Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy. @*Materials and Methods@#We analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease- free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors. @*Results@#Independent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group. @*Conclusion@#We developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

Liver recurrence in early endometrial cancer with focal myometrial invasion

Endometrial cancer is the most common malignancy of the female genital tract. The cancer spreads by direct extension, transtubal dissemination, lymphatic dissemination, and/or by hematogenous spread, usually results in lung metastasis, but may less commonly involve liver, brain, and bone. Here, we describe a patient with stage IA endometrial cancer who developed liver recurrence 17 months after surgery.

Bilateral transient osteoporosis of the hip associated with pregnancy: A case report / 대한산부인과학회지

Transient osteoporosis of the hip (TOH) associated with pregnancy is a rare, self- limiting skeletal disorder affecting women, usually in the third trimester, which resolves spontaneously within several months postpartum. Magnetic resonance imaging (MRI) is used primarily for early diagnosis and monitoring the disease progression. Early differentiation from more aggressive conditions such as avascular osteonecrosis, septic coxitis, arthritis, osteomyelitis with long-term sequela is essential to avoid unnecessary treatment. Unilateral involvement of TOH is common. To our knowledge, there has been no case with bilateral involvement of TOH during pregnancy in Korea. We report a rare case with bilateral TOH associated with pregnancy.

E-cadherin expression and mutation in endometrial carcinomas and endometrial hyperplasias / 대한산부인과학회지

OBJECTIVE: Reduced tumor cell adhesion is associated with invasive growth and unfavorable prognosis. In endometrial carcinoma, the prognostic impact of adhesion marker such as E-cadherin is partly known. The purpose of this study is to investigate the correlation of the expression and the mutation of E-cadherin in endometrioid endometrial adenocarcinomas and endometrial hyperplasias and to correlate their results with various clinicopathological factors. METHODS: The expression of E-cadherin by using immunohistochemical staining (IHC) and the mutation of E-cadherin gene by using polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and sequencing were performed in tissues of 20 endometrial adenocarcinomas and 30 endometrial hyperplasias. The results were compared with previously known prognostic factors such as the stage, tumor grade and lymph node metastasis. RESULTS: Decreased expression of E-cadherin was detected in 13 of 30 (43.3%) endometrial carcinomas and in 1 of 20 (5%) endometrial hyperplasias (P=0.009). There was no statistical significance of the mutation of E-cadherin gene in between the endometrial carcinomas and endometrial hyperplasias (6.7%: 0%) (P=0.06). The incidence of the expression loss of E-cadherin in endometrial carcinomas also showed significantly higher with tumor grade 3, tumor stage above Ic or lymph nodal metastasis (P=0.01, P=0.02, P=0.03). CONCLUSION: Decreased expression of E-cadherin was detected significantly higher in endometrial carcinomas than endometrial hyperplasias. And the incidence of decreased expression of E-cadherin was more frequent in advanced stage, high histopathologic grade, and lymph nodal metasis. The mutation of E-cadherin gene was detected in only 2 cases. These results suggests that the expression of E-cadherin seems to be important in endometrial carcinomas and associated with aggressive subgroups. But the mutation of E-cadherin gene would not be related to endometrial carcinomas.

Surgical practice patterns in endometrial cancer: results of the Korean Gynecologic Oncology Group survey / 부인종양

OBJECTIVE: This study was undertaken to document current practice patterns for the surgical treatment of endometrial cancer in Korea. METHODS: Questionnaires were distributed to 131 Korean gynecologic oncologists, all members of the Korean Gynecologic Oncology Group. Questions addressed extent of hysterectomy procedure, pelvic (PEN) or paraaortic (PAN) lymph node dissection, ovarian preservation, and omentectomy. RESULTS: Completed questionnaires were returned by 64.1% (84/131) of the oncologists at 50 institutes. Extrafascial hysterectomy (EH) was used by 32% of respondents and modified radical hysterectomy (MRH) or radical hysterectomy (RH) by 17%. Hysterectomy procedures were selectively employed based on tumor-related factors by 51% of the respondents. Laparoscopic hysterectomy was routinely utilized by 49% and was more commonly used by younger surgeons with 10 years of experience or less. PEN dissection was routinely utilized by 67% and was used selectively based on tumor-related factors by 33%. PAN dissection/biopsy was used either routinely (43%) or selectively based on tumor-related factors (43%). PAN dissection/biopsy had never been employed by 12% of the respondents. Sixty-nine percent of respondents stated that grossly normal looking ovaries can be preserved during surgery in young aged patients with early stage disease, and 29% stated that bilateral oophorectomy should be performed irrespective of age or stage. Omentectomy was routinely performed by 11% of respondents, and was selectively performed when extrauterine spread was present by 41%. CONCLUSION: Surgical procedures for the treatment of endometrial cancer are still not standardized among Korean gynecologic surgeons. Clinical trials to determine the benefits of the different surgical procedures should be developed.

Validation of a nomogram for predicting outcome of vulvar cancer patients, primarily treated by surgery, in Korean population: multicenter retrospective study through Korean Gynecologic Oncology Group (KGOG-1010) / 부인종양

OBJECTIVE: Regarding vulvar cancer, a nomogram has been suggested for the prediction of relapse-free survival (RFS). While the nomogram has been developed and validated in a Western study, there was no validation in Korean population. Thus, we have undertaken the study to assess the applicability of nomogram for predicting RFS in Korean patients with vulvar cancer. METHODS: A total of 204 cases newly diagnosed as vulvar cancer between 1982 and 2006 were identified. Among them 70 cases were not eligible due to inappropriate cell type (40 cases) and radiation as primary therapy (30 cases). Forty-four cases were not evaluable due to inadequate data and persistent disease. Finally a total of 90 patients primarily treated by surgery were included for analysis. Variables including age and the characteristics of primary tumor, nodal status, and surgical margin were collected for predicting RFS based on nomogram, which was compared with actual RFS. A calibration plot was drawn showing the actual versus predicted probability for 6 groups of patients segregated according to their predicted probabilities. In addition, discrimination of the nomogram was quantified with the concordance index. RESULTS: Patients' mean age was 58 years and mean follow-up period was 47.9 months. Observed 2y- and 5y-RFS rates were 81% and 68%, respectively, corresponding to 79% and 72% in the original cohort. The trend line in calibration plot showed comparable concordance with an ideal line, having a slope of 1.04 for 2y-RFS (R(2)=.35) and 0.98 for 5y-RFS (R2=.80), respectively. The concordance index was 0.79 in the KGOG data set, which was improved to 0.82 with the data set limited to squamous cell carcinoma. CONCLUSION: The nomogram provides the predictive capacity for relapse-free survival in Korean patients with vulvar cancer.

Folic acid and vitamin B12 intake in relation to risk of endometrial cancer: Case-control study / 대한산부인과학회지

OBJECTIVE: To evaluate the role of folic acid and vitamin B12 in the etiology of endometrial cancer, we performed a case-control study comparing oral intakes of folic acid, vitamin B12 and serum levels of folate and vitamin B12 in 48 endometrial cancer patients and 563 controls. METHODS: From August 2005 to August 2006, 48 histologically diagnosed endometrial cancer patients and 563 controls were enrolled in the study. Informations about dietary intake of folic acid, vitamin B12 were obtained by semi-quantitative food frequency questionnaire (SQFFQ) and serum levels of folate and vitamin B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) were assessed with logistic regression and adjusted for energy, age, smoking status, alcohol consumption status, BMI, menopause, oral contraceptive use. RESULTS: Endometrial cancer risk was not significantly associated with intakes of folic acid and vitamin B12. After assessing tertile subgroup levels of folic acid intake, multivariate OR of 2nd tertile subgroup was 0.71 (95% CI: 0.36~1.6) and multivariate OR of 3rd tertile subgroup was 0.92 (95% CI: 0.45~1.9). And according to tertile subgroup levels of vitamin B12 intake, multivariate OR of 2nd tertile subgroup was 1.17 (95% CI: 0.57~2.39) and multivariate OR of 3rd tertile subgroup was 0.94 (95% CI: 0.43~2.05). However, serum folate and vitamin B12 levels were significantly associated with a reduction of endometrial cancer risk as a result of multivariate OR 0.42 (95% CI: 0.22~0.78) and 0.32 (95% CI: 0.15~0.68) by logistic regression. CONCLUSIONS: This study suggests that dietary intakes of folic acid and vitamin B12 are not significantly related to the risk of endometrial cancer. But we could confirm reduction of endometrial cancer risk in higher serum folate and higher serum vitamin B12 subgroup.

The analysis of the clinical results of total laparoscopic hysterectomy according to body mass index / 대한산부인과학회지

OBJECTIVE: To know impacts of BMI on clinical results of total laparoscopic hysterectomy (TLH). METHODS: We reviewed medical records of patients with myoma uteri who undergone TLH between March 2003 and February 2007, retrospectively. We classified group 1 when BMI was or =28. We reviewed age, parity, body weight and height, operation time, amount of blood loss, change of hemoglobin change and days of hospital stay, and analyze these. RESULTS: There were 83 patients (Group 1; 30, Group 2; 40, Group 3; 13). The body weight distributions of Group 1, 2, and 3 were 52.2, 60.9, and 72.0 kg and there were significant differences. But there was no difference of height distributions. The age distributions were 44.3, 47.0, 43.8 year old, and there were differences. But there was no difference of parity distribution. The weight distribution of removed uterus were 250.5, 257.4, 242.7 gm and there was no difference. The operation time distributions were 155.0, 168.2, 160.8 minutes, and there was no difference. The amount distributions of bleeding were 342.7, 356.5, 396.2 ml, and there was no difference. The change distributions of hemoglobin were 2.1, 1.8, 2.2 g/dL, and there was no difference. The day distributions of hospital stay were 5.2, 5.5, 4.8, and there was no difference. CONCLUSION: We could not find any trend between operation time, amount of bleeding, change of hemoglobin, and days of postoperative hospital stay after TLH with BMI.

Hypermethylation of E-cadherin in endometrial carcinoma / 부인종양

OBJECTIVE: Hypermethylation of CpG island is a common mechanism for the inactivation of tumor suppressor genes. Hypermethylation of the E-cadherin promoter region has been rarely studied in endometrial carcinoma of Korean women. The purpose of this study is to investigate methylation status of E-cadherin promoter region in endometrial carcinomas and endometrial hyperplasias, and analyze the correlation with clinicopathologic variables in endometrial carcinomas. METHODS: We examined the methylation status of the E-cadherin promoter region using methylation specific polymerase chain reaction and immunohistochemical expression (IHC) of E-cadherin in 30 endometrioid endometrial carcinomas and 20 endometrial hyperplasias, and correlated these results with various clinicopathological factors of endometrial carcinomas. RESULTS: Decreased expression of E-cadherin was detected in 13 of 30 (43.3%) endometrial carcinomas and in 1 of 20 (5%) endometrial hyperplasias (p=0.009). Promoter hypermethylation was detected in 12 of 30 (40%) endometrial carcinomas and 2 of 20 (10%) endometrial hyperplasias (p=0.015). Methylation status did not have a significant influence on the tumor grade and lymph node metastasis. However, the hypermethylation rate was significantly higher in stage above Ic (p=0.025). Decreased expression of E-cadherin was associated with tumor grade, tumor stage, and lymph node metastasis in endometrial carcinomas (p=0.01, p=0.02, p=0.03). There was no correlation between DNA hypermethylation and decreased expression of E-cadherin in endometrial carcinomas (p>0.05). CONCLUSION: These results indicate that hypermethylation of E-cadherin promoter region is a frequent event in endometrial carcinoma, which may play an important role in the progression of carcinogenesis. Also, the promoter methylation of E-cadherin in endometrial carcinoma was found to be significantly associated with higher stage above Ic.

Hypermethylation of E-cadherin in endometrial carcinoma / 부인종양

OBJECTIVE: Hypermethylation of CpG island is a common mechanism for the inactivation of tumor suppressor genes. Hypermethylation of the E-cadherin promoter region has been rarely studied in endometrial carcinoma of Korean women. The purpose of this study is to investigate methylation status of E-cadherin promoter region in endometrial carcinomas and endometrial hyperplasias, and analyze the correlation with clinicopathologic variables in endometrial carcinomas. METHODS: We examined the methylation status of the E-cadherin promoter region using methylation specific polymerase chain reaction and immunohistochemical expression (IHC) of E-cadherin in 30 endometrioid endometrial carcinomas and 20 endometrial hyperplasias, and correlated these results with various clinicopathological factors of endometrial carcinomas. RESULTS: Decreased expression of E-cadherin was detected in 13 of 30 (43.3%) endometrial carcinomas and in 1 of 20 (5%) endometrial hyperplasias (p=0.009). Promoter hypermethylation was detected in 12 of 30 (40%) endometrial carcinomas and 2 of 20 (10%) endometrial hyperplasias (p=0.015). Methylation status did not have a significant influence on the tumor grade and lymph node metastasis. However, the hypermethylation rate was significantly higher in stage above Ic (p=0.025). Decreased expression of E-cadherin was associated with tumor grade, tumor stage, and lymph node metastasis in endometrial carcinomas (p=0.01, p=0.02, p=0.03). There was no correlation between DNA hypermethylation and decreased expression of E-cadherin in endometrial carcinomas (p>0.05). CONCLUSION: These results indicate that hypermethylation of E-cadherin promoter region is a frequent event in endometrial carcinoma, which may play an important role in the progression of carcinogenesis. Also, the promoter methylation of E-cadherin in endometrial carcinoma was found to be significantly associated with higher stage above Ic.

An ovarian mucinous cystadenocarcinoma arising from mature cystic teratoma with para-aortic lymph node metastasis: a case report / 부인종양

Malignant transformation of a mature cystic teratoma (MCT) is an uncommon complication. The most common form of malignant transformation of a MCT is squamous cell carcinoma, representing 75% of malignant transformations. The frequency of malignant transformation of MCT to adenocarcinoma is just 6.8%. To the best of our knowledge, no case of para-aortic lymph node metastasis in mucinous adenocarcinoma arising from MCT has been reported before. The prognosis of malignant transformation of the MCT is very poor. Here, we report an unusual case of a 41-year-old woman with mucinous adenocarcinoma arising from MCT with para-aortic lymph node metastasis.

An ovarian mucinous cystadenocarcinoma arising from mature cystic teratoma with para-aortic lymph node metastasis: a case report / 부인종양

Malignant transformation of a mature cystic teratoma (MCT) is an uncommon complication. The most common form of malignant transformation of a MCT is squamous cell carcinoma, representing 75% of malignant transformations. The frequency of malignant transformation of MCT to adenocarcinoma is just 6.8%. To the best of our knowledge, no case of para-aortic lymph node metastasis in mucinous adenocarcinoma arising from MCT has been reported before. The prognosis of malignant transformation of the MCT is very poor. Here, we report an unusual case of a 41-year-old woman with mucinous adenocarcinoma arising from MCT with para-aortic lymph node metastasis.

Loss of heterozygosity of E-cadherin in endometrial carcinomas and endometrial hyperplasias / 대한산부인과학회지

OBJECTIVE: Microsatellite alteration such as loss of heterozygosity (LOH) has been reported to be a novel mechanism for the inactivation of tumor suppressor gene and related to carcinogenesis in many malignant tumors. E-cadherin protein coded by gene on chromosome 16q22.1 may play a principal role for tumor suppression. However LOH of E-cadherin has been rarely studied in endometrial carcinoma. The purpose of this study was to investigate the loss of heterozygosity (LOH) of E-cadherin in endometrial carcinoma and endometrial hyperplasia and to correlate their results with various clinicopathological factors. METHODS: LOH of E-cadherin on the chromosome 16q22.1 analysis was performed by using polymerase chain reaction (PCR) for three polymorphic microsatellite markers (D16S419, D16S3106, D16S498) and automatic laser fluorescent DNA sequencer in 30 cases of endometrioid endometrial adenocarcinomas and in 20 cases of endometrial hyperplasias. The relationship between LOH of E-cadherin and clinical profile was analyzed. RESULTS: Increased LOH of E-cadherin was found in endometrial carcinomas (50%) compared to endometrial hyperplasias (5%) (P=0.01, Fisher's exact test). The incidence of LOH of E-cadherin in endometrial carcinomas also showed significantly lower in stage below Ia. (P=0.034, Fisher's exact test) LOH of E-cadherin was not associated with histologic grade and lymph node metastasis. (P=0.42, P=0.5, Fisher's exact test) CONCLUSIONS: These results suggests that LOH of E-cadherin may contribute to the development of endometrial carcinoma, especially in above stage Ib.

Magnetic resonance evaluation of human mesenchymal stem cells in corpus cavernosa of rats and rabbits / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate whether the biological process of superparamagnetic iron oxide (SPIO)-labeled human mesenchymal stem cells (hMSCs) may be monitored non-invasively by using in vivo magnetic resonance (MR) imaging with conventional 1.5-T system examinations in corpus cavernosa of rats and rabbits.</p><p><b>METHODS</b>The labeling efficiency and viability of SPIO-labeled hMSCs were examined with Prussian blue and Tripan blue, respectively. After SPIO-labeled hMSCs were transplanted to the corpus cavernosa of rats and rabbits, serial T2-weighted MR images were taken and histological examinations were carried out over a 4-week period.</p><p><b>RESULTS</b>hMSCs loaded with SPIO compared to unlabeled cells had a similar viability. For SPIO-labeled hMSCs more than 1 X 10 (5) concentration in vitro, MR images showed a decrease in signal intensity. MR signal intensity at the areas of SPIO-labeled hMSCs in the rat and rabbit corpus cavernosa decreased and was confined locally. After injection of SPIO-labeled hMSCs into the corpus cavernosum, MR imaging demonstrated that hMSCs could be seen for at least 12 weeks after injection. The presence of iron was confirmed with Prussian blue staining in histological sections.</p><p><b>CONCLUSION</b>SPIO-labeled hMSCs in corpus cavernosa of rats and rabbits can be evaluated non-invasively by molecular MR imaging. Our findings suggest that MR imaging has the ability to test the long-term therapeutic potential of hMSCs in animals in the setting of erectile dysfunction.</p>

Immunohistochemical Analysis of Midkine Expression in Preinvasive and Invasive Squamous Cell Neoplasia of the Uterine Cervix

BACKGROUND: Midkine (MK) is a member of the heparin-binding growth factor family. Overexpression of MK is observed not only in cancerous tissue but also in precancerous lesions of the colon and the prostate. Using immunohistochemical methods, we investigated MK expression in preinvasive and invasive neoplasia of the uterine cervix. METHODS: We performed immunohistochemical analysis of archived cone biopsy and hysterectomy specimens from 161 squamous cell lesions of the uterine cervix (29 cervical intraepithelial neoplasia 1 (CIN1), 35 CIN2, 49 CIN3, 30 microinvasive squamous cell carcinomas (MIC), and 18 invasive squamous cell carcinoma). In addition, we examined if there is a correlation between MK expression and status of human papilloma virus infection determined by a commercially available DNA chip. RESULTS: None of the normal cervical mucosa showed MK immunostaining. The level of MK expression gradually increased according to the histologic grade. Moderate and strong expressions were most frequently observed in cervical tissue with CIN3 and MIC. MK immunostaining was more accentuated in the invasive border of MIC. CONCLUSION: MK may play a functional role in the disease progression of cervical squamous cell neoplasia.

Clinical Efficacy of Human Papillomavirus DNA Detection in Urine from Patients with Various Cervical Lesions

A considerable number of adult Korean women avoid a Pap smear due to fear and discomfort of the pelvic examination. A reliable but noninvasive and comfortable screening method would considerably increase the participation rate. To evaluate the clinical efficacy of urine-based human papillomavirus (HPV) detection by oligonucleotide microarray, the results of HPV test from matched cervical swab specimens were compared. HPV DNA was detected in 70 of 100 cervical samples. HPV 16 was the most prevalent type (38/70), followed by types 18, 58, 52, 33, 35, 31, and 51. HPV DNA was identified in 47 of 90 urine samples. HPV 16 was the most prevalent type (30/45), followed by types 18, 52, 35, 51, 58, 33, and 56. The HPV detection rates of the cervical swabs increased in accordance with the severity of the cytologic and histologic diagnosis. The type specific agreement of HPV DNA tests between cervical swabs and urine was good in HPV 16 (kappa index=0.64 [95% CI: 0.50-0.79]), 18, 52, and 58 and fair in HPV 33 and 35. We propose that a urine HPV test is a valuable adjunctive method for a conventional Pap smear and can be used in population screening for cervical cancer in countries where it is difficult to obtain colposcopic specimens for cultural or religious reasons.

A case of perivascular epithelioid cell tumor (PEComa) at the uterus / 대한산부인과학회지

Perivascular epithelioid cell tumors (PEComas) at the uterus are very rare tumors and about 30 cases have been reported as far as we know. As a case was experienced at our hospital, we would like to report it with a brief review of literature.

A case of right rudimentary uterus with ipsilateral renal agenesis misdiagnosed as an ovarian tumor / 대한산부인과학회지

Rudimentary uterus with ipsilateral renal agenesis is a very rare Mullerian duct malformation. The most common clinical presentation is pelvic pain and dysmenorrhea shortly after menarche, in associated with the finding of a vaginal or pelvic mass. An appropriate and prompt diagnosis and treatment will prevent unnecessary procedures and offer relief of symptoms. We report one case of rudimentary uterine horn with ipsilateral renal agenesis with a brief review of concerned literatures.

Three Cases of Primary Ovarian Transitional Cell Carcinoma / 대한산부인과학회지

Primary ovarian transitional cell carcinoma (TCC) is extremely rare tumor and recently it has been recognized as one of histologic subtype of ovarian epithelial carcinoma. We experienced three cases at Inha University Hospital and report our experiences with a brief review of literature.

When should human papillomavirus (HPV) testing be done after conization? / 대한산부인과학회지

OBJECTIVE: To know when human papillomavirus (HPV) testing should be done after conization. METHODS: Between 1997 to 2004, Large Loop Excisions of the Transformation Zone (LLETZ) were done for conization to women with cervical pathology at A University Hospital. The Pap and HPV typing were done before LLETZ procedures. After conizations, HPV typing were planned to be done every 3 months. Every HPV typing was done by HPV oligonucleotide microarray (Biomedlab Co., Seoul, South Korea). RESULTS: For 8 years, 120 LLETZ were enrolled in this study. There were 8 cases of no neoplasm, 9 cases of CIN 1, 17 cases of CIN 2, 74 cases of CIN 3, 10 cases of microinvasive cervix cancer, and 2 cases of adenocarcinoma in situ. HPV DNA before LLETZ procedures was found about 85.0% and subtype 16 was the most common type among the patients with cervical lesion (40.8%). After LLETZ, 190 HPV typing were done through 1,307 total months (average, 6.9 months/typing). 95 (79.2%) cases had negative results, and 25 (20.8%) cases had positive results. Our data showed that, after conization, about 80% turned out to negative in 6 months. CONCLUSION: Our data suggested HPV DNA testing should be done after 6 months of LLETZ, as about 80% were destined to negative in 6 months.