Yamamoto E, et al. J Gynecol Oncol. 2022 Aug;33:e72. https://doi.org/10.3802/jgo.2022.33.e72

Background: Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. Case presentation: A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. Conclusion: Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

Objective: Choriocarcinoma is the most common epithelial cancer among gestational trophoblastic diseases (GTDs); the mechanism of trophoblastic carcinogenesis is unknown. This study aimed to examine the expression of NF-B family proteins in GTDs and placental tissues as well as the roles of c-Rel in choriocarcinoma. Methods: We examined the expression of NF-B family proteins in normal placenta and hydatidiform mole tissues as well as extravillous trophoblast (EVT) and choriocarcinoma cell lines by Western blot and immunohistochemistry. Immunoprecipitation was performed to determine which proteins can bind with c-Rel in choriocarcinoma cells. To investigate the roles of c-Rel in choriocarcinoma, we examined the effects of c-Rel knockdown and overexpression on cell proliferation, migration, and invasion using small interfering RNAs and gene activation plasmid. Results: The expression of c-Rel was strong in choriocarcinoma and EVTs, but very weak in villi of normal placenta and hydatidiform mole. Immunoprecipitation suggested that c-Rel heterodimerizes with p65 in choriocarcinoma. c-Rel knockdown reduced invasion, migration, and AKT phosphorylation in choriocarcinoma cells. c-Rel overexpression in choriocarcinoma increased migratory and invasive abilities, and the effect on invasion was inhibited by a PI3K inhibitor. Conclusion: These findings suggest that c-Rel might play a role in promoting the invasion of choriocarcinoma cells through PI3K/AKT signaling.

Background: In healthcare, “speaking up” refers to when healthcare workers raise concerns regarding patient safety through questions, sharing information, or expressing their opinion to prevent harmful incidents and ensure patient safety. Conversely, withholding voice is an act of not raising concerns, which could be beneficial in certain situations. Factors associated with speaking up and withholding voices are not fully understood, especially in strong authoritarian societies, such as Malaysia. This study aimed to examine the factors associated with speaking up and withholding the voices of healthcare workers in Malaysia, thus providing suggestions that can be used in other countries facing similar patient safety challenges. Methods: This cross-sectional study was conducted in a tertiary hospital in Sarawak State, Malaysia. Data were collected from 474 healthcare workers from 43 departments using a self-administered questionnaire for speaking up and withholding voices measures in 4 weeks prior to data analysis as well as socio-demographic factors of healthcare workers (sex, age group, profession, department, weekly work hours for patient care, years of employment in the hospital, and the hierarchical level) and speaking up related climate of the working environment were recorded. Data were analyzed using descriptive statistics. Logistic regression was performed to find out (adjusted) odds ratio of frequent speaking up and withholding voices. Results: Nurse compared to doctors and healthcare workers with short weekly working hours were more likely to speak up. Healthcare workers in emergency and intensive care department, those with short years of employment, and those who worked at low hierarchical levels were less likely to speak up. Healthcare workers in discouraging environment towards speaking up were more likely to withhold their voices. Conclusions: This study demonstrates the characteristics of healthcare workers who speak up and those who withhold their voices in Malaysia. To ensure patient safety and prevent harm, it is essential to establish an encouraging environment that promotes speaking up and prevents withholding voices among healthcare worker, especially in circumstances where multiple types of healthcare workers with different socio-demographic backgrounds work together.

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

Gestational trophoblastic neoplasia (GTN) include a group of malignant neoplasms that originate from the trophoblasts of placental tissue in molar or nonmolar pregnancy. Currently, it is unclear whether the prognosis of high-risk GTN or gestational choriocarcinoma succeeding molar pregnancy or that following a nonmolar one is better. Comparison of the genetic short tandem repeat (STR) patterns of the DNA extracted from the tumor, patient, and her partner allows the genetic origins of the choriocarcinoma to be distinguished - whether it is gestational or non-gestational and whether it is derived from a molar or nonmolar pregnancy in the event it is gestational. This study aimed to investigate the causative pregnancy of patients with high-risk GTN, especially those with poor outcomes, and assess the impact of the causative pregnancy on patient outcome. We evaluated 24 patients who were diagnosed with high-risk GTN between January 2000 and October 2019, including 15 cases of pathologically proven gestational choriocarcinomas and the causative pregnancy was investigated by STR analysis in which tumor DNA could be extracted. In high-risk GTN without history of anteceding molar pregnancies, nonmolar pregnancy was the causative pregnancy, which was confirmed in three cases. Molar pregnancy appeared be the causative pregnancy of high-risk GTN in patients with a history of antecedent molar pregnancies either with or without interruption by subsequent nonmolar pregnancies prior to developing high-risk GTN. High-risk GTN in most of the evaluated deceased cases (three of four) was due to nonmolar pregnancy, while all but one case with molar pregnancy as the causative pregnancy survived. STR analysis can distinguish the causative pregnancy of high-risk GTN, and nonmolar pregnancy as the causative pregnancy might have negative effects on the outcome of the disease.