Opioid needs of terminally ill patients with gynecologic malignancies.

BACKGROUND: Little is known about patterns and predictive factors regarding opioid use for terminally ill patients with gynecologic malignancies. The aim of this study was to elucidate predictors affecting opioid requirements of end-of-life patients with gynecologic malignancies. METHODS: A retrospective study was carried out on patients with gynecological malignancies admitted to our institute and died during the years 2002 to 2012. The association between maximum opioid dose and factors affecting opioid requirements were examined. Data extracted from medical records included age, site of primary cancer, maximum total dose of opioids prescribed over 24 h, the site of recurrence and metastasis, procedures performed during the hospital stay, total number of chemotherapy courses and overall survival. RESULTS: The study identified 189 patients. Most patients had ovarian cancer (42.3 %) followed by cervical cancer (28.0 %) and then corpus malignancy (27.0 %). Opioid requirements decreased with increasing age, especially from the 50s onward. This was particularly marked in cervical cancer patients. In addition, pelvic metastasis was associated with the maximum dose of opioids and the average opioid use was highest in patients with cervical cancer. CONCLUSION: Young age and pelvic invasion were significant predictive factors regarding opioid requirements. Additionally, cervical cancer patients may require more opioids among those with gynecologic malignancies.

A recurrence-predicting prognostic factor for patients with ovarian clear-cell adenocarcinoma at reproductive age.

OBJECTIVES: We retrospectively analyzed the clinicopathological features and evaluated the prognostic indicators of recurrence in 132 patients with clear cell adenocarcinoma (CCC) of the ovary at reproductive age. PATIENTS AND METHODS: Between 1986 and 2011, as a regional population-based study, clinicopathological data on 132 young patients with CCC, collected under the central pathological review system, were subjected to uni- and multivariable analyses to evaluate recurrence-free survival (RFS). RESULTS: The median age was 40 (27-45) years. The median follow-up period for surviving patients was 46.4 months. During the observation period, there were 16 recurrences in 87 patients with stage I tumors (18.4 %), 8 in 17 with stage II (47.1 %), and 16 in 28 with III-IV (57.1 %). Subsequently, 35 patients died of the disease. Those with stage I or II did not reach the median RFS. The median RFS of stage III-IV was 21.6 months. When analysis was confined to stage I patients, there was no significant difference in the RFS of CCC patients between IA and IC(r) (intraoperative capsule rupture) (P = 0.7957). In contrast, CCC patients with IC excluding IC(r) [IC(non-r)] showed a poorer RFS than those with IC(r) (P < 0.0001). In multivariable analysis confined to stage I patients, the substage group was only an independent prognostic factor for RFS [IA vs. IC(non-r)] [hazard ratio (HR) = 9.394; 95 % CI, 1.445-61.070; P = 0.0190]. CONCLUSION: We should keep in mind the greater risk of recurrence in patients with stage IC disease or higher, other than those stage IC patients with intraoperative rupture.

Possible association between stem-like hallmark and radioresistance in human cervical carcinoma cells.

AIM: We aimed to investigate the possibility of an association between a stem-like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells. MATERIAL AND METHODS: Side-population (SP) cells and non-SP (NSP) cells in HeLa cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed Western blot analysis to evaluate the expression of stem cell markers (CXCR4, Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP and NSP cells were injected into nude mice and we assessed subcutaneous tumor formation. To examine tolerance of irradiation, colony formation and apoptosis change were confirmed in the SP and NSP cells. RESULTS: SP cells showed a higher expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP cells were easily induced to undergo apoptosis. SP cells tended to form spheroids and showed a higher level of tumorigenicity compared with NSP cells. In addition, nude mice inoculated with SP cells showed greater tumor growth compared with NSP cells. SP cells showed a higher tumorigenicity and lower apoptotic potential, leading to enhanced radiotolerance. CONCLUSION: Tumor SP cells showed higher-level stem-cell-like characters and radioresistance than NSP cells. SP cells may be useful for new therapeutic approaches for radiation-resistant cervical cancer.

Plasma Exchange in Postpartum Hemorrhage (PPH)-Associated Thrombotic Microangiopathy (TMA): A Case Report.

Thrombotic microangiopathy (TMA) is a rare yet potentially life-threatening condition. The diagnosis is difficult as there are other conditions presenting with features akin to TMA during the peripartum period such as eclampsia, preeclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and antiphospholipid syndrome. A 28-year-old woman with no significant past medical history developed TMA following a massive hemorrhage after an emergency cesarean section at 41 weeks of gestation. This case was finally diagnosed as postpartum hemorrhage (PPH)-associated TMA. The patient fully recovered after plasma exchange therapy. We posit the value of accumulating case reports, given that the documentation on the efficacy of plasma exchange in PPH-associated TMA is limited.

Contrast-enhanced ultrasonography using Sonazoid(®) is useful for diagnosis of malignant ovarian tumors: comparison with Doppler ultrasound.

PURPOSE: The purpose of this study was to assess the usefulness of Sonazoid(®)-enhanced ultrasonography (US) in the diagnosis of ovarian cancer in comparison with Doppler US. METHODS: Twenty-five ovarian tumor patients who were scheduled to undergo surgery were recruited for this study. The day before the operation, each patient was evaluated with color and power Doppler and baseline US during intravenous infusion of Sonazoid. Each lesion was classified as "benign" or "malignant" on the basis of specific criteria for a Doppler signal or Sonazoid-enhanced pattern. The reference standard was the histology of surgically removed adnexal tumors. RESULTS: Twenty patients were diagnosed with malignant tumors (invasive cancer, n = 15; metastatic cancer, n = 1; borderline tumor, n = 4), and the remaining five were diagnosed with benign tumors. Sonazoid-enhanced US correctly depicted the presence or absence of intratumoral blood flow in all patients with an accuracy of 92 %. Color Doppler ultrasound depicted the malignancies with an accuracy of 64 %, and power Doppler ultrasound depicted them with an accuracy of 76 %. CONCLUSION: Our study suggests that Sonazoid-enhanced US is superior to conventional color Doppler US for the diagnosis of malignant ovarian tumors, but not to power Doppler US. The data and their interpretation in our study should be taken with some degree of caution because of the small number of subjects. Further studies involving a larger sample size would be needed to confirm these findings.

Functional interaction between peritoneal mesothelial cells and stem cells of ovarian yolk sac tumor (SC-OYST) in peritoneal dissemination.

OBJECTIVE: In recent years it has been indicated that ecological niches play important roles in the maintenance of cancer stem cells (CSCs). We investigated interactions between peritoneal mesothelial cells and SC-OYST based on the hypothesis that peritoneal mesothelial cells have the potential to provide one of the niches for SC-OYST. METHODS: We divided NOY1 cells into CD133-positive and -negative cells. Using the co-culture of NOY1 and peritoneal mesothelial cells, we compared the expression of CD133, colony formation, and the capacity for migration and invasion. In addition, we assessed the inhibitory effects of AMD3100, a neutralizing antibody against a chemokine receptor (CXCR4). Then, we examined whether AMD3100 affects the tumorigenicity of NOY1-CD133+ cells in vivo. RESULTS: When NOY1 cells were co-cultured with peritoneal mesothelial cells, we observed the high-level expression of CD133. The number of colonies of NOY1-CD133+ cells was 2.4 times that of NOY1-CD133- cells. In contrast, on co-culture with peritoneal mesothelial cells, it was 4.3 times. When NOY1 cells were cultivated in the upper layer and peritoneal mesothelial cells were cultivated in the lower chamber, NOY1-CD133+ cells showed a greater capacity for migration and invasion than NOY1-CD133- cells. By adding AMD3100 to the co-culture systems, the colony formation, migration, and invasion of NOY1-CD133+ cells were inhibited. In addition, AMD3100 inhibited the tumorigenicity of NOY1-CD133+ cells in vivo. CONCLUSIONS: Our data suggest that peritoneal mesothelial cells have the potential to provide one of the niches for NOY1 cells. Investigation of the niches of SC-OYST will help elucidate important targets for therapeutic approaches.

Long-term clinical outcome of patients with recurrent epithelial ovarian carcinoma: is it the same for each histological type?

OBJECTIVE: This study was conducted to estimate the long-term clinical outcome of patients with recurrent ovarian carcinoma (ROC). METHODS: Six hundred three patients with ROC were analyzed in this study. The pathological slides were evaluated under central pathological review. The prognostic significances of clinicopathologic factors were evaluated using both univariate and multivariate analysis. RESULTS: The 5-year overall survival (OS) and postrecurrence survival (PRS) rates were 31.1 and 16.9%, respectively. On stratifying to treatment periods, the PRS has been prolonged over the last decade (year ≥2000) compared with before this period (year ≤1999) (P = 0.0002). In contrast, on stratifying to histological types and treatment periods, in both OS and PRS, the prognosis of patients with the nonmucinous/clear-cell histology, including serous, endometrioid, and other histological types, was significantly improved after 2000 compared with before (year ≤1999) (OS, P = 0.0009; PRS, P < 0.0001). In contrast, that of patients with the mucinous/clear-cell histology did not significantly differ regardless of the treatment period (≥2000 vs ≤1999: OS, P = 0.3887; PRS, P = 0.7617). In multivariate analysis, the stage, period of starting initial treatment, histological type, and the treatment-free interval were independent prognostic factors of a poor OS and PRS (OS/PRS: histological type: mucinous/clear-cell vs nonmucinous/clear-cell: hazard ratio, 1.300/1.498; 95% confidence interval [CI], 1.039-1.626/1.197-1.874). CONCLUSIONS: Despite the continuous administration of treatment for ROC, survival is poor, and the extent of therapeutic progress differs according to the histological type.

Postrecurrent oncologic outcome of patients with ovarian clear cell carcinoma.

OBJECTIVES: To estimate the long-term clinical outcome of patients with recurrent clear cell carcinoma (RCCC) of the ovary in comparison with those with recurrent serous adenocarcinoma (RSAC). PATIENTS AND METHODS: In this study, 113 patients with RCCC and 365 patients with RSAC were analyzed. The pathological slides were evaluated under central pathological review. End points were the overall survival (OS), postrecurrence survival (PRS), and timing of death of mortality cases. RESULTS: The 5-year OS and PRS rates of patients with RCCC were 22.5 and 13.2%, respectively. In both OS and PRS, the prognosis of patients with RCCC was significantly poorer than that of the patients with RSAC (OS: P = 0.0007; PRS: P < 0.0001). Moreover, regardless of the status of the residual tumor (RT) at the initial surgery, the OS and PRS of the patients with RCCC were markedly shorter than those with RSAC (RT [-]: OS, P = 0.0005: PRS, P = 0.0002: RT [+]: OS, P < 0.0001: PRS, P < 0.0001). In multivariable analysis, the histological type was a significantly poorer prognostic indicator for OS and PRS (OS [RCCC vs RSAC]: hazard ratio, 2.302: 95% confidence interval, 1.723-3.076; P < 0.0001: PRS [RCCC vs RSAC]; hazard ratio, 2.353: 95% confidence interval, 1.756-3.155; P < 0.0001). Even in the deceased patients (n = 350), the rate of patients with RCCC dying within 12 months of recurrence was higher than that of RSAC (RCCC, 67.8%; RSAC, 40.7%; [P < 0.0001]). CONCLUSIONS: The long-term clinical outcome of patients with RCCC was extremely poor. We confirmed that RCCC should be investigated as a different malignancy compared with RSAC.

Diagnostic utility of CD117, CD133, SALL4, OCT4, TCL1 and glypican-3 in malignant germ cell tumors of the ovary.

AIM: Primary ovarian malignant germ cell tumors (OMGCTs) are rare and difficult to diagnose. Immunohistochemistry can help in the diagnosis and development of new management strategies. The aim of this study was to investigate the frequency of CD117, CD133, SALL4, OCT4, TCL1 and glypican-3 marker expression in OMGCTs. MATERIAL AND METHODS: We examined the expression of six markers in 87 (85 pure and two mixed OMGCTs) cases of OMGCT using immunohistochemical staining. Staining was graded in a semiquantitative manner as follows: negative (no staining), 1+ (1-30% staining), 2+ (31-60% staining), or 3+ (>60% staining). RESULTS: All 27 dysgerminomas and all 31 YSTs showed CD117 expression, with only nine (29%) positively stained in immature teratomas. SALL4 and glypican-3 were strongly positive in 100 and 79.3%, respectively, of YSTs. All dysgerminomas were positive for OCT4, whereas all YSTs and immature teratomas were negative. 100% of dysgerminomas were positive for TCL1, but all immature teratomas were negative. CD133 expression showed generally the same tendency in the 3 OMGCTs. CONCLUSION: CD117 can be used as a diagnostic marker for dysgerminoma and YST. SALL4 is a more sensitive and specific marker for YSTs than glypican-3. SALL4 and OCT4 are useful in distinguishing YST from dysgerminoma.

Is there any association between retroperitoneal lymphadenectomy and survival benefit in advanced stage epithelial ovarian carcinoma patients?

AIM: The effect of systematic retroperitoneal lymphadenectomy (SRL) remains controversial in patients with advanced epithelial ovarian cancer (aEOC) who are optimally debulked. MATERIAL AND METHODS: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2009. All patients were divided into two groups. Group A (n = 93): (i) patients did not undergo SRL; and (ii) lymph node exploration or sampling was optional. Group B (n = 87): patients underwent SRL. Survival curves were calculated using the Kaplan-Meier method. Differences in survival rates were analyzed using the log-rank test. RESULTS: All pT3-4 aEOC patients were optimally debulked (residual tumor <1 cm). The median age was 55 years (range: 18-84). The 5-year progression-free survival (PFS) rates of groups A and B were 46.7 and 41.9%, respectively (P = 0.658). In addition, the 5-year overall survival (OS) rates were 62.9 and 59.0%, respectively (P = 0.853). Subsequently, there was no significant difference in OS and PFS in the two groups stratified to histological type (serous or non-serous type). Furthermore, there was no significant difference in recurrence rates in retroperitoneal lymph nodes regardless of completion of lymphadenectomy. CONCLUSION: Our data suggest that aEOC patients with optimal cytoreduction who underwent SRL did not show a significant improvement in survival irrespective of each histological type.

Prognostic factors in stage IA-IIA cervical cancer patients treated surgically: does the waiting time to the operation affect survival?

PURPOSE: This study aimed to identify prognostic factors in patients with stage IA-IIA cervical cancer who had undergone radical surgery and clarify whether the waiting time to the operation affected the recurrence and survival outcome. MATERIALS AND METHODS: We retrospectively reviewed the records of 117 patients who underwent surgical resection for stage IA-IIA cervical cancer. Patients were subdivided based on the waiting time from the initial visit to a gynecologist until surgery. Univariate analyses were performed to evaluate factors associated with recurrence-free and overall survival. RESULTS: The mean time from the first visit to surgery was 48 days (range 20-92). Recurrence-free and overall survival rates were not affected by the waiting time to the operation. On univariate analysis, lymph node metastasis (p = 0.003) and lymph-vascular space invasion (p = 0.015) were prognostic predictors of progression-free survival, while the waiting time to the operation was not (p = 0.106). Lymph node metastasis (p = 0.007), lymph-vascular space invasion (p = 0.046), and the histological diagnosis (p = 0.027) were prognostic predictors of overall survival, but the waiting time to the operation was not (p = 0.653). CONCLUSIONS: The waiting time to the operation from the initial visit to surgical intervention does not adversely affect the outcome of cervical cancer within the time frames analyzed in this study. Furthermore, surgery allows the status of the lymph nodes and lymph-vascular space invasion, dependent variables associated with survival, to be assessed accurately.

Establishment of cisplatin-resistant ovarian yolk sac tumor cells and investigation of the mechanism of cisplatin resistance using this cell line.

BACKGROUND: Cisplatin is used as a key drug for ovarian yolk sac tumor (YST), but relapse may occur. Details of the molecular mechanism responsible for cisplatin resistance remain unclear. METHODS: We established cisplatin-resistant ovarian YST cells (NOY1-CR) from parent NOY1. To characterize these cells, we examined cross-resistance to other anticancer drugs. Then, cDNA microarray analysis was performed to quantify gene expression in NOY1 and NOY1-CR cells. The expression of several potential genes related to drug resistance was compared with parent cells by real-time PCR and Western blotting. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm the genetic association with drug resistance. RESULTS: The IC(50) for cisplatin of NOY1-CR was 22.3-fold higher than that for parent cells. NOY1-CR cells showed cross-resistance to some drugs, but not to VP-16 and bleomycin. Microarray analysis identified 315 up-regulated and 412 down-regulated genes in NOY1-CR cells. Knockdown of GSTA1, which was up-regulated in resistant cells, by GSTA1 siRNA restored cisplatin sensitivity in NOY1-CR cells. CONCLUSIONS: Our data suggest the molecular mechanisms of cisplatin resistance and show the potential for GSTA1 to become a novel therapeutic target for cisplatin-resistant ovarian YST.

Strong antibody reaction against glycosphingolipids injected in liposome-embedded forms in beta3GN-T5 knockout mice.

It is known that mutant mice of the beta-1,3-N-acetylglucosaminyltransferase gene (beta3Gn-T5) respond well to T-cell dependent and independent antigens. Here, we examined the effectiveness of anti-ganglioside antibody generation by immunization of beta3Gn-T5 mutant mice with liposome-embedded glycosphingolipids such as GD1a and GT1b. Consequently, the mutant mice showed a more efficient generation of anti-GD1a or anti-GT1b antibodies than wild-type mice in an enzyme-linked immunosorbent assay using sera during immunization. Thus, the beta3Gn-T5 deficient mutant mice proved more responsive than wild-type mice to not only protein antigens, but also to carbohydrates in glycolipids. Furthermore, about 50% of monoclonal antibodies generated using splenocytes of the immunized mutant mice were of the IgG class. Besides general high responsiveness to proteins and glycolipids, it could be expected that the mutant mice of beta3Gn-T5 would be useful in the generation of monoclonal antibodies towards lacto-/neolacto-series glycolipids, since these mutants lack lacto-/neolacto-series glycolipids. In fact, they showed a good serum response in immuno-fluorescence assay with cultured living cells when immunized by glycolipids extracted from ovarian cancer cell lines. These results suggested that beta3Gn-T5 mutant mice are useful for the generation of anti-glycolipid antigens with lacto-/neolacto-core structures expressed in cancer cells.

Identification and characterization of cancer stem cells in ovarian yolk sac tumors.

Recent evidence supports the cancer stem cell theory, that is, that malignant tumors arise from cells termed cancer stem cells or tumor-initiating cells that have the ability to self-renew and are responsible for maintaining the tumor. Cells with marked tumor-initiating capacity have recently been identified in a number of solid tumors. CD133 (PROM1, human prominin-1) has been used as a marker to detect stem cells (progenitor cells) and cancer stem cells (tumor-initiating cells) in various tissues. Ovarian yolk sac tumors (YSTs) are rare and highly malignant. The present study was designed to evaluate the tumor-forming ability of CD133(+) cells in ovarian YST cell lines and to examine the characteristics of CD133(+) cells, such as cell growth and invasiveness. Our data suggest ovarian YST to be maintained by a rare fraction of cancer stem-like cells that express the cell surface marker CD133.

Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo.

Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is bound to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor, and glypicans can regulate the activity of a wide variety of growth and survival factors. We report here that GPC3 was expressed in clear cell carcinoma of the ovary, and not in other carcinomas. To evaluate the phenotype and potential preclinical relevance, we generated an ovarian cancer cell line stably transfected with plasmids encompassing shRNA targeting GPC3. We show that the clear cell carcinoma cell line with silenced GPC3 expression (GPC3 [-]) was more sensitive to paclitaxel than GPC3 (+) cells. In addition, the GPC3 silencing induced sensitization to paclitaxel was associated with the activation of an apoptosis pathway, as shown by flow cytometry. Moreover, we investigated the effect of GPC3 on peritoneal metastases using nude mice. Peritoneal metastases caused by GPC3 (-) were more sensitive to paclitaxel than those caused by GPC3 (+) cells. These results indicate that increased GPC3 expression in a clear cell carcinoma cell line may play a protective role against apoptosis, and so the downregulation of GPC3 may be a potential target to increase sensitivity to paclitaxel-induced apoptosis in clear cell carcinoma.

Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy.

OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that induces tolerance to host immune surveillance within the tumor microenvironment. The present study aimed to investigate IDO expression and its prognostic significance in invasive cervical cancer. METHODS: Immunohistochemical expression of IDO in tumor tissues and its association with clinicopathological factors and survival were analyzed in 112 stage IB-IIB cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy. RESULTS: IDO was diffusely expressed in tumor cells in 29 (26%) cases and focally expressed at the invasive front in 29 (26%) cases, while the other 54 (48%) cases were IDO-negative. IDO expression was positively correlated with clinical stage, lymph node metastasis, and lymph-vascular space invasion, but not with histological type. Patients with diffuse IDO expression had significantly reduced overall survival (OS) and disease-free survival (DFS) compared to patients with no IDO expression. The 5-year OS/DFS rates for the IDO-negative, focally positive, and diffusely positive groups were 92.3%/84.9%, 89.5%/75.8%, and 65.5%/51.7%, respectively. When we analyzed patients with stage IB disease alone (n=67), the OS and DFS for the IDO-diffusely positive group were significantly lower than those for the IDO-negative group. In multivariate analysis, diffuse IDO expression was found to be an independent prognostic factor for impaired OS and DFS. CONCLUSIONS: Diffuse expression of IDO in the tumor obtained from Stage IB-IIB cervical cancer patients who underwent radical hysterectomy was correlated with an unfavorable clinical outcome. These findings suggest that IDO may be a novel post-operative prognostic indicator for stage IB-IIB cervical cancer.

Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells.

OBJECTIVE: Ovarian clear cell carcinoma (CCC) is well known to be highly resistant to platinum-based chemotherapy. Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in only CCC of epithelial ovarian carcinoma subtypes. The purpose of this study was to identify the role of GPC3 in ovarian CCC. METHODS: To evaluate the function of GPC3 in ovarian CCC cells, we generated an ovarian cancer cell line, KOC7C cells stably transfected with plasmids encompassing shRNA targeting GPC3 (shGPC cells), and compared cell growth and the colony-forming ability to control shRNA-transfected cells (shCon cells). RESULTS: We showed that shGPC3 cells significantly increased cell growth and the colony-forming potential compared with shCon cells in 1% serum containing medium with 100 ng/ml IGF-II. Furthermore, these effects were significantly attenuated by pretreatment with 1 µM wortmannin (an inhibitor of PI3K/Akt). CONCLUSIONS: We have demonstrated for the first time the presence of elevated levels of GPC3 protein associated with cell growth inhibition in CCC cells. Our data suggest that GPC3 has the potential to become a novel therapeutic target for ovarian CCC patients.

Assessment of the predictive value of follicular fluid insulin, leptin and adiponectin in assisted reproductive cycles.

PURPOSE: To assess the correlation of intrafollicular insulin, leptin and adiponectin levels with assisted reproductive technologies (ART) outcome. METHODS: This was a retrospective study of 46 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection. Follicular fluid (FF) samples collected at oocyte retrieval were assayed for insulin, leptin and adiponectin levels using enzyme-linked immunosorbent assay, and correlations with ART outcome were analysed. RESULTS: There was no significant correlation between intrafollicular insulin, leptin and adiponectin levels. There was a significant difference in the concentration of insulin (P = 0.007), but not leptin or adiponectin, between pregnant (n = 20) and non-pregnant (n = 26) cycles. Only two pregnancies was observed in the 12 cycles in which the concentration of insulin was greater than 7 mU/l in FF, while 18 pregnancies was observed in the 34 cycles in which the concentration of insulin was less than 7 mU/l (P = 0.043). The significantly high concentration of insulin in FF was observed in non-pregnant cycles of patients with polycystic ovary syndrome (PCOS). CONCLUSIONS: Our results suggest the possible involvement of intrafollicular insulin in folliculogenesis. Insulin resistance-related substances may affect the reproductive process in patients with PCOS.

Taxol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III beta-tubulin.

The prognostic significance of histology has been well established in epithelial ovarian cancer (EOC). Clear cell and mucinous histologies are especially generally accepted to result in an adverse outcome because of their poor chemotherapy response. Previous reports suggested that class III beta-tubulin induced taxol resistance in association with a reduced effect on microtubule dynamic instability. Thus, this study aimed to evaluate class III beta-tubulin expression and examine whether the protein level of class III beta-tubulin was correlated with the histological difference in chemosensitivity. Class III beta-tubulin expression in EOC tissues (n = 80) was immunohistochemically scored into 4 groups (-, +/-, +, ++). High-level (+, ++) class III beta-tubulin expression was detected in 30 of 35 clear cell carcinomas, in 8 of 10 mucinous carcinomas, 5 of 11 endometrioid carcinomas, and 5 of 24 serous carcinomas. Nineteen patients were evaluable for response. In 5 responders, high-level class III beta-tubulin expression was not detected. On the other hand, it was detected in 10 of 14 nonresponders. In some ovarian cancer cell lines, we evaluated class III beta-tubulin expression by Western blot analysis. Class III beta-tubulin expression in nonserous carcinoma tended to be higher than that in serous carcinoma. Taxol-resistant SKOV cells showed high-level class III beta-tubulin expression compared with wild-type SKOV cells. Taxol sensitivity differing among histological subtypes in EOC is associated with the expression of class III beta-tubulin.

Long-term outcome and prognostic factors for yolk sac tumor of the ovary.

Yolk sac tumors of the ovary (YST) are rare and highly malignant tumors occurring in children and young adults. Because of its rarity, YST prognostic factors remain unclear. Our purpose was to evaluate the prognostic factors in YST. We performed a retrospective review of 36 patients with pure YST from 1986 to 2006. The 5-year overall survival and progression-free survival were 66.6% and 68.8%, respectively. Patients with stage I-II disease had a more favorable prognosis than those with stage III-IV (p < 0.05). Those with an ascites volume of less than 100 ml or a residual tumor measuring less than 1 cm had improved to a relatively good prognosis. Neither serum AFP level nor age had any significant correlation with the prognosis in this study. In conclusion, the FIGO (International Federation of Gynecology and Obstetrics) stage, ascites volume and residual tumor size tended to affect the prognosis of YST.