Wen-Ping Wang

Hollow periodic mesoporous organosilicas for highly efficient HIFU-based synergistic therapy

Nano-biotechnology provides a promising therapeutic strategy for the development of novel cancer therapeutic modalities. In this work, molecularly organic–inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs) were elaborately designed and fabricated by a silica-etching strategy for concurrent high intensity focused ultrasound (HIFU)-based synergistic therapy and combined HIFU-triggered chemotherapy. Due to the unique hollow nanostructures and well-defined spherical morphology, HPMOs themselves have been demonstrated as an efficient synergistic agent to enhance the HIFU ablation efficiency. The well-defined mesoporous shell and large hollow interior can function as the reservoirs for anticancer agents, and the drug (doxorubicin)-releasing exhibits the intelligent on demand profiles under HIFU irradiation due to the specific framework-induced π–π supramolecular stacking between benzene group-bridged framework and doxorubicin molecules. Combined with HIFU ablation and chemotherapy, HPMOs-based intelligent drug delivery nanosystems have demonstrated in vivo that anticancer drug-loaded HPMOs can significantly enhance the HIFU therapeutic outcomes due to the combined effects of concurrent enhancement of HIFU ablation and HIFU-triggered chemotherapy. This report gives the first evidence that mesoporous material-based drug delivery nanosystems (e.g., HPMOs) can improve the efficiency of focused ultrasound for cancer surgery, which can be further extended for the development of novel HIFU-based therapeutic modalities for more efficient cancer therapy with mitigated side-effects.

Organic-Inorganic hybrid hollow mesoporous organosilica nanoparticles for efficient ultrasound-based imaging and controlled drug release

A novel anticancer drug delivery system with contrast-enhanced ultrasound-imaging performance was synthesized by a typical hard-templating method using monodispersed silica nanoparticles as the templates, which was based on unique molecularly organic/inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs). The highly dispersed HPMOs show the uniform spherical morphology, large hollow interior, and well-defined mesoporous structures, which are very beneficial for ultrasound-based theranostics. The obtained HPMOs exhibit excellent performances in contrast-enhanced ultrasonography both in vitro and in vivo and can be used for the real-time determination of the progress of lesion tissues during the chemotherapeutic process. Importantly, hydrophobic paclitaxel- (PTX-) loaded HPMOs combined with ultrasound irradiation show fast ultrasound responsiveness for controlled drug release and higher in vitro and in vivo tumor inhibition rates compared with free PTX and PTX-loaded HPMOs, which is due to the enhanced ultrasound-triggered drug release and ultrasound-induced cavitation effect. Therefore, the achieved novel HPMOs-based nanoparticle systems will find broad application potentials in clinically ultrasound-based imaging and auxiliary tumor chemotherapy.

Contrast-enhanced (endoscopic) ultrasound and endoscopic ultrasound elastography in gastrointestinal stromal tumors

Background and Objectives: Gastrointestinal stromal tumors (GISTs) represent the largest group of subepithelial tumors (SET) of the upper gastrointestinal (GI) tract. They may show malignant behavior, in contrast to other SET. Endoscopic ultrasound (EUS) is frequently used to characterize SET. With the introduction of contrast-enhanced ultrasound (CEUS) into EUS (CE-EUS), distinct enhancement patterns can be detected. In the presented study, the characteristic features of CE-EUS in GIST are analyzed and compared with those of other SET. Materials and Methods: Consecutive patients from four centers with SET of the upper and middle GI tract were included and received endoscopic or transcutaneous CEUS. The results were compared with EUS-guided tissue acquisition, forceps biopsy, or surgical resection. Results: Forty-two out of 62 (68%) patients had SET of the stomach, 17/62 (27%) of the small intestine, 2/62 (3%) of the esophagus, and 1/62 (2%) extraintestinal. Eighty-one percent underwent surgery. Leiomyoma was found in 5/62 (8%) and GIST in 57/62 patients (92%). Thirty-nine out of 57 (68%) patients had GIST lesions in the stomach, 17/57 (30%) had GIST of the small intestine, and 1/57 (2%) patients had extraintestinal GISTs. GIST size was 62.6 ± 42.1 (16–200) mm. Hyperenhancement had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 98%, 100%, 100%, 93%, and 98% for the diagnosis of GIST. Fifty out of 57 patients with GIST (88%) showed avascular areas in the center of the lesions. Conclusion: CE-EUS and CEUS show hyperenhancement and avascular areas in a high percentage of GIST but not in leiomyoma. Thus, GIST and leiomyoma can be discriminated accurately.

Site-specific sonocatalytic tumor suppression by chemically engineered single-crystalline mesoporous titanium dioxide sonosensitizers

The biomedical applications of TiO2-based nanosystems develop very slowly among diverse inorganic bio-nanosystems (e.g., Fe3O4, SiO2, MnO, Au, etc.) due to the lack of adequate synthetic strategies to fabricate TiO2 nanoparticles with desirable nanostructures and their specific light responses in the ultraviolet range with potential phototoxicity and low tissue-penetrating capability. In this work, we report on the rational design and fabrication of colloidal single-crystalline and mesoporous anatase TiO2 nanoparticles (MTNs) with high dispersity, well-defined mesoporosity, uniform morphology and nanosized single-crystalline structure, employing a facile yet versatile bottom-up chemical strategy, i.e., pre-hydrolysis of titanium precursors combined with subsequent solvothermal treatment (PH-ST) simply using water as the additive. Highly biocompatible PEGylated MTNs have exerted their unique function as efficient sonosensitizers for sonodynamic therapy (SDT) of cancer, as systematically demonstrated both in vitro and in vivo. The production of reactive oxygen species (ROS) by MTN-sonosensitized SDT has been demonstrated to be the mechanism for efficient tumor SDT. The in vivo biocompatibility assay revealed that either a single dose at 150 mg kg-1 or repeated doses at as high as a total of 400 mg kg-1 exhibited no obvious in vivo toxicity. The ultrasound irradiation of MTNs in SDT is expected to break the depth shadow of light responsiveness of TiO2-based nanosystems in the ultraviolet range, and the presence of well-defined mesoporous nanostructures of MTNs shows great potential for the delivery of therapeutic agents for combined cancer therapy.

Contrast enhanced ultrasound features of hepatic cystadenoma and hepatic cystadenocarcinoma

Abstract Objective: Hepatic (biliary) cystic tumor (HBCT) is a rare focal cystic liver lesion, which has been rarely described in the literature. In our current multicenter, retrospective study, we aimed to analyze contrast enhanced ultrasound (CEUS) features and its diagnostic performance in histologically proved HBCT. Material and methods: Twenty-three patients with single HBCT were retrospectively analyzed. Histologically, 17 (73.9%) were benign hepatic (biliary) cystadenoma (HBCA), 6 (26.1%) were hepatic (biliary) cystadenocarcinoma (HBCAC). All CEUS examinations were assessed by two independent radiologists in consensus. Criteria of CEUS imaging evaluation included the contrast enhancement pattern of lesion (hypoenhancing, hyperenhancing, isoenhancing in comparison to the surrounding liver parenchyma) during the arterial, portal venous and late phases. Results: After injection of ultrasound contrast agents, most of the HBCTs (78.3%, 18/23) had typical honeycomb enhancement pattern of the cystic wall, septa or mural nodules. Comparing between HBCA and HBCAC, hyperenhancement of the honeycomb septa during the arterial phase was more common in HBCA (p = .047). However, hypoenhancement during the portal venous and late phases was the characteristic of HBCAC (p = .041). Conclusions: The EFSUMB algorithm for CEUS for characterization of solid focal liver lesions is also applicable to HBCT. CEUS evaluation can avoid further diagnostic investigations or invasive biopsy procedure.

Contrast-enhanced ultrasound of histologically proven hepatic epithelioid hemangioendothelioma

AIM To analyze contrast-enhanced ultrasound (CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma (HEHE) in comparison to other multilocular benign focal liver lesions (FLL). METHODS Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus. RESULTS HEHE manifested as a single (n = 3) or multinodular (n = 22) FLL. On CEUS, HEHE showed rim-like (18/25, 72%) or heterogeneous hyperenhancement (7/25, 28%) in the arterial phase and hypoenhancement (25/25, 100%) in the portal venous and late phases (PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas (18/25, 72%); in seven patients (7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature (P < 0.01). CONCLUSION CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE.

Contrast-Enhanced Ultrasound Guided Biopsy of Undetermined Abdominal Lesions: A Multidisciplinary Decision-Making Approach

Aim. To investigate the value of contrast-enhanced ultrasound (CEUS) guided biopsy of undetermined abdominal lesions in multidisciplinary treatment (MDT) decision-making approach. Methods. Between Jan 2012 and Dec 2015, 60 consecutive patients (male, 37; female, 23; mean age, 51.3 years ± 14.6) who presented with undetermined abdominal lesions were included. CEUS and core needle percutaneous biopsy was performed under real-time CEUS guidance in all lesions. Data were recorded and compared with conventional ultrasound (US) guidance group (n = 75). All CEUS findings and clinical data were evaluated in MDT. Results. CEUS enabled the delimitation of more (88.3% versus 41.3%) and larger (14.1 ± 10.7 mm versus 32.3 ± 18.5 mm) nonenhanced necrotic areas. More inner (20.0% versus 6.7%) and surrounding (18.3% versus 2.7%) major vessels were visualized and avoided during biopsies. CEUS-guided biopsy increased the diagnostic accuracy from 93.3% to 98.3%, with correct diagnosis in 57 of 60 lesions (95.0%). The therapeutic plan was influenced by CEUS guided biopsies findings in the majority of patients (98.3%). Conclusion. The combination of CEUS guided biopsy and MDT decision-making approach is useful in the diagnostic work-up and therapeutic management.

Value of Contrast-Enhanced Ultrasound in Guidance of Percutaneous Biopsy in Peripheral Pulmonary Lesions

Objectives. To investigate the value of contrast-enhanced ultrasound (CEUS) in guidance of percutaneous biopsy in peripheral pulmonary lesions. Methods. This study focused on 53 patients (male: 38, female: 15, and mean age: 55.7 years ± 10.7) with 53 single peripheral pulmonary lesions. Before core needle (16-gauge) percutaneous biopsy, CEUS were performed in all lesions, with injection of 2.4 mL SonoVue (Bracco, Italy). The contrast-enhancement pattern, display rate of internal necrosis (nonenhanced) and active (obviously enhanced) areas, biopsy success rate, and pathological diagnosis rate were recorded. Results. All the peripheral pulmonary lesions were proved pathologically as benign lesions (n = 7), primary malignancies (n = 41), or metastasis (n = 5). Forty (86.9%) malignant lesions and 4 (57.1%) benign lesions showed internal necrosis areas on CEUS. The detection rate and average size of internal necrosis areas had been significantly improved compared to conventional ultrasound (P < 0.05). After CEUS, core needle percutaneous biopsies were performed successfully in the active areas of all lesions. The sampling success rate and pathological diagnosis rate were 100% and 98.1%. Conclusions. CEUS before biopsy provided useful diagnostic information about peripheral pulmonary lesions. By depicting internal necrotic and active areas, it is a promising technique for guaranteeing the accuracy, success, and safety of core needle biopsy.

Serous pancreatic neoplasia, data and review

AIM To describe the imaging features of serous neoplasms of the pancreas using ultrasound, endoscopic ultrasound, computed tomography and magnetic resonance imaging. METHODS This multicenter international collaboration enhances a literature review to date, reporting features of 287 histologically confirmed cases of serous pancreatic cystic neoplasms (SPNs). RESULTS Female predominance is seen with most SPNs presenting asymptomatically in the 5th through 7th decade. Mean lesion size was 38.7 mm, 98% were single, 44.2% cystic, 46% mixed cystic and solid, and 94% hypoechoic on B-mode ultrasound. Vascular patterns and contrast-enhancement profiles are described as hypervascular and hyperenhancing. CONCLUSION The described ultrasound features can aid differentiation of SPN from other neoplastic lesions under most circumstances.

Contrast-enhanced ultrasound features of histologically proven small (≤20 mm) liver metastases

Abstract Objective: We analyzed contrast-enhanced ultrasound (CEUS) features of histologically proved small (≤20 mm) liver metastases, in comparison to small (≤20 mm) hepatocellular carcinomas (HCC), to define the differentiate diagnoses value of CEUS in clinical practice. Material and methods: Eighty-two cases of small (≤20 mm) liver metastases and 84 cases of small (≤20 mm) HCC were retrospectively reviewed. All patients had CEUS images. Two radiologists assessed CEUS enhancement pattern and time of enhancement in consensus. Statistical analyses were performed using SPSS v.19.0 (SPSS Inc., Chicago, IL). The χ2 test and the independent sample t-test were used to compare the differences. Results: Comparing to small HCCs, rapid rim-like hyper-enhancement in arterial phase (56.1% in liver metastases vs. 2.3% in HCCs, p < .01), rapid wash-out and become hypo-enhancement in late arterial phase or early portal venous phase (96.4% in liver metastases vs. 22.6% in HCCs, p < .01) with central non-enhanced area in late phase were characteristic CEUS features of small metastases. Conclusions: CEUS imaging enhancement findings reliably offer typical signs of small liver metastases, differentiate effectively with small HCCs. CEUS can help to improve the diagnostic confidence of small liver metastases.