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Biomedical subjects

C Garel

Publications and source records attributed to C Garel.

At least 19 recordsLinked to original sources

Third-trimester fetal MRI in isolated 10- to 12-mm ventriculomegaly: is it worth it?

OBJECTIVE: The justification for magnetic resonance imaging (MRI) in isolated mild ventriculomegaly remains controversial. This study was undertaken to evaluate the contribution of third-trimester MRI in isolated 10- to 12-mm fetal ventriculomegaly. DESIGN: Observational prospective cohort study. SETTING: Universitary prenatal reference centre. POPULATION: From February 2000 to May 2005, we prospectively collected data concerning fetuses referred to us for cerebral MRI following detection of ventriculomegaly by ultrasound scan (n= 310). METHODS: Among these, we identified and analysed those cases in which ventriculomegaly was isolated and did not exceed 12 mm in ultrasound examinations prior to MRI scan (n= 185). MAIN OUTCOME MEASURE: Cases in which MRI provided additional information that was likely to have an impact on prenatal management were detailed. RESULTS: During the study period, 310 MRI were performed because of fetal ventriculomegaly. Hundred and eighty-five were suspected to be isolated 10- to 12-mm ventriculomegalies in ultrasound scan and formed our database. MRI confirmed the 10- to 12-mm isolated fetal ventriculomegaly in 106 cases (57.3%) and found other abnormalities in 5 (4.7%) of these 106 cases. MRI found ventricular measurement to be less than 10 mm in 43 cases (23.3%) and more than 12 mm in 36 cases (19.4%). Among these 36 fetuses with ventricle size more than 12 mm, 6 (16.7%) had other abnormalities, whereas MRI did not find other abnormalities in the 43 cases with ventricle size below 10 mm. CONCLUSION: Before advantages of MRI to ultrasound examination can be demonstrated, it seems reasonable that MRI should remain an investigational tool, restricted to selected clinical situations in which the results are expected to modify case management. Where ultrasound scan suspects isolated ventriculomegaly of 10 to 12 mm, our data suggest that when the finding is confirmed with MRI this could be expected in around 5% of cases. Therefore, the policy of routine MRI in such cases should depend on prenatal centres' priorities.

Brain Edema↗

Hyper-echogenic colon: a prenatal sign of cystinuria?

We suggest the term 'hyper-echogenic colon' to describe a hyperechoic foetal colonic content with no other intestinal abnormality. This is a rare pattern, which to our knowledge, has never been correlated with a specific pathology. The accidental observation of a cystine kidney stone in an infant who presented with this sign during the prenatal period made it possible to diagnose this disease retrospectively in two other children.

Adult↗

Coronal measurement of the fetal lateral ventricles: comparison between ultrasonography and magnetic resonance imaging.

OBJECTIVE: Cerebral ventricular atrial diameter is routinely measured on fetal ultrasound examination and magnetic resonance imaging (MRI); however, the methods have not been compared prospectively. The aim of this study was to evaluate the agreement between fetal ultrasonography and MRI in the measurement of atrial diameter on a coronal slice. MATERIALS AND METHODS: Measurements of both lateral ventricles were performed prospectively in 106 fetuses using ultrasonography and MRI on the same day. In 39 of these fetuses, MRI was performed following the detection of ventriculomegaly on ultrasound examination. The median gestational age was 32 weeks. The following factors were recorded: the fetal position, the ventricular location (deep or superficial) and the ultrasound approach (transfontanellar or not). The measurements were performed on a coronal slice at the level of the choroid plexuses using both techniques. RESULTS: The two techniques yielded results in close agreement, independently of the three factors noted above. Ventricular atrial diameters below 10 mm tended to be slightly overestimated by ultrasonography, whereas those above 10 mm tended to be underestimated in comparison to measurements by MRI. CONCLUSIONS: Coronal measurements of the atrial diameter of both cerebral ventricles, whether deep or superficial, are similar when obtained by ultrasonography and MRI. This agreement does not appear to be influenced by the position of the fetal head or by the ultrasound approach (transfontanellar or otherwise) used.

Female↗

Meckel-Grüber syndrome: sonography and pathology.

OBJECTIVE: To define a specific sonographic pattern for the appearance of the kidneys in fetuses affected by Meckel-Grüber syndrome (MGS). METHODS: This was a retrospective analysis of 30 cases, collected from five centers, with ultrasound features suggestive of MGS. Only fetuses with a confirmed diagnosis of MGS were finally included. Analysis included a detailed evaluation of the sonographic findings and comparison with pathological follow-up. RESULTS: Seventeen cases met the pathological criteria for a diagnosis of MGS and were included in the study. In all cases, a typical sonographic pattern was seen: the kidneys were enlarged (mean, + 4.8 SD) and showed unusual corticomedullary differentiation, occurring as early as the first trimester. In most cases, the medullary areas appeared excessively large and mottled due to the presence of multiple small cysts. CONCLUSIONS: The kidneys of fetuses with MGS are enlarged, cystic and have unusual corticomedullary differentiation. These features can be observed as early as the first and early second trimesters.

Central Nervous System↗

Contribution of fetal magnetic resonance imaging and amniotic fluid digestive enzyme assays to the evaluation of gastrointestinal tract abnormalities.

OBJECTIVE: To analyze the contribution of fetal magnetic resonance imaging (MRI) and amniotic fluid digestive enzyme (AFDE) assays to the evaluation of gastrointestinal tract abnormalities. METHODS: This was a prospective study involving 24 fetuses suspected of having gastrointestinal tract abnormalities on ultrasound examination. MRI was used to analyze the location of the obstruction, the visibility of the small bowel not involved in the obstruction, and the visibility and size of the colon and rectum. Abnormalities were further evaluated by AFDE assays. The final diagnosis was based on postnatal or fetopathological examination. RESULTS: In duodenojejunal obstructions, MRI (6/6) and AFDE assays (4/4) correctly identified the level of obstruction, but were less accurate for small bowel obstructions (MRI, 10/11; AFDE assays, 7/11). The small bowel not involved in the obstruction was correctly evaluated by MRI as being viable in six cases and as abnormal in eight cases (multiple obstructions or necrosis). However, it was thought antenatally to be abnormal by MRI in four cases in which it was found to be normal on postnatal findings. Three cases in which the colon was found to have abnormal echogenicity were considered normal both by MRI and AFDE assay, in agreement with postnatal findings. Two cases of microcolon-megacystis-intestinal hypoperistalsis syndrome (MMIHS) were diagnosed both by MRI and AFDE assay. Of the three anorectal malformations, two were overlooked by ultrasonography and one by MRI. MRI also overlooked 2/3 associated rectourethral fistulas. CONCLUSION: MRI and enzyme analysis are good complementary tools to ultrasonography for identifying the level of gastrointestinal obstruction and diagnosing MMIHS. MRI can assess the normality of the intestinal tract not involved in the obstruction, but not multiple obstructions, necrosis and small urodigestive fistulas.

Amniotic Fluid↗

Prenatal isolated mild ventriculomegaly: outcome in 167 cases.

OBJECTIVE: To define the contribution of prenatal investigation and evaluate the prognosis of isolated mild ventriculomegaly (IMV). DESIGN: Retrospective study. SETTING: University hospital between January 1992 and December 2002. POPULATION: One hundred and sixty-seven cases of prenatal unilateral or bilateral IMV without any associated anomaly at the time of initial diagnosis. METHODS: Complementary investigations were performed: amniocentesis with karyotyping, screening for viruses and acetylcholinesterase electrophoresis, magnetic resonance imaging (MRI), and ultrasonography every 3-4 weeks. MAIN OUTCOME MEASURES: Results of prenatal investigations, pregnancy outcome, and postnatal psychomotor development. RESULTS: IMV was diagnosed around 26.5 weeks. Amniocentesis revealed four chromosomal anomalies and two cytomegalovirus infections. MRI diagnosed brain-associated anomalies in 15 cases and ultrasonographic monitoring highlighted malformations not initially diagnosed in 28 cases. Termination of pregnancy (TOP) was considered in 21 pregnancies (12.6%). Indications were aneuploidy, fetal infectious disease or associated malformations. In women for whom a TOP was considered, consanguinity, fetus of female sex and frontal horn enlargement were statistically more frequent, ventriculomegaly was more often bilateral and asymmetrical, atrial width, and the rate of progressive ventricular enlargement were significantly higher. One hundred and one children with prenatal IMV were assessed between 19 and 127 months (mean age 54.68 +/- 2.87 months). Twelve children had neurological disease or psychomotor delay and 89 children had a normal psychomotor development. Poor neurological outcome was more often associated with atrial width greater than or equal to 12 mm, asymmetrical bilateral enlargement, and progression of the ventriculomegaly. CONCLUSION: The detection of IMV raises the question of the child's psychomotor development and justifies meticulous prenatal investigation. In addition to associated anomalies, three criteria are often associated with an unfavourable outcome: atrial width greater than 12 mm, progression of the enlargement, and asymmetrical and bilateral ventriculomegaly.

Adult↗

Fetal cerebral biometry: normal parenchymal findings and ventricular size.

Assessing fetal cerebral biometry is one means of ascertaining that the development of the fetal central nervous system is normal. Norms have been established on large cohorts of fetuses by sonographic and neurofetopathological studies. Biometric standards have been established in MR in much smaller cohorts. The purpose of this paper is to analyse methods of measuring a few parameters in MR [biparietal diameter (BPD), fronto-occipital diameter (FOD), length of the corpus callosum (LCC), atrial diameter, transverse cerebellar diameter, height, anteroposterior diameter and surface of the vermis] and to compare US and MR in the assessment of fetal cerebral biometry.

Biometry↗

Prenatal diagnosis of a cystic type IV sacrococcygeal teratoma mimicking a cloacal anomaly: contribution of MR.

OBJECTIVE: To report a case of pelvic midline cystic mass in a female fetus without visibility of the rectum and which is not a cloacal anomaly. METHODS: Ultrasound (US) and magnetic resonance imaging (MRI) were performed respectively at 27 and 27.5 weeks' gestation and the findings of these examinations were compared with post-mortem examination after termination of pregnancy (TOP). RESULTS: US showed a pelvic midline cystic mass in a female fetus with mild enlargement of the left ureter and renal pelvis. MRI did not show the T1 hypersignal of meconium in the rectum. The analysis of MR findings were suggestive of the diagnosis of a sacrococcygeal teratoma. Pregnancy was terminated because of the possibility of severe sphincterial disorders and the fetopathological examination confirmed this diagnosis. CONCLUSION: This observation illustrates the diagnostic problems generated by the detection of a pelvic midline cystic mass in a female fetus. The absence of visibility of the T1 hypersignal of the meconium in the rectum is traditionally supposed to be highly suggestive of a cloaca, but may also be explained by the emptiness of the rectum, compressed by the mass.

Adult↗

Pial arteriovenous fistulas: dilemmas in prenatal diagnosis, counseling and postnatal treatment. Report of three cases.

We report three cases of the antenatal appearance of a pial arteriovenous fistula (AVF). In Case 1, the diagnosis of pial AVF was made by ultrasound examination at 32 + 3 weeks of gestation and confirmed by magnetic resonance imaging (MRI) at 34 + 3 weeks of gestation. After birth, the neonate had cardiac insufficiency and an embolization was performed 8 days postpartum which was followed by extended cerebral ischemia and death. In Cases 2 and 3 pial fistulae were diagnosed at birth. In Case 2, the patient was referred following the diagnosis of an aneurysmal malformation of the vein of Galen at 38 weeks of gestation. Owing to immediate delivery following her transfer, no ultrasound examination was performed and the diagnosis of pial AVF was established on the first postnatal day. An embolization was performed and the child is doing well. Case 3 presented with cardiomegaly at 30 weeks of gestation and cerebral ischemic lesions after birth. These cases highlight the difficulties encountered in the prenatal diagnosis of pial AVFs. The diagnosis should be considered in cases of unexplained cardiomegaly and it is also important to make sure that AVFs draining into the vein of Galen are not misdiagnosed as aneurysmal malformations of this vein. The complications of pial AVFs are cardiac failure and cerebral ischemia. Embolization is the treatment of choice; however it is a risky procedure in neonates.

Adult↗

Prenatal prognosis of congenital diaphragmatic hernia using magnetic resonance imaging measurement of fetal lung volume.

OBJECTIVES: To investigate the correlation between fetal lung volume (FLV), measured with magnetic resonance imaging (MRI), and postnatal mortality in newborns with prenatally diagnosed isolated congenital diaphragmatic hernia (CDH). METHODS: In a 4-year prospective multicenter study, 77 fetuses with isolated CDH diagnosed between 20 and 33 weeks' gestation underwent fast spin-echo T2-weighted lung MRI. These MRI-FLV measurements were compared with a previously published normative curve obtained in 215 fetuses without thoracoabdominal malformations and with normal ultrasound biometric findings. FLV measurements were correlated with postnatal survival. The mean gestational age at MRI was 31.3 weeks. RESULTS: The measured/expected FLV ratio was significantly lower in the newborns with CDH who died compared with those who survived (23.6 +/- 12.2 vs. 36.1 +/- 13.0, P < 0.001). When the ratio was below 25%, there was a significant decrease in postnatal survival (19% vs. 40.3%, P = 0.008). Survival was significantly lower for neonates when one lung could not be seen by fetal MRI compared with those fetuses with two visible lungs on MRI (17.9% vs. 62.1%, P < 0.001). CONCLUSION: In isolated CDH, FLV measurement by MRI is a good predictor of postnatal mortality due to pulmonary hypoplasia.

Female↗

Laparoscopic approach as primary treatment of common bile duct stones in children.

BACKGROUND: Preoperative endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy (ES) are an effective strategy for choledocholithiasis, but complications such as pancreatitis and outcome in children are unknown. The laparoscopic cholecystectomy became the new gold standard in children for cholelithiasis. For the choledocholithiasis in children, the attitude is more controversial. We analyzed our series of laparoscopic approach for the management of choledocholithiasis in children to determine if it is an effective procedure. PATIENTS AND METHOD: Between 1996 and 2001, 126 children were treated for cholelithiasis in our institution; 13 children (10.3%) were managed for a choledocholithiasis. We reviewed age at symptom onset results of paraclinical examinations, the type of laparoscopic management, and postoperative outcome. RESULTS: The mean age at clinical signs was 9.9 years (range, 3 months-15.5 years). One child was excluded because he had a preoperative ES. Twelve children had a laparoscopic cholecystectomy and cholangiogram at the same time. A choledocholithiasis was found in 10 cases. A flush of the common bile duct (CBD) was performed in all cases with a 3F or 5F ureteral catheter; the stone was pushed into the duodenum in 3 cases and successfully extracted in 3 with a 4F Dormia or Fogarty catheter. One child needed a conversion to open surgery. Three times, an ES was necessary in postoperative course in each case for clinical and biologic signs of CBD obstruction or pancreatitis (30%). All children are symptom-free with an average follow-up of 28 months. CONCLUSION: Laparoscopic CBD exploration for choledocholithiasis can be performed safely in children at the time of cholecystectomy and can clear all of the stones in the CBD in two thirds of cases. If there is residual obstruction, a postoperative ES can be performed. We suggest primary treatment of choledocholithiasis by laparoscopic approach in children.

Adolescent↗

[Gartner's cyst communicating with the bladder and vagina with associated complete vaginal diaphragm].

Gartner's duct cyst is a relatively common benign cystic lesion and represents embryologic remnants of Wolffian ducts. These cysts are usually small and asymptomatic and have been reported to occur in as many as 1% of all women. We report a case of a 30 month old baby presenting with recurrent urinary tract infection and Gartner's duct cyst communicating with the vagina and bladder with associated complete vaginal diaphragm. The diagnosis of Gartner's duct cyst was suggested by pelvic ultrasonography and MR imaging. Vaginal diaphragm and communication between the Gartner's cyst, the bladder and vagina were established during cystoscopy and vaginoscopy.

Child, Preschool↗

[Fetal thoracic MRI].

Fetal thoracic MR includes the study of the lungs and the mediastinum. Fetal lungs are T2 hyperintense because of their high water contents and are clearly delineated. Their volume can be measured with MR and normal data have been published. The evaluation of the fetal lung volume is of paramount importance in the case of suspected pulmonary hypoplasia. MR is contributive in the analysis of diaphragmatic hernias to assess the diagnosis, to detail the herniated abdominal contents and in a less extent, to predict outcome. In most of the cases, MR does not provide additional information (compared to US) in the evaluation of bronchopulmonary sequestrations or congenital cystic adenomatoid malformations. Pulmonary arteries and veins are currently poorly visualized. MR seems to be an accurate modality to assess the diagnosis of esophageal atresia.

Female↗

[Ductus venosus agenesis].

OBJECTIVE: Congenital absence of the ductus venosus is a rare anomaly in the fetus. The aim of our study was to evaluate the clinical and ultrasonographic features and outcome of the fetuses with ductus venosus agenesis. STUDY DESIGN: We describe 12 cases in the period between 1992 and 2004. The umbilical vein drained either into the right atrium directly (2 cases) or by the coronary sinus (1 case), or in the inferior vena cava (5 cases), or in the azygos vein (1 case), or in the portal vein (3 cases). Our data where analyzed with the cases published in the literature. Two groups of anastomoses where defined on the basis of the hemodynamic consequences: the group of extrahepatic anastomoses (53 cases) and the group of intrahepatic anastomoses (22 cases). RESULTS: In the group of extra hepatic anastomoses, cardiomegaly was the most common antenatal finding (39%), while in the intra hepatic group hydrops fetalis occurred most frequently (23%). Malformation rate was high in both groups (56% and 45%) and chromosomal anomalies where present in 9% of cases. CONCLUSION: Careful assessment of the umbilical venous return and the ductus venosus should be a part of examination of every fetus with cardiomegaly, polyhydramnios, ascites or hydrops. In case of absence of the ductus venosus a referral scan, a fetal echocardiography and a karyotype should be performed.

Autopsy↗

Left thoracoscopic thymectomy in children.

BACKGROUND: In the management of autoimmune myasthenia, thymectomy is recognized as effective surgical therapy. The necessity of complete radical thymectomy to achieve maximal improvement has been emphasized. Video-assisted thoracoscopic surgery has been successfully used for thymectomy in adults, and more recently in children, and has been described as achieving the same radicality and functional improvement as median sternotomy or as transcervical thymectomy. The aim of this work is to report our first thoracoscopic experience in this indication. METHODS: Patients with myasthenia gravis on anticholinesterase drugs and/or steroids are discussed for surgery in case of clinical deterioration despite increasing doses of medication or in case of no improvement. We decided to perform thoracoscopic thymectomies by a left-sided approach. Preoperative localization of thymic tissue is done by a thoracic CT exam. Patients are placed on their right side with a thoracic tilt under the thorax. Four thoracoscopic ports are used, a 10-mm for the camera and three 5-mm operating ports. The left lung was collapsed by selective intubation (double-lumen endotrachial intubation). RESULTS: Two boys, 7.5 and 14 years old, were addressed by the department of neurology for radical thymectomy. They presented an ocular myasthenia gravis for 2 years and a mild general myasthenia gravis for 7 years. The operative times were 120 and 240 min. There was no intraoperative or postoperative complication. Duration of thoracic drainage was 2 days. The children were discharged on the third postoperative day. For the second procedure, an ultrasound exam during surgery was necessary to localize the thymus exactly, thus enabling its complete resection without the need for a conversion. The follow-up is 19 and 7 months with a clinical improvement enabling the diminution of medication for both children, the end of ptosis for the first child, and the general improvement of muscle strength for the second. CONCLUSIONS: Thoracoscopic thymectomy in children with juvenile myasthenia gravis seems to offer a complete surgical resection, as do open techniques. In case of difficulties in finding the thymus, an ultrasound exam is feasible to enable complete resection. The left-sided thoracoscopic approach gives a good mediastinal and cervical exposition. Furthermore, being less painful in the postoperative period, it presents a less pronounced impairment of pulmonary function, and it presents good cosmetic effect.

Adolescent↗

Laparoscopic adrenal surgery for neuroblastomas in children.

PURPOSE: The role of laparoscopy in children with neuroblastomas has not been fully defined. The laparoscopic approach to the adrenal gland is already largely used in adults and a few cases have been reported in children. We report the experience of a single surgical team center with laparoscopic adrenal surgery for neuroblastomas in children. MATERIALS AND METHODS: Between September 2000 and October 2002 laparoscopic adrenalectomy for neuroblastoma was performed in 9 patients (6 girls and 3 boys) with a mean age of 38 months (range 2 months to 9 years). Two tumors were detected prenatally and 7 postnatally. Preoperative diagnosis was neuroblastoma stage I in 4 cases and stage IV in 3 cases, and nondetermined suprarenal calcified masses in 2 cases. A 4 or 5-trocar transperitoneal approach was used in all cases. The adrenal tumors were completely excised, placed into a plastic bag and removed through the umbilical trocar site. RESULTS: All of the adrenal tumors were well encapsulated and completely excised. One of the 9 procedures was converted to open surgery because of adhesions to renal vessels. In 1 case a second hepatic localization was removed simultaneously, and in 3 cases 1 or more lymph nodes were resected. Average operative time was 85 minutes (range 45 to 170). There were no deaths. There were no postoperative complications, except 1 port site infection that was treated locally. Blood transfusion was not required. Average hospital stay was 4.5 days (range 2 to 10). Histological analysis of the 9 specimens (maximum length 6 cm) confirmed the diagnosis of neuroblastoma. N-myc status was studied in 8 of the 9 resected neuroblastomas and was amplified in 2 cases (both stage IV with preoperative biopsy). Average postoperative followup was 15 months (range 1 to 25). There was no local recurrence or metastasis, except in the case that required conversion to open surgery (local recurrence 7 months later). CONCLUSIONS: Laparoscopic adrenalectomy for neuroblastoma is safe and feasible in children, with good results. Experience with advanced laparoscopic surgery is required to achieve this result in optimal oncological conditions. Our short-term results must be reevaluated at long term, and further studies are needed to compare laparoscopy to open surgical techniques.

Adrenal Gland Neoplasms↗

Scintigraphic screening for renal damage in siblings of children with symptomatic primary vesico-ureteric reflux.

OBJECTIVE: To define prospectively the incidence of renal parenchymal lesions in the siblings of patients treated at one institution for primary vesico-ureteric reflux (VUR). PATIENTS AND METHODS: From January 1997 to October 1998, a prospective study including renal scintigraphy (using dimercaptosuccinic acid, DMSA) and a radionuclide cystogram was proposed systematically to the asymptomatic siblings of children treated for primary VUR. The radionuclide cystograms were interpreted as showing the presence or absence of VUR and the DMSA scan as symmetrical or asymmetrical differential function, with or with no renal defect. RESULTS: Fifty-five families gave informed consent, of whom 46 completed the study (eight refused secondarily and one was omitted by exclusion criteria), representing 46 symptomatic patients and 65 siblings. There were 17 siblings with VUR (26%) including two of 13 infants and 15 of 52 children aged > 18 months. One radionuclide cystogram failed. Of the 17 refluxing siblings, four had a history of symptomatic urinary tract infection; 62 of the 65 siblings had a DMSA scan, of which 56 were normal and six (10%) showed abnormalities (five asymmetrical differential function and one parenchymal defect). Only one of these six patients had VUR at the time of the evaluation and only one had a small kidney detected by ultrasonography on one side (and no VUR). There were no adverse effects associated with screening. CONCLUSION: This study confirms a significant overall incidence of VUR (26%) in the asymptomatic siblings of patients treated for primary VUR. From the results of the DMSA scan (only one sibling had a parenchymal defect), the systematic screening of asymptomatic siblings does not appear to be beneficial.

Adolescent↗

Postnatal management of cystic neuroblastoma.

Cystic adrenal neuroblastoma (NB) is highly unusual. We report two cases of cystic NB, detected antenatally and emphasize postnatal strategy management. Case 1: a right cystic mass was detected in a foetus in the 34th week of pregnancy, and checked as the same in the 36th week. Postnatal ultrasonography confirmed the presence of a growing adrenal cystic mass. MRI and MIBG scintigraphy suggested an isolated adrenal tumour, without catecholamine secretion. Surgical resection was decided upon and pathological examination confirmed the diagnosis of cystic NB. Follow-up found a recurrence at 10 months and the patient underwent excision after chemotherapy. Histology confirmed the metastatic origin from NB. Case 2: a right adrenal cystic mass was detected during pregnancy, with no regression of tumour size on postnatal US. MRI, MIBG scintigraphy, and catechol plasma and urinalysis led to the conclusion of an isolated non-secreting lesion. A right adrenalectomy was performed at 1 month. Pathologic examination diagnosed a cystic NB. We would suggest serial US examinations and early removal of any cystic mass with characteristic US signs (thick complex wall) or without regression on one month follow-up. Prenatal diagnosis may provide the best chances for neonatal excision and good prognosis.

Adrenal Gland Neoplasms↗