Successful launch of cardiac transplantation in Japan. Osaka University Cardiac Transplant Program

Cardiac transplantation has been established as a therapeutic strategy for patients with end-stage heart failure. In Japan, however, cardiac transplantation has not been performed since the first case in 1968, and even now, after legislation for the approval of brain death was passed in 1997, it is still not performed regularly. Following long and steady efforts to enlighten Japanese society about the concept of brain death and the importance of organ transplantation, the first cardiac transplantation under the new legislation was successfully performed at Osaka University Hospital on February 1999. The patient was 47-year-old male in the dilated phase of hypertrophic cardiomyopathy who had been supported with an implantable left ventricular assist device. This article briefly reviews the situation prior to the first case of cardiac transplantation under the new legislation and discusses the current status of the therapy in Japan.     

Early complications of heart transplantation

In cyclosporine-treated cardiac allograft recipients, rejection and infection are two principal early complications. The following report describes our approach to the diagnosis and management of rejection. Infectious complications are discussed elsewhere in this journal. Lymphoproliferative disorders have not been reported in our series of transplant recipients. Other early complications particularly related to cyclosporine immuno-suppressive therapy include systemic hypertension, renal insufficiency, hepatic toxicity, and pancreatitis. Each of these is illustrated by a representative group or patient profile.     

Living-donor liver transplantation in adults: Tokyo University experience

The objective of this study was to analyze the experience of a single center with living-donor liver transplantation (LDLT) for adult patients. Ninety consecutive LDLT procedures were analyzed. Preoperative status, morbidity, hospital stay duration, and postoperative graft function and survival rates were examined. Donors showed only minimal morbidity and were discharged 15 ± 6 days after LDLT. Morbidity in the patients included acute rejection (32%), vascular complications (8%), and biliary complications (20%). The mortality rate was 6% and three additional patients experienced late death. The 2-year cumulative survival rate was 92%. The present results suggest that LDLT can be performed with an acceptable outcome in adult patients.     

原位心脏移植的初步体会

目的总结9例原位心脏移植经验,探讨该方法的近、远期疗效。方法心脏移植病人9例,均患终末期扩张型心肌病,术前射血分数(ejection fraction,EF)为0．10-0．29(0．21±0．03),均有频发室性期前收缩。用标准法处理5例,用双腔静脉法4例。供心热缺血时间2．6-6．7(4．2±1．0)min,冷缺血时间110- 175(141±16)min。抗排斥反应采用环孢素、麦考酚酸酯和甲泼尼龙三联方案,以环孢素为主。维持其血药浓度200μg／L;综合临床表现、超声心动图和心电图观察排斥反应,必要时行心内膜活检。结果手术全部成功,病人均在术后1-3月内出院,出院时心功能均恢复到0-Ⅰ级。随访4-42(27±20)个月,除1例病人在8个月时自行停服免疫抑制药因排斥反应死亡外,其余8例病人健康状况良好,6例病人已恢复工作。结论原位心脏移植是治疗终末期心脏病的有效手段。术前认真选择供体和受体,并造好血液配型及组织配型,移植过程中尽量缩短热、冷缺血时间和良好吻合是手术成功的关键。术后应用免疫抑制药和密切观察排斥反应是取得远期疗效的重点。     

Pediatric heart transplantation: 17-year Brno experience

AimTo summarize the follow-up of children who underwent orthotopic heart transplantation (HTx) in the Center of Cardiovascular and Transplantation Surgery in Brno during the past 17 years.Patients and methodsBetween May 1995 and October 2012, 42 children aged 2 months–17.5 years were listed for HTx, of these 26 underwent HTx later.ResultsOf 42 children listed for HTx, 12 died, 26 underwent HTx, 3 were excluded because of improved clinical status, and 1 is waiting for HTx. Five children died early after the transplantation, one patient died 6.5 years after HTx. The 1-year, 5-years and 10-years post-transplantation survival rates are 81%, 81%, and 76.9%, respectively. One patient underwent re-transplantation 11.5 years after HTx because of coronary artery disease affecting the graft. Long-term follow-up data are available for 21 children surviving 1.6–17.4 years (mean 8.7±5.3 years). The most common morbidities were hypertension and mild chronic kidney disease (CKD 2). Pneumonia was the most common infectious complication requiring hospitalization. EBV infection with subsequent development of post-transplant lymphoproliferative disorder (PTLD) was a severe late complication in two patients (diagnosed 8 and 15 years after transplantation). The increase in incidence of coronary artery disease during the second decade post-HTx (affecting 7.7% patients after 5 years and 42.8% patients after 10 years) leads to a significant increase in the morbidity of pediatric patients surviving more than 10 years after transplantation.ConclusionHeart transplantation currently represents an effective treatment of terminal heart failure in children. Improving outcomes of pediatric HTx mainly reflect the drop in early mortality. The main causes of late morbidity and mortality of children after HTx are the increase in incidence of coronary artery disease and malignant diseases (PTLD). Our results of long-term follow-up of children after heart transplantation are consistent with published data from other centers.     

Early pneumopericardium after heart transplantation

A 60‐year‐old woman with a history of dilated cardiomyopathy underwent heart transplantation. One month post discharge, she presented to clinic with low‐grade fever and productive cough. Her chest radiograph showed air‐fluid levels in the pericardial silhouette. Transthoracic echocardiogram showed a large complex pericardial collection with no evidence of cardiac tamponade. The patient was urgently taken to the operating room for exploration. A large “egg‐shaped” mass in the pericardium measuring 10 × 12 cm with gaseous material was aspirated. As the posterior wall of the mass was firmly adhered to the right atrium, the capsule was incompletely excised. We present the case of a potentially life‐threatening complication post transplantation that required surgical debridement and life‐long antibiotic suppressive therapy. To our knowledge, this is the first report of purulent pericardial collection caused by Enterobacter cancerogenous. Further research is required to better understand the biology of this microorganism and the role it may play as a pathogen in immunocompromised patients following solid organ transplantation.     

原位心脏移植临床经验(附10例报告)

目的 总结10例原位心脏移植经验,探讨该方法 的近、远期疗效.方法 10例心脏移植患者均为终末期扩张型心肌病,术前左室射血指数(EF)值10%～29%(21.2±3.3)%,10例患者术前均有频发室性早搏.5例患者用标准法,5例为双腔静脉法.供心热缺血时间2.6～6.7(4.2±1.0)min,冷缺血时间110～175.(141.2±16.3)min.抗排斥反应采用环孢素(CSA) 骁悉(MMF) 甲基泼尼松(Pred)三联方案.结果 10例患者均在术后1～3个月内康复出院,出院时心功能均恢复到0～I级.随访4.0～42.5(36.4±19.6)个月,晚期死亡2人,8人状况良好.结论 原位心脏移植是治疗终末期心脏病的有效手段.做好供、受体的选择,血液配型及组织配型,尽量缩短热、冷缺血时间和术中良好的吻合,是手术成功的关键.术后抗排斥反应药物的应用和抗排斥反应的密切观察是取得远期疗效的重点.     

Initial clinical experience with heart transplantation

Clinical experience with cardiac transplantation in 2 patients with terminal heart disease is described. The first patient suffered chronic and progressive heart failure due to postviral myocardial fibrosis and coronary artery disease. Following successful operation multiple complications occurred, and the patient died on the fifteenth postoperative day of gastrointestinal bleeding and gram negative sepsis. Histologic evidence of mild rejection was present at postmortem examination. The second patient presented with terminal ischemic heart disease complicated by severe pulmonary hypertension. Postoperatively severe and unremitting arterial hypoxemia caused death on the third postoperative day. Postmortem examination failed to show evidence of rejection but revealed advanced obliterative changes in the pulmonary vasculature.

Despite the disappointing outcome of these 2 cases, cardiac transplantation in man deserves extensive clinical trial. The methods of clinical study and eventual objectives are outlined.     

Renal transplantation in older patients: the University of Toronto experience

One thousand and eighteen patients who received first cadaveric renal transplants (age 18–80 yr) at the University of Toronto from 1981–1991 were reviewed in order to compare the results of patients older than 55 years of age (n=251) with the rest of the group (n=767). One- and 5-year graft survival were significantly lower in patients over 55 years of age compared to younger patients; 74% vs. 82% at one year and 49% vs. 75% at 5 years (p<0.0005) respectively. Multivariate analysis confirmed a reduced odds ratio of rejection in patients over 55 of 0.5 (P<0.001). There was no significant difference between the two groups with respect to rejection as a cause of graft failure (16% in those less than 55 vs. 16% in older than 55 vs. 9% in younger patients (p<0.005). Actuarial patient survival was significantly less in patients over 55 years of age ?85% at one year and 65% at 5 years vs. 95% at 1 year and 90% at 5 years (p<0.0005). Multivariate analysis conformed age as an independent risk factor for graft loss (relative risk 1.94,P<0.001), death (relative risk 4.75,P<0.001), and graft loss due to death (relative risk 6.28,P<0.001). These data emphasize the importance of death as a cause of graft loss in older patients.     

NK-cell related neoplasms in Osaka, Japan

The frequency of NK-cell related neoplasms was estimated among lymphoproliferative diseases diagnosed and treated in Osaka, Japan, from 1999 to 2003. The total number of registered cases was 1,400, among which 1,092 patients were diagnosed as having malignant lymphomas. There were 987 cases of non-Hodgkin's lymphoma (NHL) and 105 (9.6%) of Hodgkin's lymphoma. Immunophenotypic analysis revealed that 743 patients had B-cell lymphomas and 209 T/NK-cell lymphomas. Among the T/NK-cell lymphomas, 40 showed positive immunoreactivity for CD56, and thus they were judged to be NK/T-cell lymphomas. They included one blastic NK-cell lymphoma and 39 NK/T-cell lymphomas. NK/T-cell lymphomas were further divided into three categories based on the main site of lesions: nasal type (23 cases), non-nasal extranodal type (11 cases), and nodal type (5 cases). The positive rate of infection with the Epstein-Barr virus determined by in situ hybridization was 83%, 36%, and 25% in the nasal, non-nasal, and nodal type, respectively. A mosquito allergy was found in one patient with EBV-positive non-nasal NK/T-cell lymphoma. The present study showed that the frequency of NK-cell related neoplasms among all NHLs was 4% in an ATL-non-endemic area of Japan.     

Late complications of heart transplantation: an 11-year experience

Advances in donor and recipient selection and postoperative management of patients undergoing a heart transplant have improved survival after cardiac transplantation; nevertheless, late complications are still the main cause of mortality. Between January 1988 and March 1999, 200 heart transplants and 2 retransplants were performed at our Institution. The actuarial survival rate was 84.45% at 1 month, 75.22% at 1 year, and 69.48% at 5 years. One-hundred forty-five patients reached at least 6 months of follow-up. In this group of patients we reviewed all available pathological specimens from endomyocardial biopsies, autopsies, and hearts retrieved at retransplantation. The most frequent late complications have been: malignancies (9 patients), allograft coronary artery disease (ACAD) (6 patients), and infections (6 patients). All patients with ACAD had serological evidence of cytomegalovirus (CMV) infection and 5 of them (83.3%) of hepatitis C virus (HCV) infection. Squamous cell lung carcinoma and Kaposi's sarcoma were the most frequent neoplasms (3 patients). Twenty-six out of 145 patients died during the follow-up: sudden death occurred in 10 patients (38.46%), infections caused death in 6 patients (23.08%). ACAD in 4, and cancer in 4. Causes and rates of late mortality in patients with a cardiac transplant differ from those of early mortality. Development of infections, ACAD, or cancer is associated with a high late mortality rate. A striking correlation has been found between ACAD and HCV and/or CMV positivity. suggesting that such viruses may play a role in the development of vascular late complications in transplanted hearts.     

Initial experience with heart and lung transplantation

Between February 1983 and July 1987, twelve patients underwent heart-lung transplantation at the University of Cape Town and the University of Munich. The patients included eight men and four women, whose ages ranged from 15 to 49 years (mean, 27 years). The underlying pathologic condition was idiopathic primary pulmonary hypertension in five cases, Eisenmenger's syndrome in four cases, idiopathic pulmonary fibrosis in one case, diffuse fibrosing alveolitis in one case, and chronic emphysema in one case. The immunosuppressive regimen consisted of cyclosporine A, azathioprine, and rabbit antithymocyte globulin (RATG) during the first 2 postoperative weeks; RATG was subsequently replaced by methylprednisolone. Pulmonary rejection frequently occurred in the absence of cardiac rejection; in one case, however, this situation was reversed. Two patients required retransplantation, which was undertaken for caseating pulmonary tuberculosis with obliterative bronchiolitis after 1 year in one case and for early pulmonary insufficiency after 2 days in the other case. There were no operative deaths, but three early deaths occurred, owing to respiratory insufficiency of unknown origin (10 days postoperatively), multiorgan failure (10 days postoperatively), and acute liver dystrophy (11 days postoperatively). Five weeks after operation, a fourth patient died of multi-organ failure. There were five late deaths, all of which resulted from infectious complications. Three patients, including one who underwent retransplantation, remain alive and well, 10 to 36 months postoperatively.     

Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan

AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finall...     

Recent advances in heart transplantation: experience at Cheng Hsin General Hospital

In the 10 years to August 2000, 159 heart transplants have been conducted at the Cheng Hsin General Hospital. The actuarial survival rate for the 159 recipients at 1, 5 and 9 years was 91, 78 and 48%, respectively. The scarcity of donor organs in Taiwan, caused by religious and cultural factors impinging on donation rates, remains a problem, so maximising efficiency of any organ sharing program is essential.