Use of SATB2 and CDX2 Immunohistochemistry to Characterize and Diagnose Colorectal Cancer.

SATB2 has been reported to be highly specific for lower gastrointestinal tract tumors. On the basis of its ileum-colon conversion effects, which involve the activation of colonic genes in cooperation with CDX2 and HNF4A, we hypothesized that SATB2 and CDX2 might define the characteristics of colorectal cancers (CRCs). In the present study, the clinicopathologic and immunohistochemical characteristics of 269 CRCs were analyzed according to SATB2 and CDX2 expression. CRCs with SATB2- and/or CDX2- phenotypes showed associations with poorly differentiated histotypes (P<0.00001), mucus production (P=0.0019), and mismatch repair-deficient phenotypes (P<0.00001). SATB2-/CDX2- CRCs were significantly associated with CK20-negativity, with or without CK7 expression (P<0.00001), as well as with MUC5AC-positivity (P<0.00001), and CD10-negativity (P=0.00047). Negativity for SATB2 or CDX2 was associated with the expression of PD-L1 in both all CRC (P<0.00001) and mismatch repair-proficient CRC (P=0.000091). Multivariate Cox hazard regression analysis identified negativity for SATB2 and/or CDX2 as potential independent risk factors for patients with CRC. Regarding the diagnostic utility of SATB2, all of the 44 CRC metastases could be diagnosed as colorectal in origin if the immunohistochemical phenotypes (including CK7, CK20, and p53) of the primary lesions and patient history were considered. Among the other 684 tumors, we were unable to distinguish a case of CK7-/CK20+/CDX2+/SATB2+ ovarian mucinous cystadenocarcinoma from metastatic CRC without the patient history and clinical information.

The biological investigation of prostacyclin in preeclamptic women seen reduced endothelial function.

OBJECTIVE: Our aim was to determine the biological investigation of prostacyclin in preeclamptic women seen reduced endothelial vasodilatation by non-invasive technique in vivo. METHODS: Using a high resolution ultrasound transducer, diameters of brachial arteries were determined after reactive hyperemia in 15 non-pregnant, 20 normotensive pregnant and 20 preeclamptic women. The concentrations of 6-keto-prostaglandin F 1alpha (6keto-PGF 1alpha) in plasma and the concentrations of adenosine-3', 5'-cyclic monophosphate (cyclic AMP) in platelets and serum were measured among the groups. RESULTS: Flow-mediated vasodilatation at 1 min after reactive hyperemia was higher in normotensive pregnant than in the non-pregnant or preeclamptic women. The plasma concentration of 6 keto-PGF 1alpha as well as the serum concentration of cyclic AMP were lower in preeclamptic than those in normotensive pregnant women. The increase in cyclic AMP in the presence of a prostacyclin analogue in platelets was seen at similar levels in all three groups. CONCLUSION: From these results, the concentrations of prostacyclin in plasma and cyclic AMP in serum might be low possibly due to reduced production of prostacyclin in preeclamptic women seen reduced endothelial function.

Increase in serum concentrations of inhibin in early onset pre-eclampsia with intrauterine growth restriction.

AIM: Recently, it has been hypothesized that reduced placental blood flow in early pregnancy causes changes in endothelial function, leading to pre-eclampsia. To clarify this clinically, we assessed serum concentrations of inhibin and uric acid in pre-eclamptic women compared with those of normotensive pregnant women. METHODS: One hundred and forty normotensive pregnant women (at 20-41 weeks' gestation) and 50 women with pre-eclampsia (at 24-41 weeks' gestation) were the study subjects. Pre-eclamptic women were classified according to the new criteria for pregnancy-induced hypertension produced by the Japanese Society of Obstetrics and Gynecology (JSOG). Serum concentrations of uric acid and inhibin were measured enzymatically and by radioimmunoassay, respectively. RESULTS: Serum concentrations of inhibin and uric acid in the pre-eclamptic women were significantly higher than in gestational age-matched normotensive pregnant women. There were significant correlations among inhibin and uric acid, blood pressure and birth weight. According to JSOG criteria, of the 50 pre-eclamptic women, 18 were early onset (EO), including 16 cases complicated by intrauterine growth restriction (IUGR), and 32 cases were late onset, including 12 cases complicated by IUGR. In the patients with EO and IUGR, serum concentrations of inhibin, but not uric acid, were significantly elevated as compared with those of the other pre-eclamptic women. CONCLUSION: The results suggest that an increase in the serum concentration of inhibin seen in EO pre-eclampsia, together with IUGR, might be a cause of reduced placental blood flow.

Evaluation levels of cytokines in amniotic fluid of women with intrauterine infection in the early second trimester.

Amniotic fluid was obtained from 180 patients by amniocentesis at 16-22 weeks of gestation and assayed for the levels of interleukin (IL)-6, IL-8, leukocyte elastase (LE), and glucose. Ten of cases had clinical symptoms, such as uterine contraction, genital bleeding, and cervical ripening, and the other 170 were assessed for fetal chromosomal features. Four of the ten cases with uterine contraction developed abortion, while 10 of those screened had findings of fetal chromosomal anomalies, and 7 cases then underwent induced abortion artificially. In the cases of abortion, levels of IL-6, IL-8 and LE were higher than in the samples from the 160 pregnant women without clinical symptoms and a normal karyotype, while glucose in amniotic fluid was lower. Of 6 cases with clinical symptoms, but not developing abortion, 4 developed preterm labor, and in these IL-6 and IL-8 also were significantly elevated, with LE being slight high compared to normal. The results suggest that IL-6, IL-8, LE, and glucose in amniotic fluid at early second trimester can be used as markers of severe infection in the uterus, and with the first two being particularly sensitive.

Reduced flow-mediated vasodilation is not due to a decrease in production of nitric oxide in preeclampsia.

OBJECTIVE: Our aim was to determine the reduced function of endothelial nitric oxide in preeclampsia by use of noninvasive techniques in vivo. STUDY DESIGN: With the use of a high-resolution ultrasound transducer, diameters of brachial artery were measured after reactive hyperemia in 20 nonpregnant women, 20 normotensive pregnant women, and 15 women with preeclampsia. The concentrations of cyclic guanosine monophosphate were measured in samples of platelets from all groups. RESULTS: Flow-mediated vasodilation at 1 minute after deflation was higher in the normotensive pregnant women (115.1% +/- 6.5%) than in the nonpregnant women (108.7% +/- 3.9%); flow-mediated vasodilation was lower in women with preeclampsia (106.8% +/- 2.7%) than in the normotensive pregnant women. The concentration of platelet cyclic guanosine monophosphate was higher in the normotensive pregnant women than in the nonpregnant women (2.21 +/- 1.10 pmol/mL/10(8) cells vs 0.746 +/- 0.381 pmol/mL/10(8) cells). There was no difference between the normotensive pregnant and the preeclamptic group (2.81 +/- 1.82 pmol/mL/10(8) cells). Furthermore, the increase in cyclic guanosine monophosphate by sodium nitroprusside in platelet samples that were obtained from the normotensive pregnant women was larger than the samples from the nonpregnant women (6.20 +/- 4.2 pmol/mL/10(8) cells vs 1.62 +/- 0.81 pmol/mL/10(8) cells). The increase in cyclic guanosine monophosphate from the women with preeclampsia did not differ from that in the normotensive pregnant women (5.84 +/- 3.73 pmol/ml/10(8) cells). CONCLUSION: These results indicate that reduced endothelial nitric oxide activity might be due to a reduction of nitric oxide-cyclic guanosine monophosphate activity rather than its production in preeclampsia.

Use of aspirin and low-molecular-weight heparin to prevent recurrence of maternal floor infarction in women without evidence of antiphospholipid antibody syndrome.

During pregnancy, maternal floor infarction (MFI) and massive perivillous fibrin deposition (MFD) often cause fetal growth restriction and death, both being markedly increased by occlusion of the maternal intravenous circulation. Incident rates have been reported to be in the range of 0.09-0.5% and recurrent MFI/MFD might be more frequent in early-onset cases. Thus, prevention measures are necessary for high-risk women who have had MFI/MFD as complications in a previous pregnancy. In this report, the use of oral low-dose aspirin at the early trimester and low-molecular-weight heparin drip infusion from the mid-second trimester was examined for this purpose.

Cardiac failure caused by severe pre-eclampsia with placental abruption, and its treatment with anti-hypertensive drugs.

Pre-eclampsia is the abnormality of blood circulation in late pregnancy, often caused by renal failure, hemolysis, elevated liver enzyme, low platelet syndrome, and eclampsia. We present a case of severe pre-eclampsia with placental abruption in a 24-year-old woman, pregnant for the first time. The patient was diagnosed with congestive heart failure, which came as a result of pre-eclampsia. Anti-hypertensive drugs were used for its treatment.

Antenatal evaluation of an encephalocele in a dizygotic twin pregnancy using fast magnetic resonance imaging.

We report a case of an encephalocele in a dizygotic twin pregnancy, following ovulatory induction. In the involved fetus, an abnormal shadow like an encapsulated-solid tumor located on the occiput was found by routine maternal transabdominal ultrasonography at 17 weeks of gestation. The parents did not accept induced abortion because of the presence of another fetus with no abnormality on ultrasonography. At 35 weeks of gestation, transabdominal ultrasound examination showed a large occipital cyst, composed of protrusive fetal brain and cerebrospinal fluid. Fast-scanning magnetic resonance imaging delineated more clearly the inside of the abnormal lesion and thus allowed confirmation of the putative diagnosis of fetal encephalocele during pregnancy. Surgical report was possible in this case, and the patient had no severe physical or neurological abnormalities 10 months after birth. Since the prognosis appears to depend primarily on how prominent the brain tissue is inside the herniated sac, this approach had benefit for clinical decision making.

Prenatal diagnosis of lissencephaly (type II) by ultrasound and fast magnetic resonance imaging.

We report a case of lissencephaly which could be diagnosed by detailed examination during pregnancy. We first found bilateral enlarged ventricles in the fetus by routine abdominal ultrasonography at mid-pregnancy. Fast scanning MRI subsequently allowed confirmation of a diagnosis of lissencephaly during pregnancy.