Uterine rupture successfully treated with a damage-control strategy of hysterectomy and resuscitative endovascular balloon occlusion of the aorta-assisted cardiopulmonary resuscitation.

Background: Uterine rupture is a major cause of postpartum hemorrhage (PPH) that requires surgery. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is also helpful for PPH. However, the effectiveness of REBOA in PPH with cardiac arrest is unknown. Case Presentation: A 40-year-old woman developed hemorrhagic shock due to uterine rupture after an induced delivery. She developed cardiac arrest, but was rescued by cardiopulmonary resuscitation (CPR), REBOA, a hysterectomy, and pelvic gauze packing. The hemodynamics were too unstable to move to the operating room. Then we initiated the CPR assisted with REBOA and decided to activate massive transfusion and perform laparotomy in the emergency room. She was finally discharged home without neurological sequelae. Conclusion: Our damage control strategy, including REBOA-assisted CPR, contributed to saving the life of a patient with a life-threatening PPH.

Lower systolic blood pressure levels in early pregnancy are associated with a decreased risk of early-onset superimposed preeclampsia in women with chronic hypertension: a multicenter retrospective study.

To clarify the impact of blood pressure (BP) management ranges on pregnancy outcomes, we conducted a multicenter retrospective analysis of 215 women with singleton pregnancies diagnosed with essential hypertension either before or within 14 weeks of gestation. Patients were classified according to systolic BP (sBP; <130, 130-139, 140-159, and ≥160 mmHg) or diastolic BP (dBP; <80, 80-89, 90-109, and ≥110 mmHg) at 8-11, 12-15, and 16-19 weeks of gestation. The risk of early-onset superimposed preeclampsia and small-for-gestational-age neonates was assessed in each BP group. Moreover, a subgroup analysis was performed in 144 eligible patients whose BP was measured at both 12-13 and 14-15 weeks of gestation. At 16-19 weeks of gestation, higher sBP significantly increased the incidence of early-onset superimposed preeclampsia (13.3%, 24.6%, 32.2% and 75.0%, respectively) and small-for-gestational-age neonates (6.0%, 13.1%, 16.9% and 50.0%, respectively). Multivariate logistic regression analyses showed that women with sBP < 130 mmHg at 16-19 weeks of gestation had a significantly lower risk of early-onset superimposed preeclampsia than women with sBP of 140-159 mmHg. Subgroup analyses also showed that even at 14-15 weeks of gestation, sBP < 130 mmHg was associated with a significantly lower risk of early-onset superimposed preeclampsia than an sBP of 140-159 mmHg. In conclusion, sBP < 130 mmHg within 14 weeks of gestation reduced the risk of developing early-onset superimposed preeclampsia in women with chronic hypertension.

Pseudo-Meigs Syndrome Caused by a Giant Uterine Leiomyoma with Cystic Degeneration: A Case Report.

Pseudo-Meigs syndrome is defined as secondary accumulation of ascites and hydrothorax associated with a pelvic tumor other than benign ovarian tumors such as fibroma, which usually resolve after surgical removal of the tumor. Here we report a case of pseudo-Meigs syndrome caused by a giant uterine leiomyoma, which was initially suspected to be ovarian cancer. A 37-year-old nulliparous woman presented with a 5-month history of abdominal distension and anorexia. Abdominal ultrasonography revealed a giant cystic lesion and solid mass in the peritoneal cavity, along with plentiful ascites. Chest X-ray images showed a small pleural effusion on the right side. The patient was referred to our hospital for treatment of suspected ovarian cancer and peritonitis carcinomatosis. Although serum CA125 level was elevated (up to 331.8 U/mL), magnetic resonance imaging showed a giant sub-serosal uterine leiomyoma with cystic degeneration (27 × 15 × 13 cm). A small dermoid cyst was also detected in the right ovary. Ascites was drained and the patient underwent myomectomy and ovarian cystectomy. The patient had a degenerated leiomyoma with no pathological evidence of malignancy. Because symptoms disappeared postoperatively and serum CA125 returned to normal, without recurrence of ascites, pseudo-Meigs syndrome was diagnosed.

A Software Level Calibration Based on Bayesian Regression for a Successive Stochastic Approximation Analog-to-Digital Converter System.

Recently, a novel low-power high-precision analog-to-digital converter (ADC) called the successive stochastic approximation ADC has been proposed which has two kinds of outputs from different modes, and which requires a software-level error correction method of combining them into a high-precision total output. From the practical viewpoint, we propose an error correction method based on the Bayesian regression with an incremental learning, in which additional data are successively selected according to the uncertainty of the corresponding predictive total output, and the uncertainty is approximately estimated by evaluating the upper bound of the standard deviations of the Bayesian predictive distributions of the outputs in each block of a partition of the all data set. Through numerical experiments, we verify the performance of the proposed method.

Potent and rapid activation of tropomyosin-receptor kinase A in endometrial stromal fibroblasts by seminal plasma.

Seminal plasma (SP), the liquid fraction of semen, is not mandatory for conception, but clinical studies suggest that SP improves implantation rates. Prior in vitro studies examining the effects of SP on the endometrium, the site of implantation, surprisingly revealed that SP induces transcriptional profiles associated with neurogenesis. We investigated the presence and activity of neurogenesis pathways in the endometrium, focusing on TrkA, one of the canonical receptors associated with neurotrophic signaling. We demonstrate that TrkA is expressed in the endometrium. To determine if SP activates TrkA signaling, we isolated the two most abundant endometrial cell types-endometrial epithelial cells (eEC) and endometrial stromal fibroblasts (eSF)-and examined TrkA activity in these cells after SP exposure. While SP only moderately activated TrkA in eEC, it potently and rapidly activated TrkA in eSF. This activation occurred in both non-decidualized and decidualized eSF. Blocking this pathway resulted in dysregulation of SP-induced cytokine production by eSF. Surprisingly, while the canonical TrkA agonist nerve growth factor was detected in SP, TrkA activation was principally induced by a 30-100-kDa protein whose identity remains to be established. Our results show that TrkA signaling is highly active in eSF and is rapidly induced by SP.

Simvastatin inhibits oxidative stress via the activation of nuclear factor erythroid 2-related factor 2 signaling in trophoblast cells.

AIM: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator against oxidative stress through the induction of antioxidant and cytoprotective genes, such as heme oxygenase 1 (HO-1), glutamyl cysteine ligase catalytic (GCLC), and glutamyl cysteine ligase modulatory (GCLM). Nrf2 signaling is disrupted in pre-eclamptic placentas, although increased oxidative stress is implicated in pre-eclampsia. The aims of the study were: (i) to investigate the mechanism that underlies the impaired Nrf2 signaling in pre-eclamptic placentas, and (ii) to examine the potential therapeutic role of statin for pre-eclampsia. MATERIAL AND METHODS: Human choriocarcinoma JAR cells were cultured under normoxia (20% O2 ) or hypoxia (1% O2 ). Small-interfering ribonucleic acids were used to knockdown Nrf2. Real-time quantitative reverse transcriptase polymerase chain reaction and Western blotting were used to evaluate the influence of oxidative stress (H2O2 100 µM) and simvastatin (50 µM) on Nrf2 and its target genes. Reactive oxygen species levels were analyzed by flow cytometry in immortalized human trophoblast TCL1 cells treated with or without H2O2 (100 µM) ± simvastatin (50 µM). RESULTS: Nuclear factor erythroid 2-related factor 2 activation was significantly suppressed under hypoxic conditions. Nrf2 knockdown resulted in insufficient enhancement of HO-1, GCLC and GCLM expression under oxidative stress. In contrast, Nrf2 signaling was augmented by simvastatin, which suppressed the induction of oxidative stress in trophoblasts. CONCLUSION: Hypoxia is one of the important negative regulators of Nrf2 activation, and simvastatin inhibits oxidative stress through the activation of Nrf2 signaling in trophoblasts, indicating the potential therapeutic role of statin for pre-eclampsia.

Treatment results of image-guided high-dose-rate interstitial brachytherapy for pelvic recurrence of uterine cancer.

PURPOSE: We analyzed clinical data to evaluate the effectiveness of image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for pelvic recurrence of uterine cancer. METHODS AND MATERIALS: Between 2003 and 2011, 56 patients were treated with HDR-ISBT with or without external beam radiotherapy (EBRT). The median followup time was 33 months (range, 1-109 months). Pre-ISBT treatments included radical hysterectomy for 35 patients (Group A), radical hysterectomy with postoperative radiotherapy for 8 patients (Group B), and radical radiotherapy for 13 patients (Group C). We initiated MRI-assisted CT-based planning for the last 49 patients. The median ISBT single fraction dose was 6 Gy. The median total doses were 30 and 54 Gy with and without EBRT (range, 30-50 Gy) for Group A, respectively and 48 Gy without EBRT for Groups B and C. RESULTS: The 3-year local control (LC) rates were 85%, 75%, and 46% for Groups A, B, and C, respectively (p = 0.017). The 3-year LC rates were 84%, 73%, and 33% for clinical target volume at the time of HDR-ISBT of <10, 10-29, and ≥30 cc, respectively (p = 0.005). The 3-year LC results tended to be higher for patients whose D100 (clinical target volume) was equal or higher than 67.1 Gy (p = 0.098). A total of 13 late complications of Grades 3-5 occurred in 11 patients (20%). CONCLUSIONS: Our image-guided HDR-ISBT for pelvic recurrence of uterine cancer provided good treatment outcomes. The treatment results for patients who underwent radical surgery with or without postoperative radiotherapy are better than those for patients who underwent radical radiotherapy.

Definitive radiotherapy for primary vaginal cancer: correlation between treatment patterns and recurrence rate.

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1-169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III-IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge.

Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer.

PURPOSE: To investigate the effectiveness of our novel MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. METHODS AND MATERIALS: Between June 2005 and June 2009, 29 previously untreated patients with cervical cancer were enrolled (2 T2b, 2 T3a, 19 T3b, and 6 T4 tumors). We implanted MRI-compatible plastic catheters using our unique ambulatory technique. The total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy. RESULTS: The median D90 (high-risk clinical target volume), D(2 cc) (bladder), and D(2 cc) (rectum) per fraction were 6.9, 5, and 4.6 Gy, respectively. The 3-year local control rates were 100%, 95%, and 83% for T2, T3, and T4 tumors, respectively. Grade 3 or 4 late complications occurred in 4 patients. CONCLUSIONS: Our preliminary evaluation of image-based high-dose-rate interstitial brachytherapy showed favorable local treatment results with an acceptable complication rate.

A novel minimally invasive technique of high-dose rate image-based intracavitary brachytherapy for endometrial cancer using a single fine and soft, flexible applicator.

AIM: We report on a minimally invasive computed tomography (CT)/magnetic resonance imaging (MRI)-based image-guided intracavitary brachytherapy (ICBT) for an elder patient with endometrial cancer, who was unfit for anesthesia, using a fine and soft flexible applicator. PATIENTS AND METHODS: The patient was an 82-year-old female. She was identified as having T1bN0M0 (stage IB) tumor, and histological findings revealed grade 2 adenocarcinoma. She was contraindicated for surgery because of advanced age and severe pulmonary emphysema; therefore, she was managed with CT/MRI-based ICBT alone. The total treatment dose was 26 Gy (6.5 Gy per fraction). The dose-volume histogram of the gross tumor volume, the clinical target volume, and organs at risk were calculated. RESULTS: The patient safely completed the ICBT course without pre-medication. Tumor growth was controlled, with complete disappearance after 32 months. No acute or late adverse effects were observed. MRI-guided ICBT can visualize the gross tumor volume in the uterine body, which cannot be detected by CT. CONCLUSION: We successfully and safely performed minimally invasive CT/MRI-based ICBT without pre-medication in a patient with endometrial cancer with high surgical risks, using a fine and soft, flexible applicator.

Endothelial function progressively deteriorates during normal pregnancy.

OBJECTIVE: To elucidate changes in endothelial function throughout the gestational period in normal pregnancy and its relationship with plasma soluble fms-like tyrosine kinase-1 (sFlt-1) levels. METHODS: Endothelial function was evaluated by reactive hyperemia index (RHI) using Endo-PAT2000 and plasma sFlt-1 levels were measured simultaneously by ELISA. RESULTS: RHI gradually deteriorated with increasing gestational age. Plasma sFlt-1 levels exhibited a gradual increase at late pregnancy and were inversely correlated with RHI. CONCLUSION: Maternal endothelial function gradually deteriorates with increasing gestational age and there is an inverse correlation between endothelial function and plasma sFlt-1 levels in normal pregnancy.

Complement split product C4d deposition in placenta in systemic lupus erythematosus and pregnancy-induced hypertension.

Systemic lupus erythematosus (SLE) and pregnancy-induced hypertension (PIH) are related to premature delivery and intrauterine growth restriction (IUGR), and share histological findings of the placenta. Association with complement dysregulation has been reported in pregnancy for both disorders. The purpose of this study was to investigate the utility of C4d immunohistochemistry for placentas with SLE- and PIH-associated pregnancy. C4d staining was performed on paraffin-embedded tissue of placentas from 26 patients with SLE, 26 with PIH, and 25 control cases. We used the H-score with a range of 0-300 for the evaluation of C4d immunoreactivity. Placentas of SLE and PIH cases showed a higher H-score than control cases (average, SLE, 38.3 (P < 0.05); PIH, 17.8; control, 1.68), with linear staining on the membrane of syncytiotrophoblast. C4d-high groups comprised 50% (12/26) of SLE and 35% (9/26) of PIH cases, with H-scores ranging 14-270 and 15-170. C4d-high groups were significantly associated with low-placental weights and low birth weight in both SLE and PIH (P < 0.05), and lower gestational age (P < 0.05) in PIH cases. These results suggest that C4d might be utilized as a biomarker evaluating the subsequent risk for IUGR and disease control during the gestation period in these patients.

ATP-binding cassette transporter A1 expression is decreased in preeclamptic placentas.

Preeclampsia is a pregnancy-specific multisystem disorder characterized by hypertension and proteinuria. Accentuated maternal hyperlipidemia, especially high serum levels of oxidized low-density lipoprotein (oxLDL), is one of the features of preeclampsia. We previously reported that lectin-like oxidized LDL receptor 1 (LOX-1) expression was decreased in preeclamptic placentas. Here, we show that decreased LOX-1 expression is associated with low expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) in the placenta. The ABCA1 mediates cellular efflux of cholesterol, and liver X receptors (LXRs) are its predominant transcriptional regulators. Both ABCA1 and LXR expressions were significantly lower in preeclamptic placentas than those in normal controls. Oxidized LDL upregulated ABCA1 expression, while LOX-1 blockade resulted in the alleviation of increasing ABCA1 messenger RNA in JAR cells. These results suggest that low LOX-1 expression may lead to insufficient oxLDL uptake, thereby contributing to reduced LXR activation and decreased ABCA1 expression in preeclamptic placentas.

Serial magnetic resonance imaging of placenta percreta with bladder involvement during pregnancy and postpartum: a case report.

Whether to manage placenta previa percreta surgically or conservatively has been a controversial issue. A 30-year-old woman with placenta percreta with bladder involvement was treated conservatively. A planned cesarean section was performed at 33 weeks' gestation. A 1768-g female infant was delivered through a transverse fundal uterine incision with the placenta left inside the uterus. The following morning, a massive postpartum hemorrhage occurred, and was successfully treated with transarterial embolization. The placenta was never expelled and spontaneously disappeared 4 months after surgery. We demonstrate serial magnetic resonance imaging of the placenta percreta during pregnancy and the postpartum period.

Pyomayoma during pregnancy: a case report and review of the literature.

Pyomyoma (suppurative leiomyoma) is a rare but serious complication of uterine leiomyomas. Although the management of leiomyomas during pregnancy is usually expectant, prompt surgical intervention is mandatory for pyomyoma. We present a case of pyomyoma with peritonitis that necessitated myomectomy at 21 weeks of gestation in a 28-year-old nullipara in which the pregnancy continued to successful delivery at 37 weeks of gestation. Perinatal and neonatal outcomes in pregnancies complicated with pyomyoma may be improved by prompt surgical intervention even in the early second trimester. A brief review of the literature regarding pyomyoma associated with pregnancy is also described.

Decreased lectin-like oxidized LDL receptor 1 (LOX-1) and low Nrf2 activation in placenta are involved in preeclampsia.

CONTEXT: Serum concentration of oxidized low-density lipoprotein (oxLDL) is higher in women with preeclampsia than in normal pregnant woman. Lectin-like oxLDL receptor-1 (LOX-1) is one of the scavenger receptors for oxLDL and is abundantly expressed in placenta. It is well known that oxLDL activates nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant and cytoprotective genes such as heme oxygenase-1 (HO-1), which play an important role in preeclampsia. However, it has yet to be elucidated whether LOX-1, along with Nrf2, participates in the pathology of preeclampsia. OBJECTIVE: The objective of the study was to assess LOX-1 expression and Nrf2 activation in preeclamptic placentas and to manifest their physiological roles in preeclampsia. METHODS: Expression and regulation of LOX-1, HO-1, and Nrf2 were evaluated by real-time quantitative RT-PCR and Western blotting. The functions of LOX-1 and Nrf2 were examined using an anti-LOX-1 antibody and Nrf2 activator in JAR, a choriocarcinoma cell line, and placental explants. RESULTS: Both LOX-1 expression and Nrf2 activation were significantly decreased in preeclamptic placentas compared with normal controls. A significant decrease in LOX-1 mRNA was found in placental explant cultures under hypoxic conditions. Activation of Nrf2 up-regulated HO-1 in both the JAR cells and placental explants. Furthermore, oxLDL increased HO-1 mRNA, whereas the blockade of LOX-1 inhibited the increase of HO-1 mRNA in JAR cells. CONCLUSION: Decreasing LOX-1 expression in preeclamptic placenta may contribute to high oxLDL concentration, low Nrf2 activation, and low HO-1 expression. These findings provide novel insights into the crucial role of LOX-1 and Nrf2 in the pathogenesis of preeclampsia.

Deciduosis can cause remarkable leukocytosis and obscure abdominal pain.

Remarkable leukocytosis with obscure abdominal pain during pregnancy is clinically challenging for obstetricians. A 31-year-old pregnant woman developed persistently elevated white blood cell (approximately 30 000/µL) and C-reactive protein (3.0 mg/dL) with occasional moderate abdominal pain. At 29 gestational weeks, she underwent emergency cesarean section due to suspected abruptio placentae. Hemoperitoneum was observed with extensive hemorrhagic nodules on the peritoneal and omental surfaces. White blood cells rose 87200/µL, and C-reactive protein peaked at 44.9mg/dL after surgery. Pathologically, biopsies showed deciduosis, and decidual cells on the omental surface showed immunohistochemical staining for granulocyte colony-stimulating factor (G-CSF). Serum G-CSF concentration was 339 pg/mL at 28 weeks, and that of ascites was 312 000 pg/mL at cesarean section. G-CSF-producing deciduosis can induce leukocytosis as well as abdominal pain during pregnancy and postpartum.

Management of fetal death with placenta previa.

Management of second- and third-trimester fetal death in the presence of placenta previa is a dilemma for obstetricians. We herein describe a case of fetal death occurring at 23 weeks' gestation in the presence of placenta previa. Three weeks of expectant management failed to reduce uteroplacental blood perfusion evaluated with pulsatility index of the uterine artery. Labor was then induced with gemeprost vaginal pessary following overnight laminaria pretreatment. Vaginal delivery was achieved with total blood loss of 1900 ml. Homologous blood transfusion was obviated owing to autologous blood that had been stored during the waiting period.

Secondary postpartum hemorrhage due to uterine artery pseudoaneurysm rupture in von Willebrand disease.

We here report a case of a 33-year-old woman who experienced secondary postpartum hemorrhage (PPH) due to uterine artery pseudoaneurysm rupture. She had intrauterine balloon tamponade for unexplained primary PPH after spontaneous vaginal delivery, and subsequent angiography showed no abnormal contrast extravasation. However, profuse vaginal bleeding occurred 22 days postpartum. Color Doppler ultrasonography demonstrated an anechoic mass with turbulent flow in the lower uterine segment, corresponding to uterine artery pseudoaneurysm. She was successfully treated with selective uterine arterial embolization. Decreased levels of von Willebrand factor and factor VIII led to the diagnosis of von Willebrand disease. When it is determined that a patient has unexplained PPH or uterine artery pseudoaneurysm, a high index of suspicion and further investigation for underlying bleeding disorders is warranted.

Disseminated intravascular coagulation as the presenting sign of gastric cancer during pregnancy.

Gastric cancer during pregnancy is rare and the outcome is generally poor. A 36-year-old woman in the 28th week of gestation was complicated with disseminated intravascular coagulation (DIC), and she was diagnosed with gastric cancer with bone marrow metastasis. Cesarean delivery followed by sequential methotrexate (100 mg/m2) and 5-fluorouracil (600 mg/m2) chemotherapy was conducted. DIC was successfully managed with blood transfusion and chemotherapy. She has received chemotherapy in the outpatient clinic. This report is the second case of a pregnant woman with DIC as the initial manifestation of advanced gastric cancer. Prompt diagnosis and chemotherapy increases the chances of a relatively favorable outcome even in advanced gastric cancer presenting with DIC due to bone marrow involvement.