumulate nanoparticles, consistent with a vascular distribution. NIR-dependent heat generation was observed with nanoparticle-containing tumors, but not in background liver. No heat was generated in the absence of NIR laser light. Reactive oxygen species were formed in nanoparticle-containing tumors exposed to NIR laser light, but not in background liver treated with NIR laser or in tumors in the absence of NIR light. CONCLUSIONS: Biodegradable nanoparticle delivery to liver tumors from a transarterial approach enabled selective in vivo tumor imaging and combinatorial phototherapy.

Applications of nanoparticles in biomedical imaging.

An urgent need for early detection and diagnosis of diseases continuously pushes the advancements of imaging modalities and contrast agents. Current challenges remain for fast and detailed imaging of tissue microstructures and lesion characterization that could be achieved via development of nontoxic contrast agents with longer circulation time. Nanoparticle technology offers this possibility. Here, we review nanoparticle-based contrast agents employed in most common biomedical imaging modalities, including fluorescence imaging, MRI, CT, US, PET and SPECT, addressing their structure related features, advantages and limitations. Furthermore, their applications in each imaging modality are also reviewed using commonly studied examples. Future research will investigate multifunctional nanoplatforms to address safety, efficacy and theranostic capabilities. Nanoparticles as imaging contrast agents have promise to greatly benefit clinical practice.

Outcome of decompression using a transnasal ileus tube in malignant adhesive bowel obstruction: A retrospective study.

Malignant adhesive bowel obstruction caused by peritoneal carcinomatosis is a common complication of advanced abdominal malignancies, and surgical treatment provides little benefit. The present study was undertaken to evaluate the decompression efficacy of a transnasal ileus tube under X-ray guidance, with benign adhesive bowel obstruction patients serving as the control group. A total of 21 patients with malignant adhesive bowel obstruction and 60 patients with benign conditions were enrolled between February 2011 and March 2015. All the patients were treated with transnasal ileus intubation under X-ray guidance. A total of 9 of the 21 malignant cases and 44 of the 60 benign cases were successfully treated with transnasal ileus intubation (42.9 vs. 73.3%, respectively; P=0.01). Treatment in 8 malignant and 4 benign cases failed due to death, tube discharge, and/or therapy abandonment, all of which contributed to a significant difference between the two groups (38.1 vs. 6.7%, respectively; P=0.01). A total of 4 malignant cases and 12 benign adhesion cases received further surgical treatment, the success rate of which was 50 vs. 91.7%, respectively. The rate of successfully treated intubation cases in all resolution patients was similar between the two groups (81.8% in the malignant group and 80% in the benign group; P=0.89). In conclusion, ileus tube decompression in patients with malignant conditions was associated with a lower success rate and lower further surgical intervention success rate compared with that observed in patients with benign conditions. However, insertion of an ileus tube may successfully cure ~80% of all resolution patients in both groups; thus, it may be used as a feasible therapy in malignant adhesive bowel obstruction patients, similar to patients with benign obstruction.

The relationship between fractional anisotropy value and tumor microarchitecture in late-stage rat glioma.

OBJECTIVE: To explore the magnetic resonance diffusion tensor imaging (MR-DTI) features of in the late stage of Wistar rat C6 brain glioma, and the relationship between fractional anisotropy value and tumor microarchitecture. METHODS: The concentration of more than 1.0 × 106/10 µL glioma cells and complete medium were injected stereotactically into the right caudate nucleus of the experimental group (n = 35) and control group (n = 10), respectively. Conventional MRI, DTI, and enhanced T1WI scans were Performed using the GE Signa HD × 3.0T MRI scanner about 3-4 weeks after implantation for the rats. Postprocessing was done using the DTI specific software Function Tool to gain FA image. Many ROIs were drawn avoiding hemorrhage, necrosis areas in tumor parenchyma, the value of FA was recorded. Each surviving rat brain was examined histologically using HE and immunohistochemical staining for VEGF and CD34. Pearson correlation analysis was used to determine the relationships between FA values and VEGF, MVD, cell density, respectively. RESULTS: A total of 35 tumor-bearing rats were confirmed the tumor formation by the subsequent MRI and pathological examination. The mean FA values of the tumor and the contralateral brain tissue were 0.17 ± 0.03 and 0.31 ± 0.05 respectively, and the difference was statistically significant (t = 12.80, P < 0.05). The mean FA value of grade III glioma (n = 12) was 0.16 ± 0.03, and the average FA value of grade IV glioma (n = 23) was about 0.18 ± 0.04. There was no significant difference between the two groups (t = 1.92, P > 0.05). FA value in the late stage of Wistar rat C6 brain glioma has significant positive correlation to VEGF, MVD, cell density. The correlation coefficients between FA and VEGF, MVD, and cell density were 0.67, 0.65 and 0.71 (P < 0.05), respectively. CONCLUSIONS: The FA value of rat glioma tumor in the late stage can preoperatively provide an accurate, reliable and noninvasive imaging monitoring method to evaluate the microstructure of glioma (cell density, the extent of angiogenesis, fiber bundle integrity and tumor cell infiltration and so on), predict the biological behavior of the tumor and make out surgical plan.

[Correlation between the mRNA expression of tissue inhibitor of metalloproteinase-1 and apparent diffusion coefficient on diffusion-weighted imaging in rats' liver fibrosis].

OBJECTIVE: To explore the correlation between the apparent diffusion coefficient (ADC) and mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of liver fibrosis in rats.
 Methods: A model of liver fibrosis in rats was established by intraperitoneal injection of high-fat diet combined with porcine serum. After drug administration for 4 weeks, 48 rats served as a model group and 12 rats served as a control group, then they underwent diffusion weighted imaging (DWI) scanning. The value of ADC was calculated at b value=800 s/mm2. The rats were sacrificed and carried out pathologic examination after DWI scanning immediately. The mRNA expression of TIMP-1 was detected by real time-polymerase chain reaction (RT-PCR). The rats of hepatic fibrosis were also divided into a S0 group (n=4), a S1 group (n=11), a S2 group (n=12), a S3 group (n=10), and a S4 group (n=9) according to their pathological stage. The value of ADC and the expression of TIMP-1 mRNA among the different stage groups of liver fibrosis were compared, and the correlation between ADC and the TIMP-1 mRNA were analyzed.
 Results: The ADC value and the TIMP-1 mRNA expression were significantly different between the control group and the liver fibrosis group (F=46.54 and 53.87, P<0.05). There were significant differences in the value of ADC between every two groups (all P<0.05), except the control group vs the S1 group, the S1 group vs the S2 group, and the S2 group vs the S3 group (all P>0.05). For the comparison of TIMP-1 mRNA, there was no significant difference between the S1 group and the S2 group, the S3 group and the S4 group (both P>0.05). There were significant differences among the rest of the groups (all P<0.05). Rank correlation analysis showed that there was a negative correlation between the ADC value and the TIMP-1 mRNA expression (r=-0.76, P<0.01).
 Conclusion: When the value of ADC decreases in the progress of rats' liver fibrosis, the mRNA expression of TIMP-1 increases gradually, and there is a negative correlation between them.

Therapeutic efficacy of novel microwave-sensitized mPEG-PLGA@ZrO2@(DOX + ILS) drug-loaded microspheres in rabbit VX2 liver tumours.

The use of nanomaterials as drug delivery systems shows good effects in treating tumors. However, the effective dose of drugs targeted to tumor tissues is very low because of the effect of the reticuloendothelial system (RES) in removing such foreign substances. In order to eliminate the RES effect, we developed mPEG-PLGA@ZrO2@(DOX + ILS) (mPEG-PLGA@ZrO2@[DOX + ILS]) drug-loaded microspheres. These microwave (MW)-sensitized microspheres directly embolized the blood-supply vessels of tumors to induce tumor ischemia and hypoxia, as well as to aggregate drugs within tumor tissues in a long-lasting manner. Additionally, combination with MW ablation can triple the effects for the inhibition of tumor growth. The MW sensitive ionic liquid (ILS) in microspheres can rapidly produce a high temperature in a MW field on the basis of MW sensitization, thus accelerating the degradation of microspheres to release DOX-loaded ZrO2 into the lesions to kill tumors. Microspheres can also prolong the pharmacological time and effect of drugs through the enhanced permeability and retention (EPR) effect of nanocarriers, as well as the sustained release of nanomaterials. Studies performed in vivo revealed that mPEG-PLGA@ZrO2@(DOX + ILS) showed good biosafety. We undertook sensitized microsphere embolism therapy using novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres in a rabbit VX2 liver tumor model. Three, 6 and 9 d after treatment, computed tomography indicated no significant change in tumor size, and diffusion weighted imaging showed a marked decrease of residual tumor tissues. With the multiple functions of inducing embolisms, sensitization, and the sustained release of chemotherapeutics, novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres can achieve good therapeutic efficacy, in combination with MW ablation and chemotherapy, while embolizing the blood vessels of arterial tumors.

Tumor Thermal Ablation Enhancement by Micromaterials.

Thermal ablation is a minimally invasive therapeutic technique that has shown remarkable potential in treating unresectable tumors. However, clinical applications have stalled, due to safety ambiguities, slow heat induction, lengthy ablation times, and post-therapeutic monitoring issues. To further improve treatment efficacy, an assortment of micromaterials (e.g., nanoparticulates of gold, silica, or iron oxide and single-walled carbon nanotubes) are under study as thermal ablative adjuncts. In recent years, the micromaterial domain has become especially interesting. In vivo and in vitro animal studies have validated the use of microspheres as embolic agents in liver tumors, in advance of radiofrequency ablation. Microcapsules and microbubbles serving as ultrasound contrast and ablation sensibilizers are strong prospects for clinical applications. This review was conducted to explore benefits of the three aforementioned microscale technologies, in conjunction with tumor thermal ablation.

[Value of liver perfusion imaging of 256-slice CT in evaluation of the cirrhosis].

OBJECTIVE: To investigate the value of liver perfusion imaging of 256-slice CT in evaluating the compensated and decompensated cirrhosis. 
 METHODS: A total of 20 patients with liver cirrhosis, who were confirmed by liver biopsy, clinical symptoms and imaging, were selected from December 2012 to June 2014. According to the results of liver biopsy and the Child-Pugh classification, the patients were divided into a compensated cirrhosis group (n=8) and a decompensated cirrhosis group (n=12). Eleven cases without liver and spleen diseases were served as a control group. All subjects were under the 256-CT liver perfusion (256-CTP). The data of CTP [hepatic arterial perfusion (HAP), portal venous perfusion (PVP), total liver perfusion (TLP), hepatic perfusion index (HPI)] were obtained according to liver perfusion type, and the data of CTP [liver perfusion (LP), peak enhanced (PE), time to peak (TTP), blood volume (BV)] were obtained according to general perfusion type. Spearman rank correlation was used to analyze the correlation of liver cirrhosis with perfusion parameters. The receiver operating characteristic (ROC) curve was used to predict liver cirrhosis, and the maximized Youden index was served as the optimal cutoff value, then the area under curve, sensitivity and specificity were calculated.
 RESULTS: The PVP, TLP and PE values in the control group, the compensated cirrhosis group and the decompensated cirrhosis group were (76.63±37.26), (38.78±16.13) and (36.14±15.31) mL/(100 mL·min); (98.48±43.58), (55.63±14.47) and (54.41±20.81) mL/(100 mL·min); (55.62±18.25), (44.11±5.79) and (41.08±7.74) HU, respectively, showing a gradual downward trend and a significant difference among the 3 groups (all P <0.05). HPI values were (19.50±6.08)%, (31.81±16.48)% and (34.47±16.04)%; TTP values were (37.32±8.59), (47.06±14.61), (59.86±20.87) s, respectively, showing a gradual upward trend and significant difference among the 3 groups ( all P<0.05). There was no significant difference in the HAP, LP and BV among the 3 groups (all P>0.05). PVP, TLP, PE and LP were negatively correlated with the process of liver cirrhosis (r=-0.592, -0.567, -0.409, -0.569, all P<0.05), but HPI and TTP were positively correlated with the process of liver cirrhosis (r=0.434 and 0.538, both P<0.05). 
 CONCLUSION: 256-CTP could provide useful information for the assessment of liver cirrhosis by measuring a plurality of perfusion parameters. The hepatic microvascular changes in patients with liver cirrhosis could be quantitatively assessed by perfusion CT. TTP shows high efficiency in prediction of liver cirrhosis and decompensated liver cirrhosis.

[Feasibility study on liver CT contrast-enhanced scan with low dose of radiation and contrast agent].

OBJECTIVE: To explore the feasibility for liver contrast-enhanced CT scan with low dose of radiation and contrast agent in clinical.
 METHODS: A total of 180 cases were randomly divided into group I (low concentration of contrast agent, 270 mgI/mL of iodixanol) and group II (high concentration of contrast agent, 320 mgI/mL of iodixanol). Three scan conditions (A: 120 kV, 300 mA; B: 100 kV, 400 mA; and C: 100 kV, 300 mA) were randomly distributed in 3 phases (arterial phase, venous phase and delay phase) for liver scans in each group. The effective radiation dose (ED), image CT values and quality of images (image of noise (NI), the image signal to noise ratio (SNR), contrast to noise ratio (CNR), and overall image quality (OIQ) scores were recorded and analyzed. 
 RESULTS: ED values for the group C in the total samples were decreased by 38%, 40% and 41%, respectively compared to the group A in contrast-enhanced scan for 3 phases. The image quality was significantly different (P<0.05); ED values in the group B were decreased by 18%, 20% and 20%, respectively compared to group A in contrast-enhanced scan for 3 phases, and there were no significant differences (P>0.05) in image quality. There were significant differences between the group I and the group II in CT values at the same scanning parameters and scanning phases (P<0.05), but the image quality was not obviously different; there was no significant difference between the group A-II and the group B-I as well as the group C-I in image CT values, and there was also no significant difference between the group A-II and the group B-I in image quality (P>0.05); however the differences in image quality were statistically significant between the group A-II and the group C-I (P<0.05).
 CONCLUSION: Reduction of the tube voltage (to improve the tube current) combined with the low-dose contrast agent can not only reduce the radiation dose and contrast agent dose but also meet the needs of double-low liver contrast-enhanced CT scan.

Prognostic factors of spontaneously ruptured hepatocellular carcinoma.

AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model. RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001). CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.