Operative Results and Clinical Features of Chronic Stanford Type B Aortic Dissection: Examination of 234 Patients Over 6 Years.

OBJECTIVE/BACKGROUND: Recently, the indications for thoracic endovascular aortic repair (TEVAR) have been expanding, and the applicability of TEVAR for acute type B aortic dissection (TBAD) is proposed with regard to the high mortality of open surgery for chronic TBAD. TEVAR in the acute phase may lead to remodeling of the false lumen (FL), but it is controversial whether it completely resolves the aortic expansion in the chronic phase. In this study, operative results and the relationship between FL status and the time before surgical intervention were retrospectively analyzed. METHODS: From January 2008 to September 2013, 234 patients underwent open surgery for chronic TBAD. Most patients were on left heart bypass. By considering Japanese aortic disease treatment guidelines and the smaller physique of Japanese patients, operative indications were aneurysm >50 mm in diameter or rapid aneurysm enlargement of >5 mm in a 6 month period. RESULTS: In 180 cases, the FL was patent. The mean interval between onset of TBAD and operation was 61 ± 54 months. There was no significant difference between patients in the patent FL group and those in the thrombosed FL group (p = .44). Mean ratio of FL diameter to maximum aortic diameter (FL/AD) was 0.64 ± 0.21. There was no correlation between FL and AD before the operation (r = .12). Descending thoracic aortic replacement (DTAR) was performed in 127 cases and thoracic ascending aortic replacement (TAAR) in 107 cases (Crawford type I, n = 9; Crawford type II, n = 65; Crawford type III and IV, n = 22, respectively; Safi type V, n = 11). The overall operative mortality was 6.8%: 3.9% (5/127) for DTAR and 10.3% (11/107) for TAAR. The three year survival was 86.7, and the freedom from re-intervention rate was 97.0%. CONCLUSION: Enlargement of uncomplicated TBAD in the chronic phase was poorly related to FL status and the results of open repair have improved. However, further prospective study is necessary.

Indocyanine green angiography for intra-operative assessment in vascular surgery.

OBJECTIVES: Indocyanine green (ICG) angiography is used for the intra-operative assessment of the graft vessel in coronary artery bypass grafting to enable immediate revision if necessary. We report the feasibility and implications of an ICG colour imaging system, HyperEye Medical System (HEMS), in surgeries for arteriosclerosis obliterans (ASO) and abdominal aortic aneurysm (AAA) which carry risk of mesenteric ischaemia. METHODS: HEMS ICG angiography was used for the intra-operative assessment of 12 ASO patients and 10 AAA patients. RESULTS: In the ASO patients, HEMS angiography enabled visualisation of the graft and native artery. The fluorescent lucent region in the artery distal to the anastomosis was shown in 1 of 12 ASO patients. There was a 3-s time lag in the increase of intensity between the proximal artery and distal stenotic region. In AAA patients, HEMS angiography clearly showed the perfusion in the mesenteric arteries and intestinal wall as opaque. One AAA patient had segmental ischaemia due to thromboembolism and another one had diffuse ischaemia due to systemic malperfusion. The ischaemic region of the intestine was visualised as a fluorescent lucent area by HEMS angiography. CONCLUSION: HEMS angiography can accurately assess peripheral arterial perfusion in surgical cases with ASO and AAA.

[Insertion and removal of the intraaortic balloon pumping].

Intraaortic balloon pumping (IABP) is the most popular circulatory assist device. Although insertion and removal of IABP has proved to be a safer technique, a significant number of pitfalls have been seen. On the basis of our experience, we make several recommendations that may facilitate safer insertion and removal of IABP. Careful insertion and removal by experienced hands of cardiovascular surgeons should minimize complications.

Bilirubin oxidation provoked by nitric oxide radicals predicts the progression of acute cardiac allograft rejection.

Bilirubin, a strong intrinsic antioxidant, quenches free radicals produced under inflammatory conditions. The oxidized bilirubin metabolites, i.e. biopyrrins, are immediately excreted into urine and can indicate the intensity of oxidation in vivo. Our preliminary studies suggested the involvement of reactive nitrogen species (RNS) in generation of biopyrrins. However, little is known about biological significance of bilirubin oxidation by RNS. Here, we analyzed the correlation between bilirubin oxidation and nitric oxide (NO) radicals during rat acute cardiac allograft rejection. In allograft recipients, urinary biopyrrins steeply increased on day 3 prior to the increase in myocardial tissue damage marker, serum troponin-T. In contrast, no significant changes in urinary biopyrrins were evident in recipients of isografts or cyclosporine-A treated allografts. Urinary nitrotyrosine, a marker of oxidation by NO radicals also increased on day 3, while administration of a NO synthase inhibitor, N(G)-monomethyl-L-arginine apparently diminished the elevation of urinary biopyrrins as well as nitrotyrosine. Immunohistochemistry revealed enhanced local expression of heme oxygenase-1, biopyrrins and nitrotyrosine in allografts in accordance with the cellular infiltrates, suggesting that changes in urinary biopyrrins reflect the bilirubin oxidation in grafts undergoing rejection. These results indicate that locally evoked bilirubin oxidation by NO radicals can predict the progression of rejection.

Protective effect of a radical scavenger, MCI-186 on islet cell damages induced by oxidative stress.

Oxidative stress generated during islet isolation and transplantation causes islet cell damage. These oxidative injuries are mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). MCI-186 is an antioxidant used for clinical treatment of cerebral infarction in Japan. We examined a possible protective effect of MCI-186 on islet cells against oxidative stress. Islets isolated from Sprague-Dawley rats by collagenase P digestion were purified by density gradient centrifugation with Ficoll. Islets were treated with hydrogen peroxide (H(2)O(2); 5 to 250 micromol) in the presence or absence of MCI-186. Cell death was measured by an LDH release assay. Maximum islet cell death was observed at 250 micromol of H(2)O(2). MCI-186 inhibited islet cell death in a dose-dependent manner with significant reduction above 30 micromol. From the results observed we suggest that the antioxidant effects of MCI-186 may prove beneficial to improve the preservation of islet cells.

[Surgery for aneurysms of the aortic arch in elderly patients].

Surgery for aneurysms of the aortic arch in octogenarians can be performed with increased but operative mortality remains high. Minimally invasive operation may be required for further improvement of the outcome of surgery for aneurysms of the aortic arch in octogenarians. Aged patients with life-threatening events have excessive mortality and morbidity. We think that sugery for aneurysms of the aortic arch in octogenarians should not be withheld on the basis of age alone, but should be based on careful assessments of the relative medical risks and benefits, as well as the wishes of the patients and family.

Dielectric behavior of pulmonary edema induced in the rat lung.

The dielectric properties (conductivity, kappa and relative permittivity, epsilon) of excised rat lung are modified by lung air and water content. The measurements of these quantities were made over the frequency range of 10 kHz to 100 MHz with an open-ended coaxial probe. The following relationships were analyzed in an oleic acid-induced pulmonary edema model using 18 animals: the spectra of kappa, epsilon and the loss tangent as a function of lung air and water content. Secondly, an isolated-perfused lung system was produced to induce a gradual increase in lung water. The time course of kappa, epsilon and the loss tangent for one excised lung was analyzed. The principal findings were: (i) a decrease in kappa and epsilon with increasing air content, (ii) an increase in kappa and epsilon with increasing water content, and (iii) a good correlation between lung water content and maximum loss tangent that was insensitive to changes in air content. We conclude that this technique could provide a quantitative assessment of lung water during pulmonary edema formation.

Epidermal growth factor and insulin inhibit cell death in pancreatic beta cells by activation of PI3-kinase/AKT signaling pathway under oxidative stress.

Production of reactive oxygen species (ROS) during islet purification by enzymatic digestion as well as during warm and cold ischemia causes islet cell damage. Recent reports have shown that activated Akt, the downstream protein after phosphatidylinositol (PI) 3-kinase, is involved in cell survival by phosphorylating several proteins that mediate apoptosis. We analyzed the role of PI3-kinase/Akt pathway activation using insulin or epidermal growth factor (EGF) on islet beta cell survival during oxidative stress. Canine islets and murine beta cell line (BTC) were cultured in the presence of hydrogen peroxide (H(2)O(2)) for 12 to 20 hours. Viability and cell death were measured by MTT assay. Maximum cell damage was observed with as little as 100 micromol/L of H(2)O(2). Pretreatment with 100 ng/mL of insulin significantly decreased cell damage. Meanwhile, the protective effect of insulin was partially blocked with an inhibitor of PI3-kinase, LY294002, suggesting the utilization of PI3-kinase/Akt signaling pathway for the observed cytoprotective effect. Similar to insulin, EGF also protected beta cells from oxidative stress. Our results suggest that PI3-kinase/Akt activation by insulin or EGF is beneficial for islet beta cell protection.

[Consideration of the prognostic factors influencing survival after lung metastasectomy of renal cell carcinoma].

From 1989 to 2002, 9 patients with metastatic renal cell carcinoma to lung underwent lung resections for curative removal of metastatic disease in our department. Disease free interval (DFI), number and size of metastases resected (at first metastasectomy), and number of metastasized regional lymph nodes were studied after resection of pulmonary metastases. DFI were 0 to 60 months with mean value of 23 months. At first operation, single metastases accounted for 4 cases and multiple lesions more than 2 metastases accounted for 5 cases with mean value of 2.1. Maximal diameter of metastases was 10 to 50 mm with mean value of 24 mm. Regional lymph nodes metastases were demonstrated only 1 patient in 2 of No. 12 lymph nodes adjacent to metastases. At subsequent relapse, 1 patient had second-stage metastasectomy, 2 patients went on to a third phase. Four patients were lost, 2 are under treatment for newly relapsed lesions, and 3 are now free of metastases. Analysis was performed by Cox proportional hazards model of survival using these factors. Though lacking the statistical significance, only maximal diameter of metastases was prone to have influencing factor on prognosis. Survival was not related to DFI between 0 to 21 months and more than 21 months and numerous lung metastases between single metastasis and with 2 or more. In general, estimated survival rate of these patients according to Kaplan-Meier was 0% at 67 months. Considering the above results, surgical treatment for patients with metastatic renal cell carcinoma to lung should be planned carefully.

Study of the diagnostic difference between the clinical diagnostic criteria and results of immunohistochemical staining of multiple primary lung cancers.

AIM: When multiple synchronous or metachronous lung cancer lesions are identified, discrimination of multicentric lung cancers from intrapulmonary metastases by clinical findings is often difficult. When tissue types have the same pathological features, such as combinations of squamous cell carcinoma (SCC), adenocarcinoma (AD) or bronchiolo-alveolar cell carcinoma (BAC), it is especially difficult to distinguish a 2(nd) primary lung cancer from a metastatic lesion. A new strategy for accurate diagnosis of multiple synchronous or metachronous lung cancer is needed because of the difficulty of histological discrimination. METHODS: Of 363 patients with primary lung cancer for which surgeries were conducted at our hospital, 7 cases were diagnosed as synchronous multiple lung cancer (BAC-BAC in 4 cases and SCC-BAC in 3 cases) and 8 cases (BAC-BAC in 2 cases, AD-BAC in 1 case, AD-AD in 1 case, SCC-AD in 1 case and SCC-SCC in 3 cases) were diagnosed as metachronous multiple lung cancer according to the clinical diagnostic criteria. This study focused on 8 cases with the combinations AD-AD, AD-BAC, or BAC-BAC. For immunohistochemical staining, we used the antibodies to 6 antigens as follows: CK-19, p53, CEA, Hup-1, PE-10, and Ki-67. RESULTS: Of 4 cases diagnosed as synchronous lung cancer according to the clinical diagnostic criteria, differing immunohistochemical stained images of the lesions were observed in 3 cases, while in the 4th case almost identical immunohistochemical stained images were obtained, which indicated the 2 lesions were the primary and metastatic focuses. Of 4 cases diagnosed as metachronous lung cancer according to the clinical diagnostic criteria, almost identical stained images were seen in 3 cases, which indicated the 2 lesions were the primary and metastatic focuses. CONCLUSION: In general, Type A and Type B in Noguchi's BAC classification, tended to be multiple synchronous or metachronous lung cancer lesions, while AD and Type C in Noguchi's BAC classification tended to be the metastatic focus. For the focuses with tissue type of BAC-BAC, the staining using CK-19, PE-10, and Ki-67 was useful in distinguishing multiple primary lung cancer from pulmonary metastasis in cases with a combination of AD and BAC.

[The usefulness of induction chemotherapy in cases with tumors showing border-line pathological aspects between thymoma and thymic carcinoma].

We present 2 surgically treated cases with thymoma classified as Masaoka stage III and IV a (type B 3 thymoma), which showed the border-line pathological aspects between the thymoma and thymic carcinoma. Induction chemotherapy [CAV-PVP (cyclophosphamide, adriamycin, vincristine sulfate, etoposide) therapy in one case and ADOC (adriamycin, cisplatin, vincristine sulfate, cyclophosphamide) therapy in another case] preluded their surgical resection resulted in reduction of the tumor's size moderately or severely. After achievement of induction chemotherapy, these tumors were resected with the midsternotomy approach, along with resection of the right upper lobe and the left brachiocephalic vein replacing the expanded pdytetrafluoroethylene (ePTFE) graft following mediastinal lymphnodes dissection in one case and leaving the tumor tissue around the pulmonary trunk in another case. Postoperative irradiation of 40 Gy in one case and 60 Gy in another case were performed in the mediastinal regions. From pathological aspects especially in second case, though the specimen by preoperative needle biopsy stained positive for bcl-2 and strong immunoreactivity (20%) for MIB-1, specimens excised operatively after induction chemotherapy showed negative staining for bcl-2 and little staining (lower than 5%) for MIB-1. This fact indicates that the induction chemotherapy makes the tumor less malignant, in other words, from the face of thymic carcinoma to the face of thymoma. Induction chemotherapy performed for the purpose of reducing the tumor size was very advantage in these 2 cases with type B 3 thymoma.

[Study of the difference between the clinical diagnostic criteria and results of immunohistochemical staining].

If more than 2 lesions of cancer are observed in the lung, differences in the histology or in situ component is the basic criterion for multicentricity. In addition, remote lung mass with same histology in the absence of both distant metastasis and mediastinal lymphadenopathy is also regarded as multicentricity. We have studied the difference between the clinical diagnostic criteria and the results of immunohistochemical staining. Thirteen patients who were diagnosed as double lung cancers under the clinical of Martini et al or Cortese et al were reviewed. Of them, clinically 6 patients had synchronous double lung cancers and 7 patients had metachronous double lung cancers. Four patients in each group with combination of adenocarcinoma (AD) and bronchiolo-alveolar cell carcinoma (BAC) were studied by immunohistochemical staining. As the result, 3 patients in the former group were defined as the synchronous double lung cancers, however in the latter group, only 1 patients was defined as the metachronous double lung cancers. As for from the histological findings, if either of multiple lung cancer lesion were Noguchi's A or B typed BAC, the patients are prone to have double lung cancers. Subsequently if the histology of the both lesions were the same as AD-AD or Noguchi's C typed BAC-BAC, then the patients are prone to have the metastatic lung cancers.

Route of feeding influences the production and expression of tumor necrosis factor alpha in burned rats.

The effect of nutritional route on tumor necrosis factor alpha (TNF-alpha) production in burned rats was examined. Scald burns covering about 30% of the whole body surface area were inflicted on 43 male Wistar rats weighing about 200g. The animals were divided into three groups: CHOW (n = 10), total parenteral nutrition (TPN) (n = 22), and total enteral nutrition (TEN) (n = 11), continuously given a chow diet, TPN solution, or an enteral diet, respectively, for 7 days after the burn injury. The rate of detection of TNF-alpha in plasma on day 7 was significantly higher in the TPN group than in the CHOW or TEN groups. The messenger RNA (mRNA) expression of TNF-alpha was significantly increased in the spleen, lungs, liver, and ileum of the rats receiving TPN compared with the CHOW and TEN rats. On the other hand, the expression of TNF-alpha mRNA was markedly decreased in the thymus of the TPN group compared with the CHOW group. The mortality rate in the TPN group (63.6%) was higher than that in the CHOW (0.0%) or TEN (27.3%) groups on day 7 after burn injury. These data suggest that TPN increases the expression of TNF-alpha mRNA in organ tissues and systemic TNF-alpha production, and reduces the survival rate of rats after thermal injury, but TEN does not.

Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia.

The rate of tumor growth depends on the balance between proliferation and death of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death-promoting factors, whereas Bcl-2 protein is a death antagonist. We immunohistochemically examined the expression of Bax and apoptosis-related proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal squamous cell carcinoma (SCC) including dysplasia to determine the relationship of expression of each protein to tumor behavior and patients' prognosis. No significant relationships in immunopositivity were found among these proteins in SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The apoptotic index of caspase-3-positive lesions was significantly higher than that of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On the other hand, the apoptotic index (1.18%) was significantly correlated with Bax overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan-Meier method (P =.043). These findings suggested that Bax expressed in dysplasia may play a role as an apoptotic factor, but that it may be functionally inactive in some cancerous lesions and thus not contribute to suppression of the tumor progression in some cases of human esophageal SCCs.

Immunohistochemical study with antibody to glycoprotein GCDFP-15 for metastatic lung cancer from breast cancer.

Even when gross pathologic specimens are available, evaluation is always complicated due to the difficulty in distinguishing the pathologic diagnosis of an adenocarcinoma as a pulmonary metastasis of the breast or lung. In this paper, we describe the usefulness of a preoperative immunohistochemical study using gross cystic disease fluid protein-15 (GCDFP-15). A 50-year-old woman, who had undergone a right radical mastectomy due to an infiltrating ductal carcinoma 4 years previously, was admitted because of an abnormal shadow on chest roentgenography. A chest CT scan showed a nodule 20 mm in diameter with an irregular margin and vascular involvement in the S3 region of the right lung. Though the specimen from a percutaneous CT guided needle biopsy revealed characteristic pathologic findings of a primary lung adenocarcinoma under H.E. stain, which was recommended for lobar resection, we re-examined that specimen immunohistochemically, which disclosed that the tumor cells were negative for the antibody to pulmonary surfactant apoprotein and were positive for GCDFP-15 antibody. Therefore, the diagnosis of a metastatic breast carcinoma in the lung was established. Upon her request, a wedge resection of the right upper lobe including the tumor was performed under video-assisted thoracoscopic surgery (VATS). Her postoperative course was uneventful.

Long-term graft acceptance in rat heart transplantation by CTLA4Ig gene transfection combined with FTY720 treatment.

CTLA4Ig strongly adheres to B7 molecules on antigen-presenting cells to block intracellular signal transduction via CD28 on helper T cells, which eventually inhibits immune responses. We have demonstrated that the administration to recipient animals of adenoviral vectors containing CTLA4Ig gene (adCTLA4Ig) prolonged graft survival, although the gene expression diminished in a time-dependent manner and the grafts were finally rejected. In addition, recipient animals treated with FTY720, a new immunosuppressant, exhibited a decrease in the number of peripheral lymphocytes due to apoptosis. In this study, we performed adCTLA4Ig transfection combined with FTY720 treatment in heart-grafted rats to determine if the combination could induce a mutual effect on graft survival. The recipient animals were given injections of 1 x 10(9) plaque-forming units of adCTLA4Ig via the tail vein immediately after grafting. On the day before transplantation we administered FTY720 orally to some of these animals at a dosage of 5 mg/kg and again on the day of transplantation. The median graft survival period in the adCTLA4Ig-only group was 27 days, whereas that in the combination group was markedly prolonged to 56 days. Of 15 grafts, 5 survived indefinitely. In these groups we observed detectable levels of CTLA4Ig in the sera 49 days after grafting; the levels were always higher in the combination group than in the adCTLA4Ig-only group. As a result, this study revealed that FTY720 and adCTLA4Ig have a potent mutual effect on graft survival during rat heart transplantation. Furthermore, it is highly possible that FTY720 enhances gene expression of adCTLA4Ig, which may be related to the long-term acceptance of grafts.

A soft dual-port trocar for endoscopic subcutaneous surgery.

BACKGROUND: We developed a new trocar for endoscopic subcutaneous surgery and tested it in subfascial endoscopic perforator surgery (SEPS) for varicose veins of the lower leg. METHODS: The soft trocar is a y-shaped polyvinyl chloride bag equipped with two ports at one end and a flexible ring at the other end. We performed SEPS on 12 patients through a 2-cm incision below the knee. After dissection of the subfascial plane, the ring of the trocar was inserted beneath the fascia, and the subfascial cavity was inflated with CO2 gas. The perforating veins were divided with UltraShears (Autosuture, USSC, Norwalk, CT, USA) inserted through the second port of the trocar with an endoscope. RESULTS: There were no major device-related difficulties or wound complications. CONCLUSION: The soft trocar allowed both an endoscope and a surgical instrument to be inserted simultaneously in the tissue space through a single incision. This useful instrument may have applications in other endoscopic surgical procedures.

Insufficient effect of p27(KIP1) to inhibit cyclin D1 in human esophageal cancer in vitro.

The cell cycle is controlled by protein complexes composed of cyclins and cyclin-dependent kinases. p27KIP1 (p27) is one of the Kip/Cip family cyclin-dependent kinase inhibitory proteins which negatively regulate cell cycle progression, and have been proposed as candidate tumor suppressor genes. To examine the role of p27 in the development of human esophageal squamous cell carcinoma (ESCC), we performed Western blot and immunoprecipitation analyses of the levels of expression of p27 protein in a series of ESCC cell lines. This protein was expressed at various levels in these cell lines during exponential growth. p27 level was significantly associated with that of cyclin D1, but not of cyclin E. Further cell cycle synchronization studies demonstrated that p27 was free or bound with affinity to cyclin E-CDK2 more than to cyclin D1-CDK4 or cyclin D1-CDK6. It is known that overexpression of cyclin D1 rather than cyclin E is involved in the pathogenesis of ESCC. Our findings indicated that high expression of p27 throughout the G1 to S phase may inhibit more likely cyclin E, than cyclin D1, which promotes tumor growth of esophageal squamous cell carcinoma.