Takamitsu Terasaki

Upregulation of the apoptosis-related inflammasome in cardiac allograft rejection

BACKGROUND Inflammation is a major factor in cardiac allograft rejection. Accumulating reports have demonstrated an important role of the inflammation-induced adaptor complex, called the inflammasome, in the field of immunology. The apoptosis-associated, speck-like protein containing a caspase recruitment domain (ASC) is an adaptor protein that forms the inflammasome and regulates caspase-1-dependent generation of inflammatory cytokines. The aim of the present study was to determine how ASC is associated with the development of cardiac allograft rejection. METHODS We used a murine heterotopic cardiac transplantation model between fully incompatible strains. Donor hearts (n = 9 for each time-point) were harvested for examination on Days 1, 4, 7 and 12 after transplantation. Histopathologic findings of cardiac grafts were evaluated using rejection scores. The expression of ASC and inflammatory cytokines in cardiac grafts were analyzed by immunohistochemistry and real-time reverse transcript-polymerase chain reaction (RT-PCR). RESULTS Expression levels of both ASC and IL-1 beta were higher in the myocardial interstitium of allografts in parallel to the progress of cardiac rejection during the acute phase after transplantation. In contrast, expression of ASC and IL-1 beta remained low in isografts. Cardiac allografts treated with tacrolimus showed decreased expression of both ASC and IL-1 beta similar to that seen in isografts. Real-time RT-PCR demonstrated similar alteration of ASC and IL-1 beta mRNA expression in cardiac grafts during the acute phase. CONCLUSIONS Our results demonstrate a novel finding showing that upregulation of ASC is closely associated with the inflammation induced in cardiac grafts after transplantation in the mouse.

Complete disappearance of recurrent hepatocellular carcinoma with peritoneal dissemination and splenic metastasis : A unique clinical course after surgery

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We report a case of complete disappearance of intrahepatic, peritoneal and splenic metastases in HCC after hepatectomy using treatment with tegafur and uracil (UFT). The effect of UFT alone was not likely to have caused the disappearance of this tumour because HCC recurrence advance markedly within 5 months of surgery despite oral administration of UFT. This case demonstrates a unique postoperative clinical course that suggests spontaneous regression of HCC. This is the first case of complete disappearance of unresectable HCC with peritoneal seeding and splenic metastasis.

Surgical Outcomes of Acute Type A Aortic Dissection in Elderly Patients

BACKGROUND Age is still considered a risk factor in the repair of acute type A aortic dissection. Instead of total arch replacement, we performed hemiarch or partial arch replacement with intimal tear exclusion to reduce death in elderly patients and evaluated early-term and midterm outcomes. METHODS From January 2004 to April 2012, 59 patients older than 70 years (mean age, 77.0±4.3 years) underwent emergency operations for acute type A aortic dissection at our institution. We performed hemiarch, partial arch, or total arch replacement, according to the location of the primary entry tear. The characteristics, surgical procedures, and early-term and midterm outcomes of these patients were reviewed. RESULTS We performed hemiarch replacement in 47 patients, partial arch replacement in 4, and total arch replacement in 8. The primary entry site was excluded in 56 of 59 patients (94.9%). In-hospital mortality was 6.8%, and neurologic impairment occurred in 25.4%. We obtained midterm outcomes for 55 of 59 patients, with a mean follow-up period of 43.9±23.7 months. Fourteen patients died, two of these of aortic-related causes. One patient required repeat aortic operation for rupture of a pseudoaneurysm. Follow-up computed tomography imaging was done in 28 of 55 patients during the 12 months after the operation. No significant difference was noted in the increase in maximal aortic diameter between patients with and without residual dissection. CONCLUSIONS In-hospital mortality was 6.8%; relatively low compared with previous reports. Hemiarch and partial arch replacement with entry tear exclusion may reduce deaths associated with acute type A aortic dissection repair in elderly patients, without increasing the risk of reoperation and aortic-related death.

Prosthetic valve endocarditis caused by Staphylococcus capitis: report of 4 cases

Although Staphylococcus capitis is considered to be a rare causative organism for prosthetic valve endocarditis, we report 4 such cases that were encountered at our hospital over the past 2 years. Case 1 was a 79-year-old woman who underwent aortic valve replacement with a bioprosthetic valve and presented with fever 24 days later. Transesophageal echocardiography revealed an annular abscess in the aorto-mitral continuity and mild perivalvular regurgitation. We performed emergency surgery 5 days after the diagnosis of prosthetic valve endocarditis was made. Case 2 was a 79-year-old woman presenting with fever 40 days after aortic valve replacement with a bioprosthesis. Transesophageal echocardiography showed vegetation on the valve, and she underwent urgent surgery 2 days after prosthetic valve endocarditis was diagnosed. In case 3, a 76-year-old man presented with fever 53 days after aortic valve replacement with a bioprosthesis. Vegetation on the prosthetic leaflet could be seen by transesophageal echocardiography. He underwent emergency surgery 2 days after the diagnosis of prosthetic valve endocarditis was made. Case 4 was a 68-year-old woman who collapsed at her home 106 days after aortic and mitral valve replacement with bioprosthetic valves. Percutaneous cardiopulmonary support was started immediately after massive mitral regurgitation due to prosthetic valve detachment was revealed by transesophageal echocardiography. She was transferred to our hospital by helicopter and received surgery immediately on arrival. In all cases, we re-implanted another bioprosthesis after removal of the infected valve and annular debridement. All patients recovered without severe complications after 2 months of antibiotic treatment, and none experienced re-infection during 163 to 630 days of observation. Since the time interval between diagnosis of prosthetic valve endocarditis and valve re-replacement ranged from 0 to 5 days, early surgical removal of the infected prosthesis and an appropriate course of antibiotics were attributed to good clinical outcomes in our cases.

Platelet Function During Cardiopulmonary Bypass Using Multiple Electrode Aggregometry: Comparison of Centrifugal and Roller Pumps

Blood trauma may be lower with centrifugal pumps (CPs) than with roller pumps (RPs) during cardiopulmonary bypass (CPB), because, unlike RPs, CPs do not compress the tubing, and shear stress is considered lower in CPs than in RPs. However, relative platelet function remains unclear. Using multiple electrode aggregometry (MEA), we compared platelet function with CP and RP. Ten swine underwent CPB for 3 h, with five weaned off using CP and five using RP. Platelet function was measured using MEA, as were hemoglobin concentration and platelet count, before sternotomy, after heparin infusion, 30 min and 3 h after starting CPB, after protamine infusion, and 60 min after stopping CPB. Platelet activation was initiated with adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating protein 6 (TRAP). Fibrinogen, platelet factor 4 (PF4), and β-thromboglobin (β-TG) concentrations were measured before sternotomy and 60 min after stopping CPB. In the CP group and using ADP, aggregation was significantly reduced 30 min (P = 0.019) and 3 h (P = 0.027) after starting CPB, recovering to baseline 60 min after CPB was stopped. In the RP group, aggregation was significantly decreased 30 min (P = 0.007) and 3 h (P = 0.003) after starting CPB and after protamine administration (P = 0.028). With AA, aggregation significantly decreased 30 min after starting CPB in both the CP (P = 0.012) and RP (P = 0.016) groups, slightly increasing 3 h after starting CPB and after protamine infusion, and recovering to baseline 60 min after CPB cessation. With TRAP, aggregation in the CP and RP groups decreased 30 min after starting the pump, although changes were not significant; aggregation gradually recovered after 3 h and returned to baseline 60 min after the pumps were stopped. There were no significant differences at all sampling points of MEA. In both groups, fibrinogen, PF4, and β-TG concentrations were similar 60 min after pump cessation and before sternotomy. Platelet function, evaluated with MEA, was lowest 30 min after CPB was started but did not decrease over time in either group. As assessed by MEA, platelet function using CP and RP did not differ significantly. Platelet dysfunction was caused mainly by initial contact with foreign materials and may not be dependent on type of pump.

Tracheo-Bronchial Obstruction and Esophageal Perforation after TEVAR for Thoracic Aortic Rupture.

A 67-year-old man was referred to our hospital for an ascending aortic aneurysm, thoracoabdominal aortic aneurysm and aortic regurgitation. Graft repair of the thoracic aortic arch and aortic valve replacement was given priority and completed, however he developed descending aortic rupture before the second scheduled surgery, and endovascular stent grafting was performed. He subsequently developed tracheobronchial obstruction and esophageal perforation. The patient underwent urgent esophagectomy and enterostomy with continuity later reestablished. However, he died of sepsis 5 months after surgery. Despite the less invasive nature of endovascular treatment, esophageal perforation can nevertheless occur and postoperative vigilance is well warranted.

Innovative Application of Available Stent Grafts in Japan in Aortic Aneurysm Treatment—Significance of Innovative Debranching and Chimney Method and Coil Embolization Procedure

OBJECTIVE We here describe our experience with innovative uses of these devices. PATIENTS AND METHODS We reviewed treatment outcomes of 310 endovascular abdominal aortic repair (EVAR) and 83 thoracic endovascular aortic repair (TEVAR) cases performed between August 2007 and February 2012. We separately assessed results in elderly and high-risk patients who had a novel procedure. This group included 94 patients who underwent EVAR with IIA embolization, 10 patients who had EVAR and a renal artery chimney procedure for a short aortic neck, 20 patients who had two de-branching TEVAR or Chimney method for thoracic aortic aneurysms (TAA) and 3 patients who had debranching TEVAR for thoracic abdominal aortic aneurysms (TAAA). RESULTS Of the 393 patients given stent grafts (SGs), 3 (0.8%) died in the hospital, including 1 patient with pneumonia who underwent EVAR and IIA embolization and 1 patient with a cerebral infarction who had TEVAR. Four patients (4.3%) who were treated with EVAR with internal iliac artery (IIA) embolization presented with residual buttock claudication 6 months postoperatively, and 3 patients (3.2%) had onset of ischemic enteritis; however, in all 7 patients, the condition resolved without additional intervention. In the 10 patients who had EVAR and a renal artery chimney method, the landing zone (LZ) was ≤10 mm, but neither endoleak nor renal artery occlusion was observed perioperatively or during midterm follow-up. Of the 20 patients who had a 2-debranching TEVAR, including 9 in whom the chimney method was used with the LZ in zone 0, 1 (5%) had a residual endoleak. In 3 patients with TAAA, we used SGs to cover 4 abdominal branches and bypassed the visceral artery; the outcomes were good, with all patients being ambulatory at hospital discharge. CONCLUSION Among innovative SGs treatments, the debranching procedure and the chimney method using catheterization and the coil-embolization technique provided good outcomes, as used in addition to surgical procedures. Aortic aneurysm treatment will become increasingly noninvasive with the continuing development of more innovative ways to use the SGs currently available in Japan. (English Translation of Jpn J Vasc Surg 2012; 21: 165-173).

Structural Valve Deterioration of Porcine Bioprosthesis Soon after Mitral Valve Repair and Replacement

An 81-year-old woman, who had undergone mitral valve replacement (MVR) with a porcine bioprosthesis after mitral valve repair, presented with hemolysis 4 years and 6 months after MVR. Transthoracic echocardiography (TTE) revealed trivial mitral regurgitation, which was diagnosed based on the observed perivalvular leakage. Hemolysis gradually increased, and she developed dyspnea and edema 2 years after the appearance of mitral regurgitation. We performed a reoperation. Intraoperative transesophageal echocardiography (TEE) after intubation showed no perivalvular leakage of the mitral prosthesis, but transvalvular leakage through a leaflet perforation was present. The leaflets of the bioprosthesis had slit-shaped perforations at their hinges. There was no sign of infection on the leaflet or annulus. We implanted a new bioprosthesis after removal of the deteriorated valve. The postoperative course was uneventful. Microscopic examination verified collagen degeneration, histiocyte infiltration, and hyalinization. It is important to perform TEE to rule out structural valve deterioration (SVD) even when regurgitation occurs soon after valve replacement.

Characteristics of cardiac allograft vasculopathy induced by immunomodulation in the miniature Swine.

PURPOSE We aimed to develop swine cardiac transplantation model for study of cardiac allograft vasculopathy (CAV) and to characterize the mechanisms of its formation. METHODS Heterotropic cardiac transplantation was performed in swine leukocyte antigen mismatched miniature swine, and CAV was induced by immunomodulation by cyclosporine A (CyA). Histology and immunohistochemistry were performed to identify cellular components of CAV. Fluorescence in situ hybridization (FISH) was developed for detection of 1 and Y-chromosome for identification of cell origin in the female donor to the male recipient heart transplantation model. RESULTS CAV was successfully developed by immunomodulation of CyA. Severity of CAV revealed more prominent in the distal epicardial coronary arteries than proximal coronary arteries. Phenotype of the SMCs proliferated in the intimal thickening of CAV were mostly embryonal/secretory type. Our new chromosome specific probes for FISH method were useful for discrimination of sex of each cell, and proliferated SMCs were revealed to be mainly donor origin. CONCLUSION CAV mimicking human heart transplantation can be developed by appropriate immunomodulation in the swine. In swine CAV, proliferated SMCs seen in the intimal thickening were demonstrated to be from the donor origin.

Left atrial appendage enlarged by coronary artery fistula after surgical closure of appendage.

Two years previously, a 73-year-old man with mitral regurgitation underwent mitral annuloplasty and left atrial appendage (LAA) exclusion by suturing the orifice from the endocardium. However, the mitral regurgitation became exacerbated, and the left atrium enlarged rapidly over a 6-month period. Computed tomography showed a heterogenic mass in the LAA, and coronary angiography revealed a coronary artery–LAA fistula. Reoperation revealed a thrombus filling the appendage and two small orifices of the coronary artery–LAA fistula located in the endocardium of the appendage. We excised the LAA and closed these fistula orifices concomitant with mitral valve replacement.