Impact of three-dimensional (3D) ultrasonography and power Doppler angiography in the management of cervical cancer.

PURPOSE: To evaluate the potential role of three-dimensional (3D) ultrasound, and to assess its diagnostic performance and ability to predict therapeutic efficacy in cervical cancer. METHODS: Thirty patients with cervical cancer and 35 normal controls were studied by transvaginal 3D power Doppler ultrasound before treatment. Eleven patients who received neoadjuvant chemotherapy (n = 6), radiation (n = 3), or chemoradiation (n = 2), had further measurements taken one month and two months after treatment. RESULTS: From the receiving operating characteristics curve analysis, the best vascularization index (VI) cutoff value of 5.24 distinguished cervical cancer from the normal cervix, with a sensitivity of 73.3% and a specificity of 94.3%. Cervical tumor volume measured by magnetic resonance imaging was positively correlated with the tumor volume measured by 3D ultrasonography (r = 0.91, p < 0.0001). In six patients who received neoadjuvant chemotherapy, the percent change in tumor volume during the second month of treatment was positively correlated with the percent change in flow index (FI) during the first month of treatment (r = 0.83, p < 0.05). CONCLUSIONS: VI may be a diagnostic marker and FI may be a predictive marker of treatment response in cervical cancer.

The incidence, treatment and prognosis of cervical carcinoma in young women: a retrospective analysis of 4,975 cases in Japan.

OBJECTIVE: To determine the clinical characteristics of patients (young women) with cervical carcinoma aged less than 35 years. METHODS: Data from patients who were treated for cervical carcinomas from 1990 to 2000 in the Kinki District were retrospectively investigated for clinical stage, histologic type, treatment procedure and prognosis. RESULTS: Of a total of 4,975 cases, 441 patients were aged less than 35 years old. The incidence of cervical carcinoma in these women was 7.9% from 1990 to 1995, 9.1% from 1996 to 2000, and 9.5% from 2001 to 2005. FIGO Stage I included 374 cases, followed by, 49 in Stage II, 11 in Stage III, and seven in Stage IV. Squamous cell carcinoma incidence was 80.7% and non-squamous cell carcinoma incidence was 19.3%. Several types of surgery were performed in patients with Stage I and II, while patients with Stage III and IV were treated with radiotherapy and/or chemotherapy without any type of surgery. In patients who underwent lymphadenectomy, 21.1% cases had nodal involvement. The 5-year survival rate was 95% for Stage I disease, 73% for Stage II, 68% for Stage III, and 19% for Stage IV. CONCLUSION: The incidence of cervical carcinoma in young women slightly increased from 1990 to 2005. The prognosis of cervical carcinoma tends to be better in young women than in older patients, especially in Stage III disease.

Clinical outcome and prognostic factors in borderline tumors of the ovary. Results from 17 years' experience in the Kinki District of Japan (1990-2006).

PURPOSE OF INVESTIGATION: The clinical characteristics and long-term prognostic factors of borderline ovarian tumors (BOTs) were evaluated. METHODS: Data from patients who were treated for BOTs in the Kinki District of Japan from 1990 to 2006 were revieved. Two hundred and twenty-two cases were retrospectively investigated for stage, surgical procedure, histopathological features, adjuvant chemotherapy and prognosis. RESULTS: FIGO stages included 212 patients with Stage I disease, three with Stage II and seven with Stage III. One hundred and sixty-nine cases were diagnosed as mucinous tumor, 47 were serous, and six were others. Radical surgery was performed in 136 patients and conservative surgery in 86 patients. Only two patients showed invasive peritoneal implants. Forty patients received adjuvant chemotherapy. The survival rate was 95% at ten-years. Statistical analysis showed that earlier stage, absence of residual tumors, peritoneal implants, ovarian stromal involvement, and negative peritoneal cytology were associated with significantly better overall survival. CONCLUSION: The prognosis of patients with BOT is excellent. There are insufficient data to support a role for aggressive surgery and adjuvant chemotherapy for the possibility of prolonged survival.

Factors affecting bone mineral density of young women and predictive factors of low bone mineral density.

PURPOSE OF INVESTIGATION: We investigated various factors affecting bone mineral density (BMD) in young women and predictive factors of low BMD. METHODS: Subjects were 105 nursing school students aged from 19 to 24 years old. Body weight (BW), pituitary hormones, sex steroid hormone and bone turnover markers were selected as factors. BMD was measured at the lumbar spine at L2-L4 by dual-energy X-ray absorptiometry (DXA). RESULTS: BW (p = 0.002), serum N-terminal telopeptide of type 1 collagen (NTx) (p = 0.006) and bone specific alkaline phosphatase (BAP) (p = 0.02) were significantly correlated with BMD. For identification of the low BMD group, all subjects were divided into four groups on the basis of BW and NTx concentrations. In the group with BW under 51 kg and Ntx concentrations over 11 nMBCE/1, BMD was significantly (p = 0.0013) decreased compared with the other three groups. In this group, the ratio of women with a low BMD was significantly higher (p = 0.004) than the other groups. CONCLUSION: In young women, BW and bone turnover markers significantly affected BMD. Low BMD can be indicated using BW and NTx concentrations without measurement by DXA.

Complete remission of OC-resistant catamenial shoulder joint pain and inguinal pain associated with extraperitoneal endometriosis following personalized GnRH agonist therapy.

BACKGROUND: Patients with severe extraperitoneal endometriosis require rapid remission and cannot wait for the effects of oral contraceptive hormones (OCs) to appear. CASE: We successfully achieved personalized gonadotropin-releasing hormone agonist (GnRHa) therapy for a patient with catamenial right shoulder joint pain and right inguinal pain associated with extraperitoneal endometriosis, which was completely unable to be suppressed by OCs. A total of 15 subcutaneous GnRHa depot injections over a period of 19 months was performed according to the serum estradiol and LH levels, in order to maintain long-term amenorrhea without any estrogen-deprivation effects. No recurrence of the catamenial symptoms has been observed for more than 35 months after the final GnRHa depot injection. CONCLUSION: Personalized GnRHa therapy should become the first-choice therapy for OC-resistant inoperable extraperitoneal endometriosis.

Structural change of crystalline and amorphous-Ge(2)Sb(2)Te(5) by reverse Monte Carlo analysis of x-ray diffraction data and extended x-ray absorption fine structure data.

Reverse Monte Carlo analyses of crystalline and amorphous Ge(2)Sb(2)Te(5) thin films were carried out using x-ray diffraction data and three spectra from extended x-ray absorption fine structure measurements. To produce a crystal model, we employed a large system with 12 800 Ge, 12 800 Sb and 32 000 Te atoms. The obtained model for the crystal structure was used for the initial configuration of the amorphous model. As a result of a series of reverse Monte Carlo analyses with various constraints, we found that the partial pair distribution function in the amorphous state with the largest deviation from the crystal state is a Ge-Sb pair and the distance is less than 2.7 Å. This suggests that Sb atoms in amorphous Ge(2)Sb(2)Te(5) thin film have a four-coordinate within 3.2 Å.

Two-dimensional pattern reverse Monte Carlo method for modelling the structures of nano-particles in uniaxial elongated rubbers.

Two-dimensional pattern reverse Monte Carlo (2D pattern RMC) analysis is performed to model the structures of nano-particles in uniaxially elongated rubbers using two-dimensional patterns of structure factor of the nano-particles obtained by time-resolved two-dimensional ultra-small angle x-ray scattering. Four spot patterns are observed for a large elongation ratio and the shapes change with increasing elongation ratio. We performed the 2D pattern RMC method for the uniaxial system in order to make a model of the structures from the two-dimensional structure factors. The preliminary results of the 2D pattern RMC analysis of the two-dimensional structure factors of silica particles in a uniaxially elongated styrene-butadiene rubber are presented.

Radiation reduces carboplatin sensitivity and enhances nedaplatin sensitivity in cervical squamous cell carcinoma in vitro.

BACKGROUND: The study was performed to examine how the platinum anticancer drugs other than cisplatin, such as carboplatin (CBDCA) and nedaplatin (NEP) can be effectively used in chemoradiotherapy for cervical squamous cell carcinoma patients. MATERIALS AND METHODS: The radiosensitive human cervical squamous cell carcinoma cell line ME180 was examined to investigate the radiation effects on CBDCA and NEP sensitivities of the cells. RESULTS: Irradiation significantly reduced cellular CBDCA sensitivity. There were no significant changes in CBDCA sensitivity between the cells concurrently irradiated and those treated with CBDCA 8 h before or 8 h after irradiation. However NEP sensitivity of the cells treated 8 h before or 8 h after irradiation was significantly higher than that in cells concurrently irradiated. CONCLUSIONS: Although CBDCA sensitivity in the concurrently irradiated cells is reduced, NEP sensitivity is enhanced by irradiation. NEP, but not CBDCA, therefore, may be a candidate anticancer drug for concurrent chemoradiotherapy for cervical cancer. For the greatest efficacy, NEP should be administered to patients several hours before or after irradiation.

Irradiation reduces bleomycin sensitivity in cervical squamous cancer cells in vitro.

PURPOSE OF INVESTIGATION: The study was performed to examine how bleomycin (BLM) and peplomycin (PEM) should be effectively used in radiotherapy for cervical squamous cancer patients. METHODS: The effects of BLM on radiosensitivity and the effects of radiation on the sensitivity to BLM of cancer cells were investigated using the radiosensitive human cervical squamous cell carcinoma cell line ME180. RESULTS: BLM treatment did not affect radiosensitivity. However, irradiation significantly reduced cell BLM sensitivity in a dose-dependent manner. There was no significant difference in BLM sensitivity and PEM sensitivity between cells concurrently irradiated and those treated with BLM or PEM 8 h before or 8 h after irradiation. CONCLUSION: Since sensitivity to BLM is reduced during irradiation, BLM should be administered to cervical cancer patients as an adjuvant chemotherapeutic drug after completion of radiotherapy.

Effective chemoradiotherapy protocol with 5-fluorouracil for cervical squamous cell carcinoma in vitro.

PURPOSE OF INVESTIGATION: 5-Fluorouracil (5FU) is frequently used in concurrent chemoradiotherapy for patients with advanced cervical cancer, although its optimal chemoradiotherapy protocol has not yet been established. In search of an optimal chemoradiotherapy protocol, some in vitro experiments were carried out. METHODS: The radiosensitive human cervical squamous cell carcinoma cell line ME180 was examined to investigate the effects of 5FU on radiosensitivity and the effects of irradiation on 5FU-sensitivity. RESULTS: 5FU dose-dependently enhanced cellular radiosensitivity at therapeutic concentrations. Although high doses of y-ray irradiation significantly reduced the 5FU-sensitivity, a low dose of irradiation at therapeutic doses (< 2.5 Gy) had no effect on 5FU-sensitivity of the irradiated cells. Cells pretreated with 5FU eight hours before irradiation showed significantly higher 5FU-sensitivity than cells concurrently treated with 5FU and irradiation. In contrast, cells treated with 5FU eight hours after irradiation showed significantly lower 5FU-sensitivity than cells concurrently treated with 5FU and irradiation. Moreover, all four post-irradiation surviving subclones obtained from repeatedly irradiated ME180 cells showed significantly lower 5FU-sensitivity than the non-irradiated parent cells. CONCLUSION: 5FU acts as a radiosensitizer for cervical squamous cell carcinoma and 5FU-sensitivity is reduced in irradiated cells. Therefore, 5FU administration immediately before irradiation may be a more effective treatment than concurrent chemoradiotherapy or post-irradiation chemotherapy with 5FU.

The p16-cyclin D1/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer.

A significant positive association has been reported between p16 expression and clinical outcome for epithelial ovarian cancer patients. However, there is a reciprocal correlation between genetic alterations of single members of the p16-cyclin D1/CDK4-pRb pathway (G1 pathway). Simultaneous evaluation of these four elements may produce a better prognostic factor than p16 alone. We studied the prognostic significance of the G1 pathway in 59 epithelial ovarian cancer patients undergoing surgery and platinum-based chemotherapy by immunohistochemical technique. Abnormal expression of p16 or pRb was defined by negative nuclei staining, and that of CDK4 and cyclin D1 was defined by 50% nuclear staining. An abnormal G1 pathway was indicated in cases that have at least one abnormality among these four elements. Abnormal expression of p16, pRb, and cyclin D1/CDK4 was observed in 33.9, 3.4, and 15.3% of studied cases, respectively. Abnormal G1 pathway was detected in 49.2% (29 of 59) of all cases. The patients with normal G1 pathway tended to achieve a higher complete response rate (81.0%) to chemotherapy, compared with patients with abnormal G1 pathway (55.0%); however, there was no significant difference (P = 0.1001) between the two groups. Univariate analyses identified advanced stage [hazards ratio (HR), 3.665; P = 0.0218], histological low grade (HR, 3.625; P = 0.0066), and abnormal G1 pathway (HR, 2.935; P = 0.03) as prognostic factors for overall survival. The G1 pathway might help as a prognostic factor to select high-risk patients.

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Effects of mitomycin C on radiation-induced cell death in human cervical squamous cell carcinomas.

In order to find an effective protocol for chemoradiotherapy with mitomycin C (MMC) for advanced cervical cancer patients, effects of both MMC and irradiation on chemoradiosensitivity were examined using the radiosensitive human cervical squamous cell carcinoma cell line ME180. MMC and low doses of irradiation did not affect radiosensitivity of the cells. A high dose of gamma-ray irradiation (10 Gy) significantly reduced MMC sensitivity of the cells. All of the four post-irradiation surviving subclones that were established from repetitively irradiated ME180 cells, demonstrated significantly higher MMC sensitivity than that of the non-irradiated parent cells. However, there was no difference in MMC sensitivity among three groups of irradiated cells; (1) cells treated with MMC eight hours before irradiation, (2) cells concurrently treated with MMC and irradiation and (3) cells treated with MMC eight hours after irradiation. These results indicate that MMC injections after completion of radiotherapy may be a better therapy than concurrent chemoradiotherapy with MMC.

Radiation enhances cisplatin-sensitivity in human cervical squamous cancer cells in vitro.

UNLABELLED: PURPOSE AND METHODS OF INVESTIGATION: Cisplatin (CDDP) is regularly used in concurrent chemoradiotherapy in patients with advanced cervical cancer although an effective protocol of chemoradiotherapy with CDDP has not yet been established. In search of a better chemoradiotherapy protocol, we investigated both CDDP effects on radiosensitivity and irradiation effects on CDDP-sensitivity using the radiosensitive human cervical squamous cell carcinoma cell line ME180. RESULTS: We found that CDDP did not affect cellular radiosensitivity, and that irradiation significantly enhanced CDDP-sensitivity. Moreover, all the four post-irradiation surviving subclones obtained from repetitively irradiated ME180 cells showed significantly higher CDDP sensitivities than those of the non-irradiated parent cells. CONCLUSION: These results suggest that an effective protocol would involve the concurrent administration of CDDP with radiotherapy and further administration following completion of radiotherapy in order to achieve higher CDDP-sensitivities.

Preoperative chemotherapy with irinotecan and mitomycin for FIGO stage IIIb cervical squamous cell carcinoma: a pilot study.

PURPOSE OF INVESTIGATION: Patients with FIGO Stage IIIb cervical cancer show cancer propagation to pelvic side walls from the uterus, and the tumors cannot be completely removed by radical hysterectomy. Here, we examined the effects of preoperative irinotecan HCl (CPT-11)-combined chemotherapy on patients with unresectable Stage IIIb cervical squamous cell carcinoma. METHODS: Eleven patients agreed to participate in the pilot study and received preoperative chemotherapy. RESULTS: Cervical tumors of all 11 patients showed partial responses in tumor reduction, and radical hysterectomy was successfully performed in ten patients treated with CPT-11 and mitomycin C (MMC). One patient treated with CPT-11 and cisplatin had a 68% reduction of the primary cervical lesion but could not undergo radical surgery because of retroperitoneal cancer progression during chemotherapy. CONCLUSION: These results indicate that chemotherapy with CPT-11 and MMC could be a useful preoperative treatment for unresectable Stage IIIb cervical squamous carcinoma.

Cytokine regulation of apoptotic susceptibility in a human endometrial epithelial cell line.

The effects of four endometrial cytokines, transforming growth factor beta1 (TGF-beta1), interleukin-1beta (IL-1beta), epidermal growth factor (EGF), and hepatocyte growth factor (HGF), on Fas-mediated apoptosis in the human endometrial epithelial cell line, HHUA, were investigated. Although the cell growth of HHUA was not directly affected by TGF-beta1, IL-1beta, or EGF, pretreatment of HHUA with TGF-beta1, IL-1beta, or EGF enhanced Fas-mediated growth suppression and Fas-mediated DNA fragmentation in the cells. Flow cytometric analyses demonstrated that TGF-beta1, IL-1beta, and EGF did not induce Fas expression on the cell surface. These results suggest that TGF-beta1, IL-1beta, and EGF enhances apoptotic susceptibility of the cells. However, HGF inhibited Fas-mediated growth suppression and DNA fragmentation in the cells without any increase in Fas antigen expression on the cells. This finding suggests that HGF suppresses apoptotic susceptibility of the cells. From these results, we conclude that the endometrial cytokines may play a role in reshaping the endometrium after menstruation or in regulating apoptotic susceptibility in endometrial epithelium in the mid- to late-secretory period.

Neonatal thrombocytopenia induced by maternal anti-HLA antibodies: a potential side effect of allogenic leukocyte immunization for unexplained recurrent aborters.

Allogenic leukocyte immunization is one of several treatments tried for unexplained recurrent aborters, and is reported to have few maternal and neonatal side effects after the immunotherapy having been reported to date. In the present study, we report a rare case of neonatal thrombocytopenia (41000 cells/microl) observed in a female infant delivered by an unexplained habitual aborter. The mother was immunized with her husband's leukocytes once before pregnancy and twice at the 5th and 6th week of her successful pregnancy. Serological studies using mixed passive hemagglutination assays (MPHA) showed that maternal serum did not contain any antibodies which were reactive to 11 platelet-specific antigens, or to granulocyte antigens extracted from 9 persons. Lymphocyte cytotoxicity tests, however, showed that maternal serum but not infant serum had anti-HLA antibodies against both paternal and infant lymphocytes. Moreover, the maternal serum was found to have anti-HLA IgGs against platelet antigens extracted from the father and the infant. It is highly likely that this case of neonatal thrombocytopenia was caused by transplacental perfusion of maternal anti-HLA antibodies whose production was induced or enhanced by the allogenic leukocytes immunizations.

Immunosuppressive effect of serum in patients with ovarian carcinoma.

Cell-mediated immune response was measured in 23 patients with ovarian cystadenocarcinoma, 38 patients with benign ovarian tumor, and 44 healthy volunteers. The method used two indexes: the lymphocyte response per unit volume of peripheral blood to phytohemagglutinin (PHA) and the immunosuppressive effect of serum on the response of normal lymphocytes to PHA stimulation. The lymphocyte response per 50 microliter peripheral blood did not differ significantly between patients with ovarian cancer and healthy volunteers. The serum effect, in contrast, differed significantly between malignant and benign ovarian tumors, and was found to increase significantly even when the cancer masses were as small as about 5 x 5 x 5 cm in size, ie, in FIGO Stage I. It is our belief that the measurement of the serum effect in patients with any ovarian tumor enables the early detection of ovarian cancer.

The prognostic value of serum immunosuppressive effect in patients with ovarian cancer.

Sixteen patients who underwent surgery and postoperative chemotherapy for carcinoma of the ovary were studied. Eleven survived more than 18 months without evidence of recurrence, and 5 died more than 5 months after surgery. Serial determinations were made preoperatively and postoperatively of the immunosuppressive effect of the serums of these patients on the response of normal lymphocytes to phytohemagglutinin stimulation. These determinations were plotted for each patient; the shapes of the curves for patients who survived are markedly different from those of patients who died. The prognostic value of these findings is discussed.

Correlation between shrinkage of uterine leiomyoma treated with buserelin acetate and histopathologic findings of biopsy specimen before treatment.

OBJECTIVE: To analyze histopathologic features related to myoma volume reduction after treatment with a GnRH agonist, buserelin acetate, in needle biopsy specimens obtained before treatment. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PATIENT(S): Twenty women with normal menstrual cycles and symptomatic uterine myomas. INTERVENTION(S): Buserelin acetate was administered intranasally (900 micrograms/d) for at least 16 weeks; transcervical needle biopsy of the uterine myoma was done before this treatment. MAIN OUTCOME MEASURE(S): The relation between histopathologic features (degree of cellularity, hyaline change, and collagen content) and the percent decrease in the volume of the largest myoma at 16 weeks measured by magnetic resonance imaging. RESULT(S): The correlation between the degree of hyaline change and the percent decrease in the myoma volume was significant, as was that with the proportion of collagenous tissue in the specimens. CONCLUSION(S): We predicted myoma volume reduction after treatment with a GnRH agonist by histologic analysis of the uterine leiomyoma before treatment.