Ho-Suap Hahn

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.

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.

Distribution of maternal and infant human papillomavirus: risk factors associated with vertical transmission

OBJECTIVE To evaluate the rate of human papillomavirus (HPV) infection in pregnant women and their neonates, and the risk factors associated with vertical transmission of HPV infection from mothers to neonates. STUDY DESIGN Cervical HPV testing was undertaken in pregnant women over 36 weeks of gestation, and mouth secretions and oral mucosa of neonates were tested for HPV immediately after delivery. HPV-positive neonates were rechecked 2 months postpartum to identify the persistence of HPV infection. In HPV-positive mothers, the placenta, cord blood and maternal peripheral blood were also analysed for HPV to confirm whether transplacental HPV infection occurred. RESULTS HPV was detected in 72 of 469 pregnant women (15.4%) and in 15 neonates (3.2%). Maternal HPV positivity was associated with primiparity and abnormal cervical cytology. The rate of vertical transmission was 20.8%, and all HPV-positive neonates were born from HPV-positive mothers. Vertical transmission was associated with vaginal delivery and multiple HPV types in the mother. Neonates with HPV showed a tendency for higher maternal total HPV copy number than neonates without HPV, but this difference was not significant (p=0.081). No cases of HPV infection were found in the infants at 2 months postpartum, and no HPV was detected in placenta, cord blood or maternal blood. CONCLUSIONS Vertical transmission of HPV is associated with vaginal delivery and multiple HPV types in the mother; however, neonatal HPV infection through vertical transmission is thought to be a transient.

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.

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

Lymphovascular space invasion (LVSI) has been evaluated as a predictor for nodal metastasis or poor survival in endometrial adenocarcinoma.

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.

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.

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.

Abstract 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.