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Renal angiomyolipoma: selective arterial embolization--effectiveness and changes in angiomyogenic components in long-term follow-up.

PURPOSE: To evaluate the efficacy of selective arterial embolization in symptomatic renal angiomyolipoma (AML) and the change in angiomyogenic components during long-term follow-up after embolization. MATERIALS AND METHODS: Fourteen adult patients with symptomatic AMLs underwent 16 selective arterial embolizations. The embolic materials used were absolute alcohol with (n = 5) or without (n = 3) iodized oil, Gianturco coils (n = 4), and polyvinyl alcohol foam powder with gelatin sponge (n = 2). Follow-up ultrasonography and computed tomography (CT) were performed in six and 14 patients, respectively. The effectiveness of selective arterial embolization was evaluated on the basis of the area of the angiomyogenic components in the AML on initial and follow-up images and clinical improvement. RESULTS: All patients showed devascularization of the tumor on the postembolization angiograms. In 13 patients, clinical symptoms disappeared. The follow-up period was 7-72 months (mean, 33 months). One patient underwent nephrectomy at 7 months after embolization because of a large cystic lesion found at 1 month. In long-term CT follow-up (> or =12 months) in 12 patients, nearly all angiomyogenic components disappeared, but fatty components partially shrank with liquefactive necrosis in tumors. CONCLUSION: Selective arterial embolization is an effective and safe treatment of AML. The angiomyomatous components crucial for the prevention of bleeding were very sensitive to the embolization.

Adult↗

Obstetric embolotherapy: effect on menses and pregnancy.

PURPOSE: To determine the long-term effects of uterine embolotherapy with gelatin sponge pledgets on menses and fertility. MATERIALS AND METHODS: Between June 1990 and December 1995, 17 women (aged 20-44 years) with obstetric hemorrhage underwent selective gelatin sponge pledget embolization of uterine vessels. Gynecologic information in the 12 women who did not undergo hysterectomy was obtained by means of direct communication or from the patients' physicians. RESULTS: In 11 (92%) of the 12 women, normal menses resumed within 2-5 months of the procedure. There were no complications related to embolotherapy. The follow-up period was 1-6 years. All three patients who desired to conceive had full-term, healthy newborns. The only patient who is amenorrheic is currently receiving medroxyprogesterone acetate; her ultimate menstrual and fertility status cannot yet be determined. CONCLUSION: Selective embolization of the uterine vessels with gelatin sponge pledgets is a safe and effective method of managing pregnancy-related hemorrhage. Our results suggest that women who undergo this procedure can expect to have a return of normal menses with no adverse effect on fertility.

Adult↗

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of damage to nontumorous liver tissue-long-term prospective study.

PURPOSE: To evaluate damage to cirrhotic liver tissue after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: TACE was performed in 111 patients with HCC that involved less than 30% of the liver. Baseline liver function was evaluated with Child-Pugh scores and other indicators. Eighty-two patients had Child-Pugh class A disease, 27 had class B disease, and two had class C disease. All patients underwent chemotherapy followed by gelatin sponge particle embolization in the proper ("complete" embolization; n = 69) or right or left main ("partial" embolization; n = 42) hepatic artery. Liver function was assessed 4 months later, and 95 patients underwent a second TACE (complete embolization in 57, partial in 38). Liver function was again assessed 4 months later in 60 patients. RESULTS: No patient died. Child-Pugh scores increased in all patients from a mean 5.96 to 6.28 (not significant) and 6.51 (P =. 05) after first and second TACEs, respectively. In patients with class A disease, scores increased from a mean 5.37 to 5.73 (P =.01) and 5.89 (P =.001) after first and second TACEs, respectively; in patients with class B disease, scores changed from a mean of 7.48 to 7.67 and 7.30 after first and second TACEs, respectively (not significant). CONCLUSION: TACE does not induce significant long-term worsening of liver function in patients with class A or B cirrhosis.

Adult↗

Cost-effectiveness of hepatic arterial chemoembolization for colorectal liver metastases refractory to systemic chemotherapy.

PURPOSE: To calculate the cost-effectiveness of hepatic arterial chemoembolization (HACE) for the treatment of colorectal liver metastases (CLM) over a range of survival benefits and to determine the survival benefit that HACE must confer to meet three thresholds of cost-effectiveness. MATERIALS AND METHODS: A spreadsheet model was used to estimate the marginal direct cost of HACE compared with palliative care from a payer's perspective. Medicare reimbursement amounts represented costs, while probabilities of reembolization and complications were obtained from records of patients who underwent HACE. Marginal cost-effectiveness was calculated from marginal direct cost by varying the survival benefit of HACE compared with palliative care from 0 to 24 months. Break-even analyses were conducted to determine the survival benefit at which the cost-effectiveness of HACE would decrease below three threshold values derived from a literature review. RESULTS: The marginal cost-effectiveness of HACE compared with palliative care, given survival benefits of 3, 6, and 12 months, was $82,385, $41,193, and $21,045 per life-year (LY) gained, respectively. Cost-effectiveness thresholds of $20,000 (strict), $50,000 (moderate), and $100,000 (generous) per LY gained required survival benefits of 12.63, 4.94, and 2.47 months, respectively, more than the expected baseline. CONCLUSION: The cost-effectiveness of HACE for the treatment of CLM varies considerably according to the anticipated survival benefit. Results of future randomized controlled trials must demonstrate a survival benefit of nearly 5 months for HACE to meet the moderate cost-effectiveness standard of $50,000 per LY gained.

Antibiotics, Antineoplastic↗

Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply.

PURPOSE: To evaluate the usefulness of percutaneous radio-frequency (RF) thermal ablation of nonresectable hepatocellular carcinoma (HCC) after occlusion of the tumor arterial supply. MATERIALS AND METHODS: Sixty-two patients with cirrhosis and biopsy-proved HCC underwent RF ablation after interruption of the tumor arterial supply by means of occlusion of either the hepatic artery with a balloon catheter (40 patients) or the feeding arteries with gelatin sponge particles (22 patients). RESULTS: After a single RF procedure in 56 patients and after two procedures in six patients, spiral computed tomography (CT) demonstrated a nonenhancing area corresponding in shape to the previously identified HCC, which was suggestive of complete necrosis. No major complications occurred. Two patients subsequently underwent surgical resection; the remaining 60 patients were followed up with spiral CT. During a mean follow-up of 12.1 months, 11 HCC nodules showed areas of local progression; 49 were identified as nonenhancing areas with a 40%-75% reduction in maximum diameter. The 1-year estimate of failure risk was 19% for local recurrence and 45% for overall intrahepatic recurrence. The estimated 1-year survival was 87%. Histopathologic analysis of one autopsy and two surgical specimens revealed more than 90% necrosis in one specimen and 100% necrosis in two. CONCLUSION: HCC nodules 3.5-8.5 cm in diameter can be ablated in one or two RF sessions after occlusion of the tumor arterial supply.

Aged↗

Heparin/heparan sulfate chelation inhibits control of vascular repair by tissue-engineered endothelial cells.

The relative importance of heparin-like compounds in mediating vascular repair is unclear. We investigated how protamine, a chelator of heparin, affected endothelial cell inhibition of vascular smooth muscle cell growth and intimal hyperplasia. The 52% (P < 0.001) reduction in smooth muscle cell proliferation produced by postconfluent endothelial cell-conditioned medium was entirely reversed by pretreatment of medium with heparinase and heparitinase and was inhibited in a dose-dependent fashion by the coadministration of protamine. Pretreatment of conditioned medium with heparinase and heparitinase largely prevented protamine's mitogenic activity, suggesting that protamine affects growth by interacting with heparin-like compounds. Perivascular implantation of polymerengrafted endothelial cells reduced neointima formation in denuded rat carotid arteries by 92% (P < 0.001) and cell proliferation by 81% (P < 0.001). Coadministration of protamine abolished the inhibitory potential of the cell implants, resulting in a nearly twofold exacerbation of intimal hyperplasia compared with controls (P < 0.001). Thus heparin-like molecules are essential to the biochemical regulation of vascular repair provided by endothelial cells, and the continued routine clinical use of heparin chelators, like protamine, may be questionable.

Animals↗

Pharmacokinetics of mitomycin C following hepatic arterial chemoembolization with gelfoam.

Twelve mongrel dogs were randomly allocated into two groups using matched paired-design. Catheters were inserted into the hepatic artery, hepatic vein and the femoral vein, respectively. In the first group, gelfoam supplemented with mitomycin C (MMC) was injected into the hepatic artery, whereas the second group received a hepatic arterial injection of MMC solution alone. Simultaneous blood sampling from the hepatic and femoral vein at regular intervals was performed. MMC concentrations in plasma was determined using high performance liquid chromatography (HPLC) and the pharmacokinetics of MMC were determined. MMC concentrations in hepatic and femoral veins did not differ and no significant difference in pharmacokinetics was found when comparing MMC administration into the hepatic artery with or without gelfoam supplementation. Thus, our results revealed that gelfoam could not delay the clearance of MMC from the liver.

Animals↗

Improved tumor targeting by regional carboplatin application combined with Gelfoam. An experimental study on liver tumor-bearing rabbits.

Regional chemotherapy of liver metastases is a promising alternative to systemic chemotherapy. Despite a number of theoretical advantages, extended life expectancy has only been confirmed in two studies. Since tumors have a concentration-dependent response to cytostatics, the primary goal is to increase the cytostatic concentration applied in tumor tissue. The aim of this study on liver tumor-bearing chinchilla rabbits was to show that the regional application of carboplatin leads to an increased concentration in tumor tissue. A further increase in carboplatin concentration by additional regional application of gelatine powder (Gelfoam) was demonstrated in a subsequent test; regional compared to intravenous application increased the carboplatin concentration in the tumor tissue by a factor of 12.1 and coapplication with Gelfoam increased the cytostatic concentration by a factor of 44.3.

Animals↗

Perivascular endothelial implants inhibit intimal hyperplasia in a model of arteriovenous fistulae: a safety and efficacy study in the pig.

Vascular access complications are a major problem in hemodialysis patients. Native arteriovenous fistulae, historically the preferred mode of access, have a patency rate of only 60% at 1 year. The most common mode of failure is due to progressive stenosis at the anastomotic site. We have previously demonstrated that perivascular endothelial cell implants inhibit intimal thickening following acute balloon injury in pigs and now seek to determine if these implants provide a similar benefit in the chronic and more complex injury model of arteriovenous anastomoses. Side-to-side femoral artery-femoral vein anastomoses were created in 24 domestic swine and the toxicological, biological and immunological responses to allogeneic endothelial cell implants were investigated 3 days and 1 and 2 months postoperatively. The anastomoses were wrapped with polymer matrices containing confluent porcine aortic endothelial cells (PAE; n = 14) or control matrices without cells (n = 10). PAE implants significantly reduced intimal hyperplasia at the anastomotic sites compared to controls by 68% (p < 0.05) at 2 months. The beneficial effects of the PAE implants were not due to differences in the rates of reendothelialization between the groups. No significant immunological response to the allogeneic endothelial cells that impacted on efficacy was detected in any of the pigs. No apparent toxicity was observed in any of the animals treated with endothelial implants. These data suggest that perivascular endothelial cell implants are safe and reduce early intimal hyperplasia in a porcine model of arteriovenous anastomoses.

Animals↗

Efficacy of gene transfer through the round window membrane: an in vitro model.

The viral vector-transgene soaked gelatin-sponge method has been shown to be successful in mediating transgene expression across an intact round window membrane (RWM) in mouse in vivo. However, there are many confounding factors which make it difficult to evaluate the role of the RWM in gene transfer. We have created an in vitro model to test the feasibility of gene delivery through an intact RWM. The round window including the bony niche of a CD1 mouse was removed under an operating microscope and fixed with adhesive on the base of a petri dish through which a hole had been drilled. Toluidine blue was injected into the niche containing a hyaluronic acid ester sponge against the round window membrane. The niche was closed with a fascia. A plastic tube containing PBS was fixed on the opposite side, from where the samples were collected at different time points. The concentration of toluidine blue was evaluated spectrophotometrically. An adenoviral vector containing green fluorescent protein (GFP) marker gene was injected into the niche. Samples were collected from the opposite side at different time points. The presence of the vector was studied with GFP PCR. We also modulated the permeability of the RWM by treating it with clinically applicable detergents, histamine or silver nitrate. Silver nitrate and trichloracetic acid caused destruction of the surface epithelium of the RWM as shown by light microscopy. Both toluidine blue and adenoviral vectors passed through the RWM in a time-dependent fashion. RWM cells expressed GFP after Ad-GFP treatment. The permeability of the RWM was decreased after treatment with different detergents, histamine or silver nitrate. RWM offers an atraumatic route to the inner ear. Compared with more invasive gene delivery methods, this technique represents a safer and clinically more viable route of cochlear gene delivery.

Animals↗

Adipose tissue engineering by human adipose-derived stromal cells.

Tissue engineering has emerged as a promising alternative approach to current clinical treatments for restoration of soft tissue defects. The purpose of this study was to investigate adipose tissue formation in vitro and in vivo by using human adipose-derived stromal cells (ADSCs) utilizing a gelatin sponge (Gelform) as a scaffold. Adipogenic potentials of human ADSCs were demonstrated by Oil-O-red staining and cellular morphology. After seeding human ADSCs in a density of 3 x 10(6) cells/ml on three-dimensional gelatin sponges, tissue-engineered constructs were exposed to adipogenic differentiation medium for in vitro studies and implanted in the backs of severe combined immunodeficient (SCID) mice for in vivo adipose regeneration. Adipogenesis of ADSC-seeded gelatin sponges was confirmed by Oil-O-red staining after 4 weeks of in vitro incubation. The optical density of the elution from Oil-O-red staining of adipogenic constructs is significantly higher than that of the control group (p < 0.05, n = 4). With short-term in vitro differentiation, adipogenic constructs turned into fat tissue 4 weeks after in vivo implantation, confirmed by biochemical and immunohistochemical examination. No adipogenic-morphological change or fat formation was observed in in vitro or in vivo studies when ADSCs were exposed to a control medium without adipogenic stimulation. These results indicate that engineered adipose tissue can be achieved using human ADSCs and biocompatible and degradable gelatin sponges.

Adipose Tissue↗

Control of post renal biopsy hemorrhage by Gelfoam embolization.

A patient with severe and protracted post renal biopsy hemorrhage is presented. The bleeding site was identified by renal arteriography and the hematuria was promptly controlled by Gelfoam embolization of the artery leading directly to the bleeding site. This aggressive approach should be considered early to control hematuria and expanding perirenal hematomas in selected cases of protracted post renal biopsy hemorrhage.

Adult↗

Hepatic arterial chemoembolization for metastatic neuroendocrine tumors.

PURPOSE OF THE STUDY: To evaluate the effectiveness of chemoembolization of the liver with doxorubicin and iopamidol emulsified in ethiodized oil for the treatment of metastatic neuroendocrine tumors. PATIENTS AND METHODS: Twenty patients with hepatic islet cell or carcinoid metastases were treated with selected hepatic arterial embolization consisting of an emulsion of doxorubicin and iopamidol emulsified in ethiodol followed by Gelfoam powder embolization. Fifteen patients had failed intravenous chemotherapy. Two of the patients with carcinoid tumors had three embolizations over 4 and one 6 years earlier with gelatin sponge only. RESULTS: In 14 patients with hormonally active tumors, hormones secretion decreased 90% (range 69-98%) in 10 days with relief of symptoms in all patients. Average tumor size decrease was 84%. Average hospital stay was 8 days. Six patients are alive and asymptomatic at 14-33 months postembolization. Fourteen patients have died 2-16 months postembolization. Ten patients died 2-37 months postembolization from progressive liver disease. One of these patients was 103 months post-Gelfoam embolization and 13 months postchemoembolization. In 8 patients, the pancreas was the primary site: 5 were nonfunctioning islet cell carcinomas, 1 glucagonoma, 1 gastrinoma and 1 carcinoid. The primary site in 1 patient with carcinoid was the bronchus, and the primary site was unknown in 1 patient with gastrinoma. The remaining 4 patients died with liver disease under control from renal failure, peritonitis, carcinoid heart failure and generalized bone metastases. The response rate was 95% with median duration of response 8.5 months. The median survival was 24 months. CONCLUSION: Chemoembolization with doxorubicin and iopamidol emulsified in ethiodized oil is less morbid than embolization with particulate matter alone, is more convenient and less costly, and it is less morbid than the effects of systemic chemotherapy. The median survival, duration and response compare favorably with other reported therapies.

Adenoma, Islet Cell↗

Cost reduction of skin biopsy and surgical instrumentation.

Saving the physicians time is very desirable in rendering first-rate dermatological service at lower cost. The aim is to reduce surgical instrumentation during skin biopsy procedures and follow-up visits. A combined instrument is used to obtain skin biopsies from 100 patients, and gelatin sponge plugs are used in hemostasis and to assist healing of the biopsy wound site. Skin biopsy samples are obtained simply and with ease, and, as the tissue sample is handled minimally, it appears to be more intact and less distorted in comparison to the usual procedure. Skin biopsy samples can be obtained with the combined instrument in a more cost-effective manner with savings of the physician's time and less instrumentation.

Anesthesia, Local↗

Bioavailability of topical steroids.

This paper review our modification of the vasoconstrictor (blanching) assay for topical corticosteroids using human volunteers, which we have improved and extended so that it may be used as a useful screening test for clinical efficacy besides being employed to determine the bioavailability of steroids from topical bases. Work is reported on the blanching activities of (1) 14 novel steroids in ethanol, (2)hydrocortisone 17-butyrate in eight topical vehicles, (3) betamethasone 17-benzoate in foam, ointment, cream and gel bases, and (4) 61 commercial formulations used in Great Britain. Pharmacokinetic/pharmacodynamic relationships are discussed as aids to optimizing topical steroid treatment.

Administration, Topical↗

Experimental basis of angioinfarction for the treatment of renal hypertension.

Collateral circulation and recanalization represent the main problems of organ-ablating renal embolization. Different animal models were used to study the influence of central, peripheral, and capillary occlusion on organ necrosis. The first laboratory experiments were performed to optimize transcatheteral application of the embolization media tested (Gelfoam powder, Histoacryl, Ethibloc). Experiments with the model of a normal rat kidney (n = 400) showed that only capillary embolization homogeneously occluding the entire arterial system resulted in complete organ necrosis, while following central (renal artery ligation) or peripheral (Gelfoam powder) occlusion, areas of intact parenchyma remained. Ethibloc/glucose proved to be the embolization medium best suited for capillary embolization (radiopaque, inert, slow resorption). Studies with the model of unilateral renal hypertension of the rat (n = 146) demonstrated the equivalent therapeutic efficiency on blood pressure of Ethibloc embolization (57% cured, 21% improved) compared to surgical nephrectomy (50% cured, 29% improved), whereas renal artery ligation (85% failed) resulted in minor improvement only. In order to adapt capillary embolization with Ethibloc/glucose to clinical angiographic techniques, we performed angioinfarction of canine kidneys (n = 15): the use of a balloon catheter is mandatory. This guarantees blood stasis during the embolization procedure and avoids embolic reflux. Possible clinical indications of capillary embolization in renal hypertension as a less invasive method are, e.g.: malignant nephrosclerosis; renovascular or glomerulonephritic contracted kidneys, and renal dysplasia. Indications for super-selective vaso-occlusion are renal aneurysms, a-v malformations, and segmental hypoplasia.

Angioplasty, Balloon↗