Hepatocyte growth factor (HGF) is secreted from stromal and mesenchymal cells, and its receptor cMet is expressed on various types of cells such as smooth muscle cells, fibroblast, and endothelial cells. HGF stimulates epithelial and endothelial cell proliferation, motility, and morphogenesis in a paracrine and autocrine manner, organizing multistep of angiogenesis in many organs. In addition, HGF is recognized as a potent anti-inflammatory and anti-fibrotic growth factor, which has been proved in several animal studies, including neointimal hyperplasia and acute myocardial infarction model in rodent. Thus, as compared to other angiogenic growth factors, HGF exerts multiple effects on ischemic tissues, accompanied by the regression of tissue inflammation and fibrosis. These data suggest the therapeutic potential of the HGF for peripheral artery disease as it being accompanied with chronic tissue inflammation and fibrosis. In the present narrative review, the pleiotropic action of the HGF that differentiates it from other angiogenic growth factors is discussed first, and later, outcomes of the human clinical study with gene therapy are overviewed.

Along with the progress of global aging, the prognosis of severe ischemic heart disease (IHD) remains poor, and thus the development of effective angiogenic therapy remains an important clinical unmet need. We have developed low-energy extracorporeal cardiac shock wave therapy as an innovative minimally invasive angiogenic therapy and confirmed its efficacy in a porcine chronic myocardial ischemia model in animal experiments as well as in patients with refractory angina. Since ultrasound is more advantageous for clinical application than shock waves, we then aimed to develop ultrasound therapy for IHD. We demonstrated that specific conditions of low-intensity pulsed ultrasound (LIPUS) therapy improve myocardial ischemia in animal models through the enhancement of angiogenesis mediated by endothelial mechanotransduction. To examine the effectiveness of our LIPUS therapy in patients with severe angina pectoris, we are now conducting a prospective multicenter clinical trial in Japan. Furthermore, to overcome the current serious situation of dementia pandemic but with no effective treatments worldwide, we have recently demonstrated that our LIPUS therapy also improves cognitive impairment in mouse models of Alzheimer’s disease and vascular dementia. Here, we summarize the progress in our studies to develop angiogenic therapies with sound waves.

Although several studies showed that angiosome-guided endovascular treatment improved wound healing and major amputation rates in patients with chronic limb-threatening ischemia (CLTI), effectiveness of the angiosome concept to the treatment of ischemic foot remains to be elucidated, especially in bypass surgery. Arterial anatomy of the foot and ankle shows that there are multiple supplementary circulation including arterial–arterial connections and choke nexus, which indicates angiosome concept may carry limited importance in bypass surgery for CLTI. On the other hand, patients with diabetes or renal dysfunction have partial occlusion of arterial–arterial connections and, therefore, quite a few patients with CLTI in Japan may present with limited but impaired supplementary circulation around the ankle. This article reviews the arterial anatomy and circulation of the foot and ankle and discusses availability and limitations of angiosome-guided bypass surgery.

May–Thurner and Paget–Schroetter syndromes are rare conditions encountered by vascular surgeons. An updated knowledge about these conditions is crucial for the effective management of patients with these syndromes who are mostly young.

May–Thurner syndrome (MTS) is caused by the compression of the left common iliac vein by the right common iliac artery, and it is a risk factor for left leg deep venous thrombosis (DVT). Imaging (conventional venogram, computed tomography venography (CTV), magnetic resonance imaging (MRV)) can reveal the stenotic venous segment where the artery crosses. Stenting in symptomatic patients yields good results with minimal recurrence.

Paget–Schroetter syndrome (PSS) is an idiopathic axillary-subclavian vein thrombosis mostly affecting the young population, particularly those who have repeated overhead arm activities. Narrower costoclavicular space along with other anatomical and coagulation factors can possibly lead to this condition. Patients can present with acute DVT, post-thrombotic syndrome or subclinical syndromes. Venogram, CTV or MRV with provocative maneuvres can confirm the dynamic obstruction. Thrombolysis followed by early bony decompression is advocated in patients presenting with acute arm DVT, as this approach is associated with limited residual disability and recurrence.

This review discusses the current concepts and treatment options of both conditions.

Objective: In this study, we report our experience using the frozen elephant trunk (FET) technique for chronic aortic dissection.

Methods: Between January 2011 and December 2017, 15 patients underwent total arch replacement (TAR) with the FET technique for chronic aortic dissection (CAD).

Results: Hospital mortality was 6.7% (n=1). No patients experienced spinal cord injury. Distal stent-induced new entry (dSINE) occurred in the early postoperative period in one patient. There were four unplanned additional operations to manage dSINE. Five patients suffered from dSINE, and aortoesophageal fistula developed in three of them. Short insertion length of the FET and large angle between the distal edge of the FET and the descending aorta were significantly more common in the dSINE group than in the non-dSINE group. The cumulative survival rates at 1, 3, and 5 years were 93.3%, 93.3%, and 66.4%, respectively. The cumulative aortic event-free rates at 1, 2, and 3 years were 85.7%, 77.1%, and 52.9%, respectively.

Conclusion: The FET technique for CAD provided good early results. Short insertion length of the FET, however, can induce dSINE, which requires an additional operation at mid-term. Thus, surgical indication of the FET technique for CAD must be discussed.

Objective: Although aortofemoral bypass (AoFB) is the standard treatment for challenging aortoiliac occlusive disease (AIOD), less-invasive treatments, such as axillofemoral bypass (AxFB) or endovascular treatment (EVT) have been conducted for patients with severe comorbidities. In this study, we compared the clinical outcomes between AxFB and EVT for AIOD.

Materials and Methods: We retrospectively reviewed 9 patients with AxFB and 10 with EVT for challenging AIOD. The patients’ information and operative results were evaluated. The rates of patency and limb salvage were analyzed according to the Kaplan–Meier method.

Results: In the EVT group, 5 of 10 (50%) patients had aortic stenting alone, 3 (30%) received aorto-uniiliac stenting, and 2 (20%) received aorto-biiliac stenting. In the AxFB group, 2 cases (22.2%) showed acute graft thrombosis; however, in the EVT group, no acute thrombotic complications were seen. The primary patency rates in the AxFB and EVT groups at 5 years were 53.6% and 81.2%, respectively (log rank P=0.225), and the assisted primary patency rates at 5 years were 53.6% and 100%, respectively (log rank P=0.012).

Conclusion: EVT exhibited a more durable, better long-term patency rate than AxFB. EVT may, therefore, be a viable treatment alternative to AoFB for challenging AIOD.

Objective: Inflammatory response is central to pathogenesis of abdominal aortic aneurysm (AAA). Recently, we reported that Syk, a signaling molecule in inflammatory cells, promotes AAA development in a mouse model. In this study, we aimed to investigate the role of Syk in human AAA pathogenesis.

Materials and Methods: We obtained human AAA wall samples during open surgical aortic repair at Kurume University Hospital. Immunohistochemical analyses of AAA samples were performed for Syk activation and cell type markers. Ex vivo culture of human AAA tissue was utilized to evaluate the effect of P505-15, a Syk inhibitor, on secretions of interleukin-6 (IL-6) and matrix metalloproteinases (MMPs).

Results: Immunohistochemical analysis showed infiltration of B cells, T cells, and macrophages in AAA samples. Syk activation was localized mainly in B cells and part of macrophages. AAA tissue in culture secreted IL-6, MMP-9, and MMP-2 without any stimulation. The unstimulated secretions of IL-6, MMP-9, and MMP-2 were insensitive to P505-15. Secretions of IL-6 and MMP-9 were enhanced by exogenous normal human immunoglobulin G (IgG), which was suppressed by P505-15, whereas secretion of MMP-2 was insensitive to IgG or P505-15.

Conclusion: These results demonstrate an important role of Syk for IgG-dependent inflammatory response in human AAA.

Objectives: To review the prevalence, pattern, management, outcome, and predictive factors for limb loss of pediatric peripheral arterial injuries (PAIs) at a university hospital in Pakistan.

Methods: Medical records of children (age <18 years) managed for PAIs at the university hospital between Jan 2008 and Dec 2018 were reviewed for demographic data; mechanism, type, and severity of injury; management; and outcome.

Results: During the study period, of the 1718 children managed for trauma, 75 (67 males and 8 females) had PAI secondary to glass cut (33.3%), gunshot (28.0%), and road traffic accidents (24.0%). Forty-nine patients (65.3%) presented to the emergency room within 6 h of injury. Brachial (28.0%), superficial femoral (20.0%), and radial (20.0%) arteries were the frequently injured vessels. At presentation, the mean revised trauma score and Mangled Extremity Severity Score (MESS) were 3.86±0.55 and 3.4±1.92, respectively. Sixty-eight patients (90.66%) underwent vascular procedures: interposition saphenous vein bypass graft or PTFE graft in 38.7% and primary repair in 29.3%. Limb salvage was achieved in 92.65% of the patients. Late presentation (>6 h) was a risk factor for limb loss (p=0.014).

Conclusion: Of the 23 children who presented with trauma, 1 had major PAI. Early presentation (<6 h) and appropriate vascular interventions can salvage limbs in most of the patients.

Objective: This study aims to evaluate the chronological size changes of the prosthetic graft in the aortic arch, which is used as a landing zone for a subsequent stent grafting in hybrid aortic surgery.

Materials and Methods: Eighty-five patients who underwent total aortic arch replacement followed by computed tomography follow-up for at least 30 months after the surgery were included in the study.

Results: Prosthetic grafts used were Hemashield (Maquet, Rastatt, Germany), J-Graft (Japan Lifeline Inc., Tokyo, Japan) and Triplex (Terumo, Tokyo, Japan). There was an initial increase in diameter compared to package size after implantation (Hemashield, 1.04±0.035 vs. J-Graft, 1.06±0.027 vs. Triplex, 1.04±0.023, p=0.13). Significant difference in graft dilation ratio was observed in Triplex (1.18±0.062) at long-term compared to Hemashield (1.07±0.052, p<0.001) and J-Graft (1.10±0.071, p<0.001). Multivariate analysis showed that age (r=0.002; 95% confidence interval [CI], 0.0001–0.0037; p=0.035), knitted-type prosthesis (r=0.089; 95% CI, 0.0610–0.1163; p<0.0001), and prevalence of cerebral vascular disease (r=0.038; 95% CI, 0.0030–0.0732; p=0.034) were independently associated with graft dilation after surgery.

Conclusion: Prosthetic graft selection and appropriate sizing of the stent graft should be considered for each individual undergoing hybrid aortic surgery to maintain sufficient oversizing of the stent graft.

Objective: This study aims to determine the effect of grip exercise by the non-paretic hand on venous return in the paretic arm in stroke in sitting and supine positions.

Methods: The study population included 21 stroke patients (mean age, 59.5 years). The diameter (mm) and time-averaged mean velocity (TAMV) (cm/s) of the axillary vein on the paretic side were measured by ultrasound during three distinct conditions: resting, rhythmic non-resistive grip exercise, and resistive exercise (30% of maximum grip strength) in supine and sitting positions. The venous flow volume (ml/min) was calculated using the obtained data.

Results: In the supine and sitting positions, the venous flow volume during rhythmic non-resistive and resistive exercises was increased in comparison to resting, which resulted in more increased venous flow volume by rhythmic resistive grip exercise than by non-resistive grip exercise (both, p=0.01).

Conclusion: Grip exercise by the non-paretic hand was found to be effective for increasing the venous flow volume in the paretic hand, and resistive grip exercise caused the greatest increase. Our results suggest that rhythmic handgrip exercise may be clinically useful for reducing the incidence of hand edema in stroke patients.

An 80-year-old woman presented with abdominal and right lower limb pain. Radiological examination revealed pelvic arteriovenous malformations (pAVMs). Although transarterial embolization was repeated, dilation of the common iliac vein worsened. Four sessions of embolization were performed for the internal iliac vein. Paraplegia gradually occurred a day after the final procedure. Magnetic resonance imaging revealed thoracic spinal cord edema and paraspinal vasodilatation, suggesting spinal cord infarction. Additional angiography revealed a radiculomedullary vein draining into the spinal canal from the pAVM; hence, surgical interruption was performed. Incomplete venous embolization of the pAVM caused spinal cord congestion and infarction.

Endoleak is a major complication of endovascular aneurysm repair (EVAR). Type IIIb endoleaks, which are caused by endograft fabric disruption, are relatively rare. Although relining of the previously placed endograft with another main endograft is considered an ideal approach, it is sometimes difficult. The efficacy of parallel placement of Excluder legs has been reported in various settings. Here, we report the successful treatment of a type IIIb endoleak with parallel placement of Excluder legs during EVAR by using an AFX2 device.

A primary aorto-duodenal fistula (ADF), a rare, spontaneous development of a communication between the aorta and duodenum, is a disastrous complication of an abdominal aortic aneurysm. A 73-year-old patient with primary ADF underwent emergent endovascular aneurysm repair (EVAR), followed by staged omentopexy, without removing a stent graft (SG). The patient received long-term treatment with antibiotics, and there has been no evidence of infection during a follow-up period of three years. Emergency EVAR coupled with omentopexy, may be a treatment option for primary ADF, even when it means leaving the SG in a potentially infectious site.

Balloon expandable stents (BES), which are made of stainless steel, are vulnerable to external compression, leading to deformation or collapse/fracture of the stents. In this report, two cases of complete collapse of BES are presented. In both cases, BES were placed in a heavily calcified aorta and subsequently collapsed without any evidence of external compression. Repeated pulsation of heavily calcified aorta was presumed to be the cause of the stent collapse.

An asymptomatic 70-year-old man presented with Kommerell’s diverticulum (KD) and an aberrant left subclavian artery. Computed tomography revealed a KD diameter of 53 mm, severe aortic arch angulation, and no landing zone for thoracic endovascular aortic repair from the arch vessels to the diverticulum. We performed single-stage hybrid repair of KD of the right aortic arch, left carotid–left subclavian artery bypass, and embolization of the subclavian artery, followed by replacement of the descending aorta through deep hypothermic circulatory arrest via right thoracotomy. He was discharged home without any symptoms and remained uneventful at 1 year after the operation.

Iliac vein compression syndrome (IVCS) can occasionally be iatrogenic; however, iatrogenic IVCS cases occurring because of inappropriate length and positioning of vascular grafts have not been reported. We present the case of an 80-year-old woman with iatrogenic IVCS resulting from kinked and overlapping limbs of a bifurcated abdominal vascular prosthesis for an abdominal aortic aneurysm. She complained of discomfort in her left leg immediately after aortic replacement. Venous stenting was effective for IVCS occurring because of compression of the vascular prosthesis. Iatrogenic IVCS occurred because of inappropriate length and positioning of the vascular graft and was considered a postoperative complication.

Popliteal artery entrapment syndrome (PAES) is a rare disease. We treated siblings with this disease. An 18-year-old male consulted our hospital for intermittent claudication of the left lower limb. Contrast-enhanced computed tomography led to a diagnosis of type II PAES. After transection of the medial head of the gastrocnemius muscle, popliteal artery bypass was performed. His younger brother (6 years younger) was also diagnosed with type II PAES, and similar surgery was performed at the age of 19. These cases suggested the involvement of genetic factors in PAES in addition to embryological factors.

We report a case of a 79-year-old woman who experienced difficulty in walking. Contrast-enhanced computed tomography revealed severe stenosis and calcification of the infrarenal aorta. The minimum diameter of the infrarenal aorta was 8 mm and that of the common femoral artery was 4 mm. Other vessels with abnormalities were the hypoplastic left subclavian artery and the left-sided inferior vena cava. The patient was treated with right axillobifemoral bypass. In patients with small aorta syndrome, the graft patency rate is low, and long-term follow-up is important.

Since 2013, the Japanese Society for Vascular Surgery has started the project of nationwide registration and tracking database for patients with critical limb ischemia (CLI) who are treated by vascular surgeons. The purpose of this project is to clarify the current status of the medical practice for the patients with CLI to contribute to the improvement of the quality of medical care. This database, called JAPAN Critical Limb Ischemia Database (JCLIMB), is created on the National Clinical Database (NCD) and collects data of patients’ background, therapeutic measures, early results, and long-term prognosis as long as five years after the initial treatment. The limbs managed conservatively are also registered in JCLIMB, together with those treated by surgery and/or EVT. In 2017, 1137 CLI limbs (male 760 limbs: 67%, female 377 limbs) were registered by 84 facilities. ASO has accounted for 98% of the pathogenesis of these limbs. In this manuscript, the background data, ischemic status, treatment and the early prognosis (within 1 month) of the registered limbs are reported. (This is a translation of Jpn J Vasc Surg 2019; 28: 415–443.)