Biomedical subjects

Masataka Ikeda

Publications and source records attributed to Masataka Ikeda.

17 recordsLinked to original sources

PubMed2004

Hepatic expression of ANG2 RNA in metastatic colorectal cancer.

We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P =.002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.

Angiopoietin-1↗

PubMed2004

Current status of pulmonary embolism in general surgery in Japan.

The true incidence of pulmonary embolism (PE) after general surgery in Japan is unknown. We searched the PubMed and Japana Centra Revuo Medicina 1985-2002 databases, entering "surgery" and "pulmonary embolism" or "thromboembolism", and reviewed the reported incidence of clinical PE associated with general surgery in Japan. The overall incidence of PE after general surgery was 0.33%. Fatal PE was reported in 0.08% of the surgical population and the mortality rate of patients with PE was 31%. The incidence of PE after cancer surgery ranged from 0.57% after colon malignancy to 3.85% after pancreatic cancer surgery, and was significantly higher than that after surgery for noncancerous conditions (0.20%). The incidence of PE after various cancer operations corresponded to a moderate or high risk, as defined by the 6th American College of Chest Physicians consensus recommendations. There was no significant difference in the incidence of PE after laparoscopic and open abdominal surgery. The incidence of PE was four to six times lower in patients who had received mechanical prophylaxis, although the difference was not significant. In conclusion, the incidence of PE in Japanese surgical patients is not as low as previously thought. Perioperative prophylaxis against venous thromboembolism is important, but its benefits need to be confirmed by prospective clinical studies.

Humans↗

PubMed2004

Application of RT-PCR to clinical diagnosis of micrometastasis of colorectal cancer: A translational research study.

We previously reported in a retrospective study that CEA-based RT-PCR was useful for predicting the prognosis of patients with node-negative colorectal cancer. RT-PCR is well established for laboratory use, but many issues remain to be resolved prior to its clinical application. In addition to the false positive rate of RT-PCR, we addressed several issues, including the timing of lymph node sampling, stability of RNA after surgery, and reproducibility of results. After appropriate modification, including development of a tissue sampling kit, a multi-institutional clinical study was commenced prospectively from November 2001, and 100 patients were enrolled for examination of micrometastasis. RNA was stable in lymph nodes for up to 3 h after surgical resection. This range of sampling time was acceptable to the surgeons. RNA was well preserved in RNA later at -20 degrees C for 3 weeks. Dilutions of MKN45 and LoVo cells served as positive controls for conventional PCR since these controls were found to be highly stable and ensured reproducibility. Moreover, simultaneous use of quantitative PCR (Light Cycler) ensured double confirmation of the results. Our clinical study showed that the quality of RNA was excellent or good in most samples (98 of 100; 98%). Twenty-four of 98 (24.5%) cases were judged to be micrometastasis-positive. In conclusion, the current translational research study established a clinically feasible RT-PCR system for micrometastasis. Our system could potentially be useful as a clinical tool.

Colorectal Neoplasms↗

PubMed2004

[Case report--Complete response of liver metastasis of rectal cancer after combination chemotherapy of CPT-11 + UFT-E].

A 54-year-old man underwent abdominoperineal resection for rectal cancer. Adjuvant chemotherapy was not performed because of stage I cancer. Nine months after the operation, solitary liver metastasis, and elevated CEA and CA19-9, were found during the postoperative work-up. A combination chemotherapy of CPT-11 and UFT-E was performed before scheduled liver resection. 150 mg/m2 of CPT-11 was administered on days 1 and 15. 375 mg/m2/day of UFT-E was divided in half and administered on days 3-7, 10-14, 17-21, and 24-28 as one course of treatment. This regimen was repeated every 5 weeks. The patient had a grade 2 diarrhea and nentropenia during the treatment. Bowel obstruction was also observed after 5 courses of treatment, which required hospitalization. In addition, the liver metastasis had disappeared. There was no evidence of recurrence after 8 months of chemotherapy. It was suggested that CPT-11+UFT-E combination chemotherapy was effective for advanced colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Treatment of varicose veins: an assessment of intraoperative and postoperative compression sclerotherapy.

Since thrombotic complications, such as superficial thrombophlebitis and subsequent skin pigmentation, are common after sclerotherapy, we conducted a study to evaluate whether combining sclerotherapy with ligation of varicose veins minimizes complications and what timing for sclerotherapy would be most beneficial-accompanying surgery or several weeks postsurgery. Surgical intervention and compression sclerotherapy were performed consecutively on 111 limbs (group A), and sclerotherapy was performed 28 days after surgical intervention on 87 limbs (group B). The volume of sclerosant used and the frequency of complications (thrombus formation and pigmentation) were analyzed. Plasma levels of thrombin-antithrombin III complex (TAT) and D-dimer (DD), as markers for activation of coagulation, were compared. In group A, the total volume of sclerosant used in patients with complications was significantly higher than that in patients without complications. The frequency of thrombus formation and of pigmentation was significantly lower (p <0.01) in group B (10% and 18%, respectively) than in group A (21% and 37%, respectively). The plasma levels of TAT 7 days after treatment were significantly lower in group B (3.4 +/- 1.2 mg/L) than in group A (4.9 +/- 1.1 mg/L). Performing compression sclerotherapy 28 days after surgical intervention is effective for reducing complications and a good alternative for patients with an underlying hypercoagulable state.

Adult↗

PubMed2003

Increased platelet aggregation and production of platelet-derived microparticles after surgery for upper gastrointestinal malignancy.

BACKGROUND: Since platelet function is known to play a major role in arterial thrombosis, we investigated postsurgery alterations in platelet function that might predispose patients with upper gastrointestinal malignancy to postoperative thrombotic complications. SUBJECTS AND METHODS: Shear-induced platelet aggregation (SIPA) in platelet-rich plasma was measured in 23 patients who elected to undergo abdominal surgery. Measurement was done by cone-plate viscometer under low shear stress (12 dyn/cm(2)), a physiological condition, and under high shear stress (108 dyn/cm(2)), a pathological condition that simulates in vivo conditions such as those in stenotic arteries. Platelet microparticle (PMP) formation was analyzed by flow cytometry. Plasma von Willebrand factor (vWF) was also measured. RESULTS: SIPA under high shear stress was significantly enhanced from 44.0 +/- 13.4% preoperatively to 69.5 +/- 15.8% on postoperative day (POD) 1, and it returned to preoperative levels on POD 14. PMP formation under high shear stress was enhanced before surgery (140.8 +/- 38.7%) compared to that under a static condition, and the enhancement was further augmented on POD 1 (219.1 +/- 49.3%). The enhancement of SIPA and PMP formation had no association with disease stage. vWF levels increased significantly on POD 1. Exogenous vWF augmented SIPA and PMP formation under high shear stress, and this augmentation was inhibited by anti-vWF antibody. CONCLUSIONS: Because PMPs are highly procoagulant, increased SIPA and PMP formation induced by surgical intervention possibly contribute to thrombotic complications. Blockage of platelet interaction with vWF may prevent arterial thrombus formation perioperatively.

Adrenergic alpha-Antagonists↗

PubMed2003

Oxysterol 7alpha-hydroxylase (CYP39A1) in the ciliary nonpigmented epithelium of bovine eye.

The CYP39A1 oxysterol 7alpha-hydroxylase preferentially catalyzes the 7alpha-hydroxylation of 24-hydroxycholesterol and has been suggested to play a role in the alternative bile acid synthesis pathway in the liver. The presence of CYP39A1 oxysterol 7alpha-hydroxylase has been reported only in the liver. To investigate the physiologic characteristics of the ciliary processes in bovine ocular tissues, we raised a mAb, 42C, against nonpigmented epithelial (NPE) cells, which have tight junctions that act as a blood-aqueous barrier and are involved in producing aqueous humor and maintaining ocular homeostasis. Immunohistochemical analysis showed that 42C antibody reacted intensely with an antigen in the NPE cells of the ciliary processes but not with other ocular tissues. The SDS-PAGE profile of immunoaffinity-purified antigens from bovine ciliary processes showed a predominant protein of molecular mass of 44.0 kDa. The amino acid sequence of this antigenic protein was identical to human CYP39A1 oxysterol 7alpha-hydroxylase. Immunoreactivity with 42C antibody was found only in hepatocytes and ocular tissues. These data suggest a new physiologic function for the CYP39A1 oxysterol 7alpha-hydroxylase in addition to the production of bile acids and provide new insight into the physiologic role of the ciliary NPE cells concerning the metabolism of sterols in the eye.

Amino Acid Sequence↗

PubMed2003

[General surgery].

Perioperative prophylaxis for pulmonary embolism (PE) is now an emerging issue in Japan because its frequency is increasing very rapidly. Although the optimal prophylaxis should be performed individually on the basis of clinical evidence, the available data on the incidence and prophylaxis of PE are limited in Japanese surgical patients. Both mechanical and pharmacological methods of prophylaxis have been developed. Intermittent pneumatic compression (IPC) appears to be effective. The importance of thromboprophylaxis with anticoagulants including heparin is also emphasized. A new guideline for PE prophylaxis is expected to be established based on Japanese clinical evidence.

Humans↗

PubMed2003

[A case of local recurrence of rectal cancer in which trans-sacral resection and perineal reconstruction by femoral posterior flap were performed].

A 54-year-old woman underwent abdomino-perineal resection for rectal cancer. Six months after surgery, perineal pain and the tumor marker increased. Local recurrence of the pelvic cavity and lung metastases were diagnosed by computed tomography (CT) and positoron emission tomography (PET) using 18F-fluorodeoxygulucose (FDG). Local perineal pain continued and there was no increase in the neoplastic lesion of the lung, so surgical treatment was performed. After partial resection of the lung, local resection of the gluteus maximus and posterior wall of the vagina was performed with the patient in the Jack-knife position. To fill the defect, a femoral posterior flap was made and the perineal defect was reconstructed.

Female↗

PubMed2003

[A case of curative resection of local recurrence after abdominosacral resection of recurrent rectal cancer based on the diagnosis of PET/CT fusion images].

A 76-year-old male with local recurrence after abdominosacral resection of recurrent rectal cancer was admitted to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) indicated a recurrent tumor at the back of the prostate and seminal vesicles up to the resected sacral (S3) stump. However, positron emission tomography (PET)/CT fusion images showed no 18F-2-fluoro-2-deoxy-D-glucose (FDG) uptake at the pre-sacral region, which suggested postoperative scarring of the tissue. Based on the PET/CT diagnosis, we performed abdominoperineal en bloc resection of the recurrent tumor with bladder, seminal vesicles, prostate, internal obturator muscle, ischial spine, and gluteal muscle without resection of the sacrum. Specimen revealed no circumferential resection margin involvement by tumor on pathologic examination. The patient was discharged from the hospital on postoperative day 23 without major complications.

Aged↗

PubMed2002

Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry.

PURPOSE: Inconsistent conclusions have been drawn about the clinical significance of micrometastases in lymph nodes (LNs) of node-negative colorectal cancer (CRC) patients. We performed a comparative study of detection of micrometastases using immunohistochemistry (IHC) by anti-cytokeratin antibody and carcinoembryonic antigen (CEA)-specific reverse-transcriptase polymerase chain reaction (RT-PCR) in the same patients, in an attempt to move closer to their clinical application. PATIENTS AND METHODS: Sixty-four CRC patients, with RNA of good quality available from paraffin-embedded LN specimens, were selected from 84 stage II patients who underwent curative surgery between 1988 and 1996. We investigated associations between the presence of micrometastases by each method and prognosis. RESULTS: Micrometastases were detected in 19 (29.6%) of 64 patients by RT-PCR and in 35 (54.7%) of 64 patients by IHC. By RT-PCR analysis, patients exhibiting a positive band for CEA mRNA had a significantly worse prognosis than those who were RT-PCR-negative, with respect to both disease-free and overall survival (P =.027 and.015, respectively). By IHC analysis, the presence of micrometastasis did not predict patient outcome in terms of either disease-free or overall survival. Infiltrating pattern of tumor growth characteristic was significantly associated with shorter disease-free survival among various clinical or pathologic factors. By multivariate Cox regression analysis, micrometastasis detected by RT-PCR and the Crohn's-like lymphoid reaction were both independent prognostic factors. CONCLUSION: Micrometastases detected by RT-PCR, but not IHC, may be of clinical value in identifying patients who may be at high risk for recurrence of CRC and who are therefore likely to benefit from systemic adjuvant therapy.

Adenocarcinoma↗

PubMed2002

Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function.

PURPOSE: S-1 is a novel oral fluorouracil antitumor drug that combines tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD), and potassium oxonate (Oxo). As 50% of CDHP is excreted in the urine, renal dysfunction may directly affect the DPD inhibitory effect and lead to increased 5-fluorouracil (5-FU) concentrations. We sought to determine the influence of impaired renal function on the pharmacokinetics of S-1 in an animal model and in patients with gastric cancer. METHODS: An experimental renal failure model induced by cisplatin was developed in rabbits, and plasma concentrations of FT, 5-FU, CDHP and Oxo were determined after S-1 injection. Four patients with various degrees of renal impairment with unresectable gastric cancer were recruited to the study, and the pharmacokinetics in these four patients were analyzed following single and consecutive S-1 administrations. RESULTS: In experimental renal failure, plasma clearance of CDHP and 5-FU was retarded corresponding to the degree of renal impairment and there was a close correlation between creatinine clearance (CLcr) and plasma CDHP and 5-FU clearance. In the single administration study, half standard dose was used in three patients (CLcr > or = 50 ml/min) and one-third in the other (CLcr <50 ml/min). In patients with CLcr more than 75 ml/min, C(max), T(max), AUC((0-infinity)), and T(1/2) of 5-FU and CDHP were not different between single and consecutive administrations. In contrast, in patients with mild and moderate renal dysfunction (CLcr 55 and 36 ml/min, respectively), the T(1/2) values of CDHP with consecutive administrations (7.6 and 15.3 h, respectively) were longer than the values with single administration (4.6 and 8.2 h, respectively). The T(1/2) of 5-FU was 5.7 h with single administration and 8.5 h with consecutive administration in patients with moderate renal impairment. The AUC((0-infinity)) of 5-FU with consecutive administrations (3089.7 ng.h/ml) was far greater than with single administration (430.4 ng.h/ml). There was also a strong correlation between CLcr and plasma CDHP clearance. Based on the pharmacokinetics following multiple consecutive administrations, S-1 administration resulted in no severe adverse reactions in any of the four patients. CONCLUSIONS: CDHP clearance was prolonged in the presence of renal impairment, leading to a delayed T(1/2), and high AUC of 5-FU. These findings demonstrate that administration of S-1 to patients with impaired renal function may need individualized dosing and pharmacokinetic monitoring.

Aged↗

PubMed2002

Poor prognosis associated with thrombocytosis in patients with gastric cancer.

BACKGROUND: Thrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated. METHODS: Platelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker. RESULTS: Thrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion. CONCLUSIONS: Thrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer.

Adult↗

PubMed2002

Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor.

BACKGROUND: Angiogenesis and hemostatic activation are important factors in tumor progression and metastasis. Because surgical intervention induces tissue hypoxia and hemostatic activation, we analyzed the effect of gastric surgery on the plasma concentrations of vascular endothelial growth factor (VEGF), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf). METHODS: Plasma VEGF, sP-selectin, and vWf concentrations were measured in 14 patients with gastric cancer before operation and on postoperative day 1 (POD 1). Correlations between disease stage and the effect of surgical intervention were analyzed. RESULTS: The plasma concentrations of these three factors did not correlate with the disease stage. Plasma levels of sP-selectin did not change after operation (before surgery, 87.6 +/- 34.1 ng/ml; on POD 1, 101.1 +/- 48.1 ng/ml; P = 0.123). Plasma VEGF and vWf concentrations were significantly elevated on POD 1 (VEGF, 33.3 +/- 20.5 pg/ml before surgery and 61.9 +/- 35.6 pg/ml on POD 1; P = 0.0013; vWf, 164 +/- 31.1% before surgery and 211.1 +/- 66.1% on POD 1; P = 0.027). CONCLUSION: Because VEGF and vWf are involved in angiogenesis, tumor-platelet adhesion, and tumor-endothelial cell adhesion, surgical intervention could influence tumor growth and metastasis.

Adult↗

PubMed2002

Clinical relevance of fusion images using (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography in local recurrence of rectal cancer.

Local recurrence of rectal cancer is a critical issue. Anatomical images, such as computed tomography (CT) or magnetic resonance imaging (MRI), are sometimes insufficient for preoperative evaluation. A useful modality for diagnosis of local recurrence of rectal cancer is (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), but it does not give adequate information about anatomy. To utilize the advantages of these techniques, this study was done to validate the accuracy of using fused images and their usefulness in the decision making for surgical intervention of local recurrence of rectal cancer by directly comparing the fused images with resected specimens. PET and CT/MRI were performed for patients suspected of local recurrence of rectal cancer (n=4). PET image data were re-calculated to fit CT/MRI images and manually superimposed on the anatomical images. Fusion images were compared with resected specimens. Radical operation was carried out for three patients. Fusion images provided information on precise tumor location, and extent of tumor invasion as well as the diagnosis of tumor recurrence. All patients underwent curative operation with negative surgical margins, and the information provided by the fusion images was confirmed by comparison with resected specimens. In all cases, preoperative evaluation of tumor recurrence with fusion images provided more useful clinical information for the management of patients than the anatomical images alone. PET images, when combined with MRI or CT, may prove to be a useful adjunct in the management of patients being evaluated for resection of local recurrence of rectal cancer.

Aged↗

PubMed2002

Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer.

PURPOSE: Micrometastases are often found in regional lymph nodes of colorectal cancer (CRC). The aim of this study is to examine the extent and distribution of such lymph nodes. EXPERIMENTAL DESIGN: We immunohistochemically assessed localization and frequency of micrometastases in 878 lymph nodes from 98 patients with CRC. The anatomical position of lymph nodes was defined as level 1 to level 3 according to distance from the main tumor. RESULTS: The frequency of micrometastasis increased through observation of the 4-microm-thick lymph node sections, from one to two to five slices. With five slices, micrometastasis was frequently and extensively present in 49.1, 35.7, and 53.3% patients of histologically node-negative patients, node-positive patients at level 1, and node-positive patients at level 2, respectively. We then assessed the value of the presence of micrometastasis in node-negative patients with regard to prognosis, but no significant impact was obtained. To examine the reproducibility of the results obtained with immunohistochemistry, serial sectioning (four consecutive slices at seven different levels) of lymph nodes was additionally performed in lymph nodes initially diagnosed as micrometastasis positive. Immunohistochemical detection revealed that the sectioning level highly affected the results. CONCLUSIONS: Our results indicated frequent presence of micrometastasis in lymph nodes of CRC and that micrometastasis in node-negative CRC patients did not help in predicting the outcome, in part because of the limited reproducibility with immunohistochemistry.

Adult↗

PubMedDate not supplied

Analysis of cyclin D1 and CDK expression in colonic polyps containing neoplastic foci: a study of proteins extracted from paraffin sections.

Overexpression or amplification of G1 cyclins has been demonstrated in various types of human cancers. Overexpression of cyclin D1, an accelerator of cell cycle, is thought to be an early event in colonic multistage carcinogenesis, but its expression at transformation from benign to neoplastic foci is not clear. We analyzed the expression of cyclin D1 and its catalystic partner CDK4 in colon polyps containing neoplastic foci. For direct comparison of the expression in adenomatous tissues and neoplastic foci, proteins in adequate amounts were extracted from paraffin embedded sections. Western blot and densitometry analyses showed that cyclin D1 expression was 2.3-times and 2.5-times higher in adenomatous tissues and neoplastic foci, compared with normal colonic mucosa. In contrast, the levels of CDK4 and CDK2 expression were only modestly increased in adenomatous tissues but significantly higher in neoplastic foci, relative to normal mucosa. Expression of PCNA, a cell proliferation marker, increased from normal mucosa to adenoma to focal cancer. Our findings suggest that overexpression of cyclin D1 may be associated with high proliferative activity in adenomatous tissues and that concurrent high expression of cyclin D1 and CDK4 may further perturb cell cycle progression and play a pivotal role in colonic carcinogenesis.

Adenoma↗