Background: In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery. Exploiting this property, we delivered drug-eluting microspheres/beads (DEB) loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx-2). Purpose: The purpose of our study was to determine the pharmacokinetics and tumor-killing efficacy of DEB. Results: Our results show that plasma concentration of doxorubicin was minimal in the animals treated with DEB at all time points (0.009-0.05 Amol/L), suggesting high tumor retention of doxorubicin. This was significantly lower (70-85% decrease in plasma concentration) than control animals treated with doxorubicin intra-arterially.Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g), remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76 nmol/g), indicating continuous doxorubicin elution from beads. In control animals, peak tumor concentration of doxorubicin was 0.09 nmol/g.Tumor necrosis (approaching 100%) was greatest at 7 days, with minimal adverse local side effects reflected in liver function tests results. The plasma concentration of doxorubicinol (doxorubicin main metabolite) was minimal. Conclusions: Our results support the concept of DEBs as an effective way to deliver drugs to tumor. This new technology may prove to be a useful weapon against liver cancer.
Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary Sclerosing Cholangitis (PSC) patients pose a particularly difficult clinical dilemma, since they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. Conclusion We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers and size distribution of human biliary EVs. Utilizing Multivariate Organization of Combinatorial Alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis which demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 patients with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 patients with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility.
Purpose This study evaluates the two-year overall survival (OS), adverse event rate, local control rate and impact on pulmonary function tests (PFTs) in medically inoperable patients with stage IA NSCLC undergoing CT-guided RFA in a prospective multi-center trial. Methods 54 patients M:F=25:29, median age/range= 76/60–89 were enrolled from 16 US centers 51 patients were eligible (biopsy proven stage IA NSCLC and deemed medically inoperable by board certified thoracic surgeon) for evaluation. PFTs were obtained within 60 days of RFA, 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed by CT and FDG PET. Local control rate and recurrence patterns were analyzed. RESULTS The OS rate was 86.3% at one year and 69.8% at two years. Local tumor recurrence free rate was 68.9% at one year and 59.8% at two years and was worse for tumors >2 cm. In the 19 patients with local recurrence, 11 had retreatment with RFA, nine had radiation and three had chemotherapy. There were 21 grade 3, two grade 4 and one grade 5 AEs in 12 patients within the first 90 days after RFA. None of the grade 4 and 5 AEs were attributed to the RFA. There was no significant change in the FEV1 or DLCO after RFA. Tumor size less than 2.0 cm and performance status of 0–1 were associated with a statistically significant improved survival of 83% and 78% respectively, at two years. CONCLUSIONS RFA is a single minimally invasive procedure, that is well tolerated in medically inoperable patients, does not adversely affect PFTs and gives two year OS that is comparable to that reported following SBRT in similar patients.
Purpose To (a) evaluate the response of hepatocellular carcinoma (HCC) to chemoembolization after initial nonresponse, as determined with European Association for the Study of the Liver (EASL) criteria and modified Response Evaluation Criteria in Solid Tumors (mRECIST), and (b) compare posttreatment survival of initial nonresponders versus that of initial responders. Materials and Methods The institutional review board approved this retrospective study, which was compliant with HIPAA. A total of 116 consecutive patients (96 men, 20 women; mean age, 63 years) with unresectable HCC who underwent at least two chemoembolization procedures were included. The chemoembolization mixture consisted of 100 mg of cisplatin, 50 mg of doxorubicin, and 10 mg of mitomycin C mixed 1:1 with iodized oil. Tumor response at magnetic resonance imaging was evaluated after each chemoembolization procedure according to EASL criteria and mRECIST. The survival rate in each subgroup was calculated and correlated with response. The Wilcoxon test was used to test group comparability. Kaplan-Meier estimators were used to generate survival curves and compared by using the log-rank test. Results No response to initial chemoembolization was seen in 43% and 50% of patients according to EASL criteria and mRECIST, respectively. After a second chemoembolization procedure, 44% (EASL) and 47% (mRECIST) of initial nonresponders showed a significant response. With EASL criteria, the 1-, 2-, and 3-year survival rates (±standard error of the mean) after two chemoembolization procedures were 39% ± 10, 14% ± 7, and 0%, respectively, for non-responders and 68% ± 10, 50% ± 11, and 37% ± 11 for responders (P = .036, P = .006, and P < .005 at 1, 2, and 3 years). With mRECIST, the 1-, 2-, and 3-year survival rates after two chemoembolization procedures were 49% ± 9, 20% ± 8, and 7% ± 6 for nonresponders and 67% ± 9, 44% ± 10, and 36% ± 9 for responders (P = .174, P = .046, and P = .011 at 1, 2, and 3 years). Conclusion Patients who underwent chemoembolization for HCC showed a response (with both EASL criteria and mRECIST) and improved survival after the second chemoembolization treatment. At least two chemoembolization procedures should be performed in the same targeted lesions before further treatment is abandoned.
Purpose To conduct a pilot prospective clinical trial to evaluate the feasibility, safety, and short-term efficacy of bariatric embolization, a recently developed endovascular procedure for the treatment of obesity, in patients with severe obesity. Materials and Methods This is an institutional review board- and U.S. Food and Drug Administration-approved prospective physician-initiated investigational device exemption study. This phase of the study ran from June 2, 2014, to August 4, 2015. Five severely obese patients (four women, one man) who were 31-49 years of age and who had a mean body mass index of 43.8 kg/m ± 2.9 with no clinically important comorbidities were enrolled in this study. Transarterial embolization of the gastric fundus with fluoroscopic guidance was performed with 300-500-μm Embosphere microspheres. The primary end point was 30-day adverse events (AEs). The secondary end points included short-term weight loss, serum obesity-related hormone levels, hunger and satiety assessments, and quality of life (QOL) surveys, reported up to 3 months. Simple statistics of central tendencies and variability were calculated. No hypothesis testing was performed. Results The left gastric artery, with or without the gastroepiploic artery, was embolized in five patients, with a technical success rate of 100%. There were no major AEs. There were two minor AEs-subclinical pancreatitis and a mucosal ulcer that had healed by the time of 3-month endoscopy. A hospital stay of less than 48 hours for routine supportive care was provided for three patients. Mean excess weight loss of 5.9% ± 2.4 and 9.0% ± 4.1 was noted at 1 month and at 3 months, respectively. Mean change in serum ghrelin was 8.7% ± 34.7 and -17.5% ± 29 at 1 month and 3 months, respectively. Mean changes in serum glucagon-like peptide 1 and peptide YY were 106.6% ± 208.5 and 17.8% ± 54.8 at 1 month. There was a trend toward improvement in QOL parameters. Hunger/appetite scores decreased in the first 2 weeks after the procedure and then rose without reaching preprocedure levels. Conclusion Bariatric embolization is feasible and appears to be well tolerated in severely obese patients. In this small patient cohort, it appears to induce appetite suppression and may induce weight loss. Further expansion of this study will provide more insight into the long-term safety and efficacy of bariatric embolization. RSNA, 2017 Online supplemental material is available for this article.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.