OBJECTIVE: The purpose of this study was to investigate whether selective cyclooxygenase (COX) inhibitors promote paclitaxel-induced apoptosis in taxane-resistant ovarian cancer cells by suppressing MDR1/P-glycoprotein (P-gp) expression. METHODS: Taxane-resistant ovarian cancer cells were cultured with paclitaxel alone or combined with a selective COX inhibitors. The expression patterns of MDR1/P-gp and the ability of COX inhibitors to inhibit growth of taxane-resistant ovarian cancer cells were measured. The efficacy of prostaglandin E2 (PGE2) supplementation was measured to evaluate the mechanisms involved in suppressing MDR1 gene expression. RESULTS: P-gp was upregulated in taxane-resistant ovarian cancer cells compared to paired paclitaxel-sensitive ovarian cancer cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that selective COX inhibitors significantly enhanced the cytotoxic effects of paclitaxel in taxane-resistant ovarian cancer cells via a prostaglandin-independent mechanism. These increased apoptotic effects were further verified by measuring an increased percentage of cells in sub-G1 stage using flow cytometry. Selective COX inhibitors suppressed MDR1 and P-gp expression. Moreover, combined treatment with paclitaxel and selective COX inhibitors increased poly (ADP-ribose) polymerase (PARP) cleavage in taxane-resistant ovarian cancer cells. CONCLUSION: Selective COX inhibitors significantly promote paclitaxel-induced cell death in taxane-resistant ovarian cancer cells in a prostaglandin-independent manner. COX inhibitors could be potent therapeutic tools to promote paclitaxel sensitization of taxane-resistant ovarian cancers by suppressing MDR1/P-gp, which is responsible for the efflux of chemotherapeutic agents.
Apoptosis ; Cell Death ; Cyclooxygenase Inhibitors ; Dinoprostone ; Flow Cytometry ; Ovarian Neoplasms ; P-Glycoprotein ; Paclitaxel ; Prostaglandin-Endoperoxide Synthases ; Tetrazolium Salts ; Thiazoles

OBJECTIVE: The purpose of this study was to compare the in vivo anti-tumor efficacy of a mucoadhesive, lipid-based, oral paclitaxel formulation (DHP107) with traditional, intraperitoneal (IP) paclitaxel using an orthotopic mouse model of chemotherapy-sensitive SKOV3ip1 ovarian cancer. METHODS: To determine the optimal therapeutic dose of oral paclitaxel, DHP107 was administered per os to female athymic nude mice at 0, 25, or 50 mg/kg twice per week. Control mice received 100 microL saline once per week. IP injections of paclitaxel at 5 mg/kg once per week were used for comparison. To evaluate the potential therapeutic effect of metronomic DHP107 chemotherapy, mice received DHP107 50 mg/kg once per week per os, which was compared with 25 mg/kg twice per week and with vehicle-treated controls. RESULTS: Low-dose DHP107 (25 mg/kg) twice per week was as effective as IP paclitaxel (5 mg/kg once a week) but high-dose DHP107 (50 mg/kg once per week) was less effective at inhibiting tumor growth in an orthotopic mouse model (88%, 82%, and 36% decrease in tumor weight, respectively). Mice that received 25 mg/kg DHP107 twice per week or 50 mg/kg DHP107 once per week per os had a significant decrease in tumor weight compared with vehicle-treated controls (p<0.01, both doses). CONCLUSION: Metronomic oral chemotherapy with DHP107 showed anti-tumor efficacy in vivo similar to IP paclitaxel in an orthotopic mouse model.
Animals ; Drug Therapy ; Female ; Humans ; Mice* ; Mice, Nude ; Ovarian Neoplasms* ; Paclitaxel* ; Tumor Burden

OBJECTIVE: To assess the role of fertility preservation in the treatment of patients with early epithelial ovarian cancer (EOC). METHODS: We retrospectively analyzed the medical records of 21 patients with early EOC from January 1995 to December 2006. All eligible patients with a strong desire to preserve fertility were younger than 35 years and underwent fertility-sparing surgery with or without adjuvant chemotherapy. RESULTS: Twenty-one eligible patients with a median age of 26.7 years (range, 20 to 33 years) were identified, and the mean follow-up period was 43 months (range, 5 to 86 months). Only one patient with stage IC recurred 34 months after the first operation. A total of five patients were able to become pregnant at least once after the first fertility preserving treatment, with or without adjuvant chemotherapy. All five patients succeeded in full-term vaginal delivery with healthy infants. No patients died of their disease. CONCLUSION: Fertility preserving treatment in patients with early EOC can be considered as a proper treatment strategy in patients with early EOC, who have the strong desire for fertility preservation.
Chemotherapy, Adjuvant ; Fertility ; Fertility Preservation ; Follow-Up Studies ; Humans ; Infant ; Medical Records ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Retrospective Studies

OBJECTIVE: To evaluate the occurrence of residual or recurrent disease after conization for adenocarcinoma in situ (AIS) of the uterine cervix. METHODS: Medical records of 99 patients with a histologically diagnosis of AIS of the uterine cervix by conization between 1991 and 2008 were reviewed retrospectively. RESULTS: Seventy eight of 99 patients (78.8%) had negative and 18 (18.2%) had positive resection margins of the conization specimen, and 3 (3.0%) had unknown margin status. Of the 78 patients with negative margins, 45 underwent subsequent hysterectomy and residual AIS were present in 4.4% (2/45) of patients. Ten of the 18 patients with positive margins received subsequent hysterectomy and 3 patients (30%) had residual AIS. Twenty-eight patients had conservative treatment and during the median follow-up time of 23.5 months (range, 7 to 124 months), only one patient (3.6%) had recurrent AIS and was treated with a simple hysterectomy. Eight patients became pregnant after conization, 4 of them delivered healthy babies, one had a spontaneous abortion and 3 were ongoing pregnancies. CONCLUSION: Patients with positive resection margins after conization for AIS of the uterine cervix are significantly more likely to have residual disease. However, negative resection margin carries a lower risk for residual AIS, therefore conservative management with careful surveillance seems to be feasible in women who wish to preserve their fertility.
Abortion, Spontaneous ; Adenocarcinoma ; Cervix Uteri ; Conization ; Female ; Fertility ; Follow-Up Studies ; Humans ; Hysterectomy ; Medical Records ; Pregnancy

OBJECTIVE: To determine whether the presence of Y-chromosome microdeletion affects the outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) program. METHODS: Fourteen couples with microdeletion in azoospermic factor (AZF)c region who attempted IVF/ICSI or cryopreserved and thawed embryo transfer cycles were enrolled. All of the men showed severe oligoasthenoteratoazoospermia (OATS) or azoospermia. As a control, 12 couples with OATS or azoospermia and having normal Y-chromosome were included. Both groups were divided into two subgroups by sperm source used in ICSI such as those who underwent testicular sperm extraction (TESE) and those used ejaculate sperm. We retrospectively analyzed our database in respect to the IVF outcomes. The outcome measures were mean number of good quality embryos, fertilization rates, implantation rates, beta-hCG positive rates, early pregnancy loss and live birth rates. RESULTS: Mean number of good quality embryos, implantation rates, beta-hCG positive rates, early pregnancy loss rates and live birth rates were not significantly different between Y-chromosome microdeletion and control groups. But, fertilization rates in the Y-chromosome microdeletion group (61.1%) was significantly lower than that of control group (79.8%, p=0.003). Also, the subgroup underwent TESE and having AZFc microdeletion showed significantly lower fertilization rates (52.9%) than the subgroup underwent TESE and having normal Y-chromosome (79.5%, p=0.008). Otherwise, in the subgroups used ejaculate sperm, fertilization rates were showed tendency toward lower in couples having Y-chromosome microdeletion than couples with normal Y-chromosome. (65.5% versus 79.9%, p=0.082). But, there was no significance statistically. CONCLUSIONS: In IVF/ICSI cycles using TESE sperm, presence of Y-chromosome microdeletion may adversely affect to fertilization ability of injected sperm. But, in cases of ejaculate sperm available for ICSI, IVF outcome was not affected by presence of Y-chromosome AZFc microdeletion. However, more larger scaled prospective study was needed to support our results.
Avena ; Azoospermia ; Embryo Transfer ; Embryonic Structures ; Family Characteristics ; Fertilization ; Fertilization in Vitro* ; Humans ; Live Birth ; Male ; Outcome Assessment (Health Care) ; Pregnancy ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; Spermatozoa ; Y Chromosome*

OBJECTIVE: To compare laparoscopic surgery with laparotomy in comprehensive surgical staging of endometrial cancer. METHODS: We retrospectively analyzed the medical records of 272 patients with endometrial adenocarcinoma treated by staging operation including pelvic and paraaortic lymphadenectomy between January, 1996 and December, 2007. RESULTS: There was no significant difference between the two groups in terms of age, body mass index, or histologic type, but in the laparotomy group, grade and surgical stage were significantly higher. All the patients, 182 in the laparotomy and 90 in the laparoscopy group, had lymphadenectomy, and the mean number of pelvic and paraaortic lymph nodes (LNs) obtained were 33.1+/-13.2 and 16.1+/-11.6 in the laparoscopy group, and 32.5+/-14.5 and 19.0+/-12.7 in the laparotomy group, respectively; these differences were not statistically significant. In the laparoscopy group, the operating time and postoperative hospital length of stay were shorter than in the laparotomy group, as were the pre- and post-operative hemoglobin changes. There were no significant differences between the two groups in terms of intra- or post-operative complications, but positive lymph nodal metastasis and conducting of postoperative adjuvant therapy were highter in the laparotomy group. The operative technique did not influence overall or disease-free survival after adjusting for several confounding factors. CONCLUSION: Laparoscopic-assisted surgical staging for endometrial cancer required a shorter operating time, shorter postoperative hospital stay, and lower blood loss compared to traditional laparotomy staging, and can be a good therapeutic option for staging operation including lymphadenectomy of endometrial cancer.
Adenocarcinoma ; Body Mass Index ; Disease-Free Survival ; Endometrial Neoplasms ; Female ; Hemoglobins ; Humans ; Laparoscopy ; Laparotomy ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Retrospective Studies

OBJECTIVE: To evaluate the proper approach in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy. METHODS: We retrospectively analyzed the medical records of 108 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 2000 to 2007. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy. RESULTS: AEH was initially diagnosed by dilatation and curettage (87 cases) or endometrial biopsy with a Z-sampler (17 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 33.3% with AEH and normal endometrium found in 52.8 and 3.7% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (11/108, 10.2%). All cases were confined to the endometrium and two of those were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy. CONCLUSION: Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with an increased risk of coexisting endometrial carcinoma. When considering management strategies for women with a biopsy diagnosis of AEH, clinicians should take into account the considerable rate of concurrent endometrial cancer and the discrepancy with pathologic diagnosis.
Adenomyosis ; Biopsy ; Dilatation and Curettage ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometrium ; Female ; Humans ; Hyperplasia ; Hysterectomy ; Incidence ; Medical Records ; Retrospective Studies

OBJECTIVE: To investigate the surgical and oncological outcomes of laparoscopic surgery compared with laparotomy for the treatment of early-stage ovarian cancer. METHODS: Data from patients who underwent surgical management for early-stage ovarian cancer between 2006 and 2012 were retrospectively reviewed. All patients presented with stage I or II disease, and underwent comprehensive staging surgery consisting of a total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal cytology. RESULTS: Seventy-seven patients who underwent laparoscopic surgery (24 patients) or laparotomy (53 patients) were identified. Surgery for none of the patients was converted from laparoscopy to laparotomy. The mean operation time was shorter and the estimated blood loss was lower in the laparoscopy group than in the laparotomy group, though the differences were not statistically significant (193 min vs. 224 min, p=0.127; 698 mL vs. 973 mL, p=0.127). There were no differences in the intraoperative or postoperative complications. During a mean follow-up period of 31 months, tumor recurrence occurred in 4 patients: 2 (8.3%) in the laparoscopy group and 2 (3.8%) in the laparotomy group. The mean disease-free survival was 59 months after laparoscopy and 66 months after laparotomy (p=0.367). CONCLUSION: Laparoscopic surgery seems to be adequate and feasible for the treatment of early-stage ovarian cancer with comparable results to laparotomy in terms of the surgical outcomes and oncological safety.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Hysterectomy ; Laparoscopy* ; Laparotomy* ; Lymph Node Excision ; Ovarian Neoplasms* ; Postoperative Complications ; Recurrence ; Retrospective Studies

OBJECTIVE: The aim of this study was to evaluate the clinicopathologic characteristics of granulosa cell tumor of the ovary (OGCT). METHODS: We retrospectively reviewed the medical records of 27 patients with OGCT at our hospitals from January 1995 to December 2003. RESULTS: The mean age was 48.3 years (24~70) and mean follow up period was 56.7 months (12~102). The most common symptom was vaginal bleeding (n=11, 40.7%). The tumors were ranging from 3 cm to 21 cm in diameter (mean: 9.9). Post-surgical FIGO stage was stage I in 20 (74.1%), stage II in 6 (22.2%), and stage III in 1 (3.7%). Endoemetrial samples were available in 21 patients and the results were endometrial carcinoma in 1 and endometrial hyperplasias in 5. Staging operation was performed in 17, unilateral salpingo-oophorectomy in 6, total hysterectomy and bilateral salpingo-oophorectomy in 2, and fertility sparing operation in 2. Postoperative chemotherapy was administered in 13 patients (48.2%). Two patients had recurred and recurrence rate was 7.4% (2/27). Two recurred patients finally died of the disease at 42 months and 103 months after first operation respectively. During follow-up period, 2 patients had 3 pregnancies and all of them delivered at term. CONCLUSION: These results shows that most OGCT is detected in early stage and have relatively excellent survival. However, because OGCT is a slow-growing tumor and has a late recurrence, long time follow-up is required.
Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Fertility ; Follow-Up Studies ; Granulosa Cell Tumor ; Granulosa Cells ; Humans ; Hysterectomy ; Medical Records ; Ovary ; Pregnancy ; Recurrence ; Retrospective Studies ; Uterine Hemorrhage

OBJECTIVE: To evaluate the rates and clinical outcomes between abdominal hysterectomy (AH), laparoscopic hysterectomy (LH) and vaginal hysterectomy (VH). METHODS: Medical records of 236 patients who underwent hysterectomy (by one surgeon) for benign uterine pathology between march 2004 and april 2006 were reviewed. Primary outcome measure was the rate of each method of hysterectomy. Secondary outcome measures included perioperative and postoperative outcomes between groups. RESULTS: The mean age, weight, height, body mass index, and parity in three groups showed no difference. In two hundred and twenty two cases of hysterectomies, the rate of AH was 13.5%, LH 34.2%, and VH 52.3%. Perioperative outcomes of AH, LH and VH were as follows : operative time (83.2+/-27.1 min, 94.2+/-25.2 min, and 50.8+/-15.5 min, respectively), change in hemoglobin (2.3+/-1.5 g/dL, 2.0+/-0.9 g/dL, and 1.3+/-1.1 g/dL, respectively), duration of urinary catheterization (2.0+/-0.2 days, 1.0+/-0.0 days, and 1.0+/-0.4 days, respectively), postoperative hospitalization (5.7+/-1.2 days, 4.7+/-0.9 days, and 4.3+/-1.0 days, respectively), uterine weight (733+/-665 g, 340+/-213 g, and 300+/-156 g, respectively). Uterine weight in the AH group was significantly heavier than in the LH and VH. The benefits of LH versus AH were shorter duration of urinary catheterization and postoperative hospitalization (p<0.05). The benefits of VH versus AH were shorter operative time, a smaller drop in hemoglobin, shorter duration of urinary catheterization and postoperative hospitalization (p<0.05). The benefits of VH versus LH were shorter operative time, a smaller drop in hemoglobin, and postoperative hospitalization (p<0.05). There were no differences in complications of AH, LH and VH (13.3%, 10.5%, and 9.5%, respectively p=0.825). CONCLUSIONS: Eighty six point five percent of hysterectomy can be done vaginal or laparoscopic approach. When there is a concerted effort to increase laparoscopic or vaginal hysterectomy, abdominal hysterectomy can decrease without increasing complication rate.
Body Height ; Female ; Hospitalization ; Humans ; Hysterectomy* ; Hysterectomy, Vaginal ; Medical Records ; Operative Time ; Outcome Assessment (Health Care) ; Parity ; Pathology* ; Urinary Catheterization ; Urinary Catheters