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ABSTRACT: The purpose of the present study was to determine the incidence of increased levels of D-dimer and associated factors in preoperative patients with gynecological cancer. Furthermore, we determined the incidence and risk factors associated with preoperative venous thromboembolism (VTE). Overall, 456 patients with invasive gynecological cancer scheduled to undergo surgery were recruited. Preoperative plasma D-dimer levels were measured and patients whose plasma D-dimer concentration exceeded the pre-set cut-off value underwent computed tomography scanning. The incidence of elevated D-dimer and VTE was identified as significantly higher in patients with ovarian cancer. Multivariate analysis revealed that advanced age, low hemoglobin levels and elevated C-reactive protein (CRP) levels were independent factors for preoperative elevations in plasma D-dimer levels. Advanced age was an independent risk factor for preoperative VTE. Massive ascites and the presence of co-morbidities were independent risk factors for preoperative VTE in ovarian cancer. Advanced age and stage were independent risk factors for preoperative VTE in endometrial cancer. Advanced age was an independent risk factor for preoperative VTE in cervical cancer. Plasma D-dimer levels and the incidence of preoperative VTE were higher in patients with ovarian cancer compared with those with other gynecological cancers. Advanced age, low hemoglobin levels and elevated CRP levels were significant factors associated with elevated plasma D-dimer levels and age was an independent risk factor for preoperative VTE in gynecological cancer.
Oncology letters 01/2013; 5(1):299-304. · 0.11 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the changes in plasma soluble fibrin (SF) levels over time in gynecologic cancer patients following surgery. Furthermore, we examined the duration of the coagulation stage and determined a suitable duration for which thromboprophylaxis with anticoagulant agents should be administered. We retrospectively studied 311 patients with invasive gynecologic cancer who underwent surgery at Okayama University Hospital, Japan. The plasma SF levels were measured serially prior to the operation and on postoperative days 0, 1, 3, 5, 7, 10, 14, 21 and 28. The plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. The SF levels of patients with venous thromboembolism (VTE) were significantly different from those of VTE-negative patients on postoperative days 0-10. The SF levels on each day did not significantly differ between patients treated with chemical anticoagulants and those treated mechanically. The plasma SF levels were elevated (≥7.0 μg/ml) in 159 of the 311 patients (51.1%) on one of the days when these levels were measured. Among the patients with elevated plasma SF levels, 110 patients (69.2%) peaked on days 0-3 and only 9 patients (5.7%) peaked on days 21-28. Although only 1 of the 14 patients (7.1%) who showed peak levels on day 14 had undergone chemotherapy following surgery, 8 of the 9 patients (88.9%) whose levels peaked on days 21-28 had undergone chemotherapy following surgery (P= 0.0002). In conclusion, the plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. These levels peaked within 14 days of surgery in most cases. Therefore, chemical thromboprophylaxis may be administered for at least up to 14 days following surgery.
Oncology letters 11/2012; 4(5):1122-1124. · 0.11 Impact Factor
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ABSTRACT: PURPOSE: The purpose of this study was to investigate the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MR imaging and of the maximum standardized uptake value (SUVmax) derived from PET/CT imaging of the primary tumour in patients with endometrial cancer. METHODS: SUVmax reflects the highest tumour metabolism rate and ADCmin reflects the highest cellularity, and both parameters have been used for tumour grading and prediction of prognosis. The correlations between prognosis and SUVmax and ADCmin of the primary tumour were determined in 131 patients with endometrial cancer. The patients were divided into groups based on ADCmin and SUVmax cut-off values to predict recurrence and survival, which were derived from receiver operating characteristic curves. Disease-free survival (DFS) and overall survival (OS) of the groups were analysed using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test. RESULTS: The median DFS and OS times of all patients were 19.2 and 20.5 months (follow-up periods 1-70 months for both DFS and OS), respectively. Patients with high SUVmax had significantly lower DFS (P < 0.0001) and OS (P = 0.0092) than patients with low SUVmax. Multivariate analysis showed that high SUVmax was an independent prognostic factor for both DFS (P = 0.0161) and OS (P = 0.0232). CONCLUSION: The SUVmax of the primary tumour derived from PET/CT imaging could be an important prognostic indicator of recurrence and survival in patients with endometrial cancer.
European Journal of Nuclear Medicine 09/2012; · 4.53 Impact Factor
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ABSTRACT: OBJECTIVE: The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS: A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS: Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122×10(-3)mm(2)/s, 0.852×10(-3)mm(2)/s, 0.670×10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS: The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.
Gynecologic Oncology 08/2012; · 3.89 Impact Factor
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ABSTRACT: We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells, and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the anti-tumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.
Cancer biology & therapy 05/2012; 13(7):559-66. · 2.64 Impact Factor
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ABSTRACT: The purpose of the present study was to determine possible factors associated with parametrial spread in patients with stage IB1 cervical cancer and define parameters associated with a low risk for parametrial spread, in order to identify candidates for less radical surgery.
We retrospectively reviewed 200 patients with stage IB1 cervical cancer who had undergone radical hysterectomy (class III) and pelvic lymphadenectomy.
Overall, 20 (10.0%) of the 200 patients revealed parametrial spread, of which 11 (55%) had only direct microscopic extension of the disease, 3 (15%) had only disease spread to parametrial lymph nodes, 1 (5%) had both direct microscopic extension and disease spread to parametrial lymph nodes, and 5 (25%) had only tumor emboli within the lymph vascular channels in the parametrial tissue. Elderly age, depth of invasion, tumor size, lymph vascular space invasion (LVSI), positive pelvic nodes, and ovarian metastasis were significantly associated with parametrial involvement. The multivariate analysis model included factors that could be determined by a cone biopsy and showed LVSI, deep stromal invasion, and elderly age to be the independent predictors of parametrial involvement. Ninety-one patients had a depth of invasion of ≤10 mm and no LVSI, of which only 1 (1.1%) had parametrial involvement. When patients aged ≤50 years were further stratified into those with a depth of invasion of ≤10 mm and no LVSI, parametrial involvement was found to be 0.0% (0/68).
Patients with a tumor depth of invasion of ≤10 mm, no LVSI, and aged ≤50 years, could be considered for less radical surgery such as modified radical hysterectomy or simple hysterectomy with pelvic lymphadenectomy.
Gynecologic Oncology 06/2011; 122(3):491-4. · 3.89 Impact Factor
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ABSTRACT: Although anthracyclines are considered as being among the most potent chemotherapeutic agents for endometrial carcinoma, the majority of institutions in Japan prefer a combination of paclitaxel and carboplatin (TC) for treating this disease. We retrospectively evaluated the efficacy and feasibility of combined paclitaxel, pirarubicin, and carboplatin (TPC) therapy for endometrial carcinoma.
Thirty-nine patients with high/intermediate postoperative recurrence risks or with advanced disease received combination chemotherapy consisting of paclitaxel (150 mg/m(2)), pirarubicin (35 mg/m(2)), and carboplatin [area under the concentration time curve (AUC = 4)] from 2001 to 2006 at Okayama University Hospital. Treatment cycles were repeated every 3 weeks, and three to nine cycles were administered according to patient risk.
The 1-year overall survival (OS) and progression-free survival (PFS) rates were 94.9% and 84.6%, respectively, and the 3-year OS and PFS rate was 81.3%. Hematologic toxicities >grade 3 were: anemia 30.8%; leukopenia 84.6%; thrombocytopenia 20.5%. Neutropenia was common, and administration of granulocyte colony-stimulating factor (G-CSF) was necessary in 87.9% of treatment courses. Although grade 3 or 4 neutropenia was unavoidable, we could administer TPC therapy safely and without delay with G-CSF support. Gastrointestinal and neurological toxicity were less severe and less frequent compared with TC, and no cardiac toxicity was observed.
The 3-year PFS and OS rates even in high-risk patients were satisfactory, and we confirmed the feasibility of using this regimen for treating endometrial carcinoma.
International Journal of Clinical Oncology 10/2010; 15(5):476-83. · 1.41 Impact Factor
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ABSTRACT: Few reports delineate the pharmacokinetics of combination chemotherapy with paclitaxel and carboplatin in hemodialysis (HD) patients with epithelial ovarian cancer. However, the optimal carboplatin dose and the timing of HD have yet to be elucidated. We presented a case of an advanced-stage epithelial ovarian cancer patient with chronic renal failure requiring HD. After 4 courses of combination chemotherapy consisting of paclitaxel and carboplatin, a partial response was obtained; therefore, she underwent interval debulking surgery. Paclitaxel was administered for 3 h at a dose of 150 mg/m(2), and carboplatin was administered for 1 h at a dose of 4-7 area under the concentration/time curve (AUC), which was calculated by the Calvert formula. HD was initiated 24 h after the start of administration of carboplatin and performed for a period of 3 h. Pharmacokinetic studies showed that the AUCs of free platinum and paclitaxel were 3.48-5.55 mg·min/ml and 13.5 μg·h/ml, respectively. Combination chemotherapy consisting of paclitaxel and carboplatin is a feasible approach to improving the treatment outcome of epithelial ovarian cancer patients with chronic renal failure requiring HD. The measurement of free platinum is useful in determining the optimal dose of carboplatin in order to obtain an adequate AUC. Determining the dose of carboplatin according to the Calvert formula and initiating HD after 24 h would ensure a favorable therapeutic effect with limited side effects.
Oncology letters 05/2010; 1(3):511-513. · 0.11 Impact Factor
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ABSTRACT: Proteoglycans are ubiquitous components of the extracellular matrix and cell surface, and may mediate tumor progression and metastasis. The aim of this study was to evaluate the expression of syndecan-1 and versican in epithelial ovarian cancer. We immunohistochemically evaluated the expression of syndecan-1 and versican in 111 patients with epithelial ovarian cancer, and analyzed the correlation of this expression with various observed clinicopathological features, including patient outcome. There is a significant correlation between primary and metastatic sites with respect to syndecan-1 and versican expression. Epithelial syndecan-1 expression was significantly lower in patients with advanced disease. Epithelial versican expression was significantly higher in patients with early disease, especially in clear cell adenocarcinoma patients. Stromal syndecan-1 and versican expression was significantly higher in patients with advanced disease. Multivariate analysis showed that negative epithelial syndecan-1 expression was an independent prognostic factor for progression-free survival. Stromal syndecan-1 and versican co-expression was of borderline significance for progression-free and overall survival. Loss of epithelial syndecan-1 expression and induction of stromal syndecan-1 and versican expression may be associated with tumor progression in epithelial ovarian cancer. Syndecan-1 and versican expression status can serve as an indicator of prognosis in patients with epithelial ovarian cancer.
Oncology Reports 04/2010; 23(4):917-25. · 1.84 Impact Factor
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ABSTRACT: The purpose of the present study was to identify prognostic factors and patterns of recurrence in patients with stage IB-IIB cervical adenocarcinoma who had undergone radical surgery and to compare these patterns with those observed in squamous cell carcinoma (SCC) patients.
We retrospectively reviewed 303 patients (97 with adenocarcinoma and 206 with SCC) with stage IB-IIB cervical cancer who had undergone radical hysterectomy and pelvic lymphadenectomy.
In the case of the adenocarcinoma patients, lymph node metastasis and parametrial invasion were independent indicators of disease-free survival, whereas lymph node metastasis was the only independent prognostic factor for the overall survival of the patients. The sites of recurrence did not significantly differ between the adenocarcinoma and SCC patients. In parametrium-positive patients, adenocarcinoma was found to be an independent prognostic factor for disease-free survival. In patients with positive pelvic lymph node, adenocarcinoma was found to be an independent prognostic factor for both disease-free and overall survival.
Adenocarcinoma was found to be an independent prognostic factor for survival in patients with positive pelvic node or parametrial extension. Furthermore, the patterns of recurrence did not differ significantly between the adenocarcinoma and SCC patients.
Journal of Surgical Oncology 04/2010; 101(5):413-7. · 2.10 Impact Factor
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ABSTRACT: Endometrial carcinomas producing α-fetoprotein (AFP) are extremely rare. We report a case of AFP-producing, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. A 59-year-old multiparous woman presented with abdominal swelling. The serum level of AFP was 1292.8 ng/ml. Magnetic resonance images of the pelvis showed a markedly enlarged uterus, with a tumor growing exophytically within the endometrial cavity. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The histopathological examination demonstrated a Stage IIA, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. The endometrioid adenocarcinoma cells were partly positive for AFP immunoreactivity. The patient received adjuvant chemotherapy and was disease-free 60 months after the operation. This case confirms the existence of AFP-producing endometrioid adenocarcinomas without hepatoid features.
Oncology letters 03/2010; 1(2):243-245. · 0.11 Impact Factor
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ABSTRACT: The insulin-like growth factor I receptor (IGF-IR) is exceptionally overexpressed in many cervical-cancer-derived cell lines. It is postulated that a decrease of p53 protein levels due to human papillomavirus (HPV) infection may contribute to the up-regulation of IGF-IR expression in cervical cancer cells because transcription of IGF-IR is strictly down-regulated by p53. To evaluate this fact in clinical cervical cancer specimens, we checked the expression levels and activated status of IGF-IR by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens obtained by conization or hysterectomy were stained with anti-IGF-IR and with an antibody recognizing phosphorylated tyrosine at its c-terminus. The expression levels of IGF-IR were significantly high in cervical intraepithelial neoplasia (CIN) III and invasive cancer specimens. Phosphorylation of IGF-IR was promoted in all CIN and invasive cancer specimens, and its intensity was related to the promotion of lesions. Interestingly, IGF-IR overexpression was missing in the basal layer of CIN I and II lesions, whereas it was evenly distributed in CIN III and invasive cancer lesions. This IGF-IR overexpression pattern may be utilized in the diagnosis of HPV infection status in CIN lesions.
Acta medica Okayama 09/2008; 62(4):251-9. · 0.84 Impact Factor
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ABSTRACT: The purpose of the present study was to identify prognostic factors and recurrent patterns in pathologic parametrium-positive patients with stage IB-IIB cervical cancers treated by radical surgery and adjuvant therapy.
The patient population consisted of 84 individuals presenting with stage IB-IIB cervical cancers and histologically proven parametrial invasion. All these patients were treated postoperatively with adjuvant external whole pelvic irradiation, combination chemotherapy, or chemoradiotherapy.
The 5-year disease-free survival rate was found to be 67.2% and 5-year overall survival rate, 75.4%. Multivariate analysis revealed that vaginal invasion (p=0.0008), lymph node metastasis (p=0.002), and non-squamous histology (p=0.010) were independent indicators of the disease-free survival rates and that the vaginal invasion (p=0.009) and lymph node metastasis (p=0.011) were independent prognostic factors for the overall survival rates. The 5-year overall survival rate was approximately 90% for patients without these risk factors. Disease recurrence was observed in 26 patients (31.0%) with a median time of 16.5 months (range, 5-59 months) from the surgery. Hematogenous recurrences, including those in the lung, liver, and bone, were significantly higher in patients with non-squamous cell carcinomas (p=0.008). Distant lymph node recurrences were significantly higher in patients with positive pelvic lymph node and vaginal invasion (p=0.004 and p=0.023, respectively). Pelvic recurrences were significantly higher in patients with vaginal invasion (p=0.026).
Vaginal invasion and lymph node metastasis are independent indicators for disease-free and overall survival rates in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy. The survival rate is excellent in the patients without these risk factors. Hematogenous recurrence may be evident in patients with non-squamous cell carcinomas.
Gynecologic Oncology 07/2007; 105(3):757-61. · 3.89 Impact Factor
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ABSTRACT: The purpose of this study was to determine the value of prognostic factors and to assess the efficacy of adjuvant chemotherapy in patients with endometrial cancer confined to the uterus.
Patients surgically stage IB, IC and II endometrial cancer according to the International Federation of Gynecology and Obstetrics were enrolled in this study. Stage IIIA tumors with positive peritoneal cytology, in the absence of other evidence of extra uterine disease, were also included.
One hundred and sixty-seven patients fulfilled the eligibility criteria and 58 patients (34.7%) underwent combination chemotherapy. Disease recurrence occurred in 10 patients within a median time of 17 months. Histologic grade 3 was an independent prognostic factor for both disease-free and overall survival rates. Fourteen of 23 patients with histologic grade 3 tumors received adjuvant chemotherapy consisting of cyclophosphamide (or etoposide), epirubicin and cisplatin (in 1989-1999) or paclitaxel, pirarubicin and carboplatin (in 2000-2002). The 5-year disease-free and overall survival rates for these individuals was 92.3%, a value significantly higher than those in patients who had not undergone chemotherapy (50.0%).
Histologic grade of 3 is an independent prognostic marker in patients with endometrial cancer confined to the uterus and adjuvant chemotherapy might improve the survival rates in these patients.
European Journal of Obstetrics & Gynecology and Reproductive Biology 04/2007; 131(1):76-80. · 1.97 Impact Factor
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ABSTRACT: To discuss the usefulness of chemotherapy in high-risk early-stage endometrial cancer and the best chemotherapy regimen.
External radiation therapy has been successfully used to prevent local recurrence; however, it does not improve the overall survival and it increases the incidence of late toxicity. A recent randomized study revealed that adjuvant platinum-based combination chemotherapy might be a suitable alternative to radiotherapy for high-risk early-stage endometrial cancer. The optimal regimen is still in question because combinations of doxorubicin-cisplatin and paclitaxel-doxorubicin-cisplatin cause significant toxicity. The combination of paclitaxel-carboplatin may be better than doxorubicin-cisplatin with regard to toxicities.
Radiation treatment following surgery has been the standard adjuvant therapy for endometrial cancer for a long time. Radiotherapy decreases the local recurrence rates; however, a significant impact on the overall survival has not been demonstrated. The usefulness of adjuvant chemotherapy has been demonstrated by only a little evidence. Nonetheless, we are encouraged by a recent randomized study. In light of the excellent outcomes associated with early-stage endometrial cancer, it is important to conduct another large randomized trial based on standardization of high-risk criteria to evaluate the efficacy of adjuvant chemotherapy.
Current Opinion in Obstetrics and Gynecology 03/2007; 19(1):42-7. · 2.38 Impact Factor
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ABSTRACT: We have routinely performed staging with pelvic and/or paraaortic lymphadenectomy in patients with endometrial cancer having moderate to high risk for lymph node metastasis. The aim of this study was to investigate the risk factors for the occurrence of early and late postoperative complications in patients managed primarily by surgery in our institution.
Two-hundred and fifty-nine consecutive cases of endometrial cancer were enrolled in the study. Past history, body mass index, type of surgery, intraoperative findings, and follow-up information were collected from patient charts. Of these, 200, 127, and 30 patients underwent systematic pelvic lymphadenectomy, systematic paraaortic lymphadenectomy, and radical hysterectomy, respectively. The median numbers of dissected pelvic and paraaortic lymph nodes were 32 and 14, respectively.
None of the complications resulted in death. Of the study population, 36 early complications and 34 late complications occurred. Overall 65 patients (25.1%) had at least one complication. Multivariate analysis revealed that a longer operative time and paraaortic lymphadenectomy were independent predictors for the occurrence of early and late postoperative complications, respectively.
Since the therapeutic value of lymphadenectomy is still under evaluation, the indications for systematic pelvic and paraaortic lymphadenectomy should be carefully considered.
European Journal of Obstetrics & Gynecology and Reproductive Biology 03/2006; 124(2):222-6. · 1.97 Impact Factor
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European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2005; 121(1):81-85. · 1.97 Impact Factor
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ABSTRACT: Perlecan is a major heparan sulfate proteoglycan of basement membrane (BM) and binds to various cytokines and growth factors via its heparan sulfate glycosaminoglycan (HS-GAG) chains. The aim of this study was to investigate BM HS-GAG expression in invasive cervical cancers. We investigated the expression of BM HS-GAG by immunohistochemistry in 143 invasive cervical cancers and 30 metastatic lymph node samples, and analyzed correlations with various clinicopathological features. Furthermore, the gene expression levels of heparanase were assessed by RT-PCR in 52 invasive cervical cancer samples. HS-GAG expression index was significantly lower in cases of lymph node metastasis (p=0.01). There was no association between HS-GAG expression status and patient outcome. HS-GAG expression index in metastatic pelvic lymph nodes was significantly higher than that in the primary site (p=0.019). Furthermore, HS-GAG expression index was significantly lower in cases where heparanase mRNA expression was detectable (p=0.033). Heparanase mRNA expression is associated with the loss of BM HS-GAG expression, which is closely related to lymph node metastasis in invasive cervical cancers.
Oncology Reports 08/2005; 14(1):89-92. · 1.84 Impact Factor
