Biomedical subjects

K Kuzuya

Publications and source records attributed to K Kuzuya.

At least 19 recordsLinked to original sources

PubMed2001

Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome.

Thirty-nine patients with endometrioid adenocarcinoma (EA) and atypical hyperplasia (AH) of the endometrium who received conservative treatment to preserve fertility were collected from member institutions of the Japan Gynecologic Oncology Study Group. Twenty-nine and ten were originally diagnosed with EA without myometrial invasion and AH, respectively. We performed a central pathological review to make definite diagnoses, and the diagnosis of EA in 29 cases was changed to AH in ten, complex hyperplasia in three and atypical polypoid adenomyoma in three, and AH in ten was changed to EA in one and simple hyperplasia in one. Nine of 12 women (75%) with EA and 15 of 18 women (83%) with AH had an initial response to medroxyprogesterone acetate (MPA) treatment. Two of nine responders with EA later developed relapse, and one of them had metastasis to the left obturator lymph node. Two became pregnant, and one delivered one full-term infant. One of the responders with AH had a relapse in the endometrium. Five became pregnant, and four delivered four normal infants. The young women with endometrial carcinoma localized in the endometrium who wish to preserve fertility may be treated as successfully with MPA as those with AH.

Adenocarcinoma↗

PubMed2001

Prognostic factors of stage IV epithelial ovarian cancer: a multicenter retrospective study.

OBJECTIVE: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer. METHODS: In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods. RESULTS: Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415). CONCLUSION: Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.

Adult↗

PubMed2001

A comparison of ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix.

OBJECTIVE: The purpose of our study was to investigate a possible difference in ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix and to confirm clinicopathological variables associated with the metastases. METHODS: Clinical and pathological variables of 1064 patients with invasive squamous cell carcinoma and 240 with adenocarcinoma were studied. RESULTS: Ovarian metastasis was found in 14 patients (1.3%) with squamous cell carcinoma and 15 (6.3%) with adenocarcinoma. The mean age of patients with ovarian metastasis of squamous cell carcinoma was 57.4 years, compared to 50.2 years for adenocarcinoma. Ovarian metastasis of adenocarcinoma was more likely to be visible (40.0%) and present in both ovaries (66.7%), while these two characteristics occurred in only 21.4 and 36.7% of patients with squamous cell carcinoma. A logistic regression analysis with clinical variables indicated that clinical stage beyond IIb was a significant variable of squamous cell carcinoma, and more than 30-mm tumor size was significant in adenocarcinoma. CONCLUSION: The incidence of ovarian metastasis of adenocarcinoma of the uterine cervix was significantly higher than that of squamous cell carcinoma. The incidence of adenocarcinoma was associated more closely with tumor size than clinical stage, whereas it was more associated with clinical stage in squamous cell carcinoma. The results thus suggested that the differences in ovarian metastases were caused by the different characteristics of the two types of carcinoma.

Adenocarcinoma↗

PubMed2000

A comparison of prognoses of pathologic stage Ib adenocarcinoma and squamous cell carcinoma of the uterine cervix.

OBJECTIVES: The influence of the histology of adenocarcinoma on recurrence and survival for patients treated with radical hysterectomy and diagnosed as having pathologic stage Ib cervical cancer was investigated. METHODS: Five hundred and nine patients (405 squamous cell carcinomas, 104 adenocarcinomas) with pathologic stage Ib cervical cancer treated initially at the Aichi Cancer Center between 1976 and 1995 were studied. RESULTS: Multivariate analysis identified the prognostic variables as histology of adenocarcinoma, number of lymph nodes involved, and tumor size beyond 4 cm. Five-year overall survival and disease-free survival of patients with adenocarcinoma in the presence of lymph node metastasis were 63.2 and 47.4%, respectively, significantly poorer than for squamous cell carcinoma (83.6 and 80.6%; P < 0.001 and P = 0.002, respectively). These were not different in the absence of lymph node metastasis (adenocarcinoma, 93.9 and 92.7%; squamous cell carcinoma, 97.9% and 96.1%; P = 0.067 and P = 0.250, respectively). CONCLUSIONS: The independent significant risk factors for the recurrence and survival of pathologic stage Ib cervical cancer were the presence of lymph node metastasis, large tumor size beyond 4 cm, and histology of adenocarcinoma. The prognosis of patients with adenocarcinoma was poorer than of patients with squamous cell carcinoma in the presence of lymph node metastasis, while the prognosis of pathologic stage Ib cervical cancer was equivalent when there was no metastasis.

Adenocarcinoma↗

PubMed2000

Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancers.

We examined the subcellular localization of BRCA1 proteins using immunohistochemical staining with C-terminal (GLK-2 antibody) and N-terminal (Ab-2 antibody) monoclonal antibodies in 44 familial ovarian cancers. Among these, 24 cases were associated with 13 independent germ-line mutations of BRCA1, and loss of heterozygosity (LOH) at one or more BRCA1 microsatellite markers was found in all 21 informative tumors tested. With GLK-2 antibody, cytoplasmic staining was observed in 15 of 16 tumors (93.8%) with mutation in exon 11, and BRCA1 staining was absent in 8 of 8 tumors (100%) with mutation in exons other than exon 11. When immunohistochemical staining was performed with Ab-2 antibody, both nuclear and cytoplasmic staining were observed in 14 of 16 tumors (87.5%) with mutation in exon 11. Interestingly, nuclear staining was observed in 3 of 3 tumors (100%) with mutation downstream of exon 11, even though no staining was detected in 5 of 5 tumors (100%) with mutation upstream of exon 11. On the other hand, in familial ovarian cancers without BRCA1 mutations, nuclear staining or both nuclear and cytoplasmic staining was observed in 18 of 20 specimens (90%) and 20 of 20 specimens (100%) with GLK-2 antibody and with Ab-2 antibody, respectively. These results suggest that an immunohistochemical assay in combination with employing the C-terminal and the N-terminal antibodies appears to have potential as a reliable and useful technique for the screening of BRCA1 mutations, at least to predict the status of mutation, upstream or downstream of exon 11.

BRCA1 Protein↗

PubMed1999

Prognostic factors of adenocarcinoma of the uterine cervix.

OBJECTIVE: The prognostic importance of adenocarcinoma of the uterine cervix was investigated. Methods. One hundred ninety-three patients (144 had stage I disease, 41 stage II, and 8 stage III-IV) with invasive adenocarcinoma of the uterine cervix treated initially at the Aichi Cancer Center between 1964 and 1995 were studied. RESULTS: Of all the invasive cervical cancers, 8.8% were adenocarcinomas that had been increasing during the past decade. The overall 5-year survival for stage I was 88.8%, stage II 44.9%, and stage III-IV 0% In univariate analysis, the clinicopathological factors associated with overall survival and disease-free survival were age of patient, stage of disease, presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, tumor size, and intraperitoneal metastasis. Multivariate analysis performed in all cases identified the clinical stage of disease, the presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, and tumor size as the independent risk factors for recurrence and survival. In the analysis of stage I disease, lymph node metastasis and tumor size were the significant prognostic factors, while lymph-vascular space invasion and tumor size were the factors in advanced disease. Tumor grade and histological type were not associated with recurrence and survival. CONCLUSION: These results suggested the association of lymph node metastasis with the prognosis of early stage adenocarcinoma of the uterine cervix and lymph-vascular space invasion with the advanced stage. Tumor size was an independent risk factor throughout all stages.

Adenocarcinoma↗

PubMed1999

Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies.

Free cancer cells exfoliated from cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in patients with gastric and ovarian cancers. This study was designed to evaluate the prognostic significance of free cancer cells in peritoneal washes detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for the carcinoembryonic antigen (CEA) gene was found to be more sensitive than cytology for detection of free tumor cells in the peritoneal washes, collected at laparotomy from 199 gastric carcinoma patients, with higher detection rates for each of the T-categories in the TNM classification. Six patients with synchronous and 5 with recurrent peritoneal dissemination were found among 25 advanced cancer patients with positive PCR and negative cytology results. Positive PCR results were significantly associated with poor survival of curatively resected advanced gastric carcinoma patients (P < 0.001). A rapid method for detecting CEA mRNA using the LightCycler and the dsDNA binding dye SYBR green I was also developed. The results obtained using this technique were essentially the same as those obtained using the conventional RT-PCR method. Furthermore, RT-PCR analysis with primers specific for MUC1 epithelial mucin were performed on peritoneal washes from patients with ovarian cancer. Peritoneal washes from 21 of 25 ovarian carcinoma patients, including all 17 with positive cytology results, were positive for MUC1 mRNA, again indicating a higher sensitivity using this method than conventional cytology. Highly sensitive and rapid detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is a powerful technique to predict peritoneal dissemination in patients with gastric and ovarian cancers.

Animals↗

PubMed1999

Comparative case-referent study of risk factors among hormone-related female cancers in Japan.

To assess the impact of reproductive and anthropometric factors as a risk indicator for female cancers in hormone-related organs, i.e., the breast, endometrium and ovary, we conducted a comparative case-referent study using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The case group consisted of 1,465, 133 and 99 women who had first been diagnosed as having breast, endometrial and ovarian cancer, respectively. The referents were 25,488 female first-visit outpatients who had not previously been diagnosed with any type of cancer. The odds ratios (ORs) and their 95% confidence intervals (95%CI) were estimated using an unconditional logistic regression model. An inverse association with experience of delivery and a positive association with body mass index (BMI) and with change of BMI after 20 years of age, were observed consistently for all three cancer sites. We observed similar risk and protective factors for breast and endometrial cancer, but the effect of reproduction and overweight condition (BMI> or =25) were more prominent in endometrial cancer. Although the present study failed to find site-specific risk factors for ovarian cancer, the results provided evidence that being overweight and/or weight gain in adult life is a common risk factor for all three cancer sites. The results obtained from this study suggested that avoidance of weight gain may reduce the risk of female hormone-related cancers.

Adult↗

PubMed1999

[CA125].

Explore the source record for details and available documents.

Adult↗

PubMed1998

Sodium chloride enhances markedly the thermal stability of thermolysin as well as its catalytic activity.

Thermolysin, a thermophilic metalloproteinase, is markedly activated in the presence of high concentrations (1-5 M) of neutral salts. The activity increases in an exponential fashion with increasing salt concentration, and is enhanced 13-15 times with 4 M NaCl at pH 7.0 and 25 degreesC (K. Inouye, Effects of salts on thermolysin: activation of hydrolysis and synthesis of N-carbobenzoxy-l-aspartyl-l-phenylalanine methyl ester, and a unique change in the absorption spectrum of thermolysin, J. Biochem. 112 (1992) 335-340). In this study, the effect of NaCl on the thermal stability of thermolysin has been examined at 60-85 degreesC. The activation energy, Ea, for the thermal inactivation is 15 kcal/mol at 0 M NaCl, and increases up to 30-33 kcal/mol by the addition of 0. 5-1.5 M NaCl. Further increase in [NaCl] decreases the Ea value, and at 4 M NaCl it is almost the same as that at 0 M NaCl. Thermolysin at 0.5-1.5 M NaCl is twice as heat-stable as in the absence of NaCl. The NaCl dependence of the stability is different from that of the activity, suggesting that the effects of NaCl on activity and stability are independent. Thermolysin has been demonstrated to be not only a thermophilic enzyme but also a highly halophilic one.

Enzyme Stability↗

PubMed1998

Diagnosis of squamous cell carcinoma arising from mature cystic teratoma of the ovary.

BACKGROUND: The prognoses of patients with squamous cell carcinoma of the ovary are quite poor. However, preoperative diagnosis is difficult due to the rarity of this tumor and its similarity to mature cystic teratoma (MCT). The objective of this study was to assess the value of tumor markers and clinical characteristics in making a differential diagnosis between MCT and squamous cell carcinoma arising from MCT. METHODS: Between September 1979 and June 1996, 37 patients with ovarian squamous cell carcinoma arising from MCT were treated by the Tokai Ovarian Tumor Study Group. The authors evaluated tumor markers, tumor size, and age as parameters for differentiation between MCT and squamous cell carcinoma arising from MCT. Diagnostic efficiency was calculated as the sensitivity multiplied by the specificity. RESULTS: There were significant differences (P < or = 0.0002) in age, tumor size, and levels of squamous cell carcinoma antigen (SCC), CA125, and CEA, as well as a significant difference (P < or = 0.0396) in the CA19-9 level between MCT and squamous cell carcinoma arising from MCT. Diagnostic efficiency was highest for SCC (63.0%), followed by CA125 (50.7%). Receiver operating characteristic (ROC) curves demonstrated that CEA was the best screening marker for squamous cell carcinoma arising from MCT, whereas age and tumor size were better markers than CA125 or CA19-9. The optimal cutoff values for age and tumor size were 45 years and 99 mm, respectively, according to ROC analysis. CONCLUSIONS: These findings demonstrate that age and tumor size are important factors in making a differential diagnosis. In addition, SCC and CEA levels should be measured in patients age 45 years or older who have an MCT-like ovarian tumor larger than 99 mm in greatest dimension.

Adult↗

PubMed1998

Effect of salts on the solubility of thermolysin: a remarkable increase in the solubility as well as the activity by the addition of salts without aggregation or dispersion of thermolysin.

Thermolysin is remarkably activated in the presence of high concentrations (1-5 M) of neutral salts [Inouye, K. (1992) J. Biochem. 112, 335-340]. The activity is enhanced 13-15 times with 4 M NaCl at pH 7.0 and 25 degrees C. In this study, the effect of neutral salts on the solubility of thermolysin has been examined. Although the solubility was only 1.0-1.2 mg/ml in 40 mM Tris-HCl buffer, pH 7.5, in the temperature range between 0 and 60 degrees C, it was increased greatly by the addition of salts. With NaCl, the solubility showed a bell-shaped behavior with increasing NaCl concentration, and the maximum solubility (10 mg/ml) was at 2.0-2.5 M NaCl. With LiCl and NaI, it increased progressively to 20-50 mg/ml with increasing salt concentration up to 5 M. The solubility observed in the presence of salts decreased with increasing temperature from 0 to 60 degrees C, and also with the order of chaotropic anion effect. The molecular weight of thermolysin was estimated to be 33.0(+/-2.5) x 10(3) in the presence of 0-3 M NaCl, suggesting that thermolysin exists as a monomer in the presence or absence of 3 M NaCl. The possibility that aggregation and/or dispersion of thermolysin might be related to the remarkable activation by salt was ruled out.

Acrylates↗

PubMed1998

Smoking and dietary risk factors for cervical cancer at different age group in Japan.

The importance of the major risk and protective factors for cervical cancer in women by age group was evaluated with the use of data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. This study included 416 cervical cancer cases and 20,985 referents confirmed as free of cancer. Cases and referents were divided into three age groups: the younger, middle and older age groups (30-44, 45-54 and 55-69 years old, respectively). Logistic model was applied separately to the three groups to estimate odds ratios (ORs) of smoking, beverage and dietary habits with adjustment for marital and reproductive factors. The elevated OR of current smokers was observed consistently in all age groups, while alcohol intake did not show any increased ORs. Dietary control for health lowered ORs for all three age groups, and the effect appeared to be more pronounced among the older age group (OR = 0.49, 95% confidence interval: 0.30-0.80). Higher frequency intake of green-yellow vegetables consistently afforded lower ORs among all three age groups. This risk increment of smoking and risk reduction by dietary control were consistent in all age groups. These findings suggested practicable prevention strategy for the cervical cancer by modifying general life style.

Acculturation↗

PubMed1997

Clinical behavior of borderline ovarian tumors: a study of 150 cases.

BACKGROUND: We evaluated the clinical features, treatment, and survival status of the patients with borderline ovarian tumors. METHODS: A retrospective review of the charts of 150 patients with borderline ovarian tumor registered at the Tokai Ovarian Tumor Study Group from January 1, 1980, to December 31, 1994, was conducted to obtain clinical and pathological information. RESULTS: In stage II and III disease, the numbers of patients with no residual tumor, residual tumor of <2 cm, 2-5 cm, and >5 cm were 9, 10, 3, and 3, respectively. The sizes of residual tumors and corresponding clinical response to chemotherapy were as follows: residual tumor of <2 cm, complete response (CR), 6 patients; no change (NC), 2; progressive disease (PD), 2; tumors 2-5 cm, NC, 1 patient, PD, 2; tumors >5 cm, PD, 3 patients. The survival for patients with residual tumor <2 cm was significantly better than for those with residual tumor from 2-5 cm and of >5 cm (P < 0.05). The survival for patients with stage II and III serous tumor was significantly longer than that for patients with stage II and III mucinous tumor (P < 0.05). CONCLUSION: In advanced borderline ovarian tumor, the prognosis of patients with gross residual tumor after initial surgery, and especially with mucinous tumor, was poor.

Adolescent↗

PubMed1996

Subsite (cervix/endometrium)-specific risk and protective factors in uterus cancer.

In Japan the incidence of cervical cancer has been high, but has recently been decreasing gradually, while the incidence of endometrial cancer is running at lower levels but is gradually increasing. To clarify the common and/or specific risk and/or protective factors of cervical cancer(CC) in contrast with endometrial cancer (EC), a comparative case-control study was conducted at the Aichi Cancer Center Hospital, Japan. In total, 556 CC cases and 145 EC cases were included and 26,751 women, confirmed as free of cancer, were chosen as the common control group. Odds ratio and its 95% confidence interval (95%CI) for each exposure variable were estimated by using an unconditional logistic regression model adjusted for age and first-visit year. Habitual smoking and experience of pregnancy increased the risk of CC, while decreasing the risk of EC. Greater body mass index (>20), daily intake of fruit and more frequent intake of boiled or broiled fish (>1-2 times/week) decreased the risk of CC, whereas they increased the risk of EC. Daily intake of milk decreased the risk of CC. The results obtained from this study suggest that several EC-increasing risk factors are in fact CC-decreasing determinants. The observed risk reduction in both CC and EC by physical exercise and dietary control for health is noteworthy from the public health standpoint and warrants further investigation.

Adult↗

PubMed1996

[The efficacy of mass screening for uterine cancer].

Mass screening for uterine cancer, mainly by cytological examination, has been conducted since 1962. The total number of examinees has been increasing and has remained at the same level for the last decade. The coverage rate of screening is only 16%, much lower than the target rate of screening, at present. According to the increase in the number of examinees, the mortality has fallen gradually, because the patients with cancer detected early on are increased and treated successfully with better QOL. However, there are some problems, as follows. 1) Although the coverage rate among the first-time examinee, women in their 30s and 70s are lower than the other groups, the rate of dysplasia and uterine cancer detected among them, are higher. 2) False, negative rate of cytology is relatively high. It is suggested the systemic mass screening is effective to reduce mortality from uterine cancer. It is necessary, however, to improve and certify the further efficacy of screening in reduction of mortality of uterine cancer, referring to procedures of cytology, especially for early detection of adenocarcinoma, and registration system from the point of cost-effectiveness.

Adenocarcinoma↗

PubMed1995

Association of human leukocyte antigen-B1*03 with cervical cancer in Japanese women aged 35 years and younger.

BACKGROUND: An association of human leukocyte antigen (HLA)-DQw3 alleles with squamous cell carcinoma (SCC) of the cervix has been reported in some European populations, but the significance of HLA-DQw3 has not been examined in other populations to the authors' knowledge. The interaction between HLA-DQw3 and human papillomavirus (HPV) in SCC remains to be clarified. METHODS: To elucidate the association of HLA-DQ alleles with SCC of the cervix, DNA samples extracted from blood lymphocytes of 23 patients with SCC were amplified by the polymerase chain reaction (PCR) using specific primers for the DQB1 genes, and then, each HLA-DQB1 genotype was defined by digestion with restriction enzymes. Human papillomavirus typing also was performed in all cases by PCR, using specific primers for the E6 regions of cancer-associated HPV types (HPV 16, 18 and 33). RESULTS: Twenty patients (87%) carried a DQB1 gene-encoding HLA-DQw3, compared with 49.4% Japanese control subjects in the International Histocompatibility Workshop panel (P = 0.0003). Human papillomavirus 16 or HPV 18 DNA was detected in 86% of the patients. In 13 of the patients with invasive carcinoma with HPV, a high incidence of not only HLA-DQw3 but also of HLA-DQw1 was observed compared with that in control subjects (P = 0.0019, P = 0.047, respectively). The correlation between DQB1*03 alleles and HPV infection was not statistically significant. CONCLUSION: The frequency of HLA-DQw3 alleles was higher in the authors' patient group than in the control group, suggesting that the HLA-DQw3 molecules may influence the development of SCC of the cervix in young Japanese women. In the patients with HPV-positive invasive carcinoma, the association with HLA-DQw1 molecules suggested that it also may influence the progression of SCC.

Adult↗

PubMed1995

Prognostic evaluation of lymphadenectomy for epithelial ovarian cancer.

Between 1989 and 1991, 150 patients with ovarian cancer were treated with chemotherapy, including cisplatin, in the Tokai Ovarian Tumor Study Group. Of these patients, 25 underwent cytoreductive surgery with lymphadenectomy, including removal of either pelvic or para-aortic lymph nodes, and 36 underwent both lymphadenectomies. A significant difference was observed between survival curves of the groups with positive and negative lymph nodes, respectively (P = 0.0049). The overall survival was longer in the lymphadenectomy group than in the nonlymphadenectomy group (P = 0.0842), and a significantly longer survival time was noted for stage III patients who underwent lymphadenectomy compared with those who did not (P = 0.0185). Multivariate analysis demonstrated that lymphadenectomy is a positive prognostic factor. The authors conclude that both pelvic and para-aortic lymph nodes should be resected to improve survival as well as to assess exact staging in patients with ovarian cancer.

Carcinoma↗