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Purpose: This study aims to evaluate the safety and effectiveness of genicular artery embolization (GAE) using lipiodol in comparison to imipenem/cilastatin (IPM-CS). Materials and Methods: This retrospective study screened patients who underwent GAE between January 2022 and February 2023 for inclusion. Clinical outcomes were assessed at 1, 3, and 6 months post-procedure using the Visual Analog Scale (VAS) for pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain, stiffness, functional capacity, and total scores. Technical and clinical success rates, complications, and patient-reported outcomes were assessed. Results: A total of 42 patients were included in the study, with 13 patients treated with lipiodol and 29 with IPM-CS for GAE. Transient skin discoloration was noted in 23.1% of lipiodol patients and 31% of the IPM-CS group (p = 0.722). One patient (7.6%) in the lipiodol group developed knee edema and erythema due to drug-induced vasculitis (p = 0.309). Clinical success rates in the lipiodol group were 76.9% at 1 month, consistent at 3 months, and 69.2% at 6 months. For the IPM-CS group, success rates were 89.7, 86.2, and 75.9%, respectively, with no significant differences (p = 0.353, p = 0.657, p = 0.713). The median percentage change in WOMAC stiffness scores for the lipiodol group at 1, 3, and 6 months post-GAE were − 25%, − 16.7%, and − 16.7%, respectively, while the IPM-CS group showed decreases of − 40%, − 50%, and − 50%. Significant differences were found between the groups at all time points (p = 0.017, p = 0.009, and p = 0.002, respectively). Conclusion: Lipiodol shows comparable clinical success to IPM-CS in GAE. [ABSTRACT FROM AUTHOR]

Purpose: To create and evaluate prediction models of local tumor recurrence after successful conventional transcatheter arterial chemoembolization (c-TACE) via radiomics analysis of lipiodol deposition using cone-beam computed tomography (CBCT) images obtained at the completion of TACE. Materials and Methods: A total of 103 hepatocellular carcinoma nodules in 71 patients, who achieved a complete response (CR) based on the modified Response Evaluation Criteria in Solid Tumors 1 month after TACE, were categorized into two groups: prolonged CR and recurrence groups. Three types of areas were segmented on CBCT: whole segment (WS), tumor segment (TS), and peritumor segment (PS). From each segment, 105 radiomic features were extracted. The nodules were randomly divided into training and test datasets at a ratio of 7:3. Following feature reduction for each segment, three models (clinical, radiomics, and clinical–radiomics models) were developed to predict recurrence based on logistic regression. Results: The clinical–radiomics model of WS showed the best performance, with the area under the curve values of 0.853 (95% confidence interval: 0.765–0.941) in training and 0.752 (0.580–0.924) in test dataset. In the analysis of radiomic feature importance of all models, among all radiomic features, glcm_MaximumProbability, shape_MeshVolume and shape_MajorAxisLength had negative coefficients. In contrast, shape_SurfaceVolumeRatio, shape_Elongation, glszm_SizeZoneNonUniformityNormalized, and gldm_GrayLevelNonUniformity had positive coefficients. Conclusion: In this study, a machine-learning model based on cone-beam CT images obtained at the completion of c-TACE was able to predict local tumor recurrence after successful c-TACE. Nonuniform lipiodol deposition and irregular shapes may increase the likelihood of recurrence. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, efficacy, and long-term outcomes of transarterial chemoembolization (TACE) with bleomycin-Lipiodol for giant liver hemangiomas. Materials and Methods: Single-center retrospective study from 1998 to January 2020, including patients with giant liver hemangiomas treated with bleomycin-Lipiodol TACE and followed up >36 months. The exclusion criteria were defined as patients who had been treated but had no available follow-up above 3 years and patients who had previously been treated with any other treatment method. Clinical success was defined as the disappearance of symptoms and radiological success (responded vs. non-responded groups) as a more than 50% decrease in the volume of the giant hemangioma in follow-up CT or MRI compared to the baseline images. Results: A total of 121 patients were included. The mean maximum diameter of the hemangiomas decreased from 122 (range: 40–300) to 73 mm (range: 15–240), and the mean volume reduced from 984.4 (range: 30–7312) to 286.6 cm3 (range: 1–3835). There were 106 patients in the responded group, while only 15 patients were in the non-responded group. No significant difference was found in size and volume change percentages across these two groups based on gender, age, lesion size, lesion volume, lesion number, and second TACE. When the follow-up period was stratified in 5-year periods, the maximum volume decrease was observed in the first 5-year period and then remained constant up to > 15 years. Conclusion: TACE with bleomycin-Lipiodol is safe, reducing the size and volume of giant liver hemangiomas with stable results in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Chyle leakage (CL) is a common complication in pancreatic surgery. Lymphangiography is a therapeutic option for CL in cases of conservative treatment failure. This study investigated the effect of lymphangiography on the healing time of CL. Methods: We retrospectively evaluated 283 patients who underwent pancreatic resection between January 2016 and June 2022. The risk factors for CL and the treatment period were evaluated according to whether or not lymphangiography was performed. Results: Of the 29 patients (10.2%) that had CL, lymphangiography was performed in 6. Malignant disease, the number of harvested lymph nodes, and drain fluid volume on postoperative day 2 were identified as independent risk factors for CL. Lymphangiography was associated with the cumulative healing rate of CL, and patients who underwent lymphangiography had a significantly shorter treatment period. No lymphangiography-related adverse events were observed. Conclusion: Lymphangiography is a feasible and safe treatment option for CL. The CL treatment period after pancreatic surgery was significantly shorter in patients who underwent lymphangiography than in those who did not. Our results suggest that lymphangiography may contribute to early improvement of persistent CL. [ABSTRACT FROM AUTHOR]

Background: Radioembolization is one therapeutic option for the treatment of locally early-stage hepatocellular carcinoma. The aim of this study was to evaluate the distribution of Lipiodol® ultra-fluid and microspheres and to simulate their effectiveness with different beta emitters (90Y, 188Re, 32P, 166Ho, 131I, and 177Lu) on VX2 tumors implanted in the liver of 30 New Zealand rabbits. Results: Twenty-three out of 30 rabbits had exploitable data: 14 in the group that received Lipiodol® ultra-fluid (group L), 6 in the group that received microspheres (group M), and 3 in the control group (group C). The histologic analysis showed that the Lipiodol® ultra-fluid distributes homogeneously in the tumor up to 12 days after injection. The X-ray μCT images showed that Lipiodol® ultra-fluid has a more distal penetration in the tumor than microspheres. The entropy (disorder of the system) in the L group was significantly higher than in the M group (4.06 vs 2.67, p = 0.01). Equivalent uniform biological effective doses (EUBED) for a tumor-absorbed dose of 100 Gy were greater in the L group but without statistical significance except for 177Lu (p = 0.03). The radionuclides ranking by EUBED (from high to low) was 90Y, 188Re, 32P, 166Ho, 131I, and 177Lu. Conclusions: This study showed a higher ability of Lipiodol® ultra-fluid to penetrate the tumor that translated into a higher EUBED. This study confirms 90Y as a good candidate for radioembolization, although 32P, 166Ho, and 188Re can achieve similar results. [ABSTRACT FROM AUTHOR]

Hydrogel-based biomaterials have gained broad acceptance for tissue engineering and drug delivery applications. As their function generally depends on their localization, identifying the hydrogel position in the body is relevant and will alert physicians about potentially dangerous hydrogel migration. Monitoring the localization of hydrogels by imaging is challenging due to their high water content. Here, we developed a method to render alginate hydrogels visible on computed tomography (CT) and X-ray for real-time tracking of hydrogels inside the body. This method is based on physically immobilizing emulsion droplets of ethiodized oil, an FDA-approved positive CT contrast agent, in calcium-crosslinked alginate hydrogels. We prepared an oil-in-water emulsion of ethiodized oil with micron-sized emulsion droplets and encapsulated it in a calcium-crosslinked alginate hydrogel. This injectable in situ-forming hydrogel was stable for at least 2 weeks in vitro, visible on CT and X-ray in mice, and showed contrast agent concentration-dependent signal intensities. Hydrogels retrieved from mice after imaging had suitable rheological properties with a storage modulus of about 2 kPa and a loss modulus of about 0.35 kPa. This proof-of-concept study highlights the potential of ethiodized oil to localize hydrogels in real time inside the body and identifies a new use of this FDA-approved contrast agent. [ABSTRACT FROM AUTHOR]

This study aimed to demonstrate the effect of transcatheter arterial embolization (TAE) on hepatic segmental arterial mediolysis (SAM). The patient, a 68-year-old female, suddenly developed right upper abdominal pain in October 2021, which was initially relieved. However, she was rushed to a local hospital the next day when her abdominal pain recurred. An abdominal computed tomography scan suggested a ruptured hepatic aneurysm; therefore, she was transferred to our hospital and admitted on the same day. On the first day after admission, she underwent emergency catheterization and N-butyl-2-cyanoacrylate (NBCA)/lipiodol embolization for an aneurysm in the hepatic S6. A multi-detector computed tomography on hospital day 8 to probe for extrahepatic lesions revealed multiple beaded irregularities in the superior mesenteric and bilateral renal arteries. A head magnetic resonance angiography performed on the ninth day showed no aneurysms or irregularities. She did well after TAE, did not have rebleeding, and was discharged on hospital day 16. Rupture of an aneurysm associated with SAM occurs frequently in the colonic and gastroepiploic arteries, and rupture of a hepatic aneurysm is relatively rare. TAE hemostasis was able to save the patient by preventing intraperitoneal bleeding caused by hepatic segmental arterial mediolysis. [ABSTRACT FROM AUTHOR]

The electronic absorption spectra of solutions of aromatic and aliphatic iodine-containing substances in dimethyl sulfoxide, which are components of adhesive compounds for blood vessels, have been studied. It has been shown that, during storage of iodinated fatty acids, iodine is split off from them with the formation of an ion, with the presence of dimethyl sulfoxide and KI accelerating this process. Within 25 days, the concentration of bound iodine in solutions of iodinated fatty acids decreased three times. The stability of solutions of iodinated aromatic substances in dimethyl sulfoxide during storage for at least 6 months has been shown. [ABSTRACT FROM AUTHOR]

Pregnancy outcomes in women with recurrent implantation failure (RIF) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): does treatment with lipiodol flush matter? In this propensity score–matched study, we recruited 966 RIF patients who underwent IVF/ICSI from two tertiary hospitals. These patients were divided into groups based on whether they received lipiodol flush or not. Further stratification was applied to investigate the effect of lipiodol flush on pregnancy outcomes in RIF patients with different cycle type of embryo transferred. Then, patients subjected to lipiodol flush were categorized into three groups based on the duration of the interval: short interval (≤ 3 months), moderate interval (3–6 months), and long interval (≥ 6 months). The groups were well-matched at baseline. The lipiodol flush group exhibited a significantly lower incidence of biochemical pregnancy (46.27% vs. 56.22%, p = 0.046) and live birth (25.87% vs. 37.31%, p = 0.014). Subgroup analysis for fresh embryo transfer cycles revealed no significant differences in pregnancy outcomes. Among RIF patients underwent frozen-thawed embryo transfer cycle, a statistically significant difference in the live birth rate was observed in the lipiodol flush group when compared to the control group (26.40% vs. 37.21%, p = 0.030). Analysis of different lipiodol flush intervals demonstrated a significantly lower live birth rate in the lipiodol flush group. Our results challenge the value of lipiodol use in clinical practice for the treatment of RIF.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900024273. Registered 4 July 2019. [ABSTRACT FROM AUTHOR]

Background: Chylothorax is a relatively rare complication of esophagectomy but can lead to fatal conditions. The aim of this report was to present a case of lymphangiography from the para-aortic lymph node (PALN) under computed tomography (CT) guidance, which could be an alternative modality to ultrasound sonography from the groin. Case presentation: A 58-year-old man was diagnosed as having postoperative chylothorax after esophagectomy following neoadjuvant chemotherapy. As the pleural effusion did not improve, intranodal lipiodol lymphangiography from the inguinal lymph node was performed but was unsuccessful. Therefore, CT-guided lymphangiography from the left PALN was performed, and the pleural effusion drainage significantly disappeared. Conclusions: CT-guided lipiodol lymphangiography from the PALN for chylothorax after esophagectomy was safe and thus can be considered an alternative treatment option to ultrasonography-guided intranodal lymphangiography. The flexible use of CT and ultrasonography for lymphangiography may improve the treatment outcomes of chylothorax after esophagectomy. [ABSTRACT FROM AUTHOR]

Background and purpose: Radiofrequency ablation (RFA) is the standard of care for early stage hepatocellular carcinoma (HCC). However, the clinical outcomes of iodized oil computed tomography (IoCT) versus ultrasound (US)-guided RFA for HCC remain unclear. Methods: We retrospectively analyzed consecutive treatment-naïve patients who received curative RFA for HCC within Milan criteria from January 2016 to December 2018. Patients who underwent either IoCT-guided RFA (IoCT group) or US-guided RFA (US group) were included. Various clinical factors, including tumor location, were adjusted with a 1:1 propensity score matching. Subsequently, the cumulative incidence rates for recurrence and hazard ratios for survival were calculated. Results: We included 184 (37.9%) and 301 (62.1%) patients who received IoCT- and US-guided RFA, respectively. Before propensity score matching, IoCT guidance was significantly associated with multiple tumors, higher body mass index, lower albumin level, and tumors located at S8. After matching, the 1-, 2-, and 3-year local tumor progression rates of the IoCT group were significantly lower than those of the US group (4.4%, 6.9%, and 7.5% vs. 14.4%, 16.3%, and 16.3%, respectively, at p = 0.002, 0.009, and 0.016, respectively). In univariate analyses and multivariate analyses that adjusted for clinical and tumor location-related parameters, the IoCT group had better recurrence-free survival (hazard ratio = 0.581, 95% confidence interval 0.375–0.899) than those with US guidance but not overall survival. Conclusion: IoCT-guided RFA had a lower local tumor progression rate and better recurrence-free survival than did US-guided RFA for HCC within the Milan criteria. CT-guide RFA is a safe and effective alternative to US-guided with similar overall survival. IoCT-guided RFA might have a better local tumor control than US-guided. IoCT-guided RFA may be more suitable for male patients, aged < 70 years, a single tumor measuring 2–5 cm, and a tumor located at the subdiaphragmatic/subcardiac region. [ABSTRACT FROM AUTHOR]

Hepatic arterial infusion (HAI) of oxaliplatin allows greater liver tumour drug exposure compared to systemic infusion. However, the therapeutic index of HAI oxaliplatin remains poor. Using Pickering emulsion technology, we developed a platform able to provide sustained releases of oxaliplatin. The goal of this study was to evaluate the pharmacokinetic advantages of sustained-HAI oxaliplatin over HAI using a preclinical animal tumour model. Injections of 0.6 mg oxaliplatin in 20 min were selectively done in left hepatic arteries of 20 rabbits bearing a VX2 liver tumour in the middle left-lobe, using HAI (n = 10) or sustained-HAI (n = 10). In each group, half of the rabbits were sacrificed at 24 h and half at 72 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and oxaliplatin concentrations in tumour tissues, right- and middle left-liver lobes, spleen and lung. Compared to HAI, sustained-HAI of oxaliplatin resulted in lower plasmatic peak (Cmax: 275 ± 41 vs. 416 ± 133 ng/mL, p = 0.02) and higher concentration in the tumour at 24 h (2118 ± 2107 vs. 210 ± 93 ng/g, p = 0.008). After HAI, oxaliplatin concentration in tumours was significantly higher than in lung at 24 h (p = 0.03) but no other difference was found between oxaliplatin concentrations in tumours and in liver lobes, spleen or lung, neither at 24 h nor at 72 h. On the opposite, sustained-HAI resulted in higher concentrations of oxaliplatin in tumour compared to oxaliplatin concentrations in the middle left lobe (163 ± 86 ng/g at 24 h, p = 0.01, and 90 ± 15 ng/g at 72 h, p = 0.04), right lobe (174 ± 112 ng/g at 24 h, p = 0.01, and 112 ± 35 ng/g, p = 0.04 at 72 h), spleen (142 ± 21 ng/g at 24 h, p = 0.01, and 98 ± 12 ng/g at 72 h, p = 0.04), and lung (85 ± 11 ng/g at 24 h, p = 0.01, and 52 ± 4 ng/g at 72 h, p = 0.03). Sustained-HAI improves the therapeutic index of HAI oxaliplatin and offers a great potential for patients suffering from unresectable colorectal liver metastases or hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate associations between pathology and CT assessments made according to the mRECIST in HCC treated by conventional TACE (cTACE), and to identify predictors of complete tumor necrosis. Methods: From March 2016 to July 2018, 83 patients with a total of 100 masses were retrospectively included. Patients underwent sequential cTACE and portal vein embolization, and later hepatic surgery. Evaluation of treatment response and measurement of baseline lipiodol accumulation as mean HU was performed on CT at the time point closest to the time of operation (mean, 54.5 days after cTACE). Significant predictors associated with complete necrosis were identified by multivariate analysis. The optimal cut-off HU value of lipiodol accumulation for prediction of complete necrosis was determined using a ROC analysis. Results: According to mRECIST, complete response (CR, n = 70) and partial response (n = 30) were classified. 34.3% (24/70) masses classified as CR according to mRECIST were found to have viable lesions on pathology. On multivariate analysis, mean HU of lipiodol accumulation was the only significant predictor of complete necrosis (p =.003, odds ratio 1.746, 95% CI 1.201–2.539). On ROC analysis, 460 HU as a cut-off value was significantly associated with complete necrosis (67.4% sensitivity, 75.0% specificity). Conclusions: A threshold value for lipiodol accumulation > 460 HU was highly sensitive and specific for complete necrosis, even in complete response according to mRECIST. Therefore, if lipiodol accumulation is insufficient in post-TACE CT, recurrence should be monitored more sensitively. [ABSTRACT FROM AUTHOR]

Background: This prospective randomized trial is designed to compare the performance of conventional transarterial chemoembolization (cTACE) using Lipiodol-only with additional use of degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) in BCLC-stage-B based on metric tumor response. Methods: Sixty-one patients (44 men; 17 women; range 44–85) with HCC were evaluated in this IRB-approved HIPPA compliant study. The treatment protocol included three TACE-sessions in 4-week intervals, in all cases with Mitomycin C as a chemotherapeutic agent. Multiparametric magnetic resonance imaging (MRI) was performed prior to the first and 4 weeks after the last TACE. Two treatment groups were determined using a randomization sheet: In 30 patients, TACE was performed using Lipiodol only (group 1). In 31 cases Lipiodol was combined with DSMs (group 2). Response according to tumor volume, diameter, mRECIST criteria, and the development of necrotic areas were analyzed and compared using the Mann–Whitney-U, Kruskal–Wallis-H-test, and Spearman-Rho. Survival data were analyzed using the Kaplan–Meier estimator. Results: A mean overall tumor volume reduction of 21.45% (± 62.34%) was observed with an average tumor volume reduction of 19.95% in group 1 vs. 22.95% in group 2 (p = 0.653). Mean diameter reduction was measured with 6.26% (± 34.75%), for group 1 with 11.86% vs. 4.06% in group 2 (p = 0.678). Regarding mRECIST criteria, group 1 versus group 2 showed complete response in 0 versus 3 cases, partial response in 2 versus 7 cases, stable disease in 21 versus 17 cases, and progressive disease in 3 versus 1 cases (p = 0.010). Estimated overall survival was in mean 33.4 months (95% CI 25.5–41.4) for cTACE with Lipiosol plus DSM, and 32.5 months (95% CI 26.6–38.4), for cTACE with Lipiodol-only (p = 0.844), respectively. Conclusions: The additional application of DSM during cTACE showed a significant benefit in tumor response according to mRECIST compared to cTACE with Lipiodol-only. No benefit in survival time was observed. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prognostic potential of Lipiodol distribution for the pharmacokinetic (PK) profiles of doxorubicin (DOX) and doxorubicinol (DOXOL) after conventional transarterial chemoembolization (cTACE). Methods: This prospective clinical trial (ClinicalTrials.gov: NCT02753881) included 30 consecutive participants with liver malignancies treated with cTACE (5/2016–10/2018) using 50 mg DOX/10 mg mitomycin C emulsified 1:2 with ethiodized oil (Lipiodol). Peripheral blood was sampled at 10 timepoints for standard non-compartmental analysis of peak concentrations (Cmax) and area under the curve (AUC) with dose normalization (DN). Imaging markers included Lipiodol distribution on post-cTACE CT for patient stratification into 1 segment (n = 10), ≥ 2 segments (n = 10), and lobar cTACE (n = 10), and baseline enhancing tumor volume (ETV). Adverse events (AEs) and tumor response on MRI were recorded 3–4 weeks post-cTACE. Statistics included repeated measurement ANOVA (RM-ANOVA), Mann-Whitney, Kruskal-Wallis, Fisher's exact test, and Pearson correlation. Results: Hepatocellular (n = 26), cholangiocarcinoma (n = 1), and neuroendocrine metastases (n = 3) were included. Stratified according to Lipiodol distribution, DOX-Cmax increased from 1 segment (DOX-Cmax, 83.94 ± 75.09 ng/mL; DN-DOX-Cmax, 2.67 ± 2.02 ng/mL/mg) to ≥ 2 segments (DOX-Cmax, 139.66 ± 117.73 ng/mL; DN-DOX-Cmax, 3.68 ± 4.20 ng/mL/mg) to lobar distribution (DOX-Cmax, 334.35 ± 215.18 ng/mL; DN-DOX-Cmax, 7.11 ± 4.24 ng/mL/mg; p = 0.036). While differences in DN-DOX-AUC remained insignificant, RM-ANOVA revealed significant separation of time concentration curves for DOX (p = 0.023) and DOXOL (p = 0.041) comparing 1, ≥ 2 segments, and lobar cTACE. Additional indicators of higher DN-DOX-Cmax were high ETV (p = 0.047) and Child-Pugh B (p = 0.009). High ETV and tumoral Lipiodol coverage also correlated with tumor response. AE occurred less frequently after segmental cTACE. Conclusions: This prospective clinical trial provides updated PK data revealing Lipiodol distribution as an imaging marker predictive of DOX-Cmax and tumor response after cTACE in liver cancer. Key Points: • Prospective pharmacokinetic analysis after conventional TACE revealed Lipiodol distribution (1 vs. ≥ 2 segments vs. lobar) as an imaging marker predictive of doxorubicin peak concentrations (Cmax). • Child-Pugh B class and tumor hypervascularization, measurable as enhancing tumor volume (ETV) at baseline, were identified as additional predictors for higher dose-normalized doxorubicin Cmaxafter conventional TACE. • ETV at baseline and tumoral Lipiodol coverage can serve as predictors of volumetric tumor response after conventional TACE according to quantitative European Association for the Study of the Liver (qEASL) criteria. [ABSTRACT FROM AUTHOR]

Purpose: To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock. Materials and Methods: Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion). Result: The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52 min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8 min (P = 0.046–0.050). Suspension showed the longest release time; however, the viscosity was lowest. Conclusion: The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI. Methods: In this prospective, randomized, single-center trial, patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator. Results: Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE: n = 13, DSM-TACE: n = 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (p = 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (p = 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (p = 0.26) and study endpoint (p = 0.83). Median survival in the cTACE group was 13 months (95% confidence interval, range 5–40 months) compared to 16 months (95% confidence interval, range 1–48 months) in the DSM-TACE group, exhibiting no statistically significant difference (p = 0.75). Conclusion: DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE. Key Points: • To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM. • DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE. • Survival analysis showed a median survival of 13 months in the cTACE group compared to 16 months in the DSM-TACE group (p = 0.75). [ABSTRACT FROM AUTHOR]

Purpose: To determine whether lipiodol, which has low thermal conductivity, influences ice ball formation during cryoablation of a lipiodol-mixed-tissue phantom. Materials and Methods: Lipiodol-mixed-tissue phantoms were created by injecting lipiodol (4–6 ml) into the renal arteries of ex vivo porcine kidneys (lipiodol group). A cryoprobe (CryoHit™ Needle S) with a holder that was set with thermocouples at various positions around the cryoprobe was inserted. After freezing for 300 s, the followings were evaluated: ice ball size on CT, temperature distribution around the cryoprobe, and calculated distances at 0 °C and − 20 °C. Each variable was compared between lipiodol group (n = 6) those obtained in a control group without lipiodol injection (n = 6). Results: Mean ice ball diameter (width/length) on CT was 22.1 ± 2.3/22.9 ± 2.3 mm in the lipiodol group and 21.6 ± 0.7/22.2 ± 1.3 mm in the control group. Mean cryoprobe temperature was − 118 ± 3.0 °C in the lipiodol group and − 117 ± 2.6 °C in the control group. In both groups, temperature at the 3 mm thermocouple reached approximately − 50 °C and was < 0 °C within ~ 10 mm of the cryoprobe. Temperature of 0/− 20 °C occurred at a mean distance from the cryoprobe of 11.1 ± 0.5/6.9 ± 0.4 mm in the lipiodol group and 11.0 ± 0.2/6.9 ± 0.2 mm in the control group. There was no significant difference in any variable between the groups. Conclusion: The inclusion of lipiodol in a tissue phantom had no negative effects on ice ball formation that were related to thermal conductivity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility and safety of n-butyl cyanoacrylate (NBCA)–Lipiodol–Iopamidol (NLI) as a liquid embolic material. Materials and Methods: In vitro, the ratio of NLI components was adjusted and the configuration of the mixtures was assessed visually in saline. In vivo, 14 wide-necked aneurysms were created on the common carotid and external iliac arteries of four female swine. Under balloon occlusion, 12 aneurysms were embolized with NLI prepared at a NBCA–Lipidol–Iopamidol ratio of 2:3:1 (NLI231), and two were embolized with NBCA–Lipiodol (NL) prepared at a NBCA–Lipiodol ratio of 1:2 (NL12) as a trial group. We performed angiography to evaluate the effectiveness of embolization and adhesion of the embolic material to the balloons or microcatheters. Results: In vitro, NLI231 (33% NBCA) was considered to be the optimal ratio for aneurysm embolization based on its configuration and stability. In vivo, embolization using NLI231 was successful and no adhesion between the embolic material and the balloons or microcatheters was observed in all 12 aneurysms. Embolization with NL12 was impossible in the other two aneurysms due to leakage and adhesion of NL. Conclusion: The configuration of NLI changed at each ratio. NLI231 is a feasible and safe liquid embolic material for balloon-assisted embolization of wide-necked aneurysms in swine. [ABSTRACT FROM AUTHOR]

Purpose: To determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach. Methods: Utilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands. Results: A total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5–2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p < 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia. Conclusions: PEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the current evidence for the effectiveness of transarterial embolization (TAE) in treatment of symptomatic hepatic hemangiomas.Materials and Methods: A systematic literature review was conducted in PubMed, CINAHL and Scopus databases to identify studies of hepatic hemangiomas treated with transarterial embolization. Main outcome was defined as the mean difference between pre- and post-TAE hemangioma diameters. Treatment agents were categorized as Lipiodol based [bleomycin (L + BE), pingyangmycin (L + PYG) or ethanol (L + ethanol)] and non-Lipiodol based (polyvinyl-alcohol-only). Conventional random-effect meta-analysis technique was applied to analyze data.Results: Of 3080 initially inspected publications, 21 studies were included in the meta-analysis comprising of 1450 patients with total of 1871 hemangiomas (36.2% male, mean age: 46.3 ± 3.6 years). One hundred and twenty-six, 1666, 41 and 38 lesions were treated with L + BE, L + PYG, L + ethanol and PVA, respectively. Median follow-up time after embolization was 12 months. Lipiodol-based treatments showed significant effect in reducing hemangioma size after TAE compared to PVA (P < 0.001). Pooled diameter reduction (cm) (95% confidence interval) was - 4.37( - 5.32, - 3.42), - 4.70( - 5.70, - 3.71), - 0.93( - 2.02, 0.16) for overall TAE treatment, Lipiodol-based and non-Lipiodol-based treatments, respectively. Main complications included post-embolization syndrome and transient liver enzyme elevation (pooled incidence for Lipiodol-based and non-Lipiodol-based techniques: 36% and 33%; and 37% and 0, respectively). No fatal complications were reported. Symptomatic improvement was reported in 63.3%-100% of the cases with majority of studies (15/21) reporting improvement in all cases (pooled response rate: 98%).Conclusions: Transarterial embolization with bleomycin, pingyangmycin or ethanol in combination with Lipiodol is safe and associated with reduced size of hemangiomas resulting in symptoms alleviation. [ABSTRACT FROM AUTHOR]

Purpose: To determine the optimal ratio of n-butyl cyanoacrylate (NBCA)–Lipiodol–ethanol (NLE) mixture for balloon-assisted embolization of wide-neck aneurysms. Materials and methods: We created 32 wide-neck aneurysms on both the common carotid arteries and external iliac arteries in eight female swine. Eight aneurysms were randomly assigned to four groups. Under balloon occlusion, the aneurysms were packed using NLE at one of four ratios of NLE: 2:2:1 (NLE221; 40%NBCA); 3:6:1 (NLE361; 30%NBCA); 2:7:1 (NLE271; 20%NBCA); and 1:5:1 (NLE151; 14.3%NBCA). We performed angiography before and after embolization to assess the aneurysms, and we compared adhesion between NLE and the balloon and assessed NLE migration. Three days after embolization, the aneurysms were removed for histopathologic evaluation. Results: Embolization was performed in 27 aneurysms. Adhesion between NLE and the balloon was not observed in any group. NLE migration was found in 0/7 aneurysms in the NLE221 group, 0/6 in the NLE361 group, 5/6 in the NLE271 group, and 7/8 in the NLE151 group. NLE migration was significantly lower in the NLE221 group than in the NLE271 and NLE151 groups (P = 0.0047 and 0.0014, respectively) and was significantly lower in the NLE361 group than in the NLE271 and NLE151 groups (P = 0.0152 and 0.0047, respectively). Media necrosis of the arterial wall close to the aneurysms was observed in all groups. Conclusion: NLE with an NBCA concentration of ≥ 30% is a safe and feasible embolic material for balloon-assisted embolization of wide-neck aneurysms in swine in the short term up to 3 days after embolization. [ABSTRACT FROM AUTHOR]

Purpose: To compare the polymerization time of n-butyl cyanoacrylate (NBCA) and lipiodol mixture in a static model and a pulsating flow model simulating embolization procedure of small caliber arteries.Materials and Methods: The polymerization time of NBCA-lipiodol mixture was measured by the morphological changes of a glue droplet in a petri dish. For the flow model, we used a 2-mm-inner-diameter polyvinyl alcohol tube connected to a pulsation pump. Bovine serum was supplied from the pump and circulated into the system at 30 ml/min and 60 bpm. A 0.64-mm-inner-diameter silicon microcatheter was inserted into this system, and then, 0.5 ml of glue was injected into the tube. The flow cessation time was defined as the time it took to stop the serum draining from the end of the tube. Six samples of 100, 66, 50, 40, 33, and 20 vol% NBCA were assessed.Results: The median polymerization times for each concentration were 0.12, 3.72, 12.30, 27.41, 57.68, and 63.67 s, respectively. The median flow cessation times were 0.28, 0.78, 1.43, 3.75, 4.50, and 9.29 s, respectively. The flow cessation time was significantly shorter than the polymerization time for all samples except for 100 vol% cyanoacrylate (p < 0.05).Conclusion: The flow cessation time of cyanoacrylate glue was significantly shorter than the polymerization time in an in vitro experiment. The injected glue possibly stops the blood flow before the completion of polymerization in the vascular system. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the basic thermophysical properties at low temperatures of lipiodol, which is used as a marker by transarterial injection before CT-guided cryoablation for solid tumors, by fundamental experiments with pure lipiodol phantom.Materials and Methods: The freezing point of lipiodol was measured using differential scanning calorimeter (DSC) by detecting differences in the heating rate during heating from - 30 °C. Freezing experiments were conducted using pure lipiodol and a tissue phantom, which were prepared in an acrylic container at 37 °C. The growth of the frozen region was observed for 10 min. Temperatures were monitored at the cryoprobe surface and designated positions around the cryoprobe.Results: The DSC experiment showed that freezing was observed between - 5 and - 30 °C, which indicated that the freezing point was approximately - 5 °C. Freezing experiments revealed that the diameter of frozen region in the lipiodol was smaller than that in the tissue phantom (5 mm vs 24 mm) after 10-min freezing. The temperature at the probe surface was - 130 °C in lipiodol, which was 25 °C lower than that in the tissue phantom. There was a larger temperature gradient near the cryoprobe in lipiodol due to lower thermal conductivity.Conclusions: The present results suggest that an extremely high concentration of lipiodol (close to pure lipiodol) potentially reduces frozen region because of its lower freezing point and smaller thermal conductivity. However, since lipiodol concentrations in clinical cases differ from the current model, further studies using models that are close to clinical conditions are required.Level Of Evidence: No level of evidence, laboratory investigation. [ABSTRACT FROM AUTHOR]

Preoperative marking is necessary in thoracoscopic wedge resections of lung nodules expected to be invisible or nonpalpable during surgery. Recently, lidocaine gel was added to a dye solution containing indigo carmine and lipiodol to promote micelle formation, but the optimal mixing ratio was not determined. Thus, an in vitro experiment was performed to identify the optimal mixing ratio of lidocaine gel, indigo carmine and lipiodol. To fixed volumes of indigo carmine and lipiodol of 0.5 ml each, 0.1, 0.2, 0.3, 0.4 and 0.5 ml of lidocaine gel was added. Changes were examined every 2 h. No changes were seen in the mixtures containing 0.1 and 0.2 ml of lidocaine gel, whereas those with 0.3, 0.4 and 0.5 ml had clearly separated after 2 h. Our findings suggest that the ideal proportion of indigo carmine, lipiodol and lidocaine gel for use in preoperative marking is 5:5:2. [ABSTRACT FROM AUTHOR]

Objective: To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE).Methods: We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE.Results: Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97 months (p = 0.001) and 3.1 months vs. 5.8 months (p < 0.001). In subgroup patients, the median OS and PFS of negative and positive lipiodol deposition groups were 4.7 months vs. 10.5 months (p < 0.001) and 3.5 months vs. 7.0 months (p < 0.001), respectively.Conclusions: The patients with positive lipiodol deposition in PVTT had a longer OS than those with negative lipiodol deposition. Furthermore, the positive lipiodol deposition in PVTT can further differentiate HCC patients with favourable prognosis from SD patients.Key Points: • Lipiodol deposition in PVTT is a prognostic indicator for HCC patients after TACE treatment. • Positive lipiodol deposition in PVTT is associated with a better prognosis. [ABSTRACT FROM AUTHOR]

Purpose: This study sought to provide preliminary results on the biodistribution and dosimetry following intra-arterial liver injection of 188Re-SSS Lipiodol on hepatocellular carcinoma patients included in the Phase I Lip-Re 1 study. Methods: Results of the first six patients included are reported. Analysis of the 188Re-SSS Lipiodol biodistribution was based on planar scintigraphic and tomoscintigraphic (SPECT) studies performed at 1, 6, 24, 48, and 72 h post-administration. Quantification in blood, urine, and stool samples was performed. Determination of the tumour to non-tumour uptake ratio (T/NT) was calculated. Absorbed doses to target organs and tumours were evaluated using the MIRD formalism. Results: The mean injected activity of 188Re-SSS Lipiodol was 1645 ± 361 MBq. Uptakes were seen in the liver (tumour and healthy liver) and the lungs only. All these uptakes were stable over time. A mean 1.4 ± 0.7% of 188Re-SSS Lipiodol administered was detected in serum samples at 6 h, declining rapidly thereafter. On average, 1.5 ± 1.6% of administered activity was eliminated in urine and feces over 72 h. Overall, 90.7 ± 1.6% of detected activity on SPECT studies was found in the liver (74.9 ± 1.8% in tumours and 19.1 ± 1.7% in the healthy liver) and 9.3 ± 1.6% in the lungs (5.7 ± 1.1% in right and 3.7 ± 0.5% in left lungs). Mean doses absorbed were 7.9 ± 3.7Gy to the whole liver, 42.7 ± 34.0Gy to the tumours, 10.2 ± 3.7Gy to the healthy liver, and 1.5 ± 1.2Gy to the lungs. Four patients had stable disease on CT scans at 2 months. The first patient with rapidly progressive disease died at 1 month, most probably of massive tumour progression. Due to this early death and using a conservative approach, the trial independent evaluation committee decided to consider this event as a treatment-related toxicity. Conclusion: 188Re-SSS Lipiodol has a favorable biodistribution profile concerning radioembolization, with the highest in-vivo stability among all radiolabeled Lipiodol compounds reported to date. These preliminary results must be further confirmed while completing this Phase I Lip Re1 study. [ABSTRACT FROM AUTHOR]

Purpose: To describe the feasibility of lymphangiography and the visibility of the lymphatic system using post-lymphangiographic multidetector CT (MDCT) for preclinical lymphatic interventions in a rabbit model.Materials and Methods: Lymphangiography via the popliteal lymph node or vessel after surgical exposure was performed, using six healthy female Japanese White rabbits. Lipiodol was manually injected for lymphangiography. Post-lymphangiographic MDCT examinations were performed in all rabbits. The dataset images were subjected to image processing analysis utilizing the three-dimensional maximum intensity projection technique. Three reviewers evaluated the degree of depiction of the lymphatic system using a four-point visual score (1, poor; 2, fair; 3, good; 4, excellent). The distance between the body surface and cisterna chyli was measured on post-lymphangiographic MDCT axial image.Results: Lymphangiography was successfully performed in all rabbits. The popliteal lymph node was detectable in 90%. The visualization of lymphatic system via the popliteal node was achieved in 89%. Mean visual scores of > 3.0 were realized by the right femoral lymphatic vessel, left femoral lymphatic vessel, left iliac lymphatic vessel, left lumbar lymphatic trunks and cisterna chyli, whereas mean visual scores of < 3.0 were yielded by the right iliac lymphatic vessel, right lumbar lymphatic trunks and thoracic duct. The distance between the body surface and cisterna chyli on post-lymphangiographic MDCT axial images was 4.33 ± 0.14 cm.Conclusion: Lymphangiography is feasible, and the visibility of the lymphatic system on post-lymphangiographic MDCT in a rabbit model provides enough information for interventional radiologists to perform preclinical lymphatic interventions. [ABSTRACT FROM AUTHOR]

Purpose: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion.Materials/methods: Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations.Results: Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04).Conclusion: Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h. [ABSTRACT FROM AUTHOR]

Purpose: Water-in-oil type and stability are important properties for Lipiodol emulsions during conventional trans-arterial chemo-embolization. Our purpose is to evaluate the influence of 3 technical parameters on those properties.Materials and Methods: The Lipiodol emulsions have been formulated by repetitive back-and-forth pumping of two 10-ml syringes through a 3-way stopcock. Three parameters were compared: Lipiodol/doxorubicin ratio (2/1 vs. 3/1), doxorubicin concentration (10 vs. 20 mg/ml) and speed of incorporation of doxorubicin in Lipiodol (bolus vs. incremental vs. continuous). The percentage of water-in-oil emulsion obtained and the duration until complete coalescence (stability) for water-in-oil emulsions were, respectively, evaluated with the drop-test and static light scattering technique (Turbiscan).Results: Among the 48 emulsions formulated, 32 emulsions (67%) were water-in-oil. The percentage of water-in-oil emulsions obtained was significantly higher for incremental (94%) and for continuous (100%) injections compared to bolus injection (6%) of doxorubicin. Emulsion type was neither influenced by Lipiodol/doxorubicin ratio nor by doxorubicin concentration. The mean stability of water-in-oil emulsions was 215 ± 257 min. The emulsions stability was significantly longer when formulated using continuous compared to incremental injection (326 ± 309 vs. 96 ± 101 min, p = 0.018) and using 3/1 compared to 2/1 ratio of Lipiodol/doxorubicin (372 ± 276 vs. 47 ± 43 min, p = <0.0001). Stability was not influenced by the doxorubicin concentration.Conclusion: The continuous and incremental injections of doxorubicin in the Lipiodol result in highly predictable water-in-oil emulsion type. It also demonstrates a significant increase in stability compared to bolus injection. Higher ratio of Lipiodol/doxorubicin is a critical parameter for emulsion stability too. [ABSTRACT FROM AUTHOR]

The utility and minimal invasiveness of ultrasound-guided intranodal lymphangiography have already been reported by several researchers. Although ultrasound-guided intranodal lymphangiography is known to be not technically difficult in general, a patient's edematous groin due to hypoalbuminemia resulting from chylous ascites made it too challenging to detect and prick the lymph nodes precisely. This report describes a 71-year-old female with refractory chylous ascites due to an operation for an extrahepatic bile duct cancer, who was successfully treated by computed tomography (CT)-guided intranodal lymphangiography. After switching from ultrasound- to CT-guided lymphangiography, the procedure was successfully performed, and the refractory chylous ascites was treated. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol®-based emulsions during liver trans-arterial chemo-embolization.Materials and Methods: We compared the theranostic properties of two emulsions made of Lipiodol® and doxorubicin in two successive animal experiments (One VX2 tumour implanted in the left liver lobe of 30 rabbits). Emulsion-1 reproduced one of the most common way of preparation (ratio of oil/water: 1/1), and emulsion-2 was designed to obtain a water-in-oil emulsion with enhanced stability (ratio of oil/water: 3/1, plus an emulsifier). The first animal experiment compared the tumour selectivity of the two emulsions: seven rabbits received left hepatic arterial infusion (HAI) of emulsion-1 and eight received HAI of emulsion-2. 3D-CBCT acquisitions were acquired after HAI of every 0.1 mL to measure the densities' ratios between the tumours and the left liver lobes. The second animal experiment compared the plasmatic and tumour doxorubicin concentrations after HAI of 1.5 mg of doxorubicin administered either alone (n = 3) or in emulsion-1 (n = 6) or in emulsion-2 (n = 6).Results: Emulsion-2 resulted in densities' ratios between the tumours and the left liver lobes that were significantly higher compared to emulsion-1 (up to 0.4 mL infused). Plasmatic doxorubicin concentrations (at 5 min) were significantly lower after HAI of emulsion-2 (19.0 μg/L) than emulsion-1 (275.3 μg/L, p < 0.01) and doxorubicin alone (412.0 μg/L, p < 0.001), and tumour doxorubicin concentration (day-1) was significantly higher after HAI of emulsion-2 (20,957 ng/g) than in emulsion-1 (8093 ng/g, p < 0.05) and doxorubicin alone (2221 ng/g, p < 0.01).Conclusion: Stabilization of doxorubicin in a water-in-oil Lipiodol®-based emulsion results in better theranostic properties. [ABSTRACT FROM AUTHOR]

Lipiodol functions as an embolizing agent for trans-arterial embolization and is used to deliver localized doses of chemotherapeutic drugs as well as ionizing radiation to cancerous tissue of the liver. Therefore, an attempt was made to prepare Ga-labeled lipiodol, which may have potential as a PET radiotracer for imaging of liver cancer. Ga-labeled lipiodol was prepared by a two-step procedure involving formation of highly lipophilic Ga-oxine complex followed by its dispersion in lipiodol. Preliminary biological evaluation in normal Wistar rats revealed satisfactory hepatic retention with insignificant uptake in any other major organ/tissue indicating promising potential of the agent. [ABSTRACT FROM AUTHOR]

Purpose: To analyze imaging findings of lymphatic leakage associated with surgical lymph node dissection on lymphangiography and assess the outcome of lymphatic embolization.Materials and Methods: This retrospective study comprised 21 consecutive patients who were referred for lymphatic intervention between March 2014 and April 2015 due to postsurgical lymphatic leaks. Lymphangiography was performed through inguinal lymph nodes to identify the leak. When a leak was found, lymphatic embolization was performed by fine-needle injection of N-butyl cyanoacrylate into the site of leakage or into an inflow lymphatic vessel or into a pelvic lymph node located below the leakage. Electronic medical records and imaging studies were reviewed to assess the outcome.Result: Lymphangiography revealed single or multiple leaks in all but one patient. Lymphatic embolization was performed in 20 patients with leaks. Including the patient who did not undergo embolization, 17 patients (81.0 %) showed initial response to treatment. Three patients underwent repeated embolization with successful results. The overall success rate was 95.2 %. The mean duration of hospitalization after lymphatic intervention was 5.9 days. During a mean follow-up period of 11 months, two patients developed localized swelling in the groin following lipiodol injection. There were no complications related to lymphatic embolization. Three patients were found to have developed small, asymptomatic lymphoceles on CT or MRI that did not require further treatment.Conclusion: Lymphangiography is useful for detecting lymphatic leakage occurring after lymph node dissection. Furthermore, lymphatic embolization is feasible, effective, and safe for managing leaks demonstrated on lymphangiography. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between the improved stability of an anticancer drug-lipiodol emulsion and pharmacokinetic (PK) profile for transarterial chemoembolisation (TACE) of hepatocellular carcinoma (HCC).Methods: The stability of four doxorubicin- or idarubicin-lipiodol emulsions was evaluated over 7 days. PK and clinical data were recorded after TACE with the most stable emulsion in eight unresectable HCC patients, after institutional review board approval.Results: The most stable emulsion was the one that combined idarubicin and lipiodol (1:2 v:v). At 7 days, the percentages of aqueous, persisting emulsion and oily phases were 50-0-50, 33-0-67, 31-39-30, and 10-90-0 for the doxorubicin-lipiodol (1:1 v:v), doxorubicin-lipiodol (1:2 v:v), idarubicin-lipiodol (1:1 v:v), and the idarubicin-lipiodol (1:2 v:v) emulsion, respectively. After TACE, mean idarubicin Cmax and AUC0-24h were 12.5 ± 9.4 ng/mL and 52 ± 16 ng/mL*h. Within 24 h after injection, 40% of the idarubicin was in the liver, either in vessels, tumours, or hepatocytes. During the 2 months after TACE, no clinical grade >3 adverse events occurred. One complete response, five partial responses, one stabilisation, and one progression were observed at 2 months.Conclusion: This study showed a promising and favourable PK and safety profile for the idarubicin-lipiodol (1:2 v:v) emulsion for TACE.Key Points: • Transarterial chemoembolisation (TACE) regimens that improve survival in hepatocellular carcinoma are needed. • Improved emulsion stability for TACE resulted in a favourable pharmacokinetic profile. • Preliminary safety and efficacy data for the idarubicin-lipiodol emulsion for TACE were encouraging. [ABSTRACT FROM AUTHOR]

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Background: Knowing the exact location of gastrointestinal tumors both preoperatively and intraoperatively is essential for planning and performing laparoscopic surgery. Different techniques have been introduced to ascertain tumor locations during surgery, but none of these are fully satisfactory at establishing the minimum margins for organ resection while retaining curability. A new, non-blurring tissue marker, detectable by both X-ray computed tomography (CT) and near-infrared (NIR) fluorescence laparoscopy, has been developed, and we here examine its utility using an animal model. Methods: Liposomes, comprised phospholipids and an NIR fluorescent dye (an indocyanine green derivative), and emulsions, consisting of phospholipids and oily radiographic contrast medium, were combined with polyglycerol-polyricinoleate to form giant cluster-like vesicles. This vesicular dispersion (300 μl) was administered into the porcine gastric submucosa using a gastroendoscope, and the detectability of the marker was examined using X-ray CT and NIR fluorescence laparoscopy. Results: One hour after the administration of the vesicular dispersion, X-ray CT identified four individual injection sites, each at a 1-cm radius of a metal hemostasis clip. NIR fluorescence laparoscopy detected individual fluorescent spots 18 hours after the administration of the vesicular dispersion. Conclusion: We anticipate that this newly developed tissue marker will contribute to the preoperative simulation of laparoscopic gastrointestinal cancer surgery and its intraoperative navigation. [ABSTRACT FROM AUTHOR]

Purpose: In an effort to apply the imaging techniques currently used in disease diagnosis for monitoring the pharmacokinetics and biodisposition of particulate drug carriers, we sought to use computed tomography (CT) scanning methodology to investigate the impact of surfactant on the blood residence time of emulsions. Methods: We prepared the iodinated oil Lipiodol emulsions with different compositions of surfactants and investigated the impact of surfactant on the blood residence time of emulsions by CT scanning. Results: The blood circulation time of emulsions was prolonged by including Tween 80 or DSPE-PEG (polyethylene glycol 2000) in emulsions. Tween 80 was less effective than DSPE-PEG in terms of prolongation effect, but the blood circulating time of emulsions was prolonged in a Tween 80 content-dependent manner. As a proof-of-concept demonstration of the usefulness of CT-guided screening in the process of formulating drugs that need to be loaded in emulsions, paclitaxel was loaded in emulsions prepared with 87 or 65% Tween 80-containing surfactant mixtures. A pharmacokinetics study showed that paclitaxel loaded in 87% Tween 80 emulsions circulated longer in the bloodstream compared to those in 65% Tween 80 emulsions, as predicted by CT imaging. Conclusions: CT-visible, Lipiodol emulsions enabled the simple evaluation of surfactant composition effects on the biodisposition of emulsions. [ABSTRACT FROM AUTHOR]

Cyanoacrylates are a group of fast-acting adhesives. They form low viscosity liquids in the monomer state and instantly polymerize to become adhesive upon contact with ionic substances. Since the 1950s, they have been used around the world for industrial and household purposes. N-butyl cyanoacrylate (NBCA) is a cyanoacrylate that is commonly used for medical care, and the closure of skin wounds with NBCA has been found to promote hemostasis. However, in Japan, the intravascular injection of NBCA is considered to be off-label use, except during the treatment of gastric varices under endoscopy. The use of NBCA in embolotherapy is considered when the target vessels cannot be cannulated superselectively, for vascular diseases that require long segments of the target vessel to be embolized, or for patients in a hypocoagulable state. NBCA-based embolotherapy can be used to treat vascular malformations, acute hemorrhaging, tumors, and venous disease. The complications associated with NBCA-based embolotherapy include tissue ischemia, hemorrhaging, systemic or local reactions, and catheter adhesion to blood vessels. NBCA is mixed with Lipiodol to make it radiopaque and to adjust its polymerization time. Since there are various technical aspects to performing NBCA-based embolotherapy safely, it should be carried out by, or with the assistance of, proficient interventional radiologists. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Materials and methods: Fifteen VX2 tumor-bearing rabbits were randomized into five groups ( n = 3 in each group) that received either IV Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 h after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 h after injection, and tissues were evaluated for radioactivity. Results: At 1 h after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake ( P < 0.001) and higher ratios of tumor-to-normal liver uptake ( P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 h after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio ( P < 0.001) among all delivery methods. At 24 h, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 vs. 0.099 %ID/g; P < 0.001). Conclusion: Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection. [ABSTRACT FROM AUTHOR]

Objective: In our recent study, we developed a new radiopharmaceutical (Re-188 MN-16ET lipiodol) with encouraging results for the treatment of liver malignancy. In this study, we further evaluated the therapeutic efficacy of this radiopharmaceutical by measuring tumor response and survival times in rats with liver tumors after intra-hepatic arterial injection of Re-188 MN-16ET lipiodol. Methods: Twelve male rats bearing hepatic tumors were divided into three groups. Group 1 received an intra-hepatic arterial injection of 18.5 MBq Re-188 MN-16ET lipiodol; Group 2 received lipiodol and Group 3 received normal saline. Tumor size was measured by liver sonography before injection, at 2, 4, and 8 weeks after injection. Survival time and response rate were calculated. Results: All rats showed good response and survived over 60 days in Group 1 while all rats showed poor response in Group 2 and Group 3 with only 25 % of rats in Group 2 and none (0 %) in Group 3 survived over 60 days. The p value was 0.0067 between Group 1 and Group 3; 0.04 between Group 1 and Group 2; and 0.034 between Group 2 and Group 3. Conclusion: Re-188 MN-16ET lipiodol has good potential for the treatment of hepatoma. [ABSTRACT FROM AUTHOR]

Background: Injection of a suspension of miriplatin into the hepatic artery has been employed for the treatment of hepatocellular carcinoma (HCC). The efficacy and safety of transcatheter arterial chemoembolization (TACE) using miriplatin were evaluated.Methods: A total of 236 patients with unresectable HCC received miriplatin administration through the hepatic artery, followed by embolization with porous gelatin particles. The efficacy of this treatment modality was evaluated by contrast-enhanced computed tomography performed 1 month later and its safety based on the Common Terminology Criteria for Adverse Events (CTCAE).Results: Miriplatin was used at a median dose of 66 mg. The therapeutic efficacy was evaluated in 130 patients, and the overall and complete response rates were 70.0 and 37.7%, respectively. The efficacies differed depending on the staging and Japan integrated staging (JIS) scores of the HCCs, with the overall and complete response rates being 87.7 and 66.7% for stage I and stage II HCC, and 56.2 and 15.1% for stage III and stage IV HCC, respectively; the corresponding rates were 93.2 and 70.5%, respectively, for HCCs with score 0 and score 1, and 58.1 and 20.9%, respectively, for those with scores 2-4. The stage of HCC was a significant independent factor associated with curative effects of TACE using miriplatin. Grade 3 elevation of serum transaminase levels was found in 23.4% of the patients; however, the values returned to the baseline levels.Conclusions: Miriplatin is a useful and safe agent for TACE in patients with HCC stage I or II and/or JIS score 0 or 1 only when radiofrequency ablation and liver resection cannot be performed. [ABSTRACT FROM AUTHOR]

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Background: Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. Patients and methods: All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. Results: Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months ( P = 0.032) and 104 versus 19 months ( P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. Conclusion: The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival. [ABSTRACT FROM AUTHOR]

The need for computed tomography (CT) of reticuloendothelial system (RES)-rich organs such as the liver is increasing, particularly in patients with suspected hepatic metastasis. CT images of the liver have been improved by encapsulating currently used, water-soluble iodine contrast agent in liposomes. The present study was performed to investigate a possibility to overcome the limitations of entrapped iodine in liposomes by preparing liposomes co-loaded with iopamidol, a water-soluble iodinated compound, and lipiodol, an iodized oil. Iopamidol and lipiodol were simultaneously loaded in liposomes by modified reverse-phase evaporation method. The entrapped iodine concentration, mean particle size and polydispersity index of resulting liposomes were evaluated. Following intravenous injection of these liposomes into rats, CT scanning was performed. Simultaneous loading of iopamidol and lipiodol into liposomes resulted in entrapped iodine concentrations as high as 49.2 iodine mg/ml. The mean particle size was 280 nm, and the mean polydispersity index was 0.230. CT scanning with these iopamidol/lipiodol (I/L) liposomes into rats resulted in more pronounced and more persistent increases in RES-rich organs, liver and spleen, compared with free liposomes or liposomes loaded with iopamidol alone. These findings indicate that I/L liposomes have the potential to allow thorough CT examination of RES-rich organs. [ABSTRACT FROM AUTHOR]

Miriplatin (formerly SM-11355), a novel lipophilic platinum complex developed to treat hepatocellular carcinoma, is administered into the hepatic artery using an oily lymphographic agent (Lipiodol Ultra-Fluide®) as a carrier. We clarified the usefulness of miriplatin as an agent for transarterial chemoembolization. Platinum compounds released from miriplatin into serum, medium and Earle’s balanced salt solution were examined. Then, miriplatin and cisplatin were administered to rats bearing hepatoma AH109A tumors in livers. Platinum concentrations in tissues and DNA were assessed. Miriplatin showed a more sustained release than cisplatin. Dichloro[(1 R, 2 R)-1, 2-cyclohexane diamine- N, N′]platinum, the most abundant platinum compound released from miriplatin, was as effective as cisplatin in inhibiting the growth of cells. Miriplatin was selectively disposed of in tumors, maintained in tumors longer than cisplatin and caused apparent tumor regression inducing platinum-DNA adducts to form and massive apoptosis. Miriplatin appears to be a suitable chemotherapeutic agent for transarterial chemoembolization. [ABSTRACT FROM AUTHOR]

The purpose of this study was to retrospectively clarify the current status in Japan of TACE using Lipiodol together with anticancer agents to treat hepatocellular carcinoma (HCC). We retrospectively surveyed 4,659 (average annual total) procedures for HCC over the years 2002–2004 at 17 institutions included in the TACE Study Group of Japan. The survey included six questions that were related mainly to TACE and Lipiodol for HCC treatment. The most frequently applied among the 4,659 procedures at the 17 institutions were TACE (2,310; 50%) and local ablation (1,395; 30%). Five of the institutions applied 201–300 procedures and 4 applied 101–200. Lipiodol was used in “all procedures” and in “90% or more” at seven and nine institutions, respectively. Almost all institutions applied 4–6 (mean, 5) ml of Lipiodol during TACE to treat tumors 5 cm in diameter. In conclusion, this survey clarified that TACE using Lipiodol and anticancer agents is a popular option for HCC treatment in Japan. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the feasibility and safety of lung volume reduction by transbronchial alcohol and lipiodol suspension infusion with the aid of balloon-tipped catheter occlusion. Twenty-six healthy adult rabbits were divided into four treatment groups: alcohol and lipiodol suspension infusion ( n = 8), lipiodol infusion ( n = 8), alcohol infusion ( n = 5), or bronchial lumen occlusion ( n = 5). After selective lobar or segmental bronchial catheterization using a balloon-tipped occlusion catheter, the corresponding drug infusion was performed. Bone cement was used to occlude the bronchial lumen in the occlusion group. The animals were followed up for 10 weeks by chest X-ray and computed tomography (CT), and then the whole lungs were harvested for histological examination. Alcohol and lipiodol suspension or lipiodol could be stably retained in alveoli in the first two groups based on chest X-ray and CT, but obvious collapse only occurred in the group receiving alcohol and lipiodol suspension or the bronchial lumen occlusion group. Histological examination revealed damage and disruption of the alveolar epithelium and fibrosis in related lung tissue in the group receiving alcohol and lipiodol suspension. Similar changes were seen in the bronchial lumen occlusion group, apart from obvious marginal emphysema of the target areas in two animals. Interstitial pneumonia and dilated alveoli existed in some tissue in target areas in the lipiodol group, in which pulmonary fibrosis obliterating alveoli also occurred. Chronic alveolitis and pleural adhesion in target areas occurred in the group infused with alcohol alone, whereas visceral pleura of the other three groups was regular and no pleural effusion or adhesion was found. Alcohol and lipiodol suspension that is stably retained in alveoli can result in significant lung volume reduction. Through alcohol and lipiodol suspension infusion, obstructive emphysema or pneumonia arising from bronchial lumen occlusion could be avoided. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to determine the safety and efficacy of chemoembolization (TACE) as palliative treatment for patients with unresectable intrahepatic cholangiocarcinoma (CCA) and to compare the results with those in the literature. Fifteen patients with histology-proven CCA (5 men, 10 women) had received palliative treatment with TACE over a 6-year period. The treatment protocol comprised repeated TACE at a minimum of 8-week intervals. TACE was performed with a mixture of 10 ml Lipiodol and 10 mg mitomycin C injected into the tumor-supplying vessels. Follow-up investigations after 8–10 weeks comprised contrast-enhanced multislice spiral CT and laboratory control. Statistical evaluation included survival analysis using the Kaplan-Meier method. During the investigation period 58 TACEs (3.9 ± 3.8; 1–15) were performed in 15 patients. Mean tumor size was 10.8 ± 4.6 cm (range, 2.0–18.0 cm). Unifocal tumor disease was diagnosed in eight patients, and multifocal disease in seven. Mean survival was 21.1 months (95% CI, 9.4–32.5 months). At the end of the investigation period 3 patients are still alive, and 12 patients have died. The 1-, 2-, and 3-year survival rate was 51.3%, 27.5%, and 27.5% respectively. According to RECIST criteria interim best response to therapy was stable disease in 9 of 15 patients, a partial response in 1 of 15 patients, and tumor progression in 4 of 15 patients. No deaths and no acute liver failure occurred under TACE therapy. Major complications were observed in two patients, comprising anaphylactic shock owing to contrast medium administration in one and gastric ulceration due to lipiodol displacement in the second patient. These results demonstrate that TACE is a safe procedure with a moderate number of complications for patients suffering from inoperable CCA. According to recently published data on i.v. chemotherapy we suggest that TACE might be able to prolong survival in selected patients who would succumb under other palliative treatment modalities. [ABSTRACT FROM AUTHOR]