Preliminary application of 3D-printed coplanar template for iodine-125 seed implantation therapy in patients with advanced pancreatic cancer

AIM To evaluate a 3 D-printed coplanar template for iodine-125 seed implantation therapy in patients with pancreatic cancer. METHODS A retrospective analysis of our database was performed, and a total of 25 patients with pancreatic cancer who underwent iodine-125 seed implantation between January 2014 and November 2017 were analyzed. Of these, 12 implantations were assisted by a 3 D-printed coplanar template(group A), and 13 implantations performed freehand were selected as a control group(group B). A 3 D coplanar template was designed and printed according to a preoperative CT scan and treatment planning system. The iodine-125 seeds were then implanted using the template as a guide. Dosimetric verification was performed after implantation. Pre-and postoperative D90, V100, and V150 were calculated. The success rate of iodine-125 seed implantation, dosimetric parameters, and complications were analyzed and compared between the two groups.RESULTS Iodine-125 seed implantation was successfully performed in both groups. In group A, the median pre-and postoperative D90 values were 155.32 ± 8.05 Gy and 154.82 ± 16.43 Gy, respectively; the difference between these values was minimal and not statistically significant(P > 0.05). Postoperative V100 and V150 were 91.05% ± 4.06% and 64.54% ± 13.40%, respectively, which met the treatment requirement. A better dosimetric parameter was observed in group A than in group B, and the difference was statistically significant(V100: 91.05% ± 4.06% vs 72.91% ± 13.78%, P < 0.05). No major procedure-related complications were observed in either group. For group A, mild hemorrhage was observed in 1 patient with a peritoneal local hematoma due to mesenteric vein damage from the iodine-125 seed implantation needle. The hematoma resolved spontaneously without treatment. Postoperative blood amylase levels remained within the normal range for all patients.CONCLUSION A 3 D-printed coplanar template appears to be a safe and effective iodine-125 seed implantation guidance tool to improve implantation accuracy and optimize dosimetric distribution.

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.

Evaluation of numerical wave model for typhoon wave simulation in South China Sea

The simulating waves nearshore(SWAN) model has typically been designed for wave simulations in near-shore regions. In this study, the model's applicability to the simulation of typhoon waves in the South China Sea(SCS) was evaluated. A blended wind field, consisting of an interior domain based on Fujita's model and an exterior domain based on Takahashi's model, was used as the driving wind field. The waves driven by Typhoon Kai-tak over the SCS that occurred in 2012 were selected for the numerical simulation research. Sensitivity analyses of time step, grid resolution, and angle resolution were performed in order to obtain optimal model settings. Through sensitivity analyses, it can be found that the time step has a large influence on the results, while grid resolution and angle resolution have a little effect on the results.

Flap failure prediction in microvascular tissue reconstruction using machine learning algorithms

BACKGROUND Microvascular tissue reconstruction is a well-established,commonly used technique for a wide variety of the tissue defects.However,flap failure is associated with an additional hospital stay,medical cost burden,and mental stress.Therefore,understanding of the risk factors associated with this event is of utmost importance.AIM To develop machine learning-based predictive models for flap failure to identify the potential factors and screen out high-risk patients.METHODS Using the data set of 946 consecutive patients,who underwent microvascular tissue reconstruction of free flap reconstruction for head and neck,breast,back,and extremity,we established three machine learning models including random forest classifier,support vector machine,and gradient boosting.Model performances were evaluated by the indicators such as area under the curve of receiver operating characteristic curve,accuracy,precision,recall,and F1 score.A multivariable regression analysis was performed for the most critical variables in the random forest model.RESULTS Post-surgery,the flap failure event occurred in 34 patients(3.6%).The machine learning models based on various preoperative and intraoperative variables were successfully developed.Among them,the random forest classifier reached the best performance in receiver operating characteristic curve,with an area under the curve score of 0.770 in the test set.The top 10 variables in the random forest were age,body mass index,ischemia time,smoking,diabetes,experience,prior chemotherapy,hypertension,insulin,and obesity.Interestingly,only age,body mass index, and ischemic time were statistically associated with the outcomes.CONCLUSIONMachine learning-based algorithms, especially the random forest classifier, were very important incategorizing patients at high risk of flap failure. The occurrence of flap failure was a multifactordrivenevent and was identified with numerous factors that warrant further investigation.Importantly, the successful application of machine learning models may help the clinician indecision-making, understanding the underlying pathologic mechanisms of the disease, andimproving the long-term outcome of patients.

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide nanoparticles.However,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast.Ultra-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast agents.We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro.AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODS The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model.Following intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h post-injection.At the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor samples.RESULTS T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection levels.Additionally,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,respectively.Comparison of U-,UA-,UG-,and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG-or UA-treated mice.CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe(UAG)for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.

NIR Emission Nanoparticles Based on FRET Composed of AIE Luminogens and NIR Dyes for Two-photon Fluorescence Imaging

Near-infrared(NIR) nanoparticles(NPs) based on fluorescence resonance energy transfer(FRET) were prepared by coencapsulation of a red aggregation-induced emission(AIE) molecule, 2-(4-bromophenyl)-3-(4-(4-(diphenylamino)styryl)phenyl)fumaronitrile(TB), and a commercial NIR fluorescence dye, silicon 2,3-naphthalocyanine bis(trihexylsilyloxide)(NIR775) with an amphiphilic polymer poly(styrene-co-maleic anhydride)(PSMA). The surface of the NPs, PSMA@TB/NIR775, was modified with poly(ethylene glycol)(PEG) to increase the in vivo biocompatibility of the NPs. The PSMA@TB/NIR775 NPs showed a strong NIR(780 nm) narrow emission and excellent two-photon absorption property. Moreover, the NPs exhibited good monodispersity, stability, and low cytotoxicity.Under the excitation of a 1040 nm femtosecond(fs) laser, the emission peaks at 680 nm of TB and 780 nm of NIR775 excited by FRET were obtained. We utilized PSMA@TB/NIR775 NPs as fluorescent contrast agents for two-photon excited NIR microscopic imaging, and good NIR imaging effect of mouse brain vasculature was obtained with the imaging depth of about 150 μm. The FRET strategy by coencapsulating AIE molecule and NIR dye will be helpful in preparing more narrow emission NIR probes for deep-tissue biological imaging.

Outcomes of Chimney and/or Periscope Techniques in the Endovascular Management of Complex Aortic Pathologies

Background：The chimney/periscope technique has been used to address complex aortic pathologies.This study aimed to report the outcomes and experiences of chimney and/or periscope grafts （CPGs） used in the endovascular management of complex aortic pathologies.Methods：Twenty-two patients with complex aortic pathologies were retrospectively studied from January 2013 to August 2016 in two vascular centers of teaching hospitals.All patients were diagnosed using computed tomography angiography （CTA）.The patients were followed up at postoperative 1,3,6,and 12 months and yearly thereafter with X-ray,ultrasound,and/or CTA.Results：Twenty-two cases （17 males;mean age 60.7 ＆#177; 16.3 years） with complex aortic pathologies were analyzed.Nineteen patients underwent CPGs only,and the other three cases underwent the simultaneous implantation of chimney/periscope and fenestrated/scallop grafts.Twenty-six arteries were managed with forty CPGs during the procedures.Complete angiographies revealed two Type Ⅰ endoleaks,one Type Ⅲ endoleak,and one Type Ⅳ endoleak.Other intraoperative complications included brachial thrombosis,external iliac artery rupture,and left renal stenosis.The 30-day mortality was 0.The mean follow-up was 26.1 ＆#177; 10.1 months with a range of 2-39 months.During the follow-up,two Type Ⅰ endoleaks and one Type Ⅳ endoleak were observed.One right renal stent occlusion occurred in the 5th month and turned patent after reintervention.Three patients died during the follow-up,one due to an aneurysm rupture as a Type Ⅰ endoleak,and two due to myocardial infarction.The instant technical success was 96%.The primary and secondary patencies were 92%and 96%,respectively.The overall survival rates were 95%,84%,and 84% at 12,24,and 36 months,respectively.Stent migration was not observed in any patient.Conclusions：Chimney/periscope techniques could be used to tackle complex aortic pathologies,but the indications must be strictly controlled,and additional experiences are required.