Gastric adenocarcinoma with germ cell tumor components: a rare case report

Germ cell tumors (GCTs) often occur in male testes and female ovaries. Extragonadal GCTs account for approximately 2% to 5% of all GCTs and mainly occur in the mediastinum, retroperitoneum, and pineal gland. In this study, we reported a rare case of gastric adenocarcinoma with GCT components. The patient’s serum α-fetoprotein (AFP) level was higher than normal. Abdominal computed tomography (CT) showed a 10-cm × 10-cm tumor between the spleen and the bottom of the stomach. Gastric endoscopy indicated an ulcerative lesion extending from the bottom of the stomach to the antrum. Tissue biopsy identified the tumor as an adenocarcinoma. The patient underwent abdominal tumor resection, subtotal gastrectomy, D2 lymphadenectomy, and splenectomy. Postoperative histopathology showed that the tumor was a moderately to poorly differentiated adenocarcinoma. Immunohistochemistry analysis revealed positive staining for AFP, glypican-3, and placental alkaline phosphatase. Gastric adenocarcinoma with GCT components is particularly uncommon and rarely reported. Elevated serum AFP and/or β-human chorionic gonadotropin levels, abdominal CT, histopathology, and immunohistochemistry may help diagnose GCTs. Radical surgery resection is the primary treatment method for GCTs. Adjuvant chemotherapy and radiotherapy are effective for advanced GCTs.

Circulating Placental Alkaline Phosphatase Expressing Exosomes in Maternal Blood Showed Temporal Regulation of Placental Genes

Background: Analysis of placental genes could unravel maternal-fetal complications. However, inaccessibility to placental tissue during early pregnancy has limited this effort. We tested if exosomes (Exo) released by human placenta in the maternal circulation harbor crucial placental genes.Methods: Placental alkaline phosphate positive exosomes (ExoPLAP) were enriched from maternal blood collected at the following gestational weeks; 6–8th (T1), 12–14th (T2), 20–24th (T3), and 28th−32nd (T4). Nanotracking analysis, electron microscopy, dynamic light scattering, and immunoblotting were used for characterization. We used microarray for transcriptome and quantitative PCR (qPCR) for gene analysis in ExoPLAP.Results: Physical characterization and presence of CD63 and CD9 proteins confirmed the successful ExoPLAP enrichment. Four of the selected 36 placental genes did not amplify in ExoPLAP, while 32 showed regulations (n = 3–8/time point). Most genes in ExoPLAP showed significantly lower expression at T2–T4, relative to T1 (p < 0.05), such as NOS3, TNFSF10, OR5H6, APOL3, and NEDD4L. In contrast, genes, such as ATF6, NEDD1, and IGF2, had significantly higher expression at T2–T4 relative to T1. Unbiased gene profiling by microarray also confirmed expression of above genes in ExoPLAP-transcriptome. In addition, repeated measure ANOVA showed a significant change in the ExoPLAP transcriptome from T2 to T4 (n = 5/time point).Conclusion: Placental alkaline phosphate positive exosomes transcriptome changed with gestational age advancement in healthy women. The transcriptome expressed crucial placental genes involved in early embryonic development, such as actin cytoskeleton organization, appropriate cell positioning, DNA replication, and B-cell regulation for protecting mammalian fetuses from rejection. Thus, ExoPLAP in maternal blood could be a promising source to study the placental genes regulation for non-invasive monitoring of placental health.

Clinical significance of predictive and diagnostic indices of fetal pathology associated with placental insufficiency in women with endometriosis

BACKGROUND: Modern achievements of pharmacology, surgery and reproductive medicine have determined an increase in the implementation of reproductive function in endometriosis of various localization. The onset of pregnancy in presence of impaired endometrial receptivity and progesterone resistance, pro-inflammatory and pro-thrombotic status, abnormal functioning of the immune system, structural changes in the reproductive organs leads to impaired formation of the embryo (feto) placental system, early reproductive losses, complicated pregnancy and adverse perinatal outcomes. In this regard, the endometriosis and pregnancy issue requires close study and specific proposals to optimize pregnancy management. AIM: The aim of this study was to develop predictive (PIs) and diagnostic (DIs) indices of placenta-associated fetal pathology in pregnant women with endometriosis, to determine their prognostically and diagnostically significant parameters. MATERIALS AND METHODS: This prospective study in the dynamics of gestation included a comprehensive clinical and laboratory examination of 175 pregnant women with endometriosis (100 subjects with adenomyosis and 75 subjects with ovarian endometriosis). To develop PIs and DIs, two comparison groups with fetal pathology due to placental insufficiency were retrospectively identified, depending on the location of endometriosis. Group I consisted of 49 pregnant women with adenomyosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia; Group II comprised 29 pregnant women with ovarian endometriosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia. The control group (Group III) included 30 healthy pregnant women with a normal course of gestation. The examination was performed at 10-14 weeks, 20-24 weeks, and 28-34 weeks of gestation and included an assessment of placental insufficiency markers such as placental growth factor (PlGF), placental -1-microglobulin (PAMG-1), tumor necrosis factor (TNF), lymphocytes with membrane receptor FasR (L CD95+), C-reactive protein, placental alkaline phosphatase (PAPh), and fetal hemoglobin (HbF). The information value of individual parameters and indices was determined by ROC analysis, odds ratio, and clinical epidemiology tests. RESULTS: Pregnancy in presence of endometriosis in 100% of cases was complicated by placental insufficiency of varying severity (with fetal pathology in 81.5% of cases), the frequency of which had statistically significant differences between the groups of pregnant women with adenomyosis and ovarian endometriosis (2 = 4.06, p = 0.04). To predict growth retardation and / or chronic fetal hypoxia, we have developed PI I (PlGF / TNF 100) and PI II (PAMG-1 / PlGF 100), which characterize the state of placental angio-and vasculogenesis depending on systemic inflammatory response level. For early diagnosis of fetal pathology, we have proposed DI I (CRP / PAPh 100), DI II (HbF / PlGF 100) and DI III (L CD95+ / PAPh 100), which allow for diagnosing placental alterations with impaired placental energy supply due to an increase in inflammatory status. Evaluation of prognostic and diagnostic significance of PIs and DIs showed that the most informative tools are PI I (Se = 86.1%, Sp = 80.5%) and DI I (Se = 88.3%, Sp = 83.7%). CONCLUSIONS: The use of PIs allows for risk stratification of pregnant women from the 1st trimester of gestation to address the issue of the prevention method. The clinical capabilities of DIs optimize obstetric tactics for the timely prescription of therapy for placental insufficiency and targeted diagnosis of fetal pathology. Pregnant women with endometriosis should be classified as a high perinatal risk group, and therefore the proposed PIs and DIs should be included in the dynamic examination complex.

Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome

BackgroundPre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.Methodsperipheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.Resultscirculating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P<0.01).ConclusionsAberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.

Comparison of immunohistochemical profiles of ovarian germ cells in dysgerminomas of a captive maned wolf and domestic dogs

We characterized the immunohistochemical expression profiles of dysgerminomas from a 16-y-old maned wolf and 13 domestic dogs using the following biomarkers: Sal-like protein 4 (SALL4), octamer-binding transcription factor 3/4 (OCT3/4), placental alkaline phosphatase (PLAP), c-kit, and vimentin. The maned wolf had nonspecific and long-standing clinical signs of lethargy, anorexia, and weight loss, and was euthanized because of poor prognosis. At autopsy, the left ovary was effaced by a 12 × 8 × 6 cm mass, comprised of anaplastic cells with a mitotic count of 20 mitoses in 10 high power fields. Dysgerminomas from 7 of 13 domestic dogs had nuclear expression of SALL4. Dysgerminomas from the maned wolf and 2 domestic dogs had both nuclear and cytoplasmic expression of SALL4. Cytoplasmic expression of PLAP and OCT3/4 was present in dysgerminomas from the maned wolf and 3 (PLAP) or 4 (OCT3/4) domestic dogs. All dysgerminomas expressed vimentin. Membranous c-kit expression was rare in the dysgerminoma from the maned wolf, and variable in dysgerminomas from 4 domestic dogs. A dysgerminoma from a domestic dog had cytoplasmic expression of c-kit. SALL4 is a useful marker to confirm germ cell origin of dysgerminoma in canids.

Capsaicin pretreatment alleviates postoperative pain and reduces primary sensory neuron Ca2+ activity

After surgeries, especially thoracotomy incision, patients develop unbearable pain. Opioids are used for reducing pain but often cause serious side effects. Previously, we found that capsaicin pretreatment of the incision area alleviated spontaneous and thermal pain in a postoperative pain animal model. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in in vivo dorsal root ganglia (DRG) in a postoperative pain model using Pirt-GCaMP3 treated with capsaicin or controls. Intraplantar injection of capsaicin (0.05%) alleviated spontaneous, mechanical, and thermal postoperative pain. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared to contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment alleviates postoperative pain by suppressing Ca2+ response due to degeneration of primary sensory nerve fibers in the skin.

Gingival Crevicular Placental Alkaline Phosphatase Is an Early Pregnancy Biomarker for Pre-Eclampsia

Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11–14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p < 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11–14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07; 95% CI 1.01–1.11; p = 0.004 and OR:1.008, 95% CI 1.000–1.015; p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.