Practice guidelines for management of cervical cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement / 부인종양

Clinical practice guidelines for gynecologic cancers have been developed by academic society from several countries. Each guideline reflected their own insurance system and unique medical environment, based on the published evidence. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to develop the third edition of the guidelines in an advanced format based on evidence-based medicine, embracing up-to-date clinical trials and qualified Korean data. These guidelines cover strategies for diagnosis and treatment of primary and recurrent cervical cancer. The committee members and many gynecologic oncologists derived key questions through discussions, and a number of relevant scientific literature were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, along with the details. The objective of these practice guidelines is to establish standard policies on issues in clinical practice related to the management in cervical cancer based on the results in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Right ventricular metastatic tumor from a primary carcinoma of uterine cervix: A cause of pulmonary embolism

The presence of intracavitary cardiac metastasis from squamous cell carcinoma of the uterine cervix is extremely rare. The diagnosis is made almost exclusively postmortem. Apart from causing intracardiac obstruction, it can present as pulmonary emboli and the prognosis is extremely poor. It is important to suspect this diagnosis in patient with recurrent pulmonary emboli. Due to the rarity of this condition it is very difficult to standardize care for these patients. However, it is possible that aggressive therapy may lengthen patients' survival and quality of life. We present a case of isolated intracavitary cardiac metastasis arising from a squamous cell carcinoma of the cervix, 44-year-old woman, diagnosed as stage complaint of fatigue and dyspnea on mild exertion. The echocardiogram showed a mass in the right ventricle and suspicious pulmonary embolism. We took an aggressive therapeutic approach. The pathological examination of the resected tissue revealed metastatic squamous cell carcinoma.

Syndrome of inappropriate antidiuretic hormone secretion following irinotecan-cisplatin administration as a treatment for recurrent ovarian clear cell carcinoma

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) has various causes including central nervous system disorders, pulmonary and endocrine diseases, paraneoplastic syndromes, and use of certain drugs. SIADH induced by chemotherapy with irinotecan-cisplatin is not a common complication. Here, we review a case of SIADH after treatment with irinotecan-cisplatin. A 45-year-old woman received adjuvant chemotherapy (paclitaxel-carboplatin) for ovarian clear cell carcinoma, but the cancer recurred within 9 months of chemotherapy. Subsequently, a second line of combination chemotherapy containing irinotecan-cisplatin was initiated. However, 5 days after chemotherapy administration, her general condition began to deteriorate; her hematological tests revealed hyponatremia. Therefore, it is imperative to consider the possibility of SIADH in patients being treated with irinotecan-cisplatin–based chemotherapy. Proper monitoring of serum sodium levels and assessment of clinical symptoms should be performed in such patients for early diagnosis and prompt management.

Abnormally high level of CA-19-9 in a benign ovarian cyst

CA-19-9 antigen is mainly elevated in cases of gastrointestinal tract malignancy, including of the pancreas, colorectum, and biliary tract. CA 19-9 antigen can also be elevated in ovarian mucinous neoplasms, however, as well as in many benign conditions. Markedly raised levels of more than 10,000 U/mL were almost observed in advanced stage of malignancy. We report herein the case of a 37-year-old woman who presented with an abnormally high level of CA 19-9 antigen associated with benign mucinous cystadenoma.

Epidemiologic characteristics of cervical cancer in Korean women / 부인종양

Cervical cancer is the most common female genital tract malignancy in Korean women. Although age-standardized cancer incidence rate of cervical cancer has decreased from 18.6 per 100,000 women in 1999 to 12.3 per 100,000 women in 2010 in Korea with widespread routine screening, several epidemiologic characteristics are still present. Incidence of cervical cancer still varies according to geographic area, and a significant portion of cases are detected at a locoregionally advanced stage, without significant improvement of five-year survival rate.2014-01-15 Cervical screening techniques such as the Pap smear should be the gold standard strategy to decrease incidence and to improve the survival outcomes of patients with cervical cancer. In addition, screening programs for cervical cancer should be designed, organized and directed within the context of a nationwide program for cancer control.

The predictive factors for injury severity and pregnancy outcomes after traffic accidents during pregnancy / 대한산부인과학회지

OBJECTIVE: To estimate the predictive factors associated with traffic injury severity and pregnancy outcomes in traffic accidents during pregnancy. METHODS: We performed a retrospective case review study to assess 109 pregnant women who were injured by traffic accidents and were admitted to Gangneung Asan Hospital and KyungHee University Hospital from September 1996 to January 2009. The clinical data of maternal age, parity, gestational age, symptoms of the patients that happened after accidents, accident location, seat position in vehicle, maternal injury severity which was quantified with injury severity score (ISS), pregnancy outcomes, and subchorionic hematoma were reviewed with the medical records or the telephone interviews. Adverse pregnant outcomes included abortion, preterm delivery and fetal death in uterus. Multiple logistic regression analysis was performed to evaluate the predictive factors for injury severity and pregnancy outcomes after traffic accidents. RESULTS: Pedestrian injury and first trimester were significantly associated with severity of maternal injury. Multivariate analysis revealed that abdominal pain was independently predictive factor for the severity of maternal injury. The second trimester, pedestrian injury, right front seat of vehicle, severity of maternal injury and subchorionic hematoma were significantly associated with adverse pregnancy outcomes. Multivariate analysis revealed that severity of maternal injury and subchorionic hematoma were independently predictive factors for adverse pregnancy outcomes. CONCLUSION: According to predictive factors for pregnancy outcomes, the severity of maternal injury estimated with ISS score and subchorionic hematoma seems to be helpful indicators in the management of traffic accident injuries during pregnancy.

Pulmonary Toxicity after a Quick Course of Combinatorial Vincristine, Bleomycin, and Cisplatin Neoadjuvant Chemotherapy in Cervical Cancer

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.

Clinical analysis of Bell's palsy in pregnancy / 대한산부인과학회지

OBJECTIVE: Although Bell's palsy is not common in pregnancy, it is more prevalent among pregnant women than among non-pregnant women. Since the exact clinical characteristics of this condition are not fully understood, we evaluated the epidemiology, pathophysiology, onset time, as well as the recovery rate according to treatment modality of Bell's palsy in pregnancy, and compared them to those of the non-pregnant population in this study. METHODS: Between March 1996 and February 2006, we identified 43 patients who suffered from Bell's palsy during pregnancy and postpartum with a minimum 6 month follow up at Kyung Hee University Hospital. We conducted retrospective medical records analysis and compared them to similary chosen Bell's palsy case in non pregnant women who were matched for age. RESULTS: The median gestational age at the onset of Bell's palsy was 32 weeks. Among the 43 patients who had been diagnosed with Bell's palsy in pregnancy, 81.4% (35 of 43) showed a satisfactory outcome. Among the 36 patients with complete palsy, 77.8% (28 of 36) showed a satisfactory recovery. Recovery rate according to treatment modality in pregnant patients with Bell's palsy were 28/35 (80.0%) in the acupuncture group, 3/3 (100%) in the steroid therapy group, and 4/5 (80.0%) in the combined acupuncture and steroid therapy group, respectively. CONCLUSION: We did not detect any difference in clinical characteristics of Bell's palsy in the pregnant group compared with the non-pregnant group. Further study will be needed to select the method of treatment for Bell's palsy in pregnant women.

Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers / 부인종양

OBJECTIVE: To define the molecular basis of TGF-beta1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta1, TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling pathway, in human cervical cancers. METHODS: Expression of TGF-beta1, TGF-beta1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by quantitative genomic PCR. RESULTS: Abnormal overexpression of TGF-beta1 and abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis. CONCLUSION: Our study demonstrates that disruption of TGF-beta/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor suppression function.

The effect of HER-2 polymorphism according to age on the risk and pathologic feature of endometrial cancer / 대한산부인과학회지

OBJECTIVE: To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene and age on the risk and pathologic feature of endometrial cancer. METHODS: We included 125 women with histologically confirmed endometrioid adenocarcinoma who underwent complete surgical staging. The control group consisted of 302 patients with benign gynecologic disease who underwent hysterectomy. Nine SNPs spanning the HER-2 gene were genotyped by SNP-IT assay using SNPstream(r) Genotyping System. Of 9 SNPs, 5 that were either monomorphic or had a lowallele frequency ( or =10%; these were included in the final analysis. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for BMI. RESULTS: The mean age for endometrial cancer patients was 53.4+/-11.5 (range, 29-81) years. Forty-seven patients (38%) were or =50 years. Cases had a significantly higher BMI than controls (P<0.001). After adjustment for BMI, there was no significant relationship between HER-2 polymorphism and the risk of endometrial cancer based on age. Furthermore, HER-2 polymorphism did not affect the pathologic features of endometrial cancer based on age. CONCLUSION: Although there is no potential association among HER-2 polymorphisms, age, and endometrial cancer risk, large studies are needed in the future to assess the role of this polymorphism in endometrial cancer and for its combined effect.

The effect of HER-2 polymorphism according to age on the risk and pathologic feature of endometrial cancer / 대한산부인과학회지

OBJECTIVE: To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene and age on the risk and pathologic feature of endometrial cancer. METHODS: We included 125 women with histologically confirmed endometrioid adenocarcinoma who underwent complete surgical staging. The control group consisted of 302 patients with benign gynecologic disease who underwent hysterectomy. Nine SNPs spanning the HER-2 gene were genotyped by SNP-IT assay using SNPstream(r) Genotyping System. Of 9 SNPs, 5 that were either monomorphic or had a lowallele frequency ( or =10%; these were included in the final analysis. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for BMI. RESULTS: The mean age for endometrial cancer patients was 53.4+/-11.5 (range, 29-81) years. Forty-seven patients (38%) were or =50 years. Cases had a significantly higher BMI than controls (P<0.001). After adjustment for BMI, there was no significant relationship between HER-2 polymorphism and the risk of endometrial cancer based on age. Furthermore, HER-2 polymorphism did not affect the pathologic features of endometrial cancer based on age. CONCLUSION: Although there is no potential association among HER-2 polymorphisms, age, and endometrial cancer risk, large studies are needed in the future to assess the role of this polymorphism in endometrial cancer and for its combined effect.

Expression of MTA1 and nm23-H1 protein in ovarian carcinomas in relation to lymph node metastasis / 부인종양

OBJECTIVE: Cancer metastasis is a complex process involving a sequential series of multi-step genetic events, which produces an imbalance between stimulatory and inhibitory genes for metastasis. Presently, we examined the expression of metastatic tumor antigen 1 (MTA1) and nonmetastatic protein 23 homologue H1 (nm23-H1) proteins in metastasized epithelial ovarian cancer cells. METHODS: Fifty-one primary epithelial ovarian tumors and corresponding lymph nodes (LNs) were examined immunohistochemically for expression of MTA1 and nm23-H1. Expression of these proteins was statistically evaluated. RESULTS: The frequency of MTA1 expression was 30.3% (10/33) in stage III/IV LNs but was absent (0/18) in stage I/II LNs (p=0.01). MTA1 expression was observed in 50% (6/12) of metastasizing LNs but in only 10.3% (4/39) of non-metastasizing LNs (p=0.01). In contrast with MTA1, nm23-H1 expression was evident in 16 of 18 (88.9%) stage I/II ovarian cancer tissue samples but only in 20 of 33 (60.6%) stage III/IV tissues (p=0.05), and nm23-H1 production was also observed in 75.6% (34/45) of ovarian cancer tissue with residual tumors under 2 cm in diameter, but in 2/6 (33.3%) of cancer tissue with residual tumors exceeding 2 cm in diameter (p=0.03). CONCLUSION: The degree of expression and imbalance of MTA1 and nm23H1 are correlated with ovarian cancer LN metastasis.

Role of 5'-CpG island hypermethylation of the FHIT gene in cervical carcinoma / 부인종양

OBJECTIVE: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer. METHODS: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing. RESULTS: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics. CONCLUSION: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort.

The Follicular Fluid and Serum Concentrations of Vascular Endothelial Growth Factor in patients during IVF-ET Cycles / 대한산부인과학회지

OBJECTIVE: Several aspects of female reproduction, from folliculogenesis to corpus luteum function, are related to angiogenesis. The purpose of this study is to measure the concentrations of vascular endothelial growth factor (VEGF) in follicular fluid and serum in patients during In Vitro Fertilization-Embryo Transfer (IVF-ET) cycles. METHODS: In our prospective study, twenty-nine patients who underwent in vitro fertilization by GnRH agonist short protocol were assessed at the our infertility clinic from Aug. 2003 to July 2005. Serum VEGF and follicular fluid VEGF levels were measured in all patients at the time of oocytes retrieval. The assay technique used in this study was ELISA for serum and follicular fluid VEGF. RESULTS: Of 29 cycles, 10 cycles were pregnant (34.5%). A positive correlation existed for follicular fluid VEGF and chronologic age (r=0.428, p-value=0.021). Follicular fluid VEGF concentration showed an inverse relationship with the total number of oocytes retrieved and follicles (r=-0.493, p-value=0.007; r=-0.474, p-value=0.009). But there was no statistically significant relationship between follicular fluid VEGF concentration and serum VEGF concentration (rho=0.347). Follicular fluid VEGF concentration was significantly higher in the non-pregnant group (1468.38+/-727.33 pg/mL) compared to the pregnant group (676.48+/-542.07 pg/mL) (p-value=0.003). CONCLUSION: Our data provide some of the evidences that elevated VEGF concentrations in the follicular fluid are associated with poor conception rates in the IVF-ET cycles.

A Case of Ovarian Malignant Melanoma showing Peritoneal Dissemination with Unknown Primary Origin / 대한산부인과학회지

Malignant melanoma is a neoplasm of the skin and mucous membrane which very rarely occurs in the ovary. Malignant melanomas occurring in the ovary must be differentiated from primary and metastatic malignant melanoma. Primary malignant melanoma of the ovary is extremely rare and is thought to originate from a cystic teratoma. Malignant melanoma of ovary without evidence of residual teratoma must be considered metastatic even in the absence of a previously cutaneous or mucocutaneous lesion. Opinions about its histogenesis, diagnostic criteria and elective treatment are controversial because of rare manifestations, and the prognosis remains poor in spite of the variety of therapeutic measures. After thoroughly surveying the specific literature, we report case of malignant melanoma with multiple metastases located in the stomach, the omentum and both ovaries with unknown site of primary origin.

A case of elevated serum transaminase levels associated with the use of ritodrine during pregnancy / 대한산부인과학회지

Ritodrine hydrochloride (Yutopar) is commonly used for the treatment of preterm labor. Published reports claim that many complications of prematurity have been averted by the administration of this drug. However, ritodrine hydrochloride has many side effects, including cardiovascular problem and metabolic error. Only a few reports have described the transient hepatitis (elevated transaminase) all over the world. The clinical significance and incidence of this side effect are still unclear. In this report, we present a case of elevated serum transaminase levels associated with the use of ritodrine during pregnancy with a brief review of the literatures.

A case report: A case of fibroepithelial polyp on vulvoperineal area / 대한산부인과학회지

A case of fibroepithelial polyp on vulvoperineal area is described. Her age is 20 year old and the tumor measured 9 cm in its largest diameter and was connected to the left labium majus. This case is very unusual in that almost all reported vulvar fibroepithelial polyps are small and sessile, and should distinguish from malignant cancer. We have experienced an unusually large vulvoperineal mass that was surgically excised and histologically diagnosed as benign fibroepithelial polyp and present this case with a brief review of literature.