Heart donation in Japan before and after the revision of the Japanese Transplantation Act.

INTRODUCTION: After the revision of the Organ Transplant Act in July 2010, brain dead organ donation increased from 13 to 45 per year, and heart donation increased. The purpose of this study was to review 166 consecutive brain dead heart donors to evaluate our strategies to identify and manage organ donors. METHODS: This study reviewed 166 consecutive brain dead heart donors since the Act was issued. Whereas 69 heart donations were performed between October 1997 and July 2010 before the revision of the Act, 97 heart donations were performed for the 3 years after the revision. Since November 2002, special transplant management doctors were sent to donor hospitals to assess donor organ function and to identify which organs could be transplanted. They also intensively cared for the donors to stabilize hemodynamics and to improve cardiac function by giving intravenous antidiuretic hormones and by pulmonary toileting via bronchofiberscope. RESULTS: The mean heart donor age increased from 41.0 to 43.9 years after the revision. Notably, 11 hearts from donors more than 60 years old were transplanted successfully after the revision. Before the revision, the cause of death was 37 cerebrovascular disease (SAH 34, stroke 1, bleeding 2), 18 head trauma, 13 asphyxia, and 2 postresuscitation brain damage. After the revision, there were 49 cerebrovascular disease (SAH 37, stroke 2, bleeding 16, and other 4), 17 head trauma, 10 asphyxia, and 11 postresuscitation brain damage. A total of 58 donors had a history of cardiac arrest, 58 required a high dose of catecholamine drip infusion, and only 1 recipient died of primary graft dysfunction. Patient survival rate at 3 years after heart transplantation was not different before and after the revision of the Act (98.6% vs 92.2%). CONCLUSIONS: Although donor age was increased and donors who died of cerebral bleeding or postresuscitation after the revision of the Act increased, the outcome after heart transplantation was not changed.

Japanese strategies to maximize heart and lung availabilities: experience from 100 consecutive brain-dead donors.

OBJECTIVE: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies have been established to maximize heart and lung transplantations (HTs and LTs, respectively). We reviewed 100 consecutive brain-dead donors to evaluate our strategies to identify and manage heart and lung donors. METHODS: We retrospectively reviewed all 100 consecutive brain-dead donors procured since the law was issued in 1997. There were 56 mens and the overall mean donor age was 43.5 years. The causes of death were cerebrovascular disease (n = 62), head trauma (n = 20), and asphyxia (n = 16): Since November 2002, special transplant management doctors were sent to donor hospitals to assess cardiac and lung functions, seeking to identify transplant opportunities. They stabilized donor hemodynamics and lung function by administering antidiuretic hormone intravenously and performing bronchofibroscopy for pulmonary toilet. RESULTS: Seventy-nine HTs, 1 heart-lung transplantations, and 78 LTs (46 single and 32 bilateral) were performed. By applying these strategies organs per donor were increased from 4.5 to 6.8. Among heart donors, 61/80 were marginal: high inotrope requirement (n = 29), cardiopulmonary resuscitation (n = 28), and/or >55 years old (n = 20). None of the 80 HT recipients died of primary graft failure (PGF). Patient survival rate at 10 years after HT was 95.4%. Among lung donors, 48/65 were marginal: pneumonia (n = 41), chest trauma (n = 4), and >55 years old (n = 9). Only 2/78 LT recipients died of PGF. Patient survival rate at 3 years after LT was 72.2%. After inducing frequent pulmonary toilet, lung procurement and patient survival rates increased significantly after LT. CONCLUSIONS: Although the number of cases was still small, the availability of organs has been greater and the outcomes of HT/LT acceptable.

Donor evaluation and management system (medical consultant system) in Japan: experience from 200 consecutive brain-dead organ donation.

PURPOSE: As the donor shortage is extremely severe in Japan because of a strict Organ Transplantation Act, special strategies must be established to maximize organ transplant opportunities. The purpose of this study was to evaluate our strategies to identify and manage 200 consecutive brain-dead organ donors. METHODS AND MATERIALS: We retrospectively reviewed the 200 donors procured since the Organ Transplantation Act was issued in 1997, including 118 males, a mean overall age of 45.1 years and cause of death being cerebrovascular disease (n = 119), head trauma (n = 37), and asphyxia (n = 44). DONOR EVALUATION AND MANAGEMENT SYSTEM: Since November in 2002, special transplant management doctors ("medical consultants") were sent to donor hospitals to assess organ function and identify transplantable organs. They also provided intensive care to stabilize hemodynamics and improve cardiac and lung functions by administering antidiuretic hormone intravenously and providing bronchofiberscopic pulmonary toilet. RESULTS: We obtained 146 heart, 1 heart-lung, and 154 lung (87 single and 67 bilateral), 175 liver (28 splitted liver), 142 pancreas (114 pancreas-kidney), 253 kidney and 12 small bowel grafts. Organs procured from 1 donor increased from 4.5 to 6.8 after applying these strategies. CONCLUSIONS: Although the number of cases was still small, the availability of organs and outcomes of transplantation have been acceptable.

[Atheromatous aorta: clinical pitfall in cardiovascular surgery].

A highly atheromatous aorta has been reported to bring about devastating complications such as endorgan ischemia with or without aortic manipulation. One of the complications has been perioperative stroke known that almost the halves suffered have been dead even in recent era. The other of the devastating complications has been called cholesterol crystal embolization or blue toe syndrome, meaning scattered embolization by small cholesterol crystals towards splanchnic organs or lower extremities respectively, which has also known to be critical. Nowadays, new devices have encouraged cardiovascular clinician to have a plan for a safe cardiovascular intervention including aortic manipulation even with highly atheromatous aorta. Before the manipulation, modern powerful modalities such as transesophageal echocardiography, epiaortic ultrasonography and computed tomography (CT), have already become common based on many evidences. During operation, evolving techniques and technologies such as off-pump coronary artery bypass grafting (OPCAB) and axillary artery cannulation both of which are aorta non-touch techniques, which are technically demanding, has proved to reduce perioperative stroke recently even though severe complications still occur in lower percentages.

[Is emergency aortic root replacement combined with arch replacement safe?].

BACKGROUND: Aortic root replacement (ARR) combined with aortic arch replacement (AAR) is an invasive procedure even in elective cases. Nevertheless, such combined operations are often mandatory in acute type A aortic dissection. We examined whether emergency operation might have further incremental risks compared with elective surgery in this type of operations. METHODS: Forty-six cases of ARR combined with AAR were divided into 2 groups, the emergency (EM) group and the elective (EL) group. The EM group consisted of 10 cases of acute type A aortic dissection, whereas the EL group of 36:23 of chronic aortic dissection and 13 of true aneurysm. RESULTS: There were no statistical differences between the 2 groups in the durations of aortic crossclamp, selective cerebral perfusion and cardiopulmonary bypass. The incidences in the EM and EL groups were as follows:in-hospital death; 0 vs 3( 8%), respiratory failure; 4 (40%) vs 14 (39%), renal failure; 0 vs 6 (17%), IABP requirement; 1 (10%) vs 3 (8%), and cerebral infarction; 0 vs 1 (3%), respectively. CONCLUSION: Early surgical results of emergency ARR combined with AAR were almost equal to those in elective surgery.

Disruption of Tacc3 function leads to in vivo tumor regression.

The formation of the bipolar spindle is responsible for accurate chromosomal segregation during mitosis. The dynamic instability of microtubules has an important role in this process, and has been shown to be an effective target for cancer chemotherapy. Several agents that target non-microtubule mitotic proteins, including the motor protein Eg5, Aurora kinases and Polo-like kinases, are currently being developed as chemotherapeutic drugs. However, because the efficacies of these drugs remain elusive, new molecular targets that have essential roles in tumor cells are desired. Here, we provide in vivo evidence that transforming acidic coiled-coil-3 (Tacc3) is a potential target for cancer chemotherapy. Using MRI, we showed that Tacc3 loss led to the regression of mouse thymic lymphoma in vivo, which was accompanied by massive apoptosis. By contrast, normal tissues, including the thymus, showed no overt abnormalities, despite high Tacc3 expression. in vitro analysis indicated that Tacc3 depletion induced multi-polar spindle formation, which led to mitotic arrest, followed by apoptosis. Similar responses have been observed in Burkitt's lymphoma and T-ALL. These results show that Tacc3 is a vulnerable component of the spindle assembly in lymphoma cells and is a promising cancer chemotherapy target.

[Aortic root surgery in patients with previous aortic root or valve operations].

OBJECTIVES: To assess the operative indication, risk factors, procedures, and outcomes of aortic root surgery in patients with previous aortic root or valve surgery. PATIENTS AND METHODS: Between 1995 and 2007, aortic root surgery was performed in 137 patients. Thirty-five of those, who had previous root replacement, root remodeling or aortic valve surgery, were evaluated retrospectively. RESULTS: Indications for redo surgery included lesions at coronary artery reconstruction site after root procedures, aneurysmal formation or dissection of sinus Valsalva after aortic valve procedures, and prosthetic material infection. Two cases with prior graft infection died of sepsis, and one case with extended aortic dissection died of esophageal bleeding. Hospital mortalities were, hence, 8.6% in redo cases, which was comparable to 5.0% in primary root surgery cases. Multivariate risk factor analysis of root surgery revealed that preceding infective aortic root lesion was the only significant independent risk factor for postoperative mortality, whereas redo procedure per se was not a significant risk. CONCLUSIONS: Redo aortic root surgery can be performed with a reasonably low operative risk. Graft infection in patients with previous aortic root surgery remains a challenging lesion.

Efficacy of perfusion cooling of the epidural space and cerebrospinal fluid drainage during repair of extent I and II thoracoabdominal aneurysm.

AIM: The aim of this study was to evaluate spinal cord injury and mortality resulting from repair of extent I and II thoracoabdominal aneurysm. The authors compared patients operated under mild hypothermia with or without epidural perfusion cooling (EPC) and cerebrospinal fluid drainage (CSFD). METHODS: From 1988 to 2007, 116 patients underwent replacement of the thoracoabdominal aorta; the procedure was performed in 38 patients with the aid of mild hypothermia alone (group A), and in 78 patients with the aid of EPC, mild hypothermia and CSFD (group B). Two catheters for epidural perfusion cooling were inserted in group B, in which one catheter was inserted into the epidural space to infuse chilled saline, and the other was inserted into the subdural space to drain the cerebrospinal fluid and to measure temperature and pressure. There were no significant differences in mean age, etiology of aortic disease, and aneurysm extent between the two groups. RESULTS: There were no significant differences in cardiopulmonary bypass time, the lowest nasopharyngeal temperature and operation time between the two study groups. The incidence of spinal cord injury in group A (16.2%) was significantly higher than in group B (3.8%, P=0.03). Hospital mortality in groups A and B was 10.5% and 2.6%, respectively (P=0.08). There was no significant difference in postoperative complications between the two study groups. CONCLUSION: The combination of EPC and CSFD was effective in lowering the incidence of postoperative spinal cord injury in the repair of extent I and II thoracoabdominal aortic aneurysm.

Functional results of intersphincteric resection for low rectal cancer.

BACKGROUND: Intersphincteric resection (ISR) is the ultimate sphincter-preserving operation for very low rectal cancer. The aim of this study was to assess defaecatory function after ISR in relation to the degree of resection of the internal anal sphincter. METHODS: Between 2001 and 2003, 35 consecutive patients with low rectal cancer had curative ISR, categorized as total, subtotal or partial resection of the internal anal sphincter. Defaecatory function was assessed in terms of frequency of bowel movements and continence. Sphincter function was evaluated by manometric study and anorectal sensation testing before surgery and 3, 6 and 12 months afterwards. RESULTS: Defaecatory function was satisfactory after ISR; 34 of 35 patients were grossly continent. The maximum resting anal canal pressure fell after all three procedures. Patients who had total ISR had reduced anal canal sensation at 3 months, but this had improved by 12 months after surgery. CONCLUSION: These functional results suggest that ISR should be considered as an alternative to abdominoperineal resection for low rectal cancer. However, as the outcome for continence is worse after total ISR than subtotal or partial ISR, the indication for total ISR should strictly take into account the preoperative sphincter function.

Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in macroprolactinemia.

Macroprolactinemia, in which serum prolactin (PRL) mainly consists of PRL with a molecular mass greater than 100 kDa, has been demonstrated to be associated with hyperprolactinemia. We previously reported that anti-PRL autoantibody is the major cause of macroprolactinemia. In this study, the autoantibody-binding sites (epitopes) on the PRL molecule were examined using deletion mutant PRL. The sera from 159 patients with hyperprolactinemia were screened for macroprolactinemia using the polyethylene glycol method and 18 patients (11%) were diagnosed with macroprolactinemia. The sera from these patients were incubated with glutathione S-transferase-human prolactin (hPRL) fragment fusion proteins immobilized on glutathione sepharose and the amounts of bound immunoglobulin G (IgG) were measured using ELISA. IgG was bound to full-length hPRL1-199 in significantly greater amounts in sera from 14 of 18 patients with macroprolactinemia than in controls. hPRL, but not PRL of other species such as bovine, porcine, rat, or human GH, dose-dependently displaced the binding, suggesting that these patients had hPRL-specific autoantibodies. Deletion of 34 amino acid residues from N-and/or C-terminals significantly reduced the binding and N- or C-terminal fragment alone showed partial but significant binding, suggesting that the major epitopes recognized by anti-PRL autoantibodies are located in both N- and C-terminal residues of the PRL molecule.

Repair of congenital ascending aortic aneurysm.

We report a case of congenital ascending aortic aneurysm associated with double-outlet right ventricle that has been successfully repaired by graft replacement and extracardiac total cavo-pulmonary connection.

[Emergent coronary artery bypass grafting using percutaneous cardiopulmonary support in a patient with a quadricuspid aortic valve; report of a case].

A 63-year-old man was admitted to our hospital for acute myocardial infarction. A cardiac catheter study showed 3 vessels coronary disease. He was treated by percutaneous coronary intervention for a left anterior descending arterial (LAD) lesion. Unfortunately, cardiac tamponade following stenting for LAD was complicated. A percutaneous cardiopulmonary support system was commenced along with an emergent coronary artery bypass grafting to the LAD and obtuse marginal branch. A quadricuspid aortic valve was discovered by an aortotomy and identified as Hurwitz-Roberts classification type b. Blood from the left coronary main trunk had already stopped. Intraaortic balloon pumping was instituted while weaning from the cardiopulmonary bypass. The patient's postoperative course was uneventful and all bypass grafts were sufficient. He was well 1 year after the operation.

[Spinal cord protection during most or all of descending thoracic or thoracoabdominal aneurysm repair].

OBJECTIVES: The purpose of this study is to evaluate usefulness of perfusion cooling for regional spinal cord hypothermia during most or all of thoracic or thoracoabdominal aneurysm repair. METHODS: From 1987 to 2003, 103 patients underwent most or all of thoracic or thoracoabdominal aneurysm repair. Forty-eight patients underwent operation using distal aortic perfusion, mild hypothermia and segment sequential repair (group MH). Fifty-five patients underwent the same operation as group MH except epidural perfusion cooling and drainage of cerebrospinal fluid (CSF) [group EC & CSFD]. The aorta was replaced sequentially in segment and several paris of intercostal and lumbar arteries were reconstructed in 2 groups. RESULTS: Cardiopulmonary bypass time of group MH and group EC & CSFD was averaged 235 and 241 minutes, respectively. The lowest CSF temperature in group EC & CSFD was averaged 24.7 degrees C, and the difference between nasopharyngeal and CSF temperature was averaged 6.4 degrees C. The rate of spinal cord injury of group MH and EC & CSFD was 10.4% and 3.6%, respectively. Hospital mortality of group MH and EC & CSFD was 8.3% and 5.5%, respectively. The incidence of spinal cord injury and hospital mortality of group EC & CSFD were decreased compared to them of group MH. CONCLUSION: We conclude that the perfusion cooling of epidural space and CSF drainage are effective method in reducing postoperative spinal cord injury.

Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.

Dieulafoy's lesion is an arterial malformation in the subumucosal layer of the gastrointestinal tract that can cause massive bleeding. The esophagus is not a common location for this lesion. We present here a first report of Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.

Blalock-Taussig shunt for a neonatal case of Ebstein's anomaly with unobstructed right ventricular outflow tract.

A neonate with Ebstein's anomaly presented with severe cyanosis because of massive right-to-left shunt through an atrial septal defect and reduced blood flow through an unobstructed right ventricular outflow tract. This atypical patient underwent a right modified Blalock-Taussig shunt, which resolved the respiratory.

Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer.

If oesophageal carcinoma is detected in the superficial stage, the prognosis is better than for advanced oesophageal carcinoma. But the factors which predict the prognosis and treatment policy remain unclear. Matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) have been reported to have close associations with tumour invasion and metastasis. In this study, we retrospectively studied the relations between MMP-7 and MMP-9 expression in immunohistochemistry, clinicopathologic factors, and prognosis in 55 superficial oesophageal carcinomas. MMP-7 and MMP-9 expression occurred in 23.6% and 47.3% of the patients, respectively. MMP-7 expression was significantly correlated with the presence of nodal metastasis (P=0.004). MMP-9 expression was significantly correlated with the depth of tumour invasion (P=0.004), lymphatic permeation (P=0.001), nodal metastasis (P=0.049), and pathologic differentiation grade (P=0.003). By the log-rank test, MMP-7 expression and MMP-9 expression on the invasive front were related to the prognosis. In multivariate analysis, MMP-9 expression on the invasive front was an independent prognostic indicator. The combined expression of MMP-7 and MMP-9 may be a good marker for the degree of malignancy of oesophageal cancer and for the presence of lymphatic metastasis.

Pulmonary vascular changes induced by unilateral pulmonary venous obstruction.

The relation of pulmonary hemodynamics to pathological change in the pulmonary vasculature was examined in a model of unilateral pulmonary venous (PV) obstruction. The left upper pulmonary vein (A group, n=6) or both the left upper and left lower pulmonary veins (B group, n=6) of two-week-old piglets were banded; the control group (n=6) was sham operated. At eight weeks after PV banding, mean pulmonary arterial pressure was highest in the B group, intermediate in the A group and lowest in the control group. In all groups, the media of the pulmonary artery was equally thickened in both lungs, whereas the media of the pulmonary vein was thickened only in those lung lobes having stenotic pulmonary veins. For all animals from three groups, left pulmonary arterial wedge pressure (PAWP) correlated with medial thickness of the pulmonary arteries of the right lung (r=0.76, p=0.003), the left upper lobe (r=0.54, p<0.03), the left lower lobe (r=0.49, p=0.04). This finding suggests that the pathogenesis of PAWP-related medial thickening of the bilateral lung pulmonary artery begins with the sensing by the bilateral lung of PV pressure buildup in the unilateral lung.

Intraocular hemangiopericytoma. A case report.

A 55-year-old man presented with a smoothly elevated solid choroidal mass with choroidal detachment in the temporal region of the left eye. Both fluorescein and indocyanine green angiography suggested a vascularized lesion such as an angioma. However, radiographic examination revealed a solid, circumscribed, dome-shaped mass. During a 3-month observation, the mass gradually enlarged and invaded the iris. The possibility of malignant melanoma could not be ruled out. Due to rapid and continued growth of the tumor, the eye was enucleated. Histopathologic examination revealed proliferation of spindle-shaped cells surrounding reticulin-positive vessels, which is characteristic of hemangiopericytoma. To our knowledge, this is only the fourth reported case of intraocular hemangiopericytoma and the first diagnosed in a male patient.

pH paradox and neonatal heart.

BACKGROUND: To evaluate the functional status of the Na+/H+ exchanger in the neonatal heart. METHODS: On the Langendorff system, isolated neonatal rabbit hearts were arrested by using cardioplegia with or without a specific Na+/H+ exchanger blocker, 5-(N,N dimethyl) amiloride (DMA) (20 microM). Ischemic period was 40 minutes at 37 degrees C or 120 minutes at 20 degrees C before 30 minutes of reperfusion at 37 degrees C. When DMA was added to the cardioplegia solution, it was also added to the reperfusate for the first 5 minutes of reperfusion (20 microM). RESULTS: Postischemic developed pressure was 50.3+/-7.1 mmHg in the DMA group versus 25.9+/-6 mmHg in the control group (p<0.05) at 37 degrees C and 74.8+/-14.6 mmHg in the DMA group versus 60.6+/-11.5 mmHg in the control group (p<0.05) at 20 degrees C. Postischeimic diastolic pressure was 40.4+/-3.3 mmHg in the DMA group versus 28.4+/-7 mmHg in the control group (p<0.05) at 37 degrees C and 9.6+/-3.1 mmHg in the DMA group versus 15+/-3.7 in the control group (p<0.05) at 20 degrees C. Creatine kinase washout was 296+/-97 IU/L in the DMA group versus 1253+/-537 IU/L in the control group (p<0.05) at 37 degrees C and 370+/-156 IU/L in the DMA group versus 524+/-104 IU/L in the control group (p<0.05) at 20 degrees C. CONCLUSIONS: 1) The Na+/H+ exchanger is active in the neonatal heart. 2) The Na+/H+ exchanger plays a key-role in the pathogenesis of reperfusion injury of the neonatal myocardium. 3) This exchanger is sensitive even for low H+ transmembrane gradients and even under hypothermic conditions.