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Shin-ichi Takeda

Publications and source records attributed to Shin-ichi Takeda.

At least 37 records · Page 2Linked to original sources

Risk stratification for lung cancer surgery: impact of induction therapy and extended resection.

STUDY OBJECTIVES: Current surgical strategies for lung cancer are directed toward the following two distinct targets: the increased prevalence of early-stage lung cancer; and locally advanced lung cancer treated with induction therapy (IT). To establish the risk stratification for operative morbidity from this viewpoint, we evaluated the impact of IT and/or an extended surgical procedure on operative results. DESIGN: Retrospective study. SETTING: A 674-bed teaching hospital. PATIENTS AND METHODS: The morbidity and mortality of 758 consecutive patients who underwent surgery for the treatment of non-small cell lung cancer were analyzed. There were 666 patients who underwent surgery alone (S group; 560 standard lobectomies and 106 extended resections) and 92 patients who received IT (IT group; 35 standard lobectomies and 57 extended resections). Comparisons between the groups were performed using unpaired t tests or chi(2) tests. Univariate and multivariate logistic regression analyses were used to determine the risk factors for operative morbidity and mortality. RESULTS: IT and extended surgery were strong independent factors for predicting postoperative morbidity (p < 0.0001). Significant differences were observed for pathologic stage (p < 0.0001), preoperative hemoglobin and Dlco levels (p < 0.001), the ratio of extended resection (p < 0.0001), and operation time and intraoperative bleeding (p < 0.001) between the S and IT groups. The overall morbidity and mortality rates were 16.8% and 0.9%, respectively, in the S group, and 55.4% and 5.4%, respectively, in the IT group (p < 0.01). The overall morbidity and mortality rates were 63.2% and 7.0%, respectively, for extended resection after IT, and 12.8% and 0.3%, respectively, for those who underwent a standard resection without IT. CONCLUSIONS: The morbidity and mortality of lung resection are both significantly increased after IT, and the patients with the greatest risk are those who have undergone IT and extended resection. The impact of IT on risk stratification should be emphasized in perioperative care.

Adenocarcinoma↗

Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats.

BACKGROUND: Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat. METHODS: GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis. CONCLUSIONS: These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.

Animals↗

Pulmonary benign metastasizing leiomyoma from the uterus in a postmenopausal woman: report of a case.

We report a case of pulmonary benign metastasizing leiomyoma (BML) from the uterus in a 77-year-old woman. The patient presented for investigation of multiple pulmonary nodules on a routine chest roentgenogram. Because a preoperative diagnosis could not be made, the largest tumor, 3.5 cm in diameter, was resected from the right lower lobe, and histological examination confirmed BML. She had undergone hysterectomy with oophorectomy for uterine leiomyomas 12 years earlier, at the age of 65. The microscopic findings of the lung tumor were similar to those of the uterine leiomyoma, and both lesions were histologically benign. Although this disease is considered to be hormone-dependent, metastasis was found in this elderly postmenopausal woman whose tumor was negative for estrogen receptor.

Aged↗

Thymic carcinoma with a large cystic lesion.

A 59-year-old man presented with a large anterior mediastinal mass. A computed tomography (CT) and magnetic resonance imaging showed a well-circumscribed cystic mass, 12 cm in size adjacent to the heart border and superior vena cava (SVC). A CT guided needle biopsy was performed, and instead of detecting malignant tissues but finding that gray muddy fluid was suctioned, suggesting cystic teratoma. At surgery, the tumor was confirmed advanced thymic carcinoma with pleural dissemination, then the tumor was extirpated with resection of SVC, followed by 2 cycles of chemotherapy. Histologically, the cystic wall was lined with malignant cells. We herein present a diagnostic pitfall case of thymic carcinoma having a large cystic component with which rare association should be recognized.

Carcinoma, Squamous Cell↗

Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma.

BACKGROUND: A pulmonary metastasectomy for colorectal carcinoma is a generally accepted procedure, although several prognostic predictors have been reported. The aim of this study is to define the patients who benefit from pulmonary metastasectomy for colorectal carcinoma. METHODS: Retrospective survival analysis was performed using 128 patients who underwent curative pulmonary resection. RESULTS: The overall 5-year survival rate was 45.3%. Univariate analysis showed the number of metastases, location (unilateral or bilateral), prethoracotomy carcinoembryonic antigen (CEA) level, hilar or mediastinal lymph-node metastasis, and Dukes' stage to be considerable prognostic factors. Among these, Dukes' A for the primary lesion and unilateral pulmonary metastasis were shown to be independent predictors of longer survival by multivariate analysis (p = 0.0093 and p = 0.0182, respectively). In patients treated with both pulmonary and hepatic metastastasectomies, a better prognosis was observed in those who received metachronous resection. Recurrence after a pulmonary metastasectomy frequently occurred in the thorax and the 3-year survival rate was 44.6% in patients who underwent a repeat thoracotomy. CONCLUSIONS: Patients with unilateral metastasis and Dukes' A for the primary tumor benefit most from the resection of pulmonary metastasis from colorectal carcinoma. Further, the number of metastases, prethoracotomy CEA level, and hilar or mediastinal lymph-node involvement should be considered to determine the operative indication. Finally, periodic follow-up examinations for thoracic recurrence should be carefully performed as these patients may have a heightened risk of requiring a repeat thoracotomy.

Adenocarcinoma↗

Thymic carcinoma. Clinical institutional experience with 15 patients.

OBJECTIVE: We retrospectively evaluated 15 patients with thymic carcinoma treated with various modalities and investigated overall management of this disease. METHODS: From 1983 to 2003, we treated 15 patients with thymic carcinoma (12 squamous cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma). According to Masaoka's staging system, they consisted of 2 at stage II, 5 at stage III, 4 at stage IVa and 4 at stage IVb. RESULTS: Ten patients were histologically diagnosed preoperatively, and 5 patients underwent an exploratory procedure under the diagnosis of thymoma or benign teratoma. Complete resection was performed in 9 patients (2 stage II, 5 stage III and 2 stage IVa), which included 4 patients who received induction therapy, 4 who received postoperative radiation therapy, and 1 who received postoperative chemotherapy. Six patients with unresectable tumors were treated by irradiation (40-60 Gy) with or without chemotherapy. The median survival was 13 months for patients without resection, and 57 months for patients with a complete resection. Total 3-year and 5-year survival rates were 51.9 and 39.0%, respectively. CONCLUSIONS: We concluded that a complete resection is mainstay of therapy when possible, but chemoradiation therapy being potential benefit in the management of thymic carcinoma. However, considering the high prevalence of advanced stage patients, to establish the effective regimen of induction therapy in the additional multicenter trials should be mandatory.

Adenocarcinoma↗

Results of surgical intervention for p-stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe.

OBJECTIVES: Non-small cell lung cancer with mediastinal lymph node involvement is a heterogeneous entity different from single mediastinal lymph node metastasis to multiple nodes or extranodal disease. The objective of this study was to identify the subpopulation of patients with N2 disease who can benefit from surgical intervention. METHODS: We reviewed 219 consecutive patients with N2 non-small cell lung cancer treated with a thoracotomy between November 1980 and June 2002 and retrospectively analyzed 154 of those who had p-stage IIIA disease and underwent a complete resection. Age, sex, side (right or left), histology, location (upper or middle-lower lobe), tumor size, c-N factor, and N2 level (single or multiple) were used as prognostic variables. RESULTS: The 3- and 5-year survivals were 45.3% and 28.1%, respectively, in patients with p-stage IIIA (N2) disease. Survival for those with single N2 non-small cell lung cancer was significantly better than in those with multiple N2 disease (P =.0001), and patients with a tumor in the upper lobe showed a significantly longer survival than those with middle-lower lobe involvement (P =.0467). The 3- and 5-year survivals for patients with single N2 disease with a primary tumor in the upper lobe were 74.9% and 53.5%, respectively. A multivariate analysis with Cox regression identified 5 predictors of better prognosis: younger age, squamous cell carcinoma as determined by histology, primary tumor location in the upper lobe, c-N0 status, and a single station of mediastinal node metastasis. CONCLUSION: Our results suggest that of the heterogeneity of N2 diseases, patients with single N2 disease with non-small cell lung cancer in the upper lobe are good candidates for pulmonary resection.

Adenocarcinoma↗

Conversion from cyclosporine A to mycophenolate mofetil protects recipient kidney and prevents intimal hyperplasia in rat aortic allografts.

BACKGROUND: Recent studies have demonstrated that complete conversion from cyclosporine A (CsA) to mycophenolate mofetil (MMF) prolongs graft survival in patients undergoing clinical organ transplantation. We investigated the effects of conversion from CsA to MMF on recipient kidneys and transplant arteriosclerosis in a rat aortic allograft model as a high responder combination. METHODS: DA (MHC haplotype, RT1a) rat abdominal aortic grafts were orthotopically transplanted into Lewis (RT1l) rats. The recipients were divided into four oral treatment groups: (1) vehicle group, (2) CsA group (15 mg/kg/day), (3) CsA/MMF40 group (conversion from CsA 15 mg/kg/day to MMF 40 mg/kg/day on day 14), and (4) CsA/MMF20 group (conversion from CsA 15 mg/kg/day to MMF 20 mg/kg/day on day 14). On day 28 after transplantation, the rats were sacrificed and the hematoserological parameters were analyzed. The grafted aortas and recipient kidneys also were evaluated histologically and immunohistochemically. RESULTS: The CsA group developed serological renal dysfunction, arteriolar hyalinosis, and apoptosis in the recipient kidneys, whereas the CsA/MMF40 and CsA/MMF20 groups did not. In the vehicle group, we observed remarkable intimal hyperplasia and marked inflammatory cell infiltration including macrophages and T cells. In the CsA group, intimal hyperplasia was evident without infiltration of macrophages or T cells. In the CsA/MMF40 and CsA/MMF20 groups, intimal hyperplasia was abrogated, while adventitial infiltration of and adhesion to the endothelium by macrophages and T cells occurred. CONCLUSIONS: Conversion from CsA to MMF protected recipient kidneys and prevented transplant arteriosclerosis. However, insufficient immunosuppression by MMF might reactivate immune cells. This conversion therapy has preventive potential in transplant patients with CsA-associated nephrotoxicity and transplant arteriosclerosis.

Animals↗

Role of cyclins in cAMP inhibition of glomerular mesangial cell proliferation.

MC (mesangial cell) proliferation is closely linked to the progression of glomerular disease. It has been reported that cAMP effectors suppress MC proliferation, inhibiting activation of MAPK (mitogen-activated protein kinase). In fibroblasts, activation of MAPK induces the expression of type D cyclin, whereas, in MCs, this induction has not been shown. In the present study, we explored the effects of cAMP on MAPK and expression of cell-cycle-regulated proteins. PDGF (platelet-derived growth factor) stimulated MAPK activity, up-regulated protein levels of cyclin D1, CDK2 (cyclin-dependent kinase 2) and PCNA (proliferating cell nuclear antigen), decreased the protein level of p27 and increased DNA synthesis. Fsk (forskolin) or PD98059 suppressed PDGF-induced DNA synthesis. Both agents inhibited PDGF-stimulated mRNA and protein expression of cyclin D1 and CDK2. Fsk or PD98059 also inhibited protein expression of PCNA and blocked a decrease in p27 protein. Fsk induced the phosphorylation of Raf-1 at Ser259, which was inhibited by KT5720. These data suggest that cAMP inhibits MC proliferation through inhibition of MAPK activity, and this mechanism partly involves alteration in the levels of cell-cycle-regulated proteins.

Animals↗

Successful gene transfer using adeno-associated virus vectors into the kidney: comparison among adeno-associated virus serotype 1-5 vectors in vitro and in vivo.

BACKGROUND/AIM: Gene transfer into the kidney has great potential as a novel therapeutic approach. However, an efficient method of gene transfer into the kidney has not been established. We explored the transduction efficiency of renal cells in vitro and in vivo using adeno-associated virus (AAV) serotype 1-5 vectors encoding the beta-galactosidase gene. METHODS: In the in vitro study, rat kidney epithelial cell line NRK52E cells were transfected with AAV serotype derived vectors. In the in vivo study, AAV serotype derived vectors were selectively injected into the kidney using a catheter-based gene delivery system in rats and mice mimicking the clinical procedure. The efficiency of gene expression was histologically evaluated on the basis of the beta-galactosidase expression. RESULTS: AAV serotype 1, 2, and 5 vectors transduced in rat kidney epithelial cell line NRK52E cells in vitro, whereas AAV serotype 3 or 4 vectors showed no transduction. In addition, the kidney-specific injection of AAV serotype 2 vectors successfully transduced in tubular epithelial cells, but not in glomerular, blood vessel, or interstitial cells in vivo, whereas the rest of the serotypes showed no transduction. CONCLUSION: Since kidney-specific gene delivery via the renal artery by catheterization is highly feasible in humans, these findings provide useful information for promising strategies in renal gene therapy.

Animals↗

Establishment of lacZ-transgenic rats: a tool for regenerative research in myocardium.

Animals transgenic (Tg) for reporter genes would be useful to following a given cell lineage during differentiation and regeneration processes. Here, we established a beta-galactosidase (lacZ) Tg rat to use as a tool for regenerative research. Strong lacZ expression was observed in the skeletal muscles, myocardium, pancreas, and skin obtained from these lacZ-Tg rats, and moderate lacZ expression was observed in the liver, spleen, kidney, and cartilage. In contrast, brain, vessels, lung, adrenal gland, small intestine, blood leukocytes, bone marrow (BM) cells, and peripheral blood cells showed no lacZ expression. To test whether this lacZ-Tg rat could be used for regenerative research in myocardium, we induced myocardial injury after a lacZ-Tg BM transplant (BMT) into wild-type rats. The results show that lacZ-positive cardiomyocytes were found in the peri-infarct and uninjured myocardium in the BMT recipient rats. These findings suggest that lacZ-Tg rats are useful tool for regenerative research in the myocardium.

Animals↗

Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution.

BACKGROUND: Primary germ cell tumors (GCT) of the mediastinum share similar clinical and biologic characteristics, which are different from their testicular counterpart. The purpose of the current study was to review the authors' institutional experience of mediastinal GCT, emphasizing the clinical spectrum, time trends of treatment, and recent advances in therapeutic modalities for malignant GCT. METHODS: Between 1951 and 2000, 129 patients (70 males and 59 females) underwent surgical treatment for GCT, which accounted for 16.0% of the mediastinal tumors during the same period. There were 95 patients with mature teratomas, 13 patients with seminomas, and 21 patients with nonseminomatous germ cell tumors (NSGCT) with median ages of 26.4 years, 27.6 years, and 28.5 years, respectively. RESULTS: Adult patients with mature teratomas were less symptomatic (33.3%) than pediatric patients (52.4%). All patients with mature teratoma were cured by resection alone. Eight of the 13 patients (61.5%) with seminoma were symptomatic and 10 of 13 patients (83.3%) survived after surgery and radiation with/without chemotherapy. Nineteen of 21 patients (90.5%) with NSGCT had dyspnea, chest pain, and superior vena cava syndrome. Before 1985, patients received radical resection and/or chemoradiotherapy. However, all patients died due to disease progression, with a median survival period of 7.6 months. After 1986, six of eight patients received cisplatin-based chemotherapy, including three who received additional high-dose chemotherapy with a supporting peripheral blood stem cell transplantation until tumor markers normalized. Five patients who underwent salvage resection are currently disease free with a median survival period of 58.3 months. CONCLUSIONS: The institutional experience indicates the benign nature of mediastinal mature teratomas and the excellent prognosis for patients with seminomas after resection. An improved survival advantage was ensured with cisplatin-based preoperative chemotherapy in patients with NSGCT.

Adolescent↗

Clinical spectrum of primary mediastinal tumors: a comparison of adult and pediatric populations at a single Japanese institution.

BACKGROUND AND OBJECTIVES: The purpose of this study was to review our Japanese institutional experience of mediastinal tumors and to compare differences in the clinical spectrum between adults and children. METHODS: We retrospectively reviewed the records of 806 patients (676 adults and 130 children) between 1951 and 2000 at our institution. RESULTS: There were 244 thymomas (36%), 106 germ cell tumors (16%), 95 congenital cysts (14%), 82 lymphomas (12%), 76 neurogenic tumors (11%), and 24 thyroid tumors (4%) in adult patients. There were 60 neurogenic tumors (46%), 24 germ cell tumor (19%), 17 lymphoma (13%), 10 congenital cysts (8%), and 5 thymomas (4%) in the pediatric patients. There was a significant higher incidence of neurogenic tumors and a lower incidence of thymomas and thyroid tumors in children than adults. The most common location was the anterior compartment (68%) in adults and the posterior compartment in children (52%). The prevalence of malignancy in pediatric patients was lower than adults (37% vs. 47%; P < 0.05). Symptoms due to compression or direct invasion into adjacent structures may have caused the higher incidence of dyspnea or respiratory distress in the pediatric group compared to the adults (15.4% vs. 4.0%; P < 0.001). There were fewer incidences of facial edema in children compared to adults (2.6% vs. 10.7%; P < 0.02). Emergent operations were required more often in the pediatric group than the adult group. CONCLUSIONS: We demonstrated definite differences in histologic distribution, location, and symptomatology in mediastinal tumors between adult and pediatric populations, which should be considered in the evaluation and planning of a therapeutic modality for mediastinal tumors.

Adolescent↗

Prognostic significance of persistent mediastinal metastasis following induction therapy in large (> or = 2 cm) N2 or N3 non-small cell lung cancer.

OBJECTIVE: It is controversial whether or not surgery is beneficial for patients with non-small cell lung cancer accompanied by persistent lymph node metastasis in the mediastinum following induction therapy. We have therefore conducted a retrospective study to assess this issue. METHODS: Eligibility criteria were defined as follows: 1) the period of treatment was between January 1991 and April 1998, 2) the clinical stages were IIIA (N2) or IIB (N3) with large lymph nodes (> or = 2 cm), 3) induction therapy had been administered, 4) tumor was resected completely, 5) at least one mediastinal lymph node had necrosis or scar if the pathological N status was p-N0 or p-N1 and 6) the p-stage was not IV. Dichotomous variables included the radiographic response of the tumor, the T status, and the N status. RESULTS: Thirty-nine patients were eligible. There were 29 males and 10 females aged from 27 to 74 years, and involved 20 cases of adenocarcinoma. The pathological N status was as follows: p-N0 in 18 patients, p-N1 in 3, p-N2 in 16, and p-N3 in the other 2. In overall survival, the median survival time (MST) was 34 months and the actuarial 5-year-survival rate (5-YSR) was 28%. The group of patients with either N0 or N1 (n = 21) had a 71-month MST and a 54% 5-YSR, and the group of patients with either N2 or N3 (n = 18) had a 13-month MST and a 5-YSR of 0% (p < 0.0001). On multivariate analysis, the pathological N factor was confirmed as an independently significant. CONCLUSIONS: Our retrospective study found that the survival rate of patients with persistent mediastinal nodal metastasis was very poor. A prospective study is needed to investigate whether or not surgery is beneficial for these patients.

Adult↗

Immunohistochemical analysis of resected clinical stage I pulmonary adenocarcinomas with high preoperative levels of serum carcinoembryonic antigen.

BACKGROUND: Clinical stage I pulmonary adenocarcinoma (AD) patients with persistently high serum carcinoembryonic antigen (CEA) levels after surgery have a poor prognosis. Although CEA staining pattern is reported to be a prognostic indicator for patients with colorectal cancer, the relationship with lung cancer is unclear. METHODS: One hundred eighteen patients with clinical stage I AD underwent surgery from 1993 to 1997. Of them, 19 (16%) patients with a high preoperative serum level of CEA and 19 randomly selected control patients with preoperatively normal CEA were studied. CEA staining of tumor specimens from each of the 38 patients was performed, and the staining patterns were then classified into two types: apical and diffuse. RESULTS: Patients with normal postoperative serum CEA levels (group HN, n = 13) had a 5-year survival rate higher than those with persistently high postoperative serum CEA (group HH, n = 6). In a comparison between the two groups, apical patterns (n = 10) were only seen in group HN, and those who demonstrated an apical CEA staining pattern had a 5-year survival rate (5-YSR) of 80% as compared with 13% for those HN patients with only a diffuse pattern (p = 0.01). In the control group, 16 (84%) patients had an apical staining pattern and the other 3 patients showed no staining. CONCLUSIONS: Patients with normalized serum CEA levels had a high chance of showing an apical staining pattern, which may be a very good prognosis predictor for patients with high preoperative levels of CEA.

Adenocarcinoma↗