Therapeutic efficacy of 188Re-MN-16ET lipiodol in an animal model of hepatocellular carcinoma

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.     

The value of paradoxical uptake of hepatocellular carcinoma on the hepatobiliary phase of gadoxetic acid-enhanced liver magnetic resonance imaging for the prediction of lipiodol uptake after transcatheter arterial chemoembolization

PurposeTo compare the response to transcatheter arterial chemoembolization (TACE) between hepatocellular carcinoma (HCC) with paradoxical uptake on the hepatobiliary phase (HBP) (HCC_para) and HCC with defect on the HBP (HCC_def), and to identify some imaging features that can differentiate between two groups.Materials and methodsNinety-three HCCs from 54 patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) prior to TACE were included. HCCs were classified into two groups according to the signal intensity (SI) on the HBP: HCC_para and HCC_def. Using post-TACE computed tomography (CT) as a reference standard, initial compact lipiodol uptake was assessed and compared between groups. The arterial enhancement ratio (AER), SI ratios of the arterial phase and HBP, and presence of the capsule appearance were compared between groups. After initial response, local tumor recurrence within 6 and 18 months was evaluated based on follow-up CT or MRI.ResultsFifteen HCC_para and 78 HCC_def were included. Compared to HCC_def, HCC_para showed more frequent initial compact lipiodol uptake (p = 0.009), larger mean size (p = 0.019), lower AER (p = 0.005), higher SI ratio of the HBP (p < 0.0001), and more frequent capsule appearance (p < 0.0001). Local tumor recurrence rate within 6 months was also significantly lower in HCC_para than in HCC_def (p = 0.008).ConclusionDespite larger size and lower AER, HCC_para showed more frequent initial compact lipiodol uptake and lower early local recurrence rate after TACE than did HCC_def.     

Early response evaluation using CT-perfusion one day after transarterial chemoembolization for HCC predicts treatment response and long-term disease control

PurposeTo determine the value of CT perfusion (CTP) for early response assessment after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Materials and methodsBetween April 2013 and April 2015, 41 HCC (16 patients) were included in this study. CT perfusion was performed before and one day after TACE. Blood flow (BF), blood volume (BV), time to start (TTS), arterial liver perfusion (ALP), portal liver perfusion (PVP) and hepatic perfusion index (HPI) were measured. Quantitative perfusion values before and after TACE were compared to the response assessed using mRECIST criteria six weeks after TACE and long-term outcome was assessed.ResultsTwenty-one lesions (51%) had complete remission (CR) and five (12%) had partial response (PR) six weeks after TACE. CTP parameters were significantly reduced after TACE in responders (PR, CR, p < 0.001) while no difference was observed in non-responders. ALP_post was superior in the prediction of CR compared to BF_post and BV_post (p < 0.001) with a sensitivity, specificity, PPV, NPV, and accuracy of 90%, 90%, 91%, 90%, and 91%, respectively. Only 3/21 lesions with CR recurred, with a mean local-recurrence-free survival of 19.6 months.ConclusionCT perfusion detects lesions with complete response one day after TACE, and is a feasible tool for early response assessment.     

Biodistribution of phenylboric acid derivative entrapped lipiodol and 4-borono-2-18F-fluoro-l-phenylalanine-fructose in GP7TB liver tumor bearing rats for BNCT

A new phenylboric acid derivative entrapped lipiodol (PBAD-lipiodol) was developed as a boron carrier for the boron neutron capture therapy (BNCT) of hepatoma in Taiwan. The biodistribution of both PBAD-lipiodol and BPA-fructose was assayed in GP7TB hepatoma-bearing rat model. The highest uptake of PBAD-lipiodol was found at 2 h post injection. The application of BNCT for the hepatoma treatment in tumor-bearing rats is suggested to be 2–4 h post PBAD-lipiodol injection.     

Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

IntroductionIn spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium(¹⁸⁸Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy.MethodsMice bearing A2058 melanoma xenografts were treated with either 1.5 mCi ¹⁸⁸Re-6D2 antibody, saline, unlabeled 6D2 antibody or ¹⁸⁸Re-labeled non-specific IgM.ResultsOn Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells.ConclusionsThese results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers.     

Percutaneous treatment of non-contained lumbar disc herniation by injection of oxygen–ozone combined with collagenase

PurposeTo evaluate the therapeutic results of oxygen–ozone combined collagenase injection for the treatment of lumbar disc herniation compared to the surgery. And to explore the role of this minimally invasive treatment as an alternative to disc surgery.Materials and methodsTwo groups of patients (n = 108) were treated with different ways respectively. Minimally invasive group of patients was treated with the injection of oxygen–ozone combined with collagenase into the lumbar disc or the epidural space; the other group was treated with traditional surgery. After the treatment, the patients were followed-up and the therapeutic effect was assessed at 2 weeks, 3 and 12 months by the modified Macnab criteria.ResultsThe success rate was 86.11% and 88.89% in minimally invasive group at 3 and 12 months respectively, while 92.59% and 95.37% in surgical group. There was no statistically significant difference between two groups at 3 and 12 months (P = 0.123, P = 0.08). However, the surgical group produced a statistically significant greater improvement for back pain and disability in the first few weeks (P = 0.0001). The success rate was 51.86% and 85.18% at 2 weeks in minimally invasive group and surgical group respectively. No serious complication occurred in this group.ConclusionsThe combination of the oxygen–ozone with collagenase shows significant reductions in pain and improvements in function at 3 and 12 months, it can be considered as an option for the treatment of non-contained lumbar disc herniation instead of surgery.     

Progressive resistance training might improve vascular function in older women but not in older men

ObjectivesResistance exercise training increases strength and muscle mass in older adults however there is no consensus for its effect on arterial health. The aim of this study was to determine the effect of community based resistance training versus flexibility training on indicators of arterial stiffness and central blood pressure in healthy older adults and to test whether the effects of training are gender specific.DesignA randomised crossover intervention study.MethodsForty-nine healthy elderly participants (23 males) aged 66.7 ± 4.3 years (mean ± SD) participated in this study which involved undertaking 16 weeks of resistance training and 16 weeks of flexibility training in a random order separated by a four week washout period of usual activity. Prior to and following each training protocol period, participants underwent testing of arterial stiffness as augmentation index; and central blood pressure.ResultsWhen all participants were compared no changes in any measure of arterial stiffness or central blood pressure following resistance training compared to flexibility training were found. When male and female participants were analysed separately, a statistically significant decrease in augmentation index was observed in females (?5.28%; 95% CI: ?10.29 to ?0.26; p = 0.04) but not males (+1.72%; 95% CI: ?3.04 to 6.48; p = 0.48).ConclusionsCommunity based resistance exercise training does not adversely affect vascular function in apparently healthy older adults and may actually improve arterial function in females.     

Comparative study of post-transplant outcomes in hepatocellular carcinoma patients treated with chemoembolization or radioembolization

PurposeTo analyze long-term outcomes in patients bridged/downstaged to orthotopic liver transplantation (OLT) by transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y90) for hepatocellular carcinoma (HCC).Methods172 HCC patients who underwent OLT after being treated with transarterial liver-directed therapies (LDTs) (Y90: 93; TACE: 79) were identified. Pre-LDT and pre-OLT clinical/imaging/laboratory characteristics including United Network for Organ Sharing (UNOS) staging and alpha-fetoprotein values (AFP) were tabulated. Post-OLT HCC recurrence was assessed by imaging follow-up per standard of care. Recurrence-free (RFS) and overall survival (OS) were calculated. Uni/multivariate and sub-stratification analyses were performed.ResultsTime-to-OLT was longer in the Y90 group (Y90: 6.5 months; TACE: 4.8 months; p = 0.02). With a median post-OLT follow-up of 26.1 months (IQR: 11.1–49.7), tumor recurrence was found in 6/79 (8%) TACE and 8/93 (9%) Y90 patients. Time-to-recurrence was 26.6 (CI: 7.0–49.5) and 15.9 months (CI: 7.8–46.8) for TACE and Y90, respectively (p = 0.48). RFS (Y90: 79 months; TACE: 77 months; p = 0.84) and OS (Y90: 57% alive at 100 months; TACE: 84.2 months; p = 0.57) were similar. 54/155 patients (Y90: 29; TACE: 25) were downstaged to UNOS T2 or less. RFS hazard ratios for patients downstaged to ≤T2 versus those that were not were 0.6 (CI: 0.33–1.1) and 1.7 (CI: 0.9–3.1) respectively (p = 0.13). 17/155 patients (Y90: 8; TACE: 9) that were >T2 were downstaged to UNOS T2 or less (within transplant criteria). Distribution (unilobar/bilobar), AFP, and pre-transplant UNOS stage affected RFS on univariate analyses.ConclusionDespite longer time-to-OLT for Y90 patients, post-OLT outcomes were similar between patients bridged or downstaged by TACE or Y90. A trend towards improved RFS for downstaged patients was identified.     

Scan time adapted contrast agent injection protocols with low volume for low-tube voltage CT angiography: An in vitro study

PurposeThe aims of this study were twofold. First, we investigated the extent of changes in arterial peak enhancement and changes in the duration of a diagnostic arterial enhancement when small amounts of CA volumes (≤30 mL) were administered at varying tube voltages. Second, we investigated how to optimize CA injection protocols for CT-angiography with long scan times at various tube voltages to achieve optimal vascular enhancement at the lowest reasonable CA dose.Materials and methodsMeasurements were performed with a custom-made dynamic flow phantom. For CTA protocols with a short scan time, we investigated the effect of various tube voltages (70–120 kVp) on the arterial enhancement profile with very small CA volumes (20 and 30 mL of Iobitridol 350 mg I/mL) at a flow rate of 5 mL/s. For CTA protocols with a long scan time, we utilized an optimized multi-bolus technique switching rapidly between 13 “micro-boli” of CA (total, 60 mL) and saline (total, 24 mL) at a flow rate of 4 mL/s. The peak arterial enhancement (PAE) and the time period of diagnostic aortic enhancement ≥200 HU (T200) were analyzed.ResultsFor the short scan time protocols, a diagnostic peak enhancement was achieved using 20 mL of CA at 70 and 80 kVp (PAE: 327 ± 10 and 255 ± 15 HU, respectively) or 30 mL of CA at 70, 80 and 100 kVp (PAE 451 ± 10, 367 ± 9, and 253 ± 15 HU). For the long scan time, the optimized multi-bolus injection protocol extended T200 at 100 kVp by 6 s (40%) compared to a linear injection protocol (21 ± 1 s and 15 ± 1 s, respectively; p < 0.001).ConclusionOptimized CTA protocols comprising alternations of tube voltage and the CA injection protocol can save radiation doses and CA volumes at the same time.     

Diagnostic value of dynamic contrast-enhanced CT with perfusion imaging in the quantitative assessment of tumor response to sorafenib in patients with advanced hepatocellular carcinoma: A feasibility study

PurposeTo investigate the feasibility of perfusion-CT (p-CT) measurements in quantitative assessment of hemodynamic changes related to sorafenib in patients with advanced hepatocellular carcinoma (HCC).Materials and methodsTwenty-two patients with advanced HCC underwent p-CT study (256-MDCT scanner) before and 2 months after sorafenib administration. Dedicated perfusion software generated a quantitative map of arterial and portal perfusion and calculated the following perfusion parameters in target liver lesion: hepatic perfusion (HP), time-to-peak (TTP), blood volume (BV), arterial perfusion (AP), and hepatic perfusion index (HPI). After the follow-up scan, patients were categorized as responders and non-responders, according to mRECIST. Perfusion values were analyzed and compared in HCC lesions and in the cirrhotic parenchyma (n = 22), such as between baseline and follow-up in progressors and non-progressors.ResultsBefore treatment, all mean perfusion values were significantly higher in HCC lesions than in the cirrhotic parenchyma (HP 47.8 ± 17.2 vs 13.3 ± 6.3 mL/s per 100 g; AP 47.9 ± 18.1 vs 12.9 ± 10.7 mL/s; p < 0.001). The group that responded to sorafenib (n = 17) showed a significant reduction of values in HCC target lesions after therapy (HP 29.2 ± 23.3 vs 48.1 ± 15.1; AP 29.4 ± 24.6 vs 49.2 ± 17.4; p < 0.01), in comparison with the non-responder group (n = 5) that demonstrated no significant variation before and after treatment of HP (46.9 ± 25.1 vs 46.7 ± 24.1) and AP (43.4 ± 21.7 vs 43.5 ± 24.6). Among the responder group, HP percentage variation (Δ) in target lesions, during treatment, showed a significantly different (p = 0.04) ΔHP in the group with complete response (79%) compared to the group with partial response or stable disease (16%).Conclusionsp-CT technique can be used for HCC quantitative assessment of changes related to anti-angiogenic therapy. Identification of response predictors might help clinicians in selection of patients who may benefit from targeted-therapy allowing for optimization of individualized treatment.     

High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: Long-term follow-up and clinical analysis

ObjectiveHigh-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) has been used to treat unresectable HCC, but its long-term effects and major prognostic factors remain to be determined. The purpose of this study was to assess its long-term effects and find major prognostic factors to help us select eligible patients in the future.Methods73 patients with unresectable HCC received follow-up after HIFU + TACE. The variables of sex, age, AFP level, liver function, tumor location, tumor number, tumor size, TNM staging (5th edition), TNM staging (6th edition), portal vein invasion, ultrasonic pathway of HIFU, TACE session and ablation response were evaluated by univariate analysis. Those variables with significant difference were assessed by multivariate analysis.ResultsThe mean follow-up time was 11.7 ± 11.1 months (range, 1–60 months). The median survival time and overall survival rates of 1, 2, 3-year were 12 months, 49.1%, 18.8%, 8.4%, respectively. 45.2% patients achieved complete ablation. At the end of follow-up, 51 patients (69.9%) died from tumor progression (27 patients), liver function failure (18 patients), hemorrhage of upper digestive tract (3 patients) and infection (3 patients). 1 with liver abscess, 2 with serious skin burns and 2 with rib fracture were observed after HIFU. On univariate analysis, age (P = 0.017), tumor size (P = 0.000), tumor number (P = 0.039), the 5th edition of TNM staging (P = 0.023), portal vein invasion (P = 0.02) and ablation response (P = 0.000) had significant difference. On multivariate analysis, ablation response (P = 0.001) and tumor size (P = 0.013) were major prognostic factors.ConclusionHIFU combined with TACE is a safe method with a low rate of severe complications. As major prognostic factors, ablation response and tumor size may help us predict the survival and select eligible patients clinically.     

Basic Study of a Mixture of N-butyl Cyanoacrylate,Ethanol, and Lipiodol as a New Embolic Material

PurposeTo clarify the configuration change of N-butyl cyanoacrylate (NBCA) polymerization with increasing proportion of ethanol, the properties of a mixture of NBCA with lipiodol plus ethanol (NLE), and the feasibility of use of NLE for aneurysm packing in a swine model.Materials and MethodsThe polymerization configuration of NLE was explored using ratios of 1–4 parts NBCA and 1–3 parts ethanol per 1 part of lipiodol; a 1:1 ratio of NBCA to lipiodol (NLE110) was used as a control. The distance that NLE migrated into saline flowing in a tube was measured. A carotid artery aneurysm was created in each of 18 swine. Aneurysmal packing with three configurations—NLE110, NLE at a ratio of 1:1:2 (NLE112), and NLE at a ratio of 1:1:3 (NLE113)—was attempted in six swine for each configuration.ResultsRegardless of NBCA composition, medium-sized droplets, a single large droplet, and a noodle-shaped extrusion were observed in NLE with lipiodol versus ethanol ratios of 1:1, 1:2, and 1:3. NLE110 migrated as viscous fluid to 190 cm from the injection site, whereas NLE112 migrated for 81 cm±11 and NLE113 migrated for 74 cm±9. Instant outflow of NLE110 from the six aneurysms caused occlusion of the parent artery, with adhesion to the microcatheter. Packing was achieved with minimal adhesion for all six of the aneurysms packed with NLE112 or with NLE113.ConclusionsWith high ratios of ethanol, the NLE polymerization configuration acquired solid-like properties with potent occlusive ability and negligible adhesion to the microcatheter, suggesting its feasibility for packing of aneurysms.     

A comparative analysis of dual-phase dual-energy CT and FDG-PET/CT for the prediction of histopathological invasiveness of non-small cell lung cancer

PurposeTo compare dual-phase dual-energy CT (DE-CT) with FDG-PET/CT for predicting histopathological locoregional invasiveness of non-small cell lung cancers (NSCLCs).Materials and methodsWe selected 63 consecutive patients with NSCLC lesions (37 males, 26 females; age range, 44–85 years; mean age, 69 years) who were evaluated preoperatively by both DE-CT and PET/CT at our institution. Postoperative microscopic invasiveness (lymphatic permeation, vascular invasion, and/or pleural involvement) was reviewed, and we defined locoregionally invasive tumors as those that had at least one positive finding of microscopic invasiveness. DE-CT scanning in the arterial and delayed phases was performed after injection of iodinated contrast media using 140-kVp and 80-kVp tube voltages. Three-dimensional iodine-related attenuation of primary tumors in the arterial and delayed phases was quantified automatically using “syngo Dual Energy Lung Nodules” application software, and the ratio of arterial phase to delayed phase enhancement (A/D ratio) was calculated. The A/D ratio and SUVmax on PET/CT were evaluated with respect to postoperative invasiveness by univariate logistic regression analysis.ResultsThe A/D ratio was significantly correlated with lymphatic permeation, vascular invasion, and pleural involvement (p = 0.011, p = 0.021, and p = 0.010, respectively). In contrast, the SUVmax was significantly correlated with pleural involvement (p = 0.020) but not with lymphatic permeation or vascular invasion (p = 0.088 and p = 0.100, respectively). In the subgroup of patients with lesion diameters ≤2 cm, the A/D ratio was significantly correlated with locoregional invasiveness (p = 0.040), while the SUVmax was not (p = 0.121).ConclusionFor the prediction of microscopic invasiveness of NSCLCs, the diagnostic performance of dual-phase DE-CT may be comparable to that of FDG-PET/CT.     

Gadoxetic acid-enhanced high temporal-resolution hepatic arterial-phase imaging with view-sharing technique: Impact on the LI-RADS category

PurposeTo evaluate the value of view-sharing multi-hepatic arterial-phase (mHAP) imaging for diagnosis of hypervascular hepatocellular carcinoma (HCC).Materials and methodsForty-seven consecutive patients with HCC underwent gadoxetic acid-enhanced magnetic resonance (MR) imaging before angiographic and lipiodol CT. Hepatic arterial-phase images were obtained at 5 consecutive phases with shared central k-space of 25%, followed by portal venous, late (2 and 3 min), and hepatobiliary phase imaging. One-hundred-eight HCC nodules (size: 5–88 mm, mean size: 18.2 mm) confirmed on angiographic CT and lipiodol CT were evaluated for LI-RADS category and compared with single arterial-phase and mHAP findings regarding wash out, capsule, corona enhancement, and image quality.ResultsTwenty-four HCCs (22.2%) (size: 6–19 mm, mean size: 12.3 mm) were categorized as LR-3 based on the single arterial-phase. Capsule appearance (25.9%) and washout (57.4%) were most frequently observed in late phase (2 min). Corona enhancement was observed in 73.1% of all HCCs on mHAP. For the 24 HCCs of LR-3, corona enhancement was observed in 75% on mHAP and contributed to upgrade category. No significant difference was found in the frequency of corona enhancement between mHAP and angiographic CT (P = 0.11). Image quality was valued as good or excellent in all cases.ConclusionView-sharing mHAP was feasible without compromising image quality and contributed to the improvement in diagnostic confidence for hypervascular HCC in gadoxetic acid-enhance MR imaging.     

Resistance training enhances delayed memory in healthy middle-aged and older adults: A randomised controlled trial

ObjectivesHigh-intensity exercise is a potential therapeutic tool to postpone or prevent the onset of cognitive decline. However, there is a lack of sufficient evidence regarding the longitudinal effects of structured resistance training on cognitive function in healthy adults. The purpose of this study was to investigate the effect of two ecologically valid, intense 12-week resistance training programs on cognitive function in late middle-aged adults.DesignSingle-site parallel randomised controlled trial at the Department of Exercise Science strength and conditioning laboratory. Groups allocated by minimisation randomisation.MethodsForty-five healthy adults (age range = 41–69 years) were enrolled and randomised into (A) high-load, long rest resistance training (n = 14), or (B) moderate-load, short rest resistance training (n = 15) twice per week for 12 weeks, or a non-exercising control (n = 16). Follow-up within seven days. Data were collected September 2016–December 2017. Cognitive function assessed using the CogState computerised battery. Assessors were blinded to participant group allocation. Secondary outcomes were maximal muscle strength and body composition.ResultsForty-four participants were analysed in 2018. Delayed verbal memory performance was improved (p = 0.02) in resistance training groups (g = 0.67–0.79) when compared to the control group, with no differences between training groups. Likewise, increases in maximal muscle strength were observed (p < 0.01) in resistance training groups when compared to the control group, with no differences between training groups. No differences in body composition were observed. There were no adverse events or side-effects of the intervention.Conclusions12 weeks of intense resistance training improves delayed verbal memory irrespective of training design (i.e., high-load vs. moderate-load).Trial registrationThis study is registered at www.anzctr.org.au ACTRN12616000690459.     

Polyvinyl alcohol terminal chemoembolization for hepatocellular carcinoma with hepatic arteriovenous shunts: Safety,efficacy, and prognostic factors

PurposeTo evaluate the safety and efficacy of polyvinyl alcohol (PVA) terminal chemoembolization and to identify the prognostic factors associated with survival in hepatocellular carcinoma (HCC) patients with hepatic arteriovenous shunts (HAVS).Materials and methodsOf 133 patients’ managements were retrospectively analyzed. HAVS was classified into three types: slow-flow, intermediate-flow and high-flow. The size of the PVA used was determined following the scheme: slow-flow HAVS: 300–500 μm PVA; intermediate-flow HAVS: 500–710 μm PVA; high-flow HAVS: 710–1000 μm PVA. The HCCs with slow-flow and intermediate-flow HAVS were embolized by PVA plus chemotherapeutic agents lipiodol emulsion, while the high-flow HAVS were treated by PVA with chemotherapeutic agents. Survival curves were calculated by Kaplan-Meier method and compared by log-rank test. The influence of possible prognostic factors on survival were analyzed by multivariate Cox proportional-hazards method.ResultsThe median overall survival (OS) of 133 patients was 9.1 months. The median OS of the slow-flow type, intermediate-flow type and high-flow type patients were 10.8, 9.1 and 7.3 months, respectively. There was no statistically significant difference among different HAVS types (P = 0.239). The 30-day mortality was 3.8%. Cox multivariate survival analysis revealed that initial preoperative AFP value ≥ 400 ng/ml (HR = 2.105, P = 0.006) was an independent risk factor. While multiple embolization (HR = 0.482, P = 0.011), tumor remission (HR = 0.431, P = 0.041) and multimodality therapy (HR = 0.416, P = 0.004) were independent protection factors.ConclusionIt is safe and effective for HCCs with HAVS treated by terminal chemoembolization therapy with PVA plus chemotherapeutic agents lipiodol emulsion (or PVA plus chemotherapeutic agents). The HCCs with HAVS achieves good prognosis with multiple embolization, tumor remission and multimodality therapy, while achieves poor prognosis with inital preoperative high AFP value (≥400 ng/ml).     

Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin photodynamic therapy: A prospective study

BackgroundThe available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response.AimTo explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC.MethodsPatients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT + stent group, n = 12) or stent-only (stent group, n = 27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months.ResultsAverage survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT + stent group were significantly increased compared with the stent group. KPS scores in the PDT + stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT + stent group.ConclusionHematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response.     

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT

PurposeTo directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy.Materials and methodsFifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR + PR) and 2) stable or progressive disease (SD + PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV_max, and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared.ResultsThe step-wise regression test showed that therapeutic effect (r² = 0.63, p = 0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV_max. Mean overall survival showed a significant difference for total perfusion (p = 0.003) and systemic arterial perfusion (p = 0.04).ConclusionDynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.     

A comparison of the antibacterial activity of the two methods of photodynamic therapy (using diode laser 810 nm and LED lamp 630 nm) against Enterococcus faecalis in extracted human anterior teeth

BackgroundFailure of endodontic treatment is usually due to an inadequate disinfection of the root canal system. Enterococcus faecalis has been widely used as a valuable microbiological marker for in-vitro studies because of its ability to colonize in a biofilm like style in root canals, invading dentinal tubules and resistance to some endodontic treatments.The aim of this study was to investigate the antibacterial effects of two methods of photodynamic therapy using a light emitting diode lamp (LED lamp, 630 nm) and a diode laser (810 nm) on E. faecalis biofilms in anterior extracted human teeth.MethodsFifty six single-rooted extracted teeth were used in this study. After routine root canal cleansing, shaping and sterilization, the teeth were incubated with E. faecalis for a period of two weeks. Teeth were then divided into two experimental groups (nu = 23) and two control groups (nu = 5). Teeth in one experimental group were exposed to a diode laser (810 nm), and in the other group samples were exposed to a LED lamp (630 nm). Intracanal bacterial sampling was done, and bacterial survival rate was then evaluated for each group.ResultsThe Colony Forming Unit (CFU) in LED group (log 10 CFUs = 4.88 ± 0.82) was significantly lower than the laser group (log CFUs = 5.49 ± 0.71) (p value = 0.021). CFUs in positive control group (Log 10 CFUs = 10.96 ± 0.44) were significantly higher than the treatment group (p ˂ 0.001). No bacterial colony was found in negative control group.ConclusionThe results of this research show that photodynamic therapy could be an effective supplement in root canal disinfection. PDT using LED lamp was more effective than diode laser 810 nm in reducing CFUs of E. faecalis in human teeth.     

Antimicrobial photodynamic therapy combined to periodontal treatment: Experimental model

BackgroundAntimicrobial photodynamic therapy (aPDT) has been used as an adjuvant treatment for periodontitis. It combines a photosensitizer with a light source to induce reactive oxygen species and kill microbial cells. PpNetNI is a protoporphyrin derivative, and it has a chemical binding site at biofilm and great affinity to microbial cells. The aim of this study was to investigate the effects of aPDT as an adjuvant treatment for periodontitis.MethodsThirty healthy male rats Wistar (Rattus norvegicus) were used in this study (Approved by UNINOVE Ethical committee AN0029/2015). Periodontitis was induced by placing a cotton ligature around the first mandibular molar in a subgengival position. The contralateral mandibular first molar received neither a ligature nor any treatment, and was used as a control. After 7 days, the ligature was removed and all animals received scaling and root planing (SRP) and were divided according to the following treatments: SRP group (received SRP and irrigation with PpNetNI, 10 μM) and aPDT group (PpNetNI 10 μM followed by LED irradiation). aPDT was performed with a LED (630 nm) with an output power of 400 mW (fluence-rate 200 mW/cm²; fluence 18 J/cm²). Rats were euthanized at 24 h, 48 h and 7 days postoperatively. The area of bone loss in vestibular region of the first molar was evaluated by Optical Coherence Tomography (OCT, THORLABS LTD., Ely, UK). Data were analyzed statistically (ANOVA and Tukey tests, p < 0.05).ResultsThe animals treated by aPDT showed bone gain of approximately 30% compared to the SRP group following 7 days from the treatment.ConclusionaPDT promoted bone recovery 7 days after periodontal intervention.