Persistent low-level elevation of serum human chorionic gonadotropin after termination of pregnancy: a rare case of peritoneal trophoblastic implant

Peritoneal trophoblastic implant can occur after treatment of ectopic pregnancy. Similarly, after termination of intrauterine pregnancy, trophoblastic implants are rare but can be a complication of perforation during dilatation and curettage. We report an extremely rare case of trophoblastic implant on the myometrium, ovarian surface, and peritoneal wall 4 months after uncomplicated dilatation and curettage. To the best of our knowledge, this is the first case of peritoneal trophoblastic implant following dilatation and curettage without uterine perforation. Knowledge of this case is useful for the management of patients with persistent low-level elevation of serum human chorionic gonadotropin after termination of pregnancy.

Small cell neuroendocrine carcinoma of the uterine cervix presenting with syndrome of inappropriate antidiuretic hormone secretion

Small cell carcinoma of the uterine cervix is rare. It is estimated that 10% of patients with small-cell lung cancer have syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and hyponatremia has been reported to be significantly associated with a poor prognosis. A proportion of small cell carcinoma of the uterine cervix exhibit neuroendocrine characteristics as revealed by immunohistochemistry, However, cases presenting typical symptoms due to SIADH are extremely rare. This report of the SIADH of the uterine cervix is a rare case in the small cell carcinoma of the cervix presenting with tumor-associated paraneoplastic syndrome.

Efficacy of human papillomavirus vaccines including cross protection : A review of recent evidence / 대한산부인과학회지

The efficacy and immunogenicity of human papillomavirus (HPV) vaccines has proven excellent in several phase 2 and phase 3 trials involving tens of thousand women. Two versions of HPV vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. We have summarized the recent review of all randomized controlled trials in which vaccines against HPV were compared with placebo regarding efficacy, safety, and immunogenicity. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. Data strongly suggest that both vaccines can have a variable level of cross protection against HPV types genetically and antigenically-closely related to vaccine types. Demonstration of cross protection against combined endpoints [cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in situ] for HPV-31 has been reached for the quadrivalent vaccine. Bivalent HPV vaccine showed significant type-specific cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45. The bivalent vaccine is also registered for above age 26 in Australia, Israel and Korea. In our country, we have already set up the clinical guideline of both vaccines. Although these prophylactic vaccination is likely to provide important gains in the prevention of cervical cancer, we should have need to establish the new screening guideline in post-vaccination period and to make next version of vaccination-guidelines related of specific subgroups of patients who would benefit from the vaccine (women older than 26 years, boys, and men).

A Case Report of Acute Hepatitis A Infection in Pregnancy / 대한주산의학회잡지

Hepatitis A virus infection is the most common cause of acute hepatitis but is rarely reported during pregnancy. We report a case of acute hepatitis A in a 28-year old pregnant woman at 40 weeks of gestation. Her initial complaint was fever. Three days after, she developed spontaneous labor and delivered a healthy baby vaginally. Her laboratory examination showed thrombocytopenia, elevated D-dimer and decreased Fibrinogen level as well as markedly elevated liver enzymes. In addition, oliguria and pulmonary effusion were also noted. Hepatitis A infection during pregnancy may be associated with development of labor. And the differential diagnosis with preeclampsia and acute fatty liver of pregnancy is very important for the management.

A case of advanced gynecologic pelvic tumors showing the diagnostic utility of HPV analysis / 부인종양

Gynecologic malignancies may have similar histological characteristics. This may lead to difficulties in determining the origin of the cancer and to distinguish a synchronous neoplasm from a metastatic cancer in advanced cases. Recently, we treated a 59-year-old patient with adenocarcinoma of the uterine cervix, endometrium, fallopian tubes, and ovaries. It was difficult to determine whether the cancer was a single origin metastatic cancer or a synchronous neoplasm. The patient was finally diagnosed with metastatic cancer that originated from the uterine cervix by human papillomavirus (HPV) test. Here we report the case and briefly review of the medical literature.

Effect of topical Paclitaxel using PEG/PLGA polymer on the animal model of cervical cancer / 부인종양

OBJECTIVE: Paclitaxel is one of the most effective antineoplastic drugs. HPV-related cervical lesions have only managed with invasive procedure. Topical drug administration with temperature sensitive copolymer gels are useful approaches to clinical situation. In this study, we evaluated the activity of multiblock copolymers of PEG/PLA (poly(L-lactic acid)/polyethylene glycol) gels with paclitaxel (PTX) formulation administered by topical treatment to mice bearing human cervical cancer cell lines (HeLa). METHODS: We have synthesized gels of PEG/PLLA (poly(L-lactic acid)/polyethylene glycol) multiblock copolymers containing Paclitaxel which have temperature-sensitivecharacteristics. This Paclitaxel-containg copolymers has the sol-gel-sol transition temperature at body temperature. The efficacy of PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment. Tumors were harvested at day 10 and stained with hematoxylin and eosine to measure tumor. RESULTS: PTX-containing PEG/PLA mutiblock copolymer significantly decreased tumor growth at day 8, as measured by tumor size; ie, PEG/PLA mutiblock copolymer only goup ; 1.43+/-0.26 m versus intraperitoneal treatment of Paclitaxel : 0.75+/-0.07 mm and topical treatment of PTX-containing PEG/PLA copolymer containing Paclitaxel : 0.28 mm (Min; 0.1 mm-Maxu0.8 mm). CONCLUSION: This demonstration that PTX-containing PEG/PLA mutiblock copolymer have a useful topical drug deliversy system carrying temperature sensitive characetersitics in HPV-related cervical lesions.

Value of Human Papilloma Virus load in hybrid capture II assay to predict high grade cervical intraepithelial neoplasia in menopausal women with ASCUS or LSIL / 대한산부인과학회지

OBJECTIVE: To evaluate whether determination of the Human Papilloma Virus (HPV) viral load is helpful to predict the presence of high-grade cervical intraepithelial neoplasia (CIN) that requires aggressive treatment in menopausal women who have presented with an unsatisfactory colposcopic finding and ASCUS or LSIL. METHODS: In menopausal women with ASCUS or LSIL and with who were positive for HPV, 54 women had diagnostic conization were analyzed retrospectively. We used the Hybrid Capture II method. We classified women in a low-risk group (chronic cervicitis, CIN I) and a high-risk group (> or =CIN II) according to the pathological results of conization. We also classified patients into the HPV viral load or =100 RLU/PC group. We analyzed the relationship between the pathological results of conization and viral load. RESULTS: For the conization, 30 women had chronic cervicitis, nine women had CIN I, three women had CIN II and 12 women had CIN III. In the low Hybrid Capture titer-group ( or =CIN II pathology but in the high Hybrid Capture titer-group (> or =100 RLU/PC), 11 women had high risk pathology this finding was statistically significant (P=0.013). Compared to the low Hybrid Capture titer group, the relative risk of high grade CIN (> or =CIN II) in the high Hybrid Capture titer group was 2.043 (95% CI, 1.216~3.432). CONCLUSIONS: For menopausal women with an unsatisfactory colposcopic finding and also have ASCUS or LSIL women with high HPV viral load might have tendency of > or =CIN II pathology.

A case of endometrioma at the uterine incision scar of previous cesarean section / 대한산부인과학회지

Endometriosis is defined as condition, which is ectopic location of endometrial tissue other than uterus and cause many clinical symptoms. Among extrapelvic endometriosis, scar endometriosis secondary to surgery or procedure is very rare condition. We have experienced one interesting case of endometrioma in uterine wall cesarean section scar. The diagnosis was confirmed by histopathologic examination of the scar tissue taken after total abdominal hysterectomy.

Recommendation guideline of Korean Society of Gynecologic Oncology and Colposcopy for quadrivalent human papillomavirus vaccine / 부인종양

Genital HPV infection is the most common sexually transmitted infection, but the majority of infections are self-limited. However, persistent infection with high-risk types can cause cervical cancer in women, which is the most common female genital cancer in Korea. In addition, HPV infection is the cause of genital warts and is associated with other anogenital cancers. The HPV vaccine is composed of the HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein in yeast using recombinant DNA technology produces noninfectious virus-like particles (VLP) that resemble HPV virions. The quadrivalent HPV vaccine is a mixture of four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18 combined with an aluminum adjuvant. Clinical trials indicate that the vaccine has high efficacy in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV types 6, 11, 16, or 18 among females who have not already been infected with the respective HPV type. The recommended age for primary vaccination of Korean females is 15-17 years, considering sexual debut and duration of protection of the vaccine. Vaccine can be administered as young as age 9 years. Catch-up vaccination is recommended for females aged 18-26 years who have not been previously vaccinated. Vaccination is not a substitute for routine cervical cancer screening, and vaccinated females should have cervical cancer screening as recommended.

Development of a therapeutic method in the HPV-related cervical lesion using pH/temperature sensitive polymer spray formulation / 부인종양

OBJECTIVE: The causal link between oncogenic HPV(Human Papilloma Viruses) and the development of CIN (rvical intraepithelial neoplasia) and cervical cancer are now well established. Several medical therapeutic candidates aimd at the treatment of precancerous lesions and invasive carcinoma of the cervix. The objective of this study was to develop the pH-sensitive chitosan/alginate gels (pH=3.8-4.5) and temperature sensitive multiblock copolymers of PEG/PLA (poly (L-lactic acid)/polyethylene glycol) gels (temperature=37 degrees C) for controlled delivery of the paclitaxel (PTX). We had also evaluated whether PTX entrapped in chitosan/alginate gels or multiblock copolymers of PEG/PLA 1 could inhibit tumor growth in vivo. METHODS: PTX entrapped as microsphere in Chitosan/Alginate Microspheres were obtained using a spray-drying method. PTX-entrapped PEG/PLA gels were prepared by the solvent displacement method. We had prepared the multiblock copolymers of PEG/PLA which has the sol-gel-sol transition temperature at body temperature. The in-vivo efficacy of PTX in chitosan microphere or PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment. RESULTS: On 8 days after the transcutaneous treatment of PTX-containing chitosan microphere or PTX in PEG/PLA mutiblock copolymer micelle. significant inhibition in tumor growth was observed in balb/c nu/nu nude mouse carrying xenograft tumors (HeLa cells; HPV-18 positive state). Among these formulations, PTX in PEG/PLA mutiblock copolymer have shown improved therapeutic efficacy as compared to PTX-ivgroup. CONCLUSION: PTX-containing chitosan microphere or PTX in PEG/PLA mutiblock copolymer nanoparticles are a unique pH-sensitive and temperature sensitive drug delivery system. These formulations elicits enhanced efficacy as an effective and minimally invasive treatment in mice bearing human cervical cancer (HeLa Cells) xenograft.

A case of abdominal pregnancy implanted on uterosacral ligament / 대한산부인과학회지

Abdominal pregnancy, a rare type of ectopic pregnancy is difficult to be suspected at its first presentation. The diagnosis of this rare disease may often be delayed, since early symptoms are usually non-specific. In some cases, delayed diagnosis of abdominal preganacy can be associated with catastrophic hemorrhage secondary to placental separation. A 24-year old woman visited our emergency unit, presenting with a sudden-onset low abdominal pain. She had undergone uterine curettage 3 weeks before. Transvaginal sonogram of the cul-de-sac revealed complex fluid consistent with blood. On diagnostic laparoscopic operation, we found a ruptured cystic, conception-like structure near the right uterosacral ligament. Histology of the resected structure finally showed chorionic villi consistent with abdominal pregnancy. In this report, we present an unusual case of abdominal pregnancy. This case underscores the careful ultrasonic determination of gestational location at early pregnancy.

Cytotoxic effects of Belotecan in the cervical cancer cell lines / 대한산부인과학회지

OBJECTIVE: In our domestic market, Belotecan (Camptobel(R), chongkeundang, Korea) is newly introduced recently. Belotecan has many advantages of improved water solubility and fewer side effects like severe diarrhea or GI bleeding compare to other camptothecin derivatives. In this study, primary focus is aiming to evaluate the effectiveness of belotecan by providing the cytotoxicity and apoptotic pathway on cervical cancer cells. METHODS: Cervical cancer cell line, HeLa and Caski were used. Belotecan applied on both cell lines and checked whether it has anti tumor effect on cancer cell by using MTT assay. DNA fragmentation and western blot was performed to confirm cellular apoptosis pathway. Also cDNA microarray and RT-PCR were serially carried out in order to identify responsible genes for apoptosis. RESULT: Dose- and time- dependent inhibition of cell proliferation is noted on the Belotecan applied HeLa and CaSki cervical carcinoma cell line by MTT assay. DNA fragmentation assay showed the DNA ladder indicating apopoptosis. Also apoptotic pathway and genes that are related with Belotecan activities are identified. Apoptosis, cell cycle, and drug metabolism related gene, and DNA repair gene were found to be differently regulated by treatment of Belotecan in HeLa cells. Among the DNA repair gene, RT-PCR reconfirmed the increased expression of CIB1(Calcium and intergrin binding 1), APEX1 (APEX nuclease 1) and the decresed expression of EXO1 (Exonuclease 1), WDR33 (WD repeat domain 33), and GADD45A (Growth arrest and DNA-damage-inducible, alpha). CONCLUSION: The first domestically introduced 1st line anti- tumor agent, Belotecan shows its excellent inhibiting action on cervical cancer cell proliferation by apoptotic pathway in this study. Also genetic alterations in cDNA microarray leads to the new fact that Belotecan, as a topoisomerase I inhibitor, is not only involved with apoptotic, cell cycle-related pathway but also involved in DNA repair.

Diagnosis of an Interstitial Pregnancy with 3-dimensional Transvaginal Sonography / 대한주산의학회잡지

Interstitial pregnancy is an ectopic pregnancy which is located in the intramural portion of the tube covered by myometrium. Rupture usually results in catastrophic hemorrhage, since there is an anastomosis of uterine artery and tuboovarian vessels. Therefore, the early diagnosis is important to decrease maternal morbidity. However, the diagnosis using the conventional 2-dimensional transvaginal sonography has some difficulties in differentiation from corneal pregnancy. In this case, we diagnosed an interstitial pregnancy using the 3-dimensional sonography in a woman with amenorrhea for 7 weeks and 1 days, which was resected through laparoscopic operation. The 3-dimensional sonography has a potential role to define the location of pregnancy implanted on the outer site of uterine fundus.

Diagnosis of an Interstitial Pregnancy with 3-dimensional Transvaginal Sonography / 대한주산의학회잡지

Interstitial pregnancy is an ectopic pregnancy which is located in the intramural portion of the tube covered by myometrium. Rupture usually results in catastrophic hemorrhage, since there is an anastomosis of uterine artery and tuboovarian vessels. Therefore, the early diagnosis is important to decrease maternal morbidity. However, the diagnosis using the conventional 2-dimensional transvaginal sonography has some difficulties in differentiation from corneal pregnancy. In this case, we diagnosed an interstitial pregnancy using the 3-dimensional sonography in a woman with amenorrhea for 7 weeks and 1 days, which was resected through laparoscopic operation. The 3-dimensional sonography has a potential role to define the location of pregnancy implanted on the outer site of uterine fundus.

A case of cystolithiasis after intravesical migration of Copper T intrauterine device / 대한산부인과학회지

An intrauterine device (IUD) is one of the most commonly used contraceptive method in the world. One of the major complications of intrauterine contraception is the perforation through the uterine wall into the pelvic or abdominal cavity. The incidence is 0.9 people per 1000. However, bladder perforation is even more rare. It happens mostly at the time when it was inserted. The symptom varies from no symptom at all to low abdominal pain, massive bleeding, et cetera. We report a case with displaced intrauterine device in bladder, producing the bladder stone which was managed with cystoscopic lithotripsy and intrauterine device removal, followed by a review of the literature.

Prognosis of Threatened Abortion according to Embryonic Heart Rate / 대한주산의학회잡지

OBJECTIVE: The purpose of our study was to investigate the relationship between prognosis of threatened abortion and embryonic heart rate at diagnosis. METHODS: The study group included 86 patients in which a singleton fetus with cardiac activity was initially documented. The study population was divided into successful pregnancy group (73 cases, pregnancy was maintained above 20 weeks of gestation) and spontaneous abortion group (13 cases). We compared the embryonic heart rate, age of mother, gestational age at diagnosis between two groups. RESULTS: A significant difference of embryonic heart rate was noted between the successful group and the spontaneous abortion group (153.1+/-22.9 vs 134.6+/-18.8 beats/min, p=0.0076). There was no statistical difference in the gestational age at diagnosis (8.0+/-1.9 vs 7.5+/-1.9 weeks), the age of mother, and primi para proportion. CONCLUSION: The prognosis of threatened abortion was related to the embryonic heart rate. Embryos with slow heart rates had a greater risk of spontaneous abortion. All cases with slow embryonic heart rate (<110 beats/min) had occurred spontaneous abortion. Therefore, these case were needed more information and aggressive treatment.

Ras association domain family 1A (RASSF1A) Ala133Ser polymorphism is associated with cervical cancer in Korean women / 부인종양

OBJECTIVE: The ras association domain family 1A (RASSF1A) gene plays an important part in carcinogenesis by inactivation via promoter hypermethylation in several cancers. We aimed to examine the effect of the RASSF1A Ala133Ser polymorphism on cervical carcinogenesis in reference to environmental factors, such as smoking and age at first sexual intercourse. METHODS: Seven hundred five patients who were diagnosed with cervical neoplasia and who had a positive results for human papillomavirus were enrolled to experimental group, and 641 of normal healthy women were enrolled as controls. All of the subjects were genotyped using the SNaPshot single base primer extension assay. RESULTS: Compared with RASSF1A TT/GT, the odds ratio (95% confidence interval) for RASSF1A GG was 1.4 (0.9-2.1) for invasive cervical cancer and 1.1 (0.7-1.7) for cervical intraepithelial neoplasia (CIN) II or III. The risks for cervical cancer were higher in patients under 40 years old at diagnosis (1.6, 1.0-2.6), than in patients over 40 years old at diagnosis (1.0, 0.7-1.5). Women with RASSF1A GG who currently smoke had a 2.7 (1.3-5.9) times higher risk of cervical cancer. Women with RASSF1A GG who had an early age of first intercourse, as compared with RASSF1A TT/GT, were also at increased risk. CONCLUSION: The RASSF1A Ala133Ser polymorphism is associated with a higher risk of cervical cancer and particularly with an early onset of cervical carcinogenesis.

Sexual behavior of Korean young women: preliminary study for the introducing of HPV prophylactic vaccine / 부인종양

OBJECTIVE: The decision of optimal age for administration of recently approved prophylactic human papillomavirus (HPV) vaccines in the world depend on the basis of the sexual behavior of each countries. The aim of the study was to survey the age-specific sexual behavior including the sexual debut time and sexual experience in the Korean young women to design the tailored HPV vaccination. METHODS: This study was conducted by the Synovate Healthcare in the 6 city of Korea e.g. Seoul, Pusan, Daegu, Incheon, Kwangju and Daejon. By a stratified sampling methods 2,400 women aged 12-29 years old were included. The measures of sexual behavior presented in this report were collected by a Computer-Assisted Self-Interviewing (ACASI), in which the respondent enters her own answers into a computer without telling them to an interviewer. RESULTS: Among women 12-29 years of age, 39 percent of women (934 persons in 2,400 women) and 33 percent of single women (724 persons in 2,190 women) have had vaginal intercourse; 8 percent of women under 19 years old single women (79 persons in 1,045) and 56 percent of single women with 20-29 years old (645 persons in 1,145). Number of sexual partner was 2.8 person and 54 percent of women had more than 2 partners. Age of the first sexual activity (sexual debut) was 21 years old. The age of partner at the sexual debut was 23.2 years old. Sexual experience before 15 years old was only 2%. About the condom, 41% did not use or rarely use. CONCLUSION: Our data demonstrate that the sexual debut time of young Korean women differ from other countries in which the prophylactic HPV vaccine had already used. We conclude that the optimal age for HPV vaccination in Korea would be determined at 15-17 years old by this situation.

Transcutaneous DNA immunization of HPV-16 E7 with hair-follicle specific promoter in mice / 대한산부인과학회지

OBJECTIVE: Previous reports have shown that transcutaneous immunization (TCI) with proteins or peptides in combination with adjuvants efficiently induces specific cellular and humoral immune responses. We compared the immune response after TCI with new construct which was derived from HPV-16 E7opt+K and pK6hf promoter instead of pCMV promoter and various adjuvant. METHODS: First, we made new construct ligated with HPV-16 E7 opt+K to Hair-follicle Specific pK6hf Promoter. Second, we applied pk6hf-E7 opt+K DNA with or without Lipofectamine 2000 and a combination of cholera toxin (CT) and CpG oligodeoxynucleotide (CpG) onto cold wax-depilated and hydrated bare skin of C57 BL/6 mice. To assess the ability of CTL(cytotoxic T-lymphocyte) activity, we performed intracellular cytokine staining with flow cytometric analysis to determine the number of E7-specific IFN-gamma- secreting CD8+ T cells generated in vaccinated mice with the DNA vaccine. RESULTS: Female C57BL/6 mice immunized by TCI methods with 30 microgram of pk6hf-E7 opt+K DNA with Lipofectamine2000 and CT efficiently generated E7-specific CD8(+) T cells compared with the group of pk6hf-E7 opt+K DNA only or DNA with Lipofectamine2000. CONCLUSION: Our results demonstrate that TCI of the linkaged-E7 DNA , E7 opt+K DNA to pk6hf, and Lipofectamine2000 and CT induced an antigen-specific CTL response. This result is of potential relevance for the development of therapeutic HPV-specific DNA vaccines with TCI and pK6hf promoter can be used safely.

Clinicopathologic characteristics and prognostic factors in adenocarcinoma of the uterine cervix / 대한산부인과학회지

OBJECTIVE: To evaluate clinicopathologic characteristics and prognostic factors in adenocarcinoma of the uterine cervix. METHODS: Medical records of patients with adenocarcinoma of the cervix who primarily underwent radical hysterectomy and pelvic lymphadenectomy (n=72) at A Hospital from August 1998 to July 2004 were retrospectively reviewed. Patients with stage IA1-IIB lesions were included in the study. Clinical and pathological data were reviewed and analyzed. RESULTS: Mean age at presentation was 46.5 years. The mean follow-up time for surviving patients was 35 months. The overall survival rate was 91.7% and disease free survival rate was 88.9%. Using univariate analysis, stage, lymph-vascular space invasion (LVSI), parametrial invasion, pelvic lymph node invasion and depth of stromal invasion were significant for survival, whereas grade, age, endometrial invasion were not significant. But using multivariate analysis, only stage and pelvic lymph node invasion remained significant independent predictors for survival. CONCLUSION: Our study demonstrates that survival rate is high for patients with early stage, after primary surgery. We found stage and pelvic lymph node invasion of significant prognostic value for survival in cervical adenocarcinoma.