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Background Not every elderly person is frail, and whether it would be beneficial to perform endovascular aneurysm repair (EVAR) solely because a patient is older is unclear. This study aimed to compare the results of EVAR and open surgical repair (OSR) in elderly individuals.Methods and Results:From May 1998 to March 2021, 828 EVAR patients and 886 OSR patients with abdominal aortic aneurysm (AAA) were reviewed. Patients aged ≥80 years were included among them. After propensity score matching by age, sex, and American Society of Anesthesiologists (ASA) classification, the outcomes were compared between patients who underwent EVAR and OSR. The study cohort was composed of 351 EVAR patients and 90 OSR patients. The groups had similar comorbidities, except that EVAR patients were significantly older and had higher ASA classifications. After propensity score matching, 79 pairs of patients were selected. The 30-day mortality (0 vs. 1.2%) and aneurysm-related death (ARD) rates during follow up (2.3% vs. 2.3%, respectively) were similar between the groups. Kaplan-Meier curves revealed that estimated overall survival and freedom from ARD were also similar. Conclusions This study suggests that EVAR cannot improve survival outcomes compared with OSR if applied solely because a patient is aged ≥80 years. Not only age but also other risk factors and quality of life after surgery need to be further studied.

Sarcopenia and malnutrition are often used as surrogates for frailty, which is predictive of poor prognosis after surgery. We investigated the effects of sarcopenia and malnutrition on mortality after endovascular aneurysm repair (EVAR). The subjects of this study were patients who underwent EVAR at our hospital between June 2007 and December 2013, excluding those who underwent reintervention. The psoas muscle area at the L4 level was used as an indicator of sarcopenia. The Geriatric Nutritional Risk Index was used as an indicator of malnutrition. There were 324 patients included in the study, with a mean age of 78.1 years and a median follow-up period of 56.7 months. Multivariate analysis revealed that sarcopenia (HR, 1.79; p = .042) and malnutrition (HR, 1.78; p = .043) were independent prognostic factors. Patients with both factors were classified as the high-risk group and others were classified as the low-risk group. The survival rate was significantly lower in the high-risk group than in the low-risk groups (p

Background: Several reports have indicated that suprarenal (SR) fixation may impair renal function after endovascular abdominal aortic aneurysm repair (EVAR). However, most were short-term or at most, 1-year observational studies; therefore, the midterm effects on renal function remain unclear. This study aimed to identify predictors of midterm renal dysfunction after EVAR and compare renal outcomes in patients after EVAR with SR and infrarenal (IR) fixation. Methods: A total of 467 patients who underwent EVAR of nonruptured IR abdominal aortic aneurysm between 2007 and 2014 were reviewed in a prospectively collected database. Patients on hemodialysis at baseline were excluded. Among the remaining patients, those with 3-year laboratory testing were included in this study. Patients who developed acute kidney injury were excluded from the late renal function estimation. Predictors of 3-year renal function decline were estimated using logistic regression analysis. In addition, patients undergoing EVAR with IR (IR group) and SR fixation devices (SR group) were propensity matched by age, sex, baseline renal function, baseline aneurysm diameter, comorbidities, smoking habits, and regular use of medicines that may act on kidney function. Changes in renal function after surgery were compared between the IR group and the SR group. Results: During the study period, 237 patients (102 IRs and 135 SRs) were followed up with laboratory testing 3 years after surgery. Logistic regression analysis revealed that the use of a SR fixation device was independently predictive of a more than 20% decrease in the estimated glomerular filtration rate at 3 years after EVAR (odds ratio, 2.06; 95% confidence interval, 1.18-3.58; P = .011). Eleven patients who developed acute kidney injury (1 IR and 10 SRs) were excluded from the subsequent analysis. After propensity score matching, 87 pairs were selected (mean age, 77.2 ± 6.3 years; 151 males [86.8%]). The mean follow-up duration was 5.5 ± 1.8 years. In the SR group, estimated glomerular filtration rate at 3 years after surgery decreased significantly more than that in the IR group (mean of 17.8% vs 11.6%, respectively; P = .034). Conclusions: This study suggests that, compared with EVAR with IR endograft fixation, EVAR with SR endograft fixation is associated with worse outcomes for midterm renal function., ファイル公開：2021-02-01

Background : Although we have witnessed several cases of late proximal type I endoleak (T1AEL) after endovascular aneurysm repair (EVAR), most patients did not have “hostile neck” preoperatively. We hypothesized that the distance between the lowest renal artery and the neck angulation point and neck length are the two most important factors for maintaining long-term proximal sealing. This study evaluated “neck hostility”, which is the product of the distance to the angulation point and the neck length, as a preoperative morphological risk factor for the development of late T1AEL after EVAR. Methods : A retrospective review of a prospectively assembled database was performed for all patients who had undergone EVAR at a single institution from June 2007 to May 2017. Patient demographics and preoperative imaging data were collected, and Cox regression analysis was performed to identify the risk factors for late T1AEL. Results : Of the 655 patients who underwent EVAR during the study period, 115 were excluded due to complex EVAR (n=14), primary indications for iliac aneurysms (n=86), primary T1AEL (n = 3), or other reasons (n=15). Of the remaining 537 patients, twelve patients (2.2%) developed late T1AEL a median of 3.2 (interquartile range [IQR]; 3.0, 5.4) years after EVAR. Receiver operating characteristic (ROC) curve analysis revealed a neck hostility cutoff value of 8. Cox regression analysis revealed that a neck hostility value ≤8 and conical neck anatomy were risk factors for the development of late T1AEL after EVAR. Well-known hostile neck factors such as short neck, severe angulated neck, and severe calcification/thrombus in the proximal neck were not significantly different. Conclusions : The present study demonstrated a correlation between late T1AEL and the product of the angulation distance and the neck length. This factor may be useful for predicting poor late proximal outcomes after EVAR.

Background Early spontaneous shrinkage (ESS) of abdominal aortic aneurysm (AAA) within 1 year after endovascular aortic aneurysm repair (EVAR) could be a predictor of durable success. However, late spontaneous shrinkage (LSS) during longer follow-up has not been well addressed. We compared late complications of ESS and LSS. Methods Our series of elective EVAR for infrarenal AAA from June 2007 to December 2017 was reviewed. Patients with ≥1 year of follow-up with computed tomography (CT) studies were included. Patients with any reintervention within 1 year were excluded. Spontaneous shrinkage (SpS) was defined as a diameter reduction ≥10 mm without any reintervention. ESS was defined as SpS within 1 year, and LSS was defined as SpS occurring after 1 year of follow-up. Aneurysms that became larger than the original size after SpS were defined as re-expansion. Late complications (re-expansion, reintervention, and aneurysm-related death) and related factors were compared between ESS and LSS. Results A total of 495 patients were enrolled. Median follow-up was 43 months [24–67, interquartile range (IQR)]. Among patients, 126 ESS and 55 LSS occurred. The cumulative rates of SpS were 25.7±2.0%, 37.4±2.4%, and 47.3±3.7% at 1, 3, and 7 years, respectively. There was 1 re-expansion and 6 reinterventions during further follow-up after SpS. The rates of freedom from late complications at 5 years were not significantly different between ESS (89.2±4.0%) and LSS (95.8±4.1%) (P = 0.465). Regression analysis revealed that the Zenith device was significantly related to ESS compared to the Excluder (P = 0.006) and Endurant (P = 0.040) . More than 6 preoperative patent lumbar arteries negatively correlated with ESS (P = 0.023). However, these factors had no significant impact on LSS. Conclusions The rates of late complications after SpS were comparable between ESS and LSS. Patients with delayed sac shrinkage with a reduction in diameter ≥10 mm should expect the same durable success as patients with quick shrinkage.

Endovenous laser ablation (EVLA) with concomitant phlebectomy is commonly performed in many institutions. However, phlebectomy is associated with cosmetic complications such as surgical scarring, hemorrhage, and hematoma. This study aims to compare the need for additional sclerotherapy during follow-up after EVLA with and without concomitant phlebectomy.Between November 2013 and December 2018, we performed EVLA on 1,363 limbs in 1,009 patients with symptomatic primary varicose veins, of which 954 limbs in 771 patients with great saphenous vein (GSV) or small saphenous vein (SSV) insufficiency were included in this study. Data were collected prospectively and supplemented with retrospective medical record review. Demographic and clinical characteristic profiles were collected. The outcomes of EVLA with or without concomitant phlebectomy were compared. Logistic regression was used to assess predictors for additional sclerotherapy after EVLA.CEAP classification (P 0.001), operative time (P 0.001), laser device type (P 0.001), length of the treated vein (P 0.001), linear endovenous energy density (P 0.001), and tumescent local anesthesia volume (P 0.001) differed significantly. Pain after EVLA was significantly more frequent in the nonphlebectomy group than in the phlebectomy group (P = 0.005). During follow-up, 34 of 954 limbs (3.6%) underwent additional sclerotherapy for residual visible varicose veins after EVLA. No statistical difference was found in the rate of additional sclerotherapy between the groups (P = 0.849). Logistic regression showed that female sex (odds ratio [OR], 6.18; 95% confidence interval [CI], 1.86-20.6; P = 0.003) is significantly associated with additional sclerotherapy, and concomitant phlebectomy is not a significant predictor of additional sclerotherapy (OR, 0.844; 95% CI, 0.375-1.90; P = 0.682).Patient preference for additional sclerotherapy was comparable between those who underwent EVLA with and without concomitant phlebectomy. This result supports our present strategy of avoiding simultaneous phlebectomy at the time of primary EVLA.

A popliteal artery aneurysm is one of the most common peripheral arterial aneurysms. These aneurysms can cause distal embolization and thrombosis, leading to limb loss. However, their rupture is unusual. Here we report a case in which a popliteal aneurysm with chronic occlusion at its outflow artery developed a nonfatal, painful rupture. We performed only coil embolization of the proximal artery, and the aneurysm was successfully excluded. After the procedure, collateral circulation was maintained. No ischemic symptoms such as intermittent claudication or pain at rest were observed. This approach may be useful in treating similar cases.

Background In thoracic endovascular aortic repair (TEVAR), covering the celiac artery (CA) is sometimes necessary to secure the distal seal. We report the outcomes of planned CA coverage in our experience with TEVAR. Methods Cases requiring CA coverage during TEVAR from October 2008 to September 2018 were retrospectively reviewed. Patient demographics, indications for CA coverage, communication between the CA and the superior mesenteric artery (SMA), concomitant CA embolization, and perioperative and late results were collected in a prospective database and analyzed. Results During the study decade, 357 patients underwent TEVAR at our institution. Of these patients, 15 (4.2%) required CA coverage. All 15 patients were male, and the mean age was 72.8 years (range, 44-80 years). The mean aneurysm size was 67.5 mm (range, 50-82 mm). The etiologies included 10 degenerative aneurysms (66.7%; 2 ruptures [13.3%], 4 dissecting aneurysms [26.7%], and 1 case of type IB endoleak [6.7%]) after TEVAR. Communicating collaterals between the CA and the SMA were confirmed by preoperative computed tomography angiography in eight patients (53.3%) and by intraoperative angiography in four patients (26.7%). Seven patients (46.7%) underwent concomitant embolization of the CA. CA coverage offered a mean extension of 20.3 mm (range, 12-22 mm) in the length of the distal seal. Postoperative computed tomography angiography revealed a type IB endoleak that resolved spontaneously in one patient (6.7%). Postoperative complications included splenic infarction/pancreatitis in one patient (6.7%) and spinal cord ischemia in two patients (13.3%). There were no cases of postoperative in-hospital mortality. During the follow-up period (mean, 3.6 years; range, 0.9-8.0 years), two patients developed a new type IB endoleak. One patient underwent distal extension of the stent graft with ilio-SMA bypass, and one patient was observed conservatively in accordance with the patient's decision. There were no cases of type II endoleak via the CA. Most aneurysms (86.7%) were stable or reduced in size at the most recent follow-up. There were no cases of targeted aneurysm-related death during the follow-up period. Conclusions Our study demonstrates the safety and efficacy of CA coverage in facilitating adequate distal sealing in selected patients undergoing TEVAR. Because the distal sealing length is not completely sufficient in most cases requiring CA coverage, the long-term efficacy of CA coverage during TEVAR should be determined in a large prospective study.

Similar to open surgical repair, thoracic endovascular aortic repair (TEVAR) carries a risk of spinal cord ischemia (SCI). However, the generally lower incidence of SCI after TEVAR compared with that after open surgical repair, despite the inability to preserve the intercostal arteries, indicates different pathophysiologic mechanisms with the two procedures. We hypothesized that a microembolism from an aortic mural thrombus is the main cause of SCI. Thus, we evaluated the association between the density of a mural thrombus in the descending thoracic aorta and the development of SCI.A retrospective review of a prospectively assembled database was performed for all patients who had undergone surgery at a single institution from October 2008 to December 2018. Patient demographics and procedure-related variables were collected. The volume and Hounsfield unit (HU) value of mural thrombi in the whole descending thoracic aorta were estimated on preoperative computed tomography using a three-dimensional workstation. Logistic regression analysis was performed to identify the risk factors for SCI development.Of the 367 patients who had undergone TEVAR during the study period, 155 were excluded because of previous arch surgery (n = 59), previous descending thoracic aortic surgery (n = 6), previous TEVAR (n = 6), unavailability of optimal preoperative computed tomography data (n = 17), double-barreled dissection (n = 40), and other reasons. The mean ± standard deviation age of the remaining 212 patients was 75.8 ± 6.4 years, and 42 (19.8%) were women. Of the 212 patients, 14 (6.6%) developed SCI after TEVAR. The low mean density of the mural thrombus, total thrombus volume, low-density (≥-100 HU but 30 HU) thrombus volume, intermediate-density (≥30 HU but 150 HU) thrombus volume, treatment length, urgent surgery, and baseline dialysis differed significantly between patients with and without SCI. Although subsequent multivariate analysis could not be performed owing to the small number of SCI events, vulnerable low-density thrombus/plaque was a stronger predictor among the aneurysm-related factors of SCI after TEVAR on univariate analysis. Well-known risk factors, such as distal coverage between T8 and L1, left subclavian artery coverage, previous abdominal aortic surgery, and prophylactic spinal drainage, did not show significant differences.The results from the present study have demonstrated that among aneurysm-related factors, a lower density mural thrombus/plaque in the descending thoracic aorta is a predictor of SCI development after TEVAR. These results suggest that microembolism is one of the important mechanisms of SCI after TEVAR, which might change the prophylactic strategy.

Summary CD4+ T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40Lhigh iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40Lhigh iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia., Graphical Abstract, Highlights • iPSC-derived T cells have molecular similarity to group 1 innate lymphoid cells • iPSC-derived CD40Lhigh T cell-adjuvants induce leukemia-specific CTLs via DCs, Kaneko and colleagues describe the generation of CD4+ T helper clone-derived iPSCs and differentiation of the cells into T-lineage cells, which had molecular signatures and functional properties more consistent with group 1 innate lymphoid cells. CD4 transduction and CD40 ligand high population purification of the regenerated cells enhanced the antigen-specific adjuvant responses via dendritic cells in an antigen-specific manner.

Chimeric antigen receptor (CAR) is an artificial protein that provides HLA-independent antigen specificity to T cells. CAR-T therapy has shown remarkable clinical responses especially in hematologic malignancies. But this therapy needs cell preparation for each patient. That limits its applicability. We have reported regeneration of T cells from iPSCs (Cell Stem Cell 2013). This technology provides unlimited number of T cells, so CAR-T therapy using iPSCs can broadens its applicability. Regenerated T cells previously described in some reports including ours have some different characters from peripheral T cells. In particular, they express only CD8α, and do not express CD8β. We successfully generate CAR-iPS-T cells expressing CD8β with some modification of differentiation protocols. We assayed the function of CAR-iPS-T cells in view of the difference between CD8β positive and negative iPS-T cells. We found CD8β positive CAR-iPS-T cells showed enhanced function to suppress tumor progression compared with CD8β negative CAR-iPS-T cells in subcutaneous xenograft model. In vivo kinetics study revealed that CD8β positive CAR-iPS-T cells have superior function to traffic to target expressing tumor site and enhanced sustainability in vivo compared with CD8β negative CAR-iPS-T cells. These findings indicate that CD8β positive CAR-iPS-T cells may be a potent cell source for iPSC-based cancer immunotherapy. Citation Format: Tatsuki Ueda, Shoichi Iriguchi, Yohei Kawai, Atsutaka Minagawa, Hiroyuki Miyoshi, Seitaro Terakura, Yasushi Uemura, Knut Woltjen, Yuzo Kodama, Hiroshi Seno, Yasumichi Hitoshi, Tetsuya Nakatsura, Koji Tamada, Shin Kaneko. Generation of CAR-iPS-T cells expressing CD8β [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2550.

The use of antigen-specific T cell derived induced iPSCs as a cell source for regeneration of cytotoxic T lymphocytes (CTLs) have advantages in rejuvenation profile, and reproducible number of CTLs. However for the safe and efficient regenerated T cell immunotherapy, strict antigen specificity is essential. Here we report CD8αβ T cells differentiated from T cell-derived iPSCs underwent additional rearrangement of the T cell receptor (TCR) α-chain gene at the CD4/CD8 double positive stage during in vitro differentiation and lost antigen specificity. CRISPR knockout of a recombinase gene in the T-iPSCs successfully prevented this additional TCR rearrangement. Moreover, when CD8αβ T cells were differentiated from non-T cell-derived but antigen-specific TCR-transduced iPSCs, they showed monoclonal expression of the transduced TCR. TCR stabilized regenerated CD8αβ T cells effectively inhibit tumor growth in xenograft cancer models. These approaches could contribute to safe and effective regenerative T cell immunotherapies. Citation Format: Atsutaka Minagawa, Akitsu Hotta, Yohei Kawai, Yutaka Yasui, Yasushi Uemura, Masaki Yasukawa, Tetsuya Nakatsura, Shin Kaneko. T cell receptor-stabilized regenerated CD8ab cytotoxic T lymphocytes for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3585.