Bungo Shirasawa

Enhanced Tumor Necrosis Factor-α Expression in Small Sized Abdominal Aortic Aneurysms

Circulating levels of tumor necrosis factor α (TNF-α) are elevated in the patients with abdominal aortic aneurysm (AAA). We investigated TNF-α expression and cellular infiltration in the walls of AAAs of different sizes. Twenty-seven surgical specimens of AAAs were categorized according to the maximum aneurysm diameter into a small size group (less than 50 mm in diameter, n = 8; S group), a medium-sized group (50 to 59 mm in diameter, n = 11; M group), and a large size group (larger than 59 mm in diameter, n = 8; L group). The level of TNF-α and interleukin-1β(IL-1β) in the aneurysm wall was measured by ELISA. Immunohistochemical staining was performed to observe the TNF-α expression and the infiltration of macrophages and lymphocytes in aneurysm walls. Enzyme-linked immunosorbent assay showed that the level of TNF-α in the S group (5.47 ± 3.48 pg/mg protein) was significantly higher (p < 0.05) than that in the M group (2.70 ± 1.33 pg/mg protein) or the L group (1.82 ± 1.21 pg/mg protein). No significant difference in IL-1β was observed between the S, M, and L groups. Immunohistochemical analysis also showed that TNF-α was expressed strongly in the S group but was negative or weakly positive in the M and L groups. Furthermore, the expression of TNF-α was seen mainly where the aneurysm wall showed atheromatous change and macrophage infiltration. These results indicated that the expression of TNF-α in the aneurysm wall was enhanced in small AAAs, and this enhancement might be related to the infiltration of macrophages.

Identification of Risk Factors Related to Poor Angiogenic Potency of Bone Marrow Cells From Different Patients

Background— Therapeutic angiogenesis induced by the implantation of autologous bone marrow–derived cells has been used for the treatment of ischemic diseases. However, as the outcomes of cell implantation obviously vary among patients, it is essential to identify patients that would benefit the most from this treatment. Methods and Results— We collected clinical and laboratory data from 25 patients scheduled to undergo sternotomy for various surgical procedures. Then, we aspirated bone marrow cells from the sternum during the operation and investigated the cell quality in vitro by cultivation, and their angiogenic potency in vivo using an ischemic limb model of mice. The angiogenic potency of bone marrow cells differed among patients. Aging, renal failure, anemia, and high serum levels of triglyceride, C-reactive protein, interleukin-6, and type I collagen cross-linked N-telopeptide (NTX) significantly correlated with poor angiogenic potency of bone marrow cells. We assigned scores to these risk factors, and found a strong correlation between the risk scores of patients and the angiogenic potency of their bone marrow cells (r=−0.883, P<0.001). These risk scores can predict the angiogenic potency of bone marrow cells for inducing therapeutic angiogenesis with an accuracy of 80%. Conclusions— We have identified the risk factors related to poor angiogenic potency of bone marrow cells and developed a new scoring system to predict their angiogenic potency for the treatment of ischemic diseases. Our results may help select patients for this treatment in future clinical trials.

Surgery for abdominal aortic aneurysms associated with malignancy

Of 148 patients treated for abdominal aortic aneurysms (AAA), 33 (22%) also had cancer. According to the classification of Szilagyi, there were 13 patients in group I, 19 in group II, and 1 in group IV. In group I, the mean interval between the cancer and AAA operations was 7 years (range 1–14 years). Aneurysmectomy was performed in 9 patients, wrapping in 2, and no operation in 2. In group II, a two-stage operation was performed in 8 patients, a single-stage operation in 4, only surgery for cancer in 4, and no operation in 3. Of 4 patients undergoing single-stage operations, 3 had colorectal cancer, and there were no postoperative complications such as graft infection or anastomotic breakdown. In group I, 6 of 13 patients died, but there were no cancer deaths. In group II, 9 of 19 patients died, 6 from progressive cancer. The group IV patient also died of cancer. These results suggest that if a patient can tolerate surgery for both diseases, a single-stage operation is preferable.

Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting lymphangiogenesis

OBJECTIVE Although secondary lymphedema is a common complication after surgical and radiation therapy for cancer, the treatment options for lymphedema remain limited and largely ineffective. We thus studied the effect of extracorporeal shock wave therapy on promoting lymphangiogenesis and improving secondary lymphedema. METHODS A rabbit ear model of lymphedema was created by disruption of lymphatic vessels. Two weeks after surgery, the lymphedematous ear was treated with or without low-energy shock waves (0.09 mJ/mm(2), 200 shots), three times per week for 4 weeks. RESULTS Western blot analysis showed that the expression of vascular endothelial growth factor (VEGF)-C (1.23-fold, P < .05) and VEGF receptor 3 (VEGFR3; 1.53-fold, P < .05) was significantly increased in the ears treated with shock wave than in the untreated lymphedematous ears. Compared with the control group, shock wave treatment led to a significant decrease in the thickness of lymphedematous ears (3.80 +/- 0.25 mm vs 4.54 +/- 0.18 mm, P < .05). Immunohistochemistry for VEGFR3 showed the density of lymphatic vessels was significantly increased by shock wave treatment (P < .05). CONCLUSION Extracorporeal shock wave therapy promotes lymphangiogenesis and ameliorates secondary lymphedema, suggesting that extracorporeal shock wave therapy may be a novel, feasible, effective, and noninvasive treatment for lymphedema.

Secondary omental and pectoralis major double flap reconstruction following aggressive sternectomy for deep sternal wound infections after cardiac surgery

BackgroundDeep sternal wound infection after cardiac surgery carries high morbidity and mortality. Our strategy for deep sternal wound infection is aggressive strenal debridement followed by vacuum-assisted closure (VAC) therapy and omental-muscle flap reconstrucion. We describe this strategy and examine the outcome and long-term quality of life (QOL) it achieves.MethodsWe retrospectively examined 16 patients treated for deep sternal wound infection between 2001 and 2007. The most recent nine patients were treated with total sternal resection followed by VAC therapy and secondary closure with omental-muscle flap reconstruction (recent group); whereas the former seven patients were treated with sternal preservation if possible, without VAC therapy, and four of these patients underwent primary closure (former group). We assessed long-term quality of life after DSWI by using the Short Form 36-Item Health Survey, Version 2 (SF36v2).ResultsOne patient died and four required further surgery for recurrence of deep sternal wound infection in the former group. The duration of treatment for deep sternal wound infection in the recent group was significantly shorter than that in previous group (63.4 ± 54.1 days vs. 120.0 ± 31.8 days, respectively; p = 0.039). Despite aggressive sternal resection, the QOL of patients treated for DSWI was only minimally compromised compared with age-, sex-, surgical procedures-matched patients without deep sternal wound infection.ConclusionsAggressive sternal debridement followed by VAC therapy and secondary closure with an omental-muscle flap is effective for deep sternal wound infection. In this series, it resulted in a lower incidence of recurrent infection, shorter hospitalization, and it did not compromise long-term QOL greatly.

Aortic arch surgery in octogenarians: is it justified?

OBJECTIVES Elderly patients are sometimes denied aortic arch surgery because of the perception of poor outcomes and an unacceptable quality of life (QOL). In this study, we evaluated the early clinical outcomes, long-term survival and QOL following surgical treatment for aortic arch disease in octogenarian patients. METHODS A total of 47 consecutive patients over the age of 80 years were referred to our institutions. Of these patients, 20 underwent surgical intervention (surgical group) and 27 were treated medically (medical group). Kaplan-Meier survival analysis was performed between the two groups, and the results were compared with age-matched population data. The risk factors for mortality were determined using a Cox regression analysis. A QOL assessment was performed using the 36-item Short Form Health Survey. RESULTS The patient characteristics at baseline were not significantly different between the two groups. In the surgical cases, conventional total aortic arch replacement was performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR) in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients. No hospital deaths occurred in the surgical groups. Reoperation for bleeding was required in 2 patients, and prolonged mechanical ventilation was required in 4 patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3% in the surgical group and 32.3% in the medical group (P = 0.01). There were no differences in the 5-year survival between patients undergoing surgical intervention and the sex- and age-matched population (P = 0.80), whereas the 5-year survival was significantly lower in patients who received medical therapy relative to the sex- and age-matched population (P < 0.001). Medical therapy was the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the survivors at mid-term, the quality-of-life measures were similar between those in the surgical group and those in the medical group. CONCLUSIONS Surgical intervention for aortic arch disease in octogenarians can yield satisfactory early clinical outcomes and acceptable mid-term survival with adequate daily activity. This study indicates that among octogenarians, age alone should not disqualify a patient from receiving an aortic arch intervention.

Transapical extirpation of a left ventricular thrombus in takotsubo cardiomyopathy

A 58-year-old Japanese female was referred to our hospital. Although the electrocardiogram showed ST elevation, coronary angiography showed intact coronary artery. We diagnosed Takotsubo cardiomyopathy and a left ventricular thrombus. Anticoagulation was administered; however, the left ventricular thrombus had become mobile and protrusive. We extirpated the left ventricular thrombus via trans-apical approach. Left ventricular thrombus is rare in Takotsubo cardiomyopathy, but these patients are at a higher risk of thromboembolism, especially if the thrombi are mobile and protruding.

Simple Geometrical Infarct Exclusion Technique With a Single Patch for Postinfarction Ventricular Septal Perforation

Six consecutive patients underwent emergency surgical repair of a postinfarction ventricular septal perforation. The principle of this technique is a simple three-dimensional repair with a nontailored square patch beforehand, which provides an adequate-sized pouch and prevents dehiscence of the patch being caused by excessive tension on the suture line. It also prevents a residual shunt. A single equine pericardium was sutured to the viable muscle circumferentially around the infarcted area to be excluded, after which the free edge of the patch was tailored and sutured in a pouch configuration. This technique seems to provide satisfactory early results in the acute phase of myocardial infarction.

Contribution of proliferating leukocytes to phenotypic change in smooth muscle cells during the development of coronary arteriosclerosis in transplanted hearts.

Background: It is well known that coronary arteriosclerosis after heart transplantation is concentric and rich in smooth muscle cells (SMCs); however, the role played by rejection in the intimal thickening caused by SMCs in coronary arteriosclerosis remains unclear. In this study, we examined the process of intimal hyperplasia caused by SMCs and evaluated the relationship between the differentiation state of SMCs and local inflammation caused by rejection. Methods: Lewis rat hearts were heterotopically transplanted into F344 rats (allotransplantation group) or other Lewis rats (isotransplantation group). Cyclosporin A (5 mg/kg/day) was injected intramuscularly for 20 days after transplantation in both groups. The transplanted hearts were examined immunohistochemically using several monoclonal antibodies; namely, HHF-35, CGA7, vimentin, α-actin, HIS36, R73 and proliferating cell nuclear antigen (PCNA). To evaluate the degree of local immunological response caused by rejection, the anti-PCNA antibody was used. To reveal the subtypes of proliferating cells in the thickened intima, HIS36 and R73 antibodies were used. Results: In the allotransplantation group, SMCs in the media began to undergo a phenotypic change toward a poorly differentiated state 30 days after transplantation. Intimal hyperplasia was observed 60 days after transplantation, the thickened intima being composed mainly of dedifferentiated SMCs with abundant PCNA+, most of which were macrophages and T cells. The state of differentiation of SMCs in the thickened intima 90 days after transplantation varied from a dedifferentiated to a highly differentiated state. These changes were strongly correlated with the expression of PCNA. Conclusion: The expression of PCNA was strongly correlated with the differentiation state of SMCs. Thus, local inflammation caused by rejection may play an important role in the initiation of phenotypic change in SMCs.

Correlations among Expression of Intercellular Adhesion Molecule 1, Cellular Infiltration, and Coronary Arteriosclerosis during Chronic Rejection Using the Rat Heart Transplantation Model

Immunologic mechanisms contribute to the development of coronary arteriosclerosis. In this study the rat heart transplantation model was used to investigate correlations among the expression of intercellular adhesion molecule 1, cellular infiltrate, and coronary arteriosclerosis during chronic rejection. Lewis rats served as heart donors and F-344 rats as recipients. Heart transplantations were performed heterotopically. The recipients were treated with ciclosporin A (5 mg/kg/day) by daily intramuscular injection for 30 days, beginning on the day of transplantation. Rejection grade and the intimal area were measured. The expression of intercellular adhesion molecule 1 and the numbers of infiltrating CD4- and CD8-positive cells and macrophages were examined immunohistochemically. The area of the intima was significantly increased in the allograft group after transplantation. In the allograft group, the level of expression of intercellular adhesion molecule 1 was considerably increased over the same time period. There was increased cellular infiltration in the 60-day group, and many expressed intercellular adhesion molecule 1. The expression of intercellular adhesion molecule 1 in vascular endothelium, infiltrating cells, and the sarcolemmal membrane of myocytes remained constant up to 120 days in the allograft group. In the allograft group, the number of infiltrating CD4- and CD8-positive cells and macrophages increased significantly between 30 and 60 days, and the infiltration of these cells remained constant. Continuous expression of intercellular adhesion molecule 1 induces the infiltration of T cells and macrophages, and the inflammation caused by such cells and their soluble products contributes to the arteriosclerotic process.