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.

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.

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.

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.

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.

Phase II study of irinotecan plus doxorubicin for early recurrent or platinum-refractory ovarian cancer: interim analysis.

The aim of this study was to evaluate the efficacy and toxicity of irinotecan and doxorubicin in the treatment of patients with early recurrent or platinum-refractory ovarian cancer. Nineteen woman from five different institutions were treated. Two patients had platinum-refractory cancer, 11 had platinum-resistant disease, and 6 had platinum-sensitive tumors. An intravenous infusion of Irinotecan (50 mg/m(2)) was given on days 1, 8, and 15, while doxorubicin (40 mg/m(2)) was administered as an intravenous bolus on day 3. This treatment schedule was repeated every 4 weeks. Among the 13 patients defined as having platinum-refractory/platinum-resistant disease, 4 patients achieved a clinical response (30.8%, 95% CI: 9.1-61.4), while only one of 6 patients defined as having platinum-sensitive disease achieved a clinical response (16.7%, 95% CI: 0.4-64.1). Leukopenia and neutropenia were the major dose-limiting toxicities. Grade 3 or 4 leukopenia and neutropenia were noted in 24 (48%) and 33 (66%) of the courses, while febrile neutropenia occurred in 2 courses. Five patients (26%) had grade 2 or worse diarrhea during 7 courses. Our data demonstrated that this regimen might be comparable to standard approved agents in patients with early recurrent or platinum refractory ovarian cancer.

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.

Clinical outcomes of uterine sarcomas: results from 14 years worth of experience in the Kinki district in Japan (1990-2003).

To review clinical outcomes and therapeutic varieties, we were invited to submit data from the patients who were treated for uterine sarcomas in Japan from 1990 to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36 (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46 (47.4%) with CS. Median age at diagnosis was 59 (21-85) years. Clinical stages based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34 (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period for all patients was 13 (1-108) months and median disease-free period was 9 (0-96) months. The 1-year survival rate and disease-free survival (DFS) rate were calculated in patients with all sarcomas (overall survival [OAS], 61.3%; DFS, 46.6%). Statistical analysis showed that younger age (less than 50 years), early stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and radical hysterectomy [RH]) were associated with significantly better OAS. Histologic types did not affect the survival period. In conclusion, aggressive surgery including EH or RH at the time of initial operation offers the possibility of prolonged survival.

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.

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.

Usefulness of positron emission tomography for diagnosis of malignancy in a calcified lesion: a case report.

When calcified lesions in the liver or spleen are found during follow-up of patients who have undergone debulking surgery and chemotherapy for advanced ovarian carcinoma, it is very difficult to differentiate recurrent cancer from secondary change after chemotherapy. We present here a patient in whom calcified lesions in the liver and spleen were diagnosed as malignancy on the basis of a preoperative PET study. Malignancy was confirmed by histologic examination after surgery.

Production of activin A in hyperplasia and adenocarcinoma of the human endometrium.

OBJECTIVES: To examine the possible localization and production of activin A in human normal endometrium, endometrial hyperplasia, and adenocarcinoma tissues. METHODS: Human endometrial tissues were collected from 45 patients who were undergoing abdominal hysterectomy. Tissue sections were stained with monoclonal antibodies against the inhibin/activin alpha- and beta A-subunits and activin A using an avidin-biotin-peroxidase complex technique. Concentrations of activin A and inhibin A in tissue extracts of the endometrial tissues were measured using enzyme-linked immunosorbent assays (ELISAs). The expressions of the inhibin alpha-subunit and activin beta A-subunit messenger RNA (mRNA) in the endometrial tissues were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. RESULTS: No immunostaining with an antibody against the inhibin alpha-subunit was observed in human normal endometrium, endometrial hyperplasia, and adenocarcinoma. By contrast, immunostaining for the activin beta A-subunit and activin A was observed in the cytoplasm of glandular cells in normal endometrium, endometrial hyperplasia, and tumor cells of endometrial adenocarcinoma. The percentages of stained cells in endometrial adenocarcinoma were higher than those in normal endometrium. Also, the percentages of stained tumor cells with poor differentiation were higher than those with good and moderate differentiation of the endometrium. The stromal cells in normal endometrium, endometrial hyperplasia, and adenocarcinoma were weakly immunoreactive with antibodies against the beta A-subunit and activin A. Immunoreactivity of activin A in tissue extracts from normal endometrium and endometrial adenocarcinoma was detected by the two-site ELISA. Immunoreactivity of activin A was significantly higher in adenocarcinoma than in normal endometrium. On the other hand, the immunoreactive inhibin A was not detected. The expression of the alpha-subunit mRNA in endometrial tissues was demonstrated as the RT-PCR products migrated at 905 bp and the PCR products of the beta A-subunit showed a band at 366 bp. CONCLUSIONS: It is suggested that activin A, but not inhibins, are produced by endometrial tissues. The amounts of produced activin A were higher in adenocarcinoma tissues than in normal endometrium. Activin A might be involved in human endometrial tumorigenesis.

Positron emission tomography using 2-[(18)F] fluoro-2-deoxy-D-glucose in the diagnosis of uterine leiomyosarcoma: a case report.

The preoperative diagnosis of uterine leiomyosarcoma (LMS) is very difficult. Magnetic resonance (MR) imaging is usually used for it; however, precise diagnosis by MR imaging is limited to typical LMS with coagulative tumor cell necrosis. We presented a case of LMS that was diagnosed preoperatively by positron emission tomography (PET) using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG).

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.

Interleukin-11 enhances cell survival of decidualized normal human endometrial stromal cells.

High expression of interleukin-11 (IL-11) and the IL-11 receptor alpha chain in developing decidual cells in mice has been reported, and mice lacking IL-11 receptor expression have been reported to show impaired implantation owing to defective decidualization. However, the direct effect of IL-11 on endometrial stromal cells has not been studied. In this study, we examined the direct effects of IL-11 on normal human endometrial stromal cells using an in vitro decidualization assay system. IL-11 enhanced cell viability and prolactin secretion of 8-Br-cAMP-induced decidualized cells but not of non-stimulated stromal cells. IL-11 dose-dependently enhanced the viability of stromal cells co-stimulated with 8-Br-cAMP and IL-11 without any significant effect on prolactin secretion from the cells. The extracellular matrix did not affect the effect of IL-11 on the viability of 8-Br-cAMP-stimulated stromal cells. These results indicate that IL-11 enhances the viability of 8-Br-cAMP-stimulated stromal cells and of decidualized stromal cells, and that the cell survival signals generated by IL-11 are independent of those generated by the extracellular matrix. IL-11 produced locally in decidual tissues may enhance the viability of decidualized stromal cells and possibly protect against cell damage during embryo implantation and trophoblastic invasion.