Biomedical subjects

John R Haaga

Publications and source records attributed to John R Haaga.

9 recordsLinked to original sources

PubMed2006

Injectable polymer depot combined with radiofrequency ablation for treatment of experimental carcinoma in rat.

OBJECTIVE: The purpose of this study was to investigate whether an intralesional chemotherapy depot with or without a chemosensitizer could improve the efficacy of radiofrequency (RF) ablation in treatment of experimental carcinoma in rats. MATERIALS AND METHODS: Eighteen BD-IX rats were inoculated with bilateral subcutaneous tumors via injection of DHD/K12TRb rat colorectal carcinoma cells in suspension. Four weeks after inoculation, one tumor in each rat was treated with RF ablation at 80 degrees C for 2 minutes and the other with RF ablation followed by intralesional chemotherapy with carboplatin. The drug was administered via 2 different in situ-forming poly(D,L-lactide-coglycolide) (PLGA) depot formulations either with or without a chemosensitizer. Treatment efficacy was assessed by comparing the change in tumor diameter compared with control, percent of coagulation necrosis and a rating of treatment completeness. RESULTS: Tumors treated with ablation and carboplatin + sensitizer (n = 9) showed a diameter decrease of 49.4 +/- 24.5% at the end point relative to ablation control, while those treated with ablation and carboplatin only (n = 8) showed a 7.1 +/- 12.6% decrease. Use of sensitizer also showed increased tissue necrosis (81.9 +/- 9.7% compared with 68.7 +/- 26.7% for ablation only) and double the number of complete treatments (6/9 or 66.7%) compared with ablation control (3/9 or 33.3%). CONCLUSIONS: From these results, we conclude that intralesional administration of a carboplatin and sensitizer-loaded polymer depot after RF ablation has the potential to improve the outcome of ablation by increasing effectiveness of local adjuvant chemotherapy in preventing progression of tumor unaffected by the ablation treatment.

Animals↗

PubMed2005

Combined tumor therapy by using radiofrequency ablation and 5-FU-laden polymer implants: evaluation in rats and rabbits.

PURPOSE: To evaluate the use of 5-fluorouracil (5-FU)-laden polymer implants as an adjunct to radiofrequency (RF) ablation for tumor treatment. MATERIALS AND METHODS: All animal studies were performed in compliance with the Case Western Reserve University Institutional Animal Care and Use Committee guidelines. Three studies were performed to investigate (a) in vitro dissolution of 5-FU-laden polymer implants in saline and bovine serum, (b) tissue distribution of 5-FU and its metabolite, 5-fluorouridine (5-FUrd), in the ablated liver tissue of rats (n = 4), and (c) efficacy of combined approach (n = 4) compared with that of ablation alone (n = 6) for VX2 liver tumor model in rabbits. Characterization of 5-FU release in vitro and distribution of 5-FU in rat liver tissue were analyzed by using high performance liquid chromatography; in vivo efficacy was assessed by using computed tomography and pathologic examination. RESULTS: Results of the in vitro dissolution study showed that a 75% release of 5-FU occurred in 2 days when exposed to bovine serum and in 9 days when exposed to phosphate-buffered saline. In the ablated rat liver, the 5-FU level was higher at the center and lower at the periphery of the tissue both at 24 hours (41.0 mg per kilogram tissue vs 15.0 mg per kilogram tissue, respectively) and at 48 hours (8.0 mg per kilogram tissue vs 2.0 mg per kilogram tissue, respectively). The 5-FUrd concentration was twofold higher peripherally than centrally and was higher at 48 hours than at 24 hours. In rabbits, local delivery of 5-FU immediately after RF ablation provided a significant (P < .05) reduction in tumor size compared with ablation alone (1.80 cm3 +/- 0.28 [standard error] vs 3.53 cm3 +/- 0.52, respectively; P = .034) and a more than 20-fold reduction in tumor size compared with the control (1.80 cm3 +/- 0.28 vs 41.95 cm3 +/- 11.58, respectively; P = .018). CONCLUSION: Combined treatment by using 5-FU polymer implants and RF ablation shows uniform sustained release of 5-FU for 48 hours at least 8 mm from the edge of the ablation zone and appears to be successful at controlling the growth of an experimental tumor in rabbits appreciably better than does ablation alone.

Animals↗

PubMed2005

Interventional CT: 30 years' experience.

CT-guided procedures remain an important tool for diagnosis and tissue acquisition for primary diagnosis and molecular/tissue correlation. New imaging devices such as MDCT and PET/CT will improve diagnosis but percutaneous procedures will be needed to confirm and support new molecular and DNA treatments. Coagulopathic patients can be treated with LIBE a new method to prevent bleeding. Vasoactive drugs can be used to improve differentiation of malignant and benign diseases.

Biomarkers↗

PubMed2004

Quantitative computed tomography analysis of local chemotherapy in liver tissue after radiofrequency ablation.

RATIONALE AND OBJECTIVES: Computed tomography (CT) was used to noninvasively monitor local drug pharmacokinetics from polymer implants in rat livers before and following radiofrequency ablation. MATERIALS AND METHODS: Polymer matrixes containing carboplatin (a platinum-containing chemotherapeutic agent) were implanted into rat livers either immediately after radiofrequency ablation (n = 15) or without prior treatment (n = 15). The animals were divided into five subgroups (n = 3 per group) and subjected to a terminal CT scan at 6, 24, 48, 96, or 144 hours. Carboplatin concentration in tissue and within the implant matrix was correlated with CT intensity, and standard curves were produced for each environment. This correlation was used to evaluate the differences in drug transport properties between normal and ablated rat livers. A quantitative image analysis method was developed and used to evaluate the release rate and tissue distribution of carboplatin in normal and ablated liver tissue. The CT data were validated by previously reported atomic absorption spectroscopy measurement of implant and tissue drug levels. RESULTS: Correlation of carboplatin concentration and Hounsfield units results in a linear relationship with correlation coefficients (slopes) of 15 and 4 Hounsfield units/(mg/mL), for carboplatin in tissue and polymer, respectively. Noninvasive monitoring of local pharmacokinetics in normal and ablated tissues indicates that ablation before local carboplatin delivery increases the retention of carboplatin within the polymer matrix and drastically increases the drug retention in the ablated tissue volume (over 3-fold difference) resulting in a higher average dose to the surrounding tissue. At 1.6 mm from the implant boundary, carboplatin concentration is significantly higher in ablated tissue at 48, 96, and 144 hours (P <.05), and reaches 4.7 mg/mL in ablated tissue at 48 hours. In comparison, the concentration in normal liver at 1.6 mm reaches only 0.7 mg/mL at the same time point. The drug penetrates 3.1 mm in ablated liver compared with 2.3 mm in normal liver also at 48 hours. After 144 hours, the drug is still detected at 3.1 mm in ablated liver but not in normal liver. The differences are significant (P <.05) at both 48 and 144 hours. Correlation with chemical analysis suggests that CT data accurately predicts the drug pharmacokinetics in both ablated and normal livers. CONCLUSION: This work shows that X-ray CT imaging is a useful and promising technique for in vivo monitoring of the release kinetics of locally delivered radiopaque agents.

Animals↗

PubMed2004

Emergent ultrasound interventions.

The interventionist can perform many emergent procedures with ultrasound guidance, because of its real-time, multiplanar imaging capability and portability. With the use of color Doppler, additional important information, such as aberrant vessels, can be ascertained to help plan needle trajectory. Ultrasound is also useful for nonemergent procedures, such as biopsies. All interventionists are encouraged to be facile with the use of ultrasound.

Abdominal Abscess↗

PubMed2004

A feasibility study of high intensity focused ultrasound for liver biopsy hemostasis.

This study was conducted to demonstrate the feasibility of high intensity focused ultrasound (HIFU) application to control post-liver-biopsy hemorrhage. Anesthetized Yorkshire pigs (n = 3; mean weight = 23.0 kg) were used and the liver organ was exposed surgically by an open laparotomy. Core biopsies were performed on the hepatic parenchyma with 14-gauge (n = 41) and 18-gauge (n = 33) core biopsy needles. The focus of HIFU (4.23 MHz) field was applied for 15 to 45 s to the needle entry site in the liver immediately after needle retraction. Blood loss from a biopsy site was determined using surgical sponges as absorbent applied at the site. Mean blood loss for control sites was 6.16 g (14-gauge, n = 20) and 1.22 g (18-gauge, n = 10). Virtually no blood loss was measured for biopsies after HIFU application (n = 44) for using needles of both sizes. Our results indicate that intraoperative HIFU application could successfully induce hemostasis after liver biopsy in a porcine model.

Animals↗

PubMed2004

Phase II clinical trial of interactive MR imaging-guided interstitial radiofrequency thermal ablation of primary kidney tumors: initial experience.

PURPOSE: To perform a phase II clinical trial to evaluate efficacy and safety of interactive magnetic resonance (MR) imaging-guided radiofrequency (RF) interstitial thermal ablation (ITA) of primary renal tumors. MATERIALS AND METHODS: Ten male patients (age range, 25-83 years) with peripheral renal cell carcinoma and contraindications to surgery were treated with percutaneous RF ITA entirely guided and monitored with a 0.2-T MR imaging unit. By using a 200-W RF ablation system and custom-fabricated MR imaging-compatible cool-tip electrodes, pulsed RF current was applied for single or multiple ablation cycle(s) of 12-15 minutes until the entire tumor was replaced by an enlarging zone of low signal intensity on T2-weighted and/or short inversion time inversion-recovery images acquired intermittently during the procedure. Kidney MR images were acquired before, immediately after, and 2 weeks after ablation and then every 3 months for 1 year and every 6 months thereafter. Intra- and postprocedural complications were assessed with clinical evaluation of patients for pain and hemodynamic instability and evaluation of MR images for evidence of hemorrhage or other unexpected findings. Follow-up images were assessed for delayed complications such as renal ischemia, infarct, urinoma, or tumor recurrence. RESULTS: Treated tumors ranged between 0.63 and 16.90 mL in volume and 1.0 and 3.6 cm in maximum diameter. Successful RF electrode insertion and/or repositioning into the renal mass was achieved in all cases with direct MR "fluoroscopic" guidance. Thirty ablation cycles were conducted at 21 electrode positions in the 10 procedures, and complete ablation, as defined with MR imaging, was achieved in all cases by the end of the procedure. Apart from two small self-limited perirenal hematomas, no intra- or postprocedural complications were observed. No delayed complications or tumor recurrence occurred during a mean follow-up period of 25 months +/- 9.4 (standard deviation). CONCLUSION: Although these results are preliminary, interactive MR imaging-guided RF ITA for treatment of primary renal tumors has a high success rate.

Adult↗

PubMed2003

Noninvasive monitoring of local drug release using X-ray computed tomography: optimization and in vitro/in vivo validation.

In vivo release profiles of drug-loaded biodegradable implants were noninvasively monitored and characterized using X-ray computed tomography (CT). The imaging method was adapted and optimized to quantitatively examine the release of an active agent from a model cylindrical PLGA device (the millirod) into rabbit livers over 48 h. Iohexol, a CT contrast agent, served as a model drug; optimization of CT acquisition parameters yielded a sensitivity of 0.21 mg/mL (or 95 microg iodine/mL) for this agent. In vitro validation of the method was carried out by tracking release of iohexol in gelatin gel phantoms. In vivo release in rabbit livers was characterized through quantitative analysis of CT images and compared with UV-Vis analysis of the explanted devices at three implantation times. After correction for respiratory motion, CT analysis correlates well with the extracted iohexol data at all time points. The percent error between the actual and experimental image data was below 10%. This study demonstrates the potential of using computed tomography to noninvasively quantify the rate of agent release from controlled delivery devices in vivo.

Animals↗

PubMed2002

Noninvasive monitoring of local drug release in a rabbit radiofrequency (RF) ablation model using X-ray computed tomography.

In this study, X-ray computed tomography (CT) was utilized as a noninvasive method to directly examine local drug release kinetics in livers before and following radiofrequency thermal ablation. Iohexol, a CT contrast agent, was used as a drug-mimicking molecule. Release of iohexol in healthy and ablated rabbit livers over 48 h was quantified and correlated with the release profiles from phosphate-buffered saline (PBS) in vitro. The results show that iohexol release in ablated livers is significantly slower than both release in normal livers and in vitro. The time at which 50% of the drug was released (t(1/2)) into ablated liver (20.6+/-5.9 h) was 1.7 times longer than in normal liver (12.1+/-5.4 h) and approximately two times longer than that in PBS (10.1+/-1.2 h). The slower release in ablated livers is a result of severe tissue damage inflicted by thermal ablation, as supported by histological examination. This data suggests that a noninvasive imaging method provides a superior measurement over in vitro release studies in accurately quantifying the local release kinetics of an agent in an altered physiological system in vivo. Because the development of a successful local drug therapy is dependent on the understanding of the agent release kinetics at the implantation site, the noninvasive data may be indispensable in effectively predicting the implant behavior in a physiological system.

Animals↗