complications in infants with CDH [3,4]. With the recognition that the initial treatment should be directed at minimizing pulmonary hypertension due to the ...
Master Universitario II livello in Chirurgia Mininvasiva Pediatrica Direttore: Prof. Mario Lima
Minimally Invasive Surgery for Congenital Diaphragmatic Hernias: Single-Center Experience over the Last 7 Years
Tesi di Master
Relatore
Dr. Raed Al-Taher
Chiar.mo Prof. Mario Lima
Anno Accademico 2014-2015
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TABLE OF CONTENTS INTRODUCTION .......................................................................................................................................... 4 EMBRYOLOGY AND PATHOGENESIS............................................................................................................ 5 PREVALENCE AND EPIDEMIOLOGY.............................................................................................................. 7 CLASSIFICATION .......................................................................................................................................... 8 DIAGNOSIS................................................................................................................................................ 10 PRENATAL DIAGNOSIS ...................................................................................................................................... 10 POSTNATAL DIAGNOSIS..................................................................................................................................... 14 DIFFERENTIAL DIAGNOSIS ......................................................................................................................... 15 PRENATAL ...................................................................................................................................................... 15 POSTNATAL .................................................................................................................................................... 15 CLINICAL MANIFESTATIONS ...................................................................................................................... 15 PRENATAL PRESENTATION ................................................................................................................................. 15 POSTNATAL PRESENTATION................................................................................................................................ 15 LATE PRESENTATION ........................................................................................................................................ 16 PROGNOSTIC FACTORS ............................................................................................................................. 17 PRENATAL MANAGEMENT ........................................................................................................................ 19 IN UTERO FETAL THERAPY .................................................................................................................................. 20 POSTNATAL MANAGEMENT ..................................................................................................................... 21 OVERVIEW ..................................................................................................................................................... 21 PREOPERATIVE MEDICAL MANAGEMENT ............................................................................................................... 22 OPERATIVE MANAGEMENT ................................................................................................................................ 27 COMPLICATIONS ....................................................................................................................................... 37 ACUTE COMPLICATIONS .................................................................................................................................... 37 LATE COMPLICATIONS ....................................................................................................................................... 37 SURVIVAL.................................................................................................................................................. 40 POST-DISCHARGE MANAGEMENT ............................................................................................................. 41 MATERIAL AND METHODS ........................................................................................................................ 42 RESULTS .................................................................................................................................................... 50 BOCHDALEK HERNIAS ....................................................................................................................................... 51 MORGAGNI HERNIAS ....................................................................................................................................... 60 CENTRAL HERNIA AND DIAPHRAGMATIC EVENTRATION ........................................................................................... 63 DISCUSSION .............................................................................................................................................. 66 CONCLUSION ............................................................................................................................................ 73 REFERENCES .............................................................................................................................................. 75
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INTRODUCTION Congenital diaphragmatic hernia (CDH) is a developmental discontinuity of the diaphragm that allows abdominal viscera to herniate into the chest. It is one of the most commonly encountered congenital anomalies, with an incidence of approximately 1 in 3,000 live births [1]. Affected neonates usually present in the first few hours of life with respiratory distress that may be mild or so severe as to be incompatible with life. Although the diaphragmatic defect is surgically correctable, in utero herniation of viscera results in pulmonary hypoplasia and pulmonary hypertension, which are often fatal. With the advent of antenatal diagnosis and improvement of neonatal care, survival has improved, exceeding 90% in some centers [2], but there still remains significant risk of death and complications in infants with CDH [3,4]. With the recognition that the initial treatment should be directed at minimizing pulmonary hypertension due to the pulmonary hypoplasia associated with CDH, a tremendous focus has centered on the initial medical management of children with CDH prior to any surgical correction. During the past decade, there has been no significant evolution in the surgical management of neonatal CDH. The arrival of small videoscopic instrumentation allowed the management of neonatal CDH by pediatric surgeons trained to perform minimally invasive surgical (MIS) procedures, which can lead to less postoperative morbidity, faster recovery, and shorter hospitalization, and in the other hand, it can also precipitate complications such as pulmonary acidosis, hypoxemia, pulmonary hypertension, and mortality [5]. The first report of a laparoscopic CDH repair was published in 1995 by Van der Zee and Bax [6], and it was a left posterolateral hernia in a 6-month-old infant. In 2000, Lima et al. [7], have published a report of successful laparoscopic primary repair of Morgagni-Larrey hernia in a 3-year-old girl. Also, in 2001, Lima et al., have published five cases of diaphragmatic diseases which were managed laparoscopically (2 Morgagni-Larrey hernias, 1 recurrent left Bochdalek hernia, 1 diaphragmatic dysontogenetic cyst, and 1 huge congenital sliding and rolling hiatal hernia) [8]. In 2001, Becmeur et al. [9], have published a report of successful thoracoscopic repair in three cases of late-presenting CDH. Later on, the use of MIS for neonatal cases was shown to be feasible and safe. Liem, in 2003, has published nine cases of thoracoscopic repair of CDHs, three of them were 4
neonates with left Bochdalek hernia [10]. Until most recently, Gomes Ferreira et al. in 2009 has published a multicenter study for neonatal MIS CDH repair comparing laparoscopic and thoracoscopic approaches [11]. In our institution, MIS has been widely used for the repair of anterior (Morgagni-Larrey), postero-lateral (Bochdalek), central diaphragmatic hernias, as well as diaphragmatic eventration in neonates, infants, and children. We review our experience with minimally invasive congenital diaphragmatic hernia repair and evaluate patient selection, operative technique, feasibility, safety, operating time, and clinical outcomes.
EMBRYOLOGY AND PATHOGENESIS The development of the human diaphragm is a complex, multicellular, multi-tissue interaction that is poorly understood. Precursors to the diaphragm begin to form during the fourth week of gestation. The diaphragm is thought to develop from the fusion of four embryonic components: anteriorly by the septum transversum, dorsolaterally by the pleuroperitoneal folds (PPF), dorsally by the crura from the esophageal mesentery, and posteriorly by the body wall mesoderm (Figure 1). As the embryo begins to form, the septum transversum migrates dorsally and separates the pleuropericardial cavity from the peritoneal cavity. At this point, the pleural and peritoneal cavities still communicate. The septum transversum interacts with the PPF and mesodermal tissue surrounding the developing esophagus and other foregut structures, resulting in the formation of primitive diaphragmatic structures. Bound by pericardial, pleural, and peritoneal folds, the paired PPFs now separate the pleuropericardial and peritoneal cavities. Eventually, the septum transversum develops into the central tendon [12]. As the PPF develops during the sixth week of gestation, concurrently, the pleuroperitoneal membranes close and separate the pleural and abdominal cavities by the eighth week of gestation. Typically, the right side closes before the left. Ultimately, the phrenic axons and myogenic cells destined for neuromuscularization migrate to the PPF and form the mature diaphragm [13]. 5
Figure 1. Embryogenesis of the diaphragm. (From Lima M, Ruggeri G (2015) Difetti Diaframmatici. In: Chirurgia Pediatrica. EdiSES, Napoli, pp 97-120)
The musculariztion of the primitive diaphragm is thought to be from the inner thoracic musculature as the diaphragm closes. Another theory for CDH development is failure of muscularization of the future diaphragm prior to complete closure of the canal [14]. Inadequate closure of the pleuroperitoneal canal allows the abdominal viscera to enter the thoracic cavity when it returns from the extraembryonic coelom as well as the liver to herniate into the chest. Consequently, the limited intrathoracic space, due to the visceral herniation, results in pulmonary hypoplasia. Visceral herniation into the thoracic cavity occurs during the critical period of lung development when the bronchi and pulmonary arteries are undergoing branching, from just after the third week post-fertilization through the 16th week of gestation. Interference with normal lung development at this time results in decreased bronchiolar branching and loss of pulmonary mass (pulmonary hypoplasia) [15], as well as truncation and over-muscularization of the pulmonary arterial tree, leading to pulmonary hypertension with structural and functional pulmonary vascular abnormalities after birth [16]. Pulmonary hypoplasia is most severe on the ipsilateral side. However, pulmonary hypoplasia may develop on the contralateral side if the mediastinum shifts and compresses the lung. Abnormal development of the lung also results in a dysfunctional
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surfactant system late in gestation and after birth [17,18] and may cause hypoplasia of ipsilateral cardiac structures [19]. The pathogenesis of CDH has not been established definitively. The leading theories are that it is due to failure of normal closure of the pleuroperitoneal folds during the 4 to 10 weeks post-fertilization or to genetic or environmental triggers that disrupt differentiation of mesenchymal cells during formation of the diaphragm and other somatic structures [20]. Familial cases involving autosomal recessive, autosomal dominant and X-linked inheritance patterns have been reported [21]. However, the vast majority of CDH occurs sporadically, with no identifiable familial link. Even among monozygotic twin pairs, concordance for CDH is rare [22]. Many different genetic defects (e.g., aneuploidies, deletions, duplications, translocations) have been identified among sporadic cases [23]. These cases may represent de novo mutational events in genes for normal diaphragmatic development or reflect polygenic or multifactorial inheritance, or both. The possibility of an environmental trigger is supported by cases of CDH as a manifestation of vitamin A deficiency [24,25] and after exposure to thalidomide, anticonvulsants, and quinine [26].
PREVALENCE AND EPIDEMIOLOGY The prevalence of CDH is approximately 1 to 4 per 10,000 births [27,28]. An analysis of data from 31 population-based European registers over a 29-year period and including over 12 million births reported the prevalence of CDH was 2.3 per 10,000 births and the prevalence of isolated CDH was 1.6 per 10,000 births [28]. Most series have not observed a sex association, although some reported a slightly higher incidence in males. Prevalence does not appear to be associated with maternal age [28].
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CLASSIFICATION An anatomical system of classification is used (Figure 2) [29]:
Figure 2. Scheme of the various types of diaphragmatic hernias. (From Lima M, Ruggeri G (2015) Difetti Diaframmatici. In: Chirurgia Pediatrica. EdiSES, Napoli, pp 97-120)
Postero-lateral Hernia (Hernia of Bochdalek); the most common type of all diaphragmatic hernias (80-90%). Occurs on the left side in 80-85% of cases, 15-20% on the right side, and very rarely it could be bilateral. Anterior Hernia (Hernia of Morgagni-Larrey); the defect occurs through the foramen of Morgagni at the anterior part of the diaphragm and usually is accompanied with hernial sac. It constitutes 2% of all diaphragmatic hernias. Central Hernia; it is very rare, and involves the central tendon of the diaphragm. Diaphragmatic Eventration; it is a displacement of abdominal contents into the thorax as a result of a congenitally thin, hypoplastic but intact diaphragm. It is rare and usually has less severe effects on lung development and function than CDH. Diaphragm Agenesis; the hernial defect is very large, and it involves the absence of most or all of the hemidiaphragm. 8
The diaphragmatic defect is usually (80-90%) posterolateral (Bochdalek hernia), but may be anterior retrosternal or peristernal (Morgagni-Larrey hernia), or rarely central. Herniation usually occurs on the left (80 to 85%); right-sided diaphragmatic hernias occur in only 10 to 15 percent of cases [30,31]. Bilateral herniation is uncommon (85 percent or postductal PaO2 >30 mmHg Peak inspiratory pressure >28 cm H2O or mean airway pressure >15 cm H2O Hypotension that is resistant to fluid and inotropic support Inadequate oxygen delivery with persistent metabolic acidosis
Exclusionary criteria for ECMO vary between institutions. Most ECMO centers exclude patients with lethal chromosomal abnormalities or severe intracranial hemorrhage. As a result, traditional inclusion criteria for ECMO also include all of the following [95]: Birth weight >2 kg Gestational age >34 weeks Absence of intracranial hemorrhage >grade I Absence of chromosomal anomalies Criterion for withdrawal of ECMO support includes any extension of intracranial hemorrhage. Infants are at risk for intracranial bleeding due to the need for continuous anticoagulation with heparin. Head ultrasounds used to monitor for intracranial bleeding are performed before initiation of ECMO, daily for the first five days and then every other day while on ECMO support to detect and monitor any extension of intracranial hemorrhage. In addition, head ultrasounds are performed emergently for onset of seizures, change in neurologic status, or following any significant clinical event (e.g.,
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surgical repair of CDH, and episodes of hypotension or hypertension). Another consideration for withdrawal is worsening clinical status despite optimal therapy. It is difficult to accurately assess the benefit of ECMO given the absence of clinical trials. However, efficacy is demonstrated by comparing observational data showing 50 percent survival for these patients who have failed conventional therapy, with historical data suggesting a much lower survival rate without ECMO intervention [96].
Operative Management Timing of Operation With an improved understanding of its pathophysiology, repair of CDH is no longer considered an emergency procedure. However, the optimal timing for repair remains unclear. Historically, early repair was thought to improve ventilation by reducing intrathoracic pressures after reduction of the herniated viscera. However, this strategy often led to urgent procedures being performed on unstable infants [97]. A paradigm shift in management to delay the operative repair until the infant is stable became widely adopted in the early 1990s [98]. Several studies have shown no difference in mortality rate or the need for ECMO in infants undergoing early vs late repairs [99], including two randomized trials of early (50% which can occur as a result of a tight abdominal wall closure [103]. Careful attention should be paid to the peak airway pressures as the abdominal fascia is closed. Respiratory compromise should alert the surgeon to leave the abdomen open. This approach is more often needed in CDH infants on ECMO [104]. Temporary closure can be achieved using just the skin or a prosthetic silo.
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Delayed closure, especially in those infants on ECMO, should be attempted after the generalized edema has resolved or the intra-abdominal domain has enlarged [105]. The routine use of chest tubes after CDH repair to drain pleural fluid has been abandoned [101]. One concern is that the chest tube can cause ipsi- and contralateral lung injury secondary to mediastinal shift, especially if connected to suction. The thoracic space will eventually fill with fluid, and the lung will gradually grow. Tube thoracostomy should only be used for postoperative chylothorax or pleural fluid causing hemodynamic compromise [106]. If a chest tube is needed, it is positioned in the thoracic cavity prior to final closure of the diaphragm, and should be removed early to avoid infectious complications.
Minimally Invasive Techniques The respiratory sequelae and other morbidity seen after open CDH repair has prompted surgeons to adopt minimally invasive surgical (MIS) approaches. Both thoracoscopic and laparoscopic repairs have been performed (Figure 7) [107-109]. Data from the CDHR show that laparoscopic and thoracoscopic strategies are being used worldwide, and have been utilized in 20% of centers since 1995 [107]. MIS techniques have been used for primary repair as well as prosthetic patch closure with suggested advantages of less postoperative pain, avoidance of thoracotomy-associated complications, and an overall reduction of surgical stress [110].
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Figure 7. Thoracoscopic patch repair of left CDH in a 3-day-old neonate.
The sensitivity of CDH infants to hypercapnia and acidosis has drawn concerns regarding the utilization of MIS. The overall benefits of MIS are questioned because: CDH neonates may absorb the CO2 insufflation [111]; and insufflation with CO2 can raise intracavity pressures that may limit venous return, end-organ perfusion, and tidal volume. The combination of CDH-related pulmonary hypoplasia, PHTN, and labile pulmonary vascular reactivity may be detrimental during MIS operations. Although increases in CO2 absorption during MIS are generally well tolerated in infants, CDH neonates specifically demonstrate greater changes in end-tidal CO2 (ETCO2) and impaired elimination of CO2 during thoracoscopy and laparoscopy [112]. Hypercapnia and the associated acidosis may result in increased pulmonary shunting. Patient selection is paramount for successful completion of an MIS repair as well as for minimizing operative morbidity. Historically, MIS was reserved for stable infants with
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anticipated small defects. Utilizing anatomic markers such as stomach herniation, surgeons have attempted to predict which defects might be amenable to MIS repairs [113]. Initially, the radiographic presence of the nasogastric tube within the abdomen and minimal respiratory compromise (PIP < 24 mmHg) were thought to predict a successful thoracoscopic repair. One group reported 95% success rates with thoracoscopic repairs when patients did not have a significant congenital cardiac anomaly or the need for preoperative ECMO, and had a PIP ≤ 26 cmH2O, and an oxygenation index ≤5 on the day of surgery [114]. Another group has advocated for strict preoperative selection criteria for thoracoscopic repair, including minimal ventilatory support (PIP < 24 mmHg), no clinical or sonographic evidence of PHTN, and an intra-abdominal stomach [113]. On the other hand, infants requiring preoperative ECMO have undergone successful repair with an MIS approach [111]. Large defects that require patch repairs [114,111] and right-sided defects are no longer contraindications to MIS [115]. Although success with laparoscopic and thoracoscopic repairs have been reported, comparative evidence between MIS and open approaches has been limited to singleinstitution experiences or retrospective analyses. A recent single-institution review of 54 neonates undergoing unilateral CDH repair between 2006–2010 was published [116]. Thirty-five neonates underwent attempted thoracoscopic repair with 26 being successfully completed. During the same time interval, 19 open CDH repairs were performed. Recurrence was higher after the thoracoscopic repair (23% vs 0%). There were no individual factors that were found to be predictive of recurrence with the thoracoscopic approach. In another report, a systematic review and meta-analysis of neonatal endosurgical CDH repairs identified only three eligible studies comparing open to endosurgical repair [117]. The overall survival rate for MIS patients was significantly higher compared with patients undergoing open repair (82.9% open and 98.7% MIS, P < 0.01) [114]. These results suggest a significant survival advantage for the MIS approach, even after risk-adjustment. However, the data are more likely the result of selection bias based on surgeon preference regarding which patients were good candidates for MIS.
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Although the ability to perform MIS repair of CDH has been shown, the short- and longterm outcomes regarding the durability and recurrence rates for an MIS approach are less clear. The reported overall recurrence rates for MIS repair range from 5–23.1% [114,111], with early recurrences as high as 23–33% [116]. In another study, MIS repairs were performed in only 3.4% infants with CDH, but had a significantly higher in-hospital recurrence rate compared to open (7.9% vs 2.7%, P < 0.05) [107]. The true risks and benefits of the MIS approach for CDH repair, including the impact of re-operations, remain unclear. At the very least, recurrence seems to be higher. Robotic CDH repair has been demonstrated to be feasible and safe [118-120]. Proponents of robotic CDH repair tout the increased degrees of freedom of the articulating instruments for suturing.
Diaphragmatic Replacements Repair of large diaphragmatic defects is a challenge, usually requiring diaphragmatic replacement with a prosthetic patch or autologous tissue. In one large study, 48.3% of infants undergoing CDH repair required diaphragmatic replacement [107]. Comparative studies between patch and primary repairs have consistently shown increased morbidity and mortality in the patch groups, most likely due to the large defect size and the associated severity of the pulmonary hypoplasia [121]. In many studies, patch repair has been utilized as a surrogate for defect size and disease severity (i.e., larger the defect = increased severity of disease).
Nonabsorbable Synthetic Patches Synthetic patches such as polytetrafluoroethylene (PTFE or Gore-Tex®) or composite polypropylene (Marlex®) represent the majority of the mesh replacements used in neonates with a large CDH [122]. Advantages to synthetic patches include: (1) immediate availability; (2) minimal preparation time; (3) easily cut to fit the diaphragmatic defect;
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and (4) less tissue dissection, reducing the risk of hemorrhage, especially during repair on ECMO. However, there are several disadvantages to synthetic patches for CDH repair. PTFE, anchored to the chest wall, can potentially produce a tethering point for creating a pectus-type deformity. There is an increased incidence of bowel obstruction, need for splenectomy, patch infections, and abdominal wall deformities [123]. The overall recurrence rate has been reported to be as high as 50% with a bimodal distribution showing early recurrence in the first months after repair and late recurrence years later [122]. Early recurrences for defects requiring a patch are most likely due to lack of tissue adhesion or scarring and an incomplete muscular rim, which then requires anchoring the patch to the ribs or esophagus. PTFE tends to scar and retract over time, which may lead to late recurrences in the growing child. In an effort to prevent CDH recurrence, one group described a cone-shaped, double-fixed PTFE patch to allow expansion over time [124]. The recurrence rate decreased from 46% to 9% at one year after repair. Similar results have been seen with a mesh plug and patch technique in the setting of a recurrent CDH [125]. Another group described a double-sided composite patch consisting of PTFE and type-1 monofilament, macroporous Marlex. Utilizing a pledgeted, nonabsorbable running suture, the recurrence rate was 2.2% with a mean follow-up of 49 months [126].
Absorbable Biosynthetic Patches Absorbable biosynthetic materials have been utilized as an alternative replacement to synthetic patches. They have been reported to decrease complications by offering a lower risk of infection and the ability of the patch to grow with the patient. Surgisis® (SIS) is an acellular, bioengineered porcine intestinal submucosal matrix that consists of a type-I collagen lattice with embedded growth factors. This non-crosslinked biological matrix promotes fibroblast migration and cellular differentiation. First described for repair of incisional, inguinal, and paraesophageal hernias, SIS® has also been utilized for CDH repair [127]. Permacol® is an acellular porcine dermal collagen patch consisting of collagen fibers with cross-linked lysine and hydroxylysine. By promoting an inflammatory response in a manner similar to wound healing, the neodiaphragm is more pliable and, subsequently, 34
less prone to recurrence. One group reported no recurrences observed with a median follow-up of 20 months, while recurrences were noted in 2% of patients with primary repair and 28% with PTFE [128]. AlloDerm® is an acellular human cadaveric dermal patch that is cross-linked for rapid revascularization. Animal studies have demonstrated revascularization and cell repopulation within one month. Surgimend® is an acellular fetal bovine interwoven dermal collagen that promotes increased type-III collagen. Because there is no cross-linking, there is increased collagen resistance leading to greater durability. Poly-lactic-co-glycolic acid (PLGA) is a collagen scaffold that promotes neovascularization
and
autologous
tissue
regeneration.
Animal
studies
have
demonstrated ingrowth of fibroblasts resulting in a thicker neodiaphragm [129]. Despite the theoretical advantages, these absorbable biosynthetic patches remain imperfect as diaphragmatic substitutes. Thinning of the patch and incomplete muscular ingrowth, especially in large defects where native diaphragmatic muscle is absent, have been found. These biosynthetic patches are also prone to recurrences, similar to nonabsorbable patches. In addition, organ adherence may be required for neovascularization, and these organs often include the small bowel, spleen, or liver. Subsequently, biologic patches can be associated with adhesive bowel obstruction [130].
Autologous Tissue Patches Complications with synthetic and biosynthetic patches have prompted some surgeons to advocate for primary or staged repair with autologous muscle flaps for large diaphragmatic defects. Muscle flaps offer the advantage of using a vascularized tissue that will grow with the infant and has a minimal inflammatory response. In 1962, Meeker and Snyder first described using the anterior abdominal wall for CDH repair [131]. A few years later came the description of a split abdominal wall muscle flap used to repair a large defect in a newborn. More recently, another group described using a split abdominal muscle flap consisting of the internal oblique and transversus abdominis muscles for primary repair of large defects. Another approach is to use a lower abdominal incision and the transversus abdominis muscle for repair on ECMO. Due to the avascular dissection 35
plane between the muscle layers, this approach may minimize the risk of bleeding while on ECMO. In a recent report, the recurrence rate for split abdominal wall muscle flaps was only 4.3%, while the recurrence rate for patch repair was 50% [132]. Chest wall muscles, such as the latissimus dorsi muscle, have also been used as diaphragmatic substitutes. For very large defects, such as agenesis of the diaphragm, the combination of the latissimus dorsi and serratus anterior muscles has been described [133]. The disadvantage with using local chest wall muscle flaps is the resulting body wall deformity. Consequently, chest wall muscle flaps have been primarily reserved for patients with a recurrent CDH. Although autologous muscle flaps are vascularized and tend to grow with the child, these diaphragmatic reconstructions with latissimus dorsi/serratus muscle flaps have been shown to atrophy over time due to denervation of the graft [133]. In addition, the lack of innervation prevents the natural physiologic movement of the diaphragm. As a result, the reverse latissimus dorsi flap with a microneural anastomosis of the phrenic nerve to the thoracodorsal nerve has been tried to prevent muscle atrophy and to allow physiological muscle movement [133].
Tissue Engineered Patches Tissue engineered muscle may provide a replacement for functional skeletal muscle and does not atrophy. Although the supporting three-dimensional scaffold is a key component of tissue engineering, skeletal muscle regeneration relies on a cell source with myogenic potential. Amniotic fluid is an abundant source of stem cells with myogenic potential. Tissue engineering strategies could utilize amniotic stem cells collected at the time of amniocentesis to develop a muscular patch used during postnatal repair. Fuchs and colleagues have developed a fetal tissue-based diaphragm engineered from mesenchymal amniocytes [134]. In preclinical studies, these bioengineered diaphragms demonstrated improved mechanical and functional outcomes when compared to acellular bioprosthetic patches [135].
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COMPLICATIONS Acute complications The most serious complication post-repair of CDH is persistent pulmonary hypertension. Some patients may require extracorporeal membrane oxygenation (ECMO). Other complications early in the postoperative course include hemorrhage, chylothorax, and patch infection [136].
Late complications Late complications include chronic respiratory disease, recurrent hernia/patch problems, spinal/chest wall abnormalities, gastrointestinal difficulties, and neurological sequelae [137]. Pulmonary — Survivors treated with ECMO are at risk for respiratory infections and chronic lung disease during the first two years of life. However, pulmonary function and status improve in most patients by 24 months of age with lung growth [138]. Outcome studies have reported that adolescent survivors have mild to moderate airway obstruction detected by pulmonary function studies and a mild decrease in exercise capacity [139]. In most cases, there is little to no impact on daily life activities. Recurrent hernia — Recurrent diaphragmatic hernia occurs in 2 to 22 percent of all CDH survivors. Recurrent diaphragmatic herniation is usually diagnosed by chest or contrast studies prompted by respiratory or gastrointestinal symptoms. Earlier case series reported recurrence was highest (27 to 57 percent) in patients requiring patch repairs and ECMO support, as they generally had larger defects [121,140]. However, subsequent reports have noted a substantially lower rate of recurrent herniation in patients corrected with a patch repair. The site of recurrence with a patch is typically medial. Patch-related — Patches may become chronically infected, requiring removal of the patch and diaphragmatic reconstruction, preferably with native tissue [121]. Although
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repair using a patch was generally associated with a high rate of recurrence of hernia (up to 40 percent) in earlier case series, subsequently lower recurrence rates of 4 to 5 percent have been reported using Gore-Tex® patches [141]. The need for patch repair has been associated with a higher rate of chest wall deformities such as pectus excavatum, pectus carinatum, and thoracic scoliosis. Chest wall deformities have been reported in up to 50 percent of patients who were initially repaired with a patch [140]. It remains uncertain whether the deformity is directly related to the use of a patch, or a consequence of the severity of the CDH and subsequent incongruent lung growth. Gastrointestinal — Gastroesophageal reflux disease (GERD) and foregut dysmotility are prominent chronic abnormalities in CDH patients. The reported incidence of GERD in patients with CDH ranges from 40 to 50 percent [142]. In several case series, antireflux surgery is performed in 15 to 20 percent of all patients with CDH [142]. There are several anatomic factors that may contribute to the development of reflux [143]: Disturbance of normal esophageal and gastroesophageal junction due to mediastinal shift and compression. Shortened intraabdominal esophagus. Obtuse angle of His. Deformation of the diaphragmatic crus by closure. Pressure changes related to increased work of breathing. Potential neurological defects. Intestinal obstruction secondary to adhesions occurs in 10 percent of patients with CDH. All patients with CDH have malrotation or malfixation of the intestines, and, thus, a predisposition to development of volvulus. Rates of this potentially devastating complication vary from 3 to 9 percent [144]. Failure to thrive — Subsequent failure to thrive (FTT) has been reported in 30 to 86 percent of infants with CDH. Risk factors include prematurity, prolonged ventilation and oxygen requirement at discharge [145]. Increased work of breathing may also contribute to FTT by making oral feeding and swallowing challenging.
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Affected patients may require supplemental feeding via nasogastric or gastrostomy tubes for adequate caloric intake. Many patients will require gastrostomy tube feedings because of oral aversion to feeding due to reflux or need for supplementation. The incidence of gastrostomy tube feedings may be increasing with the increase in survival rate, especially in patients with severe CDH [145]. Neurodevelopment impairment — Abnormalities detected by cranial imaging include intraventricular hemorrhage, infarction, periventricular leukomalacia, and extra-axial fluid collections. MR imaging of survivors of severe CDH demonstrates delayed maturation and structural brain abnormalities including periventricular leukomalacia and varying degrees of intracranial hemorrhage [146]. These
abnormalities
likely
lead
to
long-term
neurologic
complications.
Neurodevelopmental impairment has been reported in 30 to 80 percent of patients, and has included both motor and cognitive function. Neurocognitive impairment and delay has been reported to persist into school age. In particular, hearing loss is common, with reported prevalence of 30 to 50 percent [147]. The prevalence of sensorineural hearing loss (SNHL) ranges from none in some series to 100% in others [148,149]. SNHL has been detected in as many as 50% of CDH children that initially tested as normal [149]. The etiology of SNHL is unclear. Most likely, SNHL is due to a combination of treatments and severity of disease. Because of the increased risk of SNHL in CDH children, audiological testing is warranted as early as 6 months of age [150]. Musculoskeletal deformities — Chest deformities including pectus excavatum, pectus carinatum, and scoliosis are common, particularly in patients with repaired large CDH [151].
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SURVIVAL The postnatal survival rate at tertiary centers has improved, with reported rates of 70 to 92 percent [152]. This increased survival rate appears to be a result of the shift from early surgical intervention to intensive preoperative supportive care aimed at avoiding lung injury, followed by surgical correction. However, these data represent the survival rate of cases of CDH that were full term infants born or transferred to tertiary care centers with available skilled personnel and access to advanced technology (e.g., ECMO). These survival rates do not account for the cases of CDH that are stillborn or died outside a tertiary center, or fetal loss due to spontaneous or therapeutic abortion [152]. Factors associated with decreased survival include: Prematurity – A review from the Congenital Diaphragmatic Hernia Study Group (CDHSG) reported lower survival for preterm infants compared with term infants (54 versus 73%) [153]. Cardiac abnormalities – Data from the CDHSG showed that patients with major complex cardiac defects (e.g., single ventricle physiology, left heart obstructive lesions, and transposition of the great arteries) have a significantly lower survival rate (36%) compared with those with either minor heart defects (67%) or no heart defect (73%) [154]. Persistent and severe pulmonary hypertension [155] Need for transport – Neonatal transport of patients with CDH is associated with poorer survival compared with infants who are inborn at a tertiary center with expertise in the management of CDH [156]. Low preductal oxygen and high carbon dioxide saturation – Survival is poorer in infants whose highest recorded preductal oxygen saturation is below 85 percent in the first 24 hours of life compared with those with higher levels. In addition, elevated arterial blood gas PaCO2 greater than 70 mmHg is associated with decreased survival [157]. 40
Defect size – Infants with very large defects have a poorer outcome [158]. Right versus left-sided lesion – It is unclear whether the side of the lesion affects survival. In one case series of 267 patients, disease severity appeared to be greater in patients with right-sided lesions, resulting in a lower survival rate (50 versus 75 percent) [60]. However, in two other large case series of 220 patients, there was no difference in survival between patients with right versus left-sided lesions, although patients with right-sided lesions were more likely to undergo a patch repair and have a recurrent hernia [159,155].
POST-DISCHARGE MANAGEMENT Because of the associated significant morbidities (i.e., pulmonary complications, neurodevelopmental delay, gastroesophageal reflux, hearing loss, and poor growth), care of survivors with CDH following discharge from the hospital is challenging. Structured follow-up, often involving a multidisciplinary team, facilitates recognition and treatment of these complications. In 2008, the American Academy of Pediatrics section on Surgery and the Committee on Fetus and Newborn published a comprehensive plan for the detection and management of the associated morbidities for clinicians who provide care for these patients [150]. This plan provides a recommended schedule that includes the following:
Measurement of growth parameters at each visit Chest radiography if a patch was used in repair of the defect or if there are respiratory or gastrointestinal symptoms Pulmonary function testing based upon clinical status Respiratory syncytial virus prophylaxis Echocardiography if previously abnormal or supplemental oxygen used Brain imaging if previous abnormal head ultrasound, abnormal neurologic status, patch repair, or ECMO used Hearing evaluation Developmental screening Oral feeding assessment Upper gastrointestinal study based upon clinical status Scoliosis and chest wall deformity screening
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MATERIAL AND METHODS We have retrospectively revised the electronic registry system of the pediatric surgery department in S. Orsola University Hospital of Bologna from January 2008 until November 2015 (7 years period) searching for all cases that were assigned as CDH whatever the type is and underwent a surgical intervention. All cases of CDH with an initial attempt at MIS repair have been investigated. For every patient, we have collected the following data: demographic indicators, perinatal history, mode of presentation, diagnostic studies, associated anomalies, prenatal management, postnatal management, timing of surgery, surgical technique, herniated organs, use of prosthesis, duration of procedure, length of ICU stay, length of hospital stay, surgery related complications, disorder related complications, and post-discharge
management.
Comparative analysis of the
aforementioned data was conducted. All of the patients who were considered hemodynamically stable have been offered the possibility of MIS, in particular, those cases of posterolateral diapgragmatic hernias with antenatal diagnosis or early postnatal diagnosis due to respiratory distress. Most of the anterior diaphragmatic hernias and some of the right posterolateral hernias were those of late presentation and an incidental diagnosis upon work up for another reason, were stable patients and have been managed in minimally invasive technique. Those, with antenatal diagnosis, were delivered as close to term as possible to ensure lung maturation, and usually electively by cesarean section to ensure delivery in our hospital where the tertiary level of care is present, consisting of neonatal intensive care unit with experienced neonatologists, pediatric surgery department with experienced surgeons, and pediatric ICU with experienced intensivists and anesthesiologists, and to avoid transportation of unstable neonates. We used to intubate our patients immediately after birth or as soon as we had early postnatal diagnosis, and a nasogastric tube (NGT) is introduced to decompress the stomach and to prevent bowel distension. In addition, we check the position of NGT on xray to rule out gastric herniation. All are ventilated using High Frequency Oscillating 42
ventilator (HFOV) with adjusted parameters (RR 10Hz, IT 33%, MAP 9.5-13.5 cmH2O, FiO2 50-100%, amplitude (delta-p) 26-40) to ensure optimized respiratory support, high preand post-ductal O2 saturation, decreased pulmonary artery pressure, avoidance of barotrauma, and correction of acid-base disturbances. Inhaled nitric oxide (iNO), inotropic agents, seldinafel, and surfactant were used in selected cases according to the cardiorespiratory status of the patient. Good analgesic and sedating agents were also used (Fentanyl 1-2 mcg/kg & midazolam 100-200mcg/kg). Insertion of central venous catheter, and insurance of good hydration status. All had thoracoabdominal x-ray to submit or to confirm the diagnosis of CDH. Ecocardiography is done to assess the presence of pulmonary hypertension, right to left shunting through patent foramen ovale or patent ductus arteriosus, and right sided heart failure. Cardio-respiratory monitoring to asses lung maturity, lung hypoplasia, hypoxia, and response for management. Screening for associated malformations is done also for all the patients. Parameters of stability that were considered for patient selection for surgical intervention are [160]: Hemodynamic: MAP within normal limits per age, reduction in right to left shunting, urine output >1.5 ml/kg/hr, serum level of lactic acid 7.35, PaCO2 0.5, OI (oxygenation index)
