Incidence, diagnosis and treatment of popliteal artery entrapment syndrome in current vascular practice in Japan.

Few data regarding popliteal artery entrapment syndrome (PAES) is available in Japan. In this study, we investigated incidence, diagnosis and treatment of PAES in current vascular practice. A retrospective analysis of all patients with PAES visiting 31 participating institutes between 2003 and 2015 was conducted. Thirty-five limbs (28 patients) were identified during the 13-year study period, and the incidence of PAES was 0.12% of all peripheral artery disease cases revascularized. Mean age was 32.0 ± 16.9 years old, and 60 and more years old was 10.7%. Also, 92.9% were male and 39.3% were athletes. Most frequent initial symptoms were intermittent claudication in 23 limbs (65.7%); 4 limbs (11.4%) had chronic limb-threatening ischemia. CT scan was most frequently (94.3%) used for the diagnostic imaging followed by MRI (45.7%) and duplex ultrasound (45.7%). Stress test such as dorsal flexion during duplex ultrasound was used only in 28.6%. Thirty-two limbs (91.4%) received surgical treatment, including 23 arterial reconstructions (71.9%); there were no major perioperative complications. All patients achieved improvement of their symptoms, and the average ankle brachial index increased from 0.69 ± 0.22 to 1.00 ± 0.14 post-surgery. The average postoperative follow-up period was 26.0 months with only one reintervention during the follow-up. In conclusion, PAES was a rare condition and traditional surgical treatment was solid. However, given a broad spectrum of clinical feature of PAES and less usage of diagnostic duplex ultrasound with stress test, there might be a miss- or delayed diagnosis of PAES even in the current vascular practice.

Characteristics and Risk Factors for Type 2 Endoleak in an East Asian Population From a Japanese Multicenter Database.

BACKGROUND: Clinically distinct differences exist between East Asian and Caucasian subjects, but data for type 2 endoleak (T2EL) are limited in the East Asian population. The aim of this study was to analyze the characteristics of East Asian T2EL using a Japanese multicenter database. METHODS AND RESULTS: Retrospective analysis of 832 endovascular aneurysm repairs performed from 2008 to 2014 were conducted. T2EL was observed in 234 cases (28.1%), and in 32 cases (3.8%) it led to sac expansion >5 mm caused by isolated T2EL (median follow-up, 35.6 months). On univariate and multivariate analysis, non-smoker status (odds ratio [OR], 2.216; P<0.001), Excluder stent graft (OR, 2.027; P<0.001), and T2EL at final angiogram (OR, 2.080; P<0.001) were risk factors for T2EL. On multivariate analysis for isolated T2EL with sac expansion, only non-smoker status remained (OR, 2.671; P<0.001). Other than T1EL, isolated T2EL was the most significant risk factor for sac expansion (OR, 18.486; P<0.001). Furthermore, out of 11 transarterial embolization procedures initiated, 4 led to rupture during follow-up. CONCLUSIONS: East Asian T2EL had a strong relationship with non-smoker status. Also, T2EL was a significant risk factor for sac expansion, which sometimes led to rupture even after intervention. Along with the high prevalence of T2EL observed, East Asian T2EL may not always be benign.

Endovascular repair of abdominal aortic aneurysm using bifurcated stent-graft in a patient with complete occlusion from the common to the external iliac artery.

Extensive iliofemoral occlusive disease can limit the use of endovascular aortic aneurysm repair (EVAR), and the treatment strategy varies depending on severity of the lesion. In cases of mild iliac artery (IA) stenosis, predilation using a balloon catheter before EVAR is relatively common, and for severe IA stenosis, the technique of internal endoconduits has been reported with good results. In contrast, EVAR using an aortouni-iliac stent graft with femorofemoral crossover bypass has traditionally been used for abdominal aortic aneurysm with IA occlusion. However, EVAR using a bifurcated stent graft has some clear advantages over aortouni-iliac stent grafts. In this report, we describe and discuss technical aspects and feasibility of chronically occluded iliac artery recanalization before EVAR to facilitate the use of bifurcated stent grafts in a patient with concomitant complete common to external IA occlusion.

Role of complement and NK cells in antibody mediated rejection.

Despite extensive research on T cells and potent immunosuppressive regimens that target cellular mediated rejection, few regimens have been proved to be effective on antibody-mediated rejection (AMR), particularly in the chronic setting. C4d deposition in the graft has been proved to be a useful marker for AMR; however, there is an imperfect association between C4d and AMR. While complement has been considered as the main player in acute AMR, the effector mechanisms in chronic AMR are still debated. Recent studies support the role of NK cells and direct effects of antibody on endothelium cells in a mechanism suggesting the presence of a complement-independent pathway. Here, we review the history, currently available systems and progress in experimental animal research. Although there are consistent findings from human and animal research, transposing the experimental results from rodent to human has been hampered by the differences in endothelial functions between species. We briefly describe the findings from patients and compare them with results from animals, to propose a combined perspective.

Polylactide-cyclosporin A nanoparticles for targeted immunosuppression.

Polymeric nanoparticles (NPs), prepared via coprecipitation of drugs and polymers, are promising drug delivery vehicles for treating diseases with improved efficacy and reduced toxicity. Here, we report an unprecedented strategy for preparing polylactide-cyclosporine A (PLA-CsA) NPs (termed CsA-NPs) through CsA-initiated ring-opening polymerization of lactide (LA) followed by nanoprecipitation. The resulting CsA-NPs have sub-100 nm sizes and narrow particle size distributions, and release CsA in a sustained manner without a "burst"-release effect. Both free CsA and CsA-NPs displayed comparable suppression of T-cell proliferation and production of inflammatory cytokines in various T-cell assays in a dose-dependent manner. The IC(50) values for CsA and CsA-NPs were 27.5 and 72.0 ng/ml, respectively. As lymph nodes are the main loci for T-cell activation, we coupled dendritic cells (DCs) with CsA-NPs and successfully delivered CsA selectively to the lymph nodes. Our studies indicated that CsA-NPs could be internalized in the DCs with a sustained release of CsA to the culture medium, suppressing alloreactive T-cell proliferation. Allogeneic DCs loaded with CsA-NPs were able to migrate to the draining lymph nodes where the T-cell priming was significantly reduced without any systemic release. This innovative nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and reduced toxicity.

[A case of advanced rectal cancer responding to neoadjuvant chemotherapy with CPT-11, 5-FU and l-LV after coronary artery bypass graft].

A 75-year-old man was referred to our hospital with a diagnosis of lower rectal cancer. Unstable angina attack occurred after admission and cardiac angiography revealed stenosis of three coronary arteries which were treated by percutaneous transluminal coronary angioplasty unsuccessfully. Coronary artery bypass graft was performed after colostomy. It is possible for operative stress, extracorporeal circulation and blood transfusion to diminish immunocompetence and increase the risk of recurrence. Therefore, CPT-11/5-FU/l-LV combination therapy (CPT-11 80 mg/m(2), 5-FU 500 mg/m(2), l-LV 250 mg/m(2) day 1, 8, 15 every 5 weeks) was carried out as neoadjuvant chemotherapy. The tumor decreased in size, and the level of tumor marker was normalized after two courses of the combination therapy. The patient is alive without recurrence three years after abdominoperineal resection.

Prolongation of survival of fully allogeneic cardiac grafts and generation of regulatory cells by a histamine receptor 2 antagonist.

BACKGROUND: The effects of histamine on immunologic responses via the histamine receptor 2 (HR2) have been studied, but few investigations explored the immunomodulatory role of histamine in vivo. We examined whether the HR2 antagonist ranitidine affects the alloimmune response in a murine model of cardiac transplantation. METHODS: CBA (H-2k) recipients were given no treatment or one intravenous injection of ranitidine on the day of transplantation of a heart from C57BL/10 (H-2b) donors. Survival of the allografts was recorded. The effect of the ranitidine treatment on cell proliferation and cytokine production was assessed by mixed leukocyte culture and enzyme-linked immunosorbent assays. An adoptive transfer study was conducted to determine whether regulatory cells were generated. The effect on graft survival of adding FK506 to the ranitidine treatment was also examined. RESULTS: CBA recipients given ranitidine (60 mg/kg) had prolonged graft survival (median survival time [MST], 87 days). Ranitidine treatment also suppressed the proliferation of splenocytes and production of interleukin (IL)-2 and up-regulated IL-10 production. Adoptive transfer of splenocytes and CD4 cells from ranitidine-treated allograft recipients induced significant prolongation of allograft survival in naive secondary recipients (MST, 71 and >100 days, respectively). CBA recipients given both ranitidine and FK506 (0.1 mg/kg/day for 14 days) had indefinite survival of cardiac allografts (MST, >100 days). CBA recipients treated with FK506 alone rejected the allografts (MST, 27 days). CONCLUSION: In our model, ranitidine treatment induced significantly prolonged survival of fully allogeneic cardiac grafts, generated CD4 regulatory cells, and indefinite survival when combined with FK506 (0.1 mg/kg/day).

Induction of indefinite survival of fully mismatched cardiac allografts and generation of regulatory cells by sarpogrelate hydrochloride.

BACKGROUND: At initiation of the immunologic response, platelets rapidly release chemical mediators such as serotonin (5-hydroxytryptamine, [5-HT]) and cytokines. Sarpogrelate hydrochloride (SH), a selective 5-HT2-receptor antagonist, is used to treat patients with peripheral arterial disease. We investigated the effect of SH on the alloimmune response in a murine cardiac transplantation model. METHODS: CBA mice underwent transplantation of a C57BL/10 heart and received a short course of SH treatment. Survival of the allograft was recorded. An adoptive transfer study was performed to determine whether regulatory cells were generated. Immunohistochemistry studies of intercellular adhesion molecule 1 (ICAM-1), histological, cell-proliferation, and cytokine assessments were performed. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST], 8 days). In mice given 10 mg/kg of SH, all allografts survived indefinitely (MST, >100 days); these mice also had significantly prolonged survival of donor-specific skin grafts but acute rejection of third-party skin grafts. Secondary CBA recipients given not only whole but also CD4 splenocytes from primary SH-treated CBA recipients with C57BL/10 cardiac allograft had indefinite survival of C57BL/10 hearts (MST, >100 days). SH inhibited upregulation of ICAM-1 on endothelial cells in the allografts. Graft acceptance and hyporesponsiveness were confirmed by the histological and cell-proliferation studies, respectively. Production of interleukin-4 and interleukin-10 from splenocytes of SH-treated transplant recipients increased compared to that from splenocytes of untreated recipients. CONCLUSION: SH induced indefinite survival of fully allogeneic cardiac allografts, generated CD4 regulatory cells, inhibited ICAM-1 expression in the allografts, and upregulated IL-4 and IL-10 production.

Surgical and endovascular procedures for treating isolated iliac artery aneurysms: ten-year experience.

Characteristics of atherosclerotic isolated iliac artery aneurysms (IAAs) and various strategies for their treatment were assessed retrospectively. The computerized medical records of 18 patients who underwent surgical or endovascular treatment of an IAA during the 10 years from April 1993 to March 2003 at our university hospital were reviewed to obtain information on patient demographics, risk factors, type of IAA treatment, and outcome. Additional data were obtained by mail and telephone. Patients with an IAA were compared with 168 patients treated for an abdominal aortic aneurysm (AAA) also at our institution. Early in the series of isolated IAA repairs, patients underwent prosthetic graft interposition ( n = 7) or thromboexclusion ( n = 4). Subsequently, patients had either endovascular thromboembolization ( n = 4) or endovascular thromboembolization with femorofemoral crossover bypass ( n = 3). No perioperative deaths occurred in the series. Deep venous thrombosis developed postoperatively in one patient; there were no other serious complications. The cumulative patency rate for the implanted interposition grafts during the mean observation time of 5.5 years was 100%. No endoleakage was observed after the endovascular procedures. In the long-term, five patients died of causes unrelated to the IAA treatment. A statistical analysis revealed no significant differences between the IAA group and the AAA group with respect to atherosclerotic risk factors. In conclusion, open surgical procedures to repair isolated IAAs generally have a good outcome, although the risk of injury to adjacent iliac veins remains. Endovascular treatments appear to have some advantages, but studies including long-term follow-up are needed to assess the efficacy and durability of prosthetic grafts used for these procedures.