Kyeong A. So

Mild Obesity, Physical Activity, Calorie Intake, and the Risks of Cervical Intraepithelial Neoplasia and Cervical Cancer

Objective We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods We enrolled 1125 women (age, 18–65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. Results Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5–23 kg/m2), the multivariate ORs (95% CIs) for those overweight (23–25 kg/m2) and mild obesity (≥25 kg/m2) were 1.25 (0.79–2.00) and 1.70 (1.10–2.63), respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week), the ORs (95% CIs) for cervical cancer were 0.95 (0.61–1.48) and 0.61 (0.38–0.98) for women with medium physical activity (38.5–71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend  = 0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week), the ORs (95% CIs) for CIN2/3 were 0.64 (0.40–1.01) and 0.58 (0.36–0.93) for the medium and high physical activity groups, respectively (p for linear trend  = 0.02). Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders. Conclusion Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer.

Prophylactic Hypogastric Artery Ballooning in a Patient with Complete Placenta Previa and Increta

Abnormal attachment of the placenta (Placenta accreta, increta, and percreta) is an uncommon but potentially lethal cause of maternal mortality from massive postpartum hemorrhage. A 33-yr-old woman, who had been diagnosed with a placenta previa, was referred at 30 weeks gestation. On ultrasound, a complete type of placenta previa and multiple intraplacental lacunae, suggestive of placenta accreta, were noted. For further evaluation of the placenta, pelvis MRI was performed and revealed findings suspicious of a placenta increta. An elective cesarean delivery and subsequent hysterectomy were planned for the patient at 38 weeks gestation. On the day of delivery, endovascular catheters for balloon occlusion were placed within the hypogastric arteries, prior to the cesarean section. In the operating room, immediately after the delivery of the baby, bilateral hypogastric arteries were occluded by inflation of the balloons in the catheters previously placed within. With the placenta retained within the uterus, a total hysterectomy was performed in the usual fashion. The occluding balloons were deflated after closure of the vaginal cuff with hemostasis. The patient had stable vital signs and normal laboratory findings during the recovery period; she was discharged six days after delivery without complications. The final pathology confirmed a placenta increta.

The prognostic significance of preoperative leukocytosis in epithelial ovarian carcinoma: a retrospective cohort study.

OBJECTIVE Preoperative leukocytosis is known to be a negative prognostic factor for several gynecologic malignancies, but its relationship with epithelial ovarian carcinoma (EOC) is unknown. We sought to evaluate the prognostic implications of preoperative leukocytosis for women with EOC. METHODS We retrospectively reviewed the medical records of patients who underwent primary debulking surgery and adjuvant platinum-based chemotherapy for EOC between January 1993 and October 2011. Associations between leukocytosis and recurrence-free survival (RFS) and overall survival (OS) were determined by univariate analyses. Multivariate Cox proportional hazards regression was used to identify independent prognostic factors for RFS and OS. RESULTS Of 155 women, 23 (14.8%) had leukocytosis and 132 (85.2%) did not have leukocytosis. RFS and OS were significantly shorter for women with leukocytosis than for women without leukocytosis (P=0.009 and P<0.0001, respectively). The mortality rate was also higher among women with leukocytosis (P<0.0001). Multivariate analysis revealed that preoperative leukocytosis (hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.55-4.41; P=0.009), advanced stage (HR: 3.12; 95% CI: 1.44-6.75; P=0.004), and optimal cytoreduction (HR: 0.38; 95% CI: 0.14-0.70; P=0.031) were independent prognostic factors for RFS. Additionally, preoperative leukocytosis was independently associated with decreased OS (HR: 7.66; 95% CI: 2.78-21.16; P<0.0001). CONCLUSIONS Among women with EOC, preoperative leukocytosis might be an independent prognostic factor for RFS and OS. A larger-scaled, prospective study is needed to verify these results.

The utility of the human papillomavirus DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia.

OBJECTIVE We evaluated the human papillomavirus (HPV) DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia (VAIN). METHODS A retrospective review of the medical records of patients with a pathological diagnosis of VAIN was performed. Eligible women (N=48) were followed for cytology and HPV DNA test, and colposcopic biopsies were taken at 3- to 6-month intervals. Thirty-seven patients were followed for more than 6 months; their HPV DNA test results were compared to the cytology results for the prediction of disease prognosis. RESULTS The degree of VAIN was more severe in patients with a high initial HPV DNA load (p=0.009). Patients with VAIN 2 and VAIN 3 were older than those with VAIN 1 (p=0.005 and 0.008, respectively). In 26 out of 37 patients (70.3%), the VAIN resolved. The other patients had persistent lesions with no progression to invasive vaginal carcinoma. The last follow-up HPV DNA load was significantly higher in the group with persistent VAIN compared to the group with resolved VAIN (p<0.0001). Negative cytology was observed in 25 out of 26 patients in the VAIN resolved group and in nine out of 11 patients in the VAIN persistent group (p=0.205). CONCLUSION These results suggest that the HPV DNA test, especially for viral load, was more effective for the diagnosis and prediction of persistent VAIN than cytology.

Interleukin-6 expression by interactions between gynecologic cancer cells and human mesenchymal stem cells promotes epithelial-mesenchymal transition

Epithelial-to-mesenchymal transition (EMT) facilitates the invasion and metastasis of cancer cells. EMT seems to be mediated by the interaction between cancer cells and human mesenchymal stem cells (hMSCs) in the tumor microenvironment. The present study is intended to identify specific cytokines as potent inducers of EMT associated hMSCs-tumor interactions. We used ovarian cancer cell lines (SKOV-3 and IGROV-1), endometrial cancer cell line (Ishikawa) and hMSCs (bone marrow MSC, amniotic membrane MSC and decidua MSC). The expressions of EMT markers (E-cadherin, Snail, Twist and N-cadherin) were analyzed using quantitative RT-PCR, immunofluorescence and western blot analysis. Matrix metalloproteinases (MMP-2 and MMP-9), Matrigel invasion assay, and wound healing assay were used to analyze cell migration and invasion. Gynecologic cancer cells directly co-cultured with hMSCs had contact-dependent altered morphology and growth patterns. IL-6 was elevated in all co-cultures using a human cytokine array. After IL-6 treatment of cancer cell lines, RT-PCR and western blot analysis indicated a decrease in an epithelial marker and an increase in mesenchymal markers. Also, cancer cells with IL-6 significantly increase in MMP-2 and MMP-9 and significantly enhance the migration ability compared to untreated cells (P<0.05), as shown by wound healing assay. On Matrigel invasion assay, treated cells displayed significantly increased invasiveness compared to untreated cancer cells. Gyneocologic cancer cells exposed to IL-6 acquired mesenchymal properties that facilitated metastasis and invasion by promoting EMT. The present study suggests that IL-6 of the tumor microenvironment has a critical role in oncogenic EMT.

Human Papillomavirus Prevalence and Type Distribution Among 968 Women in South Korea

Background: Geographic variation in the prevalence of carcinogenic types and human papillomavirus (HPV) genotype distribution is closely associated with the impact of HPV prophylactic vaccines. We determined the prevalence and distribution of HPV genotypes among healthy women in Korea. Methods: This study included 968 healthy women who were examined at a health promotion center of the Korea University Guro Hospital between January and June 2013. Each participant had a Pap test and a HPV DNA test using the Anyplex™ II HPV 28 Detection system, which detects 19 high-risk HPVs (HR HPVs) and 9 low-risk HPVs (LR HPVs). Women with abnormal cytology and/or positivity for HR HPVs were referred to colposcopic biopsy. Results: Overall HR HPV prevalence based on the assay was 33.7%. Among them, 225 women had single infection and 101 women had multiple infection. The most frequently occurring HR HPV types were 53 (6.5%), 52 (6.1%), 58 (4.8%), 16 (4.5%), and 68 (4.2%). The most frequently occurring LR HPV types were 54 (5.4%), 70 (3.8%), 42 (3.6%), 61 (3.4%), and 44 (3.1%). The prevalence of HPV 16 was highest (17.6%) among women with cervical intraepithelial neoplasia (CIN) and HPV 16 was strongly associated with a diagnosis of CIN2/3 (odds ratio = 20.5; 95% confidence interval: 3.9–107.1; P < 0.0001). Conclusions: HPV 53, 52, 58, 16, and 68 were common HR HPV types among healthy Korean women. HPV16 was the most common type in high-grade CIN lesions, as shown in most studies worldwide. The results might be useful information for cervical cancer prevention in South Korea.

Type-specific persistence or regression of human papillomavirus genotypes in women with cervical intraepithelial neoplasia 1: A prospective cohort study

Objective To evaluate the type-specific human papillomavirus (HPV) persistence or regression in women with or less than low-grade cervical intraepithelial neoplasia (CIN). Methods This prospective cohort study included patients with or less than cytological low-grade squamous intraepithelial lesion (or histologically CIN 1 when biopsy was performed) combined with HPV infection. The cohort was collected from July 2006 to November 2011 at Korea University Guro Hospital. Follow-up was performed with liquid-based Papanicolaou test, hybrid capture 2 test, AnyplexTM II HPV 28 Detection, colposcopic biopsy if necessary every 4 months. All patients were prospectively observed without treatment. Results One hundred and thirty-seven patients were enrolled. Of these, 21 patients whose minimum follow-up periods were less than 8 months were excluded. Finally, one hundred sixteen patients were included and followed-up. Median follow-up period was 16 months. In case of high-risk HPVs, HPV 53 was the most prevalent type, followed by HPV 52, 68, 66, and 16. HPV 16 took 10.6 months to regress spontaneously, which was the longest period among the 10 most prevalent high-risk HPV genotypes. In case of spontaneous regression, HPV clearance was always accompanied by lesion clearance. A total of 13 patients showed disease progression either cytologically or histologically. Two cases of CIN 3 were confirmed by colposcopy-directed biopsy during follow-up, which were subsequently managed by conization. Conclusion HPV 16 is the most persistent HPV genotypes. Studies with longer term follow-up and larger sample size are needed to demonstrate whether persistence of HPV 16 is directly correlated with progression of low-grade lesions.

Leiomyosarcoma of the rectum mimicking primary ovarian carcinoma: a case report

Leiomyosarcoma of the rectum is a very rare mesenchymal tumor. Because of its rarity, its diagnosis, treatment, and pathology often present challenges to the clinician. The characteristics of this tumor, such as its anatomical location, heterogeneous solid features on imaging, and nonspecific lower gastrointestinal tract symptoms, can be confused with those of primary ovarian carcinoma. Here, we report the case of a 52-year-old-woman presenting with a low abdominal mass that was later pathologically confirmed to be a rectal leiomyosarcoma. The findings of preoperative ultrasonography, pelvic magnetic resonance imaging, and abdominopelvic computed tomography were suggestive of a malignant pelvic mass, most likely a primary ovarian carcinoma. The patient underwent explorative laparotomy, and intraoperative frozen examination revealed a sarcoma originating from the gastrointestinal tract. Low anterior resection and supracervical hysterectomy with bilateral salpingo-oophorectomy were performed. The patient’s postoperative course was uneventful, and adjuvant chemotherapy is currently being administered.

The effects of DNA methylation and epigenetic factors on the expression of CD133 in ovarian cancers

BackgroundTo identifying the effects of DNA methylation and epigenetic factors on the expression of CD133, a cancer stem cell marker, in gynecologic cancer cell lines.MethodsOvarian cancer cell lines (OVCAR-8 and IGROV-1) and an endometrial cancer cell line (Ishikawa) were treated with 5-aza-2`-deoxycytidine (DAC) or Trichostatin A (TSA). Expression of CD133 was evaluated by quantitative real-time PCR, methylation-specific PCR (MSP), reverse transcription- PCR, western blot, and FACS analysis. All results are representative of three independent experiments.ResultsCD133 mRNA expression varied among the different cell lines; the weakest expression was observed in OVCAR-8 cells, while it was strongly expressed in Ishikawa cells. The degree of methylation of the CD133 P2 promoter was 61% in OVCAR-8 cells, 53% in IGROV-1 cells, and 43% in Ishikawa cells. CD133 expression was increased at both the mRNA and protein level after DAC treatment. On the contrary, CD133 mRNA expression decreased after TSA treatment decreased in all cell lines except OVCAR-8. In addition, MSP of the CD133 P2 promoter revealed that methylation was reduced after treatment with either DAC or TSA.ConclusionsThe expression of the CD133 antigen in primary ovarian and endometrial cancer cell lines is regulated by epigenetics, as indicated by its increased expression following DAC treatment and irregular expression pattern followed by TSA treatment. In addition, the expression of CD133 was negatively correlated with the degree of methylation of the CD133 P2 promoter.

Comparison of the Seeplex HPV4A ACE and the Cervista HPV assays for the detection of HPV in hybrid capture 2 positive media

Objective To validate the efficacy of Seeplex HPV4A ACE for the detection of high-risk (HR) human papillomavirus (HPV) and HPV 16 and/or HPV 18 genotypes as compared to the PCR method and the Cervista HPV assays in cervical swab samples. Methods Besides liquid-based cytology, additional 97 cervical swab samples were collected for HPV genotyping by HPV4A ACE, Cervista HPV assays, and PCR method. To check the statistical differences, we also conducted the paired proportion test, Cohens κ statistic, and a receiver operating characteristic curve. Results Seeplex HPV4A ACE and the Cervista HPV HR showed substantial agreement with PCR for detection of HR HPVs (88.3%, κ=0.767 and 81.7%, κ=0.636, respectively). Seeplex HPV4A ACE also showed substantial agreement with the Cervista HPV 16/18 test (89.5%, κ=0.628). Additionally, the sensitivity and specificity of Seeplex HPV4A ACE and Cervista HPV HR were 91.4% vs. 84.5% and 73.4%, vs. 72.7%, respectively, when those higher than low-grade squamous intraepithelial lesions were regarded as abnormalities. HPV genotyping for HPV 16/18 detected cervical intraepithelial neoplasias (CINs) better than HR HPV tests (66.7% vs. 24.6% by HPV4A ACE, 52.6% vs. 25.9% by Cervista HPV assays in CIN II or more, relatively). Conclusion Seeplex HPV4A ACE is an effective method as the PCR and the Cervista HPV assays for the detection of HR HPVs and for genotyping of HPV 16 and 18.