Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system.

Animal fetuses and embryos may have applications in the generation of human organs. Progenitor cells may be an appropriate cell source for regenerative organs because of their safety and availability. However, regenerative organs derived from exogenous lineage progenitors in developing animal fetuses have not yet been obtained. Here, we established a combination system through which donor cells could be precisely injected into the nephrogenic zone and native nephron progenitor cells (NPCs) could be eliminated in a time- and tissue-specific manner. We successfully achieved removal of Six2+ NPCs within the nephrogenic niche and complete replacement of transplanted NPCs with donor cells. These NPCs developed into mature glomeruli and renal tubules, and blood flow was observed following transplantation in vivo. Furthermore, this artificial nephron could be obtained using NPCs from different species. Thus, this technique enables in vivo differentiation from progenitor cells into nephrons, providing insights into nephrogenesis and organ regeneration.

Perioperative outcomes for elective open abdominal aortic aneurysm repair since the adoption of endovascular grafting procedures.

OBJECTIVES: The objective of this study was to evaluate and compare our perioperative outcomes for open abdominal aortic aneurysm (AAA) between the pre-endovascular aneurysm repair (pre-EVAR) and EVAR eras and to analyse whether the AAA that was excluded from EVAR could affect the perioperative outcome. MATERIALS AND METHODS: The Kurume University Hospital vascular registry was reviewed to identify all patients undergoing an elective open AAA repair from January 2004 through November 2006 (pre-EVAR era, n = 99) and from December 2006 through June 2010 (EVAR era, n = 125). The early clinical outcomes between the two groups were compared. RESULTS: In the EVAR era, the proportion of EVAR in all elective AAA repairs was 43.4%. The EVAR era had a significantly higher proportion of very elderly patients over 80 years of age (23.2% vs. 11.1%, P = 0.0391). The morbidity rates were similar between the two groups (22.3% vs. 24,8%) and the mortality rate was 0% for both. CONCLUSION: Despite the increased complexity of OAR in the EVAR era, we believe that OAR remains a valid procedure for AAA repair.

Association between expression of vascular endothelial growth factor C, chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer.

OBJECTIVES: Lymph node metastasis is one of the determining factors of a poor prognosis for colorectal cancer. Recent studies have reported that cancer cells can promote lymphangiogenesis and that chemokine receptors expressed by cancer cells might play a role in metastasis. In this study, we examined the correlation between the expression of vascular endothelial growth factor (VEGF) C, the chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer. METHODS: One hundred and sixty-one consecutive patients who underwent resection at our department were studied. Lymph node metastasis was observed in 69 cases (43%) and lymphatic involvement was present in 105 cases (65%). Immunohistochemical staining was performed using antibodies for VEGF-C and CXCR4. Moreover, lymphatic vessel density (LVD) was evaluated within the tumor by immunostaining with a D2-40 antibody. RESULTS: VEGF-C expression was found in 81 cases (50%) and CXCR4 expression in 87 cases (54%). Regarding the correlation between nodal metastasis and the expression of CXCR4 and VEGF-C, the incidence of nodal metastasis was significantly (p < 0.01) higher in patients with CXCR4-positive tumors than in those with CXCR4-negative tumors. In addition, a significant correlation was observed between CXCR4 and VEGF-C expression and lymphatic invasion (p < 0.01). LVD was significantly higher in VEGF-C-positive tumors compared with VEGF-C-negative tumors. However, there was no significant correlation between LVD and CXCR4 expression. Using multivariate analysis, VEGF-C, CXCR4, lymphatic invasion and wall invasion were found to be independent risk factors for lymph node metastasis. CONCLUSIONS: This study suggests that although the mechanism that promoted lymph node metastasis was different between VEGF-C and CXCR4, both VEGF-C and CXCR4 contributed to lymphatic involvement and nodal metastasis in colorectal cancer.

Hepatoblastoma associated with Beckwith-Wiedemann syndrome and hemihypertrophy.

Both Beckwith-Wiedemann syndrome (BWS) and hemihypertrophy (HH) have been recognized to be overgrowth syndromes associated with an increased risk of cancer. We report an infant with hepatoblastoma associated with both BWS and HH in whom high serum alpha-fetoprotein (AFP) levels persisted even after complete tumor resection with no tumor recurrence. This phenomenon might be partly due to the nature of the proliferative disease. It is important to recognize that in some infants with BWS prolonged high serum AFP levels mimic the existence of a tumor, and that treatment should be based not only on AFP measurement, but also on repeated radiologic imaging.

Surgery for primary cardiac tumors. Clinical experience and surgical results in 60 patients.

BACKGROUND: We reviewed our clinical experience with primary cardiac tumors, attempting to clarify the surgical management of these rare entities. METHODS: Between October 1978 and November 1999, we experienced 60 surgical cases of primary cardiac tumors. There were 23 male and 37 female patients (age range, 7 months to 84 years). Tumors included the following 3 groups: myxomas (n=49), nonmyxoma benign tumors (n=3), and malignant tumors (n=8). We reviewed the presenting symptoms, diagnostic data, anatomical findings, and surgical techniques, and evaluated the surgical RESULTS. Late follow-up was 95% complete (mean follow-up, 7.7+/-7.1 years). RESULTS: Tumors produced obstructive, embolic, and/or constitutional symptoms in most cases. Generally, echocardiography alone gave sufficient information for operation. Full-thickness excision was performed in 42 patients with myxoma. Complete excision was achieved in all of the nonmyxoma benign tumors and in none of the malignancies. Early mortalities in the 3 groups were 8.2% (4/49), 0% (0/3), and 12.5% (1/8), respectively. Late mortalities were 9.5% (4/42), 0% (0/3), and 100% (7/7), respectively. One patient with myxoma had recurrence, the cause of which was likely to be inadequate resection. The late deaths in patients with malignancies were due to metastasis or local recurrence. CONCLUSIONS: Benign tumors are generally curable if surgically excised. Preoperative refractory cardiac dysfunction or embolism should be avoided by the accurate evaluation on echocardiography. The prognosis of malignant tumors is poor if they are only debulked. However, aggressive surgery that can palliate obstruction and allow time for adjuvant therapy should be carried out.

Obstruction of St Jude medical valves in the aortic position: a consideration for pathogenic mechanism of prosthetic valve obstruction.

Between 1995 and 2000, 8 patients with St. Jude Medical (SJM) valves in the aortic position required 9 redo valve replacement for prosthetic valve obstruction. Obstruction of the prosthetic valve was diagnosed by simultaneous echocardiography and cineradiography, and process of restricted leaflet movement that progressed to hemodynamic impairment was observed by serial studies in three recent patients. An oral anticoagulation was considered to be adequate in all patients except one patient who had withdrawal of warfrain. Pannus was the sole cause of valve obstruction in seven events in 6 patients, and both thrombus and pannus in 2 patients. Pannus overgrowth was found on the inflow aspect of the SJM valve, and involved the ends of the straight edge of the leaflets over pivot guards. These results suggest that pannus might play the primary role in development of obstruction of aortic SJM valves in patients on adequate oral anticoagulation.

[Long-term results of aortic root replacement for Marfan syndrome].

Between January 1974 and December 2000, aortic root replacement was performed for 46 patients with Marfan syndrome. The hospital mortality rate amounts to 8.6% (4 patients out of 46). Fifteen (35.7% of survivor) of 42 survivor died during the period of follow-up. Eighteen of 42 survivor were developed cardiovascular events of 21 times and 11 patients had to be reoperated on at least once for a total of 12 reoperations. Nine of 15 late death patient died in relation to aortic dissection and pseudoaneurysm of distal anastomosis and coronary anastomosis. Actuarial survival rate was satisfactory for 10 years after aortic root replacement, but sharply decreased after postoperative 10 years. The use of non-sealed graft, classical Bentall method, reoperation and inclusion technique were risk factors for the late death.

Postoperative intussusception after incidental appendicectomy.

Postoperative intussusception of the appendiceal stump is a rare complication of appendicectomy. We report an infant who developed an intussusception of the appendiceal stump 2 days following an appendicectomy performed during a right inguinal herniotomy as a day case. The intussusception was diagnosed on ultrasonography and was to be treated laparoscopically, but spontaneous reduction occurred during induction of general anesthesia.

Cytomegalovirus enteritis after autologous peripheral blood stem cell transplantation.

A 61-year-old male with non-Hodgkin's lymphoma (peripheral T-cell lymphoma, unspecified, clinical stage IVb) received autologous peripheral blood stem cell transplantation (PBSCT) during first remission. He was seropositive for cytomegalovirus (CMV) prior to autologous PBSCT. His posttransplant clinical course was complicated by refractory CMV enteritis, which manifested persistent abdominal pain, diarrhea, and bloody stool. Generally, gastrointestinal CMV disease is relatively rare after autologous PBSCT. However, our case indicates that CMV infection must be considered as a differential diagnosis in cases of unexplained hemorrhagic enteritis following autologous PBSCT.

Peripheral ameloblastoma with potentially malignant features: report of a case with special regard to its keratin profile.

A peripheral ameloblastoma with atypical features occurring on the left maxillary alveolar ridge of 40-year-old man is described, along with an immunohistochemical profile of its cytokeratin (CK). The lesion apparently originated from the surface gingival epithelium. The tumor nests or strands were highly cellular with a variable degree of squamous differentiation and microcyst formation. Occasional mitotic figures and dystrophic calcification, both of which are not seen in conventional ameloblastomas, were also observed. The tumor infiltrated deep into the alveolar mucosa, including the periodontal ligament, and showed histological and topographical evidence of atypism, resulting in resorption of the underlying alveolar bone. On the CK immunohistochemistry, CK19 was demonstrated in all the types of neoplastic epithelia, including microcyst-forming cells, densely packed round or spindle cells within the tumor nests, cells with squamous metaplasia, and peripheral tall columnar cells. The CK immunohistochemical findings suggest the lesion's cell of odontogenic origin; they may reflect an immature phenotypic expression of cell differentiation in the odontogenic epithelia during the tumor growth in the gingival mucosa.

Surgical treatment of prosthetic valve endocarditis with left ventricular-aortic discontinuity: reconstruction of the left ventricular outflow tract with a xenopericardial conduit.

BACKGROUND AND AIM OF THE STUDY: Aortic prosthetic valve endocarditis (PVE) with annular destruction presents a challenge that requires techniques to eradicate the infection and correct the hemodynamic abnormality. METHODS: Between July 1, 1996 and March 31, 2000, six patients with native or PVE of the aortic valve and aortic annular destruction underwent surgical treatment. Of these patients, three (two men, one woman; mean age 71.0 years) had circumferential annular destruction of the aortic annulus, and formed the basis of this study. The microorganisms responsible for the infection were Streptococcus spp. in two patients and Staphylococcus aureus in one patient. In addition to aggressive debridement of the infected tissue, repair was achieved by reconstruction of the left ventricular outflow tract with a xenopericardial conduit and fixation of the new prosthetic valve to the conduit. RESULTS: One patient with ventricular septal perforation, multiple systemic embolism and sepsis died of low cardiac output syndrome soon after surgery. Two operative survivors were followed up for 9 and 51 months, with no late deaths. No patient has experienced recurrent infection, pericardial patch aneurysm, or prosthetic valve detachment. CONCLUSION: These operative procedures provide easy and secure fixation of the pericardial patch to the healthy tissue under excellent operative view, as well as a sturdy structure for the fixation of the new prosthesis, and complete exclusion of the abscess cavity from the blood stream.

Triple valve replacement with bileaflet mechanical valves: is the mechanical valve the proper choice for the tricuspid position?

A more durable mechanical valve may be a better choice for the tricuspid position than a bioprosthesis when the patient already has mechanical prosthesis in the left side of the heart. Eleven cases of triple valve replacement (total follow-up period, 49.5 patient years), all with mechanical valves, are reviewed to assess optimal valve selection. Nine patients had undergone a total of 12 previous cardiac surgeries. Three patients died in hospital (27.3%), but there were no late deaths among the survivors. Two cases of valve thrombosis in the tricuspid position occurred (linearized incidence: 4.04%/patient years) and 1 of these required reoperation. Because of this high incidence of valve thrombosis, the bileaflet mechanical valve is not considered to be the best choice. Even if mechanical valves are implanted in the left side of the heart, a bioprosthesis may be a better choice at the tricuspid position.

Cardio-aortic operation in octogenarians.

OBJECTIVE: Aging of the population is a current phenomenon in Japan, and life expectancy at 80 years old is getting longer. So we reviewed cardio-aortic operations on octogenarians at our institution. SUBJECTS AND METHODS: Thirty-three consecutive octogenarian patients who had undergone cardio-aortic operations from 1992 to 1998 were studied. There were 14 men and 19 women. The mean age was 81.9 years. Of the 33, 19 patients (58%) were in New York Heart Association class IV, and 21 patients (64%) were operated on urgently or in emergency. The procedures undergone were operation for coronary artery disease in 17 patients, operation for valvular disease in 7 patients, operation for thoracic-aorta in 7 patients, and others in 2 patients. RESULTS: The hospital mortality rate was 27% (9 patients). However, 89% of patients experiencing hospital death were in New York Heart Association class IV preoperatively and had required an emergency/urgent operation. On the other hand, there was only one hospital death (1/12, 8.3%) among the elective patients. The statistically significant risk factors for hospital death were renal insufficiency, shock, New York Heart Association class IV, intra-aortic balloon pumping, and longer cardiopulmonary bypass time. The one-, three-, and five-year-survival rate was 73%, 68%, and 55%, respectively. Of the survivors, 77% were in class I or II. CONCLUSION: Although octogenarians' hospital mortality was still very high, the mid-term results were acceptable and the survivors' quality of life was satisfactory. These data suggested that we should operate on cardio-aortic patients before they reach a very serious state, especially in octogenarians.

High-dose cimetidine reduces proinflammatory reaction after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Cimetidine, which is usually used for gastric ulcer, enhances cellular immunity. The effect of cimetidine on perioperative proinflammatory response after cardiac surgery with cardiopulmonary bypass was investigated. METHODS: Elective coronary artery bypass graft cases in which CPB was performed were placed randomly in a cimetidine (C) group (n = 20) or a no-treatment (N) group (n = 20). The time course of plasma levels of neutrophil elastase, interleukin (IL)-6 and IL-8, leukocyte counts, lymphocyte recovery ratio, C-reactive protein, creatine-kinase-MB, and oxygenation index were analyzed. RESULTS: The plasma levels of neutrophil elastase and IL-8 were inhibited in the C groups at 2 hours after CPB termination. In a comparison of the two groups, the C group demonstrated higher lymphocyte recovery ratio and lower C-reactive protein on postoperative day 5 and shorter intubation time. No intergroup differences were observed in IL-6, leukocyte counts, creatine-kinase-MB levels, or oxygenation index. CONCLUSIONS: Cimetidine may reduce surgical stress and augment the immune system after cardiac surgery with cardiopulmonary bypass.

Aortic dissections complicating open cardiac surgery: report of three cases.

Between June 1991 and February 1999, three patients suffered ascending aortic dissection as a complication of cardiopulmonary bypass operations with aortic cannulation at our hospital. The dissection occurred during the operation in two of the three patients and several months after the operation in one. Among a total of 2207 cardiac operations performed during this period, the incidence of perioperative ascending aortic dissection was 0.14%. In addition to visual inspection and palpation, either epicardial or transesophageal echocardiography proved extremely useful for establishing an intraoperative diagnosis of ascending aortic dissection as a complication of open cardiac operation. One of the three patients underwent closed plication but subsequently died of vital organ ischemia. In this case, failure of reapproximation of the injured intima by closed plication might have led to extension of the dissection. Despite prolonged cardiopulmonary bypass and myocardial ischemic time, graft replacement of the ascending aorta was successfully carried out in the other two patients. Thus, we believe that graft replacement of the ascending aorta should be performed for patients with extensive aortic dissection complicating an open cardiac operation.

Tricuspid valve replacement with the St. Jude Medical valve: 19 years of experience.

OBJECTIVE: The choice of the valve substitute in the tricuspid position remains controversial. A St. Jude Medical valve is a choice of valve substitute and its lower thrombogenicity and excellent hemodynamic performance have been reported even in the tricuspid position. However, little is known of the long-term durability of the St. Jude Medical valve in the tricuspid position. Our long-term experience of tricuspid valve replacement showed the higher thrombogenicity than we had expected, therefore, this study was done to reconsider our strategy for valve choice. METHODS: This study reviewed 23 patient who underwent 25 tricuspid valve replacements with the St. Jude Medical valves from 1980 to 1997. The mean age was 40 years. Eleven patients (48%) were men. There were four in-hospital deaths (17%). The remaining 19 patients were all alive and followed from 2.2 to 19.0 years (mean 11.8 years). RESULTS: The overall survival, including hospital mortality, was 83%, 10 and 15 years after surgery. Valve thrombosis occurred in six patients. Freedom from valve thrombosis was 78 and 70%, 10 and 15 years after surgery, respectively. The linearized rate of the valve thrombosis was 2.9%/patient-years. Six patients required reoperation. The mean interval to reoperation was 9.5 years. Freedom from reoperation was 83% and 75%, 10 and 15 years after surgery, respectively. The linearized rate of the reoperation was 2.8%/patient-years. No structural valve deterioration was found. Echocardiographic study showed that the function of the St. Jude Medical valve without valve-related complications was well maintained. CONCLUSIONS: The higher thrombogenicity of the St. Jude Medical valve in the tricuspid position altered our choice of valve substitutes from the St. Jude Medical valve to a bioprosthesis which is lack of need for anticoagulant therapy except for juvenile patients who are able to maintain potent anticoagulant therapy.

Biocompatibility of heparin-coated extracorporeal bypass circuits: new heparin bonded bioline system.

Biocompatibility of a new type of heparin-coated cardiopulmonary bypass equipment, the Bioline, was evaluated in coronary artery bypass surgery cases. The heparin-coated (H) group (n = 15; Quadrox Bioline oxygenator/reservior and Carmeda BioMedicus BP-80 centrifugal pump) was compared with the nonheparin-coated (N) group (n = 12; uncoated, otherwise similar oxygenator, centrifugal pump, tubing, and filter set). Both groups used full systemic heparinization. The peak values of neutrophil elastase, C3a, IL-6, and IL-8 at 2 h after cardiopulmonary bypass (CPB), and C3a levels at the end of CPB and at 2 h after CPB were significantly reduced in the H group compared with those of the N group. However, no statistically significant intergroup differences were observed in thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, or platelet factor-4. No significant differences were observed in hemostasis time, postoperative 12 h blood loss, required amount of blood transfusion, or intubation time. In conclusion, the Bioline demonstrated partially improved biocompatibility, in terms of leukocyte and complement activation, and proinflammatory cytokine production. However, it did not improve platelet activation, coagulation, or fibrinolysis cascade under full systemic heparinization. As a result, the clinical beneficial impact seemed to be the minimum.