Congenital diaphragmatic hernia associated with esophageal atresia, tracheoesophageal fistula and total anomalous pulmonary venous connection in a premature twin newborn Kongenitalna dijafragmalna kila udružena sa atrezijom jednjaka, traheoezofagealnom fistulom i totalnim anomalnim utokom plu ć nih vena kod prevremeno ro đ enog blizana č kog novoro đ en č eta

Introduction . Congenital diaphragmatic hernia (CDH) with concomitant esophageal atresia (EA) and tracheo-esophag-eal fistula (TEF) is a very rare condition, with a high mortality rate. Prematurity and congenital heart anomalies addi-tionally increase the mortality rate. This situation is a great challenge for clinicians, requiring multidisciplinary work and adequate treatment strategy. Case report. We presented a premature twin newborn at the gestational age of 33/34 weeks with body mass of 1690 g. The existence of the left CDH was established on prenatal ultrasound exam in the 24th gestational week, and the diagnosis of EA with TEF was made on admittance to our hospital. The cardiac ultrasound exam revealed the total anomalous pulmonary venous connection (TAPVC). The first operation was performed on the day of admittance and consisted of left subcostal laparotomy, diaphragmatic repair, elastic occlusion of the gastroesophageal junction and gastrostomy. The ligation of TEF and esophagoplasty were done 13 days later in the second operation. The lethal outcome during the esophagoplasty was caused by the crisis of pulmonary hypertension and associated congenital heart anomaly (TAPVC). The presence of CDH and EA/TEF in association with TAPVC in a twin newborn has not been reported before in the literature. Conclusion. The treatment of newborns with CDH and EA/TEF requires multidisciplinary well-coordi-nated team work of pediatric surgeons, anaesthesiologists, neonatologists and pulmologists. The standard protocol for the management does not exist, but well-planned staged operations could enable greater survival rate.

Introduction.Congenital diaphragmatic hernia (CDH) with concomitant esophageal atresia (EA) and tracheo-esophageal fistula (TEF) is a very rare condition, with a high mortality rate.Prematurity and congenital heart anomalies additionally increase the mortality rate.This situation is a great challenge for clinicians, requiring multidisciplinary work and adequate treatment strategy.Case report.We presented a premature twin newborn at the gestational age of 33/34 weeks with body mass of 1690 g.The existence of the left CDH was established on prenatal ultrasound exam in the 24 th gestational week, and the diagnosis of EA with TEF was made on admittance in our hospital.Cardiac ultrasound exam revealed total anomalous pulmonary venous connection (TAPVC).The first operation was performed on the day of admittance and consisted of left subcostal laparotomy, diaphragmatic repair, elastic occlusion of the gastroesophageal junction and gastrostomy.The ligation of TEF and esophagoplasty were done 13 days later in the second operation.The lethal outcome during the esophagoplasty was caused by the crisis of pulmonary hypertension and associated congenital heart anomaly (TAPVC).][4][5][6][7][8][9][10][11] , and all cases are sporadic, presented as case reports.Of those 13, there are only 3 case reports with successful management and survival of an infant with left CDH, EA, and TEF [3][4][5] .In 2015 appeared the first single-institution series of 6 newborns with CDH, EA and TEF.Five newborns were operated on, and 3 patients survived 12 .
The cause of the association of CDH and EA is still unknown.Chromosomal abnormalities have been reported, such as a mosaic duplication on the long arm of the chromosome 10, but the genetic cause has not been identified yet 1,5

Case report
A premature twin male infant was born in a provincial hospital by spontaneous vaginal delivery, at the gestational age of 33/34 weeks, with body weight of 1690 g.The existence of the left diaphragmatic hernia (Bochdalek type) was diagnosed on prenatal ultrasound exam in the 24 th gestational week.No other anomalies were found.The Apgar score at birth was 1 and 2 at the 1 st and 5 th minute, respectively.The newborn was intubated immediately after birth, but a nasogastric tube could not be placed.Chest radiography confirmed the left sided diaphragmatic hernia.His twin brother weighed 1900 g, with no diagnosed anomalies, and was further treated in the hospital where he was born.The newborn with diagnosed CDH and suspected EA was transferred to our hospital 6 hours after birth.At the admission the baby was intubated, cyanotic, without nasogastric tube.He was reintubated nasotracheally and pressure controlled mechanical ventilation was started.
The attempt of placing a nasogastric tube was unsuccessful.In the neonatal intensive care unit (NICU) a small amount of barium contrast was given in the nasoesophageal tube, and the radiography confirmed the clinical suspicion of EA.The presence of air in the stomach and intestinal loops situated in the chest pointed to the presence of TEF and left sided CDH (Figure 1).Abdominal ultrasound exam has shown the presence of intestinal loops in the left thoracic cavity, without anomalies on abdominal parenchimatous organs.Cardiac ultrasound exam diagnosed patent ductus arteriosus (DAP) and pulmonary artery hypertension (HAP) and raised the suspicion of total anomalous pulmonary venous connection (TAPVC).
The decision for urgent operative treatment was made, and 4 hours after the admittance and the use of resuscitution measures, the baby was transferred to the operating room.Through the left subcostal incision the left hemidiaphragm was approached.There was no hernial sac.Herniated organs (stomach, small intestine, colon and spleen) were pulled out of the thoracic cavity into the operative field.The anterior rim of the left diaphragm was well developed, and the posterior rim was present as underdeveloped.The chest tube was placed, and the primary reconstruction of the left hemidiaphragm was made by mattress sutures.Malrotation was managed by Ladd operation.Then, a rubber sling was placed around the gastroesophageal junction, pulled through the side hole of the shortened nasogastric tube, and both exteriorized through the abdominal wall, in order to perform moderate angulation and temporary occlusion of the esophagus, so preventing the disastrous effect of TEF.A classical Stamm gastrostomy was made, and the underwater testing of gastrostomy Pezzer tube showed no air leakage through the TEF in the stomach (Figure 2).
Through a period of 13 days mechanical ventilation and all other intensive care measures were applied, but pulmonary hypertension crisis were repeated and blood oxygenation rate varied from 32% to 82%.The chest radiography showed the recovery of the left lung.
Meropenem and vankomycin were administered initially, but acinobacter was diagnosed in the tracheal aspirate, so colistimethate sodium was added 13 .Haemocultures were sterile.
Total parenteral nutrition was administered.Nonobstructive TAPVC was confirmed on postoperative control cardiac ultrasound exam.The second operation was undertaken on the 13 th postoperative day.Through the right posterolateral thoracotomy the TEF was approached and the large fistula was ligated and transected.The operation was continued with improved blood oxygenation rate of 80% and the esophagoplasty was started.During this procedure bradicardia, desaturation crisis, arterial hypotension and pulmonary oedema developed and, in spite of all resuscitution measures, led to the lethal outcome.

Discussion
In babies with CDH and EA/TEF the operative strategy is of the greatest importance.Sapin in 1996 reported the first successfully treated infant with CDH and EA/TEF, suggesting the laparotomic repair of CDH and avoiding thoracotomy in the first operation.The ligation of the TEF and esophagoplasty were postponed for the second operation.This attitude was based on the fact that laparotomy is better tolerated than thoracotomy, especially in the presence of pulmonary hypertension and left lung hypoplasia, which are the major problems in newborns with CDH.The disastrous effects of gastric acid reflux into respiratory system through TEF the author precluded by temporary occlusion, i.e.
angulation of distal esophagus, placing a rubber sling around gastroesophageal junction.
The gastrostomy was placed for gastric decompression.The ligation of TEF and esophagoplasty were performed after the baby's recovery, 2 weeks after the first operation 3 .This attitude was applied in the case reported by Charles in 2014, also with positive outcome and the baby's survival 5 .An alternative strategy, the ligation of TEF and esophagoplasty in the first operation, and the repair of CDH in the second operation, with good outcome, was reported in 2013 4 .The third operative strategy, reported by Zahn et al.
in 2015, suggested CDH repair and ligation of distal esophagus 2 cm below TEF via transabdominal approach, and esophagoplasty 4-6 weeks later.This strategy was applied in 5 newborns and 3 patients survived 12 .
In our patient with CDH, EA and TEF, we applied the principles of staged operative repair proposed by Sapin and Charles.The first operation, consisted of diaphragmatic repair, temporary occlusion of distal esophagus by silicone rubber sling and gastrostomy, was performed without major problems in baby's respiratory and circulatory status, during and after the operation.So we could conclude that the proposed strategy is appropriate for babies with CDH and EA/TEF.The rubber sling around the gastroesophageal junction has proved to be efficient in the temporary occlusion of distal esophagus and prevention of harmful effects of TEF.In our patient there were no problems neither in the left hemidiaphragm repair, nor in the closure of the abdominal wall, so that prosthetic material need not to be applied.The recovery of the left lung, as proved on control postoperative chest radiography, was very satisfactory.The timing of the second operation, planned for the ligation of TEF and esophagoplasty, was determined according to literature suggestions and the baby's overall condition, and performed the 13 th day of life.The sudden worsening of baby's condition and lethal outcome during the esophagoplasty was caused by pulmonary hypertension crisis and associated congenital heart anomaly (TAPVC).The association of CDH with EA/TEF and TAPVC has not been reported yet in the literature.
Also, the presence of CDH and associated EA/TEF in one of twins is not mentioned in any of the references.

Conclusion
CDH (Bochdalek type) with associated EA and TEF is a very rare condition.Pulmonary hypertension and lung hypoplasia, caused by diaphragmatic hernia, and gastric acid reflux into respiratory tract and gastrointestinal distension in the chest cavity, caused by TEF, lead to very high mortality rate.The treatment of these babies requires multidisciplinary, well coordinated team work of pediatric surgeons, anaesthesiologists, neonatologists and pulmologists.The standard protocol for the management does not exist, but well planned staged operations could improve survival rate.

words: congenital diaphragmatic hernia; esophageal atresia; tracheo-esophageal fistula; total anomalous pulmonary venous connection; premature newborn; twin; surgical treatment Apstrakt Uvod.
Conclusion.The treatment of newborns with CDH and EA/TEF requires multidisciplinary well coordinated team work of pediatric surgeons, anaesthesiologists, neonatologists and pulmologists.The standard protocol for the management does not exist, but well planned staged operations could enable greater survival rate.Kongenitalna dijafragmalna kila (CDH) udružena sa atrezijom jednjaka (EA) i traheo-ezofagealnom fistulom (TEF) je veoma retko stanje, sa visokom stopom smrtnosti. of 3.318.966live births and stillbirths in the period 1983-1996, reported 433 cases with Bochdalek type CDH (1.3:10000 births), 893 cases with EA/TEF (2.7:10000 births), and 18 cases with CDH and EA/TEF (0.05:10000 births).The mortality rate of patients with CDH associated with EA/TEF is very high, and it is reported that 16 of 17 babies were stillborn or died soon after birth 1 .Until 2015 there were only two database publications in the literature, announced in 2005 and 2013, and each reports approximately 20 cases of CDH with EA from different registries 1,2 .Only 13 cases have been reported in details