PubMed Health⌕ Search

Biomedical subjects

Tadao Kakizoe

Publications and source records attributed to Tadao Kakizoe.

At least 19 recordsLinked to original sources
PubMed2006

A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months.

BACKGROUND: To investigate the optimal treatment of locally advanced prostate cancer, a prospective randomized trial was conducted to compare radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy. METHODS: One hundred patients with T2b-3N0M0 prostate cancer were enrolled and 95 were evaluated. Of 95 cases, 46 underwent radical prostatectomy with pelvic lymph node dissection and 49 were treated with external beam radiation by linear accelerator with 40-50 Gy to the whole pelvis and 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiotherapy and continued thereafter. The long-term outcome and morbidity were examined. RESULTS: Median follow-up period was 102 months. At 10 years overall survival rates in the surgery group were better than the radiation group (76.2% versus 71.1% for biochemical progression-free rates; P=0.25, 83.5% versus 66.1% for clinical progression-free rates; P=0.14, 85.7% versus 77.1% for cause-specific survival rates; P=0.06, and 67.9% versus 60.9% for overall survival rates; P=0.30), although none of them reached statistical significance. Erectile dysfunction was recognized in almost all patients as a result of continuous endocrine therapy. Incontinence requiring more than one pad per day was observed more frequently in the surgery group than the radiation group (P<0.01). CONCLUSIONS: For the treatment of patients with locally advanced prostate cancer, when combined with endocrine therapy, either radical prostatectomy or external beam radiotherapy demonstrated favorable long-term outcomes. The radiation dose of 60-70 Gy might not be enough for the local treatment of locally advanced prostate cancer.

Adenocarcinoma↗
PubMed2006

Distant metastasis of prostate cancer: early detection of recurrent tumor with dual-phase carbon-11 choline positron emission tomography/computed tomography in two cases.

Several types of recurrence may be detected by radiologic assessment after treatment in patients with prostate cancer. However, early detection of distant metastasis using positron emission tomography has so far never been published. We report two patients who underwent hormone therapy or surgical resection for prostate cancer. They developed distant metastases which were detected on whole body [C-11] choline positron emission tomography/computed tomography with significant elevation of serum PSA level. In one patient, recurrent tumor of the supraclavicular node (6 mm) diminished in size after subsequent hormone therapy. Surgical resection of recurrent tumor of the lung (12 mm) was performed in the other patient, the pathology of which confirmed the metastatic adenocarcinoma derived from the prostate. The recurrent tumor can be correctly detected by dual-phase whole body [C-11] choline positron emission tomography/computed tomography.

Adenocarcinoma↗
PubMed2006

Development and progression of urothelial carcinoma.

Urothelial carcinomas are well known to feature multifocal development in the urinary tract, both synchronously and asynchronously. This phenomenon can be explained by either seeding of cancer cells in the urinary tract or field cancerization. As there are two characteristic morphological patterns of urothelial carinomas, papillary and nodular, published papers were here reviewed to understand the development and progression of urothelial carcinoma regarding multifocality due to seeding or field changes with reference to the type of urothelial carcinoma. From animal experiments using rats, mice and dogs treated with N-butyl-N-(4-hydoroxybutyl) nitrosamine, and from pathological observation of human cystectomy specimens on step-sectioning and molecular analysis, nodular carcinomas appear to either develop via papillary carcinomas or de novo. Clinical aspects of multifocal tumor development are outside of the scope of this review, although an understanding of the mechanisms underlying multifocality and the papillary/nodular morphological relationship is important to determine follow-up strategies for patients treated for primary urothelial carcinomas and for reconstruction of the urinary tract after cystectomy.

Animals↗
PubMed2006

Comparison of observed and expected numbers of detected cancers in the research center for cancer prevention and screening program.

BACKGROUND: The Research Center for Cancer Prevention and Screening program is a one-arm prospective study designed to evaluate the effect of multiple modalities for cancer screening. Basic programs consist of screening tests for cancer of the lung, esophagus, stomach, colon, rectum, liver, gall bladder, pancreas and kidneys, in addition to prostate cancer screening for males and breast, cervical, endometrial and ovarian cancer screenings for females. OBJECTIVE: To investigate the possibility of overdiagnosis, we compared the observed numbers with expected numbers based on the model. METHODS: We calculated the expected number of cancers on the basis of negative or positive history of screening tests within the previous year, based on assumed sensitivity and sojourn time. Observed numbers of screen-detected cases for stomach, colorectal, lung, prostate and breast cancer were compared with expected numbers. RESULTS: From February 2004 to January 2005, 3786 participants were enrolled in our study. The overall cancer detection rate was 5.8% (119/2061) for males and 4.1% (71/1725) for females. No statistically significant difference was found between observed and expected cases for colorectal cancer screening, gastric cancer screening for females and lung cancer screening for males. Observed numbers of breast, prostate and lung cancer for females exceeded those expected (P < 0.05). CONCLUSIONS: Although cancer screening programs in the present study increased the detection of potentially curable cancers, these modalities, particularly lung, breast and prostate screening, might detect cancers which would not necessarily be clinically significant. We should therefore weigh up benefit and harm for such cancer screening programs.

Adult↗
PubMed2006

A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer.

BACKGROUND: There have been few randomized controlled clinical trials until now to determine the effectiveness of adjuvant treatments for pancreatic cancer, and the results reported so far are inconsistent. METHODS: Patients with invasive ductal pancreatic cancer who underwent radical surgery with clear histological margins at 11 Japanese institutions were enrolled and randomly assigned to one of two groups: surgery-alone group (no further treatment after surgery) and the surgery + chemotherapy group [two courses of postoperative adjuvant systemic chemotherapy with cisplatin (80 mg/m(2), Day 1) and 5-fluorouracil (500 mg/m(2)/day, Days 1-5)]. Patients with a positive resectional margin or with resected distant metastases were excluded from the trial in order to minimize the influence of residual cancer. RESULTS: Between 1992 and 2000, 89 patients were randomized into the two arms of the trial (45 patients to the surgery + chemotherapy arm and 44 patients to the surgery-alone arm). Four patients in total were found to be ineligible (three in the surgery + chemotherapy group and one in the surgery-alone group). The baseline characteristics were comparable between the two groups. In the surgery + chemotherapy group, four patients did not receive the adjuvant treatment because of patient refusal. Toxicity was minor and acceptable among the eligible patients in the surgery + chemotherapy group. The estimated 5-year survival rates were 26.4% in the surgery + chemotherapy group and 14.9% in the surgery-alone group, and the median duration of survival was 12.5 months and 15.8 months, respectively. The recurrence rates at 5 years were 73.6 and 80.8%, respectively, in the surgery + chemotherapy and the surgery-alone groups. The differences in the survival and recurrence rates between the two groups were not statistically significant. CONCLUSIONS: Postoperative adjuvant chemotherapy using cisplatin and 5-fluorouracil was safe and well tolerated; however, no clear survival benefit could be demonstrated.

Aged↗
PubMed2006

Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma.

Renal clear cell carcinoma (RCCC) is a malignant tumor with poor prognosis caused by the high incidence of metastasis to distal organs. Although metastatic RCCC cells frequently show aberrant cytoskeletal organization, the underlying mechanism has not been elucidated. DAL-1/4.1B is an actin-binding protein implicated in the cytoskeleton-associated processes, while its inactivation is frequently observed in lung and breast cancers and meningiomas, suggesting that 4.1B is a potential tumor suppressor. We studied a possible involvement of 4.1B in RCCCs and evaluated it as a clinical indicator. 4.1B protein was detected in the proximal convoluted tubules of human kidney, the presumed cell of origin of RCCC. On the other hand, loss or marked reduction of its expression was observed in 10 of 19 (53%) renal cell carcinoma (RCC) cells and 12 of 19 (63%) surgically resected RCCC by reverse transcription-PCR. Bisulfite sequencing or bisulfite SSCP analyses revealed that the 4.1B promoter was methylated in 9 of 19 (47%) RCC cells and 25 of 55 (45%) surgically resected RCCC, and inversely correlated with 4.1B expression (p < 0.0001). Aberrant methylation appeared to be a relatively early event because more than 40% of the tumors with pT1a showed hypermethylation. Furthermore, 4.1B methylation correlated with a nuclear grade (p = 0.017) and a recurrence-free survival (p = 0.0036) and provided an independent prognostic factor (p = 0.038, relative risk 10.5). These results indicate that the promoter methylation of the 4.1B is one of the most frequent epigenetic alterations in RCCC and could predict the metastatic recurrence of the surgically resected RCCC.

Aged↗
PubMed2006

Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.

Molecular biology is expected to provide new tools and approaches to assess the prognosis of patients with bladder cancer, by providing information on the risks of tumor recurrence and progression from superficial bladder cancer to an invasive phenotype. Genetic and epigenetic alterations have been closely associated with bladder carcinogenesis and progression, although most of these are still under investigation in a preclinical setting. This article highlights current findings from molecular studies, and describes their potential application in molecular staging of bladder cancer.

Carcinoma, Transitional Cell↗
PubMed2006

Staging performance of carbon-11 choline positron emission tomography/computed tomography in patients with bone and soft tissue sarcoma: comparison with conventional imaging.

The present study was conducted to compare the diagnostic accuracy between carbon-11 choline (11C-choline) positron emission tomography (PET)/computed tomography (CT) and conventional imaging for the staging of bone and soft tissue sarcomas. Sixteen patients who underwent 11C-choline PET/CT prior to treatment were evaluated retrospectively for staging accuracy. Conventional imaging methods consisted of 99,mTc-hydroxymethylene diphosphonate bone scintigraphy, chest CT and magnetic resonance imaging of the primary site. The images were reviewed and a consensus was reached by two board-certified radiologists who were unaware of any clinical or radiological information using hard-copy films and multimodality computer platform. Tumor stage was confirmed by histological examination and/or by an obvious progression in number and/or size of the lesions on follow-up examinations. Reviewers examining both 11C-choline PET/CT and conventional imaging classified T stage in all patients. Interpretation based on 11C-choline PET/CT, the Node (N) stage was correctly diagnosed in all patients, whereas the accuracy of conventional imaging in N stage was 63%. Tumor Node Metastasis (TNM) stage was assessed correctly with 11C-choline PET/CT in 15 of 16 patients (94%) and with conventional imaging in eight of 16 patients (50%). The overall TNM staging and N staging accuracy of 11C-choline PET/CT were significantly higher than that of conventional imaging (P < 0.05). 11C-choline PET/CT is more accurate than conventional imaging regarding clinical staging of patients with bone and soft tissue sarcomas. A whole body 11C-choline PET/CT might be acceptable for imaging studies of tumor staging prior to treatment.

Adolescent↗
PubMed2005

A flexible endoscopic surgical system: first report on a conceptual design of the system validated by experiments.

BACKGROUND: Surgery is a standard diagnostic and therapeutic procedure. However, its technical difficulty and invasiveness pose problems that are yet to be solved even by current surgical robots. Flexible endoscopes can access regions deep inside the body with less invasiveness than surgical approaches. Conceptually, this ability can be a solution to some of the surgical problems. METHODS: A flexible (surgical) endoscopic surgical system was developed consisting of an outer and two inner endoscopes introduced through two larger working channels of the outer endoscope. The concept of the system as a surgical instrument was assessed by animal experiments. RESULTS: Gastric mucosa of the swine could be successfully resected using the flexible endoscopic surgical system, thereby showing us the prospect and directions for further development of the system. CONCLUSION: The concept of a flexible endoscopic surgical system is considered to offer some solutions for problems in surgery.

Animals↗
PubMed2005

Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors.

The epidemiologic evidence that dietary fiber protects against colorectal cancer is equivocal. No large-scale clinical study of the administration of Lactobacillus casei has been reported. We examined whether dietary fiber and L. casei prevented the occurrence of colorectal tumors. Subjects were 398 men and women presently free from tumor who had had at least 2 colorectal tumors removed. Subjects were randomly assigned to 4 groups administered wheat bran, L. casei, both or neither. The primary end point was the presence or absence of new colorectal tumor(s) diagnosed by colonoscopy after 2 and 4 years. Among 380 subjects who completed the study, 95, 96, 96 and 93 were assigned to the wheat bran, L. casei, both and no treatment groups, respectively. Multivariate adjusted ORs for occurrence of tumors were 1.31 (95% CI 0.87-1.98) in the wheat bran group and 0.76 (0.50-1.15) in the L. casei group compared to the control group. There was a significantly higher number of large tumors after 4 years in the wheat bran group. The occurrence rate of tumors with a grade of moderate atypia or higher was significantly lower in the group administered L. casei. No significant difference in the development of new colorectal tumors was observed with administration of either wheat bran or L. casei. However, our results suggest that L. casei prevented atypia of colorectal tumors.

Adult↗
PubMed2005

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer.

PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Adenocarcinoma↗
PubMed2005

Loss of blood group A antigen expression in bladder cancer caused by allelic loss and/or methylation of the ABO gene.

Loss of ABO blood group antigen expression has been reported in transitional cell carcinoma (TCC) of the bladder. Synthesis of the ABO blood group antigen was genetically determined by allelic variants of the ABO gene assigned on 9q34.1. We analyzed loss of heterozygosity (LOH) and promoter hypermethylation of the ABO gene in TCC and compared them with alterations of A antigen expression in TCC, dysplasia and normal urothelium. A total of 81 samples of TCC of the bladder obtained from transurethral resection (TUR) (n=44) and radical cystectomy (n=37) were examined. Expression of the A antigen was evaluated by immunohistochemical staining (IHC) using anti-A antigen monoclonal antibody. LOH of the ABO gene locus was examined by blunt-end single-strand DNA conformational polymorphism (SSCP) analysis using flouresence-based auto sequencer. Promoter hypermethylation of the ABO gene were examined by bisulfite PCR-SSCP (BiPS) analysis and/or methylation-specific PCR (MSP). Loss of A allele and/or hypermethylation were significantly associated with abnormal expression of the A antigen in cases undergoing TUR (P=0.02) and radical cystectomy (P=0.0005). For the analysis of the concomitant dysplasia in 23 cases with TCC of the bladder, the expression of the A antigen was maintained, regardless of the A allelic loss or methylation status in the tumor. In conclusion, A allelic loss and hypermethylation in the promoter region of the ABO gene showed significant correlation with reduction of A antigen expression in TCC, while the expression of the A antigen is maintained in concomitant dysplasia or normal urothelium, suggesting that loss of the ABO gene and/or its promoter hypermethylation is a specific marker for TCC.

ABO Blood-Group System↗
PubMed2005

A new method for isolating colonocytes from naturally evacuated feces and its clinical application to colorectal cancer diagnosis.

BACKGROUND & AIMS: The early detection of colorectal cancer is desired because this cancer can be cured surgically if diagnosed early. The purpose of the present study was to determine the feasibility of a new methodology for isolating colonocytes from naturally evacuated feces, followed by cytology or molecular biology of the colonocytes to detect colorectal cancer originating from any part of the colorectum. METHODS: Several simulation studies were conducted to establish the optimal methods for retrieving colonocytes from any portion of feces. Colonocytes exfoliated into feces, which had been retrieved from 116 patients with colorectal cancer and 83 healthy volunteers, were analyzed. Part of the exfoliated colonocytes was examined cytologically, whereas the remainder was subjected to DNA analysis. The extracted DNA was examined for mutations of the APC, K-ras, and p53 genes using direct sequence analysis and was also subjected to microsatellite instability (MSI) analysis. RESULTS: In the DNA analysis, the overall sensitivity and specificity were 71% (82 of 116) of patients with colorectal cancer and 88% (73 of 83) of healthy volunteers. The sensitivity for Dukes A and B was 72% (44 of 61). Furthermore, the sensitivity for cancers on the right side of the colon was 57% (20 of 35). The detection rate for genetic alterations using our methodology was 86% (80 of 93) when the analysis was limited to cases in which genetic alterations were present in the cancer tissue. CONCLUSIONS: We have developed a new methodology for isolating colonocytes from feces. The present study describes a promising procedure for future clinical evaluations and the early detection of colorectal cancers, including right-side colon cancer.

Adult↗
PubMed2005

DNA hypomethylation on pericentromeric satellite regions significantly correlates with loss of heterozygosity on chromosome 9 in urothelial carcinomas.

PURPOSE: DNA methylation has important roles in genomic stability. Accordingly DNA hypomethylation on pericentromeric satellite regions may induce chromosomal instability through heterochromatin decondensation and chromosomal recombination enhancement. We elucidated the significance of aberrant DNA methylation on pericentromeric satellite regions during urothelial carcinogenesis. MATERIALS AND METHODS: We examined DNA methylation status on satellites 2 and 3 by Southern blotting and determined the allelic status of chromosome 9 using 6 microsatellite markers (D9S775, D9S925, D9S304, D9S303, D9S283 and D9S747) in 27 transitional cell carcinomas of the bladder, ureter or renal pelvis and corresponding noncancerous tissues. RESULTS: DNA hypomethylation on satellites 2 and 3 was detected in 2 (7%) and no (0%) noncancerous tissues, and in 11 (41%) and 12 (44%) urothelial carcinomas, respectively. DNA hypomethylation in urothelial carcinomas significantly correlated with histological grade (p = 0.0012 and 0.0043), invasion depth (p = 0.0055 and 0.0228) and morphological structure (papillary vs nodular, p = 0.0161 and 0.0297) for satellites 2 and 3, respectively. Loss of heterozygosity on at least 1 locus of chromosome 9 was detected in 14 urothelial carcinomas (52%). DNA hypomethylation on satellites 2 (p = 0.0098) and 3 (p = 0.0034) significantly correlated with loss of heterozygosity on chromosome 9. CONCLUSIONS: DNA hypomethylation on pericentromeric satellite regions may participate in the development and progression of urothelial carcinomas by inducing loss of heterozygosity on chromosome 9.

Aged↗
PubMed2005

DNA hypermethylation on multiple CpG islands associated with increased DNA methyltransferase DNMT1 protein expression during multistage urothelial carcinogenesis.

PURPOSE: We elucidated the significance of aberrant DNA methylation on multiple CpG islands and its correlation with DNA methyltransferase DNMT1 protein expression during urothelial carcinogenesis. MATERIALS AND METHODS: We examined the DNA methylation status on multiple CpG islands by methylation specific polymerase chain reaction and combined bisulfite restriction enzyme analysis in 12 specimens of normal urothelium, 23 of noncancerous urothelium showing no remarkable histological changes obtained from patients with bladder cancer (NBC) and 70 of transitional cell carcinoma (TCC). RESULTS: DNA methylation on CpG islands of the p16 (0%, 17% and 21%) and death-associated protein kinase (13%, 33% and 29%) genes, and methylated in tumor-2 (56%, 60% and 76%), 12 (0%, 6% and 30%), 25 (25%, 27% and 35%) and 31 (45%, 56% and 79%) clones was detected in normal urothelium, NBCs and TCCs, respectively. The incidence of concurrent DNA hypermethylation on 3 or more CpG islands in NBCs (38%) was significantly higher than that in normal urothelium (0%, p = 0.0455) and even higher in TCCs (59%, p = 0.0043). The incidence of the CpG island methylator phenotype in nonpapillary carcinomas (nodular invasive carcinomas and their precursors, ie flat carcinoma in situ, 71%) was significantly higher than in papillary carcinomas (40%, p = 0.0143). In all specimens examined concurrent DNA hypermethylation on 3 or more CpG islands significantly correlated with immunohistochemically evaluated DNMT1 protein over expression (p = 0.0167). CONCLUSIONS: DNA hypermethylation on multiple CpG islands in association with DNMT1 protein over expression may participate in multistage urothelial carcinogenesis even at the precancerous stage and particularly in the development of nodular invasive carcinomas of the bladder.

Carcinoma, Transitional Cell↗