Hiroshi Narita

Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits

BACKGROUND Neointimal hyperplasia is strikingly suppressed in an endothelium injury model in mice deficient in the growth factor midkine. Knockdown of midkine expression by means of antisense oligonucleotide or small interfering RNA has been shown to lead to suppression of neointimal hyperplasia in a balloon injury model and a rabbit vein graft model; therefore, midkine is an essential factor for neointimal hyperplasia. These findings, however, do not necessarily apply to the function of midkine in vascular stenoses such as in-stent restenosis, because human vascular stenosis is often accompanied by atherosclerosis. METHODS We investigated midkine expression in the neointima induced by implantation of a bare metal stent in the atheromatous lesions of hypercholesterolemic rabbits. We analyzed midkine expression during a THP-1 cell differentiation and in peritoneal macrophages exposed to low-density lipoprotein or oxidized low-density lipoprotein. RESULTS Midkine expression reached the maximum level within 7 days after stenting and was detected in infiltrating macrophages. Differentiation of THP-1 cells to macrophage-like cells did not trigger midkine expression. Neither low-density lipoprotein nor oxidized low-density lipoprotein enhanced midkine expression in peritoneal macrophages that had been activated by thioglycollate, although these cells expressed a significant amount of midkine. CONCLUSION The results indicate that macrophages are the major source of midkine in the atherosclerotic neointima. The amount of midkine expressed in macrophages may be sufficient (ie, further enhancement of the expression is not necessary) for the pathogenesis, because oxidized low-density lipoprotein stimulation did not induce the midkine expression. CLINICAL RELEVANCE The growth factor midkine is induced during vascular stenosis in mouse and rat models with normal diet. Knockdown of midkine expression suppresses neointimal hyperplasia. The vascular response after stenting differs from that after balloon injury in that the inflammation is more prolonged and the accumulation of macrophages is more abundant in stent-injured vessel. We found here that macrophages are the major source of midkine in the atherosclerotic neointima of in-stent restenosis in hypercholesterolemic rabbits. Our data suggest that midkine has an important role in in-stent restenosis of atherosclerotic vessels and is a candidate molecular target to prevent in-stent restenosis.

Primary Malignant Fibrous Histiocytoma of the Ileum: Report of a Case

Abstract We report herein a case of primary malignant fibrous histiocytoma (MFH) of the ileum. A 71-year-old Japanese man was admitted to our hospital with symptoms of abdominal pain and anorexia. Computed tomography, magnetic resonance imaging, a follow-through study of the small intestine, and angiography all demonstrated a tumor of the ileum suggestive of a primary malignancy. A partial resection of the ileum was performed. It was histopathologically and immunohistochemically diagnosed to be a storiform-type primary MFH of the ileum with peritoneal dissemination. There have been a total of 25 cases of primary small bowel MFH documented in the Japanese or Western literature including our case. The malignant potential of such tumors is high, and the prognosis tends to be very poor. Unfortunately, we could not conclude whether the poor outcome was due to a delayed diagnosis or instead to its biological malignant behavior, since the number of such reported cases is still too small to make any definitive conclusions.

Subclavian Artery Aneurysm in Marfan Syndrome

We present a case of a left subclavian artery aneurysm in a 48-year-old man with Marfan syndrome. Aneurysms of the subclavian artery are rare in patients with Marfan syndrome. Resection of the aneurysm and interposition with a synthetic graft were performed through a supra- and infraclavicular incision, without resecting the clavicle. Histological findings were compatible with Marfan syndrome. In patients with Marfan syndrome, regular follow-up is important because of the occurrence of peripheral aneurysms other than the aorta.

Validation of Patient Selection for Endovascular Aneurysm Repair or Open Repair of Abdominal Aortic Aneurysm – Single-Center Study –

BACKGROUND To validate the criteria for endovascular aneurysm repair (EVAR) or open repair of abdominal aortic aneurysm (AAA) at Nagoya University Hospital, the results of both treatments were retrospectively compared. METHODS AND RESULTS Patient selection for EVAR was primarily based on suitable anatomy, minimum age 75 years, and significant comorbidity. From June 2007 to April 2014, 426 patients were treated via EVAR (EVAR group) and 346 patients were treated with open surgery (OS group). The mortality rates of the EVAR and OS groups were not significantly different (0.2% vs. 1.1%; P=0.33). Patient age, operation time, amount of bleeding, and duration of hospital stay were significantly lower in the EVAR group compared with the OS group. The incidence of comorbidity was higher in the EVAR group compared with the OS group. The incidence of early postoperative complications was significantly higher in the OS group, whereas the incidence of late complications for both groups was similar. The cumulative aneurysm-related survival rates were similar (98.9% vs. 98.5%; P=0.767). The cumulative survival rates and reintervention-free rates at 5 years were lower for the EVAR group (76% vs. 89%, P=0.019; 81% vs. 89%, P=0.046). CONCLUSIONS Patient selection practices and criteria for EVAR and open repair at Nagoya University Hospital are generally acceptable.

Evaluation of the efficacy of venous thromboembolism prophylaxis guideline implementation in Japan.

PurposeIn Japan, the incidence of venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been relatively low; however, the incidence has recently been increasing. Since April 2004, we have developed an original computer-linked VTE prophylaxis in order to decrease the incidence of in-hospital VTE. Our objective has been to evaluate the efficacy of the VTE prophylaxis guideline.MethodsA retrospective pre- and postintervention study was conducted (preintervention phase, n = 17 854; postintervention phase, n = 26 831). Data were obtained from the clinical records of patients who underwent vascular surgery and were screened for DVT at our institution.ResultsThe frequency of patients screened for DVT increased significantly from 70 (0.4%) to 209 (0.8%) after the establishment of a guideline (P < 0.001). Asymptomatic DVT patients increased from 5 (12.5%) in the control group to 33 (50.0%) in the intervention group (P < 0.0001), while symptomatic DVT events with leg swelling decreased from 29 (72.5%) to 16 (24.2%) (P < 0.0001). Furthermore, shock and massive PE events were significantly lower (from 31.3% to 0%; P < 0.05).ConclusionOur VTE prophylaxis guidelines are considered to be useful for the detection of asymptomatic DVT patients during hospitalization, thus leading to a significantly lower incidence of postoperative VTE.