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.

Long Noncoding RNAs MALAT1 and HOTTIP Act as Serum Biomarkers for Hepatocellular Carcinoma.

BACKGROUND: Circulating tumor markers with satisfactory sensitivity and specificity play crucial roles in cancer diagnosis and therapy. This prospective study aimed to evaluate the potential of circulating lncRNAs as biomarkers for hepatocellular carcinoma (HCC). METHODS: A total of 74 patients with HCC and 94 healthy controls were enrolled. The expression levels of candidate genes in serum were detected by qRT-PCR. Receiver operating characteristic (ROC) curve analysis and logistic regression were employed to investigate the diagnostic capacity of lncRNAs. The analysis of 3-year overall survival (OS) was conducted using the Kaplan-Meier method and log-rank test. RESULTS: Of the 9 candidate genes, 6 lncRNAs could be stably detected in serum. The expression levels of circulating MALAT1 and HOTTIP in HCC patients were significantly higher than those in controls (P < 0.001). ROC analysis showed that MALAT1 and HOTTIP were more effective than alpha-fetoprotein (AFP) (P < 0.010) in the diagnosis of HCC, with AUCs of 0.896 and 0.899, respectively. Additionally, a panel consisting of MALAT1, HOTTIP, and AFP was constructed to obtain an AUC of 0.968 with a sensitivity of 87.8% and specificity of 94.7% in HCC diagnosis. Moreover, the upregulation of MALAT1 was not only related to multiple tumor lesions, HCV infection, AST level, and AFP level, but also suggested shorter OS. A high expression level of HOTTIP was associated with metastasis. CONCLUSION: Serum MALAT1 and HOTTIP play indicative roles as non-invasive biomarkers for HCC.

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.

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.

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.

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.

[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.

[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.

MR investigation in evaluation of chronic whiplash alar ligament injury in elderly patients.

OBJECTIVE: To observe the imaging features for chronic whiplash alar ligament injury in elderly patients and to provide an effective diagnostic method for long-term neck pain and headaches due to alar ligament injury in elderly patients. METHODS: A total of 134 elderly patients, who engaged in the work or activities related to whiplash motion and suffered from chronic neck pain, were enrolled for the study. All patients were performed comprehensive health examination (CT, MR, ultrasound and laboratory examination) and high resolution PDWI. The patients were divided into 2 groups according to the results of comprehensive health examination: a clear etiology group(CE group, n=96) and an unknown etiology group(UE group, n=38). Th e characteristics of PDWI signal in the ligament were analyzed between the 2 groups. RESULTS: Th e anatomy and signal characteristics of the alar ligament were clearly displayed by high resolution PDWI. Th e alar ligaments were effectively displayed by oblique coronal image. In the CE group, 7 patients (7/96) showed the positive sign of ligament injured, while 21 (21/38) patients showed positive sign of ligament injured in the UE group (P<0.01). Chronic whiplash ligament injury was proved to be the reason for long-term neck pain and headaches in 15.7% patients. CONCLUSION: Th e whiplash injury of alar ligament is an important reason for chronic neck pain in elderly patients. High resolution PDWI is an effective method to evaluate the image features of alar ligament and can provide an accurate diagnosis for chronic neck pain and headaches caused by the alar ligament whiplash injury.

Inhibition of fibroblast growth factor receptor signaling impairs metastasis of hepatocellular carcinoma.

The molecular mechanism underlying metastasis of hepatocellular carcinoma (HCC) remains elusive. Here, we showed that matrix metalloproteinase (MMP) 7 and MMP26 levels are significantly higher in the resected HCC than in the adjacent healthy hepatic cells from the patients. Moreover, a strong correlation of the levels of MMP7 or MMP26 with the phosphorylated fibroblast growth factor receptor 2 (FGFR2) was detected. To prove a causal link between the activation of FGFR signaling pathway and expression of MMP7 and MMP26, we used two human HCC lines, HepG2 and HuH-7, to study the underlying molecular basis. We found that FGF1-induced FGFR2 phosphorylation in either line resulted in significant activation of MMP7 and MMP26 and consequently an increase in cancer invasiveness. Inhibition of FGFR2 phosphorylation in HCC abolished FGF1-stimulated MMP7 and MMP26 expression, suggesting that activation of the FGFR signaling pathway in HCC may promote cancer metastasis by inducing MMP7 and MMP26 expression. To define the signal transduction cascades downstream of FGFR2 activation for MMP7 and MMP26 activation, we applied specific inhibitors for phosphatidylinositol-3 kinase (PI3K), extracellular signal-related kinase/mitogen-activated protein kinase (ERK/MAPK), and Jun N-terminal kinase (JNK), respectively, to the FGF1-stimulated HCC cells. We found that only inhibition of JNK significantly decreased the activation of MMP26 in response to FGF1 stimulation, and only inhibition of PI3K significantly decreased the activation of MMP7 in response to FGF1 stimulation, suggesting that the activation of the FGFR2 signaling may activate PI3K to activate MMP7 and activate JNK to activate MMP26, in HCC. Our study thus highlights the FGFR2 signaling pathway and MMP7 and MMP26 as novel therapeutic targets for HCC.

Radiographic morphology of fallopian tubes in women of child-bearing potential: a descriptive study.

AIM: The aim of this study was to determine the radiographic morphological characteristics of fallopian tubes in women of child-bearing age. MATERIAL AND METHODS: From 2007 to 2008 we retrospectively collected records from women aged 19-45 years undergoing fertility evaluation who had normal salpingograms. Women were excluded if they had abnormal imaging on salpingogram, ultrasound, or hysteroscopy, and if they had any history of pelvic disease or pathology, were febrile, or were taking oral contraceptives at the time of the salpingogram. RESULTS: We analyzed the salpingograms from 100 women. The interstitial portion of the tube is funnel-shaped. The mean diameter of the proximal tubal opening was 1.07 ± 0.43 mm. The mean length of the interstitial portion was 5.27 ± 4.28 mm, and the mean internal diameters of the middle and distal segments of the interstitial portion were 0.50 ± 0.22 mm and 0.32 ± 0.12 mm, respectively. The narrowest part of the fallopian tube was the distal segment of the interstitial portion, which is significantly different from the internal diameter of the isthmus (0.46 ± 0.28 mm) (P < 0.01). CONCLUSIONS: This study provides detailed data of the normal fallopian tube that may be of value in the development of new contraceptive agents, as well as infertility treatments.

[3.0T-MR high resolution proton density weighted imaging for transverse cervical ligament in healthy adolescents].

OBJECTIVE: To explore the imaging characteristics of the transverse ligament in healthy adolescents, and further understand the imaging characteristics of the ligament injury. METHODS: We used 3.0T-MR to scan the transverse ligament with proton-weighted sequence in 32 young volunteers, scanned coronally, horizontally and sagittally, and then observed the morphology, thickness, running and signal characteristics of the ligament. RESULTS: The anatomy and signal characteristics of the transverse cervical ligament were clearly displayed by high resolution proton density weighted imaging (PDWI). The whole picture of the transverse ligament was effectively displayed by coronal combined with horizontal image. The transverse ligament was located in the rear of the odontoid, and connected to the inside of both sides of the block like half-arc. The length was (20.4±3.3) mm, the ligament center was the thickest, and both sides gradually became thinner. The middle width of the ligament was (7.3±0.6) mm, the ligament ends narrowed down, and the middle was (2.1±0.4) mm thick; 75% of the transverse ligament showed homogeneous low signal in PDWI, while 25% of the local transverse ligament had high signal. CONCLUSION: High resolution PDWI with 3.0T-MR is a effective method to evaluate the structure of the transverse cervical ligament. Local high signal may not necessarily be the sign of ligament injure. There may also be some high signal in the normal adolescent ligament, so we must pay much attention to clinical diagnosis and treatment.

[Evaluation of sinus meningiomas in the region of interest by high-resolution three dimensional contrast-enhanced magnetic resonance venography].

OBJECTIVE: To determine the value of high-resolution three dimensional contrast enhanced magnetic resonance venography (3D CE-MRV) in evaluating sinus meningiomas in the region of interest (ROI). METHODS: Twenty patients with sinus meningiomas underwent 3D CE-MRV with ROI preoperatively (including 9 patients postoperatively). We observed the changes of venous sinus adjacent the tumor. RESULTS: All patients received high-resolution image, the single acquisition time was about 11.4 s, and the voxel value was about 1.3 mm3. The images of 20 patients showed the change of the sinus clearly, 6 of which with integral sinus, 14 with sinus invaded at various degrees, including 5 with sinus occlusion and 9 with stenosis. CE-MRV also showed 4 patients with clear sinuses, 1 with narrow sinus, partial interruption, and 4 with sinus removed after the surgery. CONCLUSION: Application of high-resolution 3D CE-MRV in ROI in sinus meningiomas may help obtain a series of high-resolution images in a short time, show the relationship between the tumor and venous sinus, display the degree of invasion of venous sinus clearly, provide information for the surgical treatment, and evaluate the change of sinus after the surgery.

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.

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.

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.

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.