Clinical outcomes of endovascular procedure using VIABAHN® VBX covered stent in complex aortoiliac artery disease: Result from AVOCADO study.

OBJECTIVE: To investigate the safety and efficacy of a balloon-expandable covered stent in the treatment of complex aortoiliac artery disease. BACKGROUND: Peripheral intervention in complex aortoiliac disease still remains a challenge. METHODS: We retrospectively analyzed symptomatic patients with aortoiliac disease who were treated with GORE® VIABAHN® VBX covered stent (W.L. Gore & Associates, Flagstaff, AZ). The primary study outcome was a 1-year primary patency without the necessity of any subsequent clinically-driven target revascularization (CD-TLR) based intervention. The proportion of technical success, defined in terms of the absence of residual stenosis, stent edge dissection, and procedure-related severe complications, was also reported. RESULTS: VBX covered stent was used in 231 patients. Key patient characteristics include mean age of 73.4 ± 9 years, 77% male, 45% diabetes, and 18% suffering from end-stage renal dysfunction on dialysis. TASC II CD lesions were observed in 51% patients, which included 81% calcified lesions. Combined therapy with standard self-expandable stent was performed in 40% patients. The technical success rate was 92.6%. During median follow-up after 13.1 months, the primary patency rate was estimated to be 93.4% (95% confidence interval, 90.0%-96.8%) at 12 months, whereas the rate of freedom from TLR was 95.3% (92.5%-98.2%). As per the univariate analysis, the TASC II classification, number of diseased regions, and chronic total occlusion were significantly associated with risk of restenosis. CONCLUSIONS: The results of the year-long AVOCADO study demonstrated that usage of the novel VBX covered stent has a patency-based advantage with reduced chances for subsequent revascularization procedures.

Vessel Calcification as a Risk Factor for In-Stent Restenosis in Complex Femoropopliteal Lesions After Zilver PTX Paclitaxel-Coated Stent Placement.

Purpose: To evaluate the effect of vessel calcification on in-stent restenosis (ISR) after drug-coated stent (DCS) placement in the femoropopliteal segment. Materials and Methods: A retrospective multicenter study was undertaken involving 220 consecutive symptomatic patients (mean age 73.1±8.3 years; 175 men) with femoropopliteal lesions in 230 limbs treated with the Zilver PTX DCS and having duplex surveillance after the endovascular procedures. Mean lesion length was 16.4±9.8 cm (range 2-40); there were 104 (45.2%) total occlusions and 68 (29.6%) in-stent restenoses (ISR). Twenty (8.7%) vessels had no runoff. The majority of lesions (148, 64.3%) were calcified according to the peripheral arterial calcium scoring system (PACSS). Primary patency was evaluated by duplex. Lesions were classified as either PACSS 0-2 (none or unilateral wall calcification) or PACSS 3 and 4 (bilateral wall calcification). Multivariate analysis was performed to identify variables associated with ISR; the results are given as the hazard ratio (HR) and 95% confidence interval (CI). Results: The 1-, 2-, and 5-year primary patency and freedom from clinically-driven target lesion revascularization estimates were 75.9%, 63.6%, and 45.0%, and 84.7%, 73.7%, and 54.2%, respectively. Major amputations were performed on 4 limbs during follow-up. In multivariate analysis, vessel calcification (adjusted HR 1.718, 95% CI 1.035 to 2.851, p=0.036) was significantly correlated with the occurrence of ISR, along with lesion length (adjusted HR 1.041, 95% CI 1.013 to 1.070, p=0.003), and cilostazol administration (adjusted HR 0.476, 95% CI 0.259 to 0.876, p=0.017). Conclusion: This study suggested that bilateral vessel wall calcification was an independent risk factor for ISR in complex femoropopliteal lesions after Zilver PTX DCS placement, along with lesion length; cilostazol administration had a protective effect.

Editor's Choice - Endovascular Repair Versus Surgical Repair for Japanese Patients With Ruptured Thoracic and Abdominal Aortic Aneurysms: A Nationwide Study.

OBJECTIVE: This study compared outcomes after endovascular aneurysm repair (ER) and open surgical repair (OR) of ruptured descending thoracic aortic aneurysms (rDTAA) and ruptured abdominal aortic aneurysms (rAAA) through a nationwide analysis performed in Japan. METHODS: This was a national registry based retrospective comparative study using data from the Japanese Registry of all Cardiac and Vascular Diseases Diagnostic Procedure Combination (JROAD-DPC) database, a nationwide claim based database from more than 600 hospitals. Patients admitted to certificated teaching hospitals with rDTAA and rAAA and treated by either ER or OR between 1 April 2012 and 31 March 2015 were identified. A propensity score matched analysis was performed to compare ER and OR. RESULTS: About 40% of the total cohort (n = 8,302) were managed conservatively for various reasons, including limited options in primary care facilities in certain areas. In total, 983 patients had rDTAA (OR = 511; ER = 472) and 2,320 (OR = 1,754; ER = 566) had rAAA. Altogether, 604 and 1,080 patients were matched with rDTAA and rAAA, respectively. Compared with OR, ER was associated with significantly better in hospital mortality in patients with rDTAA (ER = 22.5%; OR = 29.8% [p < .001]) and similar mortality for those with rAAA (ER = 25.7%; OR = 24.3% [p = .57]). ER involved significantly shorter hospital stays for rDTAA (ER = 25.5; OR = 32 days [p < .001]) and rAAA (ER = 16; OR = 21 days [p < .001]). The median Barthel Index at discharge was ≥75/100 for all groups, and there were no differences between ER and OR. Total medical costs were significantly lower for ER for rDTAA (ER = ¥6.47 million, OR = ¥7.28 million [p < .001]) but were higher for rAAA (ER = ¥4.65 million; OR = ¥3.43 million [p < .001]). CONCLUSION: A Japanese nationwide observational study showed that in hospital outcomes for ER vs. OR were more favourable for rDTAA and comparable for rAAA. ER resulted in an equivalently favourable functional status at discharge and significantly shorter hospital stays.

Late-Onset Malignant Neoplasms and Their Prognostic Factors after Abdominal Aortic Aneurysm Repair.

BACKGROUND: Little is known about late-onset primary malignant neoplasms after repair of abdominal aortic aneurysms (AAAs) despite malignancy being one of the primary causes of late death. We investigated the incidence and prognostic factors related to the occurrence of malignancy after AAA repair. METHODS: We performed a retrospective analysis of 589 patients who underwent AAA repair, including 264 endovascular AAA repairs and 325 open surgical repairs; 482 patients had no history of previous malignancy or concomitant malignancy, 72 had previous malignancy, and 35 had concomitant malignancy in remission at the time of AAA repair. The cumulative incidence rates of late-onset malignancy occurrence and cancer death were estimated using the cumulative incidence function in the presence of competing risks, that is, noncancer death, and prognostic factors were investigated using the Fine-Gray hazard model. RESULTS: After hospital discharge, 128 malignancies occurred in 116 patients. Overall cumulative incidence rates of late-onset malignancy occurrence at 1, 3, 5, and 10 years were 4.0%, 11.7%, 18.2%, and 38.1%, respectively. Multivariate analysis revealed that significant prognostic factors for late-onset malignancy included history of previous malignancy, current smoker, higher intraoperative blood loss, absence of allogeneic blood transfusion, lower C-reactive protein levels, and lower serum high-density lipoprotein-cholesterol levels. The type of surgical procedures for AAA repair did not affect the occurrence of malignancy. In addition, current smoker and higher intraoperative blood loss significantly increased the risk of cancer death. CONCLUSIONS: Current smoker and higher intraoperative blood loss were independent risk factors for late-onset malignancy after AAA repair. Late-onset malignancy after AAA repair should be monitored among patients at high risk and requires aggressive management to improve long-term survival.

Prognostic factors of ulcer healing and amputation-free survival in patients with critical limb ischemia.

OBJECTIVE: A multidisciplinary approach is required to treat critical limb ischemia. We determined the poor prognostic factors of ischemic ulcer healing after optimal arterial revascularization, and assessed the efficacy of the medication therapy using cilostazol, which is a selective inhibitor of phosphodiesterase 3. METHODS: In this retrospective, single-center, cohort study, 129 limbs that underwent infrainguinal arterial revascularization for Rutherford class 5 critical limb ischemia were reviewed. The primary end point was the ulcer healing time after arterial revascularization. The secondary end point was the amputation-free survival rate. RESULTS: Of the 129 limbs, endovascular therapy was performed in 69 limbs, and surgical reconstructive procedures were performed in 60 limbs for initial therapy. Complete ulcer healing was achieved in 95 limbs (74%). The median ulcer healing time was 90 days. In multivariate analysis, no cilostazol use significantly inhibited ulcer healing ( p = 0.0114). A white blood cell count >10,000 ( p = 0.0185), a major defect after debridement ( p = 0.0215), and endovascular therapy ( p = 0.0308) were significant poor prognostic factors for ulcer healing. Additionally, ischemic heart disease ( p < 0.0001), albumin levels <3 g/dl ( p = 0.0016), no cilostazol use ( p = 0.0078), and a major defect after debridement ( p = 0.0208) were significant poor prognostic factors for amputation-free survival rate. CONCLUSIONS: Ulcer healing within 90 days after arterial revascularization is impaired by no cilostazol use, a white blood cell count >10,000, a major defect after debridement, and endovascular therapy. Furthermore, cilostazol improves amputation-free survival rate in patients with critical limb ischemia.

Cilostazol Improves Wound Healing in Patients Undergoing Open Bypass for Ischemic Tissue Loss: A Propensity Score Matching Analysis.

BACKGROUND: Few reports have described the effects of medication on the wound healing of ischemic ulcers after revascularization. This study was conducted to investigate the effects of cilostazol on wound healing in patients who underwent infrainguinal bypass for ischemic tissue loss. METHODS: Two hundred sixty-three limbs undergoing de novo infrainguinal bypass for tissue loss from January 2004 to December 2015 were divided into 2 groups based on whether or not cilostazol was administered after surgery. The end point was wound healing. The 1-year outcomes of the groups were analyzed using the Kaplan-Meier method, and a propensity score matching analysis was performed to examine the effects of cilostazol on wound healing. In addition, the significant predictors were determined using a Cox proportional hazards regression analysis. RESULTS: Sixty-one and 202 limbs were included in the cilostazol and non-cilostazol group, respectively. The cilostazol group showed superior wound healing to the non-cilostazol group (cilostazol versus non-cilostazol, 1-year wound healing rate: 92% vs. 81%; median wound healing time: 45 vs. 78 days, P = 0.002). The results of the cilostazol group remained superior after a propensity score matching (cilostazol versus non-cilostazol, 1-year wound healing rate: 95% vs. 83%; median wound healing time: 45.5 vs. 57 days, P = 0.048). A Cox proportional hazards regression analysis indicated that foot infection, Rutherford classification, diabetes mellitus, coronary artery disease, angiosome, the administration of cilostazol, and graft patency were significant factors that influenced wound healing. CONCLUSIONS: The postoperative use of cilostazol help to promote wound healing after open surgery.

Primary aortoduodenal fistula with a history of distal gastrectomy.

Case: A 69-year-old man was transferred to our hospital because of an aortoduodenal fistula with hematemesis and pre-shock vital signs. He had a history of alcoholism, malnutrition, and distal gastrectomy and Billroth I reconstruction. Endovascular aneurysm repair was successfully carried out; however, the presence of comorbidities affected further radical treatment. Outcome: The patient survived for 2 months postoperatively. Conclusion: Endovascular aneurysm repair is a useful first-line treatment for high-risk aortoduodenal fistula patients; however, it requires improvement for long-term outcomes in complicated high-risk cases.

Aggressive Wound Care by a Multidisciplinary Team Improves Wound Healing after Infrainguinal Bypass in Patients with Critical Limb Ischemia.

BACKGROUND: A long period is generally required for ischemic ulcer to heal after revascularization. The strategy of postoperative wound care can affect wound healing. This study was conducted to investigate the degree to which aggressive wound care (AWC) by a team of multidisciplinary specialists actually shortens the time to wound healing and increases the rate of wound healing in limbs undergoing surgical bypass for ischemic tissue loss in a real clinical setting. METHODS: A total of consecutive 126 patients undergoing infrainguinal bypass for tissue loss from April 2011 to March 2015 were reviewed. Prior to March 2013, standard wound care (SWC) including typical daily dressing change with disinfection and irrigation, occasional surgical debridement, and negative pressure wound therapy (when necessary) was performed by vascular surgeons. Thereafter, in addition to SWC, AWC including intense daily bedside surgical debridement under a sciatic nerve block by an anesthesiologist and active skin grafting by a dermatologist, if necessary, was performed. Wound healing and major amputation were defined as the end points. The 1-year outcomes of the 2 groups were calculated using the Kaplan-Meier method and compared, and the significant predictors of each outcome were determined by a Cox proportional hazards analysis. RESULTS: The wound healing of the AWC group was superior to that of the SWC group (AWC versus SWC, 1-year wound healing rate: 92% vs. 80%; mean wound healing time: 48 days vs. 82 days; P = 0.011), and no significant difference between the 2 regimens in the freedom from major amputation was observed. AWC, Rutherford 5, no wound infection, normal serum albumin, direct angiosome, and cilostazol use were significant predictors of wound healing, and female gender and no cilostazol use were significant predictors of major amputation by a multivariate analysis. CONCLUSIONS: Aggressive wound care by the team consisting of multidisciplinary specialists remarkably shortened the time to wound healing and increased the rate of wound healing within 1 year.

BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice.

BACKGROUND: Budding uninhibited by benzimidazole-related 1 (BubR1), a cell cycle-related protein, is an essential component of the spindle checkpoint that regulates cell division. BubR1 insufficiency causes early aging-associated vascular phenotypes. We generated low-BubR1-expressing mutant (BubR1L/L) and apolipoprotein E-deficient (ApoE-/-) mice (BubR1L/L-ApoE-/- mice) to investigate the effects of BubR1 on atherosclerosis. METHODS AND RESULTS: Eight-week-old male BubR1L/L-ApoE-/- mice and age-matched ApoE-/- mice were used in this study. Atherosclerotic lesion development after being fed a high-cholesterol diet for 12 weeks was inhibited in BubR1L/L-ApoE-/- mice compared with ApoE-/- mice, and was accompanied by decreased accumulation of macrophages. To address the relative contribution of BubR1 on bone marrow-derived cells compared with non-bone marrow-derived cells, we performed bone marrow transplantation in ApoE-/- and BubR1L/L-ApoE-/- mice. Decreased BubR1 in bone marrow cells and non-bone marrow-derived cells decreased the atherosclerotic burden. In vitro assays indicated that decreased BubR1 expression impaired proliferation, but not migration, of bone marrow-derived macrophages. CONCLUSIONS: BubR1 may represent a promising new target for regulating atherosclerosis.

Raison d'etre of Tibial Artery Bypass for Intermittent Claudication in the Era of Endovascular Therapy.

BACKGROUND: There is currently no positive opinion regarding infrapopliteal revascularization for intermittent claudication (IC) in any guidelines. The aim of this study was to analyze the outcomes of infragenicular bypass and verify the adequacy of tibial artery bypass for IC. METHODS AND RESULTS: Over a 21-year period, 58 below-knee popliteal artery (BKPOP) bypasses and 35 tibial artery bypasses were performed for IC caused by arteriosclerosis obliterans. Graft patency and major amputation (MA) were examined as primary endpoints and the predictor of each outcome was estimated by multivariate analysis. The primary patency (PP), secondary patency (SP), and freedom from MA (ffMA) rates of a prosthetic/vein graft in all cases at 5 years were 19/68%, 22/86%, and 78/100% (P<0.01 in all). Limited to vein graft cases, PP and SP rates of popliteal/tibial bypass at 5 years were 73/62% (P=0.32) and 92/80% (P=0.22), respectively. In tibial artery bypass with a vein graft, the PP and SP rates of a single saphenous vein/spliced vein graft at 5 years were 71/46% (P=0.11) and 89/61% (P=0.03). A prosthetic graft was a common negative predictor for graft patency and MA by multivariate analysis. CONCLUSIONS: Tibial artery bypass is an acceptable treatment option for IC when a single saphenous vein can be harvested as a graft conduit. (Circ J 2016; 80: 1460-1469).

BubR1 insufficiency inhibits neointimal hyperplasia through impaired vascular smooth muscle cell proliferation in mice.

OBJECTIVE: BubR1, a cell cycle-related protein, is an essential component of the spindle checkpoint that regulates cell division. Mice with BubR1 expression reduced to 10% of the normal level display a phenotype characterized by progeria; however, the involvement of BubR1 in vascular diseases is still unknown. We generated mice in which BubR1 expression was reduced to 20% (BubR1(L/L) mice) of that in wild-type mice (BubR1(+/+)) to investigate the effects of BubR1 on arterial intimal hyperplasia. APPROACH AND RESULTS: Ten-week-old male BubR1(L/L) and age-matched wild-type littermates (BubR1(+/+)) were used in this study. The left common carotid artery was ligated, and histopathologic examinations were conducted 4 weeks later. Bone marrow transplantation was also performed. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta to examine cell proliferation, migration, and cell cycle progression. Severe neointimal hyperplasia was observed after artery ligation in BubR1(+/+) mice, whereas BubR1(L/L) mice displayed nearly complete inhibition of neointimal hyperplasia. Bone marrow transplantation from all donors did not affect the reconstitution of 3 hematopoietic lineages, and neointimal hyperplasia was still suppressed after bone marrow transplantation from BubR1(+/+) mice to BubR1(L/L) mice. VSMC proliferation was impaired in BubR1(L/L) mice because of delayed entry into the S phase. VSMC migration was unaffected in these BubR1(L/L) mice. p38 mitogen-activated protein kinase-inhibited VSMCs showed low expression of BubR1, and BubR1-inhibited VSMCs showed low expression of p38. CONCLUSIONS: BubR1 may represent a new target molecule for treating pathological states of vascular remodeling, such as restenosis after angioplasty.

Long-Term Results of a Hybrid Revascularization Procedure for Peripheral Arterial Disease.

OBJECTIVE: To evaluate the efficacy of hybrid procedure for peripheral arterial disease (PAD), we compared the cases treated using the hybrid procedure with those treated using open revascularization (bypass alone) in our facilities. MATERIALS AND METHODS: We retrospectively reviewed 204 patients who underwent revascularization for PAD between 2007 and 2013. We divided the patients into two groups based on the type of procedure. Group 1 included patients who underwent the hybrid procedure, that is, doing endovascular therapy (EVT) either femoral or iliac resion and added the bypass procedure (infragenicular vein bypass) to the below knee artery, and group 2 included patients who underwent only bypass procedure (used autovein), that is, central anastomotic region was femoral artery region and peripheral anastomotic region was below knee artery. We evaluated various factors between the two groups, including the primary patency rate, secondary patency rate, amputation-free survival rate, and determined the efficacy of the hybrid procedure for PAD. RESULTS: In the patient's characteristics, there was significant difference between the two groups in the cases with cerebrovascular disease, only (p = 0.03). There were no significant differences in the primary or secondary patency rates, and the amputation-free survival rate. CONCLUSIONS: Primary patency rate, secondary patency rate, and amputation-free survival rate of the hybrid procedure were comparable to those of bypass (alone) procedure. The hybrid procedure is therefore an acceptable strategy for patients with PAD.

Midterm outcomes of endovascular repair for abdominal aortic aneurysms with the on-label use compared with the off-label use of an endoprosthesis.

PURPOSE: Endovascular repair of an abdominal aortic aneurysm (EVAR) is sometimes not performed in accordance with the instructions for use (IFU) of the endoprosthesis ("off-label use"). We investigated whether the off-label use of the endograft affected the outcomes of EVAR. METHODS: Demographic, anatomical, intraoperative and follow-up data on 100 patients in whom the endograft was used on-label in EVAR were compared retrospectively with the corresponding data of 50 patients with off-label endograft use. RESULTS: The endograft IFU were most often not followed in patients with challenging aortic neck anatomy or iliac access or fixation, steep neck angulation or bilateral hypogastric artery embolization. Compared with patients in whom the device was used on-label, patients with off-label use had significantly higher rates of intraoperative type I or III endoleaks and proximal aortic cuff placement or other adjunctive procedures. However, there were no midterm differences between the two groups in the rates of type 1b or II endoleaks, sac enlargement, device-limb occlusion or patient survival. CONCLUSIONS: Most midterm outcomes of EVAR in which the endografts were used off-label were similar to those associated with on-label use of the devices. Off-label use of EVAR endoprostheses is feasible, but requires the use of special techniques in patients with challenging anatomical features.

Endovascular aneurysm repair for an abdominal aortic aneurysm and a left ruptured common iliac artery aneurysm in a patient with hepatocellular carcinoma: report of a case.

We performed an endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA) and a ruptured common iliac artery aneurysm (rCIAA) in a patient complicated by severe liver dysfunction due to obstructive jaundice resulting from hepatocellular carcinoma (HCC). A 68-year-old male presented with acute lower abdominal pain. Abdominal computed tomography (CT) showed a 4.5-cm infrarenal AAA, a 6.0-cm left rCIAA with retroperitoneal hematoma and a 13-cm mass in the liver, which was suspected to be HCC. His laboratory data showed severe liver dysfunction. An emergency EVAR was done under local anesthesia because of his liver dysfunction. He was transferred to another hospital without any complications.

Evaluation of the paramalleolar bypass for critical limb ischemia patients on hemodialysis with diabetes mellitus and chronic renal failure.

OBJECTIVE: To assess the influence of diabetes mellitus (DM) and end-stage renal failure on hemodialysis (HD) on the healing time of tissue lesions and blood flow to the foot following a paramalleolar bypass in patients with critical limb ischemia (CLI). METHODS: Consecutive patients with CLI and tissue loss (24 limbs) were followed up retrospectively after paramalleolar bypass, and the healing time of tissue lesions, graft patency, limb salvage and survival rates were analyzed. The blood flow to the foot was assessed by skin perfusion pressure (SPP) pre- and postoperatively. The delta SPP was calculated as the difference between the SPP before and after bypass. The patients were divided into 3 groups: diabetic (DM, n = 9); diabetic and end-stage renal failure on hemodialysis (HD, n = 10); or neither (n = 5). RESULTS: A total of 15 dorsal and 9 plantar artery bypasses were performed. The median follow-up was 7.3 months (range, 1-18 months). No patients required major amputations, and all tissue lesions healed. The mean duration to complete tissue healing of the DM, HD and neither groups was 2.2, 2.5 and 1.2 months, respectively, was and these were not statistically significant. A significant improvement in the delta SPP after paramalleolar bypass was observed in the neither group compared with both the DM and HD groups. CONCLUSION: Blood flow to the foot was not sufficiently improved in CLI patients with DM and HD, despite paramalleolar bypass. This may be the cause of the prolonged tissue healing duration of CLI patients with DM and HD. (English Translation of Jpn J Vasc Surg 2012; 21: 91-95).

Ex vivo generation of highly purified and activated natural killer cells from human peripheral blood.

Adoptive immunotherapy using natural killer (NK) cells has been a promising treatment for intractable malignancies; however, there remain a number of difficulties with respect to the shortage and limited anticancer potency of the effector cells. We here established a simple feeder-free method to generate purified (>90%) and highly activated NK cells from human peripheral blood-derived mononuclear cells (PBMCs). Among the several parameters, we found that CD3 depletion, high-dose interleukin (IL)-2, and use of a specific culture medium were sufficient to obtain highly purified, expanded (∼200-fold) and activated CD3(-)/CD56(+) NK cells from PBMCs, which we designated zenithal-NK (Z-NK) cells. Almost all Z-NK cells expressed the lymphocyte-activated marker CD69 and showed dramatically high expression of activation receptors (i.e., NKG2D), interferon-γ, perforin, and granzyme B. Importantly, only 2 hours of reaction at an effector/target ratio of 1:1 was sufficient to kill almost all K562 cells, and the antitumor activity was also replicated in tumor-bearing mice in vivo. Cytolysis was specific for various tumor cells, but not for normal cells, irrespective of MHC class I expression. These findings strongly indicate that Z-NK cells are purified, expanded, and near-fully activated human NK cells and warrant further investigation in a clinical setting.

DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial.

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.

Clinico-pathological features and management of lung cancer patients with atherosclerotic vascular diseases.

PURPOSE: Increased numbers of patients with both lung cancer and atherosclerotic vascular disease (AVD) may be expected in the future. The aim of this study was to report the incidence of lung cancer in patients with AVD and to discuss patient characteristics and management. METHOD: A total of 638 patients who underwent AVD treatment were investigated. RESULTS: Lung cancer was observed in 17 (2.7%) of 638 patients studied. The proportion of smoking history was significantly higher in patients with lung cancer (p = 0.0091).The pack-year index in patients with lung cancer was significantly higher than that in patients without lung cancer (p = 0.0073). Although 4 of 6 (66.7%) patients with concomitant lung cancer and AVD had stage I or II lung cancer, 5 of 7 (71.4%) patients with lung cancer diagnosed after AVD treatment had stage III or IV lung cancer. In patients with lung cancer found after AVD treatment, only 1 of 7 patients underwent surgical resections. The time until lung cancer was 12 to 198 months with a mean of62.5 months after AVD treatment. In concomitant cases, priority was given to AVD treatment in all 5 cases, and there were no serious events after the postoperative course. CONCLUSIONS: Both patients with a smoking history and heavy smokers were at high risk for lung cancer, and most lung cancers found after AVD treatment were in the advanced stages and had poor prognoses. Therefore, we recommend careful and routine follow-up for screening lung cancer after AVD treatment.

BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression.

Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named "BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.

Clinical Results of Endovascular Abdominal Aortic Aneurysm Repair in Patients with Renal Insufficiency without Hemodialysis.

OBJECTIVE: Chronic renal insufficiency may be a relative contraindication to endovascular aneurysm repair (EVAR) for the use of contrast enhanced mediums. It is thought that more contrast enhanced media are needed in patients who are not anatomically suitable for EVAR, because of procedural difficulties. We reviewed a 2 year EVAR experience at our institution to determine whether the procedure and use of contrast enhanced mediums has any deleterious effect on renal function in patients with pre-existing chronic renal insufficiency. MATERIALS AND METHODS: EVAR was performed in 46 patients with pre-existing chronic renal insufficiency without hemodialysis. Patients were retrospectively assigned to two groups on the basis of their preoperative creatinine clearance levels. Furthermore, patients were assigned to two other groups on the basis of anatomical suitability for EVAR. The absolute change in the serum creatinine (Cr) level was reviewed in the each renal insufficiency group between the preoperative and post-operative time periods. RESULTS: No increase in the serum Cr level was noted, and no patient required temporary or permanent hemodialysis, in any of the groups. CONCLUSIONS: EVAR with contrast agents can be accomplished in patients with chronic renal insufficiency without hemodialysis; therefore,elevated Cr levels maynot be a contraindication in EVAR.