Role of Common Antihypertensives in the Growth of Abdominal Aortic Aneurysm at the Presurgical Stage.

Background: Whether drug therapy slows the growth of abdominal aortic aneurysms (AAAs) in the Japanese population remains unknown. Methods and Results: In a multicenter prospective open-label study, patients with AAA at the presurgical stage (mean [±SD] AAA diameter 3.27±0.58 cm) were randomly assigned to treatment with candesartan (CAN; n=67) or amlodipine (AML; n=64) considering confounding factors (statin use, smoking, age, sex, renal function), with effects of blood pressure control minimized setting a target control level. The primary endpoint was percentage change in AAA diameter over 24 months. Secondary endpoints were changes in circulating biomarkers (high-sensitivity C-reactive protein [hs-CRP], malondialdehyde-low-density lipoprotein, tissue-specific inhibitor of metalloproteinase-1, matrix metalloproteinase [MMP] 2, MMP9, transforming growth factor-ß1, plasma renin activity [PRA], angiotensin II, aldosterone). At 24 months, percentage changes in AAA diameter were comparable between the CAN and AML groups (8.4% [95% CI 6.23-10.59%] and 6.5% [95% CI 3.65-9.43%], respectively; P=0.23]. In subanalyses, AML attenuated AAA growth in patients with comorbid chronic kidney disease (CKD; P=0.04) or systolic blood pressure (SBP) <130 mmHg (P=0.003). AML exhibited a definite trend for slowing AAA growth exclusively in never-smokers (P=0.06). Among circulating surrogate candidates for AAA growth, PRA (P=0.02) and hs-CRP (P=0.001) were lower in the AML group. Conclusions: AML may prevent AAA growth in patients with CKD or lower SBP, associated with a decline in PRA and circulating hs-CRP.

Hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma: an audit of 50 consecutive cases.

OBJECTIVE: To outline our experience with hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma, and to discuss the clinical significance of this challenging hepatectomy. SUMMARY BACKGROUND DATA: Only a few authors reported negative results for this surgery in a very limited number of patients. METHODS: We retrospectively reviewed medical records of 50 patients with advanced cholangiocarcinoma who underwent hepatectomy (left trisectionectomy in 26, left hepatectomy in 23, and right hepatectomy in 1) with simultaneous resection and reconstruction of the portal vein and hepatic artery, focusing on surgical outcome and survival. RESULTS: The operative time was 776 +/- 191 minutes, and blood loss was 2593 +/- 1890 mL. Time of vessel resection and reconstruction was 25 +/- 19 minutes for the portal vein and 119 +/- 56 minutes for the hepatic artery. A total of 27 (54.0%) patients developed several kinds of complications, including intra-abdominal abscess (n = 13), wound infection (n = 9), bile leakage from liver stump (n = 9), and liver failure (n = 7). Relaparotomy was necessary in 5 (10.0%) patients. One (2.0%) patient died of a postoperative complication. Microscopic cancer invasion of the resected portal vein was found in 44 (88.0%) patients, while that of the resected hepatic artery was found in 27 (54.0%). The distal bile duct margin, proximal bile duct margin, and radial margin were positive for cancer in 2 (4.0%), 4 (8.0%), and 17 (34.0%) patients, respectively. Consequently, R0 resection was achieved in 33 (66.0%) patients. The 1-, 3-, and 5-year survival rates were 78.9%, 36.3%, and 30.3%, respectively. Survival for 30 patients with pM0 disease who underwent R0 resection was better, being 40.7% at the 3- and 5-year time points. CONCLUSION: Major hepatectomy with simultaneous resection and reconstruction of the portal vein and hepatic artery is technically demanding. However, this surgery can be performed with acceptable mortality by an experienced surgeon and offers a better chance of long-term survival in selected patients.

Comparison of Doppler and oscillometric ankle blood pressure measurement in patients with angiographically documented lower extremity arterial occlusive disease.

To assess the reliability of the oscillometric method in patients with peripheral vascular disease, ankle blood pressure measurement by Doppler and oscillometry was compared. This study represents a prospective, non-blinded examination of pressure measurements in 168 patients. Twenty-two patients were included who had abdominal aortic aneurysms (AAA) and 146 had peripheral arterial occlusive disease (PAOD). Patients with PAOD were divided into 2 groups according to angiography results: a crural artery occlusion group (CAO, n = 32), and a no crural artery occlusion group (NCAO, n = 114). All subjects underwent pressure measurement by both Doppler and oscillometry. The correlation coefficient was 0.928 in AAA patients and 0.922 in PAOD patients. In CAO patients, there were significantly fewer patients whose oscillometric pressure was equivalent to the Doppler pressure (DP), as compared to NCAO patients, because the oscillometric pressure (OP) was 10% higher than DP in 44% of CAO patients. A high correlation exists between Doppler and oscillometric ankle pressure measurements irrespective of the type of vascular disease. However, the oscillometric method could not be substituted for the Doppler method completely, because there were several patients whose OP was greater than DP especially in those with crural artery occlusive disease.

Bi-phasic activation of eNOS in response to uni-axial cyclic stretch is mediated by differential mechanisms in BAECs.

We investigated the signaling mechanism of stretch-induced NO (Nitric oxide) production in bovine arterial endothelial cells (BAECs). BAECs cultured on an elastic silicone chamber coated with fibronectin were subjected to uni-axial cyclic stretch (1 Hz, 20% in length) and the amount of produced NO was measured by a cGMP assay. NO production increased in a bi-phasic manner and peaked at 5 min and 20 min after stretch onset. Correspondingly, the activities of endothelial nitric oxide synthase (eNOS) and Akt/PKB (measured by phosphorylation at serine 1,177 and serine 473, respectively), showed two peaks over time. Application of Gd(3+), a potent SA channel blocker, and depletion of external Ca(2+) exclusively inhibited the first peaks of eNOS and Akt activity, but exerted little effect on the second peak. On the other hand, the PI3K inhibitors, Wortmannin, LY294002, almost completely inhibited the second peak but not the first. These results suggest that up-regulation of eNOS in response to cyclic stretch was mediated by two distinct pathways, [Ca(2+)](i) increases via the SA channel in an early phase (partially Akt/PKB), and PI3K-Akt/PKB pathways in a late phase.

Current pathological and clinical aspects of Buerger's disease in Japan.

Since Buerger's disease was first described by Leo Buerger in 1908, many authors have discussed whether it indeed exists and, if so, is a definite clinical entity. Today, Buerger's disease is accepted as a definite vascular disease with a typical clinical picture, natural history, and histopathology; however, the diagnosis of Buerger's disease has been controversial, and the etiology of this vascular occlusive disease has remained unknown because many authors in different countries have their own criteria. Besides, patients with this disease have decreased in number even in Japan, while there has been no change in the number of arteriosclerosis obliterans patients. Currently, only one or two new patients per year are encountered at our outpatient clinic. The purpose of this review is to examine the current epidemiological, pathological, and clinical aspects of Buerger's disease in Japan based on the 222 patient files of our department between 1980 and 2000 and to discuss the pathogenesis, clinical presentation, and various treatment modalities.

Near-infrared spectroscopy with treadmill exercise to assess lower limb ischemia in patients with atherosclerotic occlusive disease.

PURPOSE: We used near-infrared spectroscopy (NIRS) to measure exercise-induced ischemia in patients with intermittent claudication, and compared these results with those obtained by ankle-brachial pressure index (ABPI) analysis. METHODS: Sixty-two patients with intermittent claudication caused by atherosclerotic occlusive disease exercised on a treadmill until reaching the maximal tolerated walking distance. We measured the ABPI at rest and after exercise until it returned to the baseline value. A NIRS probe was positioned on the patient's calf, which allowed the continuous monitoring of oxygen saturation (StO2), oxygenated hemoglobin (Oxy Hb), and deoxygenated hemoglobin (Deoxy Hb) in the calf muscles before, during, and after exercise. During exercise, the StO2 and Oxy Hb decreased, and the Deoxy Hb increased. The time taken for each measurement to return to the baseline value was defined as the recovery time. The recovery times obtained by NIRS and ABPI were compared. RESULTS: The recovery time for ABPI correlated well with that for StO(2 (rhos = 0.73), Oxy Hb (rhos = 0.63), and Deoxy Hb (rhos = 0.65); however, the recovery times measured by NIRS were shorter than the recovery time for the ABPI. CONCLUSIONS: Near-infrared spectroscopy is a reliable method for monitoring peripheral circulation during and after exercise, although the data generated provided slightly different information than the results obtained by ABPI.

External iliac venous aneurysm in a pregnant woman: a case report.

We report an external iliac venous aneurysm in a young pregnant woman who was diagnosed incidentally by ultrasound scanning. The aneurysm was successfully treated by tangential aneurysmectomy and lateral venorrhaphy. Primary iliac venous aneurysm is a rare vascular abnormality. The clinical significance of the disease is unknown. However, embolism, rupture, and thrombosis might occur as they can occur with popliteal venous aneurysm. In fact, three of four reported patients with iliac venous aneurysms had a thromboembolic event. For those reasons, prophylactic treatment is indicated. This is the first patient with an iliac venous aneurysm to be diagnosed without complication.

Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft.

We investigated whether fibrin glue (FG) might be useful as a carrier of amikacin (AMK) for prevention of local graft infection. After AMK (4.0 mg)-treated FG (AMK-FG) polyurethane grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, AMK concentrations in tissues surrounding the implantation sites were compared over time with concentrations at the same sites in rats given an intravenous injection of AMK (4.0 mg). In the injection group, AMK concentrations in serum were detectable only for 4 h, whereas AMK released from AMK-FG grafts remained detectable over 24 h. Until 4 h after implantation, AMK concentrations in tissues near implantation sites were significantly higher in the AMK-FG graft group than in the injection group; peak local concentrations during that time were 210 times higher for the AMK-FG graft group than for the injection group. Areas under the tissue concentration-time curve (AUC) for AMK were 171 microg x h/g and 1.35 microg x h/g in the AMK-FG graft and injection groups, respectively. FG therefore was considered to control release of AMK and to maintain a high AMK concentration in tissues surrounding the implantation site. Thus, AMK-FG polyurethane graft delivery may be useful in preventing local infection by local delivery of AMK.

Buerger's disease in a 19-year-old woman.

A 19-year-old female college student had numbness and the sensation of coldness of her left toes. She had a 3-year smoking history. Gangrene of the left foot developed rapidly. Angiography revealed peripheral arterial occlusion of both legs and arms. Detailed laboratory examination excluded collagen disease, a hypercoagulable state, and juvenile atherosclerosis. Below-knee amputation of the left leg was performed. Typical histologic findings of Buerger's disease were observed in the crural arteries and saphenous veins. The clinical course was uneventful after the patient stopped smoking. This is the second case report of Buerger's disease in a woman in the second decade of life. It is important that a correct diagnosis of Buerger's disease be established, because the disease process is benign, compared with collagen disease, if the patient stops smoking.

Mid-term results of an endovascular stent-graft by means of median sternotomy for distal aortic arch aneurysm.

Migration and perigraft leakage are major problems after endovascular stent graft (EVG) by means of median sternotomy for distal aortic arch aneurysm. Anchoring sutures have been applied to prevent these problems. We evaluate the mid-term results and the efficacy of anchoring sutures. The operation was performed on 19 men and 2 women with a mean age of 70 years (range, 59-81). The aneurysms were 19 true (12 fusiform, 7 saccular), 1 chronic dissection, and 1 penetrating aortic ulcer. EGVs were implanted by way of the aortic arch under retrograde cerebral perfusion in 13 patients and selective cerebral perfusion in 8. Total arch replacement was performed in 2 patients, and aortocoronary bypass grafting in 4. Anchoring sutures to fix the EVG were applied in 9 patients. The average follow-up period was 28 months (range, 2-56). There were no operative mortalities, but 1 paraplegia, 1 stroke, and 2 cases of temporary spinal cord dysfunction occurred. All aneurysms were thrombosed completely after surgery and reduced in diameter (66.9 +/- 17.4 mm to 57.3 +/- 15.7 mm, p < 0.0001). EVG-related complications arose in 4 patients. A chronic Type B dissection revealed impending rupture because of false lumen infection 1 year after operation, and redo surgery was performed. Migration occurred in 3 patients, all with fusiform aneurysms. One of these had a graft kink 1 year later. Another showed aneurysm enlargement with serous pleural effusion 3 years after operation. The third required redo surgery because of perigraft leakage at 3 years after surgery. There were 2 late deaths caused by stroke. There were no EVG-related complications in the 9 cases in which anchoring sutures were applied and in the 7 cases with saccular aneurysms. No spinal cord dysfunction occurred in 8 cases with low-flow antegrade perfusion by way of both axillary arteries while the aorta was opened. Logistic regression analysis showed significant relevance to complications of large aneurysms, greater than 80 mm in diameter. A large aneurysm tends to give rise to complications involving EVG migration. Anchoring sutures of EVG may prevent EVG-related complications.

Expression of angiogenesis and angiogenic factors in human aortic vascular disease.

BACKGROUND: This paper presents an investigation into the expression of endothelial cells and vascular endothelial growth factor (VEGF) in the aortic wall in vascular diseases such as atherosclerotic abdominal aortic aneurysm (AAAA), inflammatory abdominal aortic aneurysm (IAAA), and aortic occlusive disease (AOD) to determine whether the differences in both neovascularization and angiogenic factor expression are related to the pathogenesis of aortic vascular disease. MATERIALS AND METHODS: Surgical specimens of aorta (10 IAAA, 13 AAAA, 6 AOD) were studied pathologically and immunohistochemically. Representative sections of aorta were stained with hematoxylin-eosin, elastica von Gieson, CD34, and VEGF antibody. CD34-positive microvessels and VEGF-positive cells in the media and adventitia were counted, respectively. RESULTS: CD34-positive microvessels were detected in IAAA > AAAA > AOD (one-way analysis of variance (ANOVA), P < 0.0001). VEGF expression was widely detected in macrophages, monocytes, and smooth muscle cells of IAAA and AAAA; however, it was hardly recognized in AOD. VEGF-positive cells were detected in IAAA > AAAA > AOD specimens (ANOVA, P < 0.0001). CONCLUSIONS: VEGF is known to be a regulator of angiogenesis and to simultaneously stimulate elastolytic proteinases. The results of this study suggest that an angiogenic factor, such as VEGF, may play an important role in the degeneration of the aortic wall and could be strongly related to the pathogenesis of IAAA, AAAA, and AOD.