Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. MATERIALS AND METHODS: Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity. RESULTS: Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers. CONCLUSION: sTumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Preoperative serum levels of cancer antigen 125 and carcinoembryonic antigen ratio can improve differentiation between mucinous ovarian carcinoma and other epithelial ovarian carcinomas

OBJECTIVE: The main aim of this study was to evaluate cancer antigen 125 (CA125)/carcinoembryonic antigen (CEA) ratio (CCR), as a reliable marker to differentiate ovarian mucinous carcinoma from other epithelial ovarian carcinomas (EOCs), namely serous, clear cell, and endometrioid carcinomas. METHODS: Female patients suffering from different kinds of EOCs whom were subjected to elective surgery at the Gangnam Severance Hospital between January 2008 and December 2016, were included in this study. The serum levels of CA125 and CEA were assayed using commercially available kits per the manufacturer's instructions. RESULTS: The CCR in mucinous carcinoma (mean 32.1) was significantly lower than that of clear cell (mean 235.0) and endometrioid carcinoma (mean 427.0) in stage I (all P < 0.05). In stage II–IV, CCR in mucinous carcinoma (mean 37.6) was significantly lower than that of serous carcinoma (mean 148.0) (P < 0.01). The sensitivity and specificity of CCR in detecting mucinous carcinoma from other types of EOC was 75.0% and 77.5%, respectively in stage I and 100.0% and 84.4%, respectively in stage II–IV (both cut-off value < 90.7). CONCLUSION: The present results suggest that pretreatment CCR might provide higher specificity and clinically relevant information as a criterion for the differentiation between ovarian mucinous carcinoma and other types of EOC.

API5 induces cisplatin resistance through FGFR signaling in human cancer cells

Most tumors frequently undergo initial treatment with a chemotherapeutic agent but ultimately develop resistance, which limits the success of chemotherapies. As cisplatin exerts a high therapeutic effect in a variety of cancer types, it is often used in diverse strategies, such as neoadjuvant, adjuvant and combination chemotherapies. However, cisplatin resistance has often manifested regardless of cancer type, and it represents an unmet clinical need. Since we found that API5 expression was positively correlated with chemotherapy resistance in several specimens from patients with cervical cancer, we decided to investigate whether API5 is involved in the development of resistance after chemotherapy and to explore whether targeting API5 or its downstream effectors can reverse chemo-resistance. For this purpose, cisplatin-resistant cells (CaSki P3 CR) were established using three rounds of in vivo selection with cisplatin in a xenografted mouse. In the CaSki P3 CR cells, we observed that API5 acted as a chemo-resistant factor by rendering cancer cells resistant to cisplatin-induced apoptosis. Mechanistic investigations revealed that API5 mediated chemo-resistance by activating FGFR1 signaling, which led to Bim degradation. Importantly, FGFR1 inhibition using either an siRNA or a specific inhibitor disrupted cisplatin resistance in various types of API5(high) cancer cells in an in vitro cell culture system as well as in an in vivo xenograft model. Thus, our results demonstrated that API5 promotes chemo-resistance and that targeting either API5 or its downstream FGFR1 effectors can sensitize chemo-refractory cancers.

Association of isolated single umbilical artery with perinatal outcomes: Systemic review and meta-analysis

OBJECTIVE: The aim of this study was to evaluate the association between prenatally diagnosed isolated single umbilical artery (iSUA) and perinatal outcomes. METHODS: We searched Medline, Embase, the Cochrane Library, and KoreaMed from inception to January 2016, with no language or regional restrictions, for cohort and case-control studies reporting on the relationship of iSUA and perinatal outcomes. We assessed the odds ratios (ORs) and 95% confidence intervals (CIs) for the occurrence of small for gestational age, preterm birth, pregnancy-induced hypertension, neonatal intensive care unit admission, and perinatal mortality in fetuses with iSUA compared with those in fetuses with three vessel cord. RESULTS: Eleven articles totaling 1,731 pregnancies with iSUA met the selection criteria. Studies varied in design, quality, outcome definition, and results. Meta-analysis carried out within predefined groups showed that the presence of an iSUA was associated with small for gestational age (OR, 2.75; 95% CI, 1.97 to 3.83; P<0.00001), preterm birth (OR, 2.10; 95% CI, 1.72 to 2.57; P<0.00001), pregnancy-induced hypertension (OR, 1.62; 95% CI, 1.00 to 2.63; P=0.05), neonatal intensive care unit admission (OR, 2.06; 95% CI, 1.33 to 3.19; P=0.001), and perinatal mortality (OR, 2.29; 95% CI, 1.32 to 3.98; P=0.003). CONCLUSION: Pregnancies complicated by iSUA are at increased risk for small for gestational age, preterm birth, pregnancy-induced hypertension, neonatal intensive care unit admission and perinatal mortality. Further, large prospective cohort studies are required to improve the quality of prenatal counseling and the neonatal care for pregnancies with iSUA.

Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer

PURPOSE: To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. MATERIALS AND METHODS: We included 223 patients who received staging laparotomy and were diagnosed with stage IIC-IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. RESULTS: The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). CONCLUSION: Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.

Transabdominal Embryofetoscopy for the Detection of Short Rib-polydactyly Syndrome, Type II(Majewski), in the First Trimester

Our aim was to demonstrate the potential of first-trimester embryofetoscopy for prenatal diagnosis in a continuing pregnancy. A patient at risk for giving birth to an infant with short rib-polydactyly syndrome, type II (Majewski), presented for prenatal diagnosis at 9 weeks of gestation. A 1 mm semirigid fiberoptic endoscope with an 18 gauge examination sheath and a single-chip digital camera were used for transabdominal embryofetoscopy. Transabdominal embryofetoscopy was performed at 13 weeks of gestation. Direct visualization of the fetus was achieved and no gross limb or facial abnormalities were seen. This case shows that embryofetoscopy is a useful tool for early diagnosis in high-risk patients in the first trimester for continuing pregnancies.

Two Cases of Ectopic Pregnancy Implanted in the Previous Cesarean Section Scar Treated with Dilatation and Evacuation after Vaginal Misoprostol / 대한산부인과학회잡지

Implantation of a pregnancy within the scar of previous cesarean section is the rarest form of ectopic pregnancy. If diagnosed early, treatment options are capable of preserving the uterus and subsequent fertility. However, delayed diagnosis and treatment can lead to uterine rupture, hemorrhage and maternal morbidity. We present two cases of ectopic pregnancy developing in the previous cesarean section scar in which successfully treated with dilatation and evacuation after vaginal misoprostol.

A Case of Intramural Pregnancy / 대한산부인과학회잡지

Intramural pregnancy is among the rarest forms of ectopic pregnancy. Since it has been first reported by Doederlein in 1913, 37 cases were reported in worldwide literatures. The pathologic criteria required for intramural pregnancy is that the product of conception is completely surrounded by uterine musculature and is separated from the uterine cavity and the fallopian tube or round ligament. Because of the difficult early diagnosis of intramural pregnancy, most cases were found after the onset of complications such as uterine rupture, shock and hemoperitoneum. Early detection of intramural pregnancy with the use of transvaginal ultrasonogram is important, and MRI is a useful, noninvasive imaging modality. We report a case of successful conservative chemotherapy for a intramural pregnancy with brief review of literatures.

A Case of Heterotopic Pregnancy after Ovulation Induction / 대한산부인과학회잡지

Heterotopic pregnancy, simultaneous intrauterine and extrauterine pregnancy, classically was considered a exceedingly rare obstetrical phenomenon. But nowadays the natural incidence is increasing and especially in association with assisted reproductive technologies, such as use of variable methods for ovulation inductions, in-vitro fertilization and embryo transfer, and gamate intrafallopian transfer. In spite of the difficult early diagnosis, which is potentially dangerous to the mother and fetus, the maternal mortality, morbidity and fetal loss is low when the diagnosis is made in timely fashion and proper management is achieved. The presence of a intrauterine pregnancy dose not exclude the possibility of a extrauterine pregnancy, and in women associated with assisted reproductive technologies, the possibility of a heterotopic pregnancy should be considered. We report a case of a heterotopic pregnancy following ovulation induction and intrauterine insemination with brief review of literature.