Developmental Effects of Intraperitoneal Injection of Polychlorinated Biphenyls in Rats During Pregnancy

Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that are possible health hazards for human beings through a variety of pathways.In the present study,50 time mated pregnant rats were divided into five groups and injected daily from gestational days 7 to 18 with either 2,2′,4,4′- tetrachlorobiphenyl (PCB 47) or 3,3′,4,4′- tetrachlorobiphenyl (PCB 77) or seseme oil (control) to evaluate the effects of these PCBs on prenatal and postnatal development.Offspring were examined for malformations of genitalia at birth and in adulthood.Body weight gains of these animals were checked every 7 days through postnatal day (PND) 119.There were no clinical signs of toxicity in the PCB-treated dams or their offspring throughout the experiment.Litter size and sex ratio of the litters were not affected.Both PCBs produced a significant increase in the females' anogenital distance,suggesting a modification of androgen responsiveness in females resulting from PCB exposure during development.Similar effects were not seen with the males.The proportion of individuals with eyes open by PND 15 was significantly reduced by both PCBs.Exposure to 1 mg/kg body weight of PCB 77 significantly reduced body weight gains in male pups from PND 35 to 119.However,no significant differences were found in body weight gains of the pups exposed to PCB 47.

幽默

让座 一次坐公交，有位美女上车，掏出公交卡来刷，只听刷卡机回复：“滴……老人卡……!”全车人冻住了，目光一起瞅向她。她一脸黑线说：“看什么，天山童姥，没见过啊？”一大爷起身，说：“来，大娘。您坐这。”

DIAGNOSIS AND TREATMENT OF CESAREAN SCAR PREGNANCY

Objective To investigate the early diagnosis and treatment of cesarean scar pregnancy （CSP）. Methods Clinical data of 28 patients with CSP in Peking Union Medical College Hospital from January 1994 to April 2007, including age, interval from the last cesarean delivery to diagnosis, clinical presentation, location of the lesion, process of diagnosis and treatment, outcome, and follow-up, were retrospectively analyzed. Re, salts CSP constituted 1.05 % of all ectopic pregnancies, and the ratio of CSP to pregnancy was 1 ： 1 221. The mean age of the group was 31.4 years. Twenty-six women had only one prior cesarean delivery. The interval from the last cesarean delivery to diagnosis ranged from 4 months to 15 years. The most common presenting symptoms of CSP were amenorrhoea and vaginal bleeding. Seventeen cases were misdiagnosed as early intrauterine pregnancies and 2 were misdiagnosed as gestational trophoblastic tumor. The other 9 were diagnosed definitely before treatment. The diagnosis was made based on cesarean delivery history, gynecologic examination, ultrasound, and magnetic resonance imaging （MRI）. The treatment of CSP included systemic or local methotrexate administration, conservative surgery, and hysterectomy. The conservative treatment was successful in 24 cases. All of the 28 women were cured through individual therapies. Conclusions CSP is rare and usually misdiagnosed as other diseases. Ultrasound is valuable for diagnosing CSP, and MRI can be used as an adjunct to ultrasound scan. Early diagnosis offers the options of conservative treatment and greatly improves the outcome of patients. Individual therapy is strongly recommended.

Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems

Intrahepatic cholestasis of pregnancy （ICP） is the most common pregnancy-related liver disorder. Maternal effects of ICP are mild; however, there is a clear association between ICP and higher frequency of fetal distress, preterm delivery, and sudden intrauterine fetal death. The cause of ICP remains elusive, but there is evidence that mutations in genes encoding hepatobiliary transport proteins can predispose for the development of ICP. Recent data suggest that ursodeoxycholic acid is currently the most effective pharmacologic treatment, whereas obstetric management is still debated. Clinical trials are required to identify the most suitable monitoring modalities that can specifically predict poor perinatal outcome. This article aims to review current achievements and unsolved problems of ICR

Endoscopic retrograde cholangiopancreatography during pregnancy without radiation

AIM： To present our experience with pregnant patients who underwent endoscopic retrograde cholangiopancreatography （ERCP） without using radiation, and to evaluate the acceptability of this alternative therapeutic pathway for ERCP during pregnancy. METHODS： Between 2000 and 2008, six pregnant women underwent seven ERCP procedures. ERCP was performed under mild sedoanalgesia induced with pethidine HCI and midazolam. The bile duct was cannulated with a guidewire through the papilla. A catheter was slid over the guidewire and bile aspiration and/or visualization of the bile oozing around the guidewire was used to confirm correct cannulation. Following sphincterotomy, the bile duct was cleared by balloon sweeping. When indicated, stents were placed. Confirmation of successful biliary cannulation and stone extraction was made by laboratory, radiological and clinical improvement. Neither fluoroscopy nor spot radiography was used during the procedure. RESULTS： The mean age of the patients was 28 years （range, 21-33 years）. The mean gestational age for the fetus was 23 wk （range, 14-34 wk）. Five patients underwent ERCP because of choledocholithiasis and/or choledocholithiasis-induced acute cholangitis. In one case, a stone was extracted after precut papillotomy with a needle-knife, since the stone was impacted. One patient had ERCP because of persistent biliary fistula after hepatic hydatid disease surgery. Following sphincterotomy, scoleces were removed from the common bile duct. Two weeks later, because of the absence of fistula closure, repeat ERCP was performed and a stent was placed. The fistula was closed after stent placement. Neither post-ERCP complications nor premature birth or abortion was seen. CONCLUSION： Non-radiation ERCP in experienced hands can be performed during pregnancy. Stent placement should be considered in cases for which complete common bile duct clearance is dubious because of a lack of visualization of the biliary tree.

Hepatitis B in pregnancy

Chronic hepatitis B virus (HBV) infection affects about 350 million individuals worldwide. Management of HBV infection in pregnancy is difficult because of several peculiar and somewhat controversial aspects. The aim of the present review is to provide a tool that may help physicians to correctly manage HBV infection in pregnancy. This review focuses on (1) the effect of pregnancy on HBV infection and of HBV infection on pregnancy; (2) the potential viral transmission from mother to newborn despite at-birth prophylaxis with immunoglobulin and vaccine; (3) possible prevention of mother-to-child transmission through antiviral drugs, the type of antiviral drug to use considering their efficacy and potential teratogenic effect, and the timing of their administration and discontinuation; and (4) the evidence for the use of elective caesarean section vs vaginal delivery and the possibility of breastfeeding.

Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences

Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy(BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.

Safety of lamivudine treatment for chronic hepatitis B in early pregnancy

AIM:To evaluate the safety of lamivudine(LAM) treatment for chronic hepatitis B in early pregnancy.METHODS:A total of 92 pregnant women who received LAM treatment either before pregnancy or in early pregnancy were enrolled in this study.All of the pregnant women volunteered to take lamivudine during pregnancy and were not co-infected with hepatitis C virus,human immunodeficiency virus,cytomegalovirus,or other viruses.All infants received passiveactive immunoprophylaxis with 200 IU hepatitis B immunoglobulin and three doses of 10 μg hepatitis B vaccines(0-1-6 mo) according to the guidelines for the prevention and treatment of chronic hepatitis B.Adverse events were observed throughout the entire pregnancy and perinatal period,and the effectiveness of lamivudine treatment for blocking mother-to-infant transmission of hepatitis B virus(HBV) was evaluated.All adverse events in mothers and infants during pregnancy and the perinatal period and the HBV motherto-infant transmission blocking rate were compared with the literature.RESULTS:Among the 92 pregnant women,spontaneous abortions occurred in 11 cases,while 3 mothers had a second pregnancy after the initial abortion;72 mothers delivered 73 live infants,of whom 68 infants were followed up for no less than 6 mo,and 12 mothers were still pregnant.During pregnancy,the main maternal adverse events were vaginitis(12/72,16.7%),spontaneous abortion(11/95,11.6%),and gestational diabetes(6/72,8.3%);only one case had 1-2 degree elevation of the creatine kinase level(195 U/L).During the perinatal period,the main maternal adverse events were premature rupture of the membranes(8/72,11.1%),preterm delivery(5/72,6.9%),and meconium staining of the amniotic fluid(4/72,5.6%).In addition,2 infants were found to have congenital abnormalities;1 had a scalp hemangioma that did not change in size until 7 mo,and the other had early cerebral palsy,but with rehabilitation training,the infant's motor functions became totally normal at 2 years of age.The incidence of adverse events among the mothers or abnormalities in the infants was not higher than that of normal mothers or HBV-infected mothers who did not receive lamivudine treatment.In only 2 cases,mother-to-infant transmission blocking failed;the blocking rate was 97.1%(66/68),which was higher than has been previously reported.CONCLUSION:Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 wk or throughout the entire pregnancy.

Complete spontaneous regression of giant focal nodular hyperplasia of the liver: Magnetic resonance imaging evaluation with hepatobiliary contrast media

Focal nodular hyperplasia(FNH) of the liver is a benign lesion occurring in 0.6%-3% of the general population that probably reflects a local hyperplastic response of hepatocytes to a vascular abnormality. Most lesions are diagnosed incidentally and the natural history of the disease remains largely unknown. It has been shown that most FNH remain stable, or even regress, over a long follow-up period. We present a patient with FNH of the liver who was followed up for 7 years. A 26-yearold woman with a 5-year history of oral contraceptive use was referred to our hospital in February 2005 for further examination of a liver tumour. The diagnosis of FNH was made using magnetic resonance(MR) imaging with hepatospecific contrast media; this technique allows a correct diagnosis, in particular distinguishing FNH from hepatic adenoma, avoiding an invasive procedure such as the lesion biopsy. After 7-year from the diagnosis, we observed the complete spontaneous regression of the lesion by enhanced MR scanning. In this patient, discontinuation of oral contraceptive use and two childbirths may have influenced the natural history of FNH. To our knowledge, in the English literature there is no report illustrating a complete regression of giant FNH but only studies of decreasing in size. The present case suggests that a young patient with giant FNH should be managed conservatively rather than by resection, because FNH has the potential for spontaneous regression.

Role of ABCC2 common variants in intrahepatic cholestasis of pregnancy

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP), a disorder that adversely affects maternal wellbeing and fetal outcome, is unclear. However, multiple factors probably interact along with a genetic predisposition. We would like to add some comments on a paper recently published concerning the role of ABCB11 and ABCC2 polymorphisms in both ICP and contraceptive-induced cholestasis, especially in the light of our recently published findings about a positive association between ICP and ABCC2 common variants.

Liver disease in pregnancy

Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

Impact of inflammatory bowel disease activity and thiopurine therapy on birth weight: A meta-analysis

AIM To investigate the effect of disease activity or thiopurine use on low birth weight and small for gestational age in women with inflammatory bowel disease(IBD).METHODS Selection criteria included all relevant articles on the effect of disease activity or thiopurine use on the risk of low birth weight(LBW) or small for gestational age(SGA) among pregnant women with IBD. Sixtynine abstracts were identified,35 papers were full text reviewed and,only 14 of them met inclusion criteria. Raw data were extracted to generate the relative risk of LBW or SGA. Quality was assessed using the Newcastle Ottawa Scale.RESULTS This meta-analysis is reported according to PRISMA guidelines. Fourteen studies met inclusion criteria,and nine reported raw data suitable for meta-analysis. We found an increased risk ratio of both SGA and LBW in women with active IBD,when compared with women in remission: 1.3 for SGA(4 studies,95%CI: 1.0-1.6,P = 0.04) and 2.0 for LBW(4 studies,95%CI: 1.5-2.7,P < 0.0001). Women on thiopurines during pregnancy had a higher risk of LBW(RR 1.4,95%CI: 1.1-1.9,P = 0.007) compared with non-treated women,but when adjusted for disease activity there was no significant effect on LBW(RR 1.2,95%CI: 0.6-2.2,P = 0.6). No differences were observed regarding SGA(2 studies; RR 0.9,95%CI: 0.7-1.2,P = 0.5). CONCLUSION Women with active IBD during pregnancy have a higher risk of LBW and SGA in their neonates. This should be considered in treatment decisions during pregnancy.

Perinatal transmission in infants of mothers with chronic hepatitis B in California

To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in California. METHODSRetrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%. RESULTSA total of 17687 infants were born to HBsAg positive mothers in California between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%CI: 6.05-361.32, P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%CI: 12.22-247.55, P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection. CONCLUSIONIn California, transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/mL is associated with high risk of perinatal infection.

Management of chronic hepatitis B in pregnancy

Pregnancy associated with chronic hepatitis B (CHB) is a common and important problem with unique challenges. Pregnant women infected with CHB are different from the general population, and their special problems need to be considered: such as the effect of hepatitis B virus (HBV) infection on the mother and fetus, the effect of pregnancy on replication of the HBV, whether mothers should take HBV antiviral therapy during pregnancy, the effect of these treatments on the mother and fetus, how to carry out immunization of neonates, whether it can induce hepatitis activity after delivery and other serious issues. At present, there are about 350 million individuals with HBV infection worldwide, of which 50% were infected during the perinatal or neonatal period, especially in HBV-endemic countries. Currently, the rate of HBV infection in thechild-bearing age group is still at a high level, and the infection rate is as high as 8.16%. Effective prevention of mother-to-child transmission is an important means of reducing the global burden of chronic HBV infection. Even after adopting the combined immunization measures, there are still 5%-10% of babies born with HBV infection in hepatitis B e antigen positive pregnant women. As HBV perinatal transmission is the main cause of chronic HBV infection, we must consider how to prevent this transmission to reduce the burden of HBV infection. In this population of chronic HBV infected women of childbearing age, specific detection, intervention and follow-up measures are particularly worthy of attention and discussion.

Contraindications for video capsule endoscopy

Video capsule endoscopy(VCE) has been applied in the last 15 years in an increasing field of applications. Although many contraindications have been put into perspective, some precautions still have to be considered. Known stenosis of the gastrointestinal tract is a clear contraindication for VCE unless surgery is already scheduled or at least has been considered as an optional treatment modality. In patients with a higher incidence of stenosis, as in an established diagnosis of Crohn's disease, clinical signs of obstruction, prior radiation or surgical small bowel resection, a preceding test with the self-dissolving patency capsule can override this contraindication. Endoscopic placement of the capsule should be considered in patients with swallowing disorders to avoid aspiration. Esophageal or gastric motility disorders may require endoscopic capsule transport or application of prokinetics if the real-time viewer proofs delayed transit. In pregnant women, VCE should be restricted to urgent cases where diagnosis cannot be postponed after delivery, as data on safety are missing. There is theoretical and clinical evidence that patients with implanted cardiac devices such as a pacemaker, cardioverters or left heart assist devices, can safely undergo VCE in spite of still existing contraindication by manufacturers. Children from the age of 2 years have safely undergone VCE. Although video capsules are not proven safe with magnetic resonance imaging(MRI), first single cases of patients incidentally undergoing MRI with an incorporated capsule have been reported, showing susceptibility artifacts but no signs of clinical harm.

Perinatal and early life risk factors for inflammatory bowel disease

AIM:To investigate associations between perinatal risk factors and subsequent inflammatory bowel disease (IBD) in children and young adults.METHODS:Record linked abstracts of birth registrations,maternity,day case and inpatient admissions in a defined population of southern England.Investigation of 20 perinatal factors relating to the maternity or the birth:maternal age,Crohn's disease (CD) or ulcerative colitis (UC) in the mother,maternal social class,marital status,smoking in pregnancy,ABO blood group and rhesus status,pre-eclampsia,parity,the infant's presentation at birth,caesarean delivery,forceps delivery,sex,number of babies delivered,gestational age,birthweight,head circumference,breastfeeding and Apgar scores at one and five minutes.RESULTS:Maternity records were present for 180 children who subsequently developed IBD.Univariate analysis showed increased risks of CD among children of mothers with CD (P=0.011,based on two cases of CD in both mother and child) and children of mothers who smoked during pregnancy.Multivariate analysis confirmed increased risks of CD among children of mothers who smoked (odds ratio=2.04,95% CI=1.06-3.92) and for older mothers aged 35+ years (4.81,2.32-9.98).Multivariate analysis showed that there were no significant associations between CD and 17 other perinatal risk factors investigated.It also showed that,for UC,there were no significant associations with the perinatal factors studied.CONCLUSION:This study shows an association between CD in mother and child;and elevated risks of CD in children of older mothers and of mothers who smoked.

Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy:Report of a case and a review of the literature

Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology.

Bochdaleck's hernia complicating pregnancy: Case report

Diaphragmatic hernia complicating pregnancy is rare and results in a high mortality rate, particularly if early surgical intervention is not undertaken. We report a case in which a woman presenting at 23 wk＇s gestation was admitted with symptoms of respiratory failure and bowel obstruction due to incarceration of viscera through a left posterolateral defect of the diaphragm （Bochdalek＇s hernia）. Surgery （left thoracoabdominal incision） demonstrated compression atelectasis, mediastinal shift, strangulation and gangrene of the herniated viscera which led to segmental resection of the involved portion of large intestine with re-establishment of bowel continuity by end to end anastomosis. The greater omentum was partly necrotic necessitating resection. The diaphragmatic defect was closed with interrupted sutures. Postoperative period was uncomplicated. Pregnancy was allowed to continue until 39 wk＇s gestation at which time elective cesarean delivery was performed. It is concluded that symptomatic maternal diaphragmatic hernia during pregnancy is a surgical emergency and requires a high index of suspicion.