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Biomedical subjects

T M Crombleholme

Publications and source records attributed to T M Crombleholme.

At least 37 records · Page 2Linked to original sources

Adenoviral-mediated overexpression of platelet-derived growth factor-B corrects ischemic impaired wound healing.

Chronic wounds represent a major clinical problem with significant morbidity and healthcare expenditures, but no effective therapies. Topical platelet-derived growth factor-BB trials have required large and repeated doses to achieve only a modest effect. We examined the ability of an adenovirus containing the platelet-derived growth factor-B transgene to improve the rate of wound healing through induction of platelet-derived growth factor-B overexpression in cells participating in the wound healing response. We treated excisional wounds in the ischemic rabbit ear, which have a 60% delay in healing, with vehicle, 106, or 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B per wound (n = 19). At 7 d this resulted in a decrease in the epithelial gap from 3.4 +/- 1 mm (mean +/- SD) in vehicle-treated wounds to 1.9 +/- 1.8 mm (mean +/- SD, p < 0.05) when treated with 106 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B, and 0.7 +/- 1.1 mm (mean +/- SD, p < 0.001) when treated with 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B. Ischemic excisional wounds treated with 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B even healed more rapidly than non-ischemic excisional wounds treated with vehicle (p < 0.05). In contrast, 5 microg of platelet-derived growth factor-BB protein (n = 2) resulted in only modest granulation tissue at the margin, but no significant differences in epithelial gap (3 +/- 0.6 mm, mean +/- SD). Plaque-forming units (106 or 108) of an adenovirus containing the beta-galactosidase transgene (n = 4) impaired wound re-epithelialization with an epithelial gap of 5.11 +/- 0.69 mm, mean +/- SD, p < 0.004, and 3.8 +/- 0.57 mm, mean +/- SD, p < 0.07, respectively. Adenoviral-mediated gene transfer of platelet-derived growth factor-B overcame the ischemic defect in wound healing and offers promise in the treatment of chronic nonhealing wounds. The vulnerary effects of platelet-derived growth factor-B overexpression were sufficient to overcome the adverse effects of the adenovirus or transgene on wound healing.

Adenoviridae↗

Prenatal MRI evaluation of congenital diaphragmatic hernia.

The objective of this paper is to evaluate the efficacy of various magnetic resonance imaging (MRI) sequences and the general usefulness of prenatal MRI in determining the position of the fetal liver and visualizing lung tissue in fetuses who have congenital diaphragmatic hernia (CDH). This was a retrospective review of prenatal MRI of fetuses with a confirmed diagnosis by surgery or autopsy of CDH. MRI was performed in a 1.5-Tesla magnet using fast gradient echo, half-Fourier single-shot turbo spin-echo (HASTE) and echo planar images. The presence of a chest mass, position of the stomach and liver and visualization of the lungs by MRI was noted in all fetuses. This was compared to ultrasound studies performed the same day and correlated with postnatal or autopsy studies. The fetuses were 18-36 weeks gestational age (mean 24.5 weeks). MRI diagnosed left CDH (33), right CDH (4), and bilateral CDH (1) and agreed with the postnatal diagnosis in all patients. Ultrasound (US) diagnosed left CDH (33), right CDH (2), and congenital cystic adenomatoid malformation (3). MRI changed the diagnosis in four patients. The fetal liver was easily demonstrated with MRI in all fetuses and was herniated into the chest in 25 of the 38. US diagnosed liver up in 21. Correlation with postnatal studies found MRI correctly diagnosed liver position in 37 out of 38 cases. US correctly diagnosed liver position in 32 out of 38. Both lungs could be visualized in all fetuses with MRI. MRI accurately and easily diagnoses CDH and can differentiate it from other chest masses. MRI was superior to US in demonstrating the position of the fetal liver above or below the diaphragm. MRI reliably visualized fetal lung tissue. These findings are important for counseling parents, selecting fetal surgical candidates, and estimating prognosis.

Adult↗

Congenital chest lesions: diagnosis and characterization with prenatal MR imaging.

PURPOSE: To evaluate prenatal magnetic resonance (MR) imaging for diagnosis of fetal chest masses and to determine if MR imaging provides information in addition to that of ultrasonography (US). MATERIALS AND METHODS: Eighteen pregnant women were referred for MR imaging of possible fetal chest tumors seen at US (16 congenital cystic adenomatoid malformation [CCAM], two bronchopulmonary sequestration [BPS]). The presence, position, size, and characteristics of masses were determined and correlated with postnatal results. RESULTS: The MR imaging diagnoses were three cases of congenital diaphragmatic hernia, nine of CCAM, two of BPS, and one each of foregut cyst, lung atresia, tracheal atresia, and bronchial stenosis. MR imaging results were in agreement with US results in nine fetuses and in disagreement in nine. MR imaging diagnoses were confirmed at surgery or autopsy in 17 fetuses. MR imaging results led to an error in diagnosis in one fetus with BPS. CONCLUSION: Fetal chest masses had characteristic MR imaging appearances. MR imaging was accurate for distinguishing congenital diaphragmatic hernia from CCAM and was useful for less common diagnoses and determination of the origin of very large chest tumors. Prenatal diagnosis was changed in some patients owing to MR results and affected treatment and counseling of parents. MR imaging is a valuable adjunct to US for prenatal diagnosis of fetal chest masses.

Bronchopulmonary Sequestration↗

Diminished interleukin-8 (IL-8) production in the fetal wound healing response.

BACKGROUND: Fetal skin wound healing results in scarless repair with minimal cellular inflammatory response. Interleukin-8 (IL-8) stimulates inflammation in postnatal wound healing but little is known about its role in fetal wounds. We hypothesized that fetal tissues have diminished IL-8 during wound repair and in response to platelet-derived growth factor (PDGF), a growth factor central to wound healing. MATERIALS AND METHODS: To examine the IL-8 response of fibroblasts to PDGF, cultures of human fetal (17-18 weeks) and adult dermal fibroblasts were incubated 8 h with PDGF (0, 0.1, 1, or 10 ng/mL) and supernatants and cells were collected for IL-8 ELISA and IL-8 RT-PCR. To evaluate the IL-8 response to wounding, human adult and fetal skin was placed subcutaneously in the SCID mouse, wounded, and the wound cleft excised after 4, 12, 24, or 72 h for IL-8 RT-PCR. RESULTS: Fetal fibroblasts produced less IL-8 protein at baseline (50 +/- 6 pg/mL versus 450 +/- 115 pg/mL, P < 0.001) and in response to all concentrations of PDGF examined (P < 0.001). IL-8 mRNA was detected in unstimulated adult fibroblasts but not in fetal fibroblasts. Much less IL-8 mRNA was detected in stimulated fetal fibroblasts than in adult fibroblasts. IL-8 mRNA was detected 4 h after wounding in fetal and adult wounds. By 12 h no IL-8 mRNA was detected in fetal wounds, whereas adult wounds had IL-8 mRNA persisting to 72 h. CONCLUSIONS: Diminished inflammatory cytokine response by fetal tissues may be responsible for the lack of cellular recruitment and inflammation seen in fetal wound healing and may contribute to scarless wound repair.

Adult↗

Fetal lung lesions: management and outcome.

OBJECTIVE: Our purpose was to review our experience with fetal congenital cystic adenomatoid malformation and extralobar pulmonary sequestration emphasizing natural history, management, and outcome. STUDY DESIGN: We conducted a retrospective review of 175 fetal lung lesions diagnosed by antenatal ultrasonography at 2 fetal treatment centers. RESULTS: There were 134 congenital cystic adenomatoid malformation cases. Fourteen women underwent elective abortion, 101 women were managed expectantly, 13 women had fetal surgery, and 6 women had placement of a thoracoamniotic shunt. For the congenital cystic adenomatoid malformation lesions that were not associated with nonimmune hydrops, all babies survived. Of 25 large congenital cystic adenomatoid malformations that had associated hydrops that were followed expectantly, all fetuses died before or shortly after birth. Fetal surgical resection of the tumor (fetal lobectomy) was performed at 21 to 29 weeks' gestation in 13 hydropic fetuses with 8 fetuses continuing gestation with subsequent hydrops resolution, impressive in utero lung growth, and neonatal survival. Six fetuses with a very large solitary cyst underwent thoracoamniotic shunting and 5 survived. There were 41 extralobar pulmonary sequestration cases. Twenty-eight extralobar pulmonary sequestrations dramatically regressed on serial prenatal sonography, were asymptomatic after birth, and were only detectable by imaging studies postnatally (no resection required). Of the remaining 13 extralobar pulmonary sequestration cases, 2 underwent elective abortion, 7 symptomatic lesions were resected after birth with survival, 1 hydropic fetus died, and 3 fetuses had an associated tension hydrothorax with secondary hydrops that was successfully treated by either fetal thoracenteses or thoracoamniotic shunting followed by postnatal resection. CONCLUSIONS: The natural history of prenatally diagnosed lung masses is variable, and associated anomalies are rare. Most congenital cystic adenomatoid malformation lesions can be managed with maternal transport, planned term delivery, and postnatal resection. Many extralobar pulmonary sequestrations dramatically decrease in size before birth and may not need treatment after birth. Fetal therapy is now an option for lung lesions associated with nonimmune hydrops.

Amnion↗

Increased cell proliferation and decreased apoptosis characterize congenital cystic adenomatoid malformation of the lung.

BACKGROUND/PURPOSE: Congenital cystic adenomatoid malformations (CCAM) are lung lesions that demonstrate abnormalities of both mesenchymal and epithelial tissues. The pathogenesis of these tumors remains unknown. Because normal organogenesis requires a balance between cell proliferation and programmed cell death (apoptosis), the authors hypothesized that CCAM results from an increase in cell proliferation or a decrease in apoptosis within the developing lung, possibly mediated by keratinocyte growth factor (KGF). METHODS: To examine cell cycle control in CCAM, we measured indices of cell proliferation and apoptosis in lesions requiring fetal (n = 4) or neonatal (n = 8) resection compared with those of normal fetal (14 to 28 weeks' gestation; n = 14) and neonatal (n = 3) human lung. Cell proliferation was analyzed by immunostaining for a proliferation marker (Ki-67). Apoptosis was examined using an in situ digoxigenin end-labeling technique to localize apoptotic bodies. The expression of KGF protein and KGF mRNA in CCAM and normal lung was examined using immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: CCAM lesions in general showed a twofold increase in cell proliferation index (19.2% +/- 1.4% v 9.6% +/- 0.7%, P < .00005) and a fivefold decrease in apoptotic bodies (0.9 +/- 0.2 v 4.5 +/- 0.5, P < .0005) compared with age-matched normal lung. CCAMs that required resection before birth had the highest cell proliferation index. There were no differences in the expression of KGF protein or KGF mRNA in CCAM and normal lung. CONCLUSIONS: These results demonstrate that CCAM differs from normal lung by increased cell proliferation and decreased apoptosis. The increased proliferation does not appear to be mediated by the pneumocyte mitogen KGF. An examination of factors that control cell proliferation and apoptosis in CCAM may provide further insight into the pathogenesis of this tumor.

Apoptosis↗

Hyaluronan receptor expression increases in fetal excisional skin wounds and correlates with fibroplasia.

BACKGROUND/PURPOSE: The midgestation fetus heals incisional skin wounds scarlessly, whereas large excisional wounds scar. High concentrations of hyaluronan (HA) are associated with scarless fetal as opposed to scar-forming adult wound repair. Because expression of the HA receptors, CD44 and RHAMM (Receptor for HA-Mediated Motility), has been associated with adult wound fibroplasia, the authors postulated that fetal excisional wounds would show increased expression of CD44 and RHAMM as compared with incisional wounds. METHODS: Two models of fetal wound healing were examined. Fetal skin from human abortuses was heterotransplanted subcutaneously into severe combined immunodeficient (SCID) mice. Fourteen days after grafting, incisional or 2-mm excisional wounds were created (n = 6 per time-point). In addition, incisional and excisional (6 to 10 mm) wounds (n = 5 per time-point) were created on the backs of 70- to 75-day fetal lambs (term, 145 days). Tissue from both models was harvested at sequential time-points after injury. Wounds were studied histologically for fibroplasia and assayed for their HA content. CD44 and RHAMM expression were analyzed by immunohistochemistry and immunoblotting. RESULTS: As expected, in both models, incisional wounds healed scarlessly, whereas excisional wounds showed fibroplasia. Incisional wounds of fetal lambs maintained a significantly higher HA content than excisional wounds 3 days after injury. Between 1 and 7 days in either human or sheep fetal wounds, immunostaining for CD44 and RHAMM markedly increased along the margins of excisional wounds as compared with incisional wounds and unwounded skin. Immunoblot analysis confirmed this increased HA receptor expression in both models. CONCLUSIONS: HA receptor expression increased in both human and sheep fetal excisional wounds and correlated with fibroplasia and a reduced HA content. The authors speculate that strategies to limit the expression or function of HA receptors during postnatal wound repair may modify the development of scar.

Animals↗

Tracheal occlusion reverses the high impedance to flow in the fetal pulmonary circulation and normalizes its physiological response to oxygen at full term.

PURPOSE: The authors hypothesized that in utero tracheal occlusion would reverse the high impedance to pulmonary blood flow associated with congenital diaphragmatic hernia (CDH) and normalize the fetal physiological response to oxygen at term. METHODS: Three experimental groups were studied. Six fetal lambs (CDH group) underwent creation of a left CDH at 80 days' gestation, an additional six fetal lambs underwent left CDH creation at 80 days' gestation followed by fetal tracheal occlusion performed at 108 days' gestation (CDH + TO group), and four control fetal lambs (control group) underwent a sham procedure at 80 days gestation. All lambs were followed up at 2-week intervals by pulse wave Doppler echocardiography. At each time-point the pulsatility index (PI) was calculated for the left branch pulmonary artery from the Doppler blood velocity waveform. Near term (term, 145 days gestation) at 136 days gestation, measurements were repeated under maternal normoxia and hyperoxia. The fetal lungs were harvested and processed for morphometric analysis by radial alveolar counts (RAC) and lung-to-body-weight ratios (LBWR) as measures of lung growth. RESULTS: At 136 days' gestation the PI of the CDH + TO group (2.88 +/- 0.29) and control group (3.97 +/- 0.37) were significantly lower compared with the PI of the CDH group (9.02 +/- 0.50). There was a significant decrease in the PI of both the CDH + TO group and the control group with maternal hyperoxia at term, whereas the CDH group showed no change. The lungs of the CDH group fetuses were significantly smaller by LBWR and RAC than both CDH + TO and control fetuses. CONCLUSIONS: An elevated PI is associated with pulmonary hypoplasia, fetal tracheal occlusion reverses this finding, and results in a normal fetal physiological response to changes in oxygen tension at term.

Analysis of Variance↗

Anomalies and malformations affecting the fetal/neonatal chest.

Although significant anomalies of the fetal thorax are uncommon, with improvement in high-resolution ultrasonography, more of these lesions are being diagnosed prenatally. Accurate and specific prenatal diagnosis is important because different lesions have different natural histories and prognosis. Prenatal MRI is an increasingly important adjunct for identification and differentiation of these lesions and may help determine in selected cases when and if in utero fetal intervention is indicated.

Bronchopulmonary Sequestration↗

Prenatal MRI evaluation of giant neck masses in preparation for the fetal exit procedure.

Airway compromise at birth can be anticipated with giant neck masses, so that as much anatomic information as possible is necessary prior to delivery to establish a diagnosis and assess the airway. With this study, we evaluated the usefulness of prenatal magnetic resonance imaging (MRI) for evaluation of giant fetal neck masses prior to operating on placental support, the Ex Utero Intrapartum Treatment (EXIT) procedure, performed to secure the neonatal airway. Three pregnant women with an ultrasound (US) diagnosis of fetal giant neck mass were referred for prenatal MRI. As this was our initial experience performing prenatal MRI, a variety of imaging sequences were used including spin-echo, fast gradient-echo, half-fourier single shot turbo spin-echo (Haste), and echo-planar imaging (EPI). All sequences performed were able to demonstrate the fetal airway relative to the mass. In addition, the images were able to give a more global definition of the mass because of the larger field of view than could be obtained with MRI compared to US. The Haste sequence provided the best definition of a mass because of decreased motion artifacts. The prenatal diagnosis on MRI was teratoma in two and lymphangioma in one and was confirmed at birth. MRI provided essential information about the diagnosis and the anatomy of the giant neck masses and adjacent airway in three fetuses prior to selection for the EXIT surgical procedure.

Airway Obstruction↗

Intrapartum airway management for giant fetal neck masses: the EXIT (ex utero intrapartum treatment) procedure.

OBJECTIVE: Our goal was to review our experience with the EXIT (ex utero intrapartum treatment) procedure in the management of five cases with life-threatening fetal neck masses. STUDY DESIGN: We present a retrospective review of prenatal presentation and course, diagnostic accuracy of imaging studies, intraoperative management, complications, and outcomes. RESULTS: Polyhydramnios was the initial presenting symptom in three of five fetuses with a mean gestational age of 25 +/- 6 weeks. Preterm labor occurred in two patients. Fetal magnetic resonance imaging provided accurate diagnosis in all four cases whereas conventional ultrasonography led to the diagnosis in four of five cases. The mean duration of EXIT was 28 +/- 22 minutes. The mean venous cord blood gas values were pH 7.22 +/- 0.05, PCO2 61 +/- 11 mm Hg, and PO2 42 +/- 8 mm Hg. In four of five cases an airway was successfully secured. CONCLUSIONS: The EXIT procedure provides up to 1 hour of good uteroplacental support and is the procedure of choice to secure an airway in the fetus with a giant neck mass.

Airway Obstruction↗

Fetoscopic gene therapy for congenital lung disease.

Fetal gene therapy offers the promise of cure for certain genetic diseases, like cystic fibrosis and surfactant protein B deficiency. The authors hypothesized that a fetoscopic approach could attain a high level of organ-specific gene transfer to the fetal lung late in gestation. To test this hypothesis the authors examined the efficacy, specificity, and toxicity of recombinant adenovirus-mediated transfer of the beta-galactosidase marker gene to the lung of late gestation fetal sheep using a fetoscopic technique. Twelve fetal sheep of 125 to 135 days' gestation (term, 145 days) underwent fetoscopic bronchoscopy and intratracheal administration of a replication-deficient adenoviral vector that transduces the beta-galactosidase marker gene. Escape of administered virus was prevented by the fetoscopic deployment of a detachable silicone balloon in the fetal trachea. All fetuses survived until being killed at 2 days after vector delivery for the histopathologic assessment of vector efficacy and specificity. Optimal beta-galactosidase transgene expression was observed at a viral titer of 2 x 10(12) particles per milliliter of administered volume. Expression was greatest in the distal pulmonary parenchyma, particularly in type II pneumocytes, and extended out to the pleura. There was no evidence of gene transfer in either the large conducting airways or in any other fetal organ. The authors have developed a minimally invasive technique for the specific pulmonary delivery of gene therapy vectors to the fetus with no associated acute toxicity. Gene transfer to the late gestation fetus for the treatment of congenital pulmonary disease may be feasible through fetoscopy.

Adenoviruses, Human↗

Cystic lung lesions with systemic arterial blood supply: a hybrid of congenital cystic adenomatoid malformation and bronchopulmonary sequestration.

Congenital cystic adenomatoid malformation and bronchopulmonary sequestration are congenital lung tumors that are classically described as having distinct embryology, pathology, and natural history. The authors treated six patients who had prenatally diagnosed lung masses that displayed clinicopathologic features of both lesion types. At prenatal diagnosis (19 to 30 weeks' gestation), all six lesions were classified sonographically as congenital cystic adenomatoid malformation, and none of the masses appeared to have a systemic arterial blood supply as seen by color flow Doppler study. Two of the six masses showed size regression antenatally. At the time of surgery, all six lesions had a systemic vessel directly from the aorta--five cases were consistent grossly with an intralobular bronchopulmonary sequestration, and one case was consistent with an extralobular bronchopulmonary sequestration. However, all six lesions displayed congenital cystic adenomatoid malformation histology. Hydrops developed in one fetus with a huge mass, and that fetus underwent successful fetal surgical resection (left lower lobectomy) at 22 weeks' gestation with delivery at 35 weeks' gestation. One neonate with a large extralobular bronchopulmonary sequestration was treated with resection and extracorporeal membrane oxygenation (ECMO) but died of pulmonary hypoplasia. Four other patients who had much smaller masses underwent elective lower lobectomy after birth. These findings emphasize the importance of seeking an anomalous blood supply in patients who have congenital lung lesions. These "hybrid" cases suggest a similar embryological origin for congenital cystic adenomatoid malformation and bronchopulmonary sequestration.

Abnormalities, Multiple↗

Myofibroblast persistence in fetal sheep wounds is associated with scar formation.

The scarless repair capabilities of the fetus are influenced by the size of the wound and the gestational age of the fetus. Whereas small wounds heal scarlessly, large wounds in the same fetus heal with scar. Myofibroblasts are specialized fibroblasts that express alpha-smooth muscle actin (alpha-SMA), a contractile cytoskeletal protein. The authors hypothesized that small fetal wounds that heal scarlessly will have a relative absence of myofibroblasts, whereas large wounds that heal with scar will have abundant myofibroblasts. In this study, an incisional wound and four punch biopsy wounds of 2, 4, 6, and 10 mm diameter were placed on the backs of 60- to 90-day-gestation fetal sheep (term, 145 days). Fourteen days after wounding, the healed fetal wounds were harvested, the repair morphology was determined (scarless, transitional repair, or scar), and the expression of alpha-SMA was analyzed by immunohistochemistry. In the second part of this study the authors analyzed the temporal expression of alpha-SMA in fetal wounds at 1, 2, 3, and 7 days after wounding in 70-day-gestation fetal sheep. In the 14-day wounds, the authors found that alpha-SMA was not expressed in any incisional or 2-mm wound that healed scarlessly, but it was expressed in all wounds that healed with scar. Overall, alpha-SMA expression strongly correlated with increasing wound size (P < .005). Myofibroblasts were seen as early as 24 hours after wounding, and at 3 and 7 days all wounds showed strong expression of alpha-SMA. These results demonstrate that although myofibroblasts are induced early in fetal wound repair, by 14 days there is a notable lack of myofibroblasts in wounds that heal scarlessly and an abundance of myofibroblasts in those wounds that scar. By determining the factors that regulate the disappearance of the myofibroblast in scarless fetal wounds, the authors hope to gain new insights into the mechanisms of scarless fetal repair.

Actins↗

Differential collagen I gene expression in fetal fibroblasts.

PURPOSE: Fetal wound healing is characterized by the regeneration of normal dermis and the absence of scar. Transforming growth factor beta-1 (TGF-beta1) is a ubiquitous cytokine with potent fibrogenic effects in both postnatal and fetal wounds. Supplementing fetal wounds with TGF-beta1 results in increased fibrosis consisting primarily of collagen I. We hypothesized that the lack of scar formation in fetal wounds may be caused by differential collagen I gene (COL1A1) expression. The authors examined basal collagen Ia gene expression in human fetal, newborn, and adult dermal fibroblasts after stimulation with exogenous TGF-beta1. METHODS: Subconfluent human dermal fibroblasts from fetal, newborn, and adult cell lines were incubated for 24 hours, then stimulated by incubation for 4 hours with 1 ng/mL of human recombinant TGF-beta1, or with media alone for basal collagen gene expression, and then placed in guanidium isothyocyanate buffer. To quantitate COL1A1 gene expression, total cellular RNA was extracted and subjected to northern and slot blot hybridization analysis with Dig-labeled COL1A1 probes. The membrane was exposed to x-ray film for 15 minutes and developed. RESULTS: Scant COL1A1 gene transcript was detected in control fetal fibroblasts. Brief stimulation with of TGF-beta1 upregulated the COL1A1 gene transcription in fetal fibroblasts. Gene expression for COL1A1 in both postnatal cell lines appeared similar in treated and untreated cells. Housekeeping control (GAPDH) confirmed no difference in total amount of RNA at the start or end of the experiment. CONCLUSION: COL1A1 gene expression is notably absent in unstimulated fetal fibroblasts, but is upregulated by TGF-beta1. In contrast, postnatal fibroblasts demonstrate significant constitutive COL1A1 gene expression at baseline and unchanged after TGF-beta1 stimulation. This differential regulation may contribute to the ability of fetal wounds to regenerate without scar and explain the effect of exogenous TGF-beta1 to increase fibroplasia in fetal dermal incisional wounds.

Adult↗

Fetal ovarian cyst decompression to prevent torsion.

BACKGROUND/PURPOSE: Neonates who have ovarian torsion caused by an ovarian cyst often lose their ovary because the torsion and infarction occurred antenatally. Because ultrasound scan has been so effective in diagnosing ovarian cysts in utero, we have a better understanding of their natural history and can select appropriate cases for cyst decompression in utero to prevent torsion. The authors reviewed experience with seven fetuses who had fetal ovarian cyst. METHODS: During a 26-month period, seven patients were referred for the evaluation of fetal ovarian cyst. The mean gestational age at presentation was 31.9 +/- 3.6 weeks (+/-SD; range, 27 to 37 weeks). There was no history of maternal risk factors such as diabetes mellitus or fetal risk factors such as hyperthyroidism or placentomegally. All seven cases involved isolated unilateral cysts without associated anomalies or chromosomal abnormalities. Mean initial cyst diameter was 3.4 +/- 1.7 cm (+/-SD; range, 1 to 6.1). Indications used for ovarian cyst decompression included anechoic cysts with a diameter > or =4 cm, a cyst "wandering" about the abdomen on serial sonograms, or demonstrating rapid enlargement (>1 cm/wk). RESULTS: All but one cyst progressed in size during observation. One fetal ovarian cyst (diameter, 2 cm) subsequently regressed spontaneously and another (diameter, 2.1 cm) stabilized during prenatal ultrasound surveillance. One "cyst" observed with a diameter of 3.5 cm proved to be a persistent cloaca. Four fetal ovarian cysts met criteria for decompression. Because of fetal position, decompression could not be performed in one. One cyst (seen before defining criteria for decompression) with a diameter of 5 cm was observed only and underwent torsion. Two cysts (diameters, 6.1 cm and 4 cm) were decompressed in utero under local anesthesia with ultrasound guidance, of 95 mL and 35 mL, respectively. High cyst fluid progesterone (12,041 and 1,990 ng/dL, respectively) and testosterone (1,298 and 2,900 ng/dL, respectively) confirmed the etiology of the cyst as ovarian. Neither cyst recurred, and postnatal ultrasound scan confirmed resolution. There was no maternal or fetal morbidity or mortality and only the patient observed before development of criteria for decompression lost her ovary because of torsion. CONCLUSIONS: Fetal ovarian cysts tend to present as isolated unilateral lesions in normal fetuses in the third trimester. Spontaneous regression of fetal ovarian cysts may occur. Fetal ovarian cyst decompression, in select cases, may preserve ovaries at risk for torsion.

Female↗