Kazuhiko Okuyama

Histopathological prognostic factors of adult granulosa cell tumors of the ovary

Background. The prognostic factors of adult granulosa cell tumor (AGCT) have not been well defined.

Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery.

The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.

A case of intrauterine medical treatment for cystic hygroma

We report the first case of an intrauterine treatment for cystic hygroma. Guided by ultrasonography, we first removed intracystic fluid from two cysts and then injected OK-432 into each fetal cyst at 21 and 28 weeks of gestation. No re-enlargement of the cysts was subsequently observed. At 38 weeks of gestation, a male infant was delivered transvaginally. Only a slight skin fold was observed in the nuchal area of the neonate, indicating the effectiveness of OK-432 for the intrauterine treatment of cystic hygroma.

Prevalence, classification, and risk factors for postoperative lower extremity lymphedema in women with gynecologic malignancies: a retrospective study.

Objective Lower extremity lymphedema (LEL) is a major long-term complication of radical surgery. We aimed to estimate the incidence and grading of LEL in women who underwent lymphadenectomy and to evaluate risk factors associated with LEL. Materials and Methods We retrospectively reviewed 358 patients with cervical, endometrial, and ovarian cancer who underwent transabdominal complete systematic pelvic and para-aortic lymphadenectomy between 1997 and 2011. Lower extremity lymphedema was graded according to criteria of the International Society of Lymphology. Incidence of LEL and its correlation with various clinical characteristics were investigated using Kaplan-Meier survival and Cox proportional hazards methods. Results Overall incidence of LEL was 21.8% (stage 1, 60%; stage 2, 32%; and stage 3, 8%). Cumulative incidence increased with observation period: 12.9% at 1 year, 20.3% at 5 years, and 25.4% at 10 years. Age, cancer type, stage (International Federation of Gynecology and Obstetrics), body mass index, hysterectomy type, lymphocyst formation, lymph node metastasis, and chemotherapy were not associated with LEL. Multivariate analysis confirmed that removal of circumflex iliac lymph nodes (hazard ratio [HR], 4.28; 95% confidence interval [CI], 2.09–8.77; P < 0.0001), cellulitis (HR, 3.48; 95% CI, 2.03–5.98; P < 0.0001), and number of removed lymph nodes (HR, 0.99; 95% CI, 0.98–0.99; P = 0.038) were independent risk factors for LEL. Conclusions Postoperative LEL incidence increased over time. The results of the present study showed a significant correlation with removal of circumflex iliac lymph nodes and cellulitis with the incidence of LEL. Multicenter or prospective studies are required to clarify treatment efficacies.

Outcome of non-immune hydrops fetalis and a fetus with hydrothorax and/or ascites: with some trials of intrauterine treatment.

The subject of this study was 38 cases of non-immune hydrops fetalis and 11 cases of fetal hydrothorax and/ or ascites (FH/A), a syndrome characterized by the accumulation of pleural effusion and/or ascitic fluid, without generalized skin edema, due to various etiologies, admitted to the obstetrics ward of Hokkaido University Hospital during the period between 1987 and 1994. Fetal treatment consisted of (1) intravascular transfusion or intra-abdominal transfusion for anemia, (2) frequent centesis or shunt insertion for pleural effusion and ascites, (3) reduction of cystic hygroma by puncturing and OK432 injection, and (4) intravascular or maternal injection with an anti-arrhythmic drugs to treat tachycardia. The outcome of NIHF and FH/A was assessed to be able to make a prognosis in NIHF and to compare the efficacy of fetal therapy in cases with (15 cases: 9 NIHF, 6 FH/A) and without (34 cases: 29 NIHF, 5 HF/A) intrauterine treatment. The average survival rates were 23.1% in NIHF and 54.5% in FH/A. None of fetuses with a chromosomal abnormality or cystic hygroma survived. The average GW at the time of detection of NIHF by ultrasonography was week 24.9 +/- 1.1 (mean +/- S.E., n = 38). The average GW at the time of detection of FH/A by ultrasonography was week 26.6 +/- 1.8 (n = 11). NIHF was detected significantly earlier in the IUFD and early neonatal death group (GW 22.4 +/- 1.4) than in the survivor group (GW 27.6 +/- 1.2) (p < 0.05). FH/A was also detected earlier in the IUFD/early neonatal death group than in the survivor group (GW 21.8 +/- 2.4 vs. 31.1 +/- 1.1, n = 11, p < 0.05). The survival rate in the intrauterine treatment group was higher than in the nontreatment group (treatment group: 10/15; non-treatment group: 5/34, p < 0.001). After the trial of intrauterine treatment in the 15 cases mentioned above, some efficacy was observed in 7 cases (reduction of cysts, effusion or edema, disappearance of arrhythmia).

Recent trends in the prevalence of Down syndrome in Japan, 1980–1997

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.

Serum concentration of endogenous G-CSF in women during the menstrual cycle and pregnancy

Abstract. Although granulocyte‐colony stimulating factor (G‐CSF) is commonly used in the field of supportive therapy for cancer treatment, the serum concentration of endogenous G‐CSF in healthy women is still obscure due to the low sensitivity (30 pg mL‐1) of the usual enzyme immunoassay. With the development of a highly sensitive (l.0 pg mL‐1) chemiluminescent immunoassay by Kiriyama et al., we have clarified the changes of serum G‐CSF levels in healthy women during the menstrual cycle and pregnancy. The G‐CSF concentration showed a peak value of 27.3± 2.5 pg mL‐1 (mean±SEM) at the ovulatory phase during the menstrual cycle, which is significantly higher than in all other phases (P < 0.0001, unpaired t‐test). A significantly higher value compared to the menstrual cycle, except during the ovulatory phase, was also revealed throughout pregnancy (P < 0.0001, unpaired t‐test). These results suggest that G‐CSF plays an important role in ovulation and the maintenance of pregnancy.

Effect of intrauterine inflammation on fetal cerebral hemodynamics and white-matter injury in chronically instrumented fetal sheep.

OBJECTIVE The purpose of this study was to analyze the effects of intrauterine inflammation on cerebral hemodynamics and white-matter injury in premature fetal sheep. STUDY DESIGN Fetuses were given an intravenous infusion of granulocyte colony-stimulating factor and an intraamniotic infusion of endotoxin; the fetuses were then assigned randomly to an acute hemorrhage group, an exchange transfusion group, or a control group. During each insult, the cerebral hemodynamics were assessed with near-infrared spectroscopy. Finally, the fetuses were processed for neuropathologic analysis and compared statistically. RESULTS Necrotizing funisitis and chorioamnionitis were induced in all the fetuses. A significant decrease in the blood oxygen content and an increase in the brain total hemoglobin level were observed after the endotoxin infusion. Soon after hemodynamic insult, the fetuses in both the acute hemorrhage and the exchange transfusion groups showed an abrupt decrease in the total brain hemoglobin level; 4 of the 5 fetuses in each treatment group, but none of the fetuses in the control group, exhibited periventricular leukomalacia. CONCLUSION Hemorrhagic hypotension or anemic hypoxemia might induce a sudden cessation of fetal brain-sparing effects through progressive inflammatory hypoxemia, which results in focal white-matter injuries.

Analyses of factors contributing to vulnerability to antenatal periventricular leukomalacia induced by hemorrhagic hypotension in chronically instrumented fetal sheep

Our purpose was to determine factors contributing to vulnerability to antenatal periventricular leukomalacia (PVL) induced by hemorrhagic hypotension in premature fetal sheep. Systemic hypotension was induced in 10 fetal sheep by acutely withdrawing 35% to 40% of the fetoplacental blood volume at 113 d gestation. Brains were processed for histologic analysis 6 d after the insult. Statistical comparisons of physiologic parameters between fetuses suffering from PVL (n = 5) and those without PVL (n = 5) were performed. Significant correlations were found between induction of PVL and fetal brain weight, changes in fetal mean blood pressure over time, base excess, oxygen content, hematocrit, and plasma arginine vasopressin (AVP) levels in fetal abdominal aortic blood. Brain developmental stage, the magnitude of induced systemic hypotension, and baseline blood oxygen content were important intrinsic factors in the induction of antenatal PVL by hemorrhagic hypotension in premature fetal sheep.

Alpha-fetoprotein microheterogeneity: a potential biochemical marker for Down’s syndrome

Our purpose was to examine the utility of analyzing alpha-fetoprotein (AFP) microheterogeneity assessed by lectin affinity in Downs syndrome (DS) screening. Maternal sera and amniotic fluids were collected from 18 women who were carrying DS fetuses and 70 unaffected pregnancies around 16 weeks of gestation. The percentages of AFP which reacted with Lens culinaris agglutinin (AFP-L2,3) were determined by lectin affinity electrophoresis. AFP-L2,3 levels were significantly increased (P<0.0001) in both maternal serum and amniotic fluid from DS-affected versus unaffected pregnancies. The fractional areas under the receiver operating characteristic curves were 0.835 and 0.700 (P=0.106) for AFP-L3 and AFP MoM (multiples of the median) in maternal serum. No correlation was found between AFP-L3 and AFP MoM in maternal serum (r=0.006). Our data suggest that the measurement of AFP-L3 in maternal serum is a potential biochemical marker for DS.