Ruth B. Goldstein

Correction of congenital diaphragmatic hernia in utero: VI. hard-earned lessons

Extensive experimental work suggests that repair of congenital diaphragmatic hernia (CDH) in utero may salvage severely affected fetuses who otherwise have a high expected mortality despite optimal postnatal care including extracorporeal membrane oxygenation (ECMO). We have reported that repair of CDH in utero is physiologically sound and safe for the mother, but technically difficult especially when the liver is herniated into the fetal chest. In the 3 years since our last report (1989 to 1991), 61 additional patients were referred for consideration of in utero repair. Fetal repair was attempted in 14 with severe isolated left CDH diagnosed before 24 weeks gestation. Five fetuses died intraoperatively, from technical problems related to reduction of incarcerated liver and uterine contractions--problems which have subsequently been surmounted. Nine patients were successfully repaired. Four babies survived, two delivered prematurely and died, and three died in utero within 48 hours of repair. Intraoperative technical problems have been overcome; the factors limiting successful outcome are postoperative physiologic management of the maternal-fetal unit and effective tocolysis to control preterm labor.

Fetal liver position and perinatal outcome for congenital diaphragmatic hernia

Despite advances in postnatal care, patients born with a congenital diaphragmatic hernia (CDH) suffer substantial morbidity and mortality. The present study was undertaken to determine the prognostic influence of prenatally‐diagnosed liver herniation in the hemithorax in fetuses with CDH.

Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience

Review of our experience with 45 cases of prenatally diagnosed congenital diaphragmatic hernia (CDH) confirms that most fetuses (77%) will not survive despite optimal pre- and postnatal care. Polyhydramnios, associated anomalies, early diagnosis, and a large volume of herniated viscera (including liver) are associated with a particularly dismal prognosis. After extensive experimental work demonstrated the efficacy, feasibility, and safety of repair in utero, we attempted to salvage six highly selected fetuses with severe CDH by open fetal surgery. Five had liver incarcerated in the chest: three died at operation because attempts to reduce the liver compromised umbilical venous return. In one, a Goretex diaphragm was constructed around the liver, but the baby died after birth. The last two fetuses, one with incarcerated liver, were successfully repaired. Both demonstrated rapid growth of the lung in utero, had surprisingly good lung function after birth despite prematurity, had the abdominal patch removed at 2 weeks, and subsequently died of nonpulmonary problems (an unrelated nursery accident in one and intestinal complications in the other). The only maternal complication was amniotic fluid leak and preterm labor. All six women are well and four have had subsequent normal children. From this phase I experience, we conclude that fetal surgery appears safe for the mother and her reproductive potential, that fetal CDH repair is feasible in selected cases, and that the fetal lung responds quickly after decompression. However, fetal repair remains a formidable technical challenge.

Evaluation of the woman with postmenopausal bleeding: Society of radiologists in ultrasound-sponsored consensus conference statement

A panel of 14 physicians practicing medicine in the United States with expertise in radiology, obstetrics and gynecology, gynecologic oncology, hysteroscopy, epidemiology, and pathology was convened by the Society of Radiologists in Ultrasound to discuss the role of sonography in women with postmenopausal bleeding. Broad objectives of this conference were (1) to advance understanding of the utility of different diagnostic techniques for evaluating the endometrium in women with postmenopausal bleeding; (2) to formulate useful and practical guidelines for evaluation of women with postmenopausal bleeding, specifically as it relates to the use of sonography; and (3) to offer suggestions for future research projects.

Fetal intervention in obstructive uropathy: Prognosticindicators and efficacy of intervention

Management of the fetus with bilateral hydronephrosis is controversial; ability to predict outcome and efficacy of prenatal intervention are unknown. We studied 40 fetuses referred for ultrasonography, examination of fetal urine, and possible therapy. We retrospectively assigned fetuses to a good prognosis group if fetal urine was hypotonic (sodium less than 100 mEq/L, chloride less than 90 mEq/L, osmolarity less than 210 mOsm/L) and there was no ultrasonographic evidence of dysplasia; we assigned fetuses to a poor prognosis group if even one criterion was abnormal. Survival was greater in the good prognosis group than in the poor prognosis group (81% vs 12.5%; 87% vs 30%, excluding abortions) (p less than 0.005). We then attempted to assess the efficacy of prenatal urinary decompression by comparing outcome within the good and poor prognosis groups. Survival with intervention was greater in both the good prognosis group and the poor prognosis group (89% vs 70% and 30% vs 0%). In 6 of the 8 survivors in the good prognosis group, severe oligohydramnios was reversed by decompression. We conclude the fetal urine electrolyte levels and ultrasonographic appear helpful in predicting residual fetal renal function and neonatal outcome and that prenatal decompression may prevent the development of fatal pulmonary hypoplasia.

Disappearing fetal lung lesions

Cystic adenomatoid malformations and sequestrations of the lung are uncommon but potentially devastating problems of the fetus and neonate. We have followed over 50 cases of fetal lung masses from the time of prenatal diagnosis. Serial prenatal ultrasonography demonstrated that 9 large pulmonary lesions dramatically decreased in size or disappeared completely. We conclude that the natural history of prenatally diagnosed fetal lung masses is highly variable. A huge mass associated with fetal hydrops has a dismal outcome. If hydrops is not present, then the initial impression concerning prognosis may not accurately predict outcome, because there may be marked improvement during fetal life.

Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: a retrospective study of 60 patients and literature review.

Congenital diaphragmatic defects (CDDs) may occur in malformation syndromes of varied causes. Syndromic cases of CDDs due to chromosomal defects, autosomal recessive, autosomal dominant, or X-linked inheritance have been described. In order to determine the frequency and nature of syndromes, malformations, and chromosome abnormalities associated with CDDs, we reviewed the records of all patients with CDDs evaluated over a 4-year period. During the 4-year interval, a total of 60 patients was evaluated. Of these, 29 had a therapeutic or spontaneous abortion, and 31 received postnatal care. On prenatal ultrasonography, 20 of 60 (33%) of patients with CDDs had additional anomalies. Additional anomalies, besides CDDs, were present in 15 of 31 (48%) of liveborn patients on newborn evaluation. In total, 16 patients with multiple anomalies were evaluated. Of these, 12 of 16 (75%) had additional abnormalities detected by prenatal ultrasonography. The 4 of 16 (25%) without additional anomalies on prenatal sonography had multiple anomalies found neonatally, lethal multiple pterygium syndrome being diagnosed in one case. Prenatal chromosome analysis was performed in 7 of 16 patients, and all had postnatal karyotypes. All initial karyotypes were normal. Tetrasomy 12p was documented on postnatal fibroblast analysis in one case who had percutaneous umbilical blood sampling (PUBS). Syndromes diagnosed postnatally in 7 of 16 patients (44%) include: Fryns syndrome (2), Simpson-Golabi-Behmel syndrome (2), tetrasomy 12p (1), Brachmann-de Lange syndrome (1), and lethal multiple pterygium syndrome (1). We were unable to make a specific diagnosis in 9 of 16 patients (56%) with multiple malformations. In patients with CDDs, a normal prenatal karyotype, especially if obtained by PUBS, and absence of other detected abnormalities by fetal ultrasonography, do not exclude the presence of other major anomalies, including chromosome abnormalities and severe multiple malformation syndromes.

Risk of Thyroid Cancer Based on Thyroid Ultrasound Imaging Characteristics: Results of a Population-Based Study

IMPORTANCE There is wide variation in the management of thyroid nodules identified on ultrasound imaging. OBJECTIVE To quantify the risk of thyroid cancer associated with thyroid nodules based on ultrasound imaging characteristics. METHODS Retrospective case-control study of patients who underwent thyroid ultrasound imaging from January 1, 2000, through March 30, 2005. Thyroid cancers were identified through linkage with the California Cancer Registry. RESULTS A total of 8806 patients underwent 11,618 thyroid ultrasound examinations during the study period, including 105 subsequently diagnosed as having thyroid cancer. Thyroid nodules were common in patients diagnosed as having cancer (96.9%) and patients not diagnosed as having thyroid cancer (56.4%). Three ultrasound nodule characteristics--microcalcifications (odds ratio [OR], 8.1; 95% CI, 3.8-17.3), size greater than 2 cm (OR, 3.6; 95% CI, 1.7-7.6), and an entirely solid composition (OR, 4.0; 95% CI, 1.7-9.2)--were the only findings associated with the risk of thyroid cancer. If 1 characteristic is used as an indication for biopsy, most cases of thyroid cancer would be detected (sensitivity, 0.88; 95% CI, 0.80-0.94), with a high false-positive rate (0.44; 95% CI, 0.43-0.45) and a low positive likelihood ratio (2.0; 95% CI, 1.8-2.2), and 56 biopsies will be performed per cancer diagnosed. If 2 characteristics were required for biopsy, the sensitivity and false-positive rates would be lower (sensitivity, 0.52; 95% CI, 0.42-0.62; false-positive rate, 0.07; 95% CI, 0.07-0.08), the positive likelihood ratio would be higher (7.1; 95% CI, 6.2-8.2), and only 16 biopsies will be performed per cancer diagnosed. Compared with performing biopsy of all thyroid nodules larger than 5 mm, adoption of this more stringent rule requiring 2 abnormal nodule characteristics to prompt biopsy would reduce unnecessary biopsies by 90% while maintaining a low risk of cancer (5 per 1000 patients for whom biopsy is deferred). CONCLUSIONS AND RELEVANCE Thyroid ultrasound imaging could be used to identify patients who have a low risk of cancer for whom biopsy could be deferred. On the basis of these results, these findings should be validated in a large prospective cohort.

Prenatal diagnosis of esophageal atresia

The prenatal sonographic detection of esophageal atresia (EA) has been possible for more than a decade and relies on the finding of a small or absent fetal stomach bubble associated with maternal polyhydramnios. The aims of this study were to assess the accuracy of this technique and to determine whether the outcome of prenatally diagnosed EA differs from its postnatal counterpart. All fetal sonograms performed between January 1989 and October 1993 demonstrating a small or absent fetal gastric bubble were reviewed together with all neonates with EA treated during the same period. Eighty-seven fetuses with a small (n = 53) or absent stomach bubble (n = 34) were identified, representing 1.4% of all fetal sonographic surveys. Esophageal atresia was present in 15; in 13 of these, the maternal amniotic fluid volume was increased. The positive predictive value of an absent stomach bubble and polyhydramnios was 56%, and the sensitivity of prenatal sonography in the diagnosis of EA was 42%. One neonate with EA had the prenatal diagnosis established at another institution, yielding a total of 16 cases of prenatally diagnosed EA for analysis. Seven (44%) of these had trisomy 18. Of the remaining nine, two had isolated EA, two had laryngeal atresia and EA, and there were two late-gestational unexplained fetal deaths. Only four (25%) survived through the neonatal period. The prognosis of the fetus with EA is radically different from that of the neonate with EA.

Fetal Magnetic Resonance Imaging in the Evaluation of Fetuses Referred for Sonographically Suspected Abnormalities of the Corpus Callosum

Fetal magnetic resonance imaging (MRI) has been shown to be useful in assessing the developing central nervous system. However, its utility in specific brain disorders has not been well investigated. We hypothesized that fetal MRI can better assess the integrity of the brain in cases with sonographically suspected callosal abnormalities.