ヒト動脈硬化性大動脈瘤におけるマトリックスメタロプロテアーゼ: その発現・局在と大動脈瘤形成における役割

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1171号, 学位授与年月日：平成7年3月25日,学位授与年：199

Endoscopic thoracic sympathicotomy for Raynaud's phenomenon

AbstractPurpose: For many years, thoracic sympathectomy via open surgery was not used to treat Raynaud's phenomenon because of the invasiveness of this procedure and the poor long-term outcomes associated with it. However, with the introduction of endoscopic surgery, thoracic sympathectomy (or sympathicotomy) has been performed by some surgeons as a less invasive surgical option for patients with Raynaud's phenomenon. The less invasive procedure has the possibility of emphasizing merits of sympathectomy. The purpose of this study was to reevaluate the efficacy of sympathicotomy for Raynaud's phenomenon with endoscopic technique and its range of applicability. Methods: Between December 1992 and August 2001, endoscopic thoracic sympathicotomy (ETS) was performed in 28 patients with Raynaud's phenomenon (of a total of 502 patients with autonomic disorders who underwent ETS) at National Kanazawa Hospital. We considered indications for surgical treatment of Raynaud's phenomenon to include severe chronic symptoms or nonhealing digital ulceration refractory to intensive medical therapy. All patients were mailed a self-assessment questionnaire after surgery to determine the immediate and long-term results of the procedure. Data from both initial and long-term follow-up examinations were obtained. Results: Fifty-four ETS procedures were performed in 28 patients. No operative mortality was seen, and no occurrence of major complications necessitated open surgery. Initial resolution or improvement of symptoms was achieved in 26 of 28 patients (92.9%). However, later in the postoperative period, symptoms recurred in 23 of 28 patients (82.1%), although no recurrence of digital ulceration was seen throughout our observation. At the final follow-up examination (median follow-up period, 62.5 months), 25 patients (89.3%) reported overall improvement of the frequency and severity of their symptoms. Conclusion: Despite the high rate of recurrence, ETS clearly produced a high rate of initial relief. ETS did indeed promote healing of digital ulcers, and the procedure shows potential for reducing the severity of refractory symptoms. We consider ETS to be the method of choice for treatment of severe or refractory Raynaud's phenomenon, and especially for Raynaud's involving digital ulcer, because of its safety and efficacy. (J Vasc Surg 2002;36:57-61.

A clinicopathologic study of immunoglobulin G4-related disease of the femoral and popliteal arteries in the spectrum of immunoglobulin G4-related periarteritis

BackgroundImmunoglobulin (Ig) G4-related disease has recently been recognized to occur in the cardiovascular system in the aorta and main branching arteries, often manifesting as aneurysms and arteritis/periarteritis. Peripheral arteries (the femoral and popliteal arteries) are frequent sites of arteriosclerosis obliterans (ASO) and occasionally show aneurysms or arteritis. This study re-examined peripheral arterial lesions from the standpoint of IgG4-related disease.MethodsThe study comprised 104 patients who underwent surgical treatment of peripheral arterial lesions, including 30 patients with peripheral arterial aneurysms (PAAs) and 74 with ASO. IgG4-related disease was identified on the basis of diffuse infiltration of numerous IgG4-positive plasmacytes as revealed by immunohistochemical examination. Clinicopathologic features were compared between IgG4-related and IgG4-unrelated lesions.ResultsIgG4-related disease was found in four of the 30 patients with PAAs (13.3%; two in the deep femoral artery, two in the popliteal artery) but not in any patients with ASO. IgG4-related PAA displayed clinicopathologic features resembling those of other IgG4-related diseases and a characteristic saccular appearance (P = .002).ConclusionsIgG4-related disease was detected in PAA patients but not in ASO patients. IgG4-related disease thus represents one potential etiology of aneurysm in the peripheral arteries.Clinical RelevanceThis study elucidated that immunoglobulin (Ig) G4-related vascular lesions can involve the femoral and popliteal arteries in addition to the aorta and main branching arteries. IgG4-related disease in the peripheral arteries was characterized by the saccular form aneurysm and was similar to the clinicopathologic characteristics of other IgG4-related vascular lesions. The recognition that IgG4-related disease can also involve the peripheral arteries may lead to a better understanding of IgG4-related vascular lesions and an important caution for the use of steroids for treating IgG4-related disease in other organs

Disordered Balance of T‐Cell Subsets in Arterial Tertiary Lymphoid Organs in Immunoglobulin G4–Related Vascular Disease

Background Arterial/aortic tertiary lymphoid organs (ATLOs), characterized by germinal centers, control local arterial immune responses. T follicular helper cells (Tfh), resident in germinal centers, regulate immunoglobulin production and germinal center development. They consist of Tfh1, Tfh2, and Tfh17 subsets. T follicular regulatory (Tfr) cells possess suppressive functions as regulatory T cells and migrate into germinal centers. Immunoglobulin G4 (IgG4)–related diseases manifest in vascular lesions as frequently formed inflammatory aneurysms (IgG4‐related abdominal aortic aneurysm [IgG4‐AAAs]). IgG4‐AAAs contain several ATLOs. Methods and Results We performed whole‐slide immunohistochemical image analysis in surgical specimens of IgG4‐AAAs (n=21), non–IgG4‐related inflammatory AAAs (n=17), atherosclerotic AAAs (n=10), and Takayasu arteritis (n=5). IgG4‐AAA was characterized by numerous, large, irregular‐shaped ATLOs, and higher numbers of Tfr and Tfh2 cells than Tfh1 cells were present compared with others. The morphologic abnormalities (in number, area, and form) of ATLOs in IgG4‐AAAs and the increased number of Tfr cells are closely related to the activity of IgG4‐related diseases. All T‐cell subsets were more enriched within ATLOs than outside ATLOs. In particular, an increase in Tfr cells in IgG4‐AAAs was associated with ATLO formation. Increased Tfh17 cells were found in Takayasu arteritis, and atherosclerotic AAA and non–IgG4‐related inflammatory AAAs were characterized by increased Tfh1 cells. Conclusions In the classification of vascular lesions, considering the imbalance in T‐cell subsets, IgG4‐AAA should be positioned as adventitial vasculitis with predominant Tfr and Tfh2 cells, accompanied by the abnormal appearance of ATLOs