Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

Prediction Models for Two Year Overall Survival and Amputation Free Survival After Revascularisation for Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to create prediction models for two year overall survival (OS) and amputation free survival (AFS) after revascularisation in patients with chronic limb threatening ischaemia (CLTI). METHODS: This was a retrospective analysis of prospectively collected multicentre registry data (JAPAN Critical Limb Ischaemia Database; JCLIMB). Data from 3 505 unique patients with CLTI who had undergone revascularisation from 2013 to 2017 were extracted from the JCLIMB for the analysis. The cohort was randomly divided into development (2 861 patients) and validation cohorts (644 patients). In the development cohort, multivariable risk models were constructed to predict two year OS and AFS using Cox proportional hazard regression analysis. These models were applied to the validation cohort and their performances were evaluated using Harrell's C index and calibration plots. RESULTS: Kaplan-Meier estimates of two year OS and AFS post-revascularisation in the whole cohort were 69% and 62%, respectively. Strong predictors for OS consisted of age, activity, malignant neoplasm, chronic kidney disease (CKD), congestive heart failure (CHF), geriatric nutritional risk index (GNRI), and sex. Strong predictors for AFS included age, activity, malignant neoplasm, CKD, CHF, GNRI, body temperature, white blood cells, urgent revascularisation procedure, and sex. Prediction models for two year OS and AFS showed good discrimination with Harrell's C indexes of 0.73 (95% confidence interval [CI] 0.69 - 0.77) and 0.72 (95% CI 0.68 - 0.76), respectively CONCLUSION: Prediction models for two year OS and AFS post-revascularisation in patients with CLTI were created. They can assist in determining treatment strategies and serve as risk adjustment modalities for quality benchmarking for revascularisation in patients with CLTI at each facility.

Current Trends in Epidemiology and Clinical Features of Thromboangiitis Obliterans in Japan　- A Nationwide Survey Using the Medical Support System Database.

BACKGROUND: The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79-8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45-5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00-7.31) in FY 2008 to 6.12% (95% Cl: 5.98-6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya's criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis. CONCLUSIONS: The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

Preservation of the accessory renal arteries after endovascular repair of common iliac artery aneurysm using kissing stent grafts.

Exclusion of the accessory renal arteries (ARAs) is required during endovascular aneurysm repair if they arise from the sealing zone or aneurysm sac. Here, we report a case of successful endovascular treatment for a common iliac artery aneurysm located close to the aortic bifurcation and associated with nephrotic syndrome in a 51-year-old man. The bilateral ARAs were successfully preserved using kissing stent grafts. During surgery, the proximal ends of endografts inserted from the bilateral femoral arteries were adjusted so that they met at the same level in the aorta, and simultaneous balloon dilatation was performed. This method can be a useful treatment option for common iliac aneurysms in cases with large ARAs.

Favorable outcomes of very elderly patients with critical limb ischemia who undergo distal bypass surgery.

OBJECTIVE: To determine the midterm outcomes of distal bypass surgery for very elderly patients, and to determine the ideal candidates for this procedure. METHODS: Of 268 consecutive patients (328 limbs) with critical limb ischemia who were treated between 2006 and 2013, 106 (126 limbs) underwent distal bypass and were retrospectively reviewed. Nineteen patients (22 limbs) were aged ≥80 years (very elderly group) and 87 patients (104 limbs) were aged <80 years (control group). RESULTS: The baseline characteristics differed between the 2 groups in terms of regular hemodialysis rate (very elderly group, 4 [21%] vs control group, 60 [69%]; P = .0002) and the Charlson comorbidity index (very elderly group, 3.2 ± 1.7 vs control group, 5.0 ± 2.0; P = .0005). According to the Rutherford category of limb ischemia (4/5/6), the very elderly and control groups were classified as 5/17/0 and 11/87/6, respectively (P = .18). Before the surgery, 17 patients (77%) and 67 patients (64%) were ambulatory in the very elderly and control groups, respectively. At follow-up at 29 ± 22 months, the rates of primary (P = .33) and secondary patency (P = .14), limb salvage (P = .50), survival (P = .26), amputation-free survival (P = .42), major adverse limb event and also perioperative death (P = .11), and major adverse cardiovascular events (P = .36) did not significantly differ between the groups. In multivariate analysis, a history of coronary artery disease (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.9; P = .005), preoperative nonambulatory status (HR, 4.2; 95% CI, 2.1-8.1; P < .0001), and serum albumin levels <3 g/dL (HR, 2.7; 95% CI, 1.3-5.4; P = .01) were significantly related to poor amputation-free survival. Thirteen patients (59%) remained ambulatory at the latest follow-up. In 91 patients (110 limbs) with tissue loss, the Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on Wound, Ischemia, and foot Infection classification stages 3 and 4 negatively affected complete wound healing, according to multivariate analysis (HR, 0.34; 95% CI, 0.20-0.61; P = .0005). CONCLUSIONS: A very elderly age should not preclude a patient from undergoing distal bypass surgery. A history of coronary artery disease, a nonambulatory status, and hypoalbuminemia, along with the Wound, Ischemia, and foot Infection classification for patients with tissue loss, should be carefully considered to obtain the most benefit from distal bypass surgery.

Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries.

In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis.

Paramalleolar Arterial Bollinger Score in the Era of Diabetes and End-Stage Renal Disease - Usefulness for Predicting Operative Outcome of Critical Limb Ischemia.

BACKGROUND: The aim of this study was to evaluate the usefulness of paramalleolar arterial Bollinger score (PBS) for predicting postoperative outcome of infra-popliteal bypass surgery for critical limb ischemia (CLI). METHODS AND RESULTS: A total of 104 consecutive patients (118 limbs) who underwent infra-popliteal (tibial or paramalleolar) arterial bypass surgery with an autologous vein conduit for the treatment of CLI (Rutherford 4-6) between January 2002 and December 2012 were classified according to PBS ≤45 or >45. Postoperative outcome was compared between these groups. Primary outcomes were major adverse limb events plus perioperative death, and amputation-free survival (AFS). The secondary outcomes were overall survival, limb salvage and secondary graft patency. More than 80% of patients had either diabetes mellitus (DM) or end-stage renal disease (ESRD) and 30 patients with 36 limbs had PBS >45. Compared with the PBS ≤45 group, the PBS >45 group had higher CVD and carotid stenosis rate, poor nutrition status and lower malignancy rate. On overall analysis, the PBS >45 group had worse outcome for AFS and survival but this was not statistically significant (P=0.12, NS). In DM or ESRD patients, the PBS >45 group had significantly worse outcome for both AFS (P=0.04, 0.02) and overall survival rate (P=0.04, 0.03). CONCLUSIONS: PBS successfully classified CLI patients with DM or ESRD who had worse outcome after infra-popliteal bypass surgery.

Inverse Correlation Between Calcium Accumulation and the Expansion Rate of Abdominal Aortic Aneurysms.

BACKGROUND: When the maximal diameter of an abdominal aortic aneurysm (AAA) exceeds a threshold, the likelihood of catastrophic rupture increases markedly. Therefore, surveillance at optimal intervals should be offered to patients with AAA. However, other than AAA diameter, there is no useful marker or index for predicting the expansion rate of an AAA or determining the optimal intervals for surveillance. The aim of this study was to evaluate the usefulness of calcium accumulation in the AAA for predicting its expansion rate. METHODS AND RESULTS: We performed a retrospective cohort study in 414 patients with infrarenal AAA who visited The University of Tokyo Hospital. The maximal diameter and extent of calcification of each AAA were evaluated by multidetector-row computed tomography imaging. There was an inverse correlation between the extent of calcification and the subsequent AAA expansion. A lower extent of calcification in the AAA as well as the AAA diameter and absence of coronary artery disease correlated with an accelerated expansion of the AAA. CONCLUSIONS: In AAA, a lower extent of calcification correlated with accelerated expansion. The calcification index of an AAA can be a useful predictor of its expansion rate. The study findings also support the theory that the mechanisms for progression in atherosclerosis with calcification and external expansion of an aneurysm are distinct.

Distal bypass to a critically ischemic foot increases the skin perfusion pressure at the opposite site of the distal anastomosis.

INTRODUCTION: The purpose of the study was to reveal the effect of blood flow supply to the foot by analyzing the skin perfusion pressure values and the pedal arch connection after bypass surgery. PATIENTS AND METHODS: We selected 48 operated limbs whose skin perfusion pressure was measured pre- and post-operatively on the opposite site of distal anastomosis. We also assigned the ischemic limbs to three groups according to the patency of the pedal arch: good, intermediate, and poor. RESULTS: The mean value of skin perfusion pressure increased significantly from 27.0 ± 14.9 to 52.8 ± 16.0 (p < 0.001) post-operatively. Skin perfusion pressure improved in most of the limbs post-operatively and decreased or unchanged in only four limbs, all of which showed improved tissue loss. Three amputated limbs were due to infection, and all showed an increase in skin perfusion pressure. CONCLUSION: It was difficult to correlate limb prognosis to skin perfusion pressure and the pedal arch connection.

A perioperative strategy for abdominal aortic aneurysm in patients with chronic renal insufficiency.

PURPOSE: The outcomes of open surgical repair (OR) or endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) are favorable; however, pre-existing chronic renal insufficiency (CRI) is considered to be a risk factor that can affect the long-term outcome. We evaluated our surgical strategy for AAA in patients with CRI by analyzing their pre- and postoperative renal function. METHODS: We conducted a retrospective chart review of CRI patients who underwent OR (n = 28) or EVAR (n = 31) for infra-renal AAA in our institution between 2009 and 2013. Our operative strategy included pre- and postoperative adequate hydration, postoperative diuretics and low-dose dopamine for both groups, intravascular ultrasonography and carbon dioxide angiography to reduce the amount of contrast media needed in the EVAR group, and occasional intraoperative mannitol for the OR group. RESULTS: The preoperative estimated glomerular filtration rate (eGFR) increased significantly in the postoperative period and remained similar 6 months later in both groups, without any difference in changes between the groups. In-hospital postoperative complications included leg occlusion in one EVAR patient. There were no complication-related deaths in either group. CONCLUSIONS: Postoperative renal function was similar after the two approaches, indicating that both procedures could be performed safely using our strategy for patients with CRI.

EXCISION OF GIANT PELVIC LIPOSARCOMA NECESSITATING FEMORAL-FEMORAL ARTERY BYPASS AND GAUZE PACKING FOR ILIAC ARTERY INVOLVEMENT AND MASSIVE PRE-SACRAL BLEEDING-A CASE REPORT.

The patient is a 43-year-old male, presented with numbness of the left lower extremities. Imaging studies showed a pelvic tumor 20 cm in diameter, involving the left ureter, left common iliac vessels, left internal and external iliac vessels, and inferior mesenteric artery, which was deemed unresectable. Tumor biopsy confirmed liposarcoma. As chemotherapy was not effective, he was referred to us. Following femoral-femoral artery bypass in advance, the tumor was resected with the sigmoid colon, left kidney, ureter, left iliac vessels, and interior mesenteric artery. Removal of the tumor caused massive venous hemorrhage from the pre-sacral plexus, which was scarcely managed by gauze packing. Open abdominal management was selected to avoid abdominal compartment syndrome by severe intestinal edema. The packed gauze was retrieved on the fourth post-operative day, with laparotomy closed. The postoperative course was uneventful.

Family history of aortic aneurysm is an independent risk factor for more rapid growth of small abdominal aortic aneurysms in Japan.

OBJECTIVE: We aimed to investigate risk factors associated with more rapid growth of abdominal aortic aneurysms (AAA) <50 mm (small AAAs) in Japan. METHODS: We retrospectively investigated the clinical data of 374 patients with small AAAs (maximum diameter, ≤50 mm) who were referred to The University of Tokyo Hospital, Tokyo Medical University Hospital, or Saitama Medical Center, between 1995 and 2008. RESULTS: A total of 374 patients (321 men and 53 women) were followed up for a median of 66 months. The median diameter on initial examination was 40 mm, and the median growth rate of the AAAs was 2.1 mm/y. The growth rate of AAAs with an initial diameter ≥45 mm was significantly greater than those with an initial diameter <45 mm (3.3 mm/y vs 2.0 mm/y, respectively; P = .007). The growth rate of AAAs was significantly greater in patients with hypertension than in those without (2.3 mm/y vs 1.7 mm/y, respectively; P = .006) and in patients with a family history of aortic aneurysm than in those without (4.2 mm/y vs 2.0 mm/y, respectively; P = .009). Logistic regression analysis revealed that a large initial diameter and family history of aortic aneurysm were independent predictors of accelerated growth rate of small AAAs in Japan. CONCLUSIONS: In the present study, a large initial diameter and family history of aortic aneurysm were independent risk factors for more rapid growth of small AAAs. Although few studies have reported similar findings thus far, family history of aortic aneurysm should be carefully considered during follow-up of patients with small AAAs.

Poor Prognosis in Critical Limb Ischemia Without Pre-Onset Intermittent Claudication.

BACKGROUND: Some patients with critical limb ischemia (CLI) lack symptoms of intermittent claudication (IC) before the onset of CLI. We studied the outcome of such patients, because this is currently unknown. METHODS AND RESULTS: For retrospective exploratory analysis, we divided 225 patients (265 limbs) with CLI into 2 groups: 142 patients (172 limbs) without a history of IC (non-IC group) and 83 patients (93 limbs) with IC (IC group). We examined comorbid factors and found that a higher proportion of patients in the non-IC group failed to undergo arterial revascularization (49% vs. 20%, P<0.0001) due to progressed limb ischemia and infection. We then analyzed 140 patients (161 limbs) with revascularization. Patients in the non-IC group were more likely to have diabetes mellitus (P=0.03), hypoalbuminemia (P=0.02), advanced Rutherford's classification (P=0.0007), worse ambulatory function (P=0.009), and longer postoperative stay (P=0.04). Amputation-free survival was lower in the non-IC group (P=0.005). On Cox regression analysis, hemodialysis (P=0.002), coronary artery disease (P=0.04), cerebrovascular disease (P=0.02), non-ambulatory status (P=0.02), and non-IC (P=0.01) were independent risk factors for lower amputation-free survival. CONCLUSIONS: Patients without IC before CLI onset have several unique features, and non-IC is an independent risk factor for poor outcome.

Development of an Image-Based Modeling System to Investigate Evolutional Geometric Changes of a Stent Graft in an Abdominal Aortic Aneurysm.

BACKGROUND: Quantification of geometric changes of the stent graft (SG) in abdominal aortic aneurysm has been required for follow up of endovascular aneurysm repair (EVAR). The aim was to develop an image-based modeling system (V-Modeler) to investigate these changes over time. METHODS AND RESULTS: V-Modeler was applied to investigate the migration of the SG. Three sets of computed tomography images were taken at 3 different times: (1) 5 days after the implantation; (2) 7 months later when the unilateral leg migrated upward; and (3) 10 months later when the limb had migrated into the common iliac aneurysm resulting in a type 1b endoleak. A spline function was used to represent the center lines of the SG to track its evolutional geometric changes in a three-dimensional manner. The characteristics of vascular geometry, as well as the SG geometry using geometric parameters such as length, curvature, torsion, angle of tangent vector (ATV), and migrated length, was evaluated. It was observed that the strong peak of the curvature in the distal area appeared, and a conversion of the torsion disappeared chronologically. CONCLUSIONS: The V-Modeler was developed, which not only can extract vascular geometry but also can identify geometric parameter, such as curvature, torsion, and ATV, to predict adverse events following EVAR.

Incidence of periodontitis in Japanese patients with cardiovascular diseases: a comparison between abdominal aortic aneurysm and arrhythmia.

Although there is a link between periodontitis and cardiovascular disease (CVD), the influence of periodontitis on CVD is unclear. The aim of this study was to assess the relationship between periodontal bacterial burden and CVD. We studied 142 patients with tachyarrhythmia (TA) and 25 patients with abdominal aortic aneurysm (AAA). We examined periodontitis and the presence of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Prevotella intermedia in the patients' saliva and subgingival plaque using PCR. We also measured serum antibody titers against the pathogens using ELISA. We found that the patients with AAA had fewer remaining teeth (14.6 ± 2.0 vs. 20.9 ± 0.7, P < 0.05) and deeper pocket depth (3.01 ± 0.26 vs. 2.52 ± 0.05 mm, P < 0.05) compared to the TA patients. The existence of each periodontal bacterium in their saliva or subgingival plaque and serum antibody titers was comparable between the two groups. Periodontitis may have a larger affect on aneurysm progression compared to arrhythmia.

Long-term outcomes of surgical treatment in patients with popliteal artery entrapment syndrome.

The object of the study is to determine the long-term outcomes of surgical treatment of patients with popliteal artery entrapment syndrome at a single institute. We retrospectively reviewed 19 limbs of 16 consecutive patients who underwent surgery for popliteal artery entrapment syndrome at our hospital over the past 36 years. The popliteal artery was stenotic in 11 limbs, occlusive in 7 limbs, and compressed and deviated by the medial head of the gastrocnemius muscle but not damaged in 1 limb. Six limbs were treated with autologous saphenous vein bypass, 10 with bypass or venous patch graft concomitant with musculotendinous section, and 3 limbs underwent musculotendinous section alone. The 10-year cumulative patency of the 13 limbs treated with bypass was 100%, although two of them showed occlusion at 23 and 12 years after surgery. One patient who received a venous patch graft showed occlusion 15 years after surgery. Additionally, one asymptomatic patient with an apparently non-damaged popliteal artery who received preventive musculotendinous section alone showed stenosis of the artery 2 years after musculotendinous section. In conclusion, the bypass patency observed in this study was excellent in the long term. Careful examination of popliteal artery anatomy using imaging studies is essential for selecting the appropriate surgical procedure for popliteal artery entrapment syndrome.

Effect of suprarenal aortic cross-clamping.

BACKGROUND: Renal insufficiency is the most frequent complication of surgeries that involve suprarenal aortic cross-clamping. Although some studies have assessed the risk of intraoperative renal ischemia by comparing juxtarenal abdominal aortic aneurysms (AAAs) and infrarenal AAAs, a critical limitation is the difference in these patients' clinical backgrounds and aneurysmal features. The present study evaluated the effect of suprarenal aortic clamping by comparing a juxtarenal AAA group with a subgroup of infrarenal AAAs (ie, short and/or large neck). METHODS AND RESULTS: Among patients who underwent open surgery for AAA, the 2 types of AAA were selected and compared: juxtarenal AAA (JR group: n=35) and infrarenal AAA with short (<15 mm) and/or large (>28 mm) aneurysmal neck that only required infrarenal aortic clamping (SL group: n=26). Postoperative renal function was evaluated using the RIFLE classification. There were no significant differences between groups in baseline characteristics, comorbidities, and intraoperative variables. There were no adverse events leading directly to in-hospital mortality in either group. The rate of postoperative renal insufficiency (estimated glomerular filtration rate decrease ≥-25%) was not significantly different between groups. CONCLUSIONS: The outcomes of the 2 groups were similar, indicating that intraoperative renal ischemia with no specific intraoperative protection would not adversely affect postoperative outcomes.