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Biomedical subjects

N Sakuragi

Publications and source records attributed to N Sakuragi.

At least 37 records · Page 2Linked to original sources

Two cases of endometrial cancer meeting new clinical criteria for hereditary nonpolyposis colorectal cancer.

BACKGROUND: New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC) that includes extracolonic cancers were recently proposed. We present 2 endometrial cancer patients who met the new criteria of 161 endometrial cancer patients. CASE REPORTS: Case 1: A 55-year-old female was operated on for synchronous double primary cancers of the endometrium and rectum. She had also undergone an operation for metachronous ascending colon cancer at the age of 44. She had five relatives with a history of colorectal cancer. The rectal cancer tissue revealed no microsatellite instability (MSI). Case 2: A 48-year-old female underwent a radical operation for synchronous double primary cancers of the endometrium and ovaries. She had three relatives with a history of colorectal cancer. The endometrial cancer tissue showed high MSI. CONCLUSIONS: The frequency of endometrial cancer patients meeting the new HNPCC criteria was 1.2% (2/161). These are the first case reports selected from consecutive endometrial cancer patients.

Carcinoma, Endometrioid↗

Complications relating to intraperitoneal administration of cisplatin or carboplatin for ovarian carcinoma.

BACKGROUND: Complications associated with intraperitoneal (ip) chemotherapy is one of the factors that should be taken into consideration upon performing long-term intraperitoneal administration of chemotherapeutic agents for ovarian carcinoma. METHODS: From 1987 to 1996, 78 patients with primary ovarian carcinoma were treated with a total of 365 courses of ip administration of cisplatin (CDDP) or carboplatin (CBDCA) as a part of an initial chemotherapy regimen in combination with surgery including systematic retroperitoneal lymph node dissection using an implantable peritoneal cavity access catheter system. The complications that occurred in association with ip chemotherapy were analyzed. RESULTS: Complications associated with ip chemotherapy were seen in 27 of 78 (34.6%) patients, which included extensive intestinal adhesion, abdominal pain, local infection, ileus, bleeding at the site of implanted port, obstruction of the catheter, vaginal vault perforation, and bowel perforation. Major complications that required surgical treatment occurred in 3 patients, which included ileus, vaginal perforation, and an intestinal perforation. The perforations occurred after 18 and 36 months after the implantation of the catheter, respectively. CONCLUSIONS: It has been suggested that primary CDDP/CBDCA ip chemotherapy using an implantable catheter system can be carried out safely with rare major complications if employment of this method is restricted in 12 months after the installation of catheter.

Adult↗

Prevention of vaginal shortening following radical hysterectomy.

We describe a surgical procedure and post-operative management for the prevention of vaginal shortening following radical hysterectomy. A total of 452 patients who underwent hysterectomies were examined prospectively depending on the operation method. This study showed that our procedure was effective in the prevention of vaginal shortening following radical hysterectomy. Preservation of the ovaries appeared to be important in preventing vaginal shortening, and post-operative hormone replacement therapy was not as effective as the preservation of the ovaries. The effect of external irradiation on vaginal shortening was not conspicuous in the case that the ovaries were preserved.

Adolescent↗

Factor XII deficiency in women with recurrent miscarriage.

Congenital thrombophilia is known to cause significant maternal complications, and possibly has an adverse effect on normal fetal development. The aim of this study was to assess the prevalence of factor XII (FXII) deficiency in women with a history of recurrent miscarriage. Two hundred and forty-one consecutive Japanese women with a history of two or more recurrent miscarriages were prospectively assessed for their etiology by conventional screening methods. Seven women were found to have reduced FXII activity (19. 2-46.1%) and prolonged activated partial thromboplastin time (33. 3-51.3 s). Of these 7 women, 6 had experienced early pregnancy losses, while 1 woman had experienced repeated mid-trimester fetal losses with coincidental gestational thrombocytopenia. In 241 women with a history of recurrent miscarriage, the prevalence of FXII deficiency was 2.9%.

Abortion, Spontaneous↗

Reversal of intra-amniotic Chlamydia trachomatis antigen status.

Chlamydia trachomatis (CT) infection in pregnant women is related to unfavorable obstetric outcomes such as prematurity, intrauterine growth retardation, and stillbirth. A 22-year-old woman underwent transabdominal amniocentesis at 16 weeks of gestation (GW). A CT antigen test using polymerase chain reaction in the amniotic fluid was found to be positive, though the patient had no symptom of infection. Beginning at 20 GW, clarithromycin was orally administered at a dose of 400 mg/day for 2 weeks. The CT antigen test in amniotic fluid at 28 GW turned to a negative result. A female baby was vaginally born at 38 GW by spontaneous labor. The CT antigen test of her gastric contents showed a negative result and anti-CT IgM in umbilical cord blood was negative. Neither respiratory distress, pneumonia, nor conjunctivitis was detected. To the best of our knowledge, this case is the first report showing the reversal of the intra-amniotic CT antigen status by antibiotic treatment.

Adult↗

Prognostic significance of serous and clear cell adenocarcinoma in surgically staged endometrial carcinoma.

BACKGROUND: The serous adenocarcinoma (SA) and clear cell adenocarcinoma (CCA) of endometrium have been shown to be associated with high relapse rate and poor survival. It is not clear whether prognostic significance of these specific cell types of tumor is independent of retroperitoneal lymph node metastasis and other histopathologic prognostic factors in endometrial carcinoma. METHODS: We examined 240 consecutive patients with clinical stage I to stage III endometrial carcinoma who were treated prospectively with radical surgery and/or platinum-based chemotherapy. Surgery included extended hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic and paraaortic lymph node dissection. Prognostic significance of various histopathologic factors was determined by Cox regression analysis. RESULTS: SA/CCA were more frequently associated with deep myometrial invasion, high nuclear grade (G3), lymph-vascular space invasion (LVSI), and pelvic lymph node metastasis when compared to endometrioid adenocarcinoma (EMA). Of 216 clinically staged stage I or II disease, seven of 12 cases of SA/CCA had extrauterine disease. This incidence was much higher than that for EMA (46/204) (p<0.01). A multivariate Cox regression analysis revealed that cell type, grade, LVSI, and paraaortic node metastasis (PANM) were independent prognosticators. CONCLUSIONS: Prognosis of patients with endometrial carcinoma depends on cell type, grade, LVSI, and PANM. Poor prognosis for patients with SA/CCA is independent of lymph node metastasis and other histopathologic prognostic factors. The SA/CCA should be strictly discriminated from EMA.

Adenocarcinoma, Clear Cell↗

Prevention of lymphocyst formation following systematic lymphadenectomy.

BACKGROUND: The occurrence of pelvic lymphocysts is an important complication following systematic lymphadenectomy for gynecological malignancies. We employed a procedure to prevent vaginal shortening following radical hysterectomy and we examined whether this procedure could be effective in preventing pelvic lymphocyst formation. METHODS: We studied the incidence of lymphocysts in 190 patients with 84 cervical cancers, 74 endometrial cancers and 32 ovarian cancers, using computed tomographic examination at 3 and 6 months subsequent to the surgery. The surgery included radical hysterectomy and a procedure to prevent vaginal shortening (101), modified radical hysterectomy (79) and simple hysterectomy (7), with systematic lymphadenectomy. RESULTS: There was a significant difference in the incidence of pelvic lymphocysts between cervical cancer (4.8%) and ovarian cancer (18.8%). The postoperative incidence of lymphocyst formation in patients undergoing radical hysterectomy with the procedure to prevent vaginal shortening (5.9%) was significantly lower than in those who underwent modified radical hysterectomy (15.2%). CONCLUSION: Our procedure to prevent vaginal shortening could be effective in preventing not only the shortening of the vagina but also the occurrence of pelvic lymphocysts in patients undergoing radical hysterectomy with systematic lymphadenectomy for gynecological malignancies.

Adolescent↗

Telomerase activity correlates with histo-pathological factors in uterine endometrial carcinoma.

Telomerase activity has been implicated in the progression of various human tumors. Our aim was to evaluate telomerase activity and to compare it with histo-pathological factors in uterine endometrial carcinoma, to look for possible correlations. Telomerase activity was measured by dilution analysis using a PCR-based telomeric repeat amplification method and detected in 31 of 35 primary endometrial carcinoma tumor specimens. High telomerase activity, detected after 100-fold dilution of extracts, was identified in 15 specimens. There was no significant correlation between the positive telomerase activity and tumor surgical stage or histo-pathological factors. However, high telomerase activity was significantly correlated with advanced surgical stage and with pelvic lymph node metastasis. Our findings suggest that an increase in telomerase activity may be associated with tumor progression and that its level may have a prognostic value in endometrial carcinoma.

Adult↗

Incidence and distribution pattern of pelvic and paraaortic lymph node metastasis in patients with Stages IB, IIA, and IIB cervical carcinoma treated with radical hysterectomy.

BACKGROUND: The incidence and distribution pattern of retroperitoneal lymph node metastasis in patients with cervical carcinoma should be investigated based on data from systematic pelvic lymph node (PLN) and paraaortic lymph node (PAN) dissection, so that a basis can be established for determining the site of selective lymph node dissection or sampling. METHODS: A total of 208 patients with Stages IB, IIA, and IIB cervical carcinoma who underwent radical hysterectomy and systematic pelvic and PAN dissection were investigated for lymph node metastasis and histopathologic risk factors for lymph node metastasis. RESULTS: Fifty-three patients (25.5%) had lymph node metastasis. The obturator lymph nodes were most frequently involved, with a rate of 18.8% (39/208). Forty-nine of 53 node-positive patients had lymph node metastasis in the obturator, internal iliac, or common iliac lymph nodes. Of 26 solitary lymph node metastases confined to one node group, 18 were in the obturator, 3 in the internal iliac, 3 in the parametrial, and 2 in the common iliac lymph nodes. A multiple logistic regression analysis revealed that deep cervical stromal invasion and lymph-vascular space invasion were related to PLN metastasis. It was also shown that metastasis to bilateral PLNs (excluding the common iliac lymph nodes) as well as metastasis to the common iliac lymph nodes were significantly related to PAN metastasis. CONCLUSIONS: The results of this study suggest that the obturator lymph nodes can be sentinel lymph nodes of cervical carcinoma. PAN metastasis appears to occur secondarily to wide-spread PLN metastasis. These results provide a basis for determining the site of selective lymph node dissection and for estimating the existence of PAN metastasis from the pattern of metastasis in PLN in patients with cervical carcinoma.

Adult↗

BRCA1 mutation testing for Japanese patients with ovarian cancer in breast cancer screening.

From February 1996 to April 1998, 2967 women received screening for breast cancer in the gynecologic ambulatory practice of the Hokkaido University Hospital. In 116 Japanese women with epithelial ovarian cancer, mutation analysis of BRCA1 exon 11 in genomic DNA was performed by the stop codon (SC) assay and DNA sequence analysis. Clinicopathological factors were also investigated in these patients. The aim of this study was to examine the advantages of performing BRCA1 mutation testing for ovarian cancer patients during breast cancer screening. We achieved a high detection rate (6.0%) of patients with germline mutations in BRCA1. The high frequencies of breast ovarian cancer syndrome, serous adenocarcinoma, high histological grades, advanced FIGO stages, and breast cancer as double cancer were found to be characteristic of ovarian cancer with germline mutations in BRCA1. These characteristics may assist physicians in selecting BRCA1 mutation testing for ovarian cancer patients. The mean age at diagnosis of ovarian cancer was 51.0 and 51.2 years in the groups with and without mutation, respectively, and no difference was found in age at diagnosis. All of the nine living female mutation carriers were offered the options of increased surveillance or prophylactic surgery, and all chose the former. We have performed breast cancer screening and/or ovarian cancer screening every 6 months for these carriers. This may allow another advantage in establishing a relationship of mutual trust with a patient from a series of responsible follow-ups.

Adolescent↗

Induction of macrophage migration inhibitory factor in human ovary by human chorionic gonadotrophin.

The role of macrophage migration inhibitory factor (MIF) in human ovarian function remains obscure. The aim of this study was to investigate how MIF was related to ovulation by quantitative analysis of serum, follicular fluid and culture medium of granulosa cells obtained from in-vitro fertilization (IVF) and embryo transfer patients. Serum MIF concentrations in ovarian stimulation cycles for IVF-embryo transfer were higher at day 1 (median 92.6 ng/ml), which took place 35 h after human chorionic gonadotrophin (HCG) administration and just before the retrieval of oocytes, than those before day -6 (12.1 ng/ml), at day -5 to about day 0 (17.5 ng/ml) or at day 2 to about day 14 (8.2 ng/ml). MIF concentrations in the follicular fluid (113.4 ng/ml) obtained in ovarian stimulation cycles for IVF-embryo transfer were significantly higher than in serum (72.0 ng/ml) collected at the same time. MIF concentrations in the follicular fluid in natural cycles were higher in the ovulatory phase (51.6 ng/ml) than in the late follicular phase (13.8 ng/ml). MIF concentrations in the culture media of granulosa cells increased from 3.2 ng/ml to 7.2 ng/ml with HCG stimulation, and decreased from 2.4 ng/ml to 1.2 ng/ml when stimulation was withheld. These results indicate that HCG can induce the elevation of serum and follicular fluid MIF concentrations through the stimulation of ovarian cells, and that MIF is probably involved in the mechanism of ovulation.

Adult↗

Clinicopathological comparisons of familial and sporadic cases in 219 consecutive Japanese epithelial ovarian cancer patients.

BACKGROUND: It is estimated that approximately 5-10% of epithelial ovarian cancer patients in Western countries are associated with an autosomal dominant inheritance with variable penetrance. There are a few reports of familial ovarian cancer in Japan and considerable uncertainties remain regarding Japanese familial ovarian cancer. The aim of this study was to clarify the clinicopathological features of Japanese familial ovarian cancer. METHODS: We studied clinicopathological findings for 219 consecutive epithelial ovarian cancer patients treated at our institution from April 1987 to September 1997. RESULTS: Eleven patients in nine families were diagnosed as familial ovarian cancer and the incidence of familial cases was 5.0%. Most women (90.9%) with familial cases were diagnosed as the breast ovarian cancer syndrome, whereas ovarian cancer associated with hereditary nonpolyposis colorectal cancer was relatively rare (9.1%). Serous adenocarcinoma, high histological grade, advanced FIGO stage and breast cancer as multiple primary cancer were significantly more common in familial cases compared with sporadic cases (p < 0.001, p < 0.05, p < 0.005 and p < 0.005, respectively). Earlier age of onset was thought to be a characteristic of familial ovarian cancer in Western countries; however, we did not find any difference in age at diagnosis between familial and sporadic cases (53.4 vs 51.3 years). The prognosis of familial ovarian cancer remains controversial and our data did not show a significant difference (p = 0.45) in prognosis between these two groups. CONCLUSION: These findings, except for age at diagnosis, in Japanese familial ovarian cancer are in accordance with the features of familial ovarian cancer in Western countries.

Asian People↗

Malignant Brenner tumors of the ovary and tumor markers: case reports.

We investigated the tumor marker for malignant Brenner tumors, which had not been established because of the rarity and variable histological criteria. Representative areas of two cases of malignant Brenner tumor were investigated by means of the peroxidase-antiperoxidase method using monoclonal antibody to CA125 and CA72-4 antigen and the streptavidin-biotin immunoperoxidase complex method using monoclonal antibody to SCC antigen. Based on clinical course and immunohistochemical studies, serum CA125 and CA72-4 for Case 1 and SCC and CA72-4 for Case 2 were appropriate tumor markers for the establishment of the extent of tumor burden before treatment and to monitor the response to therapy. The discrepancy of the tumor markers of the two present cases is considered to be a reflection of the difference in the malignant component of these cases. However, serum CA72-4 was an appropriate tumor marker for both malignant Brenner tumors.

Aged↗

Hypocomplementemia correlates with intrauterine growth retardation in systemic lupus erythematosus.

PROBLEM: The aim of this study was to elucidate fetomaternal risks in systemic lupus erythematosus (SLE)-complicated pregnancy. METHOD OF STUDY: Pregnancy course, complications, and fetal outcome in 82 pregnancies of 55 patients with SLE were investigated. RESULTS: These 82 pregnancies resulted in 14 fetal losses and 66 live births. Without clinical manifestation of SLE-flare, 4 of 8 patients who had low serum complement activity during the pregnancies delivered small-for-date neonates. The rate of the intrauterine growth retardation was significantly higher than that observed in pregnancies with normal complement activity. The frequency of premature deliveries (60%) in patients who received more than 15 mg/day of prednisolone was significantly high when compared with pregnancies maintained by 0-15 mg/day (13.1%). CONCLUSIONS: These data demonstrate the preconceptional and perinatal management necessary in SLE and suggest that the pregnancy with hypocomplementemia, the disease activity, and/or a relatively high maintenance dose of corticosteroid should be carefully managed and monitored.

Adult↗

A sensitive, nonradioactive method for the detection of a low level of apoptosis in rat ovary and human placenta. Technical note.

Apoptosis is often characterized by internucleosomal DNA fragmentation, which is classically visualized in standard agarose gel electrophoresis. However, this technique is not sufficiently sensitive for the detection of a modest apoptotic level in intact tissues. We developed a sensitive, nonradioactive method for the qualitative and quantitative analyses of apoptotic DNA fragmentation in intact tissues. An ultrasensitive chemiluminescent substrate, CDP-Star, was used for the visualization of digoxigenin (DIG)-labeled DNA fragments, and banding patterns were densitometrically quantified. Serially diluted DNA samples from rat ovaries were labeled with DIG. As a result, only 1.56 ng of DNA could be analyzed for the presence of apoptotic DNA cleavage. The sum intensity of these bands increased almost linearly by increasing the amount of labeled DNA. In human placental tissues, clear apoptotic DNA ladders were visualized by this method, and the quantification of apoptotic DNA fragmentation was also possible. This new method provides a nonradioactive, highly sensitive and semiquantitative analysis of apoptotic DNA fragmentation and may be highly useful for the study of a low, physiological level of apoptosis.

Animals↗

Cox multivariate regression models for estimating prognosis of patients with endometrioid adenocarcinoma of the uterine corpus who underwent thorough surgical staging.

The International Federation of Gynecology and Obstetrics (FIGO) adopted surgical staging criteria in 1988. Many studies have shown that histologic grade, nuclear grade, lymph-vascular space invasion and cell type are also important predictors of survival. It has not been clarified, however, how to integrate these histopathologic variables into the process of estimating individual prognosis. We performed Cox multivariate regression analysis to create models that incorporate various histopathologic factors for estimating the prognoses of patients with endometrioid adenocarcinoma of the uterine corpus. Our study was based on data from 206 patients who underwent complete surgical staging, including systematic pelvic and para-aortic lymph node dissection. Two models resulted: one included depth of myometrial invasion, para-aortic node metastasis and the number of sites involved by the tumor among the cervix, ovary and pelvic lymph nodes (which we designated as extracorporeal spread score, ECS) and the other incorporated nuclear grade and lymph-vascular space invasion as variables. These 2 models enabled the prognosis for patients with endometrioid adenocarcinoma to be stratified into several levels according to hazard ratio. Comprehensive integration of the histopathologic prognostic factors, categorized into those relating to tumor extent and those relating to tumor virulence, should facilitate the estimation of individual prognosis more accurately than FIGO staging alone.

Adenocarcinoma↗

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma.

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.

Adenocarcinoma, Clear Cell↗