Risk factors of retained products of conception after miscarriage or termination with gemeprost in the second trimester of pregnancy: a retrospective case-controlled study in Japanese population.

Retained products of conception (RPOC) is a complication that occurs in the second trimester of pregnancy. We enrolled 98 women who had a miscarriage or termination with gemeprost in the second trimester of pregnancy. Eighteen cases (18.4%) were RPOC-positive. The gestational week at miscarriage or termination was earlier in the RPOC-positive group than those in the RPOC-negative group (p = .003). The period of the third stage of labour was longer in the RPOC-positive group than in RPOC-negative group (p = .040). The proportion of placental forceps use was higher in the RPOC-positive group than in RPOC-negative group (p = .003). Multivariate logistic regression analysis showed that gestational week (OR: 3.53; p = .04) and use of placental forceps at delivery (OR: 2.21; p = .012) were independent risk factors for RPOC. Earlier gestational weeks at miscarriage or termination and use of placental forceps at delivery were predictive factors for RPOC after second trimester miscarriage or termination with gemeprost.Impact StatementWhat is already known on this subject? There have been some reports on risk factors of RPOC. A previous report showed that the termination of pregnancy with misoprostol at earlier periods was associated with an increased risk of RPOC.What the results of this study add? There have been few studies on the risk factors of RPOC after miscarriage or termination with gemeprost. In this study, we evaluated the risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester. We found that an earlier gestational age (between 12 and 17 weeks) at delivery and using placental forceps to remove placenta were significant risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester.What the implications are of these findings for clinical practice and/or further research? An earlier gestational age and using forceps to remove placenta may be significant risk factors for RPOC. The accurate evaluation and treatment for RPOC is important for maternal life-saving efforts and subsequent pregnancies. Further research is needed to draft a standardised protocol for RPOC.

Malignant melanoma treated with pembrolizumab during pregnancy: A case report and review of the literature.

There have been very few reports on the use of immune checkpoint inhibitors for malignant tumors during pregnancy. Herein, the current study reports a case of a patient diagnosed with advanced malignant melanoma who was treated with pembrolizumab during pregnancy. A 40-year-old primigravida underwent noninvasive prenatal testing at 10 weeks of gestation, and the result was inconclusive, suggesting the possibility of maternal malignancy. A biopsy of the gluteal mass led to a diagnosis of malignant melanoma, and computed tomography revealed extensive metastases in her lungs and lymph nodes. She had a strong desire to proceed with pregnancy. In consideration of fetal growth and maturation, monotherapy was administered with pembrolizumab from 21 weeks of gestation, aiming for 28 weeks of gestation. The fetus grew well without maternal complications. At 28 weeks of pregnancy, the patient gave birth to a healthy boy by cesarean section. There was no evidence of metastasis in the placenta. The patient received nivolumab-ipilimumab combination therapy from postpartum day 13, followed by nivolumab monotherapy, and has been alive with controlled disease for 20 months.

Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice.

Preterm labor (PTL) is the most common cause of neonatal death and long-term adverse outcome. The pharmacological agents for PTL prevention are palliative and frequently fail to prevent PTL and improve neonatal outcome. It is essential to fully understand the molecular mechanisms of PTL in order to develop novel therapeutic methods against PTL. Several lines of evidence indicate some chemokines are expressed in gestational tissues during labor or PTL. To reveal the pathophysiological roles of the CX3CL1-CX3CR1 axis in PTL, we performed present study using LPS-induced PTL mice model in CX3CR1-deficient (Cx3cr1-/-) mice. We indicated that PTL was suppressed in Cx3cr1-/- mice and immunoneutralization of CX3CL1 in WT mice. From immunohistochemical and the gene expression analyses, the CX3CL1-CX3CR1 axis has detrimental roles in PTL through intrauterine recruitment of macrophages and the enhancement of macrophage-derived inflammatory mediators. Thus, the CX3CL1-CX3CR1 axis may be a good molecular target for preventing PTL.

Calreticulin Is Involved in Invasion of Human Extravillous Trophoblasts Through Functional Regulation of Integrin ß1.

Calreticulin (CRT), a molecular chaperone in the endoplasmic reticulum (ER), plays a variety of roles in cell growth, differentiation, apoptosis, immunity, and cancer biology. It has been reported that CRT is expressed in the human placenta, although its function in placental development is poorly understood. Appropriate invasion of extravillous trophoblasts (EVTs) into the maternal decidua is necessary for successful pregnancy. The objective of the present study was to investigate the expression and functional role of CRT in EVTs using the human EVT cell line HTR8/SVneo, in which CRT gene expression was knocked down. We found that CRT was highly expressed in the human placenta in the early stage of pregnancy and localized to the EVTs. CRT knockdown markedly suppressed the invasion ability of HTR8/SVneo cells. Furthermore, the adhesion to fibronectin was suppressed in the CRT-knockdown cells via the dysfunction of integrin α5ß1. In the CRT-knockdown cells, terminal sialylation and fucosylation were decreased, and the core galactose-containing structure was increased in the N-glycans of integrin ß1. In addition, the expression levels of several critical glycosyltransferases were changed in the CRT-knockdown cells, consistent with the changes in the N-glycans. These results showed that CRT regulates the function of integrin ß1 by affecting the synthesis of N-glycans in HTR8/SVneo cells. Collectively, the results of the present study demonstrate that the ER chaperone CRT plays a regulatory role in the invasion of EVTs, suggesting the importance of CRT expression in placental development during early pregnancy.

Levels of serum-circulating angiogenic factors within 1 week prior to delivery are closely related to conditions of pregnant women with pre-eclampsia, gestational hypertension, and/or fetal growth restriction.

AIM: We aimed to investigate maternal serum angiogenic marker profiles within 1 week prior to delivery in cases of gestational hypertension (GH), pre-eclampsia (PE), and/or fetal growth restriction (FGR) with different clinical conditions. METHODS: We enrolled 165 women with singleton pregnancy. The participants were classified based on three characteristics: (i) proteinuria (GH and PE); (ii) FGR (PE with FGR [PE + FGR], PE alone, and FGR alone); and (iii) onset (early onset PE [EO PE] and late-onset PE [LO PE]). All sera were obtained within 1 week prior to delivery, and soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured with enzyme-linked immunosorbent assay. RESULTS: (i) In PE, a significantly increased sFlt-1, sEng, and sFlt-1 to PlGF ratio (sFlt-1/PlGF) and significantly decreased PlGF were observed compared with GH and Term control, whereas in GH, only sFlt-1/PlGF was significantly higher than Term control. (ii) In PE + FGR, similar changes were more markedly shown compared with PE alone. The FGR alone group exhibited similar tendencies as PE, although significant differences were found in PlGF and sEng levels. (iii) In EO PE, significant changes were observed in all factors compared with LO PE or Term control, while no significant change in PlGF levels was observed between LO PE and Term control. CONCLUSION: We demonstrated that the levels of circulating angiogenic factors just before delivery are correlated with the severity of hypertensive disorders of pregnancy and FGR. Profiling these specific markers may contribute to better understanding of the clinical conditions in individual patients and their pathogenesis.

Rapidly progressing large-cell neuroendocrine carcinoma arising from the uterine corpus: A case report and review of the literature.

Large-cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor. LCNECs arising from the genital organs are highly malignant and rare, with <20 cases of LCNEC developing from the uterine endometrium reported to date. We herein present the case of a patient with LCNEC of the endometrium. The patient was a 52-year-old woman, who exhibited lower abdominal pain and rapid uterine enlargement during outpatient treatment for uterine myoma. The endometrial biopsy suggested a diagnosis of poorly differentiated carcinoma or carcinosarcoma. Based on magnetic resonance imaging and positron emission tomography/computed tomography, endometrial stromal sarcoma was suspected. The serum lactate dehydrogenase level was abnormally high. Due to the suspicion of stage IIIC malignant tumor of the uterine corpus, surgery was performed. The pathological diagnosis was stage IIIC2 LCNEC of the endometrium. Recurrence occurred in the vaginal stump, and concurrent chemoradiotherapy (CCRT) was initiated 1 month after the surgery. The residual lesions markedly shrank, but metastasis to the upper abdominal region and cervix subsequently developed. CCRT was attempted, but the associated adverse effects were severe and was switched to palliative treatment. The patient eventually succumbed to the disease 309 days after surgery.

Downregulation of indoleamine 2, 3-dioxygenase expression in the villous stromal endothelial cells of placentas with preeclampsia.

INTRODUCTION: Previous studies have shown that indoleamine 2, 3-dioxygenase (IDO), an immunosuppressive enzyme that converts tryptophan to kynurenine, is expressed in the placenta and might play a role in the maintenance of pregnancy, although its associations with the pathogeneses of preeclampsia (PE) and fetal growth restriction (FGR) remain unclear. The objective of this study was to investigate the differences in IDO expression among normal, PE, and FGR placentas, and the associations between IDO expression and clinical symptoms, or the expression of fms-like tyrosine kinase receptor-1 (Flt-1). METHODS: Immunohistochemical studies of IDO and Flt-1 expression were performed in human placentas that were complicated with FGR alone (n=19), PE alone (n=20), or both PE and FGR (n=39), and gestational age-matched controls (n=23). RESULTS: It was found that IDO was expressed on endothelial cells in the villous stroma, while Flt-1 was located on trophoblast cells. The IDO expression level of the PE alone group was significantly lower than those of the FGR alone and control groups. The IDO expression of the PE+FGR group was significantly lower than that of the FGR alone group. Lower IDO expression was significantly correlated with more severe maternal hypertension or proteinuria in PE patients, who exhibited higher Flt-1 expression. The late onset PE patients exhibited significantly lower IDO expression than the early onset PE patients. CONCLUSION: This study demonstrated that the downregulation of IDO expression on the endothelial cells of the villous stroma was associated with PE, but not FGR, suggesting that IDO might be involved in the pathophysiology of PE.

Prognostic impact of primary tumor SUVmax on preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography in endometrial cancer and uterine carcinosarcoma.

The objective of the present study was to investigate the usefulness of the maximum standardized uptake value (SUVmax) of the primary tumor on preoperative 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) as a prognostic indicator in patients with endometrial neoplasms. A total of 75 patients with endometrial cancer or uterine carcinosarcoma who underwent surgical treatment were included in the present study. All patients underwent preoperative PET/CT, and the correlation between the SUVmax of the primary tumor and clinical outcomes was analyzed. The SUVmax was significantly higher in patients with stage II/III disease, a histology of grade 3 endometrioid adenocarcinoma and carcinosarcoma, a positive lymph node (LN) status, positive lymph-vascular space involvement (LVSI), and deep (≥1/2) myometrial invasion. Receiver operating characteristic curve analysis revealed that the optimal cut-off values of SUVmax for predicting a positive LN, LVSI and deep myometrial invasion were 7.49, 6.45 and 6.45, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with those of patients with a low SUVmax using the cut-off value of 7.30. However, no significant difference was observed in the OS or PFS between the high and low SUVmax groups when analyzed in carcinosarcoma patients alone. Finally, multivariate analyses demonstrated that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in 55 endometrioid adenocarcinoma patients; however, not in all patients, including those with carcinosarcoma. The present findings demonstrated that the SUVmax of the primary tumor may be a useful biomarker for predicting clinical outcomes of patients with endometrial cancer, although its prognostic impact appears to be limited in patients with uterine carcinosarcoma.

Persistent median artery in the hand: a report with a brief review of the literature.

We encountered a persistent median artery in the forearms and hands bilaterally in a 78-year-old Japanese male cadaver during dissection practice at Wakayama Medical University. The brachial arteries divided into the ulnar and radial arteries. The ulnar artery gave off the median and posterior interosseous arteries at the same point, although the anterior interosseous artery was not found. The median artery ran along the median nerve and bifurcated in the hand. In the superficial layer of the palm, one branch of the median artery ran to the ulnar side of the thumb, whereas the other passed to the second interdigital space. The ulnar artery reached the third and fourth interdigital spaces and the ulnar side of the little finger, and showed no anastomosis with the median artery in the superficial layer of the palm. The radial artery did not give off the superficial palmar branch. Therefore, the formation of the superficial palmar arch was incomplete. In the deep layer of the palm, the radial artery formed the deep palmar arch with the deep palmar branch of the ulnar artery and gave off the princeps pollicis artery. In the dorsum of hand, the radial artery passed over the first dorsal interosseous muscle to the index finger and communicated with the palmar pollical artery from the median artery in the first interosseous space. The present study reports an unusual variation of the persistent median artery in the hand and briefly reviews the literature about the median artery.