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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Background A pulmonary metastasectomy for colorectal carcinoma is a generally accepted procedure, although several prognostic predictors have been reported. The aim of this study is to define the patients who benefit from pulmonary metastasectomy for colorectal carcinoma. Methods Retrospective survival analysis was performed using 128 patients who underwent curative pulmonary resection. Results The overall 5-year survival rate was 45.3%. Univariate analysis showed the number of metastases, location (unilateral or bilateral), prethoracotomy carcinoembryonic antigen (CEA) level, hilar or mediastinal lymph-node metastasis, and Dukes' stage to be considerable prognostic factors. Among these, Dukes' A for the primary lesion and unilateral pulmonary metastasis were shown to be independent predictors of longer survival by multivariate analysis ( p = 0.0093 and p = 0.0182, respectively). In patients treated with both pulmonary and hepatic metastastasectomies, a better prognosis was observed in those who received metachronous resection. Recurrence after a pulmonary metastasectomy frequently occurred in the thorax and the 3-year survival rate was 44.6% in patients who underwent a repeat thoracotomy. Conclusions Patients with unilateral metastasis and Dukes' A for the primary tumor benefit most from the resection of pulmonary metastasis from colorectal carcinoma. Further, the number of metastases, prethoracotomy CEA level, and hilar or mediastinal lymph-node involvement should be considered to determine the operative indication. Finally, periodic follow-up examinations for thoracic recurrence should be carefully performed as these patients may have a heightened risk of requiring a repeat thoracotomy.

A 54-year-old woman, who was severely malnourished and awaiting lung transplantation for chronic respiratory failure, was given nutritional support by home parenteral nutrition (HPN). The patient's emaciated state was further compromised by the fact that she had undergone a distal gastrectomy 4 years earlier. We decided that HPN was indicated because her oral intake was so poor and drinking enteral formula reduced her appetite. After 1 year of HPN, her body weight increased and her nutritional, anthropometric, and biochemical values were well maintained by the time of transplantation. Moreover, her progress after lung transplantation was remarkably good, indicating the effectiveness of nutritional support by HPN during the protracted waiting period.

Toll-like receptors (TLR) that recognize microbial pathogens play a critical role in innate immunity; however, their expression and function after surgery remain unknown. The aim of this study was to examine TLR2 and TLR4 expression on monocytes and their responses to each agonist after surgical insults.Blood samples were obtained from 83 patients who underwent gastrointestinal surgery. TLR2, TLR4, and inducible nitric oxide synthase expressions on peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry. Macrophage-activating lipopeptide-2 or lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-6 production was measured by enzyme-linked immunosorbent assay.TLR2 and TLR4 decreased and showed the lowest values on the postoperative days 3 and 1, respectively. Macrophage-activating lipopeptide-2-stimulated tumor necrosis factor-alpha and interleukin-6 production was decreased immediately after the operation (P.05), increased to a maximum value on postoperative day 1, and then decreased gradually. Lipopolysaccharide-stimulated tumor necrosis factor-alpha production was also suppressed immediately (P.05) after operation then showed a gradual increase to maximum values on postoperative day 3. Inducible nitric oxide synthase in cultured PBMC that was obtained immediately after operation was upregulated (P.05).Expressions of TLR2 and TLR4 were downregulated by operation, and agonist-induced cytokine production was suppressed transiently and soon increased through the activation of PBMC. The present study may offer new insights for postoperative modulation of innate immunity under surgical stress.

Background We conducted a trial of a new less invasive, locoregional modality for lung cancer with pleural spread. This study was planned to investigate the feasibility, safety, and pharmacokinetics of pleural perfusion thermochemotherapy (PPTC) under video-assisted thoracoscopic surgery (VATS) and its modified method with a short perfusion time for preventing heat damage to the lung during the procedure. Methods Seventeen patients, 59 to 79 years old, underwent surgical resection of the primary lesions and PPTC under VATS without thoracotomy. All had pleural spread with malignant effusion due to lung cancer proven before the treatment. PPTC consists of irrigating the pleural space with 42°C saline solution containing cisplatin (200 mg/m 2 ) using a devised circuit. The time for perfusion was two hours in 10 patients (group L), and one hour in 7 patients (group S). Results All patients successfully completed this treatment with acceptable toxicities. The pharmacokinetic analysis showed that high platinum levels for the regional pleural exposure, which was 20- to 40-fold greater than those for the plasma in both groups. These values were equivalent between the groups, although the levels for the plasma were higher in group L than in group S. Postoperative lung damage was seen in 4 patients with no serious conditions in group L, and none in group S. The median survival for the L and S groups was 17 and 19 months, respectively. Conclusions This less invasive modality seems to offer a safe, feasible, and pharmacokinetically advantageous procedure to have excellent local control for lung cancer with pleural spread.

For the treatment of lung cancer with advanced pleural spread, aggressive local treatment could offer a chance of cure. This study evaluates the early and midterm results of our Phase I trial for the new modality of two-stage approach combining thoracoscopic intrapleural perfusion hyperthermic chemotherapy (TIPHC) and panpleuropneumonectomy for the disease. Five patients were enrolled in this study. All had proven lung cancer with major malignant pleural effusion or numerous pleural dissemination. The combined regimen was planned first with TIPHC using high doses of cisplatin, followed by a second stage with panpleuropneumonectomy with full-thoracotomy approach as radical surgery. All patients successfully completed this treatment, and there were no serious complications. Panpleuropneumonectomy was performed 14+/-1.2 days after TIPHC, and the mean operation time was 280+/-35 min, the blood loss was 620+/-89 ml. One patient with pathological N2 developed liver metastases 8 months after surgery and died. The other four patients are living and have not experienced any recurrence to date. The mean survival time is 19 months, and the longest is 32 months. Our new treatment modality is feasible and seems to provide a possibility for safe and effective radical local tumor control for patients of lung cancer with advanced carcinomatous pleuritis.

While many retrospective and prospective observational studies have shown laparoscopic surgery to be less invasive than conventional open surgery, this issue has not been evaluated by objective parameters. Currently available clinical parameters, such as the day of first ambulation, the day food intake is commenced, and the length of postoperative hospital stay, are subjective. The purpose of this study was to investigate whether measuring postoperative physical activity with an accelerometer is a useful parameter for evaluating postoperative recovery after surgical stress.The subjects included 20 patients who underwent laparoscopic partial gastrectomy (LPG group), 35 patients who underwent open distal gastrectomy (ODG group), and 20 patients who underwent open total gastrectomy (OTG group). The cumulative acceleration of voluntary movement, measured by an Active tracer AC-301 (ACT) accelerometer for 7 days postoperatively, was compared among these three groups.The cumulative acceleration of physical activity for 24 h was significantly better in the LPG group than in the ODG and OTG groups on each postoperative day. The recovery time, defined as the day that cumulative acceleration had recovered to more than 90% of the preoperative level, was significantly shorter in the LPG group (2.8 +/- 0.9 days) than in the ODG (6.6 +/- 2.1 days) and OTG (7.8 +/- 1.2 days) groups.These results showed that convalescence differed with the degree of surgical stress, and that measurement of the cumulative acceleration of voluntary movement by using an accelerometer could be a useful objective and quantitative parameter for evaluating postoperative recovery.

The efficacy of mucosal suturing for the healing of a mucosal defect in laparoscopic intragastric surgery (LIGS) for gastric lesions is not yet known.We prospectively studied ten patients who underwent mucosal resection by LIGS for gastric tumors: four patients with early gastric cancer and six with gastric adenoma. Patients were randomly divided into two groups: group I (n = 5); patients who underwent mucosal resection by LIGS with mucosal defect suturing and group II (n = 5); patients who underwent mucosal resection by LIGS without mucosal defect suturing. We performed endoscopy on day 10, and 1 month, 2 months, and 3 months after the operation to observe the healing process of the mucosal defect. The ulcer stage by endoscopy was classified as active, healing, or scarring according to the classification of Sakita and colleagues. Patients were given an H(2)-blocker daily until the mucosal defect improved to the scarring stage.There were no significant differences in sex, age, tumor location, size of mucosal resection, or the incidence of Helicobacter pylori infection between groups I and II. The ulcer stages in group I were significantly lower than those in group II on day 10, and 1 month, 2 months, and 3 months postoperation. The medication cost (H2-blocker) in group I was significantly lower than that in group II.Mucosal defect suturing after mucosal resection by LIGS promotes more rapid healing of mucosal defects and reduces drug costs for patients.

Hepatocyte growth factor (HGF) induces angiogenesis in myocardium. In the present study, its effects in chronic ischemic myocardium were tested.Four weeks after left anterior descending coronary artery ligation in canine hearts, HVJ-liposome containing either human HGF gene (160 microg; HGF group, n = 7) or nothing (control group, n = 6) was directly injected into ischemic myocardium. Four weeks after gene transfection, the thickness fraction (TF), an index of regional myocardial contractility (assessed by epicardial pulse-Doppler crystals), the myocardial perfusion flow (assessed by color microspheres), and the capillary density (assessed by immunostaining of vessels) were evaluated in ischemic myocardium.Thickness fraction (percent of nonischemic myocardium) was significantly improved in the HGF group (80 +/- 15 from 52 +/- 16 of pregene; p0.05) whereas it was not changed in the control group (52 +/- 10 from 50 +/- 8 of pregene). The perfusion flow (% of nonischemic myocardium) was significantly improved in the HGF group (98 +/- 17 from 51 +/- 14 of pregene; p0.05) while it was not changed in the Control group (58 +/- 13 from 62 +/- 18 of pregene). The capillary density was significantly higher in the HGF group (894 +/- 211/mm2; p0.05) than that in the control group (511 +/- 127/mm2).Gene transfection of HGF improved angiogenesis, thereby improved regional myocardial function and perfusion in chronic ischemic myocardium. It indicates a potent therapeutic value of HGF gene transfection for chronic ischemic heart diseases such as myocardial infarction.

Adenovirus-mediated CTLA4Ig gene transfer has been reported to enhance graft survival in several rodent transplantation models. In this study, we investigated the efficacy of ex vivo and systemic transfer of the CTLA4Ig gene by adenoviral vectors in pancreatic islet allo-transplantation. Islet grafts from BN rats were transplanted to chemically induced diabetic LEW rats. First, ex vivo CTLA4Ig gene transfer into isolated islets was performed prior to transplantation. Survival of transduced grafts under the kidney capsule was slightly prolonged (8.6+/-1.3 days) compared with survival of untransduced grafts (6.7+/-1.2 days); when combined with a short course of FK506, graft survival was further extended (32.6+/-10.7 days vs. 13.7+/-1.0 days with FK506 alone). Secondly, systemic gene transfer was accomplished by intravenous administration immediately after the transplantation procedure. In these animals, islet grafts under the kidney capsule survived longer (15.2+/-3.3 days) than in controls (6.7+/-1.2 days), and when FK506 was administered perioperatively, all the islet grafts survived for more than 100 days. In systemically transduced recipients, the survival of islet grafts transplanted into the liver was not significantly different from that of the grafts placed under the kidney capsule. In order to examine organ-specific immunogenicity, heterotopic BN cardiac grafts were transplanted to LEW rats intra-abdominally, with the virus transferred systemically as in the islet model. In contrast to the islet grafts, all the cardiac grafts were accepted for longer than 100 days, even without FK506 therapy. Finally, the LEW recipients with long-surviving islet or cardiac grafts were re-transplanted with islet grafts from the same donor strain (BN) on day 100. The second islet grafts survived longer than 100 days in half of the cardiac recipients, but consistently failed in the islet recipients. We conclude that in this transplant model, CTLA4Ig gene transfer and FK506 treatment synergistically improved islet graft survival, systemic transfer of the gene was more effective than ex vivo transfer to the islets, and donor-specific tolerance could not be achieved for islet transplantation but was achieved for cardiac transplantation.

Objectives: Patients receiving induction therapy may have increased risk of morbidity and mortality after surgery. We retrospectively evaluated the influence of preoperative treatment in patients who underwent sleeve resection for lung cancer. Methods: A series of 48 consecutive patients who underwent sleeve resection with a telescoping anastomosis was retrospectively analyzed. A sleeve lobectomy and pneumonectomy were performed in 41 and 7 patients, respectively. Twenty patients received preoperative induction therapy; of them, 16 received induction chemoradiotherapy and 4 received only chemotherapy. Twenty-eight patients underwent the procedure without adjuvant therapy. Results: The telescopic procedure was performed by placing sutures around the proximal and distal portions of the bronchial cartilage without wrapping the anastomosis. Among the 20 patients who received induction therapy, pulmonary angioplasty was performed in 5 and chest wall resection was performed in 3. Seven of these 20 patients (35%) had postoperative complications. Among the 28 patients without preoperative adjuvant therapy, pulmonary angioplasty was performed in 3, diaphragmatic resection was performed in 1, and chest wall resection was performed in 1. Three of these 28 patients (11%) had postoperative complications. Complications relating to the anastomosis occurred in 1 patient (5.0%) who received induction therapy; however, no operative deaths occurred. Bronchoscopic examinations demonstrated that mucosal healing was prolonged in patients who underwent induction therapy. Conclusion: Induction therapy did not significantly affect morbidity or mortality among patients who underwent sleeve resection. J Thorac Cardiovasc Surg 2003;125:96-100

症例は58歳女性で, 26年前,僧帽弁置換術が施行された. 8年前に慢性C型肝炎を指摘された.今回,人工弁機能不全にて,僧帽弁再置換術予定となるが,術前に肝硬変に起因した脾機能亢進による,二次性血小板減少症(血小板数3.4×104/mm3)を認めた.血小板輸血を行うが増加を認めず,開心術に先行して,血小板増加を目的に脾臓摘出術を施行した.その結果,血小板数は,翌日に16.0×104 mm3,脾摘後21日目の開心術時には20.5×104/mm3にまで増加し,血小板凝集能,粘着率もほぼ正常であった.僧帽弁再置換術は,止血に難渋することなく安全に施行しえた.開心術での大量出血,大量輸血は肝不全, MOFにつながり注意を要する.本例での脾摘後の血小板数増加は止血,特に術後早期の出血を抑制する点で有用であった.

Background We have developed a novel test for the surgical margin of pulmonary malignant tumor using a cytologic technique (the run-across method in which a glass slide is run across the staple site), and we have assessed whether this method is useful in predicting margin relapse and prognosis. Methods From April 1996 to March 1999, 15 lesions of stage I non-small cell lung cancer (NSCLC) (maximum diameter ranged from 10 to 35 mm with a median of 20 mm) from 15 patients with cardiopulmonary impairment were excised without additional proximal resections. The surgical margin was examined using the run-across method. There were 8 male 7 female patients whose ages ranged from 51 to 80 years. One patient underwent video-assisted thoracic surgery and 14 underwent thoracotomy. The preoperative diagnoses of the patients were 13 adenocarcinomas, 2 squamous cell carcinomas, and 1 undiagnosed lesion (1 adenocarcinoma). The follow-up period ranged from 37 to 63 months. Results The rate of positive cytology was 47% in comparison with the rate of positive histology of 20%. There were 4 patients with margin relapse (3 of them contained negative histology margins) at a rate of 57% among the positive cytology patients in comparison with 0% among the negative cytology patients ( p = 0.03). In a comparison of survival between the negative cytology group and the positive cytology group, there were no statistically significant differences. Conclusions The run-across method is also useful in confirming complete resection. A positive cytology margin could lead to margin relapse even if a non-small cell lung cancer is resected with a negative histology margin.

Background and Objectives Whether a prognostic role for expression of the tumor suppressor gene (TSG) products exists in resected non–small call lung cancers (NSCLCs) remains controversial. Our study was performed to determine the value of TSGs expressions for patients survival in NSCLCs. Methods We examined 108 resected NSCLCs for the expression of TSG products, p27KIP1, p16INK4A, pRB, and p53 that govern cell cycle transition by immunohistochemistry and compared them with patient clinical characteristics and prognoses. Results Abnormal expressions of p27KIP1, p16INK4A, pRB, and p53 were found in 61 (57%), 53 (49%), 42 (39%), and 48 (44%), respectively, of the 108 NSCLCs. Univariate analysis showed abnormal expression of p27KIP1 to be a strong indicator for poor patient survival, not only in the total cohort (P = 0.0024), but also in subgroups with T1–T2 (P = 0.016), N0 (P = 0.047), and squamous cell carcinomas (P = 0.026), but not according to the expression of p16INK4A, pRB, or p53. In the Cox regression analysis, p27KIP1 expression was found to be an independent prognostic factor (P = 0.0148) and associated with pathological stage (P = 0.0278). Conclusions Our results suggest that abnormal p27KIP1 expression may be a useful indicator to predict postoperative prognosis, especially in patients with early stage NSCLCs, as compared to other TSG products examined. J. Surg. Oncol. 2002;81:177–184. © 2002 Wiley-Liss, Inc.

Objective: Hepatocyte growth factor, a potent angiogenic agent, is unique in having the effects of antiapoptosis and antifibrosis. In the present study we used the rapid pacing-induced heart failure canine model to investigate the effect of gene transfection of hepatocyte growth factor on the failing heart. Methods: Four weeks after onset of rapid pacing, either the human hepatocyte growth factor gene (160 μg; hepatocyte growth factor group, n = 7) or empty vector (control group, n = 7) was directly injected into the left ventricular myocardium by means of the hemagglutinating virus of Japan liposome method. Results: At 4 weeks after gene transfection, the left ventricular global function, assessed by means of pressure-volume loop analysis, was improved in the hepatocyte growth factor group as preload-recruitable stroke work (percentage of baseline: 80% ± 20% from 38% ± 15% before gene transfection, P =.005), whereas it was not changed in the control group (50% ± 18% from 50% ± 18%). Weekly echocardiography showed that this improvement began in the week after gene transfer. The hearts in the hepatocyte growth factor group had a large wall thickness, large myocyte diameter, high capillary density, low fibrotic area fraction, and low density of apoptotic nuclei revealed by means of histologic analysis compared with that in the control group. Myocardial perfusion flow, assessed with color microspheres, was increased in the hepatocyte growth factor group (percentage of baseline: 79% ± 16% from 48% ± 14%, P =.010), whereas it was reduced in the control group (30% ± 12% from 45% ± 17%). Conclusions: Gene transfection of hepatocyte growth factor promoted angiogenesis, improved perfusion, decreased fibrosis and apoptosis, promoted recovery from myocyte atrophy, and thereby attenuated cardiac remodeling and improved myocardial function in the failing heart. It is a novel gene therapy for human heart failure. J Thorac Cardiovasc Surg 2002;124:957-63

Background/Purpose: Interleukin (IL)-12 has been shown to possess potent antitumor activity, and an antitumor effect of systemic IL-12 administration has been reported in liver metastasis models. Methods: In this study, we examined the usefulness of local IL-12 administration into the portal system in the treatment of liver metastasis. First, we confirmed the antitumor effect of recombinant IL-12 (rIL-12) on MC-38 tumors in an intracutaneous model. In the murine liver metastasis model, 1 × 105 of MC-38 cells were injected into the portal vein on day 0, and the spleen was transpositioned subcutaneously for administration of rIL-12 continually into the portal system. From days 3 to 7, 0.1 μg rIL-12 was administered intraperitoneally or intrasplenicly, while Hanks' Balanced Salf Solution (HBSS) was injected intrasplenicly in the control group. Results: The liver weight in the rIL-12 intraperitoneal treatment group (1.88 ± 0.37 g) and that in the rIL-12 intrasplenic treatment group (1.43 ± 0.21 g) were significantly less than that in the HBSS group (2.86 ± 0.74 g; P < 0.05). The numbers of metastatic nodules in the rIL-12 intraperitoneal treatment group (22.3 ± 17.1) and in the rIL-12 intrasplenic treatment group (12.4 ± 13.8) were significantly less than that in the HBSS group (137.1 ± 44.9; P < 0.05). Complete regression of the tumor was observed in one of six mice in the rIL-12 intrasplenic treatment group. This antitumor effect of rIL-12 on MC-38 liver metastasis was not observed in interferon (IFN)-γ knockout mice. Intraportal administration of IL-12-transduced fibroblasts, which were syngeneic to C57BL/6 mice, had an antitumor effect in the MC-38 liver metastasis model. Conclusions: These results suggested that the local administration of IL-12 into the portal system would be a useful strategy for the treatment of liver metastasis.

This study investigates the functional characteristics of the pylorus in patients undergoing pylorus-preserving gastrectomy (PPG) for early gastric cancer.In study 1, postprandial symptoms and gastric emptying were compared between 2 groups of 12 patients with early gastric cancer more than 1 year after either PPG (PPG group) or distal gastrectomy (DG) (DG group). Gastric emptying was evaluated with the dual isotope technique for liquids and solids separately. In study 2, pyloric motility was evaluated with a sleeve/sidehole manometric assembly in 7 patients undergoing PPG, which was compared with that in the preoperative patients.In study 1, the overall modified Visick score of postprandial symptoms and the Sigstad dumping score were significantly lower in the PPG group compared with the DG group (P.05). Early accelerated gastric emptying was observed in both groups for liquids, but only in the DG group for solids. In study 2, isolated pyloric pressure waves induced by intraduodenal lipid infusion and phase III-like activity induced by intravenous erythromycin infusion were preserved after PPG.The quantitative analysis of postoperative symptoms revealed that PPG patients were associated with better clinical conditions than DG patients. The clinical benefits of PPG are considered to be based on the function of the preserved pylorus.

Three patients with triple-vessel disease and severe left ventricular dysfunction underwent successful revascularization on a beating heart, using a right ventricular assist system. Heparin-coated circuits with a centrifugal pump provided 2.5 to 3.5 L·min−1 of flow to maintain good hemodynamics and enable easy access to the posterior vessels during vertical displacement of the heart.

Laparoscopic surgery has had a remarkable impact on the practice of colorectal surgery. However, most operations are performed using a technique of laparoscopic assistance, whereby extracorporeal bowel division and anastomosis are made following laparoscopic mobilization of the bowel. To our knowledge, this is the first report to describe a case of chronic constipation managed by total colectomy with ileorectal anastomosis, performed completely laparoscopically. The diagnosis of slow transit constipation was made by a transit time study. After dissection of the entire colon, the colon to be resected was delivered through the open rectal stump and brought out transanally. The anvil of an intraluminal circular stapler was passed through the rectum into the peritoneal cavity and the end of the open distal rectum was closed with a linear cutting stapler. The anvil of the circular stapler was inserted into the end of the open terminal ileum and fixed with an Endo-Loop, following which an intracorporeal double-stapling anastomosis was performed. By 3 months following surgery, the patient was passing 3-4 stools a day. Thus, we highly recommend this technique as it eliminates the need for a small incision to deliver the resected colon, thereby minimizing the operative time and risk of wound infection.

Background. Anterior mediastinal masses derive from a variety of diseases. Thymomas have been shown to commonly hold CD4 + CD8 + double-positive (DP) lymphocytes, and identification of this subset by two-color flow cytometric study was suggested to help diagnosis of thymoma. Several other thymic diseases, however, possibly hold CD4 + CD8 + DP lymphocytes. In this study, we utilized the three-color flow cytometric method for further examination of the phenotypes of lymphocytes in the thymic diseases. Materials and methods. One hundred eight specimens (77 primary and 10 metastatic thymomas, 10 thymic carcinomas, 2 thymic carcinoids, 4 malignant lymphomas, 2 seminomas, an inflammatory pseudotumor, and 2 nonneoplastic thymic hyperplasias) were subjected to the study. The expressions of CD3, CD4, and CD8 on tumor-associated lymphocytes were evaluated by three-color flow cytometric study. Results. The proportion of the CD4 + CD8 + DP subset was more than 30% in all 78 lymphocyte-rich thymomas, in 2 malignant lymphomas, and in both thymic hyperplasias. CD3 expression of the CD4 + CD8 + DP subset ranged from a negative to a high level in thymomas and thymic hyperplasias, while it was restricted to a particular level in CD4 + CD8 + DP-type malignant lymphomas. The proportion of CD3 + cells in the CD4 + CD8 − single-positive subset was consistently less than 90% in the lymphocyte-rich thymomas, while it was more than 90% in the thymic hyperplasias. Conclusion. Although identification of the CD4 + CD8 + DP subset in the tumor-associated lymphocytes does not necessarily indicate thymoma, a further characterization of thymic neoplasms possessing the CD4 + CD8 + DP subset was enabled by three-color flow cytometric study, suggesting the utility of this method as an ancillary tool for differential diagnosis of these diseases.

Objectives: Recent studies have reported that cis element decoy oligodeoxynucleotides against nuclear factor-κB block the activation of genes that mediate ischemic injury. To improve brain protection during circulatory arrest in cardiac surgery, we evaluated the efficacy of nuclear factor-κB decoy oligodeoxynucleotides in preventing neuronal damage after global brain ischemia. Methods: Hemagglutinating virus of Japan–liposome complex with fluorescein isothiocyanate–labeled nuclear factor-κB decoy oligodeoxynucleotides was injected through the carotid artery during 20 minutes of global brain ischemia in rats to evaluate the efficacy of transfecting the decoy oligodeoxynucleotides. The messenger RNA levels of several factors related to ischemia-reperfusion injury in the hippocampus were estimated by a real-time polymerase chain reaction method 1 hour after reperfusion. Neuronal damage was evaluated by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling staining and by using immunohistochemical study of microtubule-associated protein 2 in the hippocampus CA-1 region 7 days after ischemia. Results: Introduction of the nuclear factor-κB decoy oligodeoxynucleotides into rat brain neurons through the carotid artery during global brain ischemia was markedly successful. The polymerase chain reaction study showed that the transfected nuclear factor-κB decoy oligodeoxynucleotides effectively inhibited the expression of tumor necrosis factor α interleukin 1β and intracellular adhesion molecule 1 messenger RNA 1 hour after global brain ischemia. Terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling staining and microtubule-associated protein 2 immunohistochemistry showed that the transfected nuclear factor-κB decoy oligodeoxynucleotides significantly attenuated the neuronal damage 7 days after global brain ischemia. Conclusions: Therapeutic transfection of nuclear factor-κB decoy oligodeoxynucleotides during brain ischemia may be useful for attenuating neuronal damage, suggesting a strategy for cerebral protection against global ischemia.