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OBJECTIVE. The purpose of this study was to clarify the natural history of unruptured visceral artery aneurysms due to segmental arterial mediolysis and the efficacy of transcatheter arterial embolization. MATERIALS AND METHODS. Patients with a pathologic or clinical diagnosis of visceral artery aneurysms due to segmental arterial mediolysis between 2005 and 2015 were enrolled. For patients with clinical diagnoses, images were collected and assessed by central radiologic review. To clarify the natural history of unruptured aneurysms, the morphologic changes were assessed. The efficacy and safety of transcatheter arterial embolization for aneurysms due to segmental arterial mediolysis were evaluated. RESULTS. Forty-five patients with 123 aneurysms due to segmental arterial mediolysis were enrolled. Among the 123 aneurysms, 70 unruptured aneurysms were evaluated for natural history. Forty-five of the 70 (64%) aneurysms had no change in morphology. Among the other 25 aneurysms, nine (13% of the 70) were reduced in size, 13 (19%) disappeared, and three (4%) were newly found at follow-up. Aneurysms of the middle colic artery were ruptured in 10 of 11 (91%) cases. Transcatheter arterial embolization was performed on 45 aneurysms and was successful in all cases but caused slight arterial injury in three cases (6.7%). CONCLUSION. At initial diagnosis, unruptured aneurysms due to segmental arterial mediolysis are likely to be stable or to resolve, but the risk of rupture of aneurysms of the middle colic artery appears high. Transcatheter arterial embolization is a useful treatment, but careful manipulation is necessary.
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Aneurisma/terapia , Artérias , Embolização Terapêutica/métodos , Vísceras/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma/etiologia , Aneurisma/patologia , Aneurisma/cirurgia , Aneurisma Roto/etiologia , Artéria Celíaca , Embolização Terapêutica/efeitos adversos , Feminino , Artéria Gástrica , Artéria Gastroepiploica , Artéria Hepática , Humanos , Japão , Masculino , Artéria Mesentérica Inferior , Artéria Mesentérica Superior , Pessoa de Meia-Idade , Estudos Retrospectivos , Artéria Esplênica , Túnica MédiaRESUMO
BACKGROUND: The lesion size is a risk factor for keloid recurrence after postoperative radiotherapy. However, it remains unclear whether the major axis diameter is the most appropriate parameter to evaluate lesion size, because keloids are often irregular in shape. Additionally, no previous study has investigated computed tomography (CT) densitometry parameters of keloids as potential predictors for recurrence after postoperative radiotherapy. MATERIALS AND METHODS: The size and CT densitometry parameters were measured for 74 lesions with CT images of sufficient quality for evaluation. The association between recurrence and size or CT densitometry parameters was analyzed for 64 lesions that could be followed up for 6 months or more. RESULTS: The major axis diameter × minor axis diameter × thickness showed the strongest correlation with volume (ρ = 0.96, P < .0001). The median follow-up period was 71 months, and 17 lesions recurred. The major axis diameter × minor axis diameter × thickness ≥2.5 cm3 (hazard ratio = 5.9, P = .0052) and volume ≥1.2 ml (hazard ratio = 4.3, P = .029) were significantly associated with keloid recurrence under multivariate analyses, while the major axis diameter alone were not. The mean and maximum CT values, and the kurtosis and skewness of density histogram were not significantly different between recurrent and non-recurrent lesions. CONCLUSION: The major axis diameter × minor axis diameter × thickness may be a better parameter than the major axis diameter alone. CT densitometry analyses may not help to predict keloid recurrence after postoperative electron beam radiotherapy.
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Densitometria , Queloide , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Queloide/diagnóstico por imagem , Queloide/patologia , Queloide/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To investigate the new risk factors for keloid recurrence after postoperative electron beam radiotherapy (RT) and evaluate the effectiveness of tranilast in combination with electron beam RT by comparing the local control rate. BACKGROUND: Identifying patients at high risk of recurrence after postoperative RT for keloids remains a challenge. Besides, no study examined the effectiveness of tranilast in combination with RT after surgery for the prevention of keloids recurrence. MATERIALS AND METHODS: This study included 75 lesions in 59 consecutive patients who had undergone postoperative RT at our institute. The follow-up period and prescription of tranilast were examined beside several potential risk factors, such as multiple lesions, size, and shape. RESULTS: The median follow-up was 72 months (range, 6-147 months). Twenty-one lesions in 17 patients recurred in a median of 12 months after treatment (range, 1-60 months). Local control rates of all 75 lesions were estimated as 93%, 78%, 70%, and 68% at 1, 2, 5, and 10 years. Multiple lesions constituted a significant risk of recurrence (Pâ¯=â¯0.03). A larger long axis was significantly related to the recurrence (P < 0.01). Irregular shape was associated with a significantly worse local control rate (Pâ¯=â¯0.02). There was no significant difference in the local control rate between patients receiving tranilast and those who did not (Pâ¯=â¯0.52). CONCLUSIONS: Multiple lesions and irregular shape were risk factors of keloid recurrence after postoperative electron beam RT. The effectiveness of tranilast was not demonstrated in the study.
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BACKGROUND: Cutaneous adverse reactions are frequently induced by mogamulizumab. Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and severe photosensitivity related to mogamulizumab have been reported. This study investigated whether severe radiation-induced dermatitis occurred in patients undergoing radiotherapy after the administration of mogamulizumab for adult T-cell leukaemia/lymphoma. METHODS: We retrospectively reviewed 46 courses of radiotherapy administered to 15 consecutive patients with adult T-cell leukaemia/lymphoma (acute, n = 7; lymphoma, n = 7; smouldering, n = 1) who received mogamulizumab before or during radiotherapy at three institutions between 2012 and 2017. RESULTS: During 43 of the 46 radiotherapy courses, patients developed Grade ≤1 radiation-induced dermatitis. No patient developed Grade ≥3 radiation-induced dermatitis. No patient was prescribed ointments as prophylactic treatment for radiation-induced dermatitis. Development of radiation-induced dermatitis was not significantly associated with the number of days since the administration of mogamulizumab prior to radiotherapy (P = 0.85), frequency of administration of mogamulizumab before/during radiotherapy (P = 0.33), administration of mogamulizumab during radiotherapy (P = 0.41) or types of lesions in adult T-cell leukaemia/lymphoma cases (cutaneous vs. non-cutaneous, P = 0.74). Development of radiation-induced dermatitis was significantly related to the total cutaneous dose (mean, 31.9 Gy [95% confidence interval: 26.6-37.1 Gy] vs. 19.7 Gy [95% confidence interval: 16.2-23.2 Gy], P = 0.0004) and total prescribed dose (mean, 31.5 Gy [95% confidence interval: 26.2-36.8 Gy] vs. 18.5 Gy [95% confidence interval: 15.0-22.0 Gy], P = 0.0002). CONCLUSION: None of the 15 patients who received moderate-dose radiotherapy developed severe radiation-induced dermatitis during the 46 courses of radiotherapy after mogamulizumab administration.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Radiodermite/induzido quimicamente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/radioterapia , Masculino , Pessoa de Meia-Idade , Radiodermite/diagnóstico por imagem , Estudos Retrospectivos , Pele/patologia , Pele/efeitos da radiação , Análise de SobrevidaRESUMO
PURPOSE: To investigate the incidence and patterns of chest compression-associated internal thoracic artery injury (CAI) during cardiopulmonary resuscitation and identify the embolization techniques used to treat hemorrhage. MATERIALS AND METHODS: A retrospective study was conducted in the patients who underwent transcatheter arterial embolization (TAE) for life-threatening hemorrhage caused by CAI at two tertiary care centers between May 2013 and December 2019. Data on background characteristics, imaging findings, embolization and outcomes were collected from the medical records. RESULTS: Among 385 patients in whom circulation returned after resuscitation, there were 9 patients (2.3%) who required TAE for CAI. Eight of 9 patients had acute myocardial infarction, and all had been started on extracorporeal membrane oxygenation before TAE. Seven patients had unilateral, and two had bilateral internal thoracic artery injuries. Main trunk injury of internal thoracic artery was seen in 27%, while branch injury in 73%. Six patients (67%) had multiple injuries in the internal thoracic artery territory, and five (56%) had injuries to other vessels. In all cases, we embolized the main trunk of the internal thoracic artery using n-butyl 2-cyanoacrylate and coils (n = 8), a gelatin sponge only (n = 2), or coils and a gelatin sponge (n = 1). TAE was technically successful in all, without any complication. The 30-day mortality rate was 44%. CONCLUSIONS: CAI needing hemostatic intervention occurred in 2.3% of patients after successful cardiopulmonary resuscitation. Branch injury was more common than main trunk injury, and multiple vessel injuries were common. TAE appears to be safe and effective for controlling life-threatening hemorrhage.
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Embolização Terapêutica , Artéria Torácica Interna , Humanos , Artéria Torácica Interna/diagnóstico por imagem , Gelatina , Estudos Retrospectivos , Incidência , Resultado do Tratamento , Hemorragia/terapia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodosRESUMO
PURPOSE: A multicenter phase I/II study of transarterial chemoembolization with a fine cisplatin powder and gelatin particles (GPs) for multifocal hepatocellular carcinoma (HCC) was conducted. Primary endpoints were dose-limiting toxicity (DLT) and recommended dose (RD). Secondary endpoints were the incidence and severity of adverse events and tumor response. MATERIALS AND METHODS: Nonselective transarterial chemoembolization was performed until all tumor enhancement disappeared. Lipiodol was not used. In the phase I study, the cisplatin dose was escalated from 35 mg/m(2) to 65 mg/m(2) in 15-mg/m(2) increments to determine DLT and RD. In the phase II study, 40 patients were treated with the RD. Toxicity was assessed by Common Toxicity Criteria for Adverse Effects (version 3.0), and tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) and European Association for the Study of the Liver (EASL) criteria. RESULTS: A total of 46 patients were enrolled. As no DLT occurred at any dose level in the phase I study, RD was determined as 65 mg/m(2). In the phase II study, the treatment was discontinued in one patient as a result of vasovagal response. Toxicities of grade 3 or higher included nausea (2.2%), pancreatitis (2.2%), cholecystitis (2.2%), thrombocytopenia (8.7%), hyperbilirubinemia (2.2%), and increased aspartate aminotransferase (28.3%) and alanine aminotransferase (21.7%) levels. Tumor response rates under RD were 25.6% and 64.1% by RECIST and EASL criteria, respectively. CONCLUSIONS: Nonselective transarterial chemoembolization with fine cisplatin powder and GPs was well tolerated and effective in patients with multifocal HCC at the RD of 65 mg/m(2).
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Cisplatino/administração & dosagem , Gelatina/administração & dosagem , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Cisplatino/efeitos adversos , Feminino , Gelatina/efeitos adversos , Humanos , Japão , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Porosidade , Pós , Fatores de Tempo , Resultado do TratamentoRESUMO
In superior vena cava occlusion, multiple collateral pathways develop to maintain venous drainage. Major patterns and pathways of venous collateral blood flow are well described, but rarely in complete chronic superior vena cava occlusion secondary to malignancy. A 59-year-old man with facial and upper extremity edema had a severely compressed superior vena cava at the initial diagnosis of stage IV mediastinal lung adenocarcinoma. The occlusion of superior vena cava progressed. After 10 months of treatment, the complete occlusion led to mild symptoms of hoarseness, muscle weakness, cough, and slight upper extremity edema. Venography clearly illustrated well-developed venous collateral blood flow through lateral thoracic, azygos-hemiazygos, and vertebral collateral venous pathways classified as Stanford type IV. The patient survived for a total of 20 months. He maintained Eastern Cooperative Oncology Group performance status of 1-2 until 2 months before death without severe symptoms of superior vena cava occlusion. This case described a rarely occurring venographic demonstration of well-developed Stanford type IV collateral pathway. Moreover, even with complete superior vena cava occlusion, well-developed Stanford type IV lateral thoracic collateral pathway can compensate for the venous flow without deterioration of performance status for a long period in certain cases.
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PURPOSE: To evaluate the impact of UAE for postpartum and postabortion hemorrhage on future infertility, especially in patients undergoing infertility treatment, along with angiographic endpoints. MATERIALS AND METHODS: Sixty-two sessions performed emergent or prophylactic UAE for postpartum or postabortion hemorrhage between 2008 and 2017 were selected. Subsequent pregnancy outcomes and complications were investigated as primary outcomes. The cases were divided into two groups based on the presence of massive hemorrhage. The relationships between angiographic endpoints and complications were also evaluated as secondary outcomes. RESULTS: The mean patient age was 34.1 ± 6.5 years. Fourteen of the 23 patients (60.9%) with desired fertility achieved pregnancy and 10 patients achieved live births (43.5%). In the patients during infertility treatment, three of the four patients had complications of severe adhesion after caesarean section or placenta accreta. In the group of patients with massive hemorrhage, the occurrence of uterine infection was significantly high (p = 0.014), but the angiographic endpoints were not significant, regardless of the occurrence of uterine infection. CONCLUSION: It was unnecessary to modify embolic endpoint according to seriousness of the hemorrhage. The pregnancy and live birth rates were acceptable, although patients undergoing infertility treatment had a higher rate of delivery complications.
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Assistência ao Convalescente/métodos , Fertilidade , Hemorragia Pós-Operatória/terapia , Hemorragia Pós-Parto/terapia , Resultado da Gravidez , Embolização da Artéria Uterina/métodos , Aborto Induzido , Adolescente , Adulto , Angiografia , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The long-term success of intra-arterial stenting remains limited by in-stent restenosis (ISR). Transforming growth factor-ß1 (TGF-ß1) can inhibit smooth muscle cell (SMC) proliferation and migration and convert SMCs into extracellular matrix (ECM)-synthesizing cells. Here, we evaluate the effects of stent-based delivery of TGF-ß1 on ISR in a rabbit model. Channeled stents loaded with TGF-ß1 or control microspheres were deployed in rabbit aortas. Stented aortas were harvested at 7 and 28 d and evaluated for Ki-67-positive cells, collagenous ECM production, and intima-to-media (I/M) ratio. At 7 d, the TGF-ß1 group exhibited fewer Ki-67-positive cells were found for the TGF-ß1 group (17.87 ± 2.18 cells per mm(2)) relative to control (25.07 ± 2.65 cells per mm(2), p = 0.04), but increased collagen content (31.4 ± 2.5 percentage area) compared with control (29.3 ± 1.2 percentage area, p = 0.019). The I/M ratio in the TGF-ß1 group was reduced by 50% and 9.1% versus control at 7 d (0.13 ± 0.02 vs. 0.26 ± 0.02, p = 0.0001) and 28 d (1.80 ± 0.05 vs. 1.98 ± 0.08, p = 0.0038), respectively. Stent-based controlled release of TGF-ß1 limits ISR and is associated with inhibition of SMC proliferation but an increase in ECM production.
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Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/cirurgia , Stents Farmacológicos , Fator de Crescimento Transformador beta1/administração & dosagem , Animais , Estenose da Valva Aórtica/patologia , Proliferação de Células , Colágeno/análise , Modelos Animais de Doenças , Matriz Extracelular/química , Antígeno Ki-67/análise , Miócitos de Músculo Liso/fisiologia , Coelhos , Resultado do Tratamento , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
BACKGROUND: Advances in imaging techniques have increased the recognition of aortic intramural hematomas (IMHs) and penetrating atherosclerotic ulcers (PAUs); however, distinction between IMH and PAU remains unclear. We intended to clarify differences between IMH coexisting with PAU and IMH not associated with PAU by comparisons of clinical features, imaging findings, and patient outcome to derive the optimal therapeutic approach. METHODS AND RESULTS: We performed a retrospective analysis of 65 symptomatic patients with aortic IMH. There were 34 patients with IMH associated with PAU (group 1) and 31 patients with IMH unaccompanied by PAU (group 2). Involvement of the ascending aorta (type A) was more frequent in group 2 (8 of 31, 26%), whereas most of the patients in group 1 had exclusive involvement of the descending aorta (type B) (31of 34, 91%). Patients were subdivided into 2 categories, those with clinical progression and those with stable disease. Forty-eight percent of patients in group 1 and 8% in group 2 were in the progressive category (P=0.002). Clinical and radiological findings were compared between those group 1 patients who had a progressive disease course (n=12) and those who were stable (n=13). Sustained or recurrent pain (P<0.0001), increasing pleural effusion (P=0.0003), and both the maximum diameter (P=0.004) and maximum depth (P=0.003) of the PAU were reliable predictors of disease progression. CONCLUSIONS: This study suggests a difference in disease behavior that argues for the prognostic importance of making a clear distinction between IMH caused by PAU and IMH not associated with PAU. IMH with PAU was significantly associated with a progressive disease course, whereas IMH without PAU typically had a stable course, especially when limited to the descending thoracic aorta.
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Doenças da Aorta/diagnóstico , Arteriosclerose/diagnóstico , Hematoma/diagnóstico , Úlcera/diagnóstico , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/terapia , Arteriosclerose/diagnóstico por imagem , Arteriosclerose/terapia , Progressão da Doença , Feminino , Hematoma/diagnóstico por imagem , Hematoma/terapia , Hospitalização , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Úlcera/diagnóstico por imagem , Úlcera/terapiaRESUMO
Surgically implanted ports have been used in continuous or repetitive intra-arterial (IA) chemotherapeutic infusions for patients with multiple liver metastases from colorectal cancer. Recently, a percutaneous implantation procedure was developed, facilitating safe and less invasive IA infusions in the treatment of various disease conditions. This article focuses on the interventional techniques for percutaneous implantation of a vascular access device, consisting of an indwelling catheter and an implantable port, to perform IA infusions. Additionally, we describe details of the alteration of blood flow by coil-embolization that can be performed to obtain selective drug distribution to the target area and to avoid side effects caused by the administration of the chemotherapeutic agent into nontarget areas.
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Cateteres de Demora , Embolização Terapêutica , Infusões Intra-Arteriais/instrumentação , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Colorretais/patologia , Artéria Hepática/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Radiografia , Radiologia Intervencionista/instrumentaçãoRESUMO
PURPOSE: To evaluate whether selective transcatheter arterial embolization (TAE) contributes to preservation of liver function and improves local control and survival in patients with hepatocellular carcinoma. MATERIALS AND METHODS: One hundred patients with hepatocellular carcinoma who underwent single or multiple TAE were retrospectively analyzed. The incidence of deterioration of liver function caused by TAE was compared between patients with Child class A disease and those having Child B/C disease. The correlation between extent of embolization and incidence of deterioration of liver function was analyzed. In addition, factors affecting deterioration of liver function after TAE were determined. Recurrence-free and overall survival rate were calculated using the Kaplan-Meier method. A Cox proportional hazard model was used to analyze prognostic factors affecting recurrence-free and overall survival. RESULTS: The incidence of deterioration of liver function in the Child B/C group (47%) was significantly higher than that in the Child A group (21%). Pretreatment Child-Pugh classification and extent of embolization were significant factors in the deterioration of liver function after TAE. Recurrence-free survival rates at 1, 2, and 3 years were 38%, 19%, and 8%, respectively. Overall survival rates at 1, 3, 5, and 7 years were 89%, 59%, 22%, and 22%, respectively. Findings of multivariate analyses of prognostic factors showed that tumor size and selectivity of TAE were significant for recurrence-free survival and the initial Child-Pugh classification was the most important factor for overall survival. CONCLUSION: Selective TAE improves local control and avoids damage to nontumorous liver tissue. The selective technique appears to be associated with a favorable outcome.
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Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Embolização Terapêutica/métodos , Feminino , Humanos , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: It is proposed that local elastase inhibition could suppress the extracellular matrix (ECM) degradation and subsequent smooth muscle cell migration and limit subsequent in-stent restenosis. This study evaluated the effect of stent-based controlled elastase inhibition on restenosis after stent implantation in a rabbit model. MATERIALS AND METHODS: Biodegradable microspheres containing the potent elastase inhibitor alpha-1-antitrypsin (AAT) were prepared. Daily release of AAT from the microspheres was confirmed in vitro. The microspheres were loaded into stents with an abluminal polymer reservoir. Implantation of the stent with AAT microspheres and blank microspheres (control) was performed in the abdominal aortae of six rabbits in each group. After stent deployment, all stents were overdilated to 125% diameter. Stent-implanted arteries were harvested after 7 days (n = 3 each) or 28 days (n = 3 each). To assess the effect of local delivery of AAT, elastase activity and elastin content of the stent-implanted aortae were analyzed. As an endpoint, intima-to-media (I/M) ratio was determined in the 7-day and 28-day specimens. RESULTS: Significant inhibition of elastase was confirmed in treated vessels versus controls at 7 days after stent implantation (P < .05). This reduction in elastase activity was sufficient to afford early and late reduction of in-stent neointima. Plaque progression in the 28-day specimens decreased to 67% with elastase inhibition relative to controls (P < .05). CONCLUSION: Stent-based controlled release of elastase inhibitor may significantly reduce ECM degradation and might limit in-stent restenosis.
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Oclusão de Enxerto Vascular/prevenção & controle , Elastase Pancreática/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , Stents , alfa 1-Antitripsina/farmacologia , Análise de Variância , Animais , Elastina/efeitos dos fármacos , Artéria Femoral/cirurgia , Técnicas In Vitro , Masculino , Ilustração Médica , Microesferas , Modelos Animais , Projetos Piloto , Coelhos , Inibidores de Serina Proteinase/administração & dosagem , Fatores de Tempo , alfa 1-Antitripsina/administração & dosagemRESUMO
PURPOSE: To evaluate the importance of angiogenesis in plaque progression after stent placement, this study examines stent-based controlled delivery of the antiangiogenic agent, angiostatin, in a rabbit model. MATERIALS AND METHODS: Controlled release biodegradable microspheres delivering angiostatin or polymer-only microspheres (polylactic-co-glycolic-acid-polyethylene glycol; PLGA/PEG) were loaded in channeled stents, anchored, and deployed in the aorta of adult New Zealand white rabbits (n = 6 animals per group, three each per time point). The stented aortas were harvested at 7 days and 28 days and evaluated for neovascularization, local inflammation, vascular smooth muscle cell proliferation, and in-stent plaque progression. RESULTS: At 7 days, neovascularization was significantly decreased in the angiostatin groups (1.6 +/- 1.6 neovessels per mm(2) plaque) versus the control group (15.4 +/- 2.6 neovessels per mm(2) plaque; P =.00081), as were local inflammation where angiostatin-treated groups demonstrated significantly lower macrophage recruitment per cross section (34.9 +/- 4.9 cells per cross section) relative to the control group (55.2 +/- 3.84 cells per cross section; P =.0037). And a significant decrease in the overall vascular smooth muscle cell proliferation (143.8 +/- 26.3 Ki-67 positive cells per mm(2)) relative to the control group (263.2 +/- 16.6 Ki-67 positive cells per mm(2); P =.00074). At both 7 and 28 days, in-stent plaque progression in the angiostatin groups was successfully limited relative to the control group by 54% (0.255 +/- 0.019% of cross section; P =.00016) and 19% (1.981 +/- 0.080; P =.0033) respectively and resulted in reduction of in-stent restenosis relative to the control group. CONCLUSION: Angiostatin-eluting stents may limit neovascularity after arterial implantation, offer insight into in-stent restenosis, and allow future refinement of bioactive stent designs and clinical strategies, particularly in light of evidence that intimal smooth muscle cells may in part be marrow-derived.
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Inibidores da Angiogênese/administração & dosagem , Angiostatinas/administração & dosagem , Aorta Abdominal , Arteriopatias Oclusivas/patologia , Materiais Revestidos Biocompatíveis , Oclusão de Enxerto Vascular/prevenção & controle , Stents , Análise de Variância , Animais , Aorta Abdominal/patologia , Géis , Masculino , Microesferas , CoelhosRESUMO
PURPOSE: To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits. MATERIALS AND METHODS: Bioerodable microspheres containing NO donor or biodegradable polymer (polylactide-co-glycolide-polyethylene glycol) were prepared and loaded in channeled stents. Daily concentrations of NO release from NO-containing microspheres were assayed in vitro. NO- and polymer-containing (control) microsphere-loaded stents were deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with statistical significance evaluated by using one-way analysis of variance. RESULTS: NO-containing microspheres released NO with an initial bolus in the 1st week, followed by sustained release for the remaining 3 weeks. Significant increase in cGMP levels and decrease in proliferating cell nuclear antigen-positive cells were found at 7 days for the NO-treated group relative to controls (P <.05). Intima-to-media ratio in the NO-treated group was reduced by 46% and 32% relative to controls at 7 and 28 days, respectively (mean, 0.14 +/- 0.01 [standard error] vs 0.26 +/- 0.02 at 7 days, P <.01; 1.34 +/- 0.05 vs 1.98 +/- 0.08 at 28 days, P <.01). CONCLUSION: Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation.