Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates.

Sulfated glycosaminoglycans (GAGs) such as heparan sulfate (HS) are heteropolysaccharides implicated in the pathology of protein aggregation diseases including localized and systemic forms of amyloidosis. Among subdomains of sulfated GAGs, highly sulfated domains of HS, called HS S-domains, have been highlighted as being critical for HS function in amyloidoses. Recent studies suggest that the tumor suppressor p53 aggregates to form amyloid fibrils and propagates in a prion-like manner; however, molecules and mechanisms that are involved in the prion-like behavior of p53 aggregates have not been addressed. Here, we identified sulfated GAGs as molecules that mediate prion-like behavior of p53 aggregates. Sulfated GAGs at the cell surface were required for cellular uptake of recombinant and cancer cell-derived p53 aggregates and extracellular release of p53 from cancer cells. We further showed that HS S-domains accumulated within p53 deposits in human ovarian cancer tissues, and enzymatic remodeling of HS S-domains by Sulf-2 extracellular sulfatase down-regulated cellular uptake of p53 aggregates. Finally, sulfated GAG-dependent cellular uptake of p53 aggregates was critical for subsequent extracellular release of the aggregates and gain of oncogenic function in recipient cells. Our work provides a mechanism of prion-like behavior of p53 aggregates and will shed light on sulfated GAGs as a common mediator of prions.

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.

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Evaluation of a routine second curettage for hydatidiform mole: a cohort study.

OBJECTIVE: The aim of this study was to evaluate routine second curettage for hydatidiform mole (HM) by comparing the characteristics and outcomes of developing gestational trophoblastic neoplasia (GTN). STUDY DESIGN: This was a cohort study including 173 patients diagnosed with HM between January 2002 and August 2019 who were followed up at Nagoya University Hospital, Japan. After an evacuation, 105 and 68 patients were managed with the routine method (routine group) and elective method (elective group) for a second curettage, respectively. The routine second curettage was performed around 7 days after the first evacuation. Patients in the elective group underwent a second curettage if there was ultrasonographic evidence of molar remnants in the uterine cavity. Socio-clinical factors were retrospectively compared between the routine and elective groups, and between patients showing regression and those who developed GTN. RESULTS: The incidence of GTN was 15.2% in the routine group and 20.6% in the elective group, and the difference was not significant (P = 0.364). The median GTN risk score was significantly higher in the routine group than in the elective group (P = 0.033). Presence of a complete HM, gestational age, and a pre-treatment human chorionic gonadotropin level of ≥ 200,000 mIU/mL were independent risk factors for GTN in molar patients. CONCLUSION: The incidence of GTN was unchanged but the risk score of GTN was higher in the routine group than in the elective group. Routine second curettage may not be necessary, but further study will be needed to confirm this.

The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia.

OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide, and actinomycin D (MEA) for patients who were diagnosed with choriocarcinoma and high-risk gestational trophoblastic neoplasia (GTN). METHODS: Between January 1999 and December 2015, 29 patients were treated with 4-day MEA after being diagnosed with choriocarcinoma or high-risk GTN. Complete remission to 4-day MEA and adverse effects were retrospectively evaluated. RESULTS: The complete remission rates were 79.3% (23/29) and 87.5% (21/24) in all patients and in those who received 4-day MEA as first-line therapy, respectively. Of six patients who developed drug resistance to 4-day MEA, three patients showed complete remission by other treatments, while the other three patients died of the disease. The major adverse effects were leukocytopenia, anemia, and nausea. Of 23 patients who were cured with 4-day MEA, treatment was changed to the etoposide and actinomycin D (EA) regimen in 14 patients, because of leukocytopenia, hepatotoxicity, and stomatitis. Among 20 patients who required hormonal therapy, 15 patients showed normal menstrual cycles after therapy. Five patients had nine conceptions (seven term live births and two spontaneous abortions). No babies were premature or had low birth weight nor did they have congenital anomalies. CONCLUSION: The results suggest that the efficacy and the adverse effects of 4-day MEA for choriocarcinoma and high-risk GTN may be the same level as EMA/CO. However, further study will be needed for determining the criteria of changing the treatment regimen from 4-day MEA to the EA regimen.

Programmed cell death ligand 1 disruption by clustered regularly interspaced short palindromic repeats/Cas9-genome editing promotes antitumor immunity and suppresses ovarian cancer progression.

Programmed cell death ligand 1 (PD-L1) on tumor cells suppresses anti-tumor immunity and has an unfavorable prognostic impact in ovarian cancer patients. We herein report the pathophysiological and therapeutic impacts of PD-L1 disruption in ovarian cancer. PD-L1 was genetically disrupted in the murine ovarian cancer cell line ID8 using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing. PD-L1 knockout (KO) and control ovarian cancer cells were intraperitoneally inoculated into syngeneic mice, and survival and tumor dissemination were evaluated. Survival times were significantly longer in the PD-L1-KO ID8-inoculated groups than in their control groups, and its therapeutic benefit was enhanced in combination with the cisplatin treatment. Tumor weights and ascites volumes were significantly lower in the PD-L1-KO ID8 groups than in their control groups. Immunohistochemical and immunofluorescence analyses showed that intratumoral CD4+ T cells, CD8+ T cells, NK cells and CD11c+ M1 macrophages were significantly increased, whereas regulatory T cells were significantly decreased in the PD-L1-KO ID8 groups compared with those in their control groups. The intratumoral mRNA expression of interferon-γ, tumor-necrosis factor-α, interleukin (IL)-2, IL-12a, CXCL9 and CXCL10 was significantly stronger, while that of IL-10, vascular endothelial growth factor, CXCL1 and CXCL2 was significantly weaker in the PD-L1-KO ID8 groups. These results indicate that CRISPR/Cas9-mediated PD-L1 disruption on tumor cells promotes anti-tumor immunity by increasing tumor-infiltrating lymphocytes and modulating cytokine/chemokine profiles within the tumor microenvironment, thereby suppressing ovarian cancer progression. These results suggest that PD-L1-targeted therapy by genome editing may be a novel therapeutic strategy for ovarian cancer.

Perinatal outcome of vaginal delivery with epidural analgesia initiated at the early or late phase of labor period: A retrospective cohort study in the Japanese population.

AIM: We compared the perinatal outcomes of vaginal delivery with epidural analgesia initiated at the early versus late phase in a Japanese population. METHODS: Women enrolled in this retrospective cohort study received intrapartum analgesia via combined spinal epidural analgesia after labor onset between May 2010 and August 2015. We compared the perinatal outcomes between two different timings of epidural analgesia: at the early phase (≤3 cm cervical dilatation) and the late phase (≥4 cm) or at the new definition-based early phase (≤5 cm) and late phase (≥6 cm). RESULTS: One hundred twenty-eight singleton pregnant women were eligible. In nulliparous women, there was no marked difference in perinatal outcomes between the early and late phase except for in the first-stage labor period (13.7 h vs 10.1 h, P = 0.016). In multiparous women, there was no marked difference in perinatal outcomes between the early and late phase except for a higher proportion of Apgar score ≤7 at 1 min in the early phase (20.0% vs 0.0%, P = 0.033). In nulliparous women, the first-stage labor period in the new early phase was significantly longer than in the new late phase (13.3 h vs 6.9 h, P = 0.035). Other variables for nulliparous women and all for multiparous women were not different between the new early and late phases. CONCLUSION: Most perinatal outcomes between the early and late phases of initiated epidural analgesia were not markedly different in our Japanese population, even when using a new definition of labor phase.

Placental mesenchymal dysplasia with severe fetal growth restriction in one placenta of a dichorionic diamniotic twin pregnancy.

We report a rare case of placental mesenchymal dysplasia (PMD) with fetal growth restriction (FGR) in one placenta of a dichorionic diamniotic (DD) twin pregnancy. A 24-year-old woman was referred to our hospital at 24 weeks' gestation due to FGR and ipsilateral placental abnormality in DD twins. Ultrasound and magnetic resonance imaging showed one placenta of the FGR fetus was bulky and had multiple cysts, while the other fetus placenta appeared normal. Cesarean section was performed at 32 weeks' gestation; the first and second neonates weighted 1799 and 1215 g, respectively. Macroscopically, chorionic vessels on the placental surface of the second neonate were prominently enlarged. Pathological findings demonstrated swelling stem villi with enlarged vessels and increased interstitial cells without trophoblast proliferation. Immunostaining for p57kip2 was negative in interstitial cells and cytotrophoblasts of the swelling stem villi. This suggested that PMD occurred in one placenta of the DD twin, leading to early-onset FGR.

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.

Japan Society of Gynecologic Oncology guidelines 2013 for the treatment of uterine body neoplasms.

The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.

Gestational Trophoblastic Neoplasia and Pregnancy Outcome After Routine Second Curettage for Hydatidiform Mole A Retrospective Observational Study.

OBJECTIVE: To investigate gestational trophoblastic neoplasia (GTN), fertility, and pregnancy outcome in molar patients who underwent routine second curettage. STUDY DESIGN: Eighty-two patients who visited our hospital for hydatidi- form mole between 2002 and 2011 were registered in this study. All patients had sec- ond curettage around the 7th day after first evacuation. We performed retrospective analysis on several factors between a remission group and a GTN group. RESULTS: Fourteen patients (17.1%) had chemotherapy after being diagnosed with GTN. Multivariate analysis revealed that the hCG value before first evac- uation was only one independent prognostic factor for GTN. The median follow-up period was 45.5 months, and 41 patients had 62 pregnancies after remission of hydatidiform mole and GTN. The fertility rate was 80% in 45 patients with desire for a baby, and 39 pregnancies (62.9%) ended in live births without congenital malformation. CONCLUSION: The incidence of GTN was not lower in hydatidiform mole with routine second curettage. An independent prognostic factor for GTN- was the hCG value before the first evac- uation in molar patients. Our results suggest that rou- tine second curettage does not affect the fertility rate or increase a risk of adverse outcomes in subsequent prej- nancies.

Clinicopathologic Factors of Cervical Adenocarcinoma Stages IB to IIB.

OBJECTIVE: The aim of this study was to clarify the clinicopathologic factors of stages IB to IIB cervical adenocarcinoma. METHODS: Several clinicopathologic factors were compared between 35 patients who underwent radical hysterectomy and pelvic lymphadenectomy due to cervical adenocarcinoma stages IB to IIB and 77 patients with squamous cell carcinoma (SCC). RESULTS: In patients with adenocarcinoma, univariate analysis demonstrated that International Federation of Gynecology and Obstetrics stage, tumor size, and lymphovascular space invasion were significantly associated with progression-free survival (PFS), whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with overall survival (OS). However, multivariate analysis revealed that FIGO stage was the only significant factor for PFS in patients with adenocarcinoma. In patients with SCC, univariate analysis demonstrated that FIGO stage and lymph node metastasis were significantly associated with PFS, whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with OS. Multivariate analysis revealed that lymph node metastasis was the only significant factor for PFS and OS in patients with SCC. In 26 patients who were positive for high-risk human papillomavirus (HPV), including both adenocarcinoma and SCC patients, univariate and multivariate analyses revealed that HPV18 was significantly associated with poorer PFS compared with non-HPV18. There was a significant difference in distribution of HPV genotype between adenocarcinoma and SCC. CONCLUSIONS: Careful treatment may be necessary for the patients with lymphovascular space invasion in early-stage cervical adenocarcinoma. The presence of HPV18 may have an influence on the prognosis of early-stage cervical carcinoma.

Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months.

Acute fatty liver of pregnancy associated with fetal mitochondrial trifunctional protein deficiency.

Acute fatty liver of pregnancy (AFLP) is a devastating disorder of the maternal liver in the third trimester. Recent studies have demonstrated an association between AFLP and fetal fatty acid oxidation disorders. Here, we report a case of AFLP caused by fetal mitochondrial trifunctional protein (TFP) deficiency. A 21-year-old parous woman presented with nausea, genital bleeding and abdominal pain at 33 weeks of gestation. Laboratory data revealed hepatic failure and disseminated intravascular coagulopathy. The patient underwent emergency cesarean section and was diagnosed with AFLP from the clinical characteristics. She was successfully treated with frequent plasma exchange. The newborn presented severe heart failure and died on the 39th day after birth. Tandem mass spectrometry indicated long-chain fatty acid oxidation disorder. Gene analysis demonstrated homozygous mutation in exon 13 of HADHB, the gene responsible for mitochondrial TFP deficiency. The parents carried a heterozygous mutation at the same location in HADHB.

Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. Our prior study showed that tumoral IDO overexpression is involved in disease progression and impaired patient survival in human ovarian cancer, although its mechanism remains unclear. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. Indoleamine 2,3-dioxygenase cDNA was transfected into the murine ovarian carcinoma cell line OV2944-HM-1, establishing stable clones of IDO-overexpressing cells (HM-1-IDO). Then HM-1-IDO or control vector-transfected cells (HM-1-mock) were i.p. transplanted into syngeneic immunocompetent mice. The HM-1-IDO-transplanted mice showed significantly shortened survival compared with HM-1-mock-transplanted (control) mice. On days 11 and 14 following transplantation, the tumor weight of peritoneal dissemination and ascites volume were significantly increased in HM-1-IDO-transplanted mice compared with those of control mice. This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-ß and interleukin-10 in ascites. Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-ß secretion. These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity. Therefore, IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.

Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer.

OBJECTIVE: The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. RESULTS: Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.

Ovarian steroid cell tumor, not otherwise specified, producing testosterone.

Steroid cell tumor, not otherwise specified, is a rare type of ovarian sex cord-stromal tumor with malignant potential. Some of these tumors produce testosterone. We describe a case of steroid cell tumor of the ovary associated with virilization. A 23-year-old nulliparous woman was found to have an ovarian tumor when she visited her primary doctor for virilization and oligomenorrhea. Magnetic resonance imaging revealed a solid left ovarian tumor 40 mm in size. Her laboratory data revealed elevated testosterone with normal levels of gonadotropins, estradiol, dehydroepiandrosterone sulfate and cortisol. She underwent left adnexectomy. On histopathologic and immunohistochemical analyses, the tumor was diagnosed as steroid cell tumor, not otherwise specified, without malignant behavior. After removal of the tumor, serum testosterone level decreased, and there have been no signs of recurrence.

Adverse perinatal and neonatal outcomes in patients with chronic abruption-oligohydramnios sequence.

AIM: Chronic abruption-oligohydramnios sequence (CAOS) is a clinical condition with lasting vaginal bleeding and oligohydramnios because of chronic placental abruption, which seems to cause preterm labor and neonatal chronic lung disease (CLD). This prompted us to explore the correlation between perinatal/neonatal outcomes and CAOS. METHODS: Patients with suspected risk of abortion with recurrent vaginal bleeding were divided into CAOS and non-CAOS groups, and we compared the perinatal/neonatal outcomes between these two groups. To examine the impact of chorioamnionitis (CAM) on the prognosis of CAOS, we also compared outcomes between the CAOS group and gestational-age-matched preterm labor due to CAM (CAM group). RESULTS: In the CAOS and non-CAOS groups, initial vaginal bleeding was seen at the first trimester. However, its duration was significantly longer in the CAOS group. Additionally, neonatal birthweight was lower, and small-for-gestational-age (SGA) incidence was higher in the CAOS group. CLD was observed in most infants from CAOS patients. In the comparison between CAOS and CAM groups, birthweight was lower and SGA incidence was higher in the CAOS group. Moreover, CLD incidence and neonatal mortality were significantly higher, despite the lower incidence of severe CAM in the CAOS group. Finally, multivariate analysis demonstrated that duration of bleeding was a significant predictive factor for CAOS. CONCLUSIONS: Our observations demonstrated that patients with CAOS were a high-risk group for poor perinatal/neonatal outcomes. Moreover, episodes of recurrent and prolonged uterine bleeding were predictive factors for CAOS. During the first trimester, prolonged bleeding is an important sign as one symptom of CAOS.

Progesterone treatment reduces food intake and body weight in ovariectomized female rats.

While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.

Monoclonality of composite large-cell neuroendocrine carcinoma and invasive intestinal-type mucinous adenocarcinoma of the cervix: a case study.

A rare case of mixed carcinoma of the cervix is reported, composed of a large-cell neuroendocrine carcinoma and an invasive intestinal-type mucinous adenocarcinoma. The large-cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium-sized to large-sized cells, and was positive for chromogranin-A and CD56. The invasive intestinal-type mucinous adenocarcinoma showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large-cell neuroendocrine carcinoma may have arisen from the invasive mucinous adenocarcinoma.