Comparison of laparoscopy and laparotomy for the management of early-stage ovarian cancer: surgical and oncological outcomes.

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.

Metronomic oral paclitaxel shows anti-tumor effects in an orthotopic mouse model of ovarian cancer.

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 µL 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.

Distribution and perinatal transmission of bacterial vaginal infections in pregnant women without vaginal symptoms.

BACKGROUND: We evaluated the distribution and vertical transmission of bacterial vaginal infections in asymptomatic pregnant women. METHODS: We performed multiplex PCR on secretions collected on cervical swabs from pregnant women at over 36 weeks of gestation and on oral secretions collected from their neonates immediately after delivery. We detected sexually transmitted infections (STIs) with the following 6 species: Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Ureaplasma urealyticum. RESULTS: Infectious agents were detected in 64 of 455 pregnant women (14.1%) and in 11 neonates (2.4%). The rate of vertical transmission was 17.2% and all the infectious agents detected in neonates were concordant with those found in their mothers. U. urealyticum was the most frequently detected in the maternal genitalia, followed by M. hominis. Women who were in labor for a longer period of time had a higher risk of vertically transmitting STI agents to their neonates. CONCLUSIONS: Vertical transmission of bacterial STIs from mothers to their infants is possible at delivery and influenced by the duration of labor. STIs should be diagnosed in pregnant women to prevent vertical transmission from the mother to the infant at the time of delivery.

Magnetic resonance imaging and intraoperative frozen sectioning for the evaluation of risk factors associated with lymph node metastasis in endometrial cancer.

INTRODUCTION: To analyze the accuracy of magnetic resonance imaging (MRI) and intraoperative frozen sectioning (IFS) for predicting the low- and high-risk patients and risk factors associated with lymph node (LN) metastasis in patients with surgically staged endometrial cancer. METHODS: The medical records of 175 patients with endometrial cancer who underwent comprehensive surgical staging including pelvic and para-aortic LN dissection between January 2008 and July 2011 were retrospectively analyzed. Results of MRI and IFS of the uterus for the evaluation of risk factors were correlated with final pathology. RESULTS: Our results showed a high specificity and negative predictive value of MRI and IFS for the evaluation of myometrial invasion and cervical stromal invasion. Of the 41 patients identified as low risk by both MRI and IFS, none had pelvic or para-aortic LN metastases in the final pathology. CONCLUSIONS: The results indicate that MRI and IFS may be useful for the evaluation of risk factors associated with LN metastasis in patients with endometrial cancer. Magnetic resonance imaging and IFS can be used to accurately identify low-risk patients who do not need comprehensive surgical staging and may prevent unnecessary lymphadenectomy.

Dual immunostaining of cervical cytology specimens with atypical squamous cells for p16/Ki-67 does not exclude the existence of a high-grade squamous intraepithelial lesion.

This study was conducted to evaluate the accuracy of p16/Ki-67 dual immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing for cervical intraepithelial neoplasia (CIN) in women with atypical squamous cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H). Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who were HPV genotyped and had histological examination of a cervical biopsy. The CINtecPLUS kit was used on residual liquid-based material, and the immunoreactivity of dual-stained cells was graded according to the number as follows: G1 (1-5 positive cells), G2 (6-10), G3 (11-20), and G4 (> 20). Accuracy was evaluated based on the histological examination of colposcopy-guided biopsy or cervical conization on follow-up. Of the 70 patients with available data, positive p16/Ki-67 was associated with histological severity as follows: 15% in negative histology, 67% in CIN 1, 90% in CIN 2, and 100% in CIN 3. The average grade of positive p16/Ki-67 staining also increased from 0.2 in histologically negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p < 0.01). For patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6% and a specificity of 75.8%, while HR-HPV testing showed a sensitivity of 67.6% and a specificity of 66.7%. p16/Ki-67 immunostaining demonstrated better accuracy than HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the higher concordance with histological diagnosis, the grading system of positive p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical practice.

Selective cyclooxygenase inhibitors increase paclitaxel sensitivity in taxane-resistant ovarian cancer by suppressing P-glycoprotein expression.

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.

Lymphovascular space invasion is highly associated with lymph node metastasis and recurrence in endometrial cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) has been evaluated as a predictor for nodal metastasis or poor survival in endometrial adenocarcinoma. AIMS: To evaluate whether LVSI is a prognostic factor for lymph node metastasis and relapse of disease in endometrial adenocarcinoma. MATERIALS & METHODS: We retrospectively analysed the medical records of 438 women with endometrial adenocarcinoma treated by surgical staging, including pelvic and paraaortic lymph node dissection, between January 1996 and July 2011. RESULTS: One hundred sixty-three women (37.2%) were LVSI-positive and 275 (62.8%) were negative. LVSI-positive women were significantly older and showed more advanced stage, poorer differentiation, and a higher frequency of non-endometrioid histology type, myometrial invasion, and positive peritoneal cytology than LVSI-negative women. Surgeries by laparotomy rather than laparoscopy and more adjuvant therapies were conducted in LVSI-positive women. The median number of pelvic and paraaortic lymph nodes removed were not different, but LVSI-positive patients showed more lymph node metastases. The LVSI-positive group also showed a higher recurrence of disease and lower survival rates than the LVSI-negative group. Negative predictive values of LVSI for lymph node metastasis and recurrence of disease were 96.4 and 97.1%, respectively. In multivariate analysis, LVSI did not influence overall or disease-free survival after adjusting for several confounding factors. CONCLUSIONS: In the cases that the nodal status has not been assessed in endometrial adenocarcinoma, the presence of LVSI may be a reasonable surrogate in addition to other risk factors, in determining the need for adjuvant therapy.

Single-port laparoscopic cornual resection for a spontaneous cornual ectopic pregnancy following ipsilateral salpingectomy.

OBJECTIVE: To describe the single-port laparoscopic management of a spontaneous cornual ectopic pregnancy following ipsilateral salpingectomy. DESIGN: Case report and technique description. SETTING: University hospital. PATIENT(S): A 28-year-old woman with a spontaneous cornual pregnancy of 5 weeks' gestation following previous ipsilateral salpingectomy. INTERVENTION(S): Single-port laparoscopic cornual resection (surgeon, Y.-W.K.). MAIN OUTCOME MEASURE(S): Serum ß-hCG levels. RESULT(S): Complete resolution of cornual pregnancy. CONCLUSION(S): We performed a successful single-port laparoscopic cornual resection for a spontaneous cornual ectopic pregnancy following ipsilateral salpingectomy.

The safety of conization in the management of adenocarcinoma in situ of the uterine cervix.

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.

Single-port laparoscopic pelvic lymph node dissection with modified radical vaginal hysterectomy in cervical cancer.

There is no doubt that laparoscopic surgeries have replaced open surgeries in many gynecologic operations and have led to the development of novel techniques such as single-port laparoscopic surgery. Single-port surgery has been performed mainly for hysterectomy or adnexectomy recently, and it has also been carefully considered for other possible single-port surgeries such as cancer operations. Although pelvic lymph node dissection is a common procedure in gynecologic cancer operations, it has been rarely performed with single-port laparoscopic access because of technical difficulties. In this report, we present a detailed description of single-port laparoscopic pelvic lymph node dissection with modified radical vaginal hysterectomy in 2 patients with cervical cancer, stage IA2. Combining either classic or modified Schauta radical vaginal hysterectomy with single-port laparoscopic technique could be a good option for the management of patients with cervical cancer.

Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia.

OBJECTIVE: To evaluate the prevalence of concurrent endometrial carcinoma in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy. STUDY DESIGN: We retrospectively analyzed the medical records of 126 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 1999 to 2008. AEH was initially diagnosed by dilatation and curettage (98 cases) or endometrial biopsy with a Z-sampler (24 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy. RESULTS: In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 27% with AEH and normal proliferative phases found in 54.7 and 7.9% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (13/126, 10.3%). Eleven of 13 cases were confined to the endometrium and the remaining two were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy. CONCLUSIONS: Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with a 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. Treatment modalities may differ depending on population as the rates of concurrent endometrial cancer with AEH and myometrial invasion vary by geographical location.

Laparoscopy-assisted vaginal versus abdominal hysterectomy in endometrial cancer.

INTRODUCTION: The purpose of this study was to compare the efficacy of a laparoscopy-assisted surgical staging with a traditional laparotomy staging for the treatment of endometrial cancer. METHODS: We retrospectively analyzed the medical records of 465 patients with endometrial adenocarcinoma treated by surgery between January 1996 and December 2007. RESULTS: There were no significant differences between the laparoscopy and the laparotomy groups in age, body mass index, and histologic type. However, in the laparotomy group, grade and surgical stage were higher, the diseases were more chronic, and more postoperative adjuvant treatments were necessary. One hundred seven (76.4%) of 140 patients in the laparoscopy group and 260 (80.0%) of the 325 patients in the laparotomy group had lymphadenectomy, and the median numbers of pelvic and paraaortic lymph nodes obtained were not statistically different. The laparoscopy group showed shorter postoperative hospital stay and lower blood loss, and the operating time was also shorter than that in the laparotomy group. There was no significant difference in intraoperative or postoperative complications, and the operative technique did not influence survival rates after adjusting several confounding factors. CONCLUSIONS: Our data of 12 years with a large number of patients show no differences in complications and impacts on survival between laparoscopy and laparotomy. Laparoscopy has advantages of shorter operating time and other advantages over laparotomy previously reported. Therefore, laparoscopy can be considered a good therapeutic option for endometrial cancer.

Conservative treatment with progestin and pregnancy outcomes in endometrial cancer.

INTRODUCTION: The purpose of this study was to evaluate the efficacy of conservative treatment with progestin and pregnancy outcomes in women with early-stage endometrial cancer. METHODS: We retrospectively analyzed the medical records of 35 patients with endometrial adenocarcinoma, who were treated with progestin from January 1996 to December 2006. Women with early-stage grade 1 endometrioid endometrial adenocarcinoma, who wanted to receive conservative treatment or preserve fertility, were included. All women were treated with medroxyprogesterone acetate or megestrol acetate, with regular dilation and curettage performed. Complete remission (CR) was defined as no evidence of endometrial adenocarcinoma or hyperplasia. Partial remission was diagnosed when the patient developed endometrial hyperplasia, and persistent disease was defined as residual endometrial adenocarcinoma by pathologic confirmation. RESULTS: The median age was 31 years (range, 21-43 years), and the median follow-up period was 39 months (range, 5-108 months). Complete remission was achieved in 22 patients (62.9%), partial remission was achieved in 1 patient (2.9%), and 12 patients (34.3%) had persistent disease. The median time to CR was 9 months (range, 2-12 months). Of the 22 patients with CR, 9 (40.9%) had recurrent disease, and the median time to recurrence was 12 months (range, 8-48 months). Ten (83.3%) of the 12 patients with CR who tried to conceive were successful, and 8 of the 10 pregnancies resulted in live births. There were no congenital anomalies in babies associated with progestin treatment. CONCLUSIONS: Conservative treatment with progestin can be considered a good therapeutic option in patients with well-differentiated early-stage endometrioid endometrial adenocarcinoma who wish to preserve their uteri or become pregnant.

Fertility preservation in patients with early epithelial ovarian cancer.

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.