Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?

Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate-severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate-severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.

Colonic inflammation in pediatric inflammatory bowel disease: detection with magnetic resonance enterography.

BACKGROUND: Colonic involvement in pediatric inflammatory bowel disease is common. Magnetic resonance (MR) enterography is considered the best imaging modality for pediatric inflammatory bowel disease evaluation. It is unclear whether the lack of a dedicated large bowel preparation prevents a reliable colonic assessment. OBJECTIVE: To determine the diagnostic performance of standard MR enterography in detecting and grading colonic inflammatory activity. MATERIALS AND METHODS: We retrospectively evaluated children who underwent both MR enterography and ileocolonoscopy with biopsies <4 weeks apart. Two radiologists independently reviewed MR examinations and quantified inflammation in each of the five colonic segments using a standardized MR score system. Findings were compared with histological examination of the corresponding segment. Mann-Whitney, Kruskal-Wallis, Jonckheere-Terpstra and Bland-Altman statistics were used. RESULTS: One hundred seventy-five segments from 37 examinations were included. MR enterography diagnostic performance for inflammation was as follows: sensitivity 94% (95% confidence interval [CI]: 90-97%), specificity: 64% (95% CI: 57-71%). A significant positive correlation was found between MR score and inflammatory activity histologically graded (P<0.001, Jonckheere-Terpstra test). The interobserver agreement was good (mean difference between MR enterography scores was -0.03; limits of agreement -2.8 to 2.7). CONCLUSION: Standard MR enterography is sensitive for the detection of actively inflamed colonic segments. MR enterography might provide useful information for guiding biopsies and its role as an alternative to ileocolonoscopy in monitoring colonic disease activity in children should be further investigated.

Late-Onset Pyloric Stenosis and Intussusception With Final Diagnosis of Food Proteins' Hypersensitivity in Schaaf-Yang Syndrome: A Case Report.

Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder whose clinical spectrum includes neurodevelopment delay, dysmorphic features, and gastrointestinal symptoms such as feeding difficulties, gastroesophageal reflux, and chronic constipation. Given the small number of patients diagnosed with this syndrome, our aim is to describe novel clinical features that have not yet been reported. The patient we are describing is a 14-year-old male affected by a severe form of SYS. Initial clinical presentation included respiratory distress at birth, feeding difficulties, and neurodevelopmental delay. Since the age of 8 months, he had been tube fed with a semi-elemental formula, and this was well tolerated. At 9 years of age, the pathological mutation (variant p.Val701fs in MAGEL2 gene) associated with SYS was diagnosed. At 13 years of age, he presented severe gastrointestinal symptoms associated to progressive feeding difficulties. He also suffered from recurrent pancreatitis, late-onset pyloric stenosis and intussusception. Histology showed duodenal villous atrophy with a negative serology for celiac disease. Food protein's hypersensitivity was diagnosed and symptoms resolved after starting an elemental formula.

Visceral plexiform schwannoma: A case series.

Plexiform schwannoma (PS) is a benign tumour of the peripheral nerve sheath that is typically found in the skin. Fewer than 15 cases of visceral PS have been reported to date in both adults and children. We herein discuss a series of 3 patients (2 male and 1 female) with abdominal PS, aged 10-16 years (mean age, 12 years). All the patients had an acute presentation with abdominal pain, which was associated with rectal bleeding in 1 case and with walking difficulties in 1 case. Radiological investigations included abdominal magnetic resonance imaging (MRI) and computed tomography, along with neurofibromatosis screening (cerebral MRI and dermatological evaluation). Complete removal of the mass was possible in 2 of the patients (in 1 case by laparoscopically assisted surgery). Follow-up was uneventful. Abdominal PS is a rare occurrence. Due to its possible association with neurofibromatosis, the diagnosis of PS should prompt an investigation for other manifestations of this disorder.

Usefulness of Gastrojejunostomy Prior to Fundoplication in Severe Gastro-Esophageal Reflux Complicating Long-Gap Esophageal Atresia Repair: A Preliminary Study.

BACKGROUND: Gastro-esophageal reflux disease (GERD), requiring surgical correction, and nutritional problems are reported after long-gap esophageal atresia (LGEA) repair and might jeopardize the postoperative course in some babies. We report an exploratory evaluation of the role of transgastric jejunostomy (TGJ) as a temporary nutritional tool before surgery for GERD in LGEA. METHODS: Seven infant patients operated on for LGEA with intra-thoracic gastro-esophageal junction (GEJ) and growth failure, requiring improvement in their nutritional profile in anticipation of surgery, were retrospectively evaluated. Post-surgical follow-up, including growth evolution, complications, and parental quality of life (QoL), were considered. RESULTS: The TGJ was placed at a mean age of 8.6 ± 5.6 months. The procedure was uneventful and well-tolerated in all seven cases. At 6.6 ± 2.0 months after TGJ placement, significant weight gain (weight z-score -2.68 ± 0.8 vs -0.9 ± 0.2, p < 0.001) was recorded, allowing the GERD surgery to proceed. A significant difference in hospital admissions between 3 months before and post-TGJ insertion was noted (4.8 ± 0.75 vs. 1.6 ± 0.52, p < 0.01). A significant amelioration of QoL after TGJ placement was also recorded; in particular, the biggest improvements were related to parents' perceptions of the general health and emotional state of their babies (p < 0.001). CONCLUSIONS: The placement of TGJ as a temporary nutritional tool in selected cases of LGEA could improve nutritional conditions and parental QoL before fundoplication, allowing successful surgical treatment of GERD to be carried out.

Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell-Riley syndrome with heterotopic gastric mucosa and duodenal atresia: a case report.

BACKGROUND: Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. RESULTS: We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including "Evading apoptosis" (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), "Proliferation" (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), "Sustained angiogenesis" (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), "Genomic instability" (BAD, BBC3) and "Insensitivity to anti-growth signals" (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as "PI3K signaling", "ERK signaling", "JAK-STAT signaling", "Calcium signaling", "Other RAS signaling", "WNT signaling". CONCLUSIONS: In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.

Foreign Body Ingestion in Neurologically Impaired Children: A Challenging Diagnosis and Management in Pediatric Surgery.

Children with intellectual disability/neurodevelopmental delay (ID-ND) commonly ingest foreign bodies (FB) and often present complications due to peculiar aspects of their condition. The aim of this paper is to report the experience of two centers in the management of ID-ND patients after FB ingestion and to discuss a possible algorithm for clinical practice. We retrospectively evaluated data of patients managed for FB ingestion (period: 2017-2021), focusing on those with ID-ND, specifically demographics and baseline diagnosis, elements related to the event, symptoms, time to endoscopy, FB location, endoscopic details, and follow-up. A total of 457 patients were managed in the study period and 19 had ID-ND (mean age 9.8 ± 3.5 years, 15 males). A total of 16/19 (84.2%) were symptomatic and required an operative approach. Recurrent ingestions and multiple FB were found in 2 and 11 patients, respectively. Endoscopy (mean time 65.6 ± 41 min) was effective in 14 cases (73.6%) and 6 patients (31.6%) developed a complication. FB ingestion in ID-ND patients represents a challenging condition for the clinician and a potentially dangerous situation. It should be addressed specifically by a multidisciplinary team considering a tailored diagnostic and management protocol.

Colonic Volvulus in Children: Surgical Management of a Challenging Condition.

Colonic volvulus (CV) is a rare but potentially life-threatening condition with unclear etiopathogenesis. To date, less than 80 pediatric cases have been described. Hirschsprung's disease (HD) is associated with CV in 17% of cases, representing a significant risk factor. Non-HD CV is an even more complex entity. The aim of this study is to describe a series of patients with CV to accentuate some peculiar aspects of this disease. We performed a retrospective study (period: 2012-2021) collecting information of patients with CV. Data analyzed included: demographics, medical history, presenting symptoms and radiological and surgical details. Eleven patients (12.5 ± 2.8 years; 7F/4M) had CV (eight sigmoid, two transverse colon, one total colon). Five patients had associated anomalies and three had HD. A two-step approach with volvulus endoscopic/radiological detorsion followed by intestinal resection was attempted in eight cases (one endoscopic approach failed). Three patients required surgery at admission. At follow-up, two patients developed recurrent intestinal obstruction, one of whom also had anastomotic stenosis. Colonic volvulus is a challenging condition that requires prompt patient care. A missed diagnosis could lead to severe complications. The evaluation of the patient should include a careful histological examination (searching for HD and alpha-actin deficiency), immunologic and metabolic screening, neurological tests and detection of chronic intestinal pseudo-obstruction (CIPO). Lifelong follow-up is mandatory for the early recognition and treatment of progressive diseases involving the proximal gastrointestinal tract.

Case Report: Eosinophilic Myenteric Ganglionitis in a Child With Hirschsprung's Disease: A Challenge in Pseudo-Obstruction.

Introduction: The presentation of eosinophilic myenteric ganglionitis (EMG) can be similar to that of Hirschsprung's disease (HD). In a limited number of cases of pediatric patients, the diagnosis of both EMG and HD are reported. A case of pseudo-obstruction in EMG occurring in a child with HD diagnosis is discussed with literature review. Case Presentation: A boy aged 2 years and 6 months presented with intractable constipation and abdominal distension. Histological HD diagnosis was carried out and transanal Soave pullthrough was performed. At the age of 3 years and 2 months, an infectious enterocolitis occurred. One month later, he presented with constipation, marked abdominal distension and melena. Full thickness colonic biopsies revealed eosinophilic myenteric ganglionitis. Specific IgE tests were positive for several foods. Dietary exclusion was adopted with resolution of clinical symptoms and histologic remission. Conclusion: EMD may occur in patients with HD. At the onset, EMD may be associated with functional intestinal obstruction. The use of an elimination diet proved effective for the relief of symptoms. Long term follow-up is mandatory to define the timing of the reintroduction of foods.

The Challenges of a Children's Hospital during the COVID-19 Pandemic: The Pediatric Surgeon's Point of View.

During the coronavirus disease of 2019 (COVID-19) emergency, in the pediatric surgical setting, it has been essential to avoid and contain infections as well as to protect both the patients and the surgical team. During this emergency, procedures and workflow were adapted to provide the safest possible environment for both the surgical team and the patients. Pediatric surgical activities were reorganized during the COVID-19 pandemic at the "Vittore Buzzi" Children's Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), Italy. Resources were optimized in order to maintain high levels of care and quality of assistance. During the COVID-19 emergency, the pediatric surgical department at the "Vittore Buzzi" Children's Hospital became an acute care surgical service. For the reorganization of surgical activities, institutional protocols were adapted in order to preserve the pediatric-specific characteristics of our service; five crucial points were specifically addressed. The pediatric surgical procedures carried out during the initial two months of the Italian lockdown are also reported. Continuity of care was maintained for children affected by severe diseases, such as tumors and neurosurgical conditions, whose treatment could not be deferred. Telemedicine and telecommunication were adopted as quick-support modalities for pre- and post-operative care. This reorganization allowed us to preserve the "pediatric specificity" and all care-related procedures offered at this high-quality/high-volume surgical care referral center.

Esophageal Atresia: Nutritional Status and Energy Metabolism to Maximize Growth Outcome.

BACKGROUND: Long-term negative sequelae of esophageal atresia (EA) may induce poor growth and impaired nutritional status in childhood. We describe the nutritional profile and energy metabolism of children with repaired EA to identify malnutrition risk factors and optimize growth management. METHODS: Twenty-one children (>4 years) were included, and anthropometric measurements, nutritional assessment, and energy metabolism were considered. The subjects were defined as undernourished if they met BMI < -2 standard deviation (SD). To grade undernutrition, we defined the prevalence of underweight, stunting, and wasting (cut-off level of <-2 SD). Medical records were reviewed for the type of EA and surgery and perinatal data. RESULTS: Malnutrition was detected in 28.6% of children. Underweight was detected in 23.8% of patients (all with undernutrition p < 0.01). Wasting was noted in 28.6% of patients, of these 5 children were undernourished (p < 0.001) and stunting was noticed in only one patient with malnutrition (p = 0.5). Resting expenditure energy (REE) was lower in undernourished subjects compared to subjects with adequate nutritional status (p < 0.001). Malnutrition was associated to: type of EA (p = 0.003, particularly type A and C); intervention including deferred anastomosis due to long-gap repair (p = 0.04) with/or without jejunostomy (p = 0.02), gastric pull-up (p = 0.04), primary anastomosis (p = 0.04), pyloromyotomy in long-gap (p < 0.01); small for gestational age condition (p = 0.001). CONCLUSIONS: undernutrition risk factors, beyond the type of malformation, surgery, and perinatal factors, must be early considered to personalize nutritional programming. Energy metabolism is important to monitor the nutritional requirements. The management of nutritional issues is surely a contributory factor able to counteract the poor growth of children with EA.

Evaluation of urinary biomarkers of exposure to benzene: correlation with blood benzene and influence of confounding factors.

PURPOSE: trans,trans-Muconic acid (t,t-MA) is generally considered as a useful biomarker of exposure to benzene. However, because of its lack of specificity, concerns about its value at low level of exposure have recently been raised. The aim of this study was (a) to compare t,t-MA, S-phenylmercapturic acid (SPMA) and benzene (B-U) as urinary biomarkers of exposure to low levels of benzene in petrochemical workers and, (b) to evaluate the influence of sorbic acid (SA) and genetic polymorphisms of biotransformation enzymes on the excretion of these biomarkers. METHOD: A total of 110 workers (including 24 smokers; 2-10 cigarettes/day) accepted to take part in the study. To assess external exposure to benzene, air samples were collected during the whole working period by a passive sampling device attached close to the breathing zone of 98 workers. Benzene was measured in blood (B-B) samples taken at the end of the shift, and was considered as the reference marker of internal dose. Urine was collected at the end of the shift for the determination of B-U, SPMA, t,t-MA, SA and creatinine (cr). B-U and B-B were determined by head-space/GC-MS, SPMA and SA by LC-MS, t,t-MA by HPLC-UV. RESULTS: Most (89%) personal measurements of airborne benzene were below the limit of detection (0.1 ppm); B-B ranged from <0.10 to 13.58 mug/l (median 0.405 microg/l). The median (range) concentrations of the urinary biomarkers were as follows: B-U 0.27 microg/l (<0.10-5.35), t,t-MA 0.060 mg/l (<0.02-0.92), SPMA 1.40 microg/l (0.20-14.70). Urinary SA concentrations ranged between <3 and 2,211 microg/l (median 28.00). Benzene concentration in blood and in urine as well as SPMA, but not t,t-MA, were significantly higher in smokers than in non-smokers. The best correlation between B-B and urinary biomarkers of exposure were obtained with benzene in urine (microg/l r = 0.514, P < 0.001; microg/g cr r = 0.478, P < 0.001) and SPMA (microg/l r = 0.495, P < 0.001; microg/g cr r = 0.426, P < 0.001) followed by t,t-MA (mg/l r = 0.363, P < 0.001; mg/g cr r = 0.300, P = 0.002). SA and t,t-MA were highly correlated (r = 0.618, P < 0.001; corrected for cr r = 0.637). Multiple linear regression showed that the variation of t,t-MA was mostly explained by SA concentration in urine (30% of the explained variance) and by B-B (12%). Variations of SPMA and B-U were explained for 18 and 29%, respectively, by B-B. About 30% of the variance of B-U and SPMA were explained by B-B and smoking status. Genetic polymorphisms for biotransformation enzymes (CYP2E1, EPHX1, GSTM1, GSTT1, GSTP1) did not significantly influence the urinary concentration of any of the three urinary biomarkers at this low level of exposure. CONCLUSION: At low levels of benzene exposure (<0.1 ppm), (1) t,t-MA is definitely not a reliable biomarker of benzene exposure because of the clear influence of SA originating from food, (2) SPMA and B-U reflect the internal dose with almost similar accuracies, (3) genetically based inter-individual variability in urinary excretion of biomarkers seems negligible. It remains to assess which biomarker is the best predictor of health effects.

Management of traumatic complete pancreatic fracture in a child: case report and review of literature.

UNLABELLED: Blunt abdominal trauma is the most common cause of pancreatic injury in children. Laparoscopic distal pancreatectomy in a child with complete duct disruption has not been reported in the literature in children, although it has been well described in adults. METHODS: In this paper report a case of a 7-year-old male, with grade 4 pancreatic trauma, who was treated nonoperatively in the acute phase and subsequently by laparoscopic distal pancreatectomy 3 months after the trauma. DISCUSSION: Although in adults the surgical management of grade 3-4 pancreatic traumatic injury is well described, including the laparoscopic approach, no report of laparoscopic distal pancreatectomy was found in the literature. We would like to emphasize the importance of using a conservative management in the acute phase of pancreatic injury, including grade 4 injuries. After this phase, the use of the high-definition computed tomography scan and endoscopic retrograde pancreatography were fundamental. CONCLUSION: Magnification of laparoscopic technique allowed us to identify the structures much better than open surgery.

Severe Dumping Syndrome in a 6-year-old Girl with Congenital Microgastria Treated by Hunt-Lawrence Pouch.

Microgastria is a rare congenital condition often associated with other anomalies. In the present report we describe the case of a 6-year-old girl with isolated CM who presented with dumping syndrome successfully treated by a Hunt-Lawrence pouch.

Mercapturic acids of styrene in man: comparability of the results obtained by LC/MS/MS and by HPLC-fluorimeter, and stability of samples under different storage conditions.

Two analytical methods (HPLC-fluorimeter [HPLC-FLD] and tandem mass spectrometry LC/MS/MS) are available to assay phenyl-hydroxyethylmercapturic acids (PHEMAs), the mercapturic acids of styrene in humans. In the past, each method was used to check different populations of subjects, but until now no attempt has been made to compare the two methods. This study was designed to verify whether the two methods actually give comparable results. The influence of different conditions of sample storage in altering the concentration of PHEMAs was also investigated. Urine samples were collected at the beginning and at the end of the workshift from 10 workers exposed to different levels of styrene. Each sample was analysed both by LC/MS/MS after storage under different conditions (respectively, at -20 and +4 degrees C, and after repeated freezing-thawing cycles), and by HPLC-FLD (in the same conditions of storage). Strong correlations were found between the two methods both for total PHEMAs and for each of the isomers measured, including the minor (S,R)-M1. Also an alternative approach, the Bland-Altman test, confirmed the agreement between the two methods. The different storage conditions tested did not decrease the concentration of PHEMAs but, surprisingly, a clear trend to increase was shown, particularly for (R,R)-M1, (S,R)-M2 and (R,R)-M2 in samples stored at +4 degrees C for 1 week. In conclusion, the study demonstrates that the methods give comparable results. Indirectly, this confirms also the main characteristics of PHEMAs, showed in the previous experiments: low biotransformation rates of styrene into PHEMAs; large inter-individual variability; and the presence of a clear preference in the excretion of the isomers deriving from (S)-styrene oxide. PHEMAs appear stable under different storage conditions, but further studies are needed to explain the increase of levels that occurs when samples are not kept frozen. To avoid pre-analytical errors, samples collected for biomonitoring or research purposes should be frozen as soon as possible, and thawed only one time just before the analysis.

High-pressure liquid chromatographic-mass spectrometric determination of sorbic acid in urine: verification of formation of trans,trans-muconic acid.

An LC-MS method is described for the determination of urinary sorbic acid (SA), a common food additive, which allows to measure down to 4 microg/L of the compound. The method involves an acidic hydrolysis followed by solid-phase extraction. The method was applied to two volunteers who ingested SA and to 36 individuals with no dietary restriction. The results confirm that a little aliquot of ingested SA is found in urine also in humans. The significant correlation found between urinary levels of SA and trans,trans-muconic acid (MA) seems to indicate that the measurement of SA in urine could allow to estimate the amount of MA excreted following a dietary intake of SA and, consequently, to enhance the specificity of MA as a biomarker of benzene exposure. A point of clarification in future studies will be the actual chemical form of SA excreted, since our results clearly demonstrate that without hydrolysis only a very little amount of SA can be found even in subjects heavily exposed to SA.

Urban air and tobacco smoke in benzene exposure in a cohort of traffic policemen.

Benzene (B) is a typical micro-pollutant present in air, especially urban air. In this study a possible correlation between personal benzene exposure and S-phenylmercapturic acid (S-PMA) as a biomarker of internal dose was evaluated in a cohort of traffic policemen. The results confirm that S-PMA is significantly correlated to benzene measured in personal air. B and S-PMA were analyzed considering seasonality, work quarters, time spent indoors, outdoors, and directing traffic, but no significant differences were recorded.

A case of ultrasound diagnosis of fetal hiatal hernia in late third trimester of pregnancy.

Congenital hiatal hernia is a condition characterized by herniation of the abdominal organs, most commonly the stomach, through a physiological but overlax esophageal hiatus into the thoracic cavity. Prenatal diagnosis of this anomaly is unusual and only eight cases have been reported in the literature. In this paper we describe a case of congenital hiatal hernia that was suspected at ultrasound at 39 weeks' gestation, on the basis of a cystic mass in the posterior mediastinum, juxtaposed to the vertebral body. Postnatal upper gastrointestinal tract series confirmed the prenatal diagnosis. Postnatal management was planned with no urgency. Hiatal hernia is not commonly considered in the differential diagnosis of fetal cystic chest anomalies. This rare case documents the importance of prenatal diagnosis of this anomaly for prenatal counseling and postnatal management.

Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers.

The effect of occupational exposure to styrene on frequencies of chromosomal aberrations and binucleated cells with micronuclei and on single-strand break levels in peripheral blood lymphocytes was studied in 86 reinforced plastic workers and 42 control individuals (including 16 maintenance workers with intermittent, low-dose exposure). In these individuals, the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines were investigated. We assessed the exposure by measuring the concentrations of styrene in air and in blood and of mandelic acid, phenylglyoxylic acid, 4-vinyl phenol conjugates and regioisomeric phenyl hydroxyethyl mercapturic acids in urine. All these parameters correlated with one another. No clear relationship was found between the styrene exposure and the frequencies of chromosomal aberrations. Binucleated cells with micronuclei were moderately related to the parameters of styrene exposure. We found a negative correlation between all exposure parameters and single-strand breaks. The positive correlation between exposure parameters and DNA repair rates suggests that particular DNA repair pathways may be induced by styrene exposure.