The validity and clinical usefulness of the sentinel node (SN) concept for breast cancer has been confirmed, and individualized limited surgery based on diagnosis of SN metastasis is presently performed. In the future, SN navigation surgery (SNNS) will be actively applied to the treatment of early gastric cancer, and an intraoperative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to detect SN micrometastasis of gastric cancer is under development. Not only anatomical factors, but also many other factors such as local immunosuppression in the SN and lymphoangiogenesis may be involved in development of SN micrometastasis, and clarification of the mechanisms of metastasis and development of treatment methods are awaited. (*English Translation of J Jpn Col Angiol 2008; 48: 137-142.)

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Lymphatics are a unidirectional transport system that carries fluid from the interstitial space and back into the blood stream. Initial lymphatics take up not only fluid but also high-molecular-weight substances, such as plasma proteins and hyaluronan; immune cells, such as lymphocytes, macrophages, and dendritic cells; and colloidal particles, such as carbon particles, bacteria, and tattoo dye. Interstitially injected colloidal particles are known to accumulate in the regional lymph nodes. This phenomenon is applied to find sentinel lymph nodes in cancer patients. Lymph flow rate and composition are influenced by interstitial fluid, lymphatic pump activity, and intra-lymphatic pressure. Lymph composition is changed during its flow downstream. In this review, the main focus is on the mechanisms of lymph formation at the initial lymphatics and lymph transport through the collecting lymphatics and lymph nodes. (*English Translation of J Jpn Coll Angiol, 2008, 48: 113-123.)

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We examined the immunohistochemical properties of selective lymph vessel markers such as LYVE-1, podoplanin, Prox-1, and VEGF R3, as well as NO synthase (NOS) and cyclo-oxygenase (COX) in two kinds of human lymphatic endothelial cell isolated from collecting and initial lymph vessels. The constitutively expressed genes in the two kinds of lymphatic endothelial cell were also evaluated using oligonucleotide microarray analysis and RT-PCR. We also investigated the effects of the oxygen concentration in culture conditions on the proliferative activities of the two kinds of human lymphatic endothelial cell. Immunoreactivity to LYVE-1 and the RT-PCR expression level of LYVE-1 mRNA in endothelial cells of initial lymph vessels were stronger than those of collecting lymph vessels. Immunoreactivity to ecNOS, iNOS, COX1, and COX2 was also found to be significantly higher than in collecting lymph vessels. In contrast, an increase in the O₂ concentration ranging from 5% to 21% caused a significant reduction in the proliferative activity of endothelial cells in collecting lymph vessels. In conclusion, these findings suggest that there exists a marked heterogeneity in the immunohistochemical, genomic, and proliferative activity of human lymphatic endothelial cells between initial and collecting lymph vessels. (*English Translation of J Jpn Coll Angiol, 2008, 48: 125-130.)

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Intestine has a well-developed lymphatic system that is closely related with its functions, such as mucosal immunological defense or absorption of nutrients. Intestinal lymphoid cells such as lymphocytes, macrophages/monocytes, or dendritic cells are continuously migrating through intestinal mucosa, thereby facilitating their immune responses. Their migrations are well controlled by well-organized molecular mechanisms including adhesion molecules, chemokines, etc. This manuscript will review how dysfunction of lymphoid cell migration is involved in intestinal inflammation, especially in the pathophysiology of intestinal bowel diseases. (*English Translation of J Jpn Coll Angiol 2008; 48: 143-149.)

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Cutaneous symptoms are observed in 25%-60% of polyarteritis nodosa (PN) patients. On the other hand, cutaneous polyarteritis nodosa (CPN) is designated for the cutaneous limited form of PN and demonstrates benign prognosis. However, there has been much debate on whether or not CPN can progress to PN. Although CPN lesions are fundamentally limited to skin, some CPN cases show extracutaneous symptoms such as peripheral neuropathy and myalgia. According to PN diagnostic criteria, a disease with both cutaneous and at least one extracutaneous symptom with appropriate histopathological findings can be diagnosed as PN. The same is true according to diagnostic criteria established by American College of Rheumatology (ACR). In addition, there are no specific diagnostic criteria for CPN. In this study, CPN cases were retrospectively collected from multiple Japanese clinics, and analyzed for detailed clinical and histopathological manifestations, in order to redefine the clinical entity of CPN and to propose appropriate diagnostic criteria for CPN and PN. According to the CPN description in Rook’s Textbook of Dermatology, one of global standard textbooks, we collected 22 cases with appropriate histopathological findings. Of the 22 cases, none progressed to PN or death during the follow-up period, 32% had peripheral neuropathy, and 27% had myalgia. Regarding extracutaneous symptoms with CPN, 17 dermatological specialists in vasculitis sustained the opinion that CPN can be accompanied by peripheral neuropathy and myalgia, but these symptoms are limited to the same area as skin lesions. Based on these results, we devised new drafts for CPN and PN diagnostic criteria. Our study shows the efficacy of these criteria, and most dermatologists recognized that our new diagnostic criteria for CPN and PN are appropriate at the present time. In conclusion, this study suggests that CPN does not progress to PN, and introduces new drafts for CPN and PN diagnostic criteria. (*English Translation of J Jpn Coll Angiol 2009; 49: 87-91.)

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The epidemiology of ANCA-associated vasculitis is substantially different between Caucasians and Japanese, which may be related to differences in genetic backgrounds. In this review, I discussed our findings on the genetics of microscopic polyangiitis (MPA) in Japanese. Analysis of HLA genes revealed a significant increase in the HLA-DRB1*09:01-DQB1*03:03 haplotype MPA. This is one of the most frequent haplotypes in Japanese, but is nearly absent in Caucasians, and has been shown to be associated with multiple autoimmune diseases.Analysis of KIR genes revealed significant decreases in the carrier frequency of an activating receptor KIR2DS3 in MPA. When KIRs were analyzed in combination with HLA ligands, the proportion of individuals carrying KIR3DL1 and HLA-Bw4 but not KIR3DS1, the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in MPA. These results suggested that decreased activation of NK and/or T cells may cause a predisposition to MPA.LILRA2 is an activating receptor involved in granulocyte and macrophage activation. LILRA2 SNP rs2241524 G >A, which disrupts the intron 6 splice acceptor site, was significantly associated with MPA. The risk allele produces an LILRA2 isoform lacking three amino acids in the linker region.These findings, when confirmed by larger-scale studies, will shed light on the molecular mechanisms of MPA. (*English Translation of J Jpn Coll Angiol 2009; 49: 31-37.)

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Transgenic rats carrying the env-pX gene of human T-cell leukemia virus type I (env-pX rats) develop necrotizing angiitis resembling human polyarteritis nodosa (PN). In the development of vasculitis in these rats, the thymus plays an important role. In this review, we provide an outline of the pathogenesis of vasculitis observed in env-pX rats, and discuss the developmental mechanism of human necrotizing angiitis such as PN with an unknown cause. (*English Translation of J Jpn Coll Angiol 2009; 49: 17-20.)

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In 1878, Winiwarter used a microscope and reported a case of 57 year-old man demonstrating Buerger disease. After that, 134 years passed. Leo Buerger and Edgar V. Allen strongly suggested that Buerger disease is an infectious disease without any doubt. Also, an etiologic point is the luminal infectious thrombus, which is thought to be the core of the disease. Many etiological factors were proposed and then discarded after academic scrutiny, but two big discoveries were made in 2005 and 2008. Namely, periodontal bacteria DNA was found in the occluded arteries of 93% of patients with Buerger disease, and periodontal bacteria (typical weak bacteria) were found to dwell in the platelets. Using these evidences, supported by genetic and epidemiological facts, we could almost explain the pathogenesis or clinical course of Buerger disease, which had been already studied.

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Despite improved outcomes of acute type A aortic dissection (AAAD), many patients die at the moment of onset, and hospital mortality is still high. This article reviews the latest literature to seek the best possible way to optimize outcomes. Delayed diagnosis is caused by variation in or absence of typical symptoms, especially in patients with neurological symptoms. Misdiagnosis as acute myocardial infarction is another problem. Improved awareness by physicians is needed. On arrival, quick admission to the OR is desirable, followed by assessment with transesophageal echocardiography, and malperfusion already exists or newly develops in the OR; thus, timely diagnosis without delay with multimodality assessment is important. Although endovascular therapy is promising, careful introduction is mandatory so as not to cause complications. While various routes are used for the systemic perfusion, not a single route is perfect, and careful monitoring is essential. Surgical treatment on octogenarians is increasingly performed and produces better outcomes than conservative therapy. Complications are not rare, and consent from the family is essential. Prevention of AAAD is another important issue because more patients die at its onset than in the following treatment. In addition to hereditary diseases, including bicuspid aortic valve disease, the management of blood pressure is important.

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Objective: In patients with isolated soleal vein thrombosis (SVT), the relation between acute thrombi and positive anti-nuclear antibody (ANA) was investigated.
Subjects and Methods: The subjects were 116 lower extremities in 86 patients with SVT. They were diagnosed and examined by ultrasonography and blood serum analysis (D-dimer, ANA), and had been followed up every three months.
Results: They had acute SVT in 35 limbs (30%) and chronic SVT in 86 limbs (70%), and they had positive ANA in 63%. They had recurrent SVT in 26%, and all were positive for ANA.
Conclusion: ANA-positivity might be a risk factor for acute thrombi in patients with SVT. (English Translation of J Jpn Coll Angiol 2010; 50: 417-422.)

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To prevent pulmonary embolism due to deep venous thrombosis (DVT), we have treated 611 patients undergoing orthopedic surgery of the lower extremities with our protocol including pre- and postoperative ultrasonic venous screening and anticoagulant therapy if necessary. A total of 118 patients (19.3%) developed DVT. Among demographic and clinical factors, the site of operation (knee joint surgery: odds ratio 5.17), age (>60: odds ratio 3.91), and operation time (>120 minutes: odds ratio 4.52) were identified as significant risk factors of development of DVT. One patient received an infusion of urokinase for DVT of femoral vein, but no patients developed serious postoperative bleeding or pulmonary thromboembolisms. (*English Translation of J Jpn Coll Angiol, 2010, 50: 95-100.)

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Purpose: We have reviewed ruptured and nonruptured infected aortoiliac aneurysms to study the clinical presentation, management and eventual outcome of patients managed with in situ prostheses, axillo-femoral prostheses grafts and endovascular reconstruction.
Design: A retrospective chart review of 16 cases treated at a single institution.
Methods: From January 2007 to March 2008, a total of 93 patients with aortoiliac aneurysms underwent surgical repair at our institution. Among these, 16 patients (17.2%) were shown to be infected aneurysms of the infrarenal (n = 6), juxtarenal (n = 2), and pararenal aorta (n = 1); the others were 5 common, 1 external, and 1 internal iliac arteries. Fourteen patients were male and 2 were female with the mean age of 66 years (range, 45-79). In all cases, the diagnosis was confirmed by abdominal computed tomography and empirical parenteral antibiotics were administered at least 1 week, unless in patients need emergency operations. At the time of an operation, all were saccular and were classified as primary infected aortoiliac aneurysms. Thirteen patients had surgical debridement with in situ graft interposition and omental wrapping, 2 underwent aneurysm exclusion and extra-anatomic (axillo-femoral) bypass, 1 underwent aneurysmectomy of left external iliac artery and polytetrafluoroethylene (PTFE) graft interposition, and 1 underwent endovascular exclusion. The parenteral antibiotics were continued in the postoperative period for 4-6 weeks. Chronic renal disease was present in 37.5% (6/16), with diabetes mellitus present in 31.25% (5/16). The most common pathogen was Salmonella sp. (n = 6) and E. coli (n = 5). Thirty-seven percent (6/16) of the patients presented late, with a 37.5% (6/16) incidence of ruptured (4 contained, 2 free ruptured) that needed emergency surgery.
Results: Disease-specific mortality was 31.25% (5/16). The 30-day mortality rate of ruptured cases is high 67% (4/6), because patients present late in the course of the disease. One patient who underwent aneurysm exclusion and extra-anatomic (axillo-femoral) bypass died 6 months later from burst aortic stump. Salmonella and E. coli are the most common pathogens.
Conclusions: Early diagnosis followed by surgical intervention with proper antibiotic coverage provides the best results. Mortality rate was still high in patients with sepsis and rupture. An in situ graft interposition and omental wrapping is a safe option for revascularization of infected aneurysms of the iliac arteries and infrarenal aorta.

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Objectives: To clarify interface pressures (IP) derived from class II and III oversize stockings.
Methods: Healthy volunteers with legs fitting size S (n = 10), M (n = 6), or L (n = 6) stockings wore class II and III stockings of various sizes up to 5L. IPs were measured in the supine and the standing position with each stocking on.
Results: In the subjects with size S legs, the IPs in the standing position while wearing S and M class III stockings were 43.5 ± 4.7 and 40.4 ± 5.4 mmHg respectively. These IPs were significantly higher than the IP while wearing the S size class II stocking (33.3 ± 5.9 mmHg). IPs derived from L, LL, 3L, 4L, 5L class III stockings were not significantly different from IP with the S size class II stocking. The results were similar for the subjects with size M legs while wearing the size M and L class III stockings and for the subjects with size L legs while wearing the size L and LL class III stockings vs. the appropriate size class II stocking.
Conclusion: Based on these findings, a larger size class III stocking can provide similar or even higher IPs compared to an appropriate size class II stocking.

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Objectives: To evaluate the interface pressure (IP) and stiffness of our elastic multilayer bandages (eMLB).
Methods: Three medical staff wrapped the legs of 10 healthy volunteers with one to six rolls of elastic bandages. The IP was measured at the medial aspect of the lower leg at the level of transposition of the medial gastrocnemius muscle into the Achilles tendon (level of B1) with the patient supine and then standing, for each number of bandages worn. The static stiffness index (SSI) was calculated as a difference between these IPs.
Results: The IPs in the standing position increased linearly for up to five bandages (21.8 ± 7.2, 32.5 ± 6.1, 41.8 ± 8.5, 52.0 ± 10.4, 60.3 ± 11.8, and 66.7 ± 13.4 mmHg, with one to six bandages). SSI also increased linearly for up to five bandages (6.8 ± 5.1, 10.2 ± 4.8, 13.4 ± 7.2, 17.4 ± 8.8, 19.7 ± 9.1, and 20.4 ± 9.4 mmHg, with one to six bandages). No significant technical variation in the IP was observed among the three operators.
Conclusions: Our eMLB provided stable, predictable and sufficient IPs and SSIs in healthy volunteers.

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Objective: A less invasive method to assess internal thoracic artery (ITA) graft function after coronary artery bypass grafting (CABG) is desired. This study reports the novel method to estimate ITA graft function using CT angiography.Materials and Methods: Fifty ITA grafts were assessed. Hounsfield Unit transition of each graft on the same cross section was detected during the Test Bolus Injection, which led to the making of a time density curve (TDC), for each ITA. Variables from the TDC were compared statistically with data obtained from Pulse Doppler Echo (PDE), the best indicator of graft function, of ITA grafts.Results: The ascending slope of the TDC was significantly associated with the following PDE data: Velocity time integral (VTI), VTI x Heart Rate (HR) and Mean Flow of ITA graft. A multivariate analysis showed an especially strong relationship with the ascending slope of the TDC and VTI x HR (R² = 0.588).Conclusion: The ascending slope of the TDC means the concentration transition of contrast media, which may be affected by the blood stream in the ITA graft. This study suggests the possibility of the ability to assess ITA graft function by CT angiography.

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Background: Subfascial endoscopic perforator surgery (SEPS) with a two-port system utilizing screw-type ports, CO₂ insufflation and an ultrasonic coagulation system, is a useful procedure that does not require burdensome apparatus and techniques. SEPS was accepted as a national advanced medical system by the Japanese Ministry of Health, Labor and Welfare in May 2009.Patients and Methods: Forty-one limbs of 35 patients with 10 active ulcers (C6) and 2 healed ulcers (C5) were treated by SEPS between February 2010 and December 2011. Thirty-three limbs had concomitant superficial vein surgery. SEPS alone was performed on 8 limbs, in 6 of which the superficial veins had already been ablated. In 2 limbs, incompetent perforating veins (IPVs) existed under the affected skin, around the scars of past surgery.Results: All stasis ulcers of the 10 C6 limbs healed between 1 week and 14 months after SEPS (mean 2.9 months), with no ulcer recurrence during the follow-up period (2 to 24 months). IPVs under the scars were easily and safely interrupted by SEPS.Conclusion: SEPS is a very useful component of a comprehensive treatment program for chronic venous insufficiency, especially in patients with venous stasis ulcers and IPVs under the scars of past surgery.

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Background: Peripheral arterial disease (PAD) has been recognized as an independent risk factor for vascular events and contributes to an adverse prognosis. Long-term administration of clopidogrel is recommended to prevent atherothrombotic events for patients with established PAD. We investigated the benefits of clopidogrel treatment in Japanese patients with PAD.
Materials and Methods: COOPER (Clopidogrel for atherOthrombOtic event management in patients with PERipheral arterial disease) was a multicenter, randomized, double-blind study to evaluate the safety and efficacy of clopidogrel (75 mg/day) compared to ticlopidine (200 mg/day) in Japanese patients with PAD. The primary endpoint was the cumulative incidence of “safety events of interest” comprising clinically significant bleeding, blood disorders, hepatic dysfunction and other serious adverse events up to 12 weeks. The other safety events and vascular events were also assessed. Patients were followed up to 52 weeks.
Results: A total of 431 patients with PAD were randomly assigned to receive either clopidogrel or ticlopidine. The cumulative incidences of “safety events of interest” at 12 weeks were 2.4% and 13.6% of patients who received clopidogrel and ticlopidine, respectively (adjusted hazard ratio, 0.161; 95% confidence interval, 0.062 to 0.416; p <0.0001). Bleeding and vascular events were similar in both groups.
Conclusion: Clopidogrel demonstrated a favorable benefit/risk profile than ticlopidine in Japanese patients with PAD.(Trial registration: ClinicalTrials.gov, Identifier: NCT00862420)

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Renal cell carcinoma is a tumor with the distinct feature that it can invade through the renal vein into the inferior vena cava, and can grow intravascularly, sometimes extending into right cardiac chambers. Surgical resection provides the only reasonable chance for a cure, and cardiopulmonary bypass with hypothermic circulatory arrest is used to resect an intracardiac extension of the tumor because the tumor-thrombus adhered strongly to the hepatic vein and to the endocardium of the right atrium (RA). We present 2 patients, with renal cell carcinoma extending into the right ventricle, who have lived for more than five years after the operation.

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A pulmonary varix is a localized dilatation of a pulmonary vein, which is usually asymptomatic presented as a mass on a chest roentgenogram, and diagnosed with pulmonary angiography. We encountered a case of 55 year-old man, in whom incidentally identified was a dilated blood vessel that passed through the minor fissure and returned to the inferior pulmonary vein, which we diagnosed as pulmonary varix. This vascular anomaly was accompanied by the occluded superior pulmonary vein, highly suggestive of the developmental mechanism of this disease.

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A 47 year-old man, presenting with sudden back pain in the absence of abdominal discomfort, was diagnosed with acute type B aortic dissection which extended to the celiac and the splenic arteries. Antihypertensive treatment was initiated. However, he subsequently complained of upper abdominal pain with increased amylase levels. Computed tomography scan (CT) revealed new accumulation of peripancreatic fluid with no signs of further aortic or visceral dissection. A protease inhibitor was administered for mild acute pancreatitis. Follow-up CT demonstrated disappearance of thrombosed false lumen of the splenic artery and reduction of the effusion. The patient was discharged without any surgical interventions.

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The patient was a 41 year-old Chinese female, a known intravenous drug abuser (IVDA), who presented with a left inguinal discharging sinus. A computed tomography (CT) scan showed inflammation in the left groin involving the left femoral vein and resulting in thrombus within the iliac veins extending to the distal portion of the inferior vena cava.Septic deep vein thrombosis is a well-recognized complication in intravenous drug abusers (IVDA) when large proximal veins are used for drug injection. Life threatening complications such as septic pulmonary embolism and right sided infective endocarditis may result.The aims of treatment are to prevent the septic thrombus from further embolisation and also to remove the thrombus. Treatment options include catheter directed thrombolysis, mechanical thrombectomy, endovascular treatment, surgical thrombectomy and excision of the involved venous segment.In our patient, we have opted for open surgical thrombectomy without excision of the involved venous segments.

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