Remarkable response of recurrent endometrial adenocarcinoma to daily oral administration of half-dose etoposide.

A 71-year-old woman with right chest and left lumbar pain was referred to our hospital. Computed tomography showed multiple recurrent tumors in the abdominal cavity and bilateral lungs. She had already received several chemotherapies for the recurrent tumor, and palliative care would be appropriate. However, she was seeking another anti-cancer therapy. Therefore, she was told about low-dose etoposide therapy and consented to its administration. Treatment was very effective; serum tumor marker levels decreased dramatically, the pain was controlled, and the recurrent masses were shrinking. However, her recurrent tumor had become refractory again in the 22nd month of treatment.

Case of pure ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin but responsive to monotherapy with weekly irinotecan.

Primary ovarian squamous cell carcinoma is uncommon, and the optimal treatment strategy for this disease has not yet been established. A 71-year-old woman diagnosed with FIGO stage IIb pure ovarian squamous cell carcinoma underwent cytoreductive surgery followed by combination chemotherapy with paclitaxel and carboplatin. After the second treatment course, a recurrent mass grew rapidly, and serum tumor maker levels increased. Monotherapy with weekly irinotecan was then instituted. This second-line chemotherapy was remarkably effective, and the patient subsequently underwent complete interval debulking surgery with a pathological complete response after the third treatment course. Weekly irinotecan is an effective choice for primary ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin.

A thick placenta: a predictor of adverse pregnancy outcomes.

PURPOSE: The aim of this study is to evaluate the efficacy of an ultrasonographic measurement of placental thickness and the correlation of a thick placenta with adverse perinatal outcome. METHODS: Placental thickness was measured in single gravidas, 16 to 40 weeks of gestation, between 2005 and 2009. Placentas were considered to be thick if their measured thickness were above the 95th percentile for gestational age. RESULTS: The incidence of thick placentas was 4.3% (138/3,183). Perinatal morbidity and neonatal conditions were worse in cases with thick placenta rather than without thick placenta. CONCLUSIONS: Ultrasonographic measurement of placental thickness is a simple method to estimate placental size. Thick placenta may be a useful predictor of adverse pregnancy outcomes.

Congenital high airway obstruction syndrome in the breech presentation managed by ex utero intrapartum treatment procedure after intraoperative external cephalic version.

Congenital high airway obstruction syndrome (CHAOS) caused by laryngeal atresia was diagnosed by prenatal ultrasound in a male fetus at 26 weeks of gestation. Findings included massive ascites, subcutaneous edema, enlarged hyperechogenic lungs with diaphragmatic inversion, dilated trachea, polyhydramnios, and breech presentation. Those findings of CHAOS spontaneously returned to normal by 33 weeks of gestation. However, the placenta was localized to the anterior uterine wall. In addition, the fetal position had been breech until delivery. At 36 weeks of gestation, a planned ex utero intrapartum treatment (EXIT) procedure was performed following intraoperative external cephalic version (ECV) in which the fetus was approached from the posterior wall of the uterus. Laryngoscopy revealed the predicted laryngeal obstruction, and tracheostomy was placed. Intraoperative ECV may be a useful technique in breech presentation before EXIT procedure.

Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium.

OBJECTIVE: To examine whether thin endometria can be improved by increasing uterine radial artery (uRA) blood flow. DESIGN: A prospective observational study. SETTING: University hospital and city general hospital. PATIENT(S): Sixty-one patients with a thin endometrium (endometrial thickness [EM] <8 mm) and high radial artery-resistance index of uRA (RA-RI >or=0.81). INTERVENTION(S): Vitamin E (600 mg/day, n = 25), l-arginine (6 g/day, n = 9), or sildenafil citrate (100 mg/day, intravaginally, n = 12) was given. MAIN OUTCOME MEASURE(S): EM and RA-RI were assessed by transvaginal color-pulsed Doppler ultrasound. RESULT(S): Vitamin E improved RA-RI in 18 (72%) out of 25 patients and EM in 13 (52%) out of 25 patients. L-arginine improved RA-RI in eight (89%) out of nine patients and EM in six (67%) patients. Sildenafil citrate improved RA-RI and EM in 11 (92%) out of 12 patients. In the control group (n = 10), who received no medication to increase uRA-blood flow, only one (10%) patient improved in RA-RI and EM. The effect of vitamin E was histologically examined in the endometrium (n = 5). Vitamin E improved the glandular epithelial growth, development of blood vessels, and vascular endothelial growth factor protein expression in the endometrium. CONCLUSION(S): Vitamin E, l-arginine, or sildenafil citrate treatment improves RA-RI and EM and may be useful for the patients with a thin endometrium.

Modified sequential laser photocoagulation of placental communicating vessels for twin-twin transfusion syndrome to prevent fetal demise of the donor twin.

AIMS: Twin-twin transfusion syndrome (TTTS) complicated with absent or reversed end-diastolic flow in the umbilical artery (UA-AREDF) of the donor has a high perinatal mortality rate. To improve the prenatal outcome, we introduced and modified the technique of sequential selective laser photocoagulation of communicating vessels (SQLPCV), and assessed the clinical efficacy. METHODS: The modified SQLPCV was designed with the following order of coagulation: (i) artery-to-artery (AA) anastomoses; (ii) venous-to-venous anastomoses; (iii) artery-to-venous anastomoses from donor to recipient; and (iv) artery-to-venous anastomoses from recipient to donor. TTTS patients with UA-AREDF of donors were recruited, and the perinatal outcome and its association with the types of anastomoses were compared in patients who underwent the standard selective laser method (SLPCV). RESULTS: Twenty-three patients underwent modified SQLPCV and 29 underwent SLPCV. Total intrauterine fetal death (IUFD) was significantly lower in modified SQLPCV than in SLPCV (9% vs 38%; P < 0.001). Donor IUFD was significantly lower in modified SQLPCV than in SLPCV (13% vs 52%; P = 0.007); however, no significant effect was noted in the recipient IUFD cases. When AA anastomoses were present, donor IUFD was significantly lower in modified SQLPCV than it was in SLPCV (18% vs 71%; P = 0.018); however, the difference was not significant when AA anastomoses were not present (8% vs 25%; P = 0.59). Logistic regression analysis revealed that modified SQLPCV served as the protective factor against the donor's IUFD (odds ratio = 0.015; 95% confidence interval [0.0001-0.775]; P = 0.037). CONCLUSION: The modified SQLPCV was useful for the prevention of the donor's IUFD in cases of TTTS with UA-AREDF.

Two cases of reversal of twin-twin transfusion syndrome diagnosed by measuring hourly fetal urine production.

Reversal of twin-twin transfusion syndrome (TTTS) is a rare complication of monochorionic pregnancy. Diagnostic criteria and satisfactory therapeutic options have not been reported. We make a suggestion of diagnosis and therapy for reversal of TTTS. We report two cases of reversal of TTTS. Measurement of the fetal urine production rate was useful for management and better comprehension of the cases. In case 1, double intrauterine fetal demise occurred before the criteria for TTTS were fulfilled, in which each fetal urine production rate reversed prior to the change of amniotic fluid volume. In case 2, elevated urine production was noted prior to progressive polyhydroamnios and congestive heart failure in the new recipient and the fetoscopic laser photocoagulation of the placental communicating vessels was performed successfully before the criteria for TTTS were fulfilled. Both infants required intensive care, but developed normally and showed no neurologic complications at 2 years after birth. Hourly fetal urine production rate was useful for immediate diagnosis of reversal of TTTS, and laser photocoagulation of the placental communicating vessels is thus a method for the correction of the fetal blood flow imbalance in cases of reversal of the donor-recipient phenotype in TTTS.

Pathophysiologic features of "thin" endometrium.

OBJECTIVE: To characterize pathophysiologic features of a "thin" endometrium. DESIGN: A prospective observational study. SETTING: University Hospital and City General Hospital. PATIENT(S): Patients with normal-thickness endometrium (Normal-Em group: endometrial thickness >or=8 mm; n = 57) and thin endometrium (Thin-Em group: endometrial thickness <8 mm; n = 17). MAIN OUTCOME MEASURE(S): Blood flow impedance of the uterine radial artery (RA) was assessed as resistance index (RI) by transvaginal color-pulsed Doppler ultrasonography. The area of glandular epithelium, the number of blood vessels, and vascular endothelial growth factor (VEGF) expression were examined in the midluteal-phase endometrium. RESULT(S): The RA-RI in the Thin-Em group was significantly higher than in the Normal-Em group throughout the menstrual cycle. Endometrial thickness was significantly correlated with RA-RI. Growth of glandular epithelium, the number of blood vessels, and VEGF expression were significantly lower in the Thin-Em group than in the Normal-Em group. CONCLUSION(S): A "thin" endometrium was characterized by high blood flow impedance of RA, poor epithelial growth, decreased VEGF expression, and poor vascular development.

Fetoscopic laser photocoagulation of placental communicating vessels for twin-reversed arterial perfusion sequence.

Twin-reversed arterial perfusion (TRAP) sequence is a rare and compromised complication in monochorionic pregnancies. The retrograde blood flow through placental communicating vessels is mainly involved to develop the syndrome. Increased cardiac output in the pump twin can lead to severe clinical manifestations. Various surgical techniques to occlude vascular communications between the pump twin and acardiac twin have been reported. A woman with TRAP sequence, at 22 weeks of gestation, complicated with progressive polyhydramnios underwent fetoscopic laser photocoagualtion of vascular communications on the placental surface. Fetoscopic observation demonstrated one artery-to-artery anastomosis and one venous-to-venous anastomosis from the pump twin to the acardiac twin, and these communications were successfully photocoagulated. The patient delivered a 2308-g female infant at 34 weeks and 1 day of gestation, following premature rupture of membrane. The infant is now 1 year old without any neurological problem. Fetoscopic laser photocoagulation of placental communicating vessels can be the procedure of choice for TRAP sequence.

Primary amenorrhea in an 18-year-old Japanese female with sensorineural hearing loss and anosmia: a new sydrome?

This report documents a case with primary amenorrhea associated with sensorineural hearing loss and anosmia. The patient presented at 18 years of age with minimal sexual development and no prior menses. Her mother also presented late onset menarche, hearing loss and anosmia, and her father was also affected with hearing loss. A chromosome analysis of the patient showed 46, XX. Basal FSH and LH levels were in normal range, but the serum estradiol level was low. A serum estradiol elevation and follicular development were recognized after the injection of human menopausal gonadotropin. Genomic DNA sequencing of FSHB, FSHR, KAL1, FGFR1, PROK2 and PROKR2 did not show any mutation. Audiometry showed severe bilateral sensorineural hearing loss and smell testing confirmed a severely impaired olfactory function. These findings probably suggested a case of delayed puberty associated with sensorineural hearing loss and anosmia.

Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate.

We investigated the relationship between oxidative stress and poor oocyte quality and whether the antioxidant melatonin improves oocyte quality. Follicular fluid was sampled at oocyte retrieval during in vitro fertilization and embryo transfer (IVF-ET). Intrafollicular concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in women with high rates of degenerate oocytes were significantly higher than those with low rates of degenerate oocytes. As there was a negative correlation between intrafollicular concentrations of 8-OHdG and melatonin, 18 patients undergoing IVF-ET were given melatonin (3 mg/day), vitamin E (600 mg/day) or both melatonin and vitamin E. Intrafollicular concentrations of 8-OHdG and hexanoyl-lysine adduct were significantly reduced by these antioxidant treatments. One hundred and fifteen patients who failed to become pregnant with a low fertilization rate (< or =50%) in the previous IVF-ET cycle were divided into two groups during the next IVF-ET procedure; 56 patients with melatonin treatment (3 mg/day) and 59 patients without melatonin treatment. The fertilization rate was improved by melatonin treatment compared to the previous IVF-ET cycle. However, the fertilization rate was not significantly changed without melatonin treatment. Oocytes recovered from preovulatory follicles in mice were incubated with H2O2 for 12 hr. The percentage of mature oocytes with a first polar body was significantly reduced by addition of H2O2 (300 microm). The inhibitory effect of H2O2 was significantly blocked by simultaneous addition of melatonin. In conclusion, oxidative stress causes toxic effects on oocyte maturation and melatonin protects oocytes from oxidative stress. Melatonin is likely to improve oocyte quality and fertilization rates.

A case of monochorionic twin pregnancy complicated with intrauterine single fetal death with successful treatment of intrauterine blood transfusion in the surviving fetus.

We report a case of monochorionic twin pregnancy complicated with single fetal demise that received successful treatment of intrauterine transfusion for severe anemia of the surviving fetus. A single fetal demise occurred at 20 weeks of gestation and middle cerebral artery peak systolic velocity (MCA-PSV), a marker for fetal anemia, showed marked elevation in the surviving fetus. Fetal blood sampling was immediately done and severe fetal anemia (hemoglobin = 5.5 g/dl, hematocrit = 16.8%) was confirmed, and then intrauterine transfusion was performed. After transfusion, MCA-PSV rapidly decreased to the normal value and remained within normal range until delivery. A healthy 2,640 g male infant was delivered at 35 weeks of gestation without anemic status and no neurological problem was found at 1-year old. The present report supports that intrauterine rescue transfusion is a useful treatment to prevent the adverse outcome of surviving fetus in monochorionic twin pregnancy complicated with single fetal demise, and monitoring of MCA-PSV is also useful to assess anemic status of the surviving fetus.

Changes in vascular leakage and expression of angiopoietins in the corpus luteum during pregnancy in rats.

The present study investigates changes in blood vessel stability and its regulation in the corpus luteum (CL) during pregnancy in the rat. First, blood vessel stability in the CL was evaluated during pregnancy based on vascular leakage, which was quantified by the Evans blue assay. Vascular leakage was highest on day 3, thereafter decreased until day 15 and increased again on day 21. Secondly, to study the regulation of vascular leakage, the expression of angiopoietins was examined in the CL during pregnancy. Angiopoietin-1 (Ang-1) effects maturation and stabilization of newly formed blood vessels, while Ang-2 produces the opposite effect by allowing vascular remodeling. An immunohistochemical study showed both Ang-1 and Ang-2 expression in luteal cells. mRNA and protein levels of Ang-1 were significantly higher on days 12 and 15 than those on days 3 and 21, whereas there was no significant change in Ang-2 expression. Since estradiol contributes to CL development during mid-pregnancy, we finally studied whether estradiol regulates vascular leakage and angiopoietin expression. Rats undergoing hypophysectomy and hysterectomy (hypox-hect) on day 12 were treated with estradiol until day 15. Vascular leakage was increased and Ang-1 expression was decreased by hypox-hect, and these effects were completely reversed by estradiol treatment. In conclusion, blood vessel stability in the CL is likely to be associated with CL development and CL regression, and may be regulated by angiopoietins. Estradiol contributes to blood vessel stabilization in the CL during mid-pregnancy, which is associated with an increase in Ang-1 expression.

Prenatal diagnosis and management for a large fetal cardiac tumor complicated with hydrops fetalis.

Fetal cardiac tumor is a rare disease, and its prognosis varies in relation to the complications such as arrhythmia and out-flow obstruction. Hydrops fetalis is one of severe complications that result in an unfavorable outcome. A case is presented herein of a large fetal cardiac tumor diagnosed at 28 weeks gestation. At 30 weeks gestation, the fetus complicated with hydrops fetalis because of impaired cardiac function. Increased peak systolic velocity in the ascending aorta and marked reversed flow in the ductus venosus were observed. Oral digoxin therapy was administered to the mother as a cardiotonic agent and the hydropic condition was immediately diminished. After normal delivery, the cardiac tumor gradually decreased in size and the infant developed normally, but required an antiarrhythmic drug. The case indicates that the in utero digoxin therapy could be a choice for hydrops fetalis caused by cardiac tumor.

Gastric emptying cycles in the human fetus.

OBJECTIVE: Fetal swallowing contributes greatly to amniotic fluid homeostasis and fetal somatic development. Despite the absorption and recirculation of significant volumes of amniotic fluid, little is known about the rates of fetal gastric emptying or gastrointestinal absorption. We sought to determine the patterns of human fetal gastric emptying cycles across gestation. STUDY DESIGN: The gastric emptying cycle of 80 normal human fetuses at 12 to 39 weeks of gestation was studied. Real-time ultrasound examination of the fetal stomach (defined as the largest gastric area inclusive of the pylorus) was recorded continuously for a minimum of 1 hour (60-112 minutes). Images were replayed with measurements of gastric size every minute. The gastric area ratio was defined as the ratio of the fetal gastric area divided by the area of the fetal abdominal transverse section. The changes in gastric area ratio of all subjects were analyzed with the discrete Fourier transform method. The calculable maximum cycle was 60 or 112 minutes, and the minimum cycle was 2 minutes. The highest and second highest peaks of all power spectrum were recorded, and each cycle was converted from frequency of each peak. RESULTS: The gastric emptying cycles of the highest peak before 24 weeks of gestation were scattered between 30 and 100 minutes with low power. At 32 to 35 weeks of gestation, cycles were focused at approximately 40 minutes with increased power. At term, the cycles increased to >80 minutes. The gastric emptying cycles of the second highest peak were constant at 20 minutes, with stronger power after 24 weeks of gestation. CONCLUSION: Fetal gastric emptying cycles normalize during the early third trimester. The near-term evidence of delayed emptying may contribute to newborn infant feeding satiation.

Ontogeny of gastric emptying patterns in the human fetus.

OBJECTIVE: Fetal swallowing and gastric emptying contribute importantly to amniotic fluid (AF) homeostasis and fetal gastrointestinal development. We speculated that fetal gastric emptying must be functional early in gestation to prevent rapid increases in AF. We sought to determine the human fetal ontogenic pattern of gastric emptying. STUDY DESIGN: Gastric emptying of eighty normal fetuses at 12-39 weeks was studied. Real-time ultrasound of the fetal stomach was continuously recorded for 1 hour. The gastric area ratio (GAR) was defined as the gastric area divided by the abdominal transverse area. The delta GAR was defined as the change between the maximum and the minimum gastric area ratiox100 (expressed as percent). A change of the fetal gastric area more than the 10th percentile of the delta GAR at 36-39 weeks was used to define gastric emptying. RESULTS: The 10th, 50th and 90th percentile of delta GAR at 36-39 weeks' was 5.2, 6.5 and 8.7%, respectively. Fetal gastric emptying was detected as early as 12 5/7 weeks of gestation. The proportion of fetuses demonstrating gastric emptying (>10th percentile delta GAR) increased with gestational age: 4/33 (12.1%) 12-23 weeks, 3/9 (33.3%) at 24-27 weeks, 8/11 (72.7%) at 28-31 weeks, 12/14 (85.7%) at 32-35 weeks, and 11/13 (84.6%) at 36-39 weeks. CONCLUSIONS: Fetal gastric emptying occurs by the beginning of the second trimester, contributing to AF regulation. The increased frequency of gastric emptying in late gestation is likely secondary to increased swallowing, altered fetal behavioral state or endogenous production of gastrointestinal motility factors.

Angiogenesis in the human corpus luteum: changes in expression of angiopoietins in the corpus luteum throughout the menstrual cycle and in early pregnancy.

CONTEXT: Blood vessel stabilization is regulated by angiopoietins and important for angiogenesis in the corpus luteum. OBJECTIVE: To study angiogenesis and blood vessel stabilization in the human corpus luteum, changes in expression of angiopoietin (Ang)-1, Ang-2, and their specific receptor, Tie-2, together with the number of blood vessels and pericytes were examined in the corpus luteum throughout the menstrual cycle and in early pregnancy. DESIGN: The number of blood vessels and pericytes was determined by immunohistochemistry for CD34 and alpha-smooth muscle actin, respectively. Ang and Tie-2 expression were examined by immunohistochemistry or RT-PCR. RESULTS: The number of blood vessels increased during the early luteal phase, whereas the number of pericytes was small in the early luteal phase and increased in the midluteal phase, suggesting that angiogenesis is undergoing during the early luteal phase and blood vessels are stabilized in the midluteal phase. Blood vessels and pericytes decreased in number during the late luteal phase. The increased number of both blood vessels and pericytes seen in the corpus luteum of early pregnancy suggests that angiogenesis is undergoing accompanied by blood vessel stabilization. Ang-2 expression with low Ang-1 expression was found during the early luteal phase. Thereafter, increasing Ang-1 expression during the midluteal phase, declining Ang-1 expression with continued Ang-2 expression during the late luteal phase, and relatively high Ang-1 expression in early pregnancy were observed. CONCLUSIONS: The change in Ang expression is closely associated with angiogenesis, blood vessel stabilization, and blood vessel regression during the divergent phases of luteal formation, luteal regression, and luteal rescue by pregnancy.

Successful treatment of primary fetal hydrothorax with a double basket catheter.

Fetal pleural effusions can sometimes be detected before birth with ultrasonography. Intervention may be warranted when there is a condition that results in hydroplastic lung and/or fetal hydrops. A 22-week-old fetus with a severe pleural effusion and hydrops was successfully treated by long-term pleural drainage with a double basket catheter from 22 to 39 weeks of gestation.