Clinicopathological features of immunoglobulin G4-related constrictive pericarditis.

AIM: Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. METHODS: Among 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. RESULTS: Compared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. CONCLUSIONS: Pericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.

Long-Term Outcomes of Endovascular Aneurysm Repair in Patients Aged ≤70 Years.

Objectives: The efficacy of endovascular aneurysm repair (EVAR) against abdominal aortic aneurysm (AAA) in younger patients remains unknown. Hence, the current study aimed to investigate whether the aneurysm-related mortality rate of EVAR is acceptable among patients aged ≤70 years. Methods: Among 644 patients, 148 underwent EVAR (EVAR group), and 496 received open surgical repair (OSR group). The cumulative incidence rates of aneurysm-related death, any intervention, and serious aneurysm-related events after AAA repair were evaluated using the cumulative incidence function in the presence of competing risks. Results: The EVAR group had higher prevalences of several comorbidities, and overall survival for the EVAR group was significantly inferior to that of the OSR group. The cumulative incidence rates of aneurysm-related death, any intervention, and serious aneurysm-related events at 5 years were 1.5%, 11.7%, and 6.4% in the EVAR group and 1.3%, 5.3%, and 5.9% in the OSR group, respectively. EVAR was not a significant prognostic factor of aneurysm-related mortality and serious aneurysm-related events. However, it was an independent poor prognostic factor of any intervention. Conclusion: EVAR was not a significant prognostic factor of aneurysm-related mortality and serious aneurysm-related events. Therefore, it demonstrated acceptable procedure-related long-term outcomes, at least in high-risk young patients.

Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

BACKGROUND: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version.Methods and Results: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. CONCLUSIONS: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

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.

One Year Outcomes of Zilver PTX Versus Eluvia for Femoropopliteal Disease in Real-World Practice: REALDES Study.

PURPOSE: This multicenter, prospective, observational study aimed to compare Zilver PTX and Eluvia stents in real-world settings for treating femoropopliteal lesions as the differences in the 1-year outcomes of these stents have not been elucidated. MATERIALS AND METHODS: Overall, 200 limbs with native femoropopliteal artery disease were treated with Zilver PTX (96 limbs) or Eluvia (104 limbs) at 8 Japanese hospitals between February 2019 and September 2020. The primary outcome measure of this study was primary patency at 12 months, defined as a peak systolic velocity ratio of ≤2.4, without clinically-driven target lesion revascularization (TLR) or stenosis ≤50% based on angiographic findings. RESULTS: The baseline clinical and lesion characteristics of Zilver PTX and Eluvia groups were roughly comparable (of all limbs analyzed, approximately 30% presented with critical limb-threatening ischemia, approximately 60% presented with Trans-Atlantic Inter-Society Consensus II C-D, and approximately half had total occlusion), except for the longer lesion lengths in the Zilver PTX group (185.7±92.0 mm vs 160.0±98.5 mm, p=0.030). The Kaplan-Meier estimates of primary patency at 12 months were 84.9% and 88.1% for Zilver PTX and Eluvia, respectively (log-rank p=0.417). Freedom from clinically-driven TLR rates were 88.8% and 90.9% for Zilver PTX and Eluvia, respectively (log-rank p=0.812). CONCLUSIONS: The results of the Zilver PTX and Eluvia stents were not different regarding primary patency and freedom from clinically-driven TLR at 12 months after treating patients with femoropopliteal peripheral artery disease in real-world settings. CLINICAL IMPACT: This is the first study to reveal that the Zilver PTX and Eluvia have similar results in real-world practice when the proper vessel preparation is performed. However, the type of restenosis in the Eluvia stent may differ from that in the Zilver PTX stent. Therefore, the results of this study may influence the selection of DES for femoropopliteal lesions in routine clinical practice.

Immunoglobulin G4-related solitary aneurysm of the deep femoral artery.

We have reported the case of an 83-year-old man with a rare immunoglobulin G4 (IgG4)-related solitary deep femoral artery aneurysm. The patient successfully underwent aneurysmectomy and vascular reconstruction with an expanded polytetrafluoroethylene graft. A definitive diagnosis was determined from the comprehensive diagnostic criteria, including histopathologic features of chronic inflammation indicated by massive infiltration of IgG4-positive plasma cells. IgG4-related aneurysmal diseases should be included in the differential diagnosis of deep femoral artery aneurysms, which have traditionally been considered to develop owing to previous trauma or surgery, intervention, infection, and autoimmune or collagen disease.

Ultrasonic Wave Pericardiectomy for IgG4-Related Constrictive Pericarditis.

An 80-year-old woman presented with rare immunoglobulin G4 (IgG4)-related constrictive pericarditis. She underwent pericardiectomy, pericardiotomy, and crosshatching incision of the epicardium using an ultrasonic wave scalpel suitable for the feature of IgG4-related disease. Thereafter, her cardiac function improved remarkably. Additional corticosteroid therapy contributed to maintaining her healthy condition. Definitive diagnosis was based on novel organ-specific criteria. Herein, we highlight that the most important point in the pathological diagnosis of IgG4-related constrictive pericarditis is to determine the presence of IgG4-positive plasma cell infiltration and storiform fibrosis or obstructive phlebitis specific to chronic inflammation.

Exacerbation of immunoglobulin G4-related inflammatory abdominal aortic aneurysm after endovascular repair.

A 78-year-old male was admitted to our hospital with lumbar pain and was found to have an abdominal aortic aneurysm (AAA) and femoral artery aneurysm (FAA). Initially, the patient underwent endovascular aneurysm repair (EVAR) for the AAA and aneurysmectomy for the FAA. The FAA was diagnosed by histology as immunoglobulin G4-related disease (IgG4-RD). The preoperative serum IgG4 level was within the normal range, although a slight serum interleukin-6 (IL-6) elevation was observed. Four years later, the AAA-sac diameter had expanded and the serum levels of both IgG4 and IL-6 levels had increased. Six years after the initial EVAR, aneurysmorrhaphy of AAA-sac was performed. The resected specimen revealed adventitial fibrosis and prominent lymphoplasmacytic infiltrate with regulatory T cells, satisfying histological diagnostic criteria for IgG4-RD. Immunoreactive matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and IL-6 were detected within numerous spindle cells in the adventitia of both the FAA and the AAA-sac. Five months after the aneurysmorrhaphy, the residual AAA-sac was again enlarged with a thickened wall that accumulated [18 F] fluoro-2-deoxy-D-glucose (FDG-PET) on positron emission tomography; these findings were paralleled by increased levels of serum IgG4 and IL-6. Therefore, persistent inflammation after EVAR may be attributed to the inflammatory sequelae of IgG4-RD.

Adventitial matrix metalloproteinase production and distribution of immunoglobulin G4-related abdominal aortic aneurysms.

OBJECTIVE: IgG4-related diseases are systemic inflammatory fibrous lesions characterized by elevated serum IgG4 and infiltration of IgG4-positive plasmacytes. They can manifest in vascular lesions as frequently formed aneurysms with prominent thickening of the adventitia (IgG4-related abdominal aortic aneurysm; IgG4-AAA). Matrix metalloproteinases (MMPs) degrade the extracellular matrix, mainly in the tunica media, resulting in destruction of aortic structures to cause enlargement of the aneurysm. However, the expression of adventitial MMPs in IgG4-AAAs is poorly understood. METHODS: MMPs and MMPs-presenting cells in the adventitia of IgG4-AAAs (n = 19) of human surgical specimens were evaluated by immunohistochemistry and dual messenger RNA in situ hybridization. The results were compared with those from control groups of non-IgG4-related inflammatory AAA (n = 18), atherosclerotic AAA (aAAA; n = 11), and autopsy cases (n = 11). Preoperative serum MMPs levels of these groups were compared with the histologic data. RESULTS: Expression of MMP-9, MMP-2, and MMP-14 at the protein and messenger RNA levels in the adventitia was significantly higher in IgG4-AAAs than in controls. Other MMPs were scarce. The total number of MMP-9-positive cells was positively correlated with the diameter of the aneurysm (R = 0.461; P = .031), the adventitial thickness (R = 0.688; P < .001), and the number of IgG4-positive cells (R = 0.764; P < .001). Within lymphoid follicles, MMP-9-presenting cells were predominantly detected in large follicular dendritic cells, followed by histiocytes, fibroblasts, and plasmacytic dendritic cells. Outside lymphoid follicles, fibroblasts, and histiocytes mainly expressed MMP-9, and tissue dendritic cells also produced MMP-9. The levels of MMP-9 derived from follicular dendritic cells and histiocytes and plasmacytic dendritic cells outside lymphoid follicles were significantly higher in IgG4-AAA group than in other groups. Expression of adventitial MMP-2 and MMP-14 by histiocytes and fibroblasts was predominantly detected outside lymphoid follicles. Serum MMP-9 levels were significantly higher in IgG4-AAAs (835 ng/mL) than in controls, and correlated with serum IgG4 levels and the total numbers of adventitial MMP-9-positive cells, whereas serum MMP-2 levels did not differ among the three aneurysmal groups. CONCLUSIONS: MMP-9 production in adventitial immune cells concerning lymphoid follicles was characteristic of IgG4-AAAs and might work in its activity with aneurysmal dilatation and adventitial thickening. Expressions of adventitial MMP-2 and MMP-14 were detected in histiocytes and fibroblasts outside lymphoid follicles, and were less concerned with the activity of IgG4-AAAs.

Influence of Type 2 Endoleaks on Long-Term Outcomes after Endovascular Repair for Abdominal Aortic Aneurysms: A National Hospital Organization Network Study for Abdominal Aortic Aneurysms in Japan.

BACKGROUND: Although endovascular repair (EVAR) is the first-line treatment for abdominal aortic aneurysm, type 2 endoleak (EL), which is associated with late sac enlargement or rupture, remains a concern. The present study aimed to assess the influence of type 2 EL on long-term outcomes after EVAR. METHODS: Among 550 patients who underwent EVAR between 2007 and 2013 at 14 Japanese national hospitals, 135 patients had type 2 EL diagnosed on follow-up computed tomography (CT) within 12 months after EVAR (EL2[+] group) and 415 patients did not have EL within 12 months (EL2[-] group). The cumulative incidences of sac enlargement, late intervention, and aneurysm-related death after EVAR were estimated using the cumulative incidence function method, and prognostic factors were investigated using the Fine-Gray hazard model. RESULTS: The median follow-up period was 5 years, and the 5-year cumulative incidence rates of sac enlargement, late intervention, and aneurysm-related death were 30.7% ± 4.4%, 25.3% ± 4.1%, and 2.6% ± 1.4%, respectively, in the EL2(+) group, and 8.7% ± 1.6%, 7.6% ± 1.4%, and 0.3% ± 0.3%, respectively, in the EL2(-) group. The cumulative incidence rates of sac enlargement (P = 0.002), late intervention (P < 0.001), and aneurysm-related death (P = 0.015) were significantly different between the 2 groups. As the first-line treatment for sac enlargement with type 2 EL, transcatheter coil embolization was performed in 30 patients. Information about sac behavior on CT after coil embolization was available in 20 of the 30 patients. Among these patients, no patients experienced sac shrinkage, and the aneurysmal sac dilated after coil embolization in 18 patients. CONCLUSIONS: Type 2 EL affects the long-term outcomes after EVAR. It is not recommended to observe large aneurysmal sacs conservatively as they tend to dilate in the presence of type 2 EL.

Inflammatory features, including symptoms, increased serum interleukin-6, and C-reactive protein, in IgG4-related vascular diseases.

Immunoglobulin (IgG) 4-related diseases (IgG4-RDs) are fibro-inflammatory conditions characterized by tumorous swelling and serum IgG4 levels. Intrapelvic IgG4-RD has been subclassified according to the localization site and aortic shape as IgG4-related aortic aneurysms (IgG4-AAs), periaortitis (IgG4-PA), and retroperitoneal fibrosis (IgG4-RF). The IgG4-AA pathogenesis would involve interleukin (IL)-6 upregulation, and Th2-predominant and Treg-activated immune conditions. We characterized the features of intrapelvic IgG4-RD lesions, including presence of vascular lesions. The clinical, serological, and pathological features, including cytokines concerning Th1/2 and Treg (IL-4, IL-6, IL-10, IL-13, and interferon-gamma) of patients with IgG4-AAs (n = 24), IgG4-PA (n = 8), and IgG4-RF (n = 10) were retrospectively compared. Clinical symptoms, such as low-grade fever, abdominal/lumber pain, and anemia, were frequently detected in IgG4-AAs but rarely in IgG4-RF. Serum IL-6 and C-reactive protein (CRP) were significantly higher in IgG4-AAs and IgG4-PA than in IgG4-RF. Pathologically, IL-6+ cells were more frequently detected in IgG4-PA and IgG4-AAs than in IgG4-RF. There were no noteworthy differences in the clinical complications, white blood cell counts, serum IgE, and serum and immunopositive cells of other cytokines between the subgroups. Among IgG4-AAs and IgG4-PA, serum IL-6 and IL-6+ cells correlated with CRP, aortic diameter, and periaortic fibrosis. IgG4-AA and IgG4-PA, but not IgG4-RF, were characterized by "inflammatory" features, such as increased CRP and serum/pathological IL-6, and clinical inflammatory symptoms; thus, IgG4-AA and IgG4-PA belong to the same group as IgG4-related vascular disease. High levels of CRP and IL-6 would be hallmarks of IgG4-related vascular disease.

IgG4-Related Arterial Disease.

Immunoglobulin G4-related diseases (IgG4-RD) are systemic inflammatory conditions, characterized by high serum IgG4 concentrations, and pathologically IgG4-positive plasmacytes infiltrations and storiform fibrosis. We described IgG4-related inflammatory abdominal aortic aneurysm in 2008, and revealed the existence of vascular lesions. IgG4-related vascular lesions frequently occur in the aorta and branching medium-sized arteries with or without aneurysmal change. The inflammatory lesion mainly involves in the adventitia, indicating remarkable adventitial fibrous thickening with infiltration of inflammatory cells. Clinical symptoms associated with IgG4-related vascular lesions might be fever, abdominal pain, hydronephrosis, or few subjective symptoms. Comprehensive diagnostic criteria is applied according to image findings of thickening lesions, high serum IgG4 levels, and histopathological findings. As a treatment, open surgical repair or endovascular aneurysm repair is performed for the aneurysmal cases, and steroid administration is used for the cases with strong inflammation. This disease can lead to a lethal situation due to the rupture following aneurysmal formation, thus special attention is needed unlike IgG4-RD occupying in the other organs. (This is a translation of Jpn J Vasc Surg 2017; 26: 129-134.).

Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4-related aortic aneurysm patients.

OBJECTIVE: Immunoglobulin (Ig) G4-related aortic aneurysms (IgG4-AAs) are a special aortic aneurysm among IgG4-related diseases (IgG4-RDs), which are inflammatory and fibrous conditions characterized by tumorous swelling of affected organs and high serum IgG4 concentrations. Recently, IgG4-RD pathogenesis was shown to be associated with T-helper-2 (Th2) and regulatory T (Treg) dominant cytokine production, such as interleukin (IL)-4, IL-10, and IL-13. IL-6 is a key proinflammatory cytokine contributing to lymphocyte and plasmacyte maturation and to atherosclerosis and aneurysm development. We serologically and histopathologically evaluated the cytokine profile in IgG4-AA patients. METHODS: Patients with IgG4-AAs (n = 10), non-IgG4-related inflammatory abdominal aortic aneurysms (non-IgG4-AAAs; n = 5), atherosclerotic AAAs (aAAAs; n = 10), and normal aortas without dilatation (n = 10) were examined for serum IL-10, IL-13, and IL-6 levels. Resected aortic tissues were evaluated for cluster of differentiation (CD) 34 (in the endothelial cells and mesenchymal cells) and CD163 (by macrophages) expression using immunohistochemistry and in situ hybridization. RESULTS: Serum IL-10 levels were rather higher in IgG4-AA patients (median, 1.3 pg/mL) than in non-IgG4-AAA and aAAA patients and in patients with normal aortas. Elevated serum IL-13 levels relative to standard values were detected in two IgG4-AA patients but not in the other groups. Cells immunopositive for IL-10 and IL-13 were more frequent in IgG4-AAs and significantly correlated with serum IgG4 levels. Serum IL-6 levels (median, 78.5 pg/mL) were also significantly higher in IgG4-AA patients than in non-IgG4-AAA and aAAA patients and control patients with normal aortas (P = .01, P = .001, and P = .004, respectively). They positively correlated with serum IgG4 levels and adventitial thickness, but other cytokines did not. The number of IL-6-immunopositive cells in the adventitia was significantly higher in IgG4-AA patients (median, 17.8/high-power field) than in aAAA patients or patients with normal aortas (P =.001 and P = .002, respectively). In situ hybridization confirmed frequent IL-6 messenger (m)RNA expression in the endothelium, mesenchymal cells, and histiocytes in IgG4-AA adventitia. In the same cells of IgG4-AAs, coexpression of IL-6 and CD34 mRNA or CD163 mRNA was detected. CONCLUSIONS: The cytokine profiles of IgG4-AA patients had two characteristics: local IL-10 and IL-13 upregulation in IgG4-AAs was related to Th2 and Treg-predominant cytokine balance, similar to other IgG4-RDs, and IL-6 upregulation in the adventitia was characterized by activated immune reactions in IgG4-AA patients. IL-6 synthesis, through contributions of mesenchymal cells and macrophages in the adventitia, is strongly involved in IgG4-AA pathogenesis or progression, or both.

Bailout Endovascular Stent Grafting for an Ascending Aortic Pseudoaneurysm Using an Infrarenal Aortic Extension Cuff.

We report successful thoracic endovascular repair of a pseudoaneurysm rupture in the ascending aorta using infrarenal endovascular devices after an aortic valve replacement. Complete exclusion of the pseudoaneurysm was achieved with no endoleak or postoperative complications. Despite limitations of the current technology, this endovascular technique was a relatively less invasive, feasible lifesaving surgical option for the repair of a pseudoaneurysm of the ascending aorta with a diameter ≤32 mm.

Clinical Outcomes After Endovascular Repair and Open Surgery to Treat Immunoglobulin G4-Related and Nonrelated Inflammatory Abdominal Aortic Aneurysms.

PURPOSE: To compare the follow-up results of endovascular aneurysm repair (EVAR) vs open surgery (OS) for inflammatory abdominal aortic aneurysms (IAAAs) with regard to immunoglobulin G4-related diseases (IgG4-RD), which are fibrous inflammatory conditions characterized by elevated serum IgG4 concentrations and numerous infiltrations of IgG4+ plasmacytes. METHODS: Between January 2005 and December 2015, 91 patients were treated with EVAR (begun in 2008) and 166 patients underwent OS for AAA. Forty of these 257 patients had IAAAs identified by a >2-mm thickness of periaortic fibrosis (PAF). Of these 40, 21 had pathologically confirmed IgG4-RD and/or serum IgG4 concentrations ≥135 mg/dL (classified IgG4+); 8 (mean age 76 years; 8 men) were treated with EVAR and 13 (mean age 71 years; 11 men) underwent OS. Of the 19 IgG4- patients with IAAA, 9 (mean age 71 years; 8 men) had EVAR and 10 (mean age 75 years; 9 men) had OS. The 4 subgroups were compared in terms of symptoms, complications, inflammation markers, PAF, and aneurysm diameter using the latest midterm follow-up data (12-24 months). RESULTS: Preoperative aneurysm diameter, PAF, gender, median age, symptoms, and median follow-up period were similar in all groups. Preoperative serum IgG4 was equal in EVAR and OS IgG4+ groups. Compared with the OS IgG4+ group, EVAR IgG4+ patients more frequently had postoperative IgG4 increase (5/8; p=0.006) and PAF progression (5/8; p=0.027), higher postoperative serum IgG4 levels (median 141 mg/dL; p=0.034), a thicker postoperative PAF (median 5.1 mm; p=0.016), and persistent clinical symptoms (p=0.006). Compared with EVAR IgG4- patients, the EVAR IgG4+ patients showed significantly thicker postoperative PAF (p=0.024) and larger increases in postoperative sac diameter (median +13.1 mm; p=0.030). Postoperative PAF and sac diameter frequently and synchronously became worse in the EVAR IgG4+ subgroup with increased IgG4 during follow-up. The rate of change in IgG4 significantly positively correlated with the rates of change in PAF (R=0.555, p=0.03) and sac diameter (R=0.902, p=0.003). CONCLUSION: Though sample sizes were rather small, this pilot study suggested that EVAR-treated IgG4+ IAAA patients have a higher risk of persistent symptoms and increases in PAF, sac diameter, and IgG4 levels. Therefore, OS should be preferred for complete recovery. Frequent monitoring of the postoperative serum IgG4 is necessary following EVAR in IgG4+ patients to detect these complications.

Late Sac Behavior after Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm.

BACKGROUND: Sac behavior after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) is considered as a surrogate for the risk of late rupture. The purpose of the study is to assess the sac behavior of AAAs after EVAR. METHODS AND RESULTS: Late sac enlargement (LSE) (≥5 mm) and late sac shrinkage (LSS) (≥5 mm) were analyzed in 589 consecutive patients who were registered at 14 national centers in Japan. The proportions of patients who had LSE at 1, 3 and 5 years were 2.6% ± 0.7%, 10.0% ± 1.6% and 19.0% ± 2.9%. The proportions of patients who had LSS at 1, 3 and 5 years were 50.1% ± 0.7%, 59.2% ± 2.3% and 61.7% ± 2.7%. Multiple logistic regression analysis identified two variables as a risk factor for LSE; persistent endoleak (Odds ratio 9.56 (4.84-19.49), P <0.001) and low platelet count (Odds ratio 0.92 (0.86-0.99), P = 0.0224). The leading cause of endoleak in patients with LSE was type II. CONCLUSIONS: The incidence of LSE is not negligible over 5 year period. Patients with persistent endoleak and/or low platelet count should carefully be observed for LSE. CLINICAL TRIAL REGISTRATION: UMIN-CTR (UMIN000008345).

Immunoglobulin G4-related periaortitis complicated by aortic rupture and aortoduodenal fistula after endovascular AAA repair.

PURPOSE: To report a rare and complicated case of immunoglobulin (Ig) G4-related periaortitis involving both the aortic wall and the retroperitoneum without aneurysmal formation. CASE REPORT: A 79-year-old man with IgG4-related periaortitis suffered aortic rupture despite a normal caliber aorta after 6 months of steroid therapy (20 mg/d). Endovascular repair with an aortic cuff sealed the rupture. Steroid therapy was halted 2 weeks later due to infection. Four months later, a biopsy during esophagogastroduodenoscopy to investigate gastrointestinal bleeding suggested a relapse of IgG4-RD in the duodenum. Subsequent aortoduodenal fistula formation proved fatal. Generally, IgG4-related periaortitis does not result in such complications due to the absence of aneurysm formation and a thick aortic wall. CONCLUSIONS: Our report highlights a rare case of IgG4-related periaortitis where complications resulted following steroid therapy and surgical intervention, emphasizing the difficulties in dealing with IgG4-related cardiovascular lesions.

Impact of introducing endovascular aneurysm repair on treatment strategy for repair of abdominal aortic aneurysm--National Hospital Organization network study in Japan.

BACKGROUND: The objective of the present study was to assess the hypothesis that the introduction of endovascular aneurysm repair (EVAR) into Japan has expanded the indication of abdominal aortic aneurysm (AAA) repair without increasing surgical mortality. METHODS AND RESULTS: From 10 national hospitals, we registered a total of 2,154 consecutive patients (Open surgery [OS]: n=1,577, EVAR: n=577) over 8 years, divided into 4 time periods: Group I (2005-2006: n=522), Group II (2007-2008: n=475), Group III (2009-2010: n=551), Group IV, (2011-2012: n=606). Mean age increased over the 4 time periods (P<0.0001). The incidences of COPD, smoking history, history of abdominal surgery and concomitant malignancy significantly increased as well, while the numbers of patients with preoperative shock or high ASA status reduced over time. The proportion of EVAR in AAA repair increased from: 0% in Group I, 11.6% in Group II, 41.0% in Group III, to 48.8% in Group IV (P<0.0001). Early mortality was 0.8% in the EVAR and 3.4% in the OS (P<0.001) groups. Survival rates among the 4 groups free of all-cause death and aneurysm-related death at 1 year were 92.1-96.3% (P=0.1555) and 95.5-96.8% (P=0.9891), respectively. Multiple logistic regression analysis for surgical death failed to demonstrate survival advantage of EVAR over OS. CONCLUSIONS: Introduction of EVAR expanded the indication of AAA repair without increasing mortality, while high risk for anesthesia and emergency cases reduced over time. UMIN-CTR (UMIN000008345).

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

BACKGROUND: Immunoglobulin (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. METHODS: The 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. RESULTS: IgG4-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). CONCLUSIONS: IgG4-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.

Early outcomes of open abdominal repair versus endovascular repair for abdominal aortic aneurysm: report from national hospital organization network study in Japan.

OBJECTIVE: Early outcomes of open abdominal repair (OS) versus endovascular repair (EVAR) for abdominal aortic aneurysm were retrospectively analyzed, after commercialized devices for EVAR had become available in Japan. PATIENTS AND METHODS: A total of 781 consecutive patients (OS, n = 522; EVAR, n = 259) were treated at ten medical centers between January 2008 and September 2010. The OS group comprised patients with preoperative shock (SOS, n = 34) and without shock (NOS, n = 488). RESULTS: Patients in the EVAR group were 3 years older than those in the NOS group. There was greater prevalence of hostile abdomen, on dialysis, chronic obstructive pulmonary disease on inhaled drug, and cerebrovascular disease in the EVAR group than in the NOS group. Surgical mortality was 16 cases (2.0% in all patients, EVAR: 0.8%, NOS: 1.4%, SOS: 21%). Hospital stay >30 days was documented in 52 (11%) with NOS, 11 (33%) with SOS, and 8 (3%) with EVAR. Thirty late deaths included 6 aneurysm related death and 14 cardiovascular causes at a mean follow up of 1.0 year. The survival rates freedom from all cause death at one year, were 95 ± 1% in NOS and 94 ± 2% in EVAR respectively. CONCLUSION: Though significant differences in patient characteristics among three groups were noted, early results were satisfactory.