Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding.

BACKGROUND & AIMS: Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known endoscopic pattern carrying a high-risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. METHODS: From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high-risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleed-free survival, overall survival and life-threatening complications of bleeding. RESULTS: High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis (p<0.001), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleed-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for non-cirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with non-cirrhotic causes and cirrhosis respectively. CONCLUSION: In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. LAY SUMMARY: In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the child's age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can be achieved by surgery or endoscopic treatment, and decreases mortality and morbidity.

The porta hepatis microcyst: an additional sonographic sign for the diagnosis of biliary atresia.

OBJECTIVES: To describe and evaluate an additional sonographic sign in the diagnosis of biliary atresia (BA), the microcyst of the porta hepatis, in comparison with previously described signs. METHODS: Ultrasound performed in 321 infants (mean age 55 days) with cholestasis were retrospectively analyzed. BA was surgically confirmed in 193 patients and excluded in 128. US evaluated gallbladder type (1: normal; 2: consistent with BA; 3: suspicious), triangular cord sign (TCS), microcyst and macrocyst, polysplenia syndrome, portal hypertension, and bile duct dilatation. T test and Pearson χ2 test were used to compare US signs between the two groups, followed by univariate regression analysis. RESULTS: The highest specificity and sensitivity for BA (p < 0.001) were respectively obtained with non-visible gallbladder (100 %-13 %), macrocyst (99 %-10 %), polysplenia (99 %-11 %), microcyst (98 %-20 %), type 2 gallbladder (98 %-34 %), and TCS (97 %-30 %). Combination of signs (macro or microcyst; cyst and no bile duct dilatation; microcyst and/or TCS; type 2 gallbladder and/or cyst) provided better sensitivities (25-49 %) with similar specificities (95-98 %) (p < 0.001). On univariate analysis, the single US signs most strongly associated with BA were polysplenia (odds ratio, OR 16.3), macrocyst (OR 14.7), TCS (OR 13.4) and microcyst (OR 8). CONCLUSIONS: Porta hepatis microcyst is a reliable US sign for BA diagnosis. KEY POINTS: • The porta hepatis microcyst is a specific sign of biliary atresia. • It was found in 31 (16.1 %) of 193 patients with biliary atresia. • Its specificity was 98 % (p < 0.001). • High frequency transducer and color Doppler can show the porta hepatis microcyst.

Ovulatory status and menstrual cycle duration assessed by self-collection of urine on pH strips in a population-based sample of French women not using hormonal contraception.

BACKGROUND: Assessing menstrual cycle function in the general population using a non-invasive method is challenging, both in non-industrialized and industrialized countries. SUBJECTS AND METHODS: The Observatory of Fecundity in France (Obseff) recruited on a nationwide basis a random sample of 943 women aged 18-44 years with unprotected intercourse. A sub-study was set up to assess the characteristics of a menstrual cycle by using a non-invasive method adapted to the general population. Voluntary women were sent a collection kit by the post and requested to collect urine samples on pH strips, together with daily recording of reproductive-related information during a full menstrual cycle. A total of 48 women collected urine every day, whereas 160 women collected urine every other day. Immunoassays were used to measure pregnanediol-3-α-glucuronide, estrone-3-glucuronide and creatinine. Ovulation occurrence and follicular phase duration were estimated using ovulation detection algorithms, compared to a gold standard consisting of three external experts in reproductive medicine. RESULTS: Every other day urine collection gave consistent results in terms of ovulation detection with every day collection (intraclass coefficient of correlation, 0.84, 95% confidence interval, 0.76-0.98). The proportion of anovulatory menstrual cycles was 8%. The characteristics of the ovulatory cycles were length 28 (26-34), follicular phase 16 (12-23), luteal phase 13 (10-16) days median (10th-90th percentiles). DISCUSSION-CONCLUSION: Assessing menstrual cycle characteristics based on urine sample spot only collected every other day in population-based studies through a non-invasive, well accepted and cost-limited procedure not requiring any direct contact with the survey team appears feasible and accurate.

Feasibility and Diagnostic Accuracy of Supersonic Shear-Wave Elastography for the Assessment of Liver Stiffness and Liver Fibrosis in Children: A Pilot Study of 96 Patients.

PURPOSE: To evaluate the feasibility of using supersonic shear-wave elastography (SSWE) in children and normal values of liver stiffness with the use of control patients of different ages (from neonates to teenagers) and the diagnostic accuracy of supersonic shear wave elastography for assessing liver fibrosis by using the histologic scoring system as the reference method in patients with liver disease, with a special concern for early stages of fibrosis. MATERIALS AND METHODS: The institutional review board approved this prospective study. Informed consent was obtained from parents and children older than 7 years. First, 51 healthy children (from neonate to 15 years) were analyzed as the control group, and univariate and multivariate comparisons were performed to study the effect of age, transducer, breathing condition, probe, and position on elasticity values. Next, 45 children (from 1 month to 17.2 years old) who underwent liver biopsy were analyzed. SSWE measurements were obtained in the same region of the liver as the biopsy specimens. Biopsy specimens were reviewed in a blinded manner by a pathologist with the use of METAVIR criteria. The areas under the receiver operating characteristics curve (AUCs) were calculated for patients with fibrosis stage F0 versus those with stage F1-F2, F2 or higher, F3 or higher, and F4 or higher. RESULTS: A successful rate of SSWE measurement was 100% in 96 patients, including neonates. Liver stiffness values were significantly higher when an SC6-1 probe (Aixplorer; SuperSonic Imagine SA, Aix-enProvence, France) was used than when an SL15-4 probe (Aixplorer) was used (mean ± standard deviation, 6.94 kPa ± 1.42 vs 5.96 kPa ± 1.31; P = .006). There was no influence of sex, the location of measurement, or respiratory status on liver elasticity values (P = .41-.93), although the power to detect such a difference was low. According to the degree of liver fibrosis at liver biopsy, 88.5%-96.8% of patients were correctly classified, with AUCs of 0.90-0.98 (95% confidence interval [CI]: 0.8, 1.0). The AUC for patients with stage F0 versus stage F1-F2 was 0.93 (95% CI: 0.87, 0.99). CONCLUSION: SSWE allows accurate assessment of liver fibrosis, even in children with early stage (F1-F2) disease, and the choice of transducer influences liver stiffness values.

Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France.

OBJECTIVE: To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. METHODS: We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression. RESULTS: By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p < 0.0001) and the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p < 0.0001). Median survival was much shorter in Ile107Val and in Val30Met mutation with late onset (>50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies. INTERPRETATION: Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large-fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing).

Progression to high-risk gastroesophageal varices in children with biliary atresia with low-risk signs at first endoscopy.

OBJECTIVES: Biliary atresia carries a risk of bleeding because of portal hypertension. Our goal was to define the factors associated with the emergence of endoscopic signs carrying a high risk of bleeding in children who did not display these signs at the first upper gastrointestinal endoscopy. METHODS: From 1989 to 2013, a total of 225 children with low-risk signs at the first endoscopic examination underwent ≥2 upper gastrointestinal endoscopic examinations. The emergence of high-risk gastroesophageal varices was observed in 76 children in the 10 years following the first endoscopic examination. A survival study using the occurrence of high-risk varices as an event was performed to identify factors related to the emergence of these varices and to describe the probability of their emergence in 2 groups of children ages older than 18 months and 18 months or younger at the time of the first endoscopy. RESULTS: High total serum bilirubin concentration, young age, and high number/grade of esophageal varices at the first endoscopy were significantly related to the emergence of high-risk varices. The probability of the emergence of high-risk signs was higher and these signs appeared faster in infants 12 months of age or younger and/or when the first endoscopic examination displayed >1 grade 1 or grade 2 varices. Progression to high-risk varices was also related to bilirubinemia in children older than 18 months at the first endoscopy. CONCLUSIONS: The results allow defining a program of repeat endoscopies to detect high-risk varices and to discuss endoscopic primary prophylaxis of bleeding or hasten liver transplantation when these signs are found.

Experience with endoscopic management of high-risk gastroesophageal varices, with and without bleeding, in children with biliary atresia.

BACKGROUND & AIMS: Biliary atresia, the most common cause of childhood cirrhosis, increases the risks for portal hypertension and gastrointestinal bleeding. We report the results from a single-center study of primary and secondary prophylaxis of bleeding in children with portal hypertension and high-risk varices. METHODS: We collected data from 66 children with major endoscopic signs of portal hypertension, including grade 3 esophageal varices or grade 2 varices with red wale markings and/or gastric varices, treated consecutively from February 2001 through May 2011. Thirty-six children (mean age, 22 mo) underwent primary prophylaxis (sclerotherapy and/or banding, depending on age and weight). Thirty children (mean age, 24 mo) who presented with gastrointestinal bleeding received endoscopic treatment to prevent a relapse of bleeding (secondary prophylaxis). RESULTS: In the primary prophylaxis group, a mean number of 4.2 sessions were needed to eradicate varices; no bleeding from gastroesophageal varices was observed after eradication. Varices reappeared in 37% of children, and 97% survived for 3 years. In the secondary prophylaxis group, a mean number of 4.6 sessions was needed to eradicate varices. Varices reappeared in 45%, and 10% had breakthrough bleeding; 84% survived for 3 years. There were no or only minor complications of either form of prophylaxis. CONCLUSIONS: Endoscopic therapy as primary or secondary prophylaxis of bleeding appears to be well tolerated and greatly reduces the risk of variceal bleeding in children with biliary atresia and high-risk gastroesophageal varices. However, there is a risk that varices will recur, therefore continued endoscopic surveillance is needed.

Statistical analysis of multi-b factor diffusion weighted images can help distinguish between vasogenic and tumor-infiltrated edema.

PURPOSE: The diffusion model can be transformed into a multicompartment model by means of multi-b factor diffusion-weighted sequences. We adapted a method of statistical analysis of these images and evaluated its performance to distinguish tumor-infiltrated edema from vasogenic edema. MATERIALS AND METHODS: Forty-nine patients with infiltrating tumors (38 patients: low to high-grade gliomas) or vasogenic edema (11 patients: metastases, abscess, extra-axial lesions) were studied by multi-b factor diffusion-weighted imaging. Comparison of histological results and morphological and perfusion MRI defined 69 characteristic volumes of interest in the peritumoral edema of 69 distinct infiltrating lesions (40) or lesions inducing vasogenic edema (29). RESULTS: The factorial analysis had a sensitivity of 92.9% and a specificity of 90.6% between tumor-infiltrated and vasogenic edema. Simplified interpretation confined to values of the high and mean diffusivity compartments had a sensitivity of 87.5% and a specificity of 89.2% between strictly tumor-infiltrated edema and vasogenic edema with the advantage of simplified interpretation based on two-color parametric mapping. CONCLUSION: Discrimination between tumor-infiltrated edema and vasogenic edema can be achieved by means of a 90-s multi-b factor diffusion-weighted sequence and factorial analysis. Simplified visual and quantitative interpretation of the results should also allow integration of multi-b factor analysis into routine neuroradiology practice.

Dating the abusive head trauma episode and perpetrator statements: key points for imaging.

Shaken baby syndrome/abusive head trauma is a leading cause of morbidity and mortality in infants. The presence of a diffuse subdural hematoma without evidence of accident is a key diagnostic clue. The hematoma is typically attributed to rupture of the cerebral bridging veins due to violent shaking, with or without impact. Dating the incident, however, remains controversial. The aim of this article is to review the most reliable features used for dating the incident, based on both legal statements by perpetrators and medical documentation. The key points are: 1) The high (yet likely underestimated) frequency of repeated shaking is around 50%, 2) Children do not behave normally immediately after shaking, and the time of onset of even mild symptoms appears to be the best clue for dating the incident and 3) Brain imaging provides strong indicators of "age-different" injuries but the ranges for dating the causal event are wide. The density pattern in a single subdural hematoma location provides no reliable clues for assessing repeated violence. Only the finding of different density in two distant subdural hematomas argues in favor of "age-different" injuries, i.e. repeated violence. MRI is difficult to interpret in terms of dating subdural hemorrhages and must be analyzed in conjunction with CT. Most importantly, all of the child's previous clinical and radiological data must be carefully studied and correlated to provide accurate information on the date and repetition of the trauma.

Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort.

OBJECTIVE: To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation. METHODS: Serum interleukin (IL)-1ß, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and <6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit. RESULTS: Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression. CONCLUSION: Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

Prognostic value of endoscopy in children with biliary atresia at risk for early development of varices and bleeding.

BACKGROUND & AIMS: Biliary atresia is the most common cause of childhood cirrhosis. We investigated prospectively the development of portal hypertension in 139 children with biliary atresia, the risk of gastrointestinal (GI) bleeding in the first years of life, and associations between endoscopic patterns of varices and risk. METHODS: Children with clinical or ultrasonographic signs of portal hypertension underwent upper GI endoscopy examinations (n = 125, median age of 13 months). Information was recorded about esophageal varices and grade, red wale markings on the variceal wall, gastric varices along the cardia, and portal hypertensive gastropathy. A second endoscopy examination was performed in 64 children after a mean interval of 51 months to study their progression or regression. RESULTS: At the first endoscopy examination, 88 of 125 children had esophageal varices, including 74 who were younger than 2 years. Grade II and III varices, red markings, gastric varices, and signs of gastropathy were present in 29, 30, 24, and 27 children, respectively. At the second endoscopy examination, progression, stability, and regression of endoscopic signs were observed in 37, 18, and 9 of the 64 children, respectively. Twenty-eight children had GI bleeding at a median age of 17 months. Multivariate analysis showed that red markings, and most importantly gastric varices, were independent factors associated with bleeding. CONCLUSIONS: Children with biliary atresia have a high risk of portal hypertension in the first years of life. Spontaneous regression of varices is rare. Children with a combination of esophageal varices and red markings and/or gastric varices along the cardia should receive primary prophylaxis of bleeding.

Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients and dialysis patients.

BACKGROUND: The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients. METHODS: 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of > 40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion). RESULTS: Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs. CONCLUSIONS: Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs.

Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations.

BACKGROUND: Since fetal exposure to anti-androgenic and/or estrogenic compounds has adverse effect on animal reproduction, such exposure could be harmful to human fetus. Data are scarce on cryptorchidism and human exposure to endocrine disruptors. METHODS: We performed a prospective case-control study to assess the incidence of cryptorchidism and fetal exposure to selected chemicals in the Nice area. One hundred and fifty-one cord bloods (67 cryptorchid, 84 tightly matched controls) and 125 colostrums (56 for cryptorchid and 69 for controls) were screened for xenobiotics, including anti-androgenic dichloro-diphenyl-trichloro-ethylene (DDE), polychlorinated biphenyls (PCBs), and dibutylphthalate (and metabolite monobutylphthalate, mBP). RESULTS: Median concentrations in colostrum were higher, although not statistically significantly, in cryptorchid versus controls. Cryptorchid boys were more likely to be classified in the most contaminated groups in colostrum for DDE, Sigma PCBs and the composite score PCB + DDE. The same trend, but again not statistically significantly was observed for mBP. Odds ratio for cryptorchidism was increased for the highest score of Sigma PCB, with a trend only for DDE and Sigma PCB + DDE versus the lowest score of those components. CONCLUSIONS: Our results support an association between congenital cryptorchidism and fetal exposure to PCBs and possibly DDE. Higher concentrations in milk could be a marker of higher exposure or for an impaired detoxification pattern in genetically predisposed individuals.

Liver disease associated with ZZ alpha1-antitrypsin deficiency and ursodeoxycholic acid therapy in children.

OBJECTIVES: To investigate the effect of ursodeoxycholic acid (UDCA) in children with liver disease associated with ZZ alpha1-antitrypsin (AAT) deficiency. PATIENTS AND METHODS: A total of 42 affected children received UDCA (30 mg x kg x day(-1)) and underwent clinical and biochemical follow-up at least yearly. RESULTS: In group 1, 22 children whose mean initial gamma-glutamyl-transpeptidase (GGT) was 7.4 x N normalized serum liver test results after a mean treatment of 2.6 years. In 16 of these children, UDCA was discontinued. Relapse was observed in 11 children, and liver test results returned to normal after UDCA resumption. In the other 5 children, liver test results remained normal during a mean period of 2.5 years. In group 2, 11 children (mean initial GGT 12.8 x N) had improved liver test results after a mean treatment of 2.3 years. In group 3, 9 children (mean initial GGT 33.8 x N) had no liver test result improvement and evolution toward cirrhosis, requiring liver transplantation in 7. Most of the children in group 1 had normal results of clinical examination after UDCA treatment, versus none in group 3 (P < or = 0.00001). Initial GGT (P < or = 0.002) and total bilirubin (P < or = 0.05) levels were significantly lower in group 1 than in group 3. Combined initial values of GGT < or =5.5 x N and total bilirubin < or =66 micromol/L were associated with normalization of liver test results in 90% of children. CONCLUSIONS: UDCA may significantly improve clinical status and liver test results in some children with liver disease associated with ZZ AAT deficiency. No beneficial effect of UDCA was shown in children with the most severe liver involvement. Initial levels of GGT and total bilirubin may be of prognostic value for therapy effectiveness.

Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization.

BACKGROUND: Based on inhibition tests, the alpha6beta1 integrin was suggested to be a sperm receptor, but further experiments using gene deletion techniques have shown that neither oocyte alpha6, nor beta1 integrin subunits were essential for mouse fertilization. RESULTS: Using Western blot analysis and immunofluorescence, we showed that the mouse sperm expresses the alpha6beta1 integrin. As for oocyte, binding of GoH3 anti-alpha6 antibody to sperm induces a specific inhibition of sperm fertilizing ability. Comparing zona-intact and zona-free eggs in fusion tests, we showed that the removal of the zona pellucida by acid treatment bypasses fertilizing oocyte alpha6beta1 integrin's function in the adhesion/fusion process. CONCLUSION: These findings show that alpha6beta1 integrin is expressed by both gametes and is functional in their membranes interaction. These results and previous reports, about fertilization of alpha6 or beta1 integrin subunits deleted oocytes by wild type sperm, suggest that the presence of alpha6beta1 integrin on one of the two gamete membranes can rescue the fertilization process. This hypothesis is further supported by the exchange of membrane fragments occurring between gametes prior to fusion that we recently reported.

Male gonadal dose of ionizing radiation delivered during X-ray examinations and monthly probability of pregnancy: a population-based retrospective study.

BACKGROUND: Male gonadal exposure to ionizing radiation may disrupt spermatogenesis, but its influence on the fecundity of couples has been rarely studied. We aimed to characterize the influence of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy. METHODS: We recruited a random sample of women who retrospectively described 1110 periods of unprotected intercourse beginning between 1985 and 1999 and leading either to a live birth or to no pregnancy; their duration was censored after 13 months. The male partner answered a telephone questionnaire on radiodiagnostic examinations. We assigned a mean gonadal dose to each type of radiodiagnostic examination. We defined male dose for each period of unprotected intercourse as the sum of the gonadal doses of the X-ray examinations experienced between 18 years of age and the date of discontinuation of contraception. Time to pregnancy was analysed using a discrete Cox model with random effect allowing to estimate hazard ratios of pregnancy. RESULTS: After adjustment for female factors likely to influence fecundity, there was no evidence of an association between male dose and the probability of pregnancy (test of homogeneity, p = 0.55). When compared to couples with a male gonadal dose between 0.01 and 0.20 milligrays (n = 321 periods of unprotected intercourse), couples with a gonadal dose above 10 milligrays had a hazard ratio of pregnancy of 1.44 (95% confidence interval, 0.73-2.86, n = 31). CONCLUSION: Our study provides no evidence of a long-term detrimental effect of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy during the year following discontinuation of contraceptive use. Classification errors due to the retrospective assessment of male gonadal exposure may have limited the statistical power of our study.

Cognitive functions in children with benign childhood epilepsy with centrotemporal spikes (BECTS).

Benign childhood epilepsy with centrotemporal spikes (BECTS) is regarded as a benign form of epilepsy because of its usually favorable outcome, in terms of seizures. Eighteen children with BECTS were studied in terms of neuropsychological and learning abilities: intellectual quotient, oral language (phonological production, naming skills, verbal fluency and syntactic comprehension), drawing and visuo-spatial skills, visual and selective attention, verbal and visuo-spatial memory, reading, numeracy and spelling. The mean IQ of the population was within the normal range, but individual results were heterogeneous. Verbal functions and memory were normal. In contrast, drawing and visuo-spatial skills, attention and visuo-spatial memory were significantly weak compared to the normal range for age. Reading, numeracy and/or spelling ability were significantly delayed by one academic year or more in ten of the children. In conclusion, despite its benign outcome in terms of epilepsy, BECTS can be accompanied by specific cognitive disorders and low academic achievement.

Endoscopic management of post-laparoscopic cholecystectomy biliary strictures. Long-term outcome in a multicenter study.

OBJECTIVES: The aim of this retrospective study was to assess the long term results of long-lasting endoscopic stenting for benign biliary strictures related to laparoscopic cholecystectomy. Additional biological and morphological data were collected from these patients during follow-up. METHODS: Patients undergoing ERCP for post-laparoscopic cholecystectomy biliary stricture in one of the three participating centers between 1990 and December 2001 were identified. Only patients with successful endoscopic stenting were subsequently included and analyzed. Follow-up data were obtained from referring centers, general practitioners and patients or relatives. Hepatic blood tests and abdominal ultrasound were proposed to all the patients who had not undergone further treatments after stent removal. RESULTS: Eight-eight patients had undergone ERCP for benign biliary stricture related to laparoscopic cholecystectomy. Stenting failed in 19 patients. Balloon dilatation alone was used in four patients. Strictures were successfully stented in 65 patients. The mean number of stents inserted at the same time was 1.6. The mean duration of stenting was 14 months (range 1-120 months). Eighteen patients (28%) developed biliary or pancreatic symptoms during stenting. ERCP was considered satisfactory at the end of stenting (i.e. no remaining stricture or minor remaining change on ERCP) in 45 patients (69%). Twenty-two patients were lost to follow-up. Twenty-nine out of forty-three patients (67%) remained symptom-free with normal updated blood tests and abdominal ultrasound during a mean follow-up of 28 months (range 12-117 months) after stent removal. None of the patients with a normal ERCP at the end of stenting developed stricture recurrence during follow-up. Eleven patients were operated (8 with persistence of stricture, 2 for stricture recurrence up to 63 months after stent removal, 1 for pancreatitis). CONCLUSION: Based on clinical, morphological and biological criteria, a long-term success was obtained in 70% of patients with post-laparoscopic cholecystectomy benign biliary strictures, after several months of endoscopic stenting.

Non-palpable incidentally found testicular tumors: Differentiation between benign, malignant, and burned-out tumors using dynamic contrast-enhanced MRI.

PURPOSE: To evaluate qualitative, semi-quantitative, and quantitative parameters obtained by dynamic contrast-enhanced (DCE)-MRI for the characterization of histologically proven, non-palpable, incidentally found intratesticular tumors. MATERIALS AND METHODS: From 2006 to 2014, we included men with non-palpable, incidentally found testicular tumors on ultrasound, normal tumoral marker levels,referred for surgery. DCE-MRI data were analyzed retrospectively and independently by two radiologists blinded to the histological diagnosis. The visual enhancement patterns, time-signal intensity curves, shape of the curves (type 0-3), maximal relative enhancement (Peak), initial enhancement slope (IS), time to peak (TTP), as well as transfer constants Ktrans and Kep were compared between the tumors. The interobserver correlation was evaluated. Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were extracted. RESULTS: Thirty-one patients (mean age of 37.3 years) were included. Tumor mean size was 1.2±0.77 cm (min=0.3cm, max=2.8cm). Regarding the histology results, three groups were defined: Twelve stromal "benign tumors" (BT) exhibited more type 2 and type 3 curves than 12 "malignant tumors" (MT) and 7 "burned-out tumors" (BOT) (p<0.0001). BT had a higher peak (96 vs. 54 and 17%), shorter TTP (215 vs. 412 and 692 sec), higher IS (73 vs. 12 and 2 arbitrary units), higher Ktrans (255 vs. 88 and 14min-1*1000) and higher Kep (554 vs. 159 and 48min-1*1000) than MT and BOT, respectively (p<0.0001, p=0.0003, p<0.0001, p<0.0001 and p<0.0001, respectively). The agreement coefficient values and the AUC extracted after gathering MT with BOT varied from 0.83 to 0.96 and from 0.868 to 0.978, respectively. CONCLUSION: DCE-MRI may assist in differentiating between benign intratesticular stromal tumors,malignant and burned-out tumors.

Is embryo-cryopreservation really neutral? A new long-term effect of embryo freezing in mice: protection of adults from induced cancer according to strain and sex.

BACKGROUND: Beneficial or harmful effects of embryo freezing have been described in man and animals, raising the question of the neutrality of this technique. OBJECTIVE: We examined, in mice, the possibility that embryo freezing influences the probability of the emergence, in adults, of an induced urinary bladder cancer. METHODS: The experiment was conducted in mice derived from embryos of two different genotypes. Females receiving embryos were parsed into two groups according to whether these embryos were cryopreserved or not. The derived adults received the chemical carcinogen N-butyl-N-4hydroxybutylnitrosamine (BBN), in the drinking water. Time to death since the onset of treatment was measured for each animal until the 300th day. RESULTS: In females from one of the two strains tested, embryo freezing led to a favorable long-term effect on the probability of resistance to induced cancer. CONCLUSION: This beneficial effect, taken together with other effects reported in the literature be they beneficial or harmful, suggests that embryo freezing in mice may not be neutral.