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Background We sought to evaluate our distributed practice program developed for training for beating heart anastomosis by employing a novel beating heart simulator. Methods Eleven trainees watched and reviewed instructional video recordings of coronary anastomosis methods with a BEAT + YOUCAN training device, then performed coronary anastomosis procedures under a beating condition. Next, they participated in a four-hour training program developed by faculty surgeons. Ten different anastomosis components were assessed on a five-point rating scale (5, good; 3, average; 1, poor). After finishing the training program, each trainee again performed a coronary anastomosis procedure. Component scores were then compared before and after the training program. Results The mean time to completion of the procedure improved from 1033 ± 424 to 795 ± 201 s (p Conclusion Trainees who participated in our four-hour focused training program for coronary anastomosis with a novel beating heart simulator showed improved ability under the beating condition in regard to technical skills related to handling instruments.

The donation of the organs after brain death (DBD) has increased after the revision of the law in 2010 and the total number of heart transplantation( HTx) has reached to over 500 in Japan. However, donor shortage is critical as the annual number as remaining under 100 with unneglectable number of waiting deaths. Recently, HTx under donation after controlled circulatory death( cDCD) has been promoted in United Kingdom (UK) and Australia with promising outcomes. The cDCD appears to be an important option to expand the donor pool in Japan. Nation-wide and cross-cutting action among transplantation organs is warranted. Status of cDCD HTx in abroad and the domestic issues are reviewed.

Background The Jarvik 2000 ventricular assist device features a miniaturized intraventricular pump and an intermittent low-speed function that facilitates aortic valve opening. Despite its long history, little is known about the Jarvik device with regard to post-implantation outcomes. Methods Prospectively collected data from 13 participating hospitals were extracted from the Japanese Registry for Mechanically Assisted Circulatory Support database to analyze mortality, morbidity and de-novo aortic regurgitation . Data on 83 patients who underwent implantation of the Jarvik 2000 were reviewed. Median support duration was 191 (maximum 758) days. All recipients underwent implantation as a bridge to transplantation. Results Overall survival proportions at 1 and 2 years were 85.0% and 79.3%, respectively. Nine patients were in INTERMACS Level 1, and 28 patients were on mechanical circulatory support at the time of implantation. Causes of death included stroke, infection and device malfunction. Three patients had their device removed: 2 at the time of heart transplantation and 1 after recovery of the left ventricle . Common adverse events included major bleeding (27.7%), new infection (31.3%), stroke (20.5%) and device malfunction (20.5%). De-novo aortic regurgitation was observed in 17 patients, 6 of whom developed at least moderate regurgitation during follow-up. Conclusions Mid-term survival after Jarvik 2000 implantation was satisfactory and comparable to that reported by other national and international registries (INTERMACS and IMACS) for continuous-flow LVADs. De novo aortic regurgitation occurred despite the intermittent low-speed effect of this device, with some recipients experiencing progressive worsening of aortic regurgitation within 2 years post-implantation.

Objective The number of older patients with acute aortic dissection type A (AAD [A]) is increasing as the population ages. We evaluated clinical outcomes for octogenarians with AAD (A) treated surgically at our hospital. Whenever possible, we limited the replacement site of the ascending aorta to the supracoronary and hemiarch. Methods Of 436 patients with AAD (A) seen in our hospital emergency room between April 2001 and August 2015, 90 were octogenarians. Surgery was performed using a simple cardiopulmonary bypass established through the right femoral artery and venous cannulation, and distal anastomosis was performed under deep hypothermic circulatory arrest at 20°C. Results Of the 90 octogenarians with AAD (A), 11 required cardiopulmonary resuscitation, 9 of whom died. Four patients with stable hemodynamics refused surgery. Thus, 77 were treated surgically. Of these 77 patients, isolated replacement of the ascending aorta or hemiarch was performed in 73 (94.8%), and total arch replacement in 4 (5.2%). Five patients (6.5%) died within 30 days, and 5 (6.5%) died in the hospital more than 30 days after surgery. Seven (9.1%) had a new stroke, 5 (6.5%) had pneumonia, and 4 (5.2%) had mediastinitis. Forty-four (57.1%) patients were discharged to their homes and 23 (30%) to rehabilitation hospitals. Three patients later required endovascular stent graft repair, which was successful in each case. The overall postoperative survival was 82%, 70%, and 62% at 1, 3, and 5 years, respectively. Conclusions Our results suggest that our limited replacement protocol for emergency AAD (A) surgery has early and midterm survival benefits for octogenarians.

Background Clinical significance of in-patient step count after cardiac surgery remains unknown. The aim of this study was to determine whether the number of steps walked during the in-patient stay after cardiac surgery predicts the risk of cardiac re-hospitalization in the following year. Methods One hundred and thirty-three patients who underwent cardiac surgery were included in this study. The number of steps was assessed using a triaxial accelerometer. One year after surgery, patients completed a postal survey to determine their health condition and occurrence of cardiac re-hospitalization. Results The mean number of steps walked during the last three in-patient days was 2460 ± 1549 (mean ± standard deviation). Of the 133 patients, there were 16 cases (12.0%) of cardiac re-hospitalization during the 1-year follow-up period. The average step count before discharge was significantly lower in the 16 patients who were re-hospitalized for cardiac causes (1297 ± 1232 versus 2620 ± 1524, p

Purposes: Endovascular abdominal aortic aneurysm repair (EVAR) is an increasingly used method of repairing abdominal aortic aneurysm (AAA). However, the treatment of persistent type II endoleak is still a controversial issue. Five cases are reported here in which we performed open surgical repair of growing aneurysm due to persistent type II endoleak. Method: Totally 128 EVAR cases were retrospectively reviewed, which were operated in our hospital from April 2008 to October 2013. These cases were followed by periodical contrast-enhanced computed tomography (CT) after EVAR. When persistent type II endoleak caused aneurysm sac growth, we performed surgical repair method for the first line treatment. In the operation, we incised the aneurysm sac by abdominal small median incision approach and sutured lumber arteries from inside of aneurysm sac and tied inferior mesenteric artery (IMA) in addition to aneurysmorrhaphy. Contrast-enhanced CT scanning was performed in a week after open repair for the confirmation of complete treatment. Results: Five of 128 cases (3.9%) were needed to be surgically repaired because of aneurysm sac growth (>5 mm), including two ruptured AAA cases. All patients recovered uneventfully. Contrast-enhanced CT scanning performed a week after these operations showed no endoleak and intact stent grafts and reduction of the aneurysm size. Conclusion: We believe open surgical repair method of persistent type II endoleak with aneurysm expansion is secure method, and can be one of the preferable options for this life threatening complication after EVAR.

Increased survival rates after corrective or palliative surgery for complex congenital heart disease (CHD) in infancy and childhood are now being coupled with increased numbers of patients who survive to adulthood with various residual lesions or sequelae. These patients are likely to deteriorate in cardiac function or end-organ function, eventually requiring lifesaving treatment including heart transplantation. Although early and late outcomes of heart transplantation have been improving for adult survivors of CHD, outcomes and pretransplant management could still be improved. Survivors of Fontan procedures are a vulnerable cohort, particularly when single ventricle physiology fails, mostly with protein-losing enteropathy and hepatic dysfunction. Therefore, we reviewed single-institution and larger database analyses of adults who underwent heart transplantation for CHD, to enable risk stratification by identifying the indications and outcomes. As the results, despite relatively high early mortality, long-term results were encouraging after heart transplantation. However, further investigations are needed to improve the indication criteria for complex CHD, especially for failed Fontan. In addition, the current system of status criteria and donor heart allocation system in heart transplantation should be arranged as suitable for adults with complex CHD. Furthermore, there is a strong need to develop ventricular assist devices as a bridge to transplantation or destination therapy, especially where right-sided circulatory support is needed.

The aim of this study was to evaluate our clinical experience with the Jarvik 2000 axial flow pump (Jarvik Heart, Inc, New York, NY, USA), a miniature axial flow left ventricular assist device (LVAD). The clinical results of eight patients, who underwent LVAD implantation with the Jarvik 2000 (median age 55.0 years; six men) between 2005 and 2010, including two who participated in a multicenter clinical trial in Japan, were reviewed. Two patients underwent LVAD implantation as destination therapy. Four patients underwent Jarvik 2000 implantation via median sternotomy, while the other four underwent implantation via left thoracotomy. There were no major complications during surgery. Four patients were supported for more than 2 years. The longest support duration was 1,618 days. Six patients successfully bridged to heart transplantation after a median 725 days of support. One patient on destination therapy died of a cerebral infarction. The other patient on destination therapy had had the LVAD for 1,618 days. The overall survival rates at 1, 2, and 3 years were 100, 86, and 86 %, respectively. The median postoperative serum lactate dehydrogenase level was 860.5 U/L at 1 month, 735 U/L at 6 months, and 692 U/L at 1 year. There were no fatal device-related infections. We found that the Jarvik 2000 with pin bearing could support patients with end-stage heart failure with acceptable mortality and morbidity rates. Further evaluations of the prevalence of thromboembolic and hemolytic events in patients with the new conical-bearing Jarvik 2000 are required.

Myocardial ischemia associated with acute aortic dissection is frequently a fatal complication, and the emergent management still remains a challenge. We report a patient with life-threatening myocardial ischemia due to acute aortic dissection managed by rescue stent grafting of the ascending aorta. Coronary blood flow improved immediately with this endovascular procedure, hemodynamic status was ameliorated dramatically, followed by uneventful open repair.

The certification system of medical specialty is going to be changed to a new regime after the proposal of reorganization conducted by the Government in 2013. This review focuses on the issue of program-based accreditation of the training institution which is the core of the new regime. In particular, the strategy for surgical subspecialty such as thoracic surgery is discussed.

To facilitate research and development (R&D) and to expedite the review processes of medical devices, the Ministry of Health, Labor and Welfare (MHLW) and the Ministry of Economy, Trade and Industry (METI) founded a joint committee to establish guidance for newly emerging technology. From 2005 to 2007, two working groups held discussions on ventricular assist devices and total artificial hearts, including out-of-hospital programs, based on previous guidance documents and standards. Based on this discussion, the METI published the R&D Guidelines for innovative artificial hearts in 2007, and in 2008 the MHLW published a Notification by Director regarding the evaluation criteria for emerging technology.

Background There are few reports on treating dilated cardiomyopathy (DCM) with myoblast transplantation, and these show limited efficacy. Hepatocyte growth factor has cardioprotective effects on failed myocardium. Here, we combined these two treatments and analyzed cardiac function in DCM hamsters. Methods Twenty-seven-week-old BIO TO-2 hamsters, which show moderate cardiac remodeling, were divided into four treatment groups: myoblast transplantation (T group, n=24), human hepatocyte growth factor gene transfection (H group, n=29), combined treatment (T+H group, n=21), and medium alone (C group, n=26). Results Significantly better fractional shortening was observed in the T+H group compared with the others (14.9% ± 1.0%, 11.7% ± 1.5%, 11.3% ± 1.3%, and 8.6% ± 1.1 %, in the T+H, H, T, and C groups, respectively). Immunohistochemical analysis showed alpha- and beta-sarcoglycan expression in the hearts of the H and T+H groups but not in the other groups. There was less myocardial fibrosis in the H and T+H groups than in the other two, and neovascularization in the T+H group was significantly greater than in the other groups (266 ± 24, 209 ± 27, 199 ± 36, and 96 ± 17 vessels/mm 2 , in the T+H, H, T, and C groups, respectively). Survival was significantly prolonged in the H and T+H groups compared with the other groups. Conclusions Hepatocyte growth factor gene transfection and myoblast transplantation preserved the cardiac function of DCM hamsters, probably through different mechanisms, and the combined treatments preserved cardiac performance better than either treatment alone. The combined therapy is a promising strategy for treating DCM.

A 41-year-old male with heterotaxy (left isomerism) and dextrocardia composed by single ventricle, absent inferior vena cava, bilateral superior vena cava (SVC), common atrioventricular valve has received orthotopic heart transplantation (HTx) after long waiting period as Status-1. Reconstructions of bilateral SVC and hepatic vein route were successful without use of prosthetic material, and the donor heart was placed in the left mediastinum. In spite of satisfactory early recovery, the patient expired 4 months after transplantation mainly from fungal infection which developed following humoral rejection. HTx for adult patients with complex congenital heart disease is demanding in technical as well as pre- and post-transplant management, and indication should be critically determined.

We evaluated the usefulness of a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for detecting occult tumor cells in histologically malignant-negative lymph nodes resected from patients with non-small cell lung cancer. First, we examined the relationship between tumor cell number and carcinoembryonic antigen (CEA) mRNA copy number using a PCR method with a cancer cell line (A549) in a serial dilution study. Next, we evaluated the relationship between nodal metastatic area size and CEA mRNA copy number using lymph nodes with histologically proven metastasis in a serial slice study. On the basis of those results, we performed RT-PCR analyses with 28 primary tumors and 211 lymph nodes from 28 patients who underwent a lobectomy with systematic node dissection. Our results in the serial dilution study showed that the detectable limitation by quantitative RT-PCR was 25-100 neoplastic cells and 20-100 CEA mRNA copy numbers. In the serial slice study, we found a correlation between CEA mRNA copy number and nodal metastatic area. In the clinical samples, amplification of CEA mRNA was obtained with all 28 primary tumors and 13 of the lymph nodes with metastasis shown by hematoxylin-eosin staining. Furthermore, 52 (25%) of 211 histologically negative lymph nodes and the specimens from 14 (64%) of the 22 pN0 patients revealed a significant level of CEA mRNA. These results indicate that micrometastases, which are not detectable with conventional examinations, can be detected by the present method of RT-PCR for CEA mRNA in a proportion of patients with resected pN0 non-small cell lung cancer.

Jejunal pouch reconstruction is used to provide reservoir function after total gastrectomy, but controversy remains regarding pouch functions and quality of life (QOL). In this study, pouch motility was studied in conjunction with postoperative QOL.Pouch motility of 23 patients with jejunal pouch interposition after total gastrectomy was examined by manometry under fasting conditions and by an emptying test using dual-scintigraphy under postprandial conditions. Residual food was graded by endoscopic examinations. QOL was evaluated using the Gastrointestinal Quality of Life Index, and a stasis- or dumping-related symptom score.The pouch showed interdigestive contractile activity. Bursts of contractile activity occurred frequently and were long-lasting compared with the migrating motor complex phase III of the control jejunum. The percentage of time of contractile bursts correlated with postprandial pouch emptying (liquid: R(2) = 0.229, P.03; solid: R(2) = 0.243, P.02). Patients with little or no residual food had more percentage of time of contractile bursts than those with moderate residual food (P.01). The percentage of time of contractile bursts was correlated with the Gastrointestinal Quality of Life Index score (R(2) = 0.262, P.02), stasis-related symptoms (R(2) = 0.279, P.01), and dumping-related symptoms (R(2) = 0.218, P.03).An interposed jejunum pouch showed bursts of contractile activity that affected postoperative gastrointestinal function and patient QOL.

Background. Although angiogenic gene therapy has been reported to be effective in restoring ischemic heart function, there are several obstacles to its clinical application, such as unreliable efficiency of transfection and uncontrollable expression. We developed human HGF (hHGF)-producing cells that regulated hHGF production using the thymidine kinase gene of Herpes Simplex Virus (TK) and the Ganciclovir (GCV) system. We tested whether these cells induced and regulated angiogenic effects in infarcted myocardium. Methods. NIH3T3 cells were stably transfected with an hHGF cDNA expression plasmid (NIH/HGF). Next, the NIH/HGF cells were stably transfected with TK (NIH/HGF/TK). The left anterior descending artery was ligated in the heart of severe combined immunodeficiency rats, and four materials were transplanted: 1) NIH/HGF (n=10), 2) NIH/HGF/TK, with orally administered GCV (n=10), 3) NIH3T3 (n= 10), and 4) culture medium (n= 10). Results. In vitro, the proliferation of NIH/HGF/TK cells was suppressed by GCV. In vivo, significant increases in cardiac performance and angiogenesis were observed in the NIH/HGF and NIH/HGF/TK groups 4 weeks after transplantation. Although tumorous lesions were detected in the NIH/HGF group, their growth was completely controlled in the NIH/HGF/TK group. Conclusions. Angiogenic gene cell therapy using the TK-GCV suicide gene system induces and regulates angiogenesis under the control of cell growth, suggesting it as a promising system for therapeutic angiogenesis.

Objective The mechanism of spinal cord injury is believed to be related to the vulnerability of spinal motor neuron cells to ischemia. The aim of this study was to investigate whether ONO-5046, a specific inhibitor of neutrophil elastase that can attenuate tissue or organ injury in various pathologic conditions, could protect against ischemic spinal cord damage. Methods After induction of spinal ischemia, ONO-5046 or vehicle was injected intravenously. Cell damage was analyzed by counting the number of motor neurons. To investigate the mechanism by which ONO-5046 prevents ischemic spinal cord damage, we observed the immunoreactivity of CPP32 (caspase3), brain-derived neurotrophic factor, and phosphorylated extracellular signal–regulated kinase. Results ONO-5046 eased the functional deficits and increased the number of motor neurons after ischemia. The induction of caspase3 was significantly reduced by ONO-5046 treatment. Furthermore, the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal–regulated kinase were prolonged. Conclusion ONO-5046 may protect motor neurons from ischemic injury by reducing caspase3 and prolonging the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal–regulated kinase. ONO-5046 may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.

Objectives: Cell therapy is a promising strategy for ischemic cardiomyopathy. However, the direct injection method has limitations for generalized cell delivery, especially in dilated cardiomyopathy (DCM). We hypothesized that a sheet-shaped myoblast graft would be superior to direct injection for improving cardiac performance in DCM. Methods: Male 27-week-old BIO TO-2 (DCM) hamsters that showed moderate cardiac remodeling were used as recipients. Myoblasts isolated from BIO F1B hamsters were cultured on dishes coated with poly( N -isopropylacrylamide), a temperature-responsive polymer, and spontaneously detached as a sheet-shaped graft at 20 °C without enzymatic treatment. Three different therapies were conducted: (1) sheet-shaped myoblast graft implantation (S group, n =29); (2) myoblast injection (M group, n =28); and (3) sham operation (C group, n =28). In the S group, two sheet-shaped myoblast grafts were implanted on the left ventricle (LV) wall, and in the M group, myoblasts were injected into the right ventricle (RV) and LV walls. Results: After the sheet-shaped myoblast grafts were implanted, echocardiography demonstrated that the dilated LV dimension was significantly reduced, whereas the hearts in other groups showed a progression of LV dilation. The fractional shortening in the M and C groups decreased significantly while that in the S group was maintained at the preoperative level for 3 months after the operation. Histological examination demonstrated that in the S group, the LV wall thickness was increased, with viable myoblasts, and myocardial fibrosis was decreased compared with the other groups. Immunohistochemical staining demonstrated alpha-sarcoglycan and beta-sarcoglycan expression on the basement membrane of the cardiomyocytes in the S group but not in the other groups. The life expectancy was significantly prolonged in the S group. Conclusion: Sheet-shaped myoblast graft implantation improved cardiac performance and prolonged life expectancy, associated with a reduction in myocardial fibrosis and re-organization of the cytoskeletal proteins in DCM hamsters. Thus, sheet-shaped autologous myoblast graft implantation may induce restoration of the heart in DCM.

The recombinant Sendai virus vector is a promising tool for human gene therapy, capable of inducing high-level expression of therapeutic genes in tissue cells in situ. The target tissues include airway epithelium, blood vessels, skeletal muscle, retina and the central nervous system, but application to hepatic tissues has not yet been achieved, because direct intraportal injection of the vector is not feasible. We report an efficient and harmless procedure of gene delivery by recombinant Sendai virus into rat parenchymal hepatocytes, based on isolated hepatic perfusion with controlled inflow. Critical parameters for successful hepatic gene delivery are a brief preperfusion period (25 degrees C, 5 min); appropriate vector concentration in the perfusate (10(7) pfu/ml); moderate portal vein pressure (12 mmHg) and a brief hyperthermic postperfusion period (42 degrees C, 5 min). Under these optimized conditions, marker genes were expressed in most parenchymal hepatocytes without significant damage to hepatic tissues. Furthermore, expression of the marker genes was undetectable in nonhepatic tissues, including the gonads, indicating that this approach strictly targets hepatic tissues and thus offers good clinical potential for human gene therapy.

We report a successful operative treatment of ruptured coronary artery aneurysm associated with coronary-pulmonary artery fistula. A 67-year-old woman was diagnosed with coronary artery fistula previously but observed without any treatment. She had medical examination at a previous hospital because of sudden onset of dyspnea, and transported to our institution with a diagnosis of cardiac tamponade. Multi-detector computed tomography (MDCT) showed massive pericardial effusion, coronary-pulmonary artery fistula and giant coronary artery aneurysm. We performed emergency operation. Under cardiopulmonary bypass, coronary artery fistula and aneurysm was resected. Postoperative MDCT showed almost complete exclusion of coronary artery fistula. Postoperative course was uneventful.

BACKGROUND The mechanism involved in the spontaneous acceptance of liver allografts in some rat strain combinations remains unclear. Immunoregulatory NKR-P1TCRalphabetaT (NKT) cells primarily produce IL-4 and IFN-gamma, and enhance the polarization of immune responses to Th2 and Th1, respectively. The aim of this study was to clarify the role of graft-derived NKT cells in inducing the spontaneous acceptance of rat orthotopic liver transplantation (OLTx) METHODS The experimental groups were divided as follows: Group 1, BN to LEW "low responder (acceptor)" combination; Group 2, DA to LEW "high responder (rejector)" combination; naive BN (Group 3) or LEW recipients (Group 4) with liver allografts from irradiated BN donors. The recipients had liver allografts from irradiated donors reconstituted from the following cell populations 24 hr before harvesting, spleen cells (SPCs, Group 5), IgSPCs (Group 6), IgNKR-P1SPCs (Group 7), and IgTCRabSPCs (Group 8) RESULTS In Group 1, the percent of graft-derived NKT cells harvested on day 7 posttransplant were significantly higher than in Group 2. In the case of BN liver allografts that had been irradiated and reconstituted with cell populations including NKT cells (Groups 5 and 6), the mean graft survival (MST) was extended to 39.2+/-5.7 and 38.8+/-8.0 days, respectively. In contrast, when NKT cells were excluded (Groups 7 and 8), the grafts were acutely rejected within MST of 17.8+/-4.0 and 18.8+/-7.7 days, respectively. The concentrations of IL-10 and TGF-beta, but not IL-4 in IgGICs culture supernatants were predominant in the acceptor, whereas those with IFN-gamma predominated in the rejector. CONCLUSIONS Graft-derived NKT cells might be responsible for spontaneous acceptance in the rat OLTx.

We studied the expression of 9,906 genes in retransplanted rat cardiac allografts that developed cardiac allograft vasculopathy (CAV) with the use of DNA microarray and real-time reverse transcriptase-polymerase chain reaction. Although only a slight difference in the timing of the retransplantation induced the later development of CAV, 1,067 genes were differentially expressed in the allografts 1 day after retransplantation. Thus, the development of CAV was determined by a robust difference in gene expression soon after retransplantation, controlled by a slight difference in retransplantation timing. In contrast, only 26 genes showed significant upregulation in the later phase of CAV development, and the time-course of the induction of 16 genes was associated with CAV progression. Of these genes, 8 were induced in 2 different aortic allograft combinations, and the time-course of the induction was correlated with the development of transplant vasculopathy. Microarray-based gene expression profiling has the potential to elucidate the mechanism of experimental chronic cardiac allograft rejection.

Background To overcome the limitations of tissue-engineered heart valves, which require cell seeding before implantation, a growth factor for in situ recellularization may be an important strategy. We developed a new decellularized valve containing a fusion protein combined fibronectin and hepatocyte growth factor. Here, we tested the hypothesis that our valve might accelerate in situ recellularization by inducing the proliferation of endothelial cells. Methods Porcine aortic valves were decellularized using detergent. Fibronectin-hepatocyte growth factor was introduced into the decellularized valves. The decellularized valves with fibronectin-hepatocyte growth factor were implanted into the pulmonary arterial trunk of dogs (F group: n=15). As controls, decellularized valves without the growth factor (C group: n=12), and with hepatocyte growth factor (H group: n=12) were implanted in the same manner. Histologic examinations were performed 1 week and 1 month after implantation. Results One week after implantation, endothelial cells partially covered the surface of the graft in the F group but not the C and H groups. Although the C and H groups had inadequate recellularization 1 month after implantation, the F group showed a monolayer of endothelial cells, underneath which were areas of additional cell layers, which were vimentin positive. Quantitative evaluation demonstrated the amount of vimentin in the F group was 71% of the native control, and it was much lower in the other groups (C, 2.8%; H, 16.8%) 1 month after implantation. Conclusions This study demonstrated that fibronectin-hepatocyte growth factor enhanced early in situ recellularization in decellularized valves.

Therapeutic angiogenesis, induced by the direct injection of angiogenic growth factors or by transmyocardial laser revascularization (TMLR), has shown great potential as a new therapeutic strategy for end-stage coronary artery disease. However, no significant differences in angiogenic effects of TMLR and vascular endothelial growth factor (VEGF) have been reported. We compared the effects of the intramyocardial injection of hepatocyte growth factor (HGF), a novel angiogenic factor, with those of TMLR, by evaluating the improvement in regional blood flow and regional function in a canine heart model of chronic ischemia.To create a model of chronic ischemia, we ligated the left anterior descending artery (LAD) in 15 beagles. We divided the dogs into three groups according to the treatment given 1 month after ligation. Four dogs were given an intracardial injection of human recombinant HGF (H group), six dogs were given TMLR (T group), and five dogs were used as a control (C group). We compared the degree of improvement in regional blood flow and regional function 1 month after the treatment.The regional myocardial blood flow and function were significantly better in the H group than in the T or C groups (P0.05). Histologically, there were significantly more von Willebrand factor-positive cells in the LAD region in the H group than in the T or C groups.The intramural injection of recombinant human HGF resulted in therapeutic angiogenesis with an intrinsic contractile state, and it may have greater advantages than TMLR for the treatment of chronic ischemic heart disease.

ObjectivesHepatocyte growth factor plays a significant role in angiogenesis, anti-apoptosis, and anti-transforming growth factor-β1–mediated fibrosis in several organs. In this study, we investigated the effect of transfection of the hepatocyte growth factor gene in attenuation of cardiac remodeling in the hypertrophied heart.MethodsTwo weeks after banding the ascending aorta of male Sprague-Dawley rats, a hemagglutinating virus of Japan-liposome complex with (H group) or without (C group) human hepatocyte growth factor cDNA was transfected into the left ventricle wall by direct injection. The hepatocyte growth factor, c-Met, and transforming growth factor-β1 mRNA levels in the left ventricle were then analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction.ResultsTwo weeks after transfection, the expression of transforming growth factor-β1 mRNA was significantly attenuated in the H group compared with the C group (P < .01). Myocardial collagen content after 4 weeks of banding was significantly lower in the H group (5.0 ± 0.6 mg/g tissue) than in the C group (7.4 ± 0.5 mg/g tissue, P < .01). Left ventricular diastolic function (E/A ratios quantified by Doppler echocardiography) showed a significant increase in the H group (1.9 ± 0.1) compared with the C group (1.1 ± 0.1, P < .01).ConclusionsOur results demonstrated that gene transfection of hepatocyte growth factor attenuated left ventricular diastolic dysfunction and cardiac fibrosis in association with a decrease in transforming growth factor-β1 in the rat heart subjected to pressure overload. Thus, the transfection of the hepatocyte growth factor gene into the hypertrophied heart may be a strategy for the hypertrophied and failing heart even for cardiac surgery.

Objective It has been postulated recently that changes in cytoskeletal and sarcolemmal proteins initiate a final common pathway for contractile dysfunction in dilated cardiomyopathy. In ischemic cardiomyopathy, hepatocyte growth factor plays an important role in reorganizing the impaired cytoskeletal proteins in several cell types. We have tested the hypothesis that hepatocyte growth factor might improve life expectancy through modification of the molecular process that contributes to impairment in dilated cardiomyopathy. Methods Adult male 27-week-old BIO TO-2 hamsters, which show moderate cardiac remodeling, were divided into treatment groups that received (1) hemagglutinating virus of Japan liposomes containing human hepatocyte growth factor cDNA (H group), (2) culture medium (C group), or (3) sham operation (S group). Results After the operation, echocardiography demonstrated that the enlarged left ventricular end-systolic dimension and decreased fractional shortening were significantly attenuated in the H group compared with the C group. There was significantly less myocardial fibrosis in the H group compared with the C group. Immunohistochemical analysis showed alpha-dystroglycan and alpha- and beta-sarcoglycan expression in the basement membrane beneath the cardiomyocytes in the H group, whereas no expression of these proteins was seen in the C group. The 40-week survival was significantly better in the H group than in the C and S groups. Conclusion An improved survival associated with transient reorganization of the cytoskeletal proteins and reduction in myocardial fibrosis was achieved by hepatocyte growth factor treatment in an adult hamster model of dilated cardiomyopathy. The results suggest a therapeutic potential of hepatocyte growth factor in the treatment of dilated cardiomyopathy.

We developed a technique of jejunal pouch interposition with a fundic-like jejunal plication (JPI-FP) for reconstruction after total gastrectomy (TG) for gastric cancer. The aim of this study was to investigate the advantages of JPI-FP over Roux-en-Y reconstruction (R-Y).Twenty-two patients who had undergone TG more than 1 year earlier were classified into two groups according to the method of reconstruction used: Group A (n = 7) underwent R-Y, and group B (n = 15) underwent JPI-FP. Group B was subdivided into two groups to examine the usefulness of additional pylorus preservation: group B1 (n = 8), pylorus (-) and group B2 (n = 7), pylorus (+).Food intake and body weight were significantly higher in group B than in group A (P0.05). Reflux esophagitis was diagnosed in two of the group A patients, but in none of the group B patients. Excessive esophageal bile exposure, determined as the fraction time of esophageal bilirubin absorbance over 0.1450%, was significantly higher in group A than in group B (P0.05). There was no significant difference in bile exposure in the jejunal pouch between groups B1 and B2.JPI-FP is a superior method of reconstruction after TG to prevent excessive esophageal bile reflux and from a nutritional aspect. The advantage of pylorus preservation remains unconfirmed.

Background A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4 + CD8 + double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of αβ or γδ T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. Materials and methods Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. Results The average proportion of TCRαβ + cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher ( P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRαβ + CD69 + CD4 + CD8 − cells in the myasthenic thymomas (8.22%) was significantly greater ( P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRαβ + CD69 + CD4 − CD8 + cells between the myasthenic and the nonmyasthenic thymomas. Conclusions The possible role of development of TCRαβ + T cells, especially the role of positive selection of TCRαβ + CD4 + CD8 − T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.

The current status and future directions of mechanical circulatory support devices (MCSDs) in Japan are reviewed. Currently used clinical MCSDs, both domestic and imported systems and continuous flow devices that are coming into the clinical arena are emphasized. Clinical MCSDs include the extracorporeal pulsatile Toyobo and Zeon systems and the implantable Novacor and HeartMate I VE. A thorough review is presented of single-ventricle continuous flow MCSDs such as the Terumo DuraHeart and the SunMedical EVAHEART and the biventricular Miwatec/Baylor systems that are on the horizon. The future directions in management of end-stage cardiac patients with MCSDs are discussed, focusing on (1) device selection - pulsatile versus continuous flow devices; (2) single-ventricle support, biventricular support, or replacement; (3) bridge to transplantation, destination therapy, or bridge to recovery; and (4) government regulatory processes and the medical industry. We hope to promote the quality of life (QOL) of end-stage cardiac patients as well as the medical industry in Japan.

Hyperbilirubinemia, a common complication associated with left ventricular assist device (LVAD) implantation, is evidence of liver dysfunction and is often a life-threatening problem after the implantation procedure. In this study we evaluated the relationship between hemodynamics after LVAD implantation and postoperative hyperbilirubinemia. Twenty-four patients who received LVADs at Osaka University Hospital between January 1994 and June 2002 were retrospectively reviewed. Patients were grouped according to the implanted LVAD: Group A (n = 4) Novacor, group B (n = 7) HeartMate 1000IP, group C (n = 13) Toyobo pneumatic pulsatile pump. Hemodynamic data and laboratory data, including total bilirubin on postoperative days (PODs) 1, 3, 7, and 14, were collected and statistically analyzed. In group C, the cardiac index (CI) on POD 1 was significantly lower (P < 0.01) than that for groups A and B. On PODs 3 and 7, total bilirubin levels in group C increased significantly over the preoperative value (P < 0.05) and were significantly higher than those in group A on POD 3 and higher than those in groups A and B on POD 7 (P < 0.05). Regression analysis of CI on POD 1 correlated significantly with total bilirubin on POD 7, as expressed by the formula y = 5.13/(x - 1.7)(0.719), where x is CI and y is total bilirubin (r(2) = 0.327, P < 0.05). Total bilirubin after LVAD implantation correlates with postoperative CI values. We suggest that it is essential to maintain the CI at the highest levels possible to avoid postoperative hyperbilirubinemia in LVAD patients.

Pancreas transplantation (PTx) has evolved as a clinical therapy to achieve sustained euglycemia. However, it remains unclear if naive diseased islets of the pancreas benefit from the avoidance of glucose toxicity by PTx. In the present study, using an animal model of type 2 diabetes, the Spontaneously Diabetic Torii (SDT; RT1a) rat, we syngeneically transplanted nondiabetic 10-week-old pancreaticduodenal grafts into diabetic 25-week-old recipients. In the control SDT rats that received no treatment, hyperglycemia developed with a mean onset time of 25 +/- 3.9 weeks of age. Few normal islet cells were found from 25 weeks and none at 40 weeks. However, in the PTx rats, the onset age (graft age) of diabetes was significantly prolonged (47 +/- 18.2 weeks). Moreover, we found that the beta-cell mass was significantly increased in the naive pancreases of 40-week-old PTx recipients (PTx40-naive). Interestingly, islet-like cell clusters of varying size were found close to ductal structures of PTx40-naive pancreases, suggesting that these cells are derived from ductal cells. Furthermore, pancreatic and duodenal homeobox factor-1 (PDX-1) was more clearly expressed in the nuclei of PTx40-naive pancreatic islet-like cell clusters. Our results demonstrate the development of duct-derived beta cells in the pancreas of type 2 diabetic recipients after PTx.

Objective: A novel hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer system has been shown to have benefits of a high efficiency of transfection and low immunogenicity. The aims of this study were to determine the effect of re-transfection of the HVJliposome system via the airway, and to quantify the distribution of gene expression between transtracheal and transplantation approaches. Methods: b-Galactosidase (b-gal) plasmid DNA was introduced into lung tissues using the HVJ-liposome method. Two groups of Sprague– Dawley (SD) rats received intratracheal instillation of 10 mg of the b-gal gene, once on Day 0 in 1 group (Group Tb-1, nZ4) and 3 times on Days 0–2 in another (Group Tb-3, nZ4). In a third group of SD rats (Group Tx, nZ5), an orthotopic left lung transplantation was performed after the donor lung was flushed with an HVJ-liposome complex solution and preserved for 1 h. Gene expression and distribution in lung tissue was then quantified by counting the X-gal stained cells. Results: Both the transtracheal and transplantation approaches resulted in low levels of transfection in the vascular endothelial cells (0.2G0.1 and 4.0G1.8%), respectively, but a moderate degree of transfection to the airway (11.0G7.1 and 28.0G20.7%) and alveolar cells (3.0G1.8 and 6.0G3.6%). Three repetitive injections via the airway increased gene expression in airway epithelial cells of 41.0G12.0% compared with the single administration of 11.0G4.3%. Conclusions: Our results suggest that the repeated transtracheal gene transfection using HVJ-liposome may have benefits for treatment of problems after lung transplantation. In addition, gene transfer using a flushing solution during harvest may provide an opportunity for gene manipulation in the setting of lung transplantation. q 2005 Elsevier B.V. All rights reserved.

Objective We sought to investigate the correlation between type of vascular reconstruction and long-term graft patency after replacement of brachiocephalic veins combined with resection of mediastinal malignancies. Methods Eighteen patients underwent surgical resection of tumors and the superior vena cava with concomitant vascular reconstruction using ringed polytetrafluoroethylene grafts. Graft patency was verified by means of venography or contrast-enhanced computed tomography at time points ranging from 3 to 77 months (median, 33 months) postoperatively. Results Seven patients underwent sole reconstruction of the right brachiocephalic vein, with occlusion observed in only 1 patient. In 6 patients who underwent reconstruction of the bilateral brachiocephalic veins with 2 separate grafts, the grafts remained patent in 2, whereas 4 patients experienced occlusion of one of the two grafts yet remained asymptomatic. Both patients who underwent reconstruction with a Y graft experienced left brachiocephalic vein graft occlusion. In the 3 patients who underwent reconstruction of a left brachiocephalic vein, the graft became occluded, and superior vena cava syndrome developed in 2 of these patients. Conclusion When replacing the superior vena cava, reconstruction of a left brachiocephalic vein alone results in a significant rate of occlusion and development of superior vena cava syndrome. Thus we advocate sole right brachiocephalic vein reconstruction or bilateral brachiocephalic vein reconstruction in this setting, and separate reconstruction of the veins is preferable to use of a Y graft.

Objective The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. Methods Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. Results Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = 1), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12–199 months). The median survival time of patients with postoperative pathologic N0 disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with N0 disease and 16.7% for patients with N2 or N3 disease ( P = .0070). Conclusions Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.

Background— Hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after lung injury. The goal of the present study was to characterize its role in pulmonary emphysema, which may lead to the development of new treatment strategies with HGF. Methods and Results— HGF mRNA and protein levels in lung tissue and plasma from elastase-induced emphysema rats transiently increased, then declined significantly to below the basal level in a time-dependent manner ( P P Conclusions— Decreased HGF expression due to a failure in sustained endogenous production after injury was associated with emphysema-related histopathologic and physiological changes in the present rat model. In addition, induction of HGF expression by a gene-transfection method resulted in improved pulmonary function via inhibition of alveolar cell apoptosis, enhancement of alveolar regeneration, and promotion of angiogenesis.

Following thoracic surgery, patients often suffer from persistent coughing. There is speculation regarding the cause. However, since few studies of that following pulmonary resection have been reported, we conducted an observational and empiric study of this issue.A cross-sectional assessment of 240 patients who had undergone a pulmonary resection was performed using a questionnaire regarding postsurgical persistent coughing. Further, therapy based on empiric results was given to 20 patients who had undergone a lobectomy and mediastinal lymph node resection for nonsmall cell lung cancer.Seventy patients were surveyed within 1 year following surgery (subchronic phase), of whom 35 (50%) suffered from coughing, as compared to 30 (18%) of 170 whose postoperative time was 1 year or more (p0.0001). Presence of lung cancer, mediastinal lymph node resection, and gastroesophageal reflux (GER) symptoms were significant factors in the group of subchronic patients. Of the 20 patients who received empiric therapy, 90% saw their coughing symptoms improve after the course of medication.In the present patients, mediastinal lymph node resection may have contributed to coughing after the procedure, which tended to improve after 1 year following the operation. Further, a secondary change, such as GER, caused by surgical intervention may also be a contributing factor in the subchronic phase.

Objective: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-kB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-kB decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. Methods: Left lung transplantation was performed in pairs of Brown Norway (RT1 n ) and Lewis (RT 1 ) rats. In Group NF (nZ6), the allografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-kB decoy and preserved for 60 min at 4 8C. A scramble decoy was used in the positive control (Group S, nZ5) and simple PBS solution in the negative control (Group C, nZ5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. Results: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445G162 vs 1305G123 ppb, P!0.02), while improvements in PaO2 (197G28 vs. 60G18 mmHg, P!0.02) and rejection score (1.8G0.3 vs. 2.5G0.4) were also observed. There were no differences in these parameters between Groups S and C. Conclusions: Inhibition of NF-kB activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings. q 2004 Elsevier B.V. All rights reserved.

With regard to a deficiency in atrial natriuretic peptide (ANP) secretion, the relationship between plasma ANP and left atrial diameter measured by echocardiography was examined and the efficacy of postoperative supplementation was evaluated.(1) Ninety-six patients with mitral valve disease from 1997 to 2002 (M:F = 65:31, mean-age 65.3 +/- 8.9 years) were studied for relationship analyses. (2) Twenty-six patients with mitral stenosis and left atrial diameteror = 60 mm undergoing mitral valve replacement (M:F = 17:9, mean-age 67.4 +/- 7.5 years) were randomly allocated to one of two groups; ANP-treated group (n = 13, 0.05 microg/kg/min of synthetic human alpha-ANP was postoperatively administered) and Control group (n = 13).(1) There were significant positive correlations between left atrial diameter and plasma renin-activity (r = 0.690, P0.01) and between left atrial diameter and plasma aldosterone (r = 0.757, P0.01). The maximum value of plasma ANP was 249.5 pg/mL accompanied with 56.2 mm of left atrial diameter in 29 patients suffering from mitral stenosis. There was a significant negative correlation between left atrial diameter and ANP in patients with left atrial diameter56.2 mm (r = - 0.725, P0.0001), whereas there was a significant positive correlation in patients with left atrial diameteror = 56.2 mm (r = 0.529, P = 0.0066). (2) At 24 hours after operation, the ANP-treated group showed significantly lower plasma renin-activity (9.2 +/- 3.3 versus 36.2 +/- 7.4 ng/mL/h) and aldosterone (113.6 +/- 36.9 versus 473.8 +/- 95.8 pg/mL) than the Control group.Left atrial diameter can be a simple and useful indicator of a deficiency in endogenous ANP secretion in patients with mitral stenosis, and postoperative ANP supplementation contributes to suppressing further activation of renin-angiotensin system during the immediate postoperative period.

Objectives: In this study, a newly synthesized cytokine inhibitor FR167653 was investigated using a rat heart ischemia-reperfusion model to prove its myocardial protective effect and its role in the inhibition of cytokine production in ischemic myocardium. Methods: Studies were performed with isolated, Langendorff-perfused Lewis rat hearts (nZ80) which were either treated with FR167653 or untreated, as the control group, and subjected to ischemia-reperfusion. Results: Reperfusion followed by 30 min of 37 8C ischemia induced marked myocardial cytokine expression and activated p38MAPK. FR167653 administered before ischemia and during reperfusion significantly reduced ischemia-activated myocardial TNFa mRNA expression (190G97 vs. 4805G3017, PZ0.024) as well as TNFa production (0 vs. 9.6G 2.5 ng/ml, P!0.05) and also inhibited p38 MAPK activation. Its administration improved recovery of cardiac contractile function during reperfusion: LVDP (130G18 vs. 82G21 mmHg (PZ0.002)), max/min dP/dt (2812G328/K2283G216 vs. 1520G424/K1325G 237 mmHg/s, PZ0.003). CPK leakage was significantly reduced in FR167653 treated hearts versus untreated hearts (54G6 vs. 0.5G0.1, P!0.05) and reduction of coronary flow was improved (110G13 vs. 77G11%) 1 h after beginning of reperfusion (P!0.05). Moreover, FR administration attenuated the number of TUNEL positive cardiomyocytes (3G1 vs. 9G2%). Conclusion: These data demonstrated positive inotropic and antiapoptotic effects of a newly synthesized compound (FR167653) of cytokine inhibitors and its inhibitory effect on myocardial TNFa production and p38 MAPK activation in ischemic-reperfused rat heart. This suggested that cytokine inhibition is significant as a method for myocardial protection against ischemia-reperfusion injury. q 2004 Elsevier B.V. All rights reserved.

BACKGROUND In heart transplantation, myocardial apoptosis during hypothermic storage contributes to graft dysfunction. On the other hand, hepatocyte growth factor (HGF) has been reported to be an antiapoptotic factor in the heart. Therefore, we assessed whether the administration of recombinant human HGF (rh-HGF) prevents apoptosis in the prolonged preserved myocardium, resulting in an improvement in the cardiac function of the graft. METHODS Isolated rat hearts were subjected to 4 hr (group A), 6 hr (group B), and 8 hr (group C: without rh-HGF vs. group D: with 100 microg of rh-HGF) of hypothermic storage followed by 60 min of normothermic reperfusion (n=5 in each group). RESULTS Compared with non-HGF-treated hearts (group C), HGF-treated hearts (group D) showed a significantly higher recovery rate of left ventricular developed pressure (38+/-5% vs. 58+/-6%, P

Nicorandil, ATP sensitive potassium channel opener, is shown to reduce coronary events for patients with stable angina. The present study was designed to examine the protective potential of nicorandil for patients undergoing off-pump coronary artery bypass grafting. Twenty-four patients undergoing off-pump coronary artery bypass grafting were randomly assigned to two groups, one receiving continuous infusion of nicorandil (1.0 microg.kg(-1).min(-1)) (n = 12) through anesthesia to next day and the other receiving no nicorandil for control (n = 12). For assessing myocardial injury, heart type fatty acid binding protein, troponin T, and creatine kinase MB isoform were determined during the first 15 hours after reperfusion. The concentration of heart type fatty acid binding protein in the nicorandil group was significantly lower than that in the control group. On the other hand, the concentrations of troponin T and creatine kinase MB isoform in the nicorandil group were lower than those in the control group, but the differences did not reach statistical significance. Furthermore, nicorandil did not affect the patients' hemodynamic variables. Our data suggest that the infusion of nicorandil provides small myocardial protection without affecting hemodynamic parameters during perioperative treatment of patients undergoing off-pump coronary artery bypass grafting.

Objective: Intrathoracic neurogenic tumors are relatively uncommon, and there have been few reports regarding their entire clinical characteristics in the Asian population. Objectives: We retrospectively reviewed our Japanese institutional experience of intrathoracic neurogenic tumors, with emphasis on the clinical spectrum. Methods: We analyzed the records of 146 patients with intrathoracic neurogenic tumors who were treated over the past 50 years. There were 60 pediatric and 86 adult patients (74 males and 72 females). Results: There were 51 ganglioneuromas, 37 schwannomas, 30 neurofibromas, 18 neuroblstomas, 5 gangliobastomas, and 5 others, of which 136 cases were located in the posterior mediastinum, 9 in the chest wall, and 1 in the lung parenchyma. Neurogenic tumors were most commonly seen as a pediatric mediastinal tumor (46.2%), as compared to 11.2% in the adult population (P!0.001). Eighty-four percent of adult patients and 60% of pediatric patients were asymptomatic. In thirteen patients (8.9%), the tumor showed an intraspinal extension, the so-called dumbbell-type. Overall, 20.5% of the neoplasms were malignant, occurring predominantly in the first 5 years of life. Complete resection was performed in 95.7% cases for benign tumors and 63.3% for malignant tumors, including a laminectomy for six cases of the dumbbell-type. There were no operative deaths and minimal morbidity. Conclusions: Age seemed to be the most important clinical parameter for distinguishing between histological type and rate of malignancy for neurogenic tumors. Recognition of this clinical spectrum will lead to the immediate and appropriate surgical intervention. q 2004 Elsevier B.V. All rights reserved.