Development of a new multi-modal Monte-Carlo radiotherapy planning system.

A new multi-modal Monte-Carlo radiotherapy planning system (developing code: JCDS-FX) is under development at Japan Atomic Energy Agency. This system builds on fundamental technologies of JCDS applied to actual boron neutron capture therapy (BNCT) trials in JRR-4. One of features of the JCDS-FX is that PHITS has been applied to particle transport calculation. PHITS is a multi-purpose particle Monte-Carlo transport code. Hence application of PHITS enables to evaluate total doses given to a patient by a combined modality therapy. Moreover, JCDS-FX with PHITS can be used for the study of accelerator based BNCT. To verify calculation accuracy of the JCDS-FX, dose evaluations for neutron irradiation of a cylindrical water phantom and for an actual clinical trial were performed, then the results were compared with calculations by JCDS with MCNP. The verification results demonstrated that JCDS-FX is applicable to BNCT treatment planning in practical use.

Performance measurement of the scintillator with optical fiber detector for boron neutron capture therapy.

The thermal neutron flux can be easily measured in real time by using the scintillator with optical fiber (SOF) detector. However the irradiation damage under high-intensity neutron flux causes deterioration of the SOF detector due to radiation damage to the plastic scintillator in which (6)LiF is blended. After irradiating the SOF detector for 4 h (thermal neutron fluence is approximately 2.0 x 10(13)neutrons/cm(2)), the sensitivity of the SOF detector decreased by 3.0%. After irradiating the SOF detector for 2 months (thermal neutron fluence approximately 6.4 x 10(14)neutrons/cm(2)), the sensitivity was reduced to 42% of baseline. Supposing that the thermal neutron fluence is 2 x 10(12)neutrons/cm(2) on the surface of a patient in a BNCT treatment, the sensitivity of the SOF detector is reduced by approximately 0.3%. This report presents investigations on the deterioration of the SOF detector in irradiation experiments.

Conceptual design of experimental equipment for large-diameter NTD-Si.

An irradiation-experimental equipment for 12in neutron transmutation doping silicon (NTD-Si) was designed conceptually by using MCNP5 in order to improve the neutron flux distribution of the radial direction. As a result of the calculations, the neutron absorption reaction ratio of the circumference to the center could be limited within 1.09 using a thermal neutron filter that covers the surface of the silicon ingot. The uniformity of the (30)Si neutron absorption was less than 5.3%.

[Coronary artery bypass in octogenarians; how to reduce operative mortality and enhance long-term quality of life].

Octogenarians are at increased risk for perioperative morbidity and mortality after coronary artery bypass. This study is aimed to elucidate the suitable operative strategy and perioperative management. A retrospective analysis was conducted of 54 consecutive patients with 80-years of age or older, who underwent elective isolated coronary artery bypass between May 1999 and May 2008. Mean follow-up was 43.3 months and 96.3% complete. Operavive mortality was 3.7% and the incidence of stroke was 3.7%. The 7-year cardiac survival was 80.4% and the 7-year cardiac event free was 65.0%. The use of arterial graft to the right coronary artery was identified as independent predictor of late cardiac event. Neither total arterial revascularization nor bilateral internal thoracic artery grafting was a significant cardiac event factor. This retrospective study suggests a benefit of the less invasive strategy in terms of operative mortality and morbidity. Application of fast-track treatment in octogenarians appears to be an effective approach to reduce perioperative morbidity and enhance long-term quality of life.

[Successful treatment for prosthetic valve endocarditis with use of strip shaped pericardum].

We presented a case of endocarditis with methicillin-resistant Staphylococcus epidermidis that was successfully treated with linezolid. Endocarditis has been hard to cure completely with either antibiotics or surgery. In particular, it is harder to eradicate disease-causing bacteria when it is staphylococci or streptococci. In this case, an innovative operative technique and a new kind of antibiotics were involved after the failure with some sorts of antibiotics. We put a strip shaped pericardium around a newly implanted artificial ring to prevent its organism from touching it. This technique costs little and may be easy to handle, thus it may become a reliable technique for endocarditis.

[Prophylactic treatment of oral sildenafil citrate for pulmonary hypertension in an infant treated with inhaled nitric oxide after open-heart surgery].

A 3-month-old boy with coarctation of the aorta (CoA), ventricular septal defect (VSD), atrial septal defect, and severe pulmonary hypertension (PH) underwent one-stage repair consisting of patch closure of VSD and coarctation repair. Inhalation of nitric oxide (iNO) was commenced to treat residual severe PH on the day of the operation. Oral sildenafil citrate was commenced on the day 1 and iNO was gradually weaned off on the day 3. There was no "rebound", severe increase in pulmonary artery pressure, which commonly occurs after discontinuation of iNO. Then the patient was extubated without any difficulties or recurrent PH. The oral sildenafil citrate therapy was ceased on the day 8. Prophylactic use of oral sildenafil citrate for PH might be an useful alternative to shorten the duration of iNO therapy and intensive care unit (ICU) stay in the selected patients after congenital open heart surgery.

[Modified technique creating fenestration in the extracardiac Fontan completion; kissing anastomosis].

Acute or subacute occlusion of a fenestration between the Fontan chamber and the atrium causes low cardiac output status, sustained pleural effusion, and protein losing enteropathy in critical cases. To achieve reliable and long patency of the fenestration in extracardiac Fontan operations, we modified our technique for creating a fenestration, namely "kissing" anastomosis, in which the atrial incision is directly sutured to the surface of the extracardiac conduit leaving a few millimeters outside from the edge of the punched-out hole (fenestration). We applied this modification in 2 cases. The diameter of the hole is 4 mm (case 1) and 3 mm (case 2). The patients were anticoagulated by warfarin potassium after the surgery. The fenestrations were patent at 3- (case 1) and 1-month (case 2) after the surgery. Peripheral oxygen saturations at discharge were 86 (case 1) and 88% (case 2). There was no death or major complication. The described procedure is an effective alternative to maintain patency and function of the fenestration in extracardiac Fontan operations.

[Mechanical complications of myocardial infarction in elderly patients].

As mechanical complications after myocardial infarction in the elderly, we described the therapeutic strategies for postinfarction ventricular septal perforation (PVSP), ischemic cardiomyopathy (ICM), and ischemic mitral regurgitation (IMR). To improve operative results for PVSP in the elderly, it is important to maintain hemodynamics by cardiac support device such as intraaortic balloon pumping, and to perform prompt surgical intervention before cardiogenic shock and multiple organ failure. Infarct exclusion technique is a standard surgery for PVSP. Both ICM and IMR are common disease caused by severe cardiac ischemia and mitral valve (MV) function is related to left ventricular (LV) geometry. We consider total MV-LV geometrical repair by LV restoration surgery, MV repair, and coronary revascularization is essential to improve morphological abnormality in LV and MV even in the elderly. To maximize LV function, septal anterior ventricular exclusion (SAVE) technique for antero-septal myocardial ischemia, apex-sparing Batista operation for lateral ischemia, and undersized mitral annuluoplasty to improve LV sphericity are procedures of choice. However, it is still difficult to save elderly patients with very low cardiac function. Novel treatments such as regenerative medicine by angiogenic cytokines and/or cell transplantation, and advanced medical treatments are waited for this high-risk group.

[Successful implantation of a metal coronary angioplasty stent for bronchomalacia of the right tracheal bronchus associated with right isomerism complex in an early infant].

One-month-old boy had severe emphysema of the right upper lobe due to the stenotic tracheal bronchus compressed between the distorted right patent ductus arteriosus (PDA) and the right aortic arch associated with right isomerism complex. He underwent a left modified Blalock-Taussig shunt and a division of the PDA on cardiopulmonary bypass. Extracorporeal lung support (ECLS) was introduced because of severe hypoxemia caused by remaining bronchomalacia of the tracheal bronchus. On postoperative day 3, a metal coronary angioplasty stent was implanted at the stenotic lesion under fluoroscopic and bronchoscopic guidance. He was successfully weaned from ECLS and then respirator after the implantation. This simple stenting procedure might be an effective alternate in the treatment of bronchomalacia or bronchial stenosis in early infancy.

Living-donor lobar lung transplantation for pulmonary and abdominopelvic lymphangioleiomyomatosis.

We performed emergency living-donor lobar lung transplantation (LLTx) successfully in a 24-year-old woman with end-stage pulmonary and massive abdominopelvic lymphangioleiomyomatosis (LAM). Preoperatively, her respiratory condition was critical, but abdominopelvic lesions had been well controlled with medication. No LAM patients with massive abdominopelvic lesions as in the present case have been reportedly treated by LLTx previously. The present case demonstrates that LLTx can be a therapeutic option for end-stage pulmonary LAM with massive abdominopelvic involvement.

[Successful resection of left ventricular myxoma in a toddler; report of a case].

A 4-year-old girl was found to have large left ventricular myxoma without any tumor-related symptoms. She underwent an urgent surgery and the myxoma was successfully removed through a left ventriculectomy. Great care was taken to prevent tumor-embolization during surgery, and to resect the endocardium attaching directly to the tumor. Future surveillance of this case warrants our operative technique described in this report.

[Isolated coronary artery bypass grafting in octogenarians].

We evaluate the outcomes of isolated coronary artery bypass grafting (CABG) in high-risk octogenarians. There are 20 cases in 5 years, which contain 1 re-operation case, and 10 emergency cases. Nineteen cases were performed off-pump CABG (OPCAB), and conventional CABG was performed for only 1 case because of unstable hemodynamics with intraaortic balloon pumping (IABP). We generally performed CABG with aorta no-touch technique. There is no death case, and no serious complication like stroke. We used 23 artery and 11 vein grafts for CABG, and mean number of grafts per patient was 1.8+/-0.7. And "hybrid therapy" with percutaneous transluminal coronary angioplasty (PTCA) was done for 5 cases. Octogenarians are at increased risk for perioperative morbidity and mortality after CABG, but we have performed OPCAB for them and have had good results. And we think that aorta no-touch technique, proper selection and use of graft are important.

[Oral sildenafil citrate as an effective alternate in the treatment of postoperative pulmonary hypertensive crisis after congenital heart surgery].

A five-month-old girl of Down syndrome underwent a corrective surgery for complete atrioventricular septal defect. Her postoperative course was complicated with pulmonary hypertensive (PH) crises despite nitroglycerin (NTG) infusion and inhaled nitric oxide (NO). Sildenafil citrate, a phosphodiesterase 5 inhibitor, was administered through a nasogastric tube at a starting dose of 0.3 mg/kg by stepwise increment to the maximum dose of 2 mg/kg 4 hourly. Sildenafil citrate dramatically lowered pulmonary arterial pressure and the patient was weaned from NTG and NO without PH crisis. There was no side effect after sildenafil citrate administration. Oral sildenafil citrate is a safe and potent adjunct to the existing therapies for postoperative PH in infants after open heart surgery.

PMEA coating of pump circuit and oxygenator may attenuate the early systemic inflammatory response in cardiopulmonary bypass surgery.

We investigated the effects of coating a cardiopulmonary bypass (CPB) circuit and oxygenator with poly-2-methoxy-ethyl acrylate (PMEA) on the systemic inflammatory response during and after CPB. Thirty patients undergoing elective cardiac surgery were randomized into three groups (each group n = 10): noncoated (group N), heparin coated (group H), and PMEA coated circuit and oxygenator (group X). Bradykinin (BK), complement 3 activation (C3a) and interleukin-6 (IL-6) levels were measured as early phase indicators of inflammatory response, as were maximum C reactive proteins (CRP) and white blood cell (WBC) levels. The alveolar-arterial oxygen gradient (A-a DO2) was measured as a parameter of respiratory function. IL-6 levels after CPB were significantly higher in group N than in groups H and X (p < 0.05). Serum BK and C3a levels showed similar patterns in all groups. A-a DO2 was lower at the end of and 3 hours after CPB in groups H and X than in group N (p < 0.05). Maximum CRP levels were lower in group X than in groups N (p < 0.05). This prospective study suggests that PMEA coated CPB may improve respiratory function and decrease systemic inflammatory response after cardiac surgery, possibly because this circuit is as biocompatible as heparin coated CPB circuit.

A new acellular vascular prosthesis as a scaffold for host tissue regeneration.

OBJECTIVE: In situ tissue engineering using acellular xenografts is a new approach to autologous tissue regeneration. In the present study, we analyzed a new regeneration scaffold comprised of xenogenic acellular vessels in a dog model. DESIGN OF STUDY AND RESULTS: Xenogenic vascular conduits of porcine carotid arteries were acellularized by a 48-hour detergent incubation to extract all the cell components of the graft. The acellularisation procedure resulted in a complete removal of all cells. After this procedure, heparinization was performed sequentially to induce antithrombogenicity in the graft. The burst pressure of the graft was tested. The bursting pressure of the fresh vessels was 2.83 +/- 0.56 x 10(3) mmHg (377 +/- 75kPa, n = 6). After detergent treatment, the bursting pressure of the grafts was 2.50 +/- 0.48 x 10(3) mmHg (334 +/- 63 kPa, n = 6); after heparinization, it was 3.44 +/- 0.38 x 10(3) mmHg (459 +/- 51 kPa, n = 5). In vivo function was tested in a dog model by transplantation to the abdominal artery. By 18 weeks, endothelial cells were aligned as in normal, healthy artery over the surface of the entire graft. Fibroblasts and macrophages had infiltrated the graft from both inside and outside. The neointima contained normal layers of smooth muscle cells, which were identified by anti alpha-smooth muscle fiber antigen staining. CONCLUSIONS: The acellular heparinized xenograft has sufficient mechanical properties and was successfully replaced with host tissue, and is thus a promising new type of vascular prosthesis.

[Total aortic arch replacement with a right femur neck fracture on chronic renal dialysis; report of a successful case].

Although recent operative outcome for aortic arch aneurysm has been improved by various newly-devised assistant measures, satisfactory results have not been obtained in cases with serious preoperative complications, such as chronic renal failure. We present here an operative case of a 67-year-old woman on chronic hemodialysis with a calcified aortic arch aneurysm and a right femur neck fracture. First, we performed femur head replacement under careful hemodynamic control. After her mobilization was achieved, total aortic arch replacement was performed in "arch-first technique" using deep hypothermia plus retrograde cerebral perfusion in consideration of her calcified vessels. Her postoperative course was uneventful. We believe that early mobilization was a key for her recovery, because it was useful to prevent postoperative complications such as pulmonary infection and atelectasis. Our experience suggested that meticulous management throughout the whole perioperative course is very important for total aortic arch replacement in such complicated cases.

Haptic reproduction and interactive visualization of a beating heart for cardiovascular surgery simulation.

This paper aims to achieve haptic reproduction and real-time visualization of a beating heart for cardiac surgery simulation. Unlike most forgoing approaches, the authors focus on time series datasets and propose a new framework for interactive simulation of active tissues. The framework handles both detection and response of collisions between a manipulator and a beating virtual heart. Physics-based force feedback of autonomous cardiac motion is also produced based on a stress-pressure model, which is adapted to elastic objects filled with fluid. Time series datasets of an adult man were applied to an integrated simulation system with a force feedback device. The system displays multi-dimensional representation of a beating heart and provides a basic training environment for surgical palpation. Finally, results of measurement and medical assessment confirm the achieved quality and performance of the presented framework.

Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide.

BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Increased pericardial fluid concentrations of the mature form of adrenomedullin in patients with cardiac remodelling.

BACKGROUND: There is evidence that adrenomedullin has autocrine or paracrine activities that oppose cardiac remodelling. However, it remains unclear whether it exerts those local functions in heart failure patients. OBJECTIVE: To investigate the relation between plasma and pericardial fluid concentrations of adrenomedullin and left ventricular haemodynamic variables. DESIGN: Samples of plasma and pericardial fluid were obtained from 50 patients undergoing cardiac surgery. They were classified into two groups: group N (n = 27) with a left ventricular end diastolic volume index (LVEDVI) < or = 90 ml/m(2); and group R (n = 23) with LVEDVI > 90 ml/m(2). Plasma and pericardial fluid concentrations of total adrenomedullin (tAM) and mature adrenomedullin (mAM) were measured and related to the preoperative haemodynamic variables. RESULTS: Pericardial fluid concentrations of mAM were much higher than the plasma concentration in both group N and group R (mean (SEM), 10.6 (1.7) v 3.3 (0.2) fmol/ml, p = 0.0001; and 21.2 (2.8) v 3.9 (0.3) fmol/ml, p < 0.0001, respectively). The ratio mAM/tAM in pericardial fluid was significantly higher than in plasma (0.56 (0.02) v 0.28 (0.02), p < 0.0001). Pericardial fluid concentrations of mAM, but not plasma concentrations, were significantly correlated with LVEDVI, left ventricular end systolic volume index, left ventricular ejection fraction, and left ventricular mass index (r = 0.60, 0.63, -0.54, and 0.47, respectively). CONCLUSIONS: Raised pericardial fluid concentrations of mAM may reflect the actions of adrenomedullin as a local mediator against cardiac remodelling in patients with left ventricular dysfunction.

Mutational analysis within the 3' region of the PKD1 gene in Japanese families.

Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that causes renal failure. One of the genes that is responsible for this disease, PKD1, has been identified and characterized. Many mutations of the PKD1 gene have been identified in the Caucasian population. We investigated the occurrence of mutations in this gene in the Japanese population. We analyzed each exon in the 3' single copy region of the gene between exons 35 and 46 in genomic DNA obtained from 69 patients, using a PCR-based direct sequencing method. Four missense mutations (T3509M, G3559R, R3718Q, R3752W), one deletion mutation (11307del61bp) and one polymorphism (L3753L) were identified, and their presence confirmed by allele-specific oligonucleotide (ASO) hybridization. These were novel mutations, except for R3752W, and three of them were identified in more than two families. Mutation analysis of the PKD1 gene in the Japanese population is being reported for the first time.