Original Paper Received: March 28, 2017 Accepted after revision: July 25, 2017 Published online: September 13, 2017
Fetal Diagn Ther DOI: 10.1159/000479793
Outcome of Bronchopulmonary Sequestration with Massive Pleural Effusion after Intrafetal Vascular Laser Ablation Ingo Gottschalk a Brigitte Strizek b Michael R. Mallmann a Andreas Müller c Annegret Geipel b Ulrich Gembruch b Philipp Klaritsch d Bence Csapo d Christoph Berg a, b a
Bereich für Pränatale Medizin und Gynäkologische Sonographie, Universitätsfrauenklinik Köln, Köln, and Abteilung für Geburtshilfe und Pränatale Medizin, Universitätsfrauenklinik Bonn, and c Bereich für Neonatologie und Pädiatrische Intensivmedizin, Zentrum für Kinderheilkunde, Universitätsklinik Bonn, Bonn, Germany; d Abteilung für Geburtshilfe, Universitätsklinik für Frauenheilkunde und Geburtshilfe, Graz, Austria b
Abstract Objective: To assess the outcome of 12 fetuses with bronchopulmonary sequestration (BPS) and massive pleural effusion after intrafetal vascular laser ablation (VLA). Methods: All fetuses with BPS and massive pleural effusion that were treated with intrafetal VLA during a 5-year period (2012– 2016) were reviewed for safety, intrauterine course, and postnatal outcome. Results: In the study period, 12 fetuses with BPS were treated with VLA. In 7 (58.3%) fetuses, complete cessation of blood flow was achieved after the first VLA, while in 5 (41.7%) fetuses, residual perfusion of the feeding vessel was demonstrated at follow-up. A second intervention was successful in 4 of 5 (80%) fetuses. Overall, in 11 of 12 (91.7%) fetuses, complete coagulation of the feeding vessel could be achieved, followed by a reduction in size or complete resolution of the BPS. All 11 fetuses with successful prenatal intervention were live-born at a median gestational age of 39+1 (range, 37+5–41+2) weeks. Postnatally, 2 (18.2%) of the 11 newborns underwent sequestrectomy, as well as
© 2017 S. Karger AG, Basel E-Mail [email protected] www.karger.com/fdt
the preterm newborn on which a second fetal intervention was not feasible. Conclusion: VLA is an effective and safe treatment of BPS that appears to be of benefit in improving prognosis and decreasing the need for postnatal sequestrectomy. © 2017 S. Karger AG, Basel
Introduction
Bronchopulmonary sequestration (BPS) is a rare congenital malformation of the lower respiratory tract, consisting of nonfunctional lung tissue that is not connected to the tracheobronchial tree and fed by a separate systemic (rather than pulmonary) artery. This arterial blood supply typically originates from the descending aorta or, rarely, from intercostal, gastric, or splenic arteries. Venous drainage can be systemic or pulmonary [1–3]. The key intrauterine sonographic feature of BPS is a solid “echogenic” mass in the thorax (Fig. 1a), usually
I. Gottschalk and B. Strizek contributed equally to the manuscript.
Dr. med. Ingo Gottschalk Bereich für Pränatale Medizin und Gynäkologische Sonographie Universitätsklinikum Köln, Kerpenerstrasse 34 DE–50931 Bonn (Germany) E-Mail ingo.gottschalk @ uk-koeln.de
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 3:45:47 PM
Keywords Bronchopulmonary sequestration · Laser · Intrauterine intervention · Fetus · Prenatal diagnosis
Color version available online
a
b
Fig. 1. a Bronchopulmonary sequestration (BPS) at 28 weeks of gestation, associated with pleural effusion (*) and mediastinal shift. b Bronchopulmonary sequestration at 28 weeks of gestation. The feeding vessel (arrow) originating from the descending aorta (*) is demonstrated on color Doppler.
2
Fetal Diagn Ther DOI: 10.1159/000479793
The aim of this study was to assess the safety and clinical success rate of VLA, the intrauterine course after intervention, the intervention-related complications, and the postnatal outcome in the so far largest published cohort of fetuses with BPS and massive pleural effusions treated with intrafetal VLA.
Methods All fetuses with BPS and severe pleural effusion that were treated with intrafetal VLA during a 5-year period (2012–2016) in 3 tertiary referral centers (University Hospitals Cologne and Bonn, Germany, and Graz, Austria) were reviewed retrospectively. Five of the 12 cases have been part of a previously published study in which the effectiveness of 2 different treatment options (VLA vs. pleuroamniotic shunting) in fetuses with BPS and severe pleural effusions were compared [4]. Prenatal diagnosis of PBS was made by 2D ultrasound in the presence of a solid hyperechogenic mass in the thorax or abdomen with atypical blood supply on color Doppler from the descending aorta (Fig. 1a, b). Massive pleural effusion was defined as complete mediastinal shifting with the heart completely displaced on the contralateral side of the thorax with worsening in at least 2 consecutive examinations. Laterality, relation to the diaphragm, presence and degree of mediastinal shifting, additional malformations, and presence of pleural effusions or hydrops were assessed. The number of VLA needed to achieve complete cessation of blood flow, regression of tumor size, and reliability of sonographic assessment of regression during pregnancy after successful VLA as well as intervention-related complications during or after VLA were documented to assess the intrauterine course. After VLA, all fetuses underwent daily follow-up ultrasound examinations for 3 days and in 4–6 weekly intervals thereafter to assess any postinter-
Gottschalk/Strizek/Mallmann/Müller/ Geipel/Gembruch/Klaritsch/Csapo/Berg
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 3:45:47 PM
unilateral, with atypical arterial blood supply from the descending aorta (Fig. 1b) [4, 5]. The latter enables a differentiation from microcystic congenital pulmonary airway malformation, although a significant subset of lesions show histological features of both diseases [1]. Most BPS show a spontaneous partial or complete regression during the course of pregnancy and can be managed expectantly with excellent prognosis, but a significant subset of BPS increases in size and may develop massive pleural effusions with mediastinal shifting. In these cases, mortality and morbidity are considerably increased and prenatal treatment might be mandatory to avoid progression to hydrops, intrauterine death, and neonatal death due to pulmonary hypoplasia [4–9]. In the past, therapeutic approaches like inotropic therapy [10], fetal pleurodesis [11], fetal lobectomy [12], and even pleuroamniotic shunting [4, 5, 13, 14] showed disappointing results and have been abandoned. In contrast, recent reports demonstrated that intrafetal vascular laser ablation of the feeding vessel (VLA) is a curative and highly effective treatment option that induces a necrotic process of BPS that leads to a significant reduction in size, avoiding postnatal sequestrectomy in a subset of newborns [4, 5, 8, 15–18]. However, due to the rarity of the disease, only small series or case reports have been published since its first description by Oepkes et al. in 2007 [15]. Thus, experience with VLA is still limited and partly controversial, including extremely good results without any need for postnatal surgery [8] as well as cases with large residual tumors after birth [5].
ventional complications, recurrence of pleural effusions, and changes in tumor size. Delivery as well as postnatal diagnostic management was carried out at the discretion of the referring institutions or in 1 of the 3 centers participating in this study. Surgery was performed exclusively in the pediatric surgery units of the 3 participating centers in Cologne, Bonn, or Graz. All newborns underwent postnatal ultrasound, but in most cases, additional chest X-ray, MRI, or CT were performed to assess any residual sequestration and to document any intervention-related collateral damage on nearby anatomic structures. Neonatal outcome and postnatal need for sequestrectomy were recorded in all cases. Complete regression of BPS was achieved if no residual tumor was detectable on postnatal ultrasound, chest X-ray, MRI, and/or CT. Partial regression of BPS after VLA was defined as a marked and progressive reduction in size, but residual tumor on postnatal examinations. During the study period, all patients underwent a complete fetal anatomic survey including fetal echocardiography and Doppler sonography. For all ultrasound examinations, 5-MHz, 7.5-MHz, or 9-MHz curved array probes were used (IU22 and Epiq 7 Philips, Hamburg, Germany; Voluson E8 and E10 GE Healthcare, Solingen, Germany). Interventions were performed by 4 specialists in fetal medicine (C.B., A.G., B.S., P.K.) with a high level of experience in intrauterine interventions. In our first case, pleuroamniotic shunting with a double pigtail catheter (Harrison Fetal Bladder Stent, Cook Medical, Bloomington, IN, USA) was performed prior to laser coagulation, using the technique previously described by Rodeck et al. [19]. In all cases, ultrasound-guided laser coagulation of the feeding artery (VLA) was performed using an Nd:YAG (neodymium:yttrium aluminium garnet) laser through an 18-G needle (Fig. 2) as previously described by Oepkes et al. [15]. All fetal interventions were performed without maternal anesthesia, and an external fetal version was performed in cases of inadequate fetal position. Prior to VLA, fetal anesthesia was performed by an intramuscular injection into the fetal thigh with fentanyl (15 μg/kg) and pancuronium
In the study period, a total of 12 fetuses with BPS and severe pleural effusions were diagnosed in the 3 centers (Table 1). The diagnosis was made at a median gestational age of 29+0 (range, 23+3–33+4) weeks. Ten (83.3%) fetuses had left-sided extralobar BPS, 2 (16.7%) had right-sided extralobar BPS, all were located in the thorax, and all were fed by an aberrant feeding vessel originating from the descending aorta. All fetuses had massive pleural effusions with significant mediastinal shifting and polyhydramnios but normal Doppler flow parameters. One fetus had additional ascites. None of our fetuses had additional malformations or chromosomal anomalies. All 12 fetuses underwent intrafetal VLA of the feeding vessel. Median gestational age at intervention was 29+3 (range, 24+0–33+5) weeks of gestation. The first case of our series underwent pleuroamniotic shunting and VLA after shunt dislocation, because pleuroamniotic shunting was the first-line treatment until 2012. All other 11 fetuses underwent VLA without previous shunting. Eleven fetuses (91.7%) were born at term at a median gestational age of 39+1 (range, 37+5–41+2) weeks. There was 1 premature delivery after PPROM at 29+4 weeks of gestation. In 7 (58.3%) fetuses, complete cessation of blood flow was achieved after a single intervention, while in 5
Intrafetal Vascular Laser Ablation of Bronchopulmonary Sequestration
Fetal Diagn Ther DOI: 10.1159/000479793
Results
3
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 3:45:47 PM
Color version available online
Fig. 2. A 700-μm Nd:YAG (neodymium:yttrium aluminium garnet) laser fiber is passed through an 18-G needle.
(2 mg/kg), using a 22-G needle under ultrasound guidance. Then an 18-G needle was inserted through the fetal thorax in the BPS with its tip directly adjacent to the feeding vessel. A 700-μm laser fiber was then passed through and to 2–3 mm beyond the tip of the needle and the feeding vessel. The feeding vessel was coagulated using an output of 50 W for 5–10 s (Fig. 3a). Color Doppler demonstrated immediate cessation of blood flow within the tumor (Fig. 3b). If color Doppler demonstrated residual flow, the tip of the laser fiber was repositioned and coagulation was repeated until complete cessation of blood flow was achieved. Prior to the removal of the needle, the pleural effusion was drained. An amniotic fluid sample was retrieved at the end of every intervention for subsequent karyotyping. The following day, ultrasound was performed to confirm complete cessation of blood flow. If residual flow was present, VLA was repeated the next day. Any intervention-related complications were documented. The postoperative evolution of the BPS was assessed at least once in the referral center, and the sonographic predelivery findings in a standardized transthoracic plane were collected from the referring centers (Fig. 3c). Obstetrical and neonatal data was obtained by chart review. Statistical analysis was performed using the Mann-Whitney U test. All values are given as median (interquartile range) unless indicated otherwise. A p value of
Fetal Diagn Ther DOI: 10.1159/000479793
Outcome of Bronchopulmonary Sequestration with Massive Pleural Effusion after Intrafetal Vascular Laser Ablation Ingo Gottschalk a Brigitte Strizek b Michael R. Mallmann a Andreas Müller c Annegret Geipel b Ulrich Gembruch b Philipp Klaritsch d Bence Csapo d Christoph Berg a, b a
Bereich für Pränatale Medizin und Gynäkologische Sonographie, Universitätsfrauenklinik Köln, Köln, and Abteilung für Geburtshilfe und Pränatale Medizin, Universitätsfrauenklinik Bonn, and c Bereich für Neonatologie und Pädiatrische Intensivmedizin, Zentrum für Kinderheilkunde, Universitätsklinik Bonn, Bonn, Germany; d Abteilung für Geburtshilfe, Universitätsklinik für Frauenheilkunde und Geburtshilfe, Graz, Austria b
Abstract Objective: To assess the outcome of 12 fetuses with bronchopulmonary sequestration (BPS) and massive pleural effusion after intrafetal vascular laser ablation (VLA). Methods: All fetuses with BPS and massive pleural effusion that were treated with intrafetal VLA during a 5-year period (2012– 2016) were reviewed for safety, intrauterine course, and postnatal outcome. Results: In the study period, 12 fetuses with BPS were treated with VLA. In 7 (58.3%) fetuses, complete cessation of blood flow was achieved after the first VLA, while in 5 (41.7%) fetuses, residual perfusion of the feeding vessel was demonstrated at follow-up. A second intervention was successful in 4 of 5 (80%) fetuses. Overall, in 11 of 12 (91.7%) fetuses, complete coagulation of the feeding vessel could be achieved, followed by a reduction in size or complete resolution of the BPS. All 11 fetuses with successful prenatal intervention were live-born at a median gestational age of 39+1 (range, 37+5–41+2) weeks. Postnatally, 2 (18.2%) of the 11 newborns underwent sequestrectomy, as well as
© 2017 S. Karger AG, Basel E-Mail [email protected] www.karger.com/fdt
the preterm newborn on which a second fetal intervention was not feasible. Conclusion: VLA is an effective and safe treatment of BPS that appears to be of benefit in improving prognosis and decreasing the need for postnatal sequestrectomy. © 2017 S. Karger AG, Basel
Introduction
Bronchopulmonary sequestration (BPS) is a rare congenital malformation of the lower respiratory tract, consisting of nonfunctional lung tissue that is not connected to the tracheobronchial tree and fed by a separate systemic (rather than pulmonary) artery. This arterial blood supply typically originates from the descending aorta or, rarely, from intercostal, gastric, or splenic arteries. Venous drainage can be systemic or pulmonary [1–3]. The key intrauterine sonographic feature of BPS is a solid “echogenic” mass in the thorax (Fig. 1a), usually
I. Gottschalk and B. Strizek contributed equally to the manuscript.
Dr. med. Ingo Gottschalk Bereich für Pränatale Medizin und Gynäkologische Sonographie Universitätsklinikum Köln, Kerpenerstrasse 34 DE–50931 Bonn (Germany) E-Mail ingo.gottschalk @ uk-koeln.de
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 3:45:47 PM
Keywords Bronchopulmonary sequestration · Laser · Intrauterine intervention · Fetus · Prenatal diagnosis
Color version available online
a
b
Fig. 1. a Bronchopulmonary sequestration (BPS) at 28 weeks of gestation, associated with pleural effusion (*) and mediastinal shift. b Bronchopulmonary sequestration at 28 weeks of gestation. The feeding vessel (arrow) originating from the descending aorta (*) is demonstrated on color Doppler.
2
Fetal Diagn Ther DOI: 10.1159/000479793
The aim of this study was to assess the safety and clinical success rate of VLA, the intrauterine course after intervention, the intervention-related complications, and the postnatal outcome in the so far largest published cohort of fetuses with BPS and massive pleural effusions treated with intrafetal VLA.
Methods All fetuses with BPS and severe pleural effusion that were treated with intrafetal VLA during a 5-year period (2012–2016) in 3 tertiary referral centers (University Hospitals Cologne and Bonn, Germany, and Graz, Austria) were reviewed retrospectively. Five of the 12 cases have been part of a previously published study in which the effectiveness of 2 different treatment options (VLA vs. pleuroamniotic shunting) in fetuses with BPS and severe pleural effusions were compared [4]. Prenatal diagnosis of PBS was made by 2D ultrasound in the presence of a solid hyperechogenic mass in the thorax or abdomen with atypical blood supply on color Doppler from the descending aorta (Fig. 1a, b). Massive pleural effusion was defined as complete mediastinal shifting with the heart completely displaced on the contralateral side of the thorax with worsening in at least 2 consecutive examinations. Laterality, relation to the diaphragm, presence and degree of mediastinal shifting, additional malformations, and presence of pleural effusions or hydrops were assessed. The number of VLA needed to achieve complete cessation of blood flow, regression of tumor size, and reliability of sonographic assessment of regression during pregnancy after successful VLA as well as intervention-related complications during or after VLA were documented to assess the intrauterine course. After VLA, all fetuses underwent daily follow-up ultrasound examinations for 3 days and in 4–6 weekly intervals thereafter to assess any postinter-
Gottschalk/Strizek/Mallmann/Müller/ Geipel/Gembruch/Klaritsch/Csapo/Berg
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 3:45:47 PM
unilateral, with atypical arterial blood supply from the descending aorta (Fig. 1b) [4, 5]. The latter enables a differentiation from microcystic congenital pulmonary airway malformation, although a significant subset of lesions show histological features of both diseases [1]. Most BPS show a spontaneous partial or complete regression during the course of pregnancy and can be managed expectantly with excellent prognosis, but a significant subset of BPS increases in size and may develop massive pleural effusions with mediastinal shifting. In these cases, mortality and morbidity are considerably increased and prenatal treatment might be mandatory to avoid progression to hydrops, intrauterine death, and neonatal death due to pulmonary hypoplasia [4–9]. In the past, therapeutic approaches like inotropic therapy [10], fetal pleurodesis [11], fetal lobectomy [12], and even pleuroamniotic shunting [4, 5, 13, 14] showed disappointing results and have been abandoned. In contrast, recent reports demonstrated that intrafetal vascular laser ablation of the feeding vessel (VLA) is a curative and highly effective treatment option that induces a necrotic process of BPS that leads to a significant reduction in size, avoiding postnatal sequestrectomy in a subset of newborns [4, 5, 8, 15–18]. However, due to the rarity of the disease, only small series or case reports have been published since its first description by Oepkes et al. in 2007 [15]. Thus, experience with VLA is still limited and partly controversial, including extremely good results without any need for postnatal surgery [8] as well as cases with large residual tumors after birth [5].
ventional complications, recurrence of pleural effusions, and changes in tumor size. Delivery as well as postnatal diagnostic management was carried out at the discretion of the referring institutions or in 1 of the 3 centers participating in this study. Surgery was performed exclusively in the pediatric surgery units of the 3 participating centers in Cologne, Bonn, or Graz. All newborns underwent postnatal ultrasound, but in most cases, additional chest X-ray, MRI, or CT were performed to assess any residual sequestration and to document any intervention-related collateral damage on nearby anatomic structures. Neonatal outcome and postnatal need for sequestrectomy were recorded in all cases. Complete regression of BPS was achieved if no residual tumor was detectable on postnatal ultrasound, chest X-ray, MRI, and/or CT. Partial regression of BPS after VLA was defined as a marked and progressive reduction in size, but residual tumor on postnatal examinations. During the study period, all patients underwent a complete fetal anatomic survey including fetal echocardiography and Doppler sonography. For all ultrasound examinations, 5-MHz, 7.5-MHz, or 9-MHz curved array probes were used (IU22 and Epiq 7 Philips, Hamburg, Germany; Voluson E8 and E10 GE Healthcare, Solingen, Germany). Interventions were performed by 4 specialists in fetal medicine (C.B., A.G., B.S., P.K.) with a high level of experience in intrauterine interventions. In our first case, pleuroamniotic shunting with a double pigtail catheter (Harrison Fetal Bladder Stent, Cook Medical, Bloomington, IN, USA) was performed prior to laser coagulation, using the technique previously described by Rodeck et al. [19]. In all cases, ultrasound-guided laser coagulation of the feeding artery (VLA) was performed using an Nd:YAG (neodymium:yttrium aluminium garnet) laser through an 18-G needle (Fig. 2) as previously described by Oepkes et al. [15]. All fetal interventions were performed without maternal anesthesia, and an external fetal version was performed in cases of inadequate fetal position. Prior to VLA, fetal anesthesia was performed by an intramuscular injection into the fetal thigh with fentanyl (15 μg/kg) and pancuronium
In the study period, a total of 12 fetuses with BPS and severe pleural effusions were diagnosed in the 3 centers (Table 1). The diagnosis was made at a median gestational age of 29+0 (range, 23+3–33+4) weeks. Ten (83.3%) fetuses had left-sided extralobar BPS, 2 (16.7%) had right-sided extralobar BPS, all were located in the thorax, and all were fed by an aberrant feeding vessel originating from the descending aorta. All fetuses had massive pleural effusions with significant mediastinal shifting and polyhydramnios but normal Doppler flow parameters. One fetus had additional ascites. None of our fetuses had additional malformations or chromosomal anomalies. All 12 fetuses underwent intrafetal VLA of the feeding vessel. Median gestational age at intervention was 29+3 (range, 24+0–33+5) weeks of gestation. The first case of our series underwent pleuroamniotic shunting and VLA after shunt dislocation, because pleuroamniotic shunting was the first-line treatment until 2012. All other 11 fetuses underwent VLA without previous shunting. Eleven fetuses (91.7%) were born at term at a median gestational age of 39+1 (range, 37+5–41+2) weeks. There was 1 premature delivery after PPROM at 29+4 weeks of gestation. In 7 (58.3%) fetuses, complete cessation of blood flow was achieved after a single intervention, while in 5
Intrafetal Vascular Laser Ablation of Bronchopulmonary Sequestration
Fetal Diagn Ther DOI: 10.1159/000479793
Results
3
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 3:45:47 PM
Color version available online
Fig. 2. A 700-μm Nd:YAG (neodymium:yttrium aluminium garnet) laser fiber is passed through an 18-G needle.
(2 mg/kg), using a 22-G needle under ultrasound guidance. Then an 18-G needle was inserted through the fetal thorax in the BPS with its tip directly adjacent to the feeding vessel. A 700-μm laser fiber was then passed through and to 2–3 mm beyond the tip of the needle and the feeding vessel. The feeding vessel was coagulated using an output of 50 W for 5–10 s (Fig. 3a). Color Doppler demonstrated immediate cessation of blood flow within the tumor (Fig. 3b). If color Doppler demonstrated residual flow, the tip of the laser fiber was repositioned and coagulation was repeated until complete cessation of blood flow was achieved. Prior to the removal of the needle, the pleural effusion was drained. An amniotic fluid sample was retrieved at the end of every intervention for subsequent karyotyping. The following day, ultrasound was performed to confirm complete cessation of blood flow. If residual flow was present, VLA was repeated the next day. Any intervention-related complications were documented. The postoperative evolution of the BPS was assessed at least once in the referral center, and the sonographic predelivery findings in a standardized transthoracic plane were collected from the referring centers (Fig. 3c). Obstetrical and neonatal data was obtained by chart review. Statistical analysis was performed using the Mann-Whitney U test. All values are given as median (interquartile range) unless indicated otherwise. A p value of
