Biomedical subjects

Go Watanabe

Publications and source records attributed to Go Watanabe.

119 records · Page 7Linked to original sources

PubMedDate not supplied

A coronary active perfusion system for off-pump coronary artery bypass: advantage over passive perfusion regarding the physiology of the coronary artery.

To avoid myocardial ischemia during off-pump coronary artery bypass, we developed a coronary active perfusion system (CAPS) that perfuses arterial blood to the coronary artery at the diastolic phase of the cardiac cycle by a syringe pump system. We report herein the details and compare CAPS with a passive shunt circuit from the femoral artery (FA shunt), regarding the physiology of the coronary artery. Six pigs were used for this study. After CAPS or FA shunt perfusion was established, coronary flow and coronary pressure were measured. The coronary flows in the native coronary artery, FA shunt perfusion, and CAPS perfusion with syringe pump stroke volume settings ranging from 0.1 to 0.4 ml were 27.2+/-3.0, 4.1+/-1.5, 12.7+/-1.2, 24.8+/-1.9, 33.3+/-1.6, and 42.2+/-1.9 ml/min, respectively. Mean coronary pressures under FA shunt perfusion and CAPS perfusion with stroke settings from 0.1 to 0.4 ml were 23.7+/-4.6, 48.8+/-5.0, 61.3+/-7.5, 70.8+/-5.4, and 82.3+/-5.2 mm Hg, respectively. CAPS had an advantage over the FA shunt regarding coronary flow with safe coronary pressure. Using CAPS, an off-pump coronary artery bypass can be performed safely without myocardial ischemia.

Anastomosis, Surgical↗

PubMedDate not supplied

Surgical treatment of congenital coronary artery fistulas: 27 years' experience and a review of the literature.

BACKGROUND AND AIM OF THE STUDY: A congenital coronary artery fistula (CAF) is a relatively rare congenital anomaly and is defined as an abnormal direct communication between any coronary artery and any of the cardiac chambers. This article reviews our experience over the past 27 years, as well as other literature, and discusses the surgical indications and methods relating to CAF. METHODS: From 1973, 25 patients aged from 2 to 69 years underwent surgical treatment for congenital CAF. Seventeen patients were diagnosed as isolated CAF. All patients under 19 years of age with isolated CAF were asymptomatic. Twenty fistulas originated from the left coronary artery and 9 from the right. The pulmonary artery was the most dominant drainage site. Four patients among the isolated CAF cases were surgically treated without a cardiopulmonary bypass. RESULTS: All patients were discharged from hospital without any perioperative complications. Postoperative coronary angiography was done on all patients with only one slightly residual CAF flow. The average follow-up time was 9.6 years and all patients were asymptomatic and doing well. CONCLUSIONS: Definitive surgical correction is safe and effective, with good results. Therefore, it should be considered even in asymptomatic patients because of the risk of future complications.

Adult↗

PubMedDate not supplied

An experimental study of a new pull-through technique for aortic arch aneurysm in a porcine model.

A new pull-through technique for placement of the aortic arch stent-graft was developed. Self-expandable curved stents (Matsui-Kitamura stents) were used on 4 pigs. With use of the endoscopic system, the sheath insertion was performed at the ascending aorta. By this pull-through method from the ascending aorta to the femoral artery, the stent was deployed into the aortic arch. All stents were successfully deployed into the correct position, and they fitted into the curvature of the aortic arch wall. By this method, stent-grafting for aortic arch aneurysm is expected to be performed with more accuracy and safety.

Animals↗

PubMedDate not supplied

Paratracheal lymph node metastasis is associated with cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: We determined which lymph node metastases were associated with cervical lymph node metastases of thoracic esophageal squamous cell carcinoma. METHODS: A total of 6464 lymph nodes derived from 155 consecutive patients with thoracic esophageal squamous cell carcinoma were stained by immunohistochemistry (antibody: AE1/AE3). Lymph node metastases were mapped according to the mapping scheme of the American Thoracic Society, as modified by Casson et al. (Ann Thorac Surg 1994;58:1569-70). Patients were divided into two groups: those with and without cervical lymph node metastasis (CLNM). Mapping data were examined by uni- and multivariate analysis. RESULTS: Hematoxylin and eosin-positive and AE1/AE3-positive lymph node metastases were found in 59% and 77% of patients, respectively. Twenty-one (55%) of 38 patients in the CLNM(+) group and 30 (26%) of 117 patients in the CLNM(-) group had AE1/AE3-positive lymph node metastasis in the thoracic paratracheal lymph node. Paratracheal lymph node metastasis is only one independent factor for (CLNM), whereas upper thoracic paraesophageal lymph node and pulmonal hilar lymph node status were also significant in univariate analysis. Three (43%) of seven patients with cervical jumping metastasis from the thoracic esophagus had micrometastasis in the paratracheal lymph node. CONCLUSIONS: The paratracheal lymph node is most associated with (CLNM) of thoracic esophageal squamous cell carcinoma.

Aged↗

PubMedDate not supplied

Evaluation of sleeve segmentectomy for early hilar lung cancer.

Roentgenographically occult lung cancers (ROLCs) are rare but are usually curable if they are properly diagnosed and treated. Between 1977 and 2000, we treated 51 patients with early hilar lung cancer (as defined by the Japan Lung Cancer Society) of ROLC form. If the occurrence of cancer is confined to segmental bronchi, we preserve the lung tissue as far as possible by using a sleeve segmentectomy. Eight of the 51 patients underwent sleeve segmentectomy. All 8 of these patients were men who were heavy smokers and had a mean age of 64.9 years (range, 59-74 years). The cancerous locations were R-B6 in 4 patients, L-B(1+2+3) in 2 patients, L-B(4+5) in 1 patient, and L-B6 in 1 patient. Two patients had double cancers (synchronous in one case and metachronous in the other). All 8 of the patients had squamous cell carcinoma, 3 of whose lesions were carcinoma in situ. The segments resected were R-S(6) in 3 patients, L-S(1+2+3) in 2 patients, L-S(4+5) in 1 patient, L-S(6) in 1 patient, and R-S6 combined with the middle lobe in 1 patient. There were no cases of morbidity or mortality. However, 1 patient who had undergone a left lower lobectomy for synchronous advanced squamous cell carcinoma 4 months before R-S(6) sleeve segmentectomy for contralateral early hilar lung cancer died of recurrence in the mediastinal lymph nodes 63 months after the first operation. Two patients died of other causes: one of pneumonia 61 months after L-S(4+5) sleeve segmentectomy and the other of myelopathy 36 months after L-S(1+2+3) sleeve segmentectomy. The remaining 5 patients are alive and well 178, 121, 109, 94, and 14 months after surgery. Sleeve segmentectomy is a curative operation for early stage squamous cell carcinoma of the segmental bronchus that preserves pulmonary function and should be used to treat patients carefully selected for the correct indications.

Adult↗

PubMedDate not supplied

Association of thymidylate synthase gene polymorphism with its mRNA and protein expression and with prognosis in gastric cancer.

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU). TS has a polymorphic repeated sequence in the 5'-UTR and the polymorphism is associated with TS protein expression. TS polymorphism has been reported to link with the efficacy of 5-FU-based chemotherapy in colorectal cancer. In this study, we examined whether the association among TS polymorphism, TS mRNA expression and TS protein expression is also observed in gastric cancer tissues and whether the TS polymorphism is a prognostic factor for patients with gastric cancer. We quantified TS mRNA isolated from 115 gastric cancer tissues by real-time reverse transcription PCR and TS protein in 72 available samples by the fluoro-dUMP binding assay. These values were compared with TS genotypes of the samples determined by a PCR assay. The tumor with the 3R/3R genotype had higher TS protein expression than that with the 2R/3R genotype, although there is no association between the TS genotype and mRNA expression. The result suggests that mRNA translation is responsible for the genotype-dependent difference of TS protein expression, as is consistent with our previous observation in colorectal cancer. This association encouraged us to further examine the link of the TS genotype with the stage of disease and the prognosis of the patients. The clinicopathological analysis showed that gastric cancers with the 3R/3R genotype are at a more advanced stage than those with the combined 2R/2R and 2R/3R genotype. We observed a longer survival in those patients with the combined 2R/2R and 2R/3R genotype, compared with the 3R/3R genotype, although it did not reach significance when the patients who had received the oral fluoropyrimidines therapy were analyzed. These results warrant further large-scale clinical study of the role of the TS genotyping for the prediction of efficacy using 5-FU-based chemotherapy and prognosis in gastric cancer.

Adult↗

PubMedDate not supplied

Hypermethylation of the CDKN2A gene in colorectal cancer is associated with shorter survival.

Promoter hypermethylation of the CDKN2A gene has been suspected to be involved in the carcinogenesis of colorectal cancers. However, the relations between CDKN2A hypermethylation and clinicopathological findings, and patient prognosis, remain inconclusive. We analyzed the CDKN2A methylation status in primary colorectal cancers using real-time methylation specific PCR (MethyLight) which enables quantitative measuring of the methylation level. CDKN2A promoter methylation was detectable in 55 (61.1%) of 90 tumor samples and the median level of the methylation was 0.187 (range 0.00-197.9). The methylation value of CDKN2A was correlated with certain clinicopathological findings, including tumor differentiation (p=0.018), and Dukes stage (p=0.016). In survival analysis, the CDKN2A methylation level was correlated with a poor prognosis of the patient with colorectal cancer for either all cases (p=0.014) or Dukes C (p=0.004) cases that were analyzed. These results suggest that CDKN2A methylation status is a prognostic factor in colorectal cancer and may be of use for the patient specific design of therapy.

Aged↗

PubMedDate not supplied

High serum soluble E-selectin levels are associated with postoperative haematogenic recurrence in esophageal squamous cell carcinoma patients.

E-selectin has been reported to be associated with haematogenic metastasis in various cancer patients. In order to evaluate the risk of postoperative haematogenic recurrence of esophageal squamous cell carcinoma (SCC) patients, we examined the preoperative serum levels of soluble E-selectin and clinicopathological data of the patients. Preoperative serum was obtained from 135 esophageal SCC patients who received esophagectomies from 1990 to 1998. Serum soluble E-selectin levels were measured by means of enzyme linked immunoreactive synthesis assay (ELISA). The expression of sialyl Lewis A and X antigens were evaluated in 58 out of 135 patients. Thirty-five patients (25.9%) had haematogenic recurrence in their postoperative course. Serum soluble E-selectin levels of the haematogenic recurrence group (mean 55.6 ng/ml) were significantly higher than those of the non-haematogenic recurrence group (mean 41.1 ng/ml). When the cut-off level of soluble E-selectin was 56 ng/ml, the logistic regression analysis showed that high serum soluble E-selectin levels, lymph node metastasis and intraepithelial spread were associated with postoperative haematogenic recurrence of the esophageal SCC patients (OR 2.99, p=0.047, OR 4.94, p=0.009 and OR 5.0, p=0.019. respectively). Univariate analysis revealed that the patients with a high serum soluble E-selectin level tended to have poor survival (p=0.078) and Cox multivariate analysis revealed that a high serum soluble E-selectin level was a prognostic factor in esophageal SCC patients (RR 1.84, p=0.065). The patients with a high serum soluble E-selectin concomitant with expression of sialyl Lewis antigens had a significant risk of postoperative haematogenic recurrence (p=0.005). These results indicated that preoperative high serum soluble E-selectin was a risk factor in the development of postoperative haematogenic recurrence and was a prognostic factor in esophageal SCC patients.

Biomarkers, Tumor↗

PubMedDate not supplied

The association between methylenetetrahydrofolate reductase polymorphism and promoter methylation in proximal colon cancer.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in folate metabolism, which is an important pathway of the methyl donor for DNA methylation. The MTHFR gene has genetic variants (C667T and A1298C), which cause reduced enzyme activity. Impaired folate metabolism by these genetic variants of MTHFR could change the methylation pattern of DNA including promoter hypermethylation, which has been frequently observed in cancer. In this study, we compared the MTHFR genotypes and haplotype to the features of colorectal cancer focusing on the promoter methylation of tumor DNA. MATERIALS AND METHODS: Genomic DNA was isolated from 194 colorectal cancer tissues and subjected to MTHFR genotyping by PCR-based restriction fragment length polymorphism analysis. The MTHFR haplotype was determined by combination of C667T and A1298C genotype and classified into 2 groups, high (H-haplotype) or low (L-haplotype) enzymatic activity of MTHFR. The methylation level of tumor suppressor genes (CDKN2A, hMLH1, ARF and TIMP3) was measured by a fluorescence-based, real-time methylation specific PCR method. RESULTS: There was no significant association of the clinicopathological features with either C667T genotype, A1298C genotype or haplotype of MTHFR. The methylation level of CDKN2A was higher in cancer with the L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal origin were considered (p=0.029). hMLH1 methylation also tended to be higher in proximal colon cancers of MTHFR L-haplotype (p=0.059). In addition, the proximal colon cancers showing CpG island methylator phenotype (CIMP) were significantly more frequent in L-haplotype than in H-haplotype. CONCLUSION: These results suggest that the haplotype with low enzymatic activity of MTHFR is linked with promoter hypermethylation and consequently modifies the risk of CIMP(+) proximal colon cancer development in the Japanese people. The relationship between MTHFR polymorphism and DNA methylation in the Japanese is contrary to the previous results in Caucasians. Further study is needed focusing on ethnic variations in the relationships among MTHFR polymorphism, DNA methylation and the development of CIMP(+) colorectal cancer.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Prognostic significance of the polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase gene in lung cancer.

BACKGROUND: Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) play important roles in folate metabolism. Previous studies have suggested that TS expression is a prognostic factor in non-small cell lung cancer (NSCLC). The TS gene has a variable number of tandem repeats (VNTR) and single nucleotide polymorphism (SNP) in the 5'-untranslated region, which are associated with TS expression. This association suggests that the TS polymorphism is a novel prognostic factor in NSCLC. In the present study, multiple genetic polymorphisms, TS VNTR, TS SNP and MTHFR C677T, were analyzed in NSCLC and compared with clinicopathological features and patients' prognoses. MATERIALS AND METHODS: Genomic DNA was isolated from 294 surgically resected NSCLC tissues. The genotypes were determined by PCR and PCR-RFLP. The TS VNTR and SNP were combined, followed by functional stratification of H/H (3G/3G), H/L (2R/3G, 3G/3C) and L/L (2R/2R, 2R/3C, 3C/3C). Patients' prognoses were compared with TS and/or MTHFR genotype groups. TS was divided into the H- (H/H, H/L) and L-groups (L/L) according to functional stratification and MTHFR C677T was divided into C- (C/C) and T-groups (C/T, T/T). RESULTS: TS VNTR, the SNP and the TS functional type, along with MTHFR C677T, showed no significant association with clinicopathological factors. There were no differences in prognosis between each genotype or functional group when the TS and MTHFR groups were considered separately. However, we found a unique association between prognosis and the TS functional group in stage I NSCLC, taking both TS and MTHFR groups into consideration. The patients in the TS L-group survived longer than those in the H-group when limited to stage I and MTHFR C-group (p = 0.086). This relationship between the TS genotype group and prognosis was statistically significant in the subgroup of stage IB and MTHFR C-group (p = 0.030). In contrast, the patients in the TS H-group survived longer than those in the L-group when limited to stage I and MTHFR T-group (p = 0.052). CONCLUSION: The TS and MTHFR genotypes can be prognostic factors in NSCLC, where gene-gene interactions between the genotypes may occur. Further validation and investigation of the involvement of genotypes of folate metabolizing enzymes in the prognosis of NSCLC patients are required.

Aged↗

PubMedDate not supplied

Prognostic significance of p16(INK4a) hypermethylation in non-small cell lung cancer is evident by quantitative DNA methylation analysis.

BACKGROUND: p16(INK4a) is a tumor suppressor gene frequently inactivated by aberrant promoter hypermethylation. In the present study, p16(INK4a) methylation was evaluated in non-small cell lung cancer (NSCLC) using a quantitative assay and the clinical significance of the methylation was explored. MATERIALS AND METHODS: A total of 244 tumor samples from formalin-fixed paraffin-embedded archives were examined in this study. p16(INK4a) methylation was analyzed by the fluorescence-based, real-time methylation-specific PCR assay, MethyLight. The quantitative methylation value was expressed as the percentage of methylated reference (PMR). RESULTS: The median level of p16(INK4) methylation was 0.55 PMR (range 0.00-503.4). The p16(INK4) methylation value was significantly higher in males (p = 0.005) and in squamous cell carcinoma (p = 0.018). Prognostic analysis using the Cox proportional hazard model showed that the p16(INK4a) methylation value was a significant prognostic factor (odds ratio, 1.005; 95% CI, 1.003 to 1.008; p < 0.0001). The p16(INK4a) methylation value remained a significant prognostic factor (p = 0.0004) in multivariate analysis including age, gender, histological type and clinical stage. Specimens were then classified into hypermethylated or non-hypermethylated groups based on the p16(INK4a) methylation value using various cut-offs from 1 to 100 PMR. There was no significant difference in prognosis between the two groups using a cut-off value of 1 PMR. On the other hand, there was a significant difference using 6 PMR or more as the cut-off value (p < 0.01). CONCLUSION: These results provide clear evidence for the prognostic significance of p16(INK4a) methylation in NSCLC using quantitative DNA methylation analysis. Careful assessment of DNA methylation is needed because qualitative methylation analysis may overestimate low levels of methylation, which have less clinical significance.

Aged↗