Clinical Usefulness of Cancer Antigen (CA) 125, Human Epididymis 4, and CA72-4 Levels and Risk of Ovarian Malignancy Algorithm Values for Diagnosing Ovarian Tumors in Korean Patients With and Without Endometriosis

BACKGROUND: Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. METHODS: In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. RESULTS: All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without (P<0.001), whereas HE4 and CA72-4 levels were not affected by endometriosis (P=0.128 and 0.271, respectively). CONCLUSIONS: ROMA value is the best marker to distinguish malignant and borderline tumors from benign tumors in pre- and postmenopausal patients. HE4 and CA72-4 levels provide information on possible CA125 elevation due to endometriosis.

Survival outcomes of adjuvant radiotherapy and chemotherapy in women with stage I serous papillary and clear cell carcinoma of the endometrium: a Korean multicenter study / 부인종양

OBJECTIVE: To compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC). METHODS: Medical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups. RESULTS: Fifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1±20.2 vs. 11.5±6.5 IU/mL, p 0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297–11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288–9.321; p=0.578) after surgery was independently associated with disease recurrence. CONCLUSION: Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.

Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer

BACKGROUND: Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis. METHODS: Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy. RESULTS: CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001). CONCLUSIONS: Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.

Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients. MATERIALS AND METHODS: Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review. RESULTS: Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (pT of BRCA2 in KoBC). CONCLUSION: The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

Differentiation Potential of Mesenchymal Stem Cells Is Related to Their Intrinsic Mechanical Properties / 대한배뇨장애요실금학회지

PURPOSE: The differentiation properties of stem cells are not yet fully understood due to their close association with multiple environmental and extrinsic factors. This study investigates the differentiation properties of mesenchymal stem cells (MSCs) and correlates them with their intrinsic mechanical properties. METHODS: A total of 3 different types of MSCs, namely bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UCSCs), and adipose-derived MSCs (ADSCs) were evaluated. These 3 MSCs were individually differentiated into adipocytes and osteoblasts for 3 weeks. The mechanical properties of the MSCs and differentiated cells were determined by atomic force microscopy. RESULTS: ADSCs showed the greatest ability to differentiate into adipocytes, followed by BMSCs and UCSCs. While UCSCs differentiated readily into osteoblasts, BMSCs and ADSCs were less likely to undergo this differentiation. UCSCs were the “hardest” cells, while ADSCs were the “softest.” The cells differentiated from “hard” MSCs were stiffer than the cells differentiated from “soft” MSCs, irrespective of lineage specification. CONCLUSIONS: The differentiation ability of MSCs and the mechanical properties of the differentiated cells were closely linked. However, there were no significant correlations regarding changes in the mechanical properties between the nuclear region and the cytoplasm during differentiation.

Prognostic value of preoperative lymphocyte-monocyte ratio in elderly patients with advanced epithelial ovarian cancer

OBJECTIVE: To investigate the prognostic significance of preoperative lymphocyte-monocyte ratio (LMR) in elderly patients with advanced epithelial ovarian cancer (EOC) receiving primary cytoreductive surgery and adjuvant platinum-based chemotherapy. METHODS: A total of 42 elderly patients (≥65 years) diagnosed with EOC who are receiving primary cytoreductive surgery and adjuvant platinum-based chemotherapy from 2009 to 2012 was included. LMR was calculated from complete blood cell count sampled before operation. Receiver operating characteristic (ROC) curves were used to calculate optimal cut-off values for LMR. Prognostic significance with respect to overall survival (OS) and progression-free survival (PFS) were determined using log-rank test and Cox regression analysis. RESULTS: The optimized LMR cut-off value determined by ROC curve analysis was 3.63 for PFS and OS. The high LMR group (LMR ≥3.63) was found to be significantly more associated with optimal debulking (P=0.045) and platinum response (P=0.018) than the low LMR group. In addition, Kaplan-Meier analysis revealed the LMR-high group was significantly more associated with high PFS and OS rates (P=0.023 and P=0.033, respectively), and univariate analysis revealed that a high LMR, histology type, and optimal debulking and platinum responses were significantly associated with prolonged PFS and OS. However, subsequent Cox multivariate analysis showed only optimal debulking and platinum response were independent prognostic factors of PFS or OS. CONCLUSION: This study suggests that LMR might be associated with treatment and survival outcomes in elderly patients with EOC receiving standard oncology treatment.

Peptide YY producing strumal carcinoid tumor of the ovary in a postmenopausal woman: a rare cause of chronic constipation

Strumal carcinoid tumor of the ovary is a rare subtype of ovarian carcinoid tumors; it is characterized by an intimate mixture of thyroid and carcinoid tissues. We present a case of a 64-year-old woman who presented with the chief complaint of persistent, severe constipation for over 5 years; she was later found to have an ovarian strumal carcinoid tumor. Computed tomography showed a well-defined solid mass measuring 6.4 cm at the right adnexa. The patient underwent right salpingo-oophorectomy and was histopathologically diagnosed as having a strumal carcinoid tumor. Immunohistochemical examination showed immunoreactivity for peptide YY (PYY), which exerts an inhibitory effect on the peristaltic actions of the distal intestine. After surgery, the patient's constipation resolved rapidly, suggesting a correlation between PYY producing ovarian carcinoid tumor and constipation. This is the first case report of PYY producing primary strumal carcinoid tumor of the ovary associated with persistent, severe constipation from Korea.

Rectouterine fistula after laparoscopic ultrasound-guided radiofrequency ablation of a uterine fibroid

In the conservative management of uterine fibroids is radiofrequency ablation (RFA) considered to be one of the safe, effective and minimal invasive approaches in selected women who desire to retain their uterus. Few studies were conducted on its adverse outcomes and most of the reported complications were minor events such as pain, discharge, adhesion which didn't require any intervention. However, although safe and effective, the RFA of a uterine myoma can be the cause for severe complications such as penetration and burn injuries of pelvic organs. In general, a rectouterine fistula is one of the rarest complications but can lead to serious adverse outcomes. Herein, to our knowledge, we report the first case involving a rectouterine fistula after laparoscopic ultrasound-guided RFA of a uterine myoma with pelvic endometriosis. In addition, we provide a brief review of the relevant literature.

Specificity of Intracellular Trans-Splicing Reaction by hTERT-Targeting Group I Intron

Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.

Functional Modification of a Specific RNA with Targeted Trans-Splicing

The self-splicing group I intron from Tetrahymena thermophila has been demonstrated to perform splicing reaction with its substrate RNA in the trans configuration. In this study, we explored the potential use of the trans-splicing group I ribozymes to replace a specific RNA with a new RNA that exerts any new function we want to introduce. We have chosen thymidine phosphorylase (TP) RNA as a target RNA that is known as a valid cancer prognostic factor. Cancer-specific expression of TP RNA was first evaluated with RT-PCR analysis of RNA from patients with gastric cancer. We determined next which regions of the TP RNA are accessible to ribozymes by employing an RNA mapping strategy, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. A specific ribozyme recognizing the most accessible sequence in the TP RNA with firefly luciferase transcript as a 3' exon was then developed. The specific trans-splicing ribozyme transferred an intended 3' exon tag sequence onto the targeted TP transcripts, resulting in a more than two fold induction of the reporter activity in the presence of TP RNA in mammalian cells, compared to the absence of the target RNA. These results suggest that the Tetrahymena ribozyme can be a potent anti-cancer agent to modify TP RNAs in tumors with a new RNA harboring anti-cancer activity.