Usefulness of Practitioner-Led Pancreatic Cancer Screening.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41-94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I-II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population.

BACKGROUND/AIMS: The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. METHODS: We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. RESULTS: A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). CONCLUSION: EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive.

Important surgical measures and techniques at cesarean hysterectomy for placenta previa accreta.

For cesarean hysterectomy with placenta previa accreta, "universally achievable" measures are required. We propose eight measures: (i) placement of intra-iliac arterial occlusion balloon catheters; (ii) placement of ureter stents; (iii) "holding the cervix" to identify the site to be transected; (iv) uterine fundal incision; (v) avoidance of uterotonics; (vi) "M cross double ligation" for ligating the ovarian ligament; (vii) "filling the bladder" to identify the bladder separation site and "opening the bladder" for placenta previa accreta with bladder invasion; and (viii) to continue to clamp the medial side of the parametrium or the cervix or employment of the "double edge pick-up" to ligate it. These eight measures are simple, easy, effective, and thus "universally achievable".

Prevalence of organic colonic lesions in patients meeting Rome III criteria for diagnosis of IBS: a prospective multi-center study utilizing colonoscopy.

BACKGROUND: It remains unknown whether the Rome III criteria can exclude organic colonic lesions prior to the diagnosis of irritable bowel syndrome (IBS). We evaluated the colonoscopy results of patients meeting the Rome III criteria for the diagnosis of IBS to determine the presence of organic colonic lesions. METHODS: This study was prospectively conducted at 17 centers in Japan. We enrolled 4528 patients who underwent diagnostic colonoscopy examinations. The diagnosis of IBS was evaluated by questionnaire results according to the Rome III criteria. RESULTS: We evaluated 4178 patients (350 were excluded because of incomplete data or previous colonic surgery), of whom 203 met the Rome III criteria (mean age 57.9 years; range 14-87 years) prior to the diagnostic colonoscopy examination. We identified organic colonic diseases in 21 of these 203 patients (10.3 %) , and these disease were also identified in 338 (8.5 %) of 3975 patients who did not fulfill the Rome III criteria. There were no differences in regard to the prevalence of organic colonic diseases between patients who did and did not fulfill the Rome III criteria. CONCLUSIONS: The prevalence of organic colonic diseases in patients who met the Rome III criteria was at an acceptably low level, indicating that the Rome III criteria are adequately specific for the diagnosis of IBS without performing a colonoscopy examination.

Hydroxysteroid (17-ß) dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia.

In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-ß) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff value=21.9 ng/mL) and 0.88/0.51 (cutoff value=30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35-15.77) and 7.83 (95% CI: 1.70-36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE.

No increase in hemorrhagic complications with thromboprophylaxis using low-molecular-weight heparin soon after cesarean section.

AIM: Data from Japanese women have been lacking regarding hemorrhagic complications due to low-molecular-weight heparin (LMWH) as thromboprophylaxis. Thus, targeting Japanese women, we made an effort to determine: (i) whether the administration of LMWH soon after cesarean section increases the risk of hemorrhagic complications compared to that of unfractionated heparin; and (ii) how it elongates the activated partial thromboplastin time. MATERIALS AND METHODS: We administered unfractionated heparin in the first half of the study period, and LMWH in the latter half. We examined: (i) the incidence rate of hemorrhagic complications; and (ii) preoperative and postoperative activated partial thromboplastin time, and we compared these in cases using unfractionated heparin and LMWH. RESULTS: No clinically discernable thromboembolism occurred in either group. Hemorrhagic complications occurred in two of 140 women in the unfractionated heparin group and one of 131 women in the LMWH group. LMWH prolonged the activated partial thromboplastin time from 29.8±2.6 to 34.8±4.0 s. This prolongation was significantly shorter than that with unfractionated heparin (from 30.2±2.6 to 36.5±6.2 s). CONCLUSIONS: Compared with thromboprophylaxis with unfractionated heparin, thromboprophylaxis with early administration of LMWH after cesarean section did not increase the incidence of hemorrhagic complications and caused less prolongation of the activated partial thromboplastin time in Japanese women.

C-reactive protein levels at pre-/post-indicated cervical cerclage predict very preterm birth.

AIMS: To investigate the relation between serum levels of C-reactive protein (CRP) at pre-/post-cerclage points and preterm birth at <33 weeks of gestation in women with indicated cervical cerclage (CC). METHODS: Fifty-eight women with CC indicated for a short or soft cervix, but no visible or protruding fetal membranes into the vagina, between 17 and 26 weeks of gestation, were reviewed. Serum CRP levels were examined three times: just before cerclage, and on day 1 and day 2 post-cerclage. RESULTS: Serum CRP levels on day 1 and day 2, but not just before cerclage, predicted the occurrence of very preterm birth. In women with cervical dilatation of <3.0 cm, serum CRP levels on post-cerclage day 1 were associated with the increase of very preterm birth [CRP ≥1.5 mg/dL vs. <1.5 mg/dL: 4/5 (80%) vs. 8/31 (26%), P=0.033]. In women with cervical dilatation of <3.0 cm, serum CRP ≥3.0 mg/dL on post-cerclage day 2 was also associated with the increase of very preterm birth. CONCLUSION: In women with indicated CC between 17 and 26 weeks of gestation, increased levels of serum CRP on post-cerclage day 1 or 2 might be ominous signs for very preterm birth.

Non-surgical management of post-cesarean uterine infection with marked myometrial gas formation.

Gas in an infected organ generally indicates a severe infection, often requiring surgery; however, data are lacking as to post-cesarean gas-forming uterine infection. A 27-year-old Japanese primigravida underwent a difficult cesarean section, after which a high fever continued. Computed tomography (CT) revealed marked gas in the uterine anterior myometrium. Diagnosing this condition as post-cesarean uterine scar infection, we recommended surgical intervention, that is, hysterectomy or at least drainage; however, the patient refused it. Considering the patient's desire and lack of organ-failure signs, we employed intensive antibiotic treatment for 6 weeks. Serial CT indicated a gradual decrement in the gas amount and she recovered completely after 8 weeks. This case suggests that surgical procedure may not always be necessary for post-cesarean gas-forming uterine infection and CT may be useful to detect/follow this condition.

Asymptomatic uterine artery pseudoaneurysm after cesarean section.

Uterine artery pseudoaneurysm is a rare but important complication of cesarean section (CS). If treated inadequately, it may cause profuse life-threatening postpartum hemorrhage. We report an asymptomatic postpartum woman with uterine artery pseudoaneurysm after CS. We also provide a review of published reports of pseudoaneurysm after CS. A 31-year-old Japanese woman underwent CS, in which the uterine incision was extended laterally. Routine postoperative evaluation with vaginal ultrasound on postpartum day 6 revealed a parauterine mass with a maximum diameter of 49 mm with swirling flow. Selective angiography confirmed this mass as a uterine artery pseudoaneurysm. Uterine artery embolization was performed with success. Uterine artery pseudoaneurysm should be listed as a differential diagnosis of pelvic mass after CS.

Prolonged activated partial thromboplastin time in thromboprophylaxis with unfractionated heparin in patients undergoing cesarean section.

AIM: Hemorrhage is an important complication of heparin-thromboprophylaxis after surgery. We attempted to clarify the incidence rate of prolonged activated partial thromboplastin time (APTT), representative of hemorrhagic tendency, in Japanese women who received thromboprophylaxis with unfractionated subcutaneous heparin administration after cesarean section (CS). We also determined factors which affected postoperative APTT. METHODS: We studied 280 women who were administered thromboprophylaxis with unfractionated subcutaneous heparin 5000 IU two times per day after CS. Postoperative APTT under heparin was measured and the incidence of its prolongation was determined. Preoperative APTT, blood loss during surgery, postoperative hematocrit, postoperative serum total protein level, and postpartum body weight were measured, and their correlation with postoperative APTT was determined. RESULTS: Preoperative and postoperative APTT values were 28.3 (26.7-30.3) and 33.8 (31.0-37.5) seconds for median (interquartile range), respectively. Overall, 7.1% of patients showed >or=45 s postoperative APTT. Two patients (0.7%) showed >or=60 s APTT, one of whom suffered subcutaneous hemorrhage around the abdominal incision with complete healing. There were no other hemorrhagic complications. Preoperative APTT positively, and postpartum body weight inversely, correlated with postoperative APTT. The amount of blood loss, postoperative hematocrit, and postoperative serum total protein level did not correlate with postoperative APTT. No discernible deep vein thrombosis or pulmonary embolism occurred. CONCLUSION: Although 7.1% of women under heparin-thromboprophylaxis showed a prolonged APTT that was 150% of the preoperative APTT, serious side effects were not observed. Subcutaneous administration of unfractionated heparin, if checking APTT prolongation 1 day after surgery, may be safe method of thromboprophylaxis after CS.

Effectiveness of bromocriptine treatment in a patient with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening disorder that occurs in late pregnancy or the early puerperium despite optimal medical therapy. Recently, oxidative stress-mediated generation of antiangiogenic and proapoptotic 16-kDa prolactin, and subsequent impaired cardiac microvascularization have been related to PPCM. In turn, prolactin blockade with bromocriptine has been proven successful in preventing the onset of PPCM in mice and in patients at high risk for the disease. Here, we report the efficacy of bromocriptine for treatment of a patient with PPCM.

Serious adverse drug reaction in a woman with hyperemesis gravidarum after first exposure to vitamin B complex containing vitamins B1, B6 and B12.

We report the case of a pregnant woman who suffered from hypotension after first exposure to intravenous administration of a combination drug containing vitamins B1, B6 and B12 (Vitamedin; Daiichi-Sankyo, Tokyo, Japan). A 27-year-old Japanese woman received an intravenous infusion of fluid containing a vitamin B complex due to hyperemesis gravidarum. Thirty minutes after the start of infusion she was found to be in hypotension. The patient had stupor, general sweating, blood pressure of 82/50 mmHg, and low percutaneous oxygen saturation (SpO(2)) of 88%. We immediately stopped the infusion, lifted her legs and administered oxygen. Three minutes after these treatments, she quickly recovered to a good general condition. A skin prick test for vitamin B12 was positive, but tests for B1, B6, mannitol and saline were negative, indicating this adverse reaction was one of drug hypersensitivity due to the vitamin B12 in Vitamedin. Patients should be observed carefully immediately after the administration of Vitamedin.

Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes.

In this study, we performed small RNA library sequencing using human placental tissues to identify placenta-specific miRNAs. We also tested the hypothesis that human chorionic villi could secrete miRNAs extracellularly via exosomes, which in turn enter into maternal circulation. By small RNA library sequencing, most placenta-specific miRNAs (e.g., MIR517A) were linked to a miRNA cluster on chromosome 19. The miRNA cluster genes were differentially expressed in placental development. Subsequent validation by real-time PCR and in situ hybridization revealed that villous trophoblasts express placenta-specific miRNAs. The analysis of small RNA libraries from the blood plasma showed that the placenta-specific miRNAs are abundant in the plasma of pregnant women. By real-time PCR, we confirmed the rapid clearance of the placenta-specific miRNAs from the plasma after delivery, indicating that such miRNAs enter into maternal circulation. By using the trophoblast cell line BeWo in culture, we demonstrated that miRNAs are indeed extracellularly released via exosomes. Taken together, our findings suggest that miRNAs are exported from the human placental syncytiotrophoblast into maternal circulation, where they could target maternal tissues. Finally, to address the biological functions of placenta-specific miRNAs, we performed a proteome analysis of BeWo cells transfected with MIR517A. Bioinformatic analysis suggests that this miRNA is possibly involved in tumor necrosis factor-mediated signaling. Our data provide important insights into miRNA biology of the human placenta.

Opening the bladder for cesarean hysterectomy for placenta previa percreta with bladder invasion.

Cesarean hysterectomy for placenta previa percreta with bladder invasion often induces not only massive hemorrhage but also severe bladder/ureter injuries. A 37-year-old woman with previous cesarean delivery suffered placenta previa percreta with bladder invasion. At the 34th week, we performed cesarean hysterectomy. Without separating the bladder from the uterus/cervix, we incised the bladder lateral wall using an automatic stapling/cutting device, leaving the bladder posterior wall adhering to the uterus and resecting it with the uterus. The bladder was easily repaired without urological sequelae. We suggest a new, simple and safe technique for cesarean hysterectomy for this disease.

Mirror syndrome associated with hydropic acardius in triplet pregnancy.

UNLABELLED: Mirror syndrome is the association of triple edema, i.e. fetal, placental and maternal edema, with maternal preeclampsia. We here report the first case of mirror syndrome resulting from hydropic acardius in triplet pregnancy. METHODS/RESULTS: A 26-year-old nulliparous woman spontaneously conceived two living fetuses and one acardius, and suffered preterm rupture of the membranes at 23 2/7 weeks of gestation. We observed triple edema, hydropic acardius, placental edema, and maternal edema, together with maternal high blood pressure, proteinuria and low hematocrit, and therefore suspected the presence of mirror syndrome. Due to the prematurity of the fetuses, we closely observed her, awaiting fetal maturity. Three days later (23 5/7 weeks), cord prolapse occurred, leading to emergent cesarean section. Female infants, weighing 492 and 554 g, respectively, were born alive; the former died on the 13th postnatal day and the latter was healthy with no sequelae. An acardius weighing 860 g had vascular communication with the 492-gram fetus. Histological examination confirmed a monochorionic, triamniotic single placenta. The mother suffered from pulmonary edema and was treated in the intensive care unit under respiratory support, but soon improved. CONCLUSIONS: When dealing with multifetal pregnancy, especially when complicated by an acardius, obstetricians must have the highest level of concern for the occurrence of mirror syndrome, a life-threatening condition both to the mother and the fetus.

Blood loss in low-lying placenta: placental edge to cervical internal os distance of less vs. more than 2 cm.

OBJECTIVE: To reconfirm that a low-lying placenta, with placental edge-internal os distance of 0-4 cm, is a risk factor for blood loss during delivery, and to determine whether blood loss differs between edge-os distance of < or =2 cm vs. >2 cm. METHODS: We compared total blood loss between 73 singleton pregnant women with edge-os distance of 0-4.0 cm vs. controls. We also compared total blood loss between pregnant women with distance of 0-2.0 cm (lower) vs. 2.1-4.0 cm (higher). RESULTS: Total blood loss was significantly greater in women with placental edge-os distance of < or =4 cm than controls in both delivery modes. The lower group showed a significantly higher incidence of excessive hemorrhage during vaginal delivery (60 vs. 19%, P=0.046) and bled more (median 1240 vs. 860 mL, P=0.059) than the higher group. Although this did not reach statistical significance, the lower group more frequently bled antepartum, required emergent cesarean section, and delivered abdominally. Regression analysis showed no association between the amount of blood loss and the edge-os distance in both delivery modes. CONCLUSION: Pregnant women with edge-os distance of 2.1-4.0 cm are of highest level of concern as are women with 0-2.0 cm distance.

Decidualization of ovarian endometriosis during pregnancy mimicking malignancy: report of three cases with a literature review.

BACKGROUND: Intracystic papillary excrescence is a characteristic morphological feature of ovarian malignancy. A few recent reports have demonstrated that ovarian endometriotic cysts, undergoing decidualization during pregnancy, occasionally show excrescence, necessitating surgery during pregnancy; however, this phenomenon is not well recognized among clinicians. CASES: Three pregnant women with decidualized ovarian endometriosis showed excrescence. Both ultrasound and magnetic resonance imaging (MRI) preoperatively suggested the presence of underlying ovarian endometriotic cysts in 2 women, but not in the other. Intracystic papillary excrescence prompted us to perform laparotomy at 14, 14, and 19 weeks of pregnancy, respectively, with 1 woman aborting in the 21st week, and with 2 delivering healthy term infants. Histological examination confirmed the diagnosis of decidualized ovarian endometriotic cysts in all 3 patients. CONCLUSIONS: We provide the first report of pregnant women in whom excrescence occurred from ovarian endometriotic cysts without preoperative evidence. Decidualized ovarian endometriosis, even without preoperative morphological features of endometriosis, should be added to the differential diagnosis of ovarian malignancy during pregnancy.

Establishing a reference value for the frequency of fetal movements using modified 'count to 10' method.

AIMS: To establish a reference value for the frequency of fetal movements perceived by the mother during the second half of pregnancy. METHODS: The study subjects consisted of 705 low risk Japanese pregnant women who continuously received antenatal care. We asked women to record the time required to perceive 10 fetal movements ('count to 10' time) everyday. We asked women to record it, not at a fixed time (i.e. evening time), but whenever they felt the fetus move the most actively. The position during counting (i.e. sitting position) was also not specified, and thus we named this method as modified 'count to 10' method. Satisfactory recordings were obtained from 690 women, which we used for analysis. RESULTS: The 'count to 10' time was almost the same from 22 weeks (10.9; 7.3-18.0 (median; interquartile range)) until 32 weeks (10.0; 6.2-15.6), and it Thirty-two weeks showed the shortest time, which gradually increased toward 40 weeks (14.8; 9.5-24.0). Its 90th percentile was approximately 25 and 35 min at 22-36 weeks and at 37-40 weeks, respectively. CONCLUSIONS: For the first time we established a reference value for perceived fetal movements throughout the second half of pregnancy. The present modified 'count to 10' method requires less time than the previous method. Approximately 98% (690/705) of women gave us satisfactory recordings. This reference value may be of use in identifying mothers with decreased fetal movements.

Femur fracture during abdominal breech delivery.

BACKGROUND: While vaginal breech delivery, although rare, can cause femur fracture, abdominal breech delivery is not expected to cause it. CASE: A 2,490-g female infant was delivered at term by elective cesarean section for breech presentation. She sustained a fracture of the femur shaft. A simple splinting led to a complete healing of the fracture without sequelae. CONCLUSION: Although abdominal breech delivery reduces the risk of birth trauma, we must be aware that femur fracture can occur regardless of the mode of delivery.