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Biomedical subjects

Tsuyoshi Itoh

Publications and source records attributed to Tsuyoshi Itoh.

At least 19 recordsLinked to original sources
PubMed2006

The Adamkiewicz artery: demonstration by intra-arterial computed tomographic angiography.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of using multidetector-row CT angiography (CTA) with intra-arterial contrast injection (IA-CTA) to depict the artery of Adamkiewicz (arteria radicularis magna, ARM). METHODS: We performed IA-CTA in 27 preoperative patients with aneurysm or dissection of the descending thoracic or thoracoabdominal aorta. ARM was examined on multiplanar and curved planar reformation images and on the paging method, and we investigated detectability and visualization of the ARM, the level of branching, and right/left frequency as well as continuity from the origin to the ARM. Furthermore, the bolus characteristic of contrast medium in IA-CTA was investigated and compared with CTA with intravenous contrast injection (IV-CTA). The bolus characteristic of the contrast medium was assessed by the determination of the CT value in the aorta in each of the 16 cases in which both IA-CTA before surgery and intravenous IV-CTA at the time of admission were performed. RESULTS: The ARMs were clearly visualized and at least one ARM to be reserved was determined in all patients (100%). The average number of ARM observed was 1.4+/-0.58 per patient (39/27). Innate origin was determined in 90% (35/39) of ARMs and it ranged between the 8th thoracic vertebra and the 3rd lumbar vertebra levels, and branching from the left accounted for 63.2% (24/38). It was possible to observe the exact continuity from the innate origin to the ARM as well as from the secondary origin to the ARM mediated by collateral vesseles in 61.5% of the total ARMs (24/39). The CT value in the aorta calculated on IA-CTA was significantly higher than that on IV-CTA (p<0.05). As a result, the high bolus characteristic of contrast medium in IA-CTA was confirmed. CONCLUSION: It was possible to detect the ARM in all patients and to obtain information about the origin by IA-CTA. This method is considered useful for preoperative assessment of a descending thoracic or a thoracoabdominal aorta for aortic aneurysm or dissection.

Adolescent↗
PubMed2006

The range of tumor extension should have precedence over the location of the deepest tumor center in determining the regional lymph node grouping for widely extending esophageal carcinomas.

BACKGROUND: The Japanese Guide Lines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus (9th edn) give precedence to the location of the deepest tumor center rather than the range of tumor extension when determining regional lymph node grouping. We evaluated the validity of this recommendation. METHODS: The subjects were 49 patients with carcinomas of the distal thoracic esophagus and cardia who had undergone esophagectomy with three-field lymph node dissection. We measured variables defining tumor location, such as the distance from the esophagogastric junction (EGJ) to the proximal margin of the tumor (DJP), the distance from the EGJ to the distal margin of the tumor (DJD), and the distance from the EGJ to the deepest tumor center (DJC). To examine the relation of tumor location to lymph node metastasis in the proximal direction, the patients were divided into two groups according to the presence (14 patients) or absence (35 patients) of middle-upper mediastinal and/or cervical lymph node metastases. These two groups were compared with respect to the above variables. To analyze lymph node metastasis in the distal direction, the patients were also divided into two groups according to the presence (12 patients) or absence (37 patients) of distant abdominal lymph node metastases. These two groups were similarly compared with respect to the above variables. RESULTS: DJP was significantly longer in the patients with middle-upper mediastinal and/or cervical lymph node metastases than in those without such metastases. Multiple logistic regression analysis showed that the DJP was a better predictor of middle-upper mediastinal and/or cervical lymph node metastases than was the DJC. The DJD was significantly longer in the patients with distant abdominal lymph node metastases. Multiple logistic regression analysis also showed that the DJD was a better predictor of distant abdominal lymph node metastases than was the DJC. CONCLUSIONS: The range of tumor extension is a more reliable predictor of the risk of distant lymph node metastases than is the location of the deepest tumor center in esophageal carcinoma.

Adenocarcinoma↗
PubMed2006

Successful induction of clinically competent dendritic cells from granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy.

Recent studies have suggested that dendritic cell (DC)-based immunotherapy is one promising approach for the treatment of cancer. We previously studied the clinical toxicity, feasibility, and efficacy of cancer vaccine therapy with peptide-pulsed DCs. In that study, we used granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood monocytes as a cell source of DCs. However, previous investigations have suggested that G-CSF-mobilized peripheral blood monocytes produce reduced levels of proinflammatory cytokines such as interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. These T helper (Th)-1-type cytokines are thought to promote antitumor immune response. In this study, we assessed the functional abilities of DCs generated from G-CSF-mobilized monocytes obtained from 13 patients with CEA-positive advanced solid cancers. Peripheral blood mononuclear cells were obtained from leukapheresis products collected before and after systemic administration of G-CSF (subcutaneous administration of high-dose [5-10 microg/kg] human recombinant G-CSF for five consecutive days). In vitro cytokine production profiles after stimulation with lipopolysaccharide (LPS) were compared between monocytes with and without G-CSF mobilization. DCs generated from monocytes were also examined with respect to cytokine production and the capacity to induce peptide-specific T cell responses. Administration of G-CSF was found to efficiently mobilize peripheral blood monocytes. Although G-CSF-mobilized monocytes (G/Mo) less effectively produced Th-1-type cytokines than control monocytes (C/Mo), DCs generated from G/Mo restored the same level of IL-12 production as that seen in DCs generated from C/Mo. T cell induction assay using recall antigen peptide and phenotypic analyses also demonstrated that DCs generated from G/Mo retained characteristics identical to those generated from C/Mo. Our results suggest that G-CSF mobilization can be used to collect monocytes as a cell source for the generation of DCs for cancer immunotherapy. DCs generated in this fashion were pulsed with HLA-A24-restricted CEA epitope peptide and administered to patients safely; immunological responses were induced in some patients.

Adult↗
PubMed2006

Direct imaging of bileaflet mechanical valve behavior in the tricuspid position.

OBJECTIVE: The optimal orientation of a bileaflet mechanical valve for tricuspid valve replacement (TVR) has not yet been determined. The aim of this study was to use fiberoptic cardioscopy to evaluate the effect of orientation of a mechanical valve implanted in the tricuspid position on bileaflet mechanical valve behavior. METHODS: Twelve pigs (50-59 kg) underwent TVR with a St. Jude Mechanical Heart Valve (25 mm standard cuff model) after cardioplegic arrest. The mechanical valve was implanted horizontally in six pigs (Group H), and vertically in another six pigs (Group V). The heart was perfused with pellucid Krebs-Henseleit solution in situ and the mechanical valve behavior was observed with a fiberoptic endoscope during different heart rates (HRs) induced by ventricular pacing (60, 90, 120, 150 min(-1)). All images were recorded on a high-speed video system every 4 ms. The closing time lag (CTL) between the valve leaflets was calculated and compared between the two groups. RESULTS: In Group H, the lower valve leaflet tended to open incompletely and close earlier than the upper leaflet. The calculated CTL was 303+/-60 ms, 65+/-48 ms, 40+/-9 ms, and 40+/-26 ms at pacing HRs of 60, 90, 120, and 150 min(-1), respectively. In contrast to Group H, there was little difference in CTL between the right and left leaflets in Group V. The calculated CTL was 9+/-12 ms, 11+/-10 ms, 1+/-3 ms, and 6+/-7 ms at pacing HRs of 60, 90, 120, and 150 min(-1), respectively. There were significant differences in CLT between the two groups at each ventricular pacing rate (P < 0.01). CONCLUSIONS: Orientation of an implanted bileaflet valve in the tricuspid position significantly influenced leaflet motion. In a horizontal orientation, the lower valve leaflet opened incompletely and closed earlier than the upper leaflet. These results suggest that the gravity might affect leaflet motion and that bileaflet mechanical valves should be implanted vertically in TVR to prevent abnormal leaflet motion and thrombus formation.

Animals↗
PubMed2006

Surgical revascularization for acute coronary syndrome: comparative surgical and long-term results.

OBJECTIVE: The purpose of this study was to evaluate the adequate timing of coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS). METHODS: In our institution, emergency CABG has been avoided when possible for ACS patients favoring stabilization with medical therapies, including intra-aortic balloon pumping or percutaneous coronary intervention. After thorough preoperative examinations, an urgent CABG is performed. A total of 67 patients with ACS underwent CABG, comprised of 33 patients receiving an emergency CABG (emergent group: E-G) and 34 patients receiving an urgent CABG (urgent group: U-G). The early and long-term results were evaluated retrospectively. RESULTS: Preoperatively, the incidences of acute myocardial infarction and cardiogenic shock were significantly higher in E-G. No significant differences were found in the intraoperative factors except for the number of distal anastomoses (2.5 in E-G vs. 3.1 in U-G, p=0.01). The hospital mortality was 9.1% in E-G, and 2.9% in U-G, with no significant difference between the groups. Moreover, no patient in U-G necessitated emergency CABG while waiting for surgery. The patency rate of the grafts was 100% in E-G, and 96.2% in U-G. The 5-year survival rate excluding in-hospital death was 80.3% in E-G, and 78% in U-G (p>0.05). The 5-year cardiac event-free rate was 80.3% in E-G, and 80.9% in U-G (p>0.05). CONCLUSION: An emergency CABG can be reserved for ACS patients when symptoms and hemodynamic state are stabilized with medical therapies. Improvements in long-term results can be expected after high quality and complete surgical revascularization.

Aged↗
PubMed2006

Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

Antigen-Presenting Cells↗
PubMed2006

Induction of cytotoxic T lymphocytes against human cancer cell lines using dendritic cell-tumor cell hybrids generated by a newly developed electrofusion technique.

Recently, dendritic cells (DCs) and DC-tumor cell hybrids (DC-tumor hybrids) have been used for cancer vaccine therapy in a clinical trial. DC-tumor hybrids combine the potent antigen-presenting capacity of DCs with the ability to present all tumor antigens expressed on tumor cells to T cells. We used DC-tumor hybrids as stimulator cells to induce tumor-specific cytotoxic T lymphocytes (CTLs) in vitro. DC-tumor hybrids were generated from human monocyte-derived DCs and human cancer-cell lines (GT3TKB, lung cancer; GCIY, gastric cancer) by our newly developed electrofusion technique, established and refined with the use of mouse cells. To evaluate the capacity of DC-tumor hybrids generated by our method to induce tumor antigen-specific CTLs, we performed a cytotoxic assay and an interferon-gamma release assay using CD8-dominant effector lymphocytes induced by them. DC-tumor hybrids more effectively induced tumor-specific primary T-cell response than did stimulation with DCs co-cultured with irradiated tumor cells overnight, irradiated tumor cells alone, or a mixture of DCs and irradiated tumor cells. DC-tumor hybrids were generated at a high fusion rate by our electrofusion technique. When CTLs were induced by DC-tumor hybrids in vitro, the high fusion rate did not contribute to the induction of CTLs with increased tumor-specific cytotoxicity. The addition of interleukin-12 to the culture medium did not augment the cytotoxicity of CTLs. Overall, our results suggest that DC-tumor hybrids effectively induce human tumor-specific CTLs and may thus be applicable for clinical trials of adoptive immunotherapy.

Adenocarcinoma↗
PubMed2006

Intraoperative pathological investigation of recurrent nerve nodal metastasis can guide the decision whether to perform cervical lymph node dissection in thoracic esophageal cancer.

Three-field lymph node dissection has been widely used to treat thoracic esophageal cancer, but is very invasive and can cause serious complications. Whether cervical lymph node dissection should be performed in all patients with thoracic esophageal cancer remains controversial. We pathologically examined the recurrent nerve lymph nodes during surgery in patients with thoracic esophageal cancer to determine the presence or absence of lymph node involvement. In patients without recurrent nerve nodal involvement, cervical lymph node dissection was not performed. Treatment outcomes were analyzed to evaluate whether intraoperative pathological investigation was a useful procedure. Among 71 patients with thoracic esophageal cancer who underwent 3-field lymph node dissection, the rate of cervical lymph node metastasis was 40.9% in patients with recurrent nerve nodal metastasis on intraoperative pathological investigation, as compared with 10.2% in patients without recurrent nerve nodal metastasis (p=0.007). Multiple logistic-regression analysis showed that recurrent nerve nodal metastasis was a strong predictor of cervical lymph node metastasis (odds ratio, 2.98; 95% confidence interval, 1.139-7.775; p=0.03). Among 41 patients who underwent intraoperative pathological investigation, 10 had recurrent nerve nodal metastasis and underwent cervical lymph node dissection. Two of these patients had histological evidence of cervical lymph node metastasis. The remaining 31 patients had no recurrent nerve nodal metastasis on intraoperative pathological examination and therefore did not receive cervical lymph node dissection. None of these patients had cervical lymph node recurrence on follow-up. We compared patients who underwent intraoperative pathological investigation with those who underwent conventional 3-field lymph node dissection (without performing intraoperative pathological investigation). The rates of cervical lymph node recurrence were similar among the groups (2.6% vs. 6.7%), but the 3-year survival rate was significantly higher in the patients who underwent intraoperative pathological dissection (83.3%) than in those who underwent 3-field dissection (57.2%; p<0.05). Although this was a retrospective study, our results suggest that outcomes of patients undergoing cervical lymph node dissection according to the results of intraoperative pathological investigation are at least as good as those in patients undergoing 3-field lymph node dissection. We conclude that intraoperative pathological investigation of recurrent nerve nodal metastasis is useful for determining whether cervical lymph node dissection should be performed in patients with thoracic esophageal cancer.

Aged↗
PubMed2006

A novel immunotherapeutic modality with direct hemoperfusion targeting transforming growth factor-beta prolongs the survival of tumor-bearing rats.

Immune responses are frequently depressed in patients with cancer. One of the reasons for a poor immune response is the presence of increased levels of immunosuppressive substances associated with tumor growth. Transforming growth factor-beta (TGF-beta), a representative immunosuppressive cytokine, plays various roles in the progression of cancer. To remove immunosuppressive substances from tumor-bearing hosts, we developed an immunosuppressive substance adsorption (ISA) column for direct hemoperfusion (DHP) treatment. It is filled with extra-fine fibers that can adsorb TGF-beta. In this study, we investigated the effects of this DHP treatment on serum levels and activities of TGF-beta, cellular immune responses, and anti-tumor effects in KDH-8 (TGF-beta-producing hepatocellular carcinoma cell line)-bearing rats. We further studied the ability of ISA fibers to adsorb tumor-associated immunosuppressive cytokines [TGF-beta, interleukin (IL)-6 and vascular endothelial growth factor (VEGF)] in samples of body fluids obtained from patients with metastatic cancer. DHP treatment decreased serum levels and activities of TGF-beta in tumor-bearing rats and restored T lymphocyte response to mitogen. Tumor growth in rats treated by DHP was significantly slower than that in untreated rats. The survival time of treated rats was significantly longer than that of untreated rats. The concentrations of TGF-beta, IL-6, and VEGF in the samples of human body fluids were decreased markedly by in vitro treatment with ISA fibers. These results suggest that DHP treatment with an ISA column, which removes TGF-beta and other immunosuppressive substances from the sera of tumor-bearing hosts, is potentially a new immunotherapeutic strategy for cancer.

Adsorption↗
PubMed2005

Potassium oxonate, an enzyme inhibitor compounded in S-1, reduces the suppression of antitumor immunity induced by 5-fluorouracil.

S-1 is an oral formulation combining tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. We examined whether Oxo reduces the immunosuppression induced by 5-fluorouracil (5-FU) in the rat. The body weight of rats treated with S-1 (FT + CDHP + Oxo) for seven consecutive days was significantly higher than that of rats treated with a combination of FT plus CDHP (FT + CDHP) for a similar period. The number of peripheral leukocytes was significantly higher in the S-1-treated rats (S-1 group) than that in the FT + CDHP-treated rats (FT + CDHP group). There was no apparent difference between the two treated groups in phenotypic changes of CD3-, CD45-, CD4-, or CD8-positive cells from the spleen or mesenteric lymph nodes. However, the natural killer activities of both spleen cells and mesenteric lymph node cells were significantly higher in the S-1 group than in the FT + CDHP group. Interleukin (IL)-2 production by spleen cells stimulated with concanavalin A was significantly lower in the FT + CDHP group than in the S-1 group. Although IL-2 production by mesenteric lymph node cells in the S-1 group was lower than that in untreated rats, it was higher than that in the FT + CDHP group. These findings suggest that Oxo in S-1 may reduce the suppression of antitumor immunity induced by 5-FU.

Animals↗
PubMed2005

Malignant fibrous histiocytoma of the trachea.

We experienced a rare case of malignant fibrous histiocytoma (MFH) arising in the trachea. A 24-year-old man with severe dyspnea had a well-defined mass in the cervical trachea on chest X-ray examination. Chest computed tomography showed a 2.0-cm diameter mass originating in the right-posterior wall of the trachea. The tumor occupied over 90% of the lumen. A radical excision of the tumor (tracheal resection) with tracheal plasty was performed. The microscopic diagnosis was MFH. The patient remains well, without evidence of recurrence, 3 months after surgery.

Adult↗
PubMed2005

[Sudden death and cardiovascular complications in Marfan syndrome: impact of surgical intervention].

Marfan syndrome is an autosomal dominant disorder of connective tissue characterized by abnormalities involving the skeletal, ocular, and cardiovascular systems. The cardiovascular complications of the syndrome lead to a reduced life expectancy for affected individuals if left untreated. Major cause of death include acute aortic dissection, aortic rupture, and sudden death, which resulted from congenital vascular fragility. Such life-threatening complications in Marfan syndrome can be managed effectively, by routine aortic imaging, beta-adrenergic blockade, and prophylactic replacement of the aortic root before the diameter exceeds 5.0 to 5.5 mm. Valve preserving aortic root reconstruction yielded improved postoperative quality of life compared with Bentall operation, by reducing late complications related to anticoagulants. It should be carried out before onset of aortic regurgitation for long-term native valve durability.

Cardiovascular Diseases↗
PubMed2005

[The effects of direct hemoperfusion using the filtration column filled with the adsorption fiber for immunosuppressive substances on cell-mediated immunity in tumor-bearing rats].

The patients with advanced cancer often lose their anti-tumor immune responses due to the increase of some immunosuppressive substances in the blood, such as cytokines and proteins derived from cancer cells or immune cells. We developed the adsorption fiber in transforming growth factor (TGF)-beta for the treatment to remove immunosuppressive substances and investigated the effects of direct hemoperfusion using the filtration column filled with this adsorption fiber in tumor-bearing rats. On day 0, KDH-8 tumor cells (1 x 10(6) cells/rat) were implanted subcutaneously into the back of WKAH/Hkm rats. On day 21 after tumor implantation, the rats underwent the direct hemoperfusion with this filtration column for 60 minutes. On day 28, the rats were sacrificed and the natural killer (NK) activities of their spleen cells were examined. As a result, the rats that underwent this treatment showed a significant increase in their NK activities compared with those of rats who underwent direct hemoperfusion with an empty column or had no treatment. Therefore, we indicated the possibility of a new immunotherapy technique against cancer using a direct hemoperfusion column filled with an adsorption fiber for immunosuppressive substances.

Adsorption↗
PubMed2004

Comparison of limited and full sternotomy in aortic valve replacement.

OBJECTIVE: The practice of minimally invasive valve surgery remains controversial. The aim of this study was to evaluate the technical feasibility and postoperative course of aortic valve replacement through limited upper sternotomy compared to conventional full sternotomy. METHODS: From May 1998 to August 2000, we performed 24 cases of isolated aortic valve replacements through the limited upper sternotomy approach (group M). During the same period, 18 patients received isolated aortic valve replacements through the conventional full sternotomy approach (group C). Operation duration, postoperative course and laboratory data were compared between the two groups. RESULTS: All patients received a valve replacement with a prosthetic valve. There was no significant difference between the two groups in mean aortic cross-clamping time, mean cardiopulmonary bypass time or mean operation duration (skin to skin). No patient required blood transfusion. Patients in the group M were extubated earlier, with less postoperative blood loss and discharged earlier after the operation than those in group C. On the first postoperative day, the peak level of lactic acid dehydrogenease was significantly lower in the group M than those in group C. CONCLUSION: Limited upper sternotomy for aortic valve replacement resulted in shorter operation duration and minimized operative risks for the patients. We believe this method brings not only cosmetic benefits but also improved postoperative course.

Adult↗
PubMed2004

Improved survival of surgery for acute type A aortic dissection: impact of noninvasive diagnosis and hemostatic surgical management.

OBJECTIVES: In the past decade, progress in cardiovascular technology has been incorporated into the surgical treatment of acute type A dissection resulting in remarkable improvement. Factors in this progress encompass rapid noninvasive diagnosis, intraoperative introduction of aprotinine, surgical glue, sealed grafts, and refined surgical technique. The objective of this study is to identify which factors contributed to the improvement of the surgical outcome of acute type A dissections. METHODS: Between January 1989 and February 2001, 78 consecutive patients had emergency surgeries for acute type A dissection. The initial 31 patients (group I) received preoperative angiography, when possible. Since 1996, the next 47 patients (group II) have received noninvasive rapid diagnosis with hemostatic surgical management. This included aggressive proximal resection and judicious use of gelatin resorcine formol glue and felt strips. Between the two groups, in-hospital mortality and morbidity, incidence of neurological complications, late survival and cardiovascular events were compared. Risk factors for in-hospital death were investigated with univariate and multivariate analysis. RESULTS: The in-hospital mortality was significantly improved in group II (4.3%) compared with group I (29.0%). Overall mortality was 14.1%. Multivariate analysis revealed preoperative limb ischemia and delayed timing of operation (> 3 hours after arrival) as independent risk factors for in-hospital death. Late survival at 5 years was 61.5+/-7.5%. Between the two groups there was no significant difference in late survival or cardiovascular events. CONCLUSIONS: Immediate surgical intervention, using rapid noninvasive diagnosis with hemostatic management, substantially improves the surgical outcome of acute aortic dissection.

Adult↗