Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer. @*Materials and Methods@#After irradiating xenograft mouse with human lung cancer cell lines, H1299 (NRAS proto-oncogene, GTPase [NRAS] Q61K) and HCC827 (epidermal growth factor receptor [EGFR] E746-750del), circulating (cell-free) tumor DNA (ctDNA) levels were monitored with quantitative polymerase chain reaction on human long interspersed nuclear element-1 and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method. @*Results@#Irradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5- fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA polymerase chain reaction analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, TLB. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy. @*Conclusion@#TLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

Periimplant Bone Regeneration in Hydroxyapatite Block Grafts with Mesenchymal Stem Cells and Bone Morphogenetic Protein-2

Hydroxyapatite (HA) blocks as an alternative material for autogenous onlay bone grafts are regarded as an insufficient substitute for osseointegration of dental implant. In this study, we evaluated the effects of dog mesenchymal stromal cells (dMSCs) with or without bone morphogenetic protein-2 (BMP) on new peri-implant bone formation after HA block graft. In four mandibular bone defects (8×8×6 mm each) in five beagle dogs, dental implants were placed with HA block loaded with autogenous dMSCs with or without BMP-2. Animals were sacrificed at eight weeks, and bone healing was evaluated among four groups consisting of 1) HA alone as a control, 2) HA+dMSCs, 3) HA+BMP-2, and 4) HA+dMSCs+BMP-2. According to histomorphometric evaluation, the MSC+BMP-2 group and the BMP-2 group showed significantly higher bone-implant-contact (BIC) length than the MSC group, while there was no significant difference in new bone formation among the groups. According to micro-CT analysis, bone volume and bone mineral density were significantly higher in the MSC+BMP-2 group compared with the control group (p<0.01 and p<0.05, respectively). BIC was significantly higher in the MSC+BMP-2 group than both the control and MSC groups (p<0.01 and p<0.05, respectively). In conclusion, our results showed that bone regeneration at peri-implant bone defects grafted with HA blocks was significantly increased by dual delivery of MSCs and BMP-2. Conversely, HA blocks with MSC or BMP-2 alone did not allow for efficient peri-implant bone regeneration.

Incidental diagnosis of vaginal schwannoma in a patient with thigh pain

Schwannoma commonly arises from Schwann cells of the neural sheath, and is rare in the groin region. Here, we describe a vaginal schwannoma incidentally detected by magnetic resonance imaging (MRI) in a patient with thigh pain. A 43-year-old woman presented with thigh pain with burning and tingling sensations in the medial aspect of her left thigh. MRI revealed a mass lesion of heterogeneous intensity 5.2 x 5.7 cm in the left vaginal wall. The mass was resected and histology revealed schwannoma.

Discrimination between Benign and Malignant Pelvic Masses Using the Risk of Malignancy Index 1 / 대한폐경학회지

OBJECTIVES: To assess the ability of risk of malignancy index (RMI) 1 to discriminate between benign and malignant pelvic masses. METHODS: Between January 2007 and December 2010, 547 women with pelvic masses were evaluated. Their medical records are reviewed here retrospectively. The sensitivity, specificity and positive and negative predictive values of the cancer antigen (CA) 125 level, ultrasound findings and menopausal status in the prediction of malignant pelvic masses were calculated and compared individually or combined using the RMI 1. RESULTS: The receiver operating characteristic (ROC) curves of CA 125, the ultrasound score and the RMI 1 were all found to be relevant predictors of malignancy. ROC analysis of the RMI 1, CA 125 serum levels, ultrasound score and menopausal status showed areas under the curves of 0.795, 0.782, 0.784 and 0.594, respectively. The RMI 1 was found to be statistically significantly correlated with menopausal status (P = 0.001), while not statistically significantly correlated with CA 125 (P = 0.628) or the ultrasound score (P = 0.541). The RMI 1 at a cut-off of 150 - with a sensitivity of 77.9%, specificity of 81.1%, positive predictive value of 51.7% and negative predictive value of 93.4% - showed the highest performance in determining the malignant tendency of pelvic masses. CONCLUSION: Accepting a RMI 1 cut-off value of 150 results in statistically more significant diagnostic criteria than menopausal status for the discrimination of benign and malignant pelvic masses.

Squamous cell carcinoma arising in an ovarian mature cystic teratoma complicating pregnancy

Mature cystic teratomas of the ovary (MCT) are usually observed in women of reproductive age with the most dreadful complication being malignant transformation which occurs in approximately 1% to 3% of MCTs. In this case report, we present a patient with squamous cell carcinoma which developed from a MCT during pregnancy. The patient was treated conservatively without adjuvant chemotherapy and was followed without evidence of disease for more than 60 months using conventional tools as well as positron emission tomography-computed tomography following the initial surgery. We report this case along with the review of literature.

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.

Clinical data of patients with endometrioid endometrial adenocarcinoma at a single institution / 대한산부인과학회지

OBJECTIVE: The incidence of endometrial cancer is increasing. We would like to report our institution's clinical data of endometrioid adenocarcinoma (EC) which is the most frequent type. METHODS: From 1998 to 2009, patients' clinical data were reviewed through medical records, retrospectively. RESULTS: For 11 years, there were 96 patients with EC. The average age was 51.1 years old and mean follow duration was 36.6 months. There were 73 patients with stage I, 10 patients with stage II, and 12 patients with stage III. 42 patients were treated by operation only and 46 patients were treated by operation and adjuvant radiotherapy. Among 95 patients who underwent operations, 32 patients did not get lymph node removal and 63 did, and 10 patients had malignant cells at the lymph nodes removed. 6 patients died of EC, 1 with stage I, 3 with stage II and 1 with stage III. CONCLUSION: This study had retrospective limitation but could show the profile of 96 patients with EC.

Effect of RHPDGF-BB and RhBMP-2 on Osseointegration of Titanium Implants at Periimplant Bone Defects Grafted with Hydroxyapatite: Micro-Ct and Histologic Analysis

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.

A case of fibroepithelial polyp of vulva / 대한산부인과학회지

Vulvar fibroepithelial polyp is a relatively uncommon benign polypoid tumor of the vulva commonly known as skin tag or occasionally acrochordon. In this case, a 18 years old girl complained of painless bulging mass at the right labium major. She has been suffering from slowly growing a vulva tumor for ten years. It was arising from the right labium major and measured 12 cm in its largest diameter. We have experienced an unusually large vulva mass that was surgically excised and histologically diagnosed as benign fibroepithelial polyp and presented this case with a brief review of literature.

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.

Hypertriglyceridemia induced acute pancreatitis in pregnancy / 대한산부인과학회지

Hypertriglyceridemia is a rare cause of pancreatits. However the relationship between acute pancreatits and severe hypertrigyceridemia is well recognized. It can be a life- threatening complication if the degree of hypertrigyceridemia is severe enough. A serum triglyceride level of more than 1,000 to 2,000 mg/dL is the identifiable risk factor. The clinical course and management of hypertriglyceridemia induced acute pancreatitis is not different from other causes. The clinical course and management of hypertriglyceridemia induced acute pancreatitis during pregnancy are similar to the one during nonpregnant state. The prevalence of acute pancreatitis in pregnancy ranges between 1 in 1,000 to 1 in 3,000. Gestational hypertrigyceridemic pancreatits can be fatal, and maternal morbidity rate has an upward trend of 20%. We report a 31-year-old woman with coexistence of hypertrigyceridemia and acute pancreatits at 32 weeks gestation with a brief review of the literatures.

Uterine artery embolization for the management of uterine artery bleeding after transobturator tape operation: A case report / 대한산부인과학회지

Transobturator tape (TOT) operation for urinary stress incontinence is associated with less complication rate than Tension free vaginal tape (TVT). The two procedures yield similar rates of success. The TOT is lead through the obturator foramen, reducing the risk of bladder injury as well as damage of structures located in the Retzii cave, e.g. nerves and blood vessels. However the complications of TOT procedure may have several complications associated with obturator foramen. They are the injury of obturator nerve and vessels, abscess formation on th obturator foramen, vulvar hematoma, etc. There is no report the uterine artery injury after TOT procedure so far. Recently we experienced a case of successful control of bleeding of the uterine artery after TOT operation via uterine artery embolization. Therefore we report our case with brief review of the literatures.

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.

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.

Increased expressions of claudin-1 and claudin-7 in cervical squamous intraepithelial neoplasias and invasive squamous cell carcinomas / 대한산부인과학회지

OBJECTIVE: The change of claudin expressions, integral transmembrane proteins for tight junction, might be related to progression of cervical premalignancy or malignancy. The aim of this study was to verify the tendency of expressions of claudin-1 and -7 according to the progression of cervical pathology of uterus. METHODS: There were 162 tissues obtained at AA institute. 25 tissues were normal, 26 were cervical intraepithelial neoplasia (CIN) 1, 30 were CIN2, 44 were CIN3, 25 were microinvasive cervical carcinomas, and 12 were invasive squamous cervical carcinomas (ISCC). H and E and immunohistochemical staining were done. RESULTS: Among normal tissues, 52% showed no expression, 48% weak expressions at claudin-1, and 28% no expression, 56% weak expressions at claudin-7. Among CIN3, 20% showed weak expressions, 41% showed moderate expressions at claudin-1, and 14% weak expressions, 52% moderate expressions at claudin-7. Among ISCC, 42% showed moderate expressions, 50% strong expressions at claudin-1, and 33% moderate expressions, and 33% strong expressions at claudin-7. These data shows the increasing tendency of claudin-1 and claudin-7 expressions according to the severity of lesions (p<0.01). CONCLUSION: The expressions of claudin-1 and claudin-7 were increased more according to the progression of cervical lesions.

Increased expressions of claudin-1 and claudin-7 in cervical squamous intraepithelial neoplasias and invasive squamous cell carcinomas / 대한산부인과학회지

OBJECTIVE: The change of claudin expressions, integral transmembrane proteins for tight junction, might be related to progression of cervical premalignancy or malignancy. The aim of this study was to verify the tendency of expressions of claudin-1 and -7 according to the progression of cervical pathology of uterus. METHODS: There were 162 tissues obtained at AA institute. 25 tissues were normal, 26 were cervical intraepithelial neoplasia (CIN) 1, 30 were CIN2, 44 were CIN3, 25 were microinvasive cervical carcinomas, and 12 were invasive squamous cervical carcinomas (ISCC). H and E and immunohistochemical staining were done. RESULTS: Among normal tissues, 52% showed no expression, 48% weak expressions at claudin-1, and 28% no expression, 56% weak expressions at claudin-7. Among CIN3, 20% showed weak expressions, 41% showed moderate expressions at claudin-1, and 14% weak expressions, 52% moderate expressions at claudin-7. Among ISCC, 42% showed moderate expressions, 50% strong expressions at claudin-1, and 33% moderate expressions, and 33% strong expressions at claudin-7. These data shows the increasing tendency of claudin-1 and claudin-7 expressions according to the severity of lesions (p<0.01). CONCLUSION: The expressions of claudin-1 and claudin-7 were increased more according to the progression of cervical lesions.