Cryopreserved allogenic fibroblast sheets: development of a promising treatment for refractory skin ulcers.

The purpose of this study was to investigate the therapeutic effect of cryopreserved allogenic fibroblast cell sheets in a mouse model of skin ulcers. It is necessary to reduce the cost of regenerative medicine for it to be widely used. We consider that cell sheets could be applied to various diseases if cryopreservation of allogenic cell sheets was possible. In this study, fibroblasts were frozen using a three-dimensional freezer. Freeze-thawed fibroblasts had ~80% cell viability, secreted ≥ 50% vascular endothelial growth factor, hepatocyte growth factor, and stromal derived factor-1α compared with non-frozen fibroblast sheets, and secreted approximately the same amount of transforming growth factor-ß1. There was no difference in wound-healing rates in the skin ulcer model between non-frozen and freeze-thawed fibroblast sheets regardless of autologous and allogenic cells. The degree of angiogenesis was comparable between autologous and allogenic cells. The number of CD3-positive cells in healed tissues was larger for allogenic fibroblast sheets compared with autologous fibroblast sheets. However, histopathological images showed that the fibrosis, microvascular density, and healing phase of the wound in allogenic freeze-thawed fibroblast sheets were more similar to autologous freeze-thawed fibroblast sheets than to allogenic non-frozen fibroblast sheets. These results suggest that allogenic freeze-thawed fibroblast sheets may be a promising therapeutic option for refractory skin ulcers.

Intimal-protected adventitial inversion technique accelerates the obliteration of a patent false lumen.

BACKGROUND AND AIMS: The optimal procedure for reconstructing the dissected aortic stump for acute type A dissection remains controversial. We routinely used the intimal-protected adventitial inversion technique (iPAIT), a modified adventitial inversion technique, to protect the fragile intima by inserting a graft and assessed the safety and efficacy of this technique. METHODS: Between August 2008 and April 2020, 146 consecutive patients with acute type A dissections underwent thoracic aortic surgery in our hospital. Extended total aortic arch replacement was performed in 119 patients (81.5%). Sixty-nine patients underwent treatment for distal aortic anastomosis with the iPAIT. To compare the iPAIT to a historical control, we assessed 69 iPAIT patients and 25 patients who underwent total arch replacement using gelatin-resorcinol-formaldehyde (GRF) glue. RESULTS: Hospital mortality was 2.9% in the iPAIT group and 8.0% in the GRF group. Perioperative characteristics were similar between the two groups. However, postoperative computed tomography revealed that the obliteration rate was significantly higher in the iPAIT group (60/66, 90.9%) than in the GRF group (15/23, 65.2%) (p = .01), not including the patients who had died or developed severe renal dysfunction. The 8-year aortic event-free survival rate in the iPAIT group (81.3%) was significantly higher than that in the GRF group (47.4%). CONCLUSIONS: The use of this technique for acute type A dissections resulted in a low mortality rate and demonstrated promising midterm survival and may accelerate the obliteration of a patent false lumen and prevent late aortic events.

Early and Long-Term Outcomes of Transcatheter Aortic Valve Replacement for Selected Nonagenarians in Japan.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being performed in very elderly patients, although its efficacy and validity remain unclear. This study evaluated real-world TAVI outcomes in Japanese nonagenarians with severe aortic stenosis.Methods and Results: This single-center study retrospectively assessed the early and long-term clinical outcomes of TAVI in nonagenarians (n=35) and in patients aged <90 years (group Y; n=171). There were no in-hospital deaths in either group. The device success rate and early safety were comparable between the 2 groups. The 5-year rates of freedom from cardiac events and deaths were equivalent in both groups. The cumulative survival rate at 5 years was non-significantly lower in nonagenarians (32.6% in nonagenarians vs. 57.5% in patients aged <90 years, P=0.49). There were no differences in the 5-year survival between nonagenarians after TAVI and the sex- and age-matched populations (P=0.18). The Cox regression model revealed that lower hemoglobin levels were associated with all-cause mortality (P=0.02), and age ≥90 years was not associated with all-cause mortality. CONCLUSIONS: The early and long-term clinical outcomes of TAVI for selected Japanese nonagenarians were comparable to those in patients aged <90 years. Nonagenarians who underwent TAVI achieved an acceptable prognosis compared to the sex- and age-matched population; thus, TAVI appears to be effective for treating aortic stenosis in Japanese nonagenarians.

Validity of direct bilateral axillary arterial cannulation in emergency surgery for acute type A aortic dissection.

BACKGROUND AND AIM OF THE STUDY: To assess the validity and long-term outcomes of direct bilateral axillary arterial cannulation for acute type A aortic dissection. METHODS: Between 2003 and 2020, 208 consecutive patients with acute type A aortic dissection underwent emergency surgical repair. Cardiopulmonary bypass was attempted to establish direct bilateral axillary arterial cannulation and bicaval drainage. Antegrade selective cerebral perfusion was established by axillary perfusion and direct cannulation of the left common carotid artery. RESULTS: Ascending aortic, partial arch, and extended total aortic arch replacement were performed in 50 (24.0%), 7 (3.4%), and 151 (72.6%) patients, respectively. Aortic root surgery and coronary artery bypass grafting were performed concomitantly in 23 and seven patients, respectively. Cardiopulmonary bypass was attempted only through bilateral axillary cannulation in all patients but was successful in 13 (6.3%) patients without bilateral axillary cannulation. No postoperative complications occurred related to this technique. There were seven hospital deaths (early mortality rate, 3.4%). Five patients had postoperative reoperation for bleeding, and nine (4.3%) were transferred to other hospitals due to postoperative permanent cerebral infarction, particularly two with arm ischemia. The 10-year survival rate of patients who underwent emergency surgical repair with this technique was 71.4%. CONCLUSIONS: Direct bilateral axillary arterial cannulation followed by selective cerebral perfusion was successful in 93.7% of patients and this may be an optimal solution for providing stable outcomes after emergency surgery for acute type A aortic dissection. However, we experienced two complications of arm ischemia, attention should be paid to potential arm ischemia.

Freezing of cell sheets using a 3D freezer produces high cell viability after thawing.

In cell therapy, transplanting an appropriate number of cells to the target site is crucial. One way to achieve this is to transplant cell sheets. Transplantation of cell sheets has already been utilized for various diseases in clinical practice. However, reducing the cost of cell sheet utilization is essential so as to facilitate the spread of regenerative medicine. Several ways to reduce costs are available, one of which is the use of allogenic cells. Another alternative is the use of cell sheets, which necessitates the development of methods for freezing cell sheets. This is the first study to report the use of a 3D Freezer for freezing cells. 3D Freezers have been used in the field of food processing and technology for a long time. The 3D Freezer freezes objects using cold air at a uniform temperature from all directions. In this study, we analyzed the cooling speed of human fibroblast sheets in 11 cell preservation solutions using a 3D Freezer and a Program Freezer. The cooling speed was -2 °C per min in the 3D Freezer. Supercooling in 10 cell preservation solutions was lower in the 3D Freezer than in the Program Freezer. Cell viability after freeze-thaw of the cell sheets using 3D Freezer was more than 70% in five cell preservation solutions. The levels of hepatocyte growth factor and transforming growth factor-ß1 were the same not only in the fibroblast sheets frozen using the five cell preservation solutions but also in the non-frozen fibroblast sheets. These results suggest that the 3D Freezer can freeze implantable cell sheets immediately after thawing.

Nuclear ß-catenin expression is positively regulated by JAB1 in human colorectal cancer cells.

Wnt/ß-catenin signaling is important for development and progression of colorectal cancer (CRC). The degradation complex for ß-catenin is functionally impaired in CRC cells, thereby resulting in the accumulation of ß-catenin and its translocation into the nucleus. Nuclear ß-catenin interacts with and co-activates T cell factor4 (TCF4), resulting in ß-catenin/TCF4-dependent transcription. Therefore, nuclear ß-catenin has been categorized as the main driving force in the tumorigenesis of CRC. Recent studies reveal that Jun activation domain-binding protein 1 (JAB1) enhances the degradation of seven in absentia homolog-1 (SIAH-1), a putative E3 ubiquitin ligase of ß-catenin, and positively regulates the expression of total ß-catenin in human CRC cells. An another recent study also shows that nuclear ß-catenin is ubiquitinated and degraded by an E3 ubiquitin ligase, tripartite motif-containing protein 33 (TRIM33). However, the regulatory mechanism for the expression of nuclear ß-catenin remains to be fully understood. In this study, we have demonstrated that JAB1 positively regulates the expression of nuclear ß-catenin, c-MYC as a ß-catenin/TCF4 target, and cell cycle regulators, such as Ki-67 and topoisomerase IIα, in human CRC cells. Taken together, these results suggest that JAB1 is considered as a promising target for novel CRC therapy.

Allogeneic fibroblast sheets accelerate cutaneous wound healing equivalent to autologous fibroblast sheets in mice.

BACKGROUND/AIMS: This study sought to confirm the difference of the wound-healing effect, cell survival, and immune response between autologous fibroblast sheets and allogeneic fibroblast sheets. METHODS: Regarding wound healing, autologous or allogeneic fibroblast sheets were transplanted onto a mouse cutaneous wound healing model and the wound contraction rate was evaluated. The luciferase-expressing fibroblast sheet was prepared and the survival of the cell sheet was evaluated by IVIS® after autologous or allogeneic transplantation. Histological evaluation was performed at five and 14 days after transplantation. RESULTS: Allogeneic fibroblast-sheet transplantation showed significant wound contraction at the early phase of wound healing, which was equivalent to that seen with the autologous fibroblast sheets. Luminescence of the autologous and allogeneic luciferase-expressing fibroblast sheets peaked on Day 5, and no luminescence was observed on Day 13. In the allogeneic fibroblast-sheet transplant group, a significant accumulation of immune cells was observed in the healed tissue but not in the early stage of wound healing. CONCLUSION: The allogeneic fibroblast sheets showed comparable rates of cell survival and wound-healing effects to those of the autologous fibroblast sheets, despite the subsequent immunogenic response. This result supports the potential practical clinical application of scaffold-free allogeneic fibroblast sheets based on the paracrine effect.

Dclk1 Inhibition Cancels 5-FU-induced Cell-cycle Arrest and Decreases Cell Survival in Colorectal Cancer.

BACKGROUND/AIM: 5-Fluorouracil (5-FU) is frequently used in colorectal cancer treatment, but with limited success. The aim of the present study was to explore the cytotoxic effects of 5-FU, in combination with inhibition of doublecortin-like kinase 1 (Dclk1), a tumor stem cell marker that regulates pro-survival signaling in colorectal cancer cells, in the human colon cancer cell line, COLO-320. MATERIALS AND METHODS: The effects of 5-FU treatment plus Dclk1 inhibition on the phosphorylation of checkpoint kinase 1 (Chk1), cell cycle, DNA damage, apoptosis, and cell survival in COLO-320 cells were evaluated. RESULTS: Combined treatment with 5-FU and a Dclk1 inhibitor, LRRK2-IN-1 (LRRK), decreased 5-FU-induced phosphorylation of Chk1 and canceled 5-FU-induced cell-cycle arrest at the S phase. Combined treatment with 5-FU and LRRK failed to induce poly (ADP-ribose) polymerase 1 (PARP-1) cleavage, but tended to decrease cell survival compared to individual treatment with 5-FU or LRRK. CONCLUSION: These results indicate that a combination of 5-FU and LRRK may be an effective, novel approach for colorectal cancer therapy.

Current Status and Perspectives on Pharmacologic Therapy for Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA), a common disease involving the segmental expansion and rupture of the aorta, has a high mortality rate. Therapeutic options for AAA are currently limited to surgical repair to prevent catastrophic rupture. Non-surgical approaches, particularly pharmacotherapy, are lacking for the treatment of AAA. OBJECTIVE: We review both basic and clinical studies and discuss the current challenges to developing medical therapy that reduces AAA progression. RESULTS: Studies using animal models of AAA progression and human AAA explant cultures have identified several potential targets for preventing AAA growth. However, no clinical studies have convincingly confirmed the efficacy of any pharmacologic treatment against the growth of AAA. Thus, there is as yet no strong recommendation regarding pharmacotherapy to reduce the risk of AAA progression and rupture. CONCLUSION: This review identifies concerns that need to be addressed for the field to progress and discusses the challenges that must be overcome in order to develop effective pharmacotherapy to reduce AAA progression in the future.

Enhancement of cytotoxic effects of gemcitabine by Dclk1 inhibition through suppression of Chk1 phosphorylation in human pancreatic cancer cells.

Although gemcitabine (GEM) is frequently used in the treatment of pancreatic cancer, the effects are limited. To increase the inhibitory effect of GEM, the identification of a molecular target is needed. Recent studies have revealed that doublecortin-like kinase 1 (Dclk1) positively regulates tumor growth, invasion, metastasis, factors related to epithelial-mesenchymal transition (EMT), pluripotency, angiogenesis, and anti-apoptosis in pancreatic cancer cells. Therefore, Dclk1 is a potential therapeutic target for pancreatic cancer. However, the Dclk1-signaling pathway including its substrate proteins remains to be elucidated. To identify the candidate substrate proteins phosphorylated by Dclk1, we performed a cancer-related phosphorylated protein microarray using Dclk1-inhibited MIA Paca2 cells. Expression levels of phosphorylated cdc25A (p-cdc25A) and phosphorylated Chk1 (p-Chk1), belonging to the ATR pathway, were decreased by treatment with Dclk1 inhibitor LRRK2-IN-1 (LRRK), indicating Dclk1 involvement in the ATR pathway. Consistent with this finding, the GEM-induced p-Chk1 expression was significantly decreased by treatment with LRRK. Notably, combined treatment with GEM and LRRK allowed cell cycle progression without arresting at S phase, while individual treatment with GEM induced cell cycle arrest at S phase. In addition, combined treatment with GEM and LRRK increased the number of γ-H2AX-positive cells compared with that upon individual treatments. Moreover, LRRK alone, and combined treatment with GEM and LRRK, induced caspase-3 activation and PARP1 cleavage, in contrast to treatment with GEM alone. Finally, combined treatment with GEM and LRRK significantly reduced cell survival compared to individual treatment with GEM. These results indicate that Dclk1 inhibition in combination with GEM treatment offers a novel approach to treat pancreatic cancer cells.

Hypoxic preconditioning of human cardiosphere-derived cell sheets enhances cellular functions via activation of the PI3K/Akt/mTOR/HIF-1α pathway.

Cell sheet technology is a promising therapeutic strategy for the treatment of ischemic diseases such as myocardial infarction. We recently developed a novel protocol, termed "hypoxic preconditioning," capable of augmenting the therapeutic efficacy of cell sheets. Following this protocol, the pro-angiogenic and anti-fibrotic activity of cell sheets were enhanced by brief incubation of cell sheets under hypoxic culture conditions. However, the precise molecular mechanism underlying the hypoxic preconditioning of cell sheets is unclear. In the present study, we examined signal transducers in cell sheets to identify those responsive to hypoxic preconditioning, using cardiosphere-derived cell (CDC) sheets. We initially tested whether sheet-like structures were suitable for hypoxic preconditioning by comparing them with individual cells. Hypoxic preconditioning was more effective in sheeted cells than in individual cells. Expression of hypoxia inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) were induced upon hypoxic preconditioning of cell sheets, as was the phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, hypoxic preconditioning increased phosphorylation of epidermal growth factor receptor (EGFR) and heat shock protein 60 (HSP60) in CDC sheets. Our findings provide novel insights into the utility of hypoxic preconditioning in cell sheet-based technologies for the treatment of ischemic diseases.

Short- and long-term outcomes of intramyocardial implantation of autologous bone marrow-derived cells for the treatment of ischaemic heart disease.

Objectives: Ischaemic heart disease remains a major cause of death in Japan. We have implanted autologous bone marrow-derived cells locally into the ischaemic region as a therapy in addition to coronary artery bypass grafting since 1999. We describe the outcomes of our cell therapy for ischaemic heart disease. Methods: Eleven patients underwent local implantation of bone marrow-derived cells into the ischaemic region during coronary artery bypass grafting. Clinical outcomes during the acute and chronic phases were recorded. Results: In the acute phase, no adverse effects were observed. Left ventricular ejection fraction values were not significantly different before and after treatment. Seven of the 11 patients showed improved blood perfusion in the area of cell therapy 1 month after treatment. In the chronic phase, 5 of 11 patients exhibited improved regional blood flow 1 year after treatment. Overall survival at 1, 5 and 10 years was 100%, 83.3% and 83.3%, respectively. Freedom from major adverse cardiac and cerebrovascular events at 1, 5 and 10 years was 100%, 80.8% and 80.8%, respectively. Death from all causes or freedom from major adverse cardiac and cerebrovascular events at 1, 5 and 10 years was 100%, 64.6% and 64.6%, respectively. Conclusions: Local implantation of bone marrow-derived cells in patients with ischaemic heart disease is safe and feasible. Cell therapy is a therapeutic option for otherwise untreatable ischaemic heart disease.

Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model.

Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts.

Development of a Highly Specific IgM Enzyme-Linked Immunosorbent Assay for Bartonella henselae Using Refined N-Lauroyl-Sarcosine-Insoluble Proteins for Serodiagnosis of Cat Scratch Disease.

The conventional anti-Bartonella henselaeIgM enzyme-linked immunosorbent assay (IgM-ELISA) methods for diagnosing cat scratch disease (CSD) remain poor in both sensitivity and specificity. We sought to develop an IgM-ELISA with improved accuracy in the serodiagnosis of CSD by exploring the antigens that are most suitable for an ELISA. We prepared 5 different protein antigens: antigen I (sonicatedB. henselaewhole-cell antigen), antigen II (N-lauroyl-sarcosine-insoluble antigen), antigen III (processed sarcosine-soluble antigen), and antigen IV and antigen V (sarcosine-insoluble and sarcosine-soluble antigens refined by DEAE-Sepharose Fast Flow ion-exchange chromatography). The IgM antibodies in the sera of 47 patients with clinically suspected CSD (24 definite, 23 suspected) and of 85 healthy individuals were examined by ELISAs using the 5 antigens, and the results were compared with those of an IgM indirect fluorescent antibody assay (IgM-IFA). In a reference panel, which consisted of 5 positive and 5 negative sera, antigen I and antigen III failed to distinguish between the two statuses, whereas the other three antigens succeeded in distinguishing between them. When the cutoff value was set at the 98th percentile of the ELISA index for healthy individuals, the sensitivity of IgM-IFA for the 24 cases of definite CSD was 54%, whereas the sensitivities of the IgM-ELISAs with antigen II, IV, and V were 75%, 83%, and 75%, respectively. The sensitivities of these three IgM-ELISAs for all 47 of the clinically suspected cases were 49%, 64%, and 51%, respectively. In contrast, the sensitivity of IgM-IFA was 28%. These results indicate that the refined sarcosine-insoluble proteins (antigen IV), which possessed the highest specificity among the 5 antigens, are the most appropriate for developing an IgM-ELISA for the highly specific serodiagnosis of CSD.

[Aortic Arch-descending Aorta Bypass for Intraoperative Lower Body Malperfusion during Chronic Type A Aortic Dissection Repair].

We present a case of intraoperative lower body malperfusion in a 55-year-old woman who was undergoing total aortic arch replacement (TAR) for chronic type A aortic dissection. We planned 2-staged operation that consisted of total aortic arch replacement using the elephant trunk technique and thoracic endovascular aneurysm repair. During the 1st surgery, hemodynamic findings after TAR indicated lower body malperfusion, with the blood pressure of the upper body of 127/46 (68) mmHg and that of the lower body of 71/46 (51) mmHg. Transesophageal echocardiography showed narrowing of the true lumen and expansion of the false lumen of the proximal descending aorta. We performed aortic arch-descending aorta bypass using the branch for arterial return of the prosthetic arch graft. After the bypass procedure, lower body malperfusion improved. The postoperative course was uneventful. Extraanatomical aortic arch-descending aorta bypass may be an option for improving intraoperative malperfusion of the lower body due to true lumen narrowing.

[Radical nephrectomy and caval tumor thrombectomy with cardiopulmonary bypass combined with right anterior minithoracotomy;report of a case].

Renal cell carcinoma is a tumor with a distinct feature that it can invade the renal vein and grow intravascularly extending to the inferior vena cava (IVC). We herein report a case of a 71-year-old female who presented with a neoplasm that involved the right kidney and an intra-IVC tumor thrombus. We performed radical nephrectomy and tumor thrombectomy under cardiopulmonary bypass through a right anterior mini thoracotomy. The patient was discharged on the 13th day after the surgery without any complication, and is currently in good health at 7 months after the operation.

Aortic arch surgery in octogenarians: is it justified?

OBJECTIVES: Elderly patients are sometimes denied aortic arch surgery because of the perception of poor outcomes and an unacceptable quality of life (QOL). In this study, we evaluated the early clinical outcomes, long-term survival and QOL following surgical treatment for aortic arch disease in octogenarian patients. METHODS: A total of 47 consecutive patients over the age of 80 years were referred to our institutions. Of these patients, 20 underwent surgical intervention (surgical group) and 27 were treated medically (medical group). Kaplan-Meier survival analysis was performed between the two groups, and the results were compared with age-matched population data. The risk factors for mortality were determined using a Cox regression analysis. A QOL assessment was performed using the 36-item Short Form Health Survey. RESULTS: The patient characteristics at baseline were not significantly different between the two groups. In the surgical cases, conventional total aortic arch replacement was performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR) in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients. No hospital deaths occurred in the surgical groups. Reoperation for bleeding was required in 2 patients, and prolonged mechanical ventilation was required in 4 patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3% in the surgical group and 32.3% in the medical group (P = 0.01). There were no differences in the 5-year survival between patients undergoing surgical intervention and the sex- and age-matched population (P = 0.80), whereas the 5-year survival was significantly lower in patients who received medical therapy relative to the sex- and age-matched population (P < 0.001). Medical therapy was the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the survivors at mid-term, the quality-of-life measures were similar between those in the surgical group and those in the medical group. CONCLUSIONS: Surgical intervention for aortic arch disease in octogenarians can yield satisfactory early clinical outcomes and acceptable mid-term survival with adequate daily activity. This study indicates that among octogenarians, age alone should not disqualify a patient from receiving an aortic arch intervention.

Mortality and morbidity after total aortic arch replacement.

BACKGROUND: Total aortic arch replacement is associated with considerable mortality and morbidity. Although operative death is the most extreme adverse clinical end point, postoperative morbidity can also be devastating for survivors. METHODS: We examined the short-term and long-term outcomes of 146 patients who underwent total aortic arch replacements between September 2003 and September 2011. RESULTS: The overall in-hospital mortality was 4.8%, and major postoperative morbidity during hospitalization occurred in 29 patients (19.9%). Multivariate analyses demonstrated that risk factors for hospital death were left thoracotomy (odds ratio [OR], 51.92; p=0.01), high preoperative serum creatinine values (OR, 3.88; p=0.02), and intraoperative blood loss (OR, 1.01; p=0.04). Ruptured aorta (OR, 7.13; p=0.02) and previous myocardial infarction (OR, 5.13; p=0.04) were identified as independent risk factors for major postoperative morbidity. The postoperative survival of all patients at 5 years was 76.7%±5%. After hospital discharge, the standardized mortality ratios showed no significant difference between hospital survivors and a comparable Japanese population and were 1.09 (p=0.41) among patients without major morbidity and 1.82 (p=0.12) among those with major morbidity. The development of renal failure requiring hemodialysis increased the risk of long-term death (hazard ratio, 5.59; p=0.03), even among hospital survivors. CONCLUSIONS: Our approach for total arch replacement resulted in low in-hospital mortality and morbidity. Long-term outcomes are stable in hospital survivors, especially in the absence of a postoperative requirement for dialysis.

[Video-assisted thoracoscopic implantation of left ventricular pacing lead;usefulness of CARTO system;report of a case].

A 70-year-old man, with a history of broad anterior myocardial infarction and repeated several hospitalizations due to heart failure, was referred to our institution for cardiac resynchronization therapy. However, as intravenous implantation of the left ventricular pacemaker lead was not possible, the patient underwent video-assisted thoracoscopic (VAT) implantation. We noted broad myocardial scarring and patent grafts, along with previously bypassed left internal thoracic artery( LITA)-left anterior descending artery (LAD) and right internal thoracic artery (RITA)-D1;thus, the area suitable for implantation of the left ventricule (LV) pacemaker was believed to be restricted. Therefore, we decided to determine the viable myocardial area by using CARTO system and identify the appropriate access port positions for the subsequent VAT surgery. After the LV pacemaker lead was implanted, the recorded pacing threshold was found to be <1.2 V at 0.5 ms. Thus, the CARTO system might be useful to preoperatively identify an area suitable for surgical implantation of a LV pacemaker lead in patients with ischemic cardiomyopathy.

[Apico-aortic valved conduit for aortic stenosis in patients who could not tolerate median sternotomy].

UNLABELLED: This report presents 3 cases treated with an apico-aortic valved conduit. Cases 1, 2:A 67-year-old female patient and a 60-year-old male patient what had undergone coronary artery bypass grafting were admitted to our hospital for severe aortic stenosis. Computed tomography showed a severe calcified ascending aorta, and coronary angiography revealed patent bypass graft. Case 3:A 71-year-old male patient that had esophagectomy with retrosternal colonic interposition for esophagus cancer after distal gastrectomy. In addition, he had experienced anterior mediastinal drainagic therapy for anastomotic leak. All 3 patients were treated by implantation of an apico-aortic valved conduit. Operation:This procedure was performed through the 5th intercostal space under a beating heart with cardiopulmonary bypass. RESULT: Postoperative courses were uneventful. All patients are still alive without procedure-related events. CONCLUSION: This surgical procedure can be an effective alternative when conventional aortic valve replacement cannot be performed for aortic stenosis patients.