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Late surgical outcomes among congenital diaphragmatic hernia (CDH) patients: Why long-term follow-up with surgeons is recommended
Journal of Pediatric Surgery (2013) 48, 935–941
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Late surgical outcomes among congenital diaphragmatic hernia (CDH) patients: Why long-term follow-up with surgeons is recommended Tim Jancelewicz, Monping Chiang, Carol Oliveira, Priscilla P. Chiu ⁎ Division of Pediatric Surgery, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8 Received 21 January 2013; accepted 3 February 2013
Key words: Congenital diaphragmatic hernia; CDH; Recurrence; Surgical complications; Long-term outcomes
Abstract Background: CDH patients experience multi-system morbidity. Despite apparent health, late childhood complications do occur. We reviewed the long-term surgical morbidity of our CDH patients to determine whether protracted clinical surveillance is warranted. Methods: A single-institution retrospective chart review of all CDH survivors treated from 1999 to 2011 who are followed at our CDH multidisciplinary clinic was performed. Descriptive and statistical analyses were performed to show risk of surgical complications over time. Results: A total of 187 CDH patients were treated with 160 surviving to discharge (86%). Primary repair was performed in 115 (73%), and 42 (27%) underwent patch repair. CDH recurrence occurred in 23 (15%) at a median time of 0.7 (range 0–8.5) years (65% asymptomatic). Seventy percent of recurrences occurred before 2 years and 17% after 4 years. Bowel obstruction occurred in 12 (8%) at a median time of 0.7 (range 0.2–7.2) years post-repair, and chest deformity occurred in 13 (8%) at a median of 5 (range 1.1–6.8) years. For patch repairs, scoliosis occurred in 4 (10%) patients at a median age of 3 (range 0.6–5) years. Conclusion: Surgical complications in CDH survivors are common, can occur many years later, and are frequently asymptomatic. Long-term surveillance of CDH patients is recommended for early identification and treatment of complications. © 2013 Elsevier Inc. All rights reserved.
There is increasing evidence that improvements in the survival of patients with severe congenital diaphragmatic hernia (CDH) have been associated with a corresponding increase in the incidence of long-term morbidity [1–3]. Postoperatively, CDH patients face a spectrum of potential complications that require long-term surveillance by clinicians, ideally in a multidisciplinary setting. Even for CDH ⁎ Corresponding author. Tel.: +1416 813 6405. E-mail address: [email protected] (P.P. Chiu). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.02.005
survivors with minimal pulmonary disease, many centers advocate protocolized out-patient visits with routine imaging so that both medical and surgical concerns may be addressed early, thus minimizing morbidity [4,5]. Unfortunately, despite these recommendations, most CDH patients do not receive structured follow-up and may not be seen by a surgeon routinely [6]. Additionally, it is not clear when or even if such careful follow-up should conclude, as truly long-term outcome patterns are not well described in the literature. Indeed, reports differ on the
936 definition of “long-term outcomes,” with some groups reporting 1 or 2 years of follow-up data as “long-term” complication rates [7,8]. Still other groups quote low hernia recurrence rates without complete follow-up of their populations in clinic or without routine surveillance imaging of healthy survivors [9]. Such perspectives carry the implicit suggestion that close follow-up is unnecessary in healthy children with CDH beyond 12–24 months of age. However, a number of studies have shown that surgical complications such as scoliosis, chest wall deformity and bowel obstruction occur years after CDH repair, and are more delayed or gradual in onset than the physiologically significant adverse nutritional, gastrointestinal, and neurodevelopmental conditions experienced by some CDH survivors [10–17]. Additionally, long-term CDH recurrence patterns are not well defined for three reasons: first, because many survivors of severe CDH defects are still relatively young; second, the durability of prosthetic patch repairs during the rapid growth phases of late childhood and adolescence has not been widely reported; and finally, there is a lack of long-term follow-up by surgeons in many CDH centers. Since 2000, CDH patients have been followed at our center in a multidisciplinary clinic with a follow-up protocol that includes routine surveillance imaging in accordance with published recommendations [1,5,6]. In Canada, access to CDH clinic is not limited by financial or insurance concerns, allowing us to see virtually all our CDH families in follow-up without undo resource burden. The purpose of this study was to describe patterns of long-term surgical morbidity seen in our cohort of CDH survivors, in order to define the long-term surgical burden of disease for CDH patients and to determine the need for long-term surveillance by surgeons along with other specialists.
1. Methods Permission for this study was obtained from the Research Ethics Board of the Hospital for Sick Children (1000010450).
1.1. Study cohort A retrospective review was performed of all CDH patients currently followed in multidisciplinary clinic at The Hospital for Sick Children, University of Toronto, with a date of birth in or after January 2000. Patients born after September 2011 were excluded from the analysis to limit bias due to short follow-up time. All patients are followed prospectively in CDH clinic, and undergo a chest x-ray at each visit, as surveillance for CDH recurrence. Clinical, operative, and outcomes data were tabulated for subgroup comparison. Specifically, the timing and clinical features of all surgical complications were documented including hernia recurrence requiring operative repair, small bowel obstruction (SBO) requiring laparotomy, major chest
T. Jancelewicz et al. wall deformity (defect sufficient to plan referral for eventual treatment), and scoliosis as assessed by physical exam and sequential imaging.
1.2. Operative repair Prior to 2005, patients underwent open repair with primary closure, muscular flap closure using the method of Simpson as previously reported [18,19], or patch closure using polytetrafluoroethylene (PTFE, Gore-Tex® or Gore® Dualmesh®, W. L. Gore and Associates, Flagstaff, AZ) or Surgisis® (SIS, Cook Medical, Bloomington, IN). After 2005, minimally invasive (MIS) repair (usually thoracoscopic) was employed in select patients without pulmonary hypertension, and the Simpson flap was no longer used due to abdominal wall deformity. Currently, patch repair is performed using PTFE at our institution due to published reports and our own observations of higher recurrence rates with bioabsorbable mesh [3].
1.3. Statistical analysis Group comparison was made using Fisher's exact test for categorical variables, and Student's t test for continuous variables, with a P b 0.05 considered significant. Since CDH recurrence can occur at any time post-repair, Kaplan–Meier survival analysis was used to assess and visually demonstrate the chronology of CDH recurrence in the CDH cohort.
2. Results 2.1. Study cohort From January 2000 to September 2011, 187 patients were treated for CDH at our institution, with 160 surviving to discharge (86%). There have been no post-discharge deaths in the cohort. Three patients were excluded due to lack of followup, leaving a study cohort of 157 patients. Of these, 115 (73%) underwent primary repair, and 42 (27%) had a patch repair. Clinical characteristics are shown in Table 1, with comparison between patch and primary repair subgroups.
2.2. Recurrence data A total of 23 patients had a CDH recurrence requiring operation for repair, yielding an overall recurrence rate of 15%. Recurrence rates stratified by repair type are presented in Table 2. The MIS group had a higher recurrence rate (32%) than patients with open repairs (11%); excluding all MIS repairs, the cohort recurrence rate was 4% for primary repairs and 27% for patch repairs. CDH recurrences were sometimes seen on surveillance xray at clinic in asymptomatic or minimally symptomatic patients, leading to elective repair; this was the case in 15
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937
Table 1 Cohort characteristics, comparing primary and patch repair subgroups. Primary repairs, Non-primary P n = 115 repairs, n = 42 (% or range) (% or range) Male gender Left-sided CDH Median GA birth (weeks) Mean birth weight (kg) Median age at repair (days) Median follow-up time (years) ECMO HFOV MIS repair
66 (57) 105 (91) 38 (28–40)
28 (67) 35 (83) 38 (31–40)
0.29 0.22 0.25
3.2 ± 0.7 3 (0–1452)
3.1 ± 0.7 4 (1–4151)
0.63 0.8
5.7 (0.7–12.3)
6.8 (1.2–12.0) 0.59
1 (1) 27 (23) 23 (20)
3 (7) 20 (48) 5 (12)
0.06 0.09 0.35
GA, gestational age; ECMO, extracorporeal membrane oxygenation; HFOV, high-frequency oscillatory ventilation; MIS, minimally invasive surgery.
(65%) of 23 patients with recurrence. In the other 8 patients with CDH recurrence (35%), presentation was to clinic or emergency room with significant clinical signs or symptoms leading to further imaging or immediate re-operation. Fig. 1 demonstrates the variable findings seen on imaging studies in patients from our cohort with hernia recurrence, reflecting the variability of findings that can make hernia recurrence difficult to detect. The median time to recurrence was 0.7 (range 0–8.5) years. Although 16 (70%) of 23 recurrences occurred within 2 years following repair, nearly a third of recurrences occurred beyond 2 years, and four patients (17%) had a recurrence 4 years or more post-repair. The latest recurrences were seen among PTFE repairs. There was a significant difference in recurrence rates between primary and patch repaired CDH patients (Table 3). Time to CDH recurrence was also variable and dependent on the type of CDH repair (Fig. 2). Of note, most recurrences among SIS repairs occurred early, and PTFE recurrences occurred over a
Table 2
Recurrences rates stratified by repair type.
Type of repair
Number of repairs (% of cohort)
Number with recurrence (%)
All Open (primary + patch) Open primary MIS (primary + patch) PTFE SIS Simpson flap
157 (100) 129 (82) 92 (59) 28 (18) 19 (12) 14 (9) 10 (6)
23 (15) 14 (11) 4 (4) 9 (32) 4 (21) 7 (50) 1 (10)
PTFE, polytetrafluoroethylene; MIS, minimally invasive surgery; SIS, Surgisis.
broad range of time. For the six patients with multiple recurrences, four (66%) had an initial SIS repair; the median time to second recurrence was 0.7 (range 0.2–0.9) years. Early recurrence (before 6 months after repair) was also seen in 11 patients (7%), with 5 of these patients having had MIS repairs. The rest were evenly distributed among muscle flap, patch, and primary repairs. Early recurrence (before 6 months after repair) was seen in 11 patients (7%), but 5 of these were MIS repairs. The rest were evenly distributed among flap, patch, and primary repairs. Thoracoscopic MIS repair was associated with a recurrence rate of 39% (n = 9/23) with exclusion of non-neonatal repairs (n = 4, no recurrences) and laparoscopic repairs (n = 1, no recurrence). Seven of 17 primary MIS repairs (41%) and 2 (40%) of 5 patch MIS repairs had a recurrence, at a median time of 162 (range: 8–447) days after initial repair (both recurrences were SIS patch repairs, and the other 3 patch repairs were PTFE). In an attempt to decrease recurrence rates, a quality improvement initiative was implemented at our institution in 2007 that involved protocolized surgical technique (use of pledgets and an extracorporeal corner stitch, more liberal use of PTFE patch repair, and lower intrathoracic pressures; also, performance of TR was restricted to two experienced surgeons). This resulted in a reduction in overall recurrence rates to 25% from 50% in patients undergoing primary thoracoscopic repair [20].
2.3. Other outcomes Other long-term surgical complications for CDH patients with primary and patch repairs include SBO, major chest deformity, and scoliosis (Table 3). SBO requiring laparotomy in the absence of CDH recurrence occurred in 12 patients (8%) at a median time of 0.7 (range 0.2–7.2) years after CDH repair. This was not significantly different between non-primary repairs (n = 5) and primary repairs (n = 7). One patient who underwent thoracoscopic primary repair suffered a CDH recurrence involving gastric herniation with volvulus and ischemia, requiring laparotomy, gastric resection and gastroduodenostomy. However, no patient with an MIS repair has had an SBO independent of recurrence. Mild chest deformity was extremely common in the cohort at all ages (data not shown), but major deformity with progression prompting referral for eventual treatment occurred in 13 patients (8%) at a median age of 5 (range 1.1–6.8) years. Although no patient with an initial MIS repair has developed a major chest deformity, the number of patients is too small and the follow-up time is too short in that subgroup to currently assess for statistical significant differences. Scoliosis was not commonly observed, but occurred exclusively in patients who underwent SIS patch (n = 2) or Simpson flap (n = 2) repair (3% of total cohort). This
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T. Jancelewicz et al.
Fig. 1 Examples of imaging findings in patients with CDH recurrence. Recurrence can be obvious (1), or more subtle as in (2) and (3) with simple absence of normal diaphragmatic contour. Images 4a–c show a 5-year-old patient with a history of right CDH repair, who presented to clinic with occasional right chest pain and growth delay; diaphragmatic irregularity seen on x-ray combined with mild symptoms led to a computed tomography scan that revealed an occult hernia recurrence posterior to the liver. Note that the PTFE patch is completely separated from the chest wall on sagittal image (4c).
represents 10% of non-primary repair patients. Mild to moderate scoliosis may be under-reported in our cohort since measurement of spinal curvature with spine x-ray was not performed and recorded unless the deformity was obvious on clinical exam and/or CXR. Referral for treatment was made when spine x-ray demonstrated progressive increased curvature on two sequential imaging studies. For the four patients referred in our cohort, the mean Cobb angle at referral was 57° (range 50°–73°) and median age at referral was 3 (range 0.6–5) years.
3. Discussion Because postnatal management of CDH has improved, there are increasing numbers of survivors who are growing into childhood and adolescence, and the prevalence of related morbidity is also increasing in these patients. In keeping with previous reports regarding long-term outcomes in CDH [1–3,5,6,8,10], we found a significant
burden of surgical complications in our cohort of patients, including an overall 15% hernia recurrence rate (4% in open primary repairs, 27% in non-primary repairs, and 32% in MIS repairs), an 8% incidence of SBO and chest wall deformity, and a 3% scoliosis rate. The median length of follow-up of nearly 7 years in this series exceeds many other reports including our own prior studies [1–3,8]; as a direct result, we found a high incidence of late complications in our cohort and, in total, these data support the concept of diligent long-term surveillance of CDH patients by surgeons with routine imaging to at least 10 years of age. Our protocol is to follow CDH patients through our out-patient clinic until age 17 (Table 4), when their care is then transitioned to an adult center. Hernia recurrence may be a particularly insidious longterm problem that is difficult to detect in some patients. Twothirds of our patients with CDH recurrence were asymptomatic at time of diagnosis, and x-ray surveillance at clinic may have made a significant difference in their outcome. We have observed presentations of patients with reherniation that
Late surgical outcome among CDH patients
939
Table 3 Surgical outcomes comparisons between primary and non-primary repairs. Primary repairs, Non-primary P n = 115 repairs, n = 2 (% or range) (% or range) Operation for CDH 11 (10) recurrence—all patients 4 (4) Operation for CDH recurrence— excluding MIS repairs Median time to 0.4 (0.0-5.1) recurrence (years) 7 (6) Early recurrence (b 6 months after first repair) Multiple recurrences 0 (0) Major chest deformity 7 (6) Operation for bowel 7 (6) obstruction Scoliosis 0 (0)
12 (29)
b 0.01
10 (27)
b 0.01
1.4 (0.0-8.5) 4 (9)
0.12 0.50
6 (14) 6 (14) 5 (12)
b 0.01 0.17 0.30
4 (10)
b 0.01
MIS, minimally invasive surgery.
varied from asymptomatic to mild chest pain to frank respiratory failure or sepsis from bowel obstruction. Plain film imaging is suggestive but may not be entirely reliable, and CT, ultrasound or upper gastrointestinal contrast studies may be warranted for some patients. Because of the potential adverse consequences of delayed repair of recurrences, we
Table 4
Hospital for Sick Children CDH Clinic Protocol.
Timeline Pre-discharge 4 weeks postdischarge 4 months of age
8 months of age
12 months of age
18 months of age
2 years of age
3 years of age
5 years of age
7 years of age
10 years of age
17 years of age
Fig. 2 Kaplan–Meier survival analysis depicting proportion of patients without hernia recurrence over number of years post-repair, stratified by repair type. (A) Primary versus non-primary repairs. (B) All repair type subgroups. “MIS primary” includes thoracoscopic and laparoscopic primary repairs (MIS, minimally invasive surgery; SIS, Surgisis; PTFE, polytetrafluoroethylene).
Follow-up Assessments ECHO, infant hearing test General surgery clinic with CXR CDH clinic (including a pediatric surgeon) with CXR Neonatal follow-up (AIMS, PFMA-I) Infant hearing test (if not already done) CDH clinic with CXR Neonatal follow-up (AIMS, PFMA-I, CSBS if concerns) Cardiology if PHTN/PDA/PFO at first assessment post-discharge (ECHO, ECG) CDH clinic with CXR Neonatal follow-up (AIMS, PFMA-I, CSBS), infant hearing test CDH clinic with CXR Neonatal follow-up (Bayley III, M-CHAT, REEL-III) CDH clinic with CXR Cardiology: if no PHTN/PDA/PFO at first assessment, ECHO, ECG, LPS) CDH/General surgery clinic with CXR Neonatal follow-up (Bayley III, BRIEF-P, CBCL, Vineland II) CDH clinic with CXR, PFT (spirometry) Cardiology: ECHO, ECG Neonatal follow-up clinic a CDH clinic with CXR, PFT (spirometry and lung volumes) Neonatal follow-up clinic a CDH clinic with CXR, PFT (complete with MIPS/MEPS) Cardiology: ECHO, ECG, CT scan, VO2 exercise test CDH clinic with CXR Cardiology: ECHO, ECG
Abbreviations: AIMS, Alberta Infant Motor Score; BRIEF-P, Behavior Rating Inventory of Executive Function–Pre-school version; CSBS, Communication and Symbolic Behavior Scale; CBCL, Child Behavior Check List; CT, computed tomography; CXR, chest x-ray; ECG, electrocardiogram; ECHO, echocardiogram; LPS, lung perfusion scan; M-CHAT, Modified Checklist for Autism in Toddlers; MIPS/MEPS, maximal inspiratory/expiratory pressures; PFMA-I, Posture and Fine Movement Assessment 1st edition; PFT, pulmonary function test; PHTN, pulmonary hypertension; PDA, patent ductus arteriosus; PFO, patent foramen ovale; REEL-III, Receptive Expressive Emergent Language Test 3rd edition; Vineland II, Vineland Adaptive Behavior Scales 2nd edition; VO2 exercise test, oxygen uptake exercise test. a To be determined if there will be 7-year follow-up replacing 5-year visit.
940 advocate thorough evaluation and either immediate repair of obvious recurrences, or else very close surveillance of small, asymptomatic recurrences, which has been described but is controversial [8]. Our data suggest that as somatic growth progresses, patch repair of CDH, such as those using PTFE, may become more vulnerable to recurrence as musculoskeletal tension increases. These initial recurrences may involve small defects at high risk for hernia incarceration, and early intervention may be warranted if a recurrence is suspected. Nearly onefifth of patients with recurrence in our cohort presented more than 4 years after repair. The durable nature of PTFE may simply delay inevitable recurrence until later in childhood, suggesting that use of a domed or cone-shaped patch with redundant material could help reduce the late recurrence rate [8,21]. However, long-term data and large series with this technique are lacking. Our experience with Surgisis bioabsorbable material for patch repair of CDH demonstrates an unacceptably high recurrence rate of 50% (compared with 21% for PTFE), as well as a high frequency of multiple recurrences in these patients. A number of other studies have reported this concern in relation to Surgisis but there is still some support for its use [7,9]. Based on our data we strongly recommend against use of Surgisis or other bioabsorbable material, and advocate use of PTFE or a composite mesh as has been suggested [10]. Neonatal MIS repair of CDH remains a controversial approach due to data suggesting a higher recurrence rate than seen with open repair [22,23]. At our institution, we have observed a very high recurrence rate for neonatal MIS repair, which made up nearly 40% of our CDH recurrences overall. Since 2008 our results have improved somewhat with a quality improvement initiative [23]. Currently, we rarely perform this technique and only after careful discussion of risks and benefits with families. More studies are required to verify the causes of high recurrence rates after MIS CDH repair, and we support a prospective registry to evaluate long-term outcomes data in these patients. Chest wall deformity and scoliosis are also late-onset complications for CDH patients, and our study correlates with previous findings. We advocate surveillance and referral as necessary for these conditions. Adverse medical or physiologic outcomes that may occur in CDH survivors include long-standing respiratory, nutritional, and neurodevelopmental problems, and these conditions necessitate appropriate monitoring along with protracted vigilance for the surgical or anatomic complications studied in this report [1,5]. Surveillance imaging and examination by a pediatric surgeon are only a part of the necessary multidisciplinary follow-up regimen for these patients. Based on our cohort and on previously published data, we have designed the Toronto CDH clinic follow-up protocol that is presented in Table 4. At centers where a multidisciplinary clinic is not available, a tailored follow-
T. Jancelewicz et al. up schedule can be designed for individual patients such that a primary care physician can conduct the majority of the required tests with referral to specialists as needed. Alternatively, telemedicine may play a valuable role for the surveillance by specialists of patients in remote locations. In summary, the high incidence of late surgical morbidity in our cohort of CDH survivors underscores the essential role of the pediatric surgeon in the long-term surveillance and management of these patients. Ideally, the development of an international, multicenter long-term outcomes registry, which we strongly advocate, will help better define the incidence patterns of surgical disease and other morbidity in children and young adults with CDH, ultimately facilitating improved treatment and better outcomes.
References [1] Chiu P, Hedrick HL. Postnatal management and long-term outcome for survivors with congenital diaphragmatic hernia. Prenat Diagn 2008;28:592-603. [2] Chiu PP, Sauer C, Mihailovic A, et al. The price of success in the management of congenital diaphragmatic hernia: is improved survival accompanied by an increase in long-term morbidity? J Pediatr Surg 2006;41:888-92. [3] Jancelewicz T, Vu LT, Keller RL, et al. Long-term surgical outcomes in congenital diaphragmatic hernia: observations from a single institution. J Pediatr Surg 2010;45:155-60. [4] Danzer E, Hedrick HL. Neurodevelopmental and neurofunctional outcomes in children with congenital diaphragmatic hernia. Early Hum Dev 2007;87:625-32. [5] Lally KP, Engle W. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics 2008;121:627-32. [6] Safavi A, Synnes AR, O'Brien K, et al. Multi-institutional follow-up of patients with congenital diaphragmatic hernia reveals severe disability and variations in practice. J Pediatr Surg 2012;47:836-41. [7] Valfre L, Braguglia A, Conforti A, et al. Long term follow-up in highrisk congenital diaphragmatic hernia survivors: patching the diaphragm affects the outcome. J Pediatr Surg 2011;46:52-6. [8] Tsai J, Sulkowski J, Adzick NS, et al. Patch repair for congenital diaphragmatic hernia: is it really a problem? J Pediatr Surg 2012;47: 637-41. [9] Riehle KJ, Magnuson DK, Waldhausen JH. Low recurrence rate after Gore-Tex/Marlex composite patch repair for posterolateral congenital diaphragmatic hernia. J Pediatr Surg 2007;42:1841-4. [10] St Peter SD, Valusek PA, Tsao K, et al. Abdominal complications related to type of repair for congenital diaphragmatic hernia. J Surg Res 2007;140:234-6. [11] Vanamo K, Rintala R, Sovijarvi A, et al. Long-term pulmonary sequelae in survivors of congenital diaphragmatic defects. J Pediatr Surg 1996;31:1096-9. [12] Vanamo K, Peltonen J, Rintala R, et al. Chest wall and spinal deformities in adults with congenital diaphragmatic defects. J Pediatr Surg 1996;31:851-4. [13] Vanamo K, Rintala RJ, Lindahl H, et al. Long-term gastrointestinal morbidity in patients with congenital diaphragmatic defects. J Pediatr Surg 1996;31:551-4. [14] Muratore CS, Utter S, Jaksic T, et al. Nutritional morbidity in survivors of congenital diaphragmatic hernia. J Pediatr Surg 2001; 36:1171-6. [15] Muratore CS, Kharasch V, Lund DP, et al. Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic. J Pediatr Surg 2001;36:133-40.
Late surgical outcome among CDH patients [16] Nobuhara KK, Lund DP, Mitchell J, et al. Long-term outlook for survivors of congenital diaphragmatic hernia. Clin Perinatol 1996;23: 873-87. [17] Lund DP, Mitchell J, Kharasch V, et al. Congenital diaphragmatic hernia: the hidden morbidity. J Pediatr Surg 1994;29:258-62. [18] Simpson JS, Gossage JD. Use of abdominal wall muscle flap in repair of large congenital diaphragmatic hernia. J Pediatr Surg 1971;6:42-4. [19] Nasr A, Struijs MC, Ein SH, et al. Outcomes after muscle flap vs prosthetic patch repair for large congenital diaphragmatic hernias. J Pediatr Surg 2010;45:151-4. [20] Jancelewicz T, Langer JC, Chiang M, et al. Thoracoscopic repair of neonatal congenital diaphragmatic hernia (CDH): outcomes after a
941 systematic quality improvement process. J Pediatr Surg 2013;48: 321-5. [21] Loff S, Wirth H, Jester I, et al. Implantation of a cone-shaped doublefixed patch increases abdominal space and prevents recurrence of large defects in congenital diaphragmatic hernia. J Pediatr Surg 2005;40: 1701-5. [22] Gander JW, Fisher JC, Gross ER, et al. Early recurrence of congenital diaphragmatic hernia is higher after thoracoscopic than open repair: a single institutional study. J Pediatr Surg 2011;46:1303-8. [23] Lansdale N, Alam S, Losty PD, et al. Neonatal endosurgical congenital diaphragmatic hernia repair: a systematic review and meta-analysis. Ann Surg 2010;252:20-6.
www.elsevier.com/locate/jpedsurg
Late surgical outcomes among congenital diaphragmatic hernia (CDH) patients: Why long-term follow-up with surgeons is recommended Tim Jancelewicz, Monping Chiang, Carol Oliveira, Priscilla P. Chiu ⁎ Division of Pediatric Surgery, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8 Received 21 January 2013; accepted 3 February 2013
Key words: Congenital diaphragmatic hernia; CDH; Recurrence; Surgical complications; Long-term outcomes
Abstract Background: CDH patients experience multi-system morbidity. Despite apparent health, late childhood complications do occur. We reviewed the long-term surgical morbidity of our CDH patients to determine whether protracted clinical surveillance is warranted. Methods: A single-institution retrospective chart review of all CDH survivors treated from 1999 to 2011 who are followed at our CDH multidisciplinary clinic was performed. Descriptive and statistical analyses were performed to show risk of surgical complications over time. Results: A total of 187 CDH patients were treated with 160 surviving to discharge (86%). Primary repair was performed in 115 (73%), and 42 (27%) underwent patch repair. CDH recurrence occurred in 23 (15%) at a median time of 0.7 (range 0–8.5) years (65% asymptomatic). Seventy percent of recurrences occurred before 2 years and 17% after 4 years. Bowel obstruction occurred in 12 (8%) at a median time of 0.7 (range 0.2–7.2) years post-repair, and chest deformity occurred in 13 (8%) at a median of 5 (range 1.1–6.8) years. For patch repairs, scoliosis occurred in 4 (10%) patients at a median age of 3 (range 0.6–5) years. Conclusion: Surgical complications in CDH survivors are common, can occur many years later, and are frequently asymptomatic. Long-term surveillance of CDH patients is recommended for early identification and treatment of complications. © 2013 Elsevier Inc. All rights reserved.
There is increasing evidence that improvements in the survival of patients with severe congenital diaphragmatic hernia (CDH) have been associated with a corresponding increase in the incidence of long-term morbidity [1–3]. Postoperatively, CDH patients face a spectrum of potential complications that require long-term surveillance by clinicians, ideally in a multidisciplinary setting. Even for CDH ⁎ Corresponding author. Tel.: +1416 813 6405. E-mail address: [email protected] (P.P. Chiu). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.02.005
survivors with minimal pulmonary disease, many centers advocate protocolized out-patient visits with routine imaging so that both medical and surgical concerns may be addressed early, thus minimizing morbidity [4,5]. Unfortunately, despite these recommendations, most CDH patients do not receive structured follow-up and may not be seen by a surgeon routinely [6]. Additionally, it is not clear when or even if such careful follow-up should conclude, as truly long-term outcome patterns are not well described in the literature. Indeed, reports differ on the
936 definition of “long-term outcomes,” with some groups reporting 1 or 2 years of follow-up data as “long-term” complication rates [7,8]. Still other groups quote low hernia recurrence rates without complete follow-up of their populations in clinic or without routine surveillance imaging of healthy survivors [9]. Such perspectives carry the implicit suggestion that close follow-up is unnecessary in healthy children with CDH beyond 12–24 months of age. However, a number of studies have shown that surgical complications such as scoliosis, chest wall deformity and bowel obstruction occur years after CDH repair, and are more delayed or gradual in onset than the physiologically significant adverse nutritional, gastrointestinal, and neurodevelopmental conditions experienced by some CDH survivors [10–17]. Additionally, long-term CDH recurrence patterns are not well defined for three reasons: first, because many survivors of severe CDH defects are still relatively young; second, the durability of prosthetic patch repairs during the rapid growth phases of late childhood and adolescence has not been widely reported; and finally, there is a lack of long-term follow-up by surgeons in many CDH centers. Since 2000, CDH patients have been followed at our center in a multidisciplinary clinic with a follow-up protocol that includes routine surveillance imaging in accordance with published recommendations [1,5,6]. In Canada, access to CDH clinic is not limited by financial or insurance concerns, allowing us to see virtually all our CDH families in follow-up without undo resource burden. The purpose of this study was to describe patterns of long-term surgical morbidity seen in our cohort of CDH survivors, in order to define the long-term surgical burden of disease for CDH patients and to determine the need for long-term surveillance by surgeons along with other specialists.
1. Methods Permission for this study was obtained from the Research Ethics Board of the Hospital for Sick Children (1000010450).
1.1. Study cohort A retrospective review was performed of all CDH patients currently followed in multidisciplinary clinic at The Hospital for Sick Children, University of Toronto, with a date of birth in or after January 2000. Patients born after September 2011 were excluded from the analysis to limit bias due to short follow-up time. All patients are followed prospectively in CDH clinic, and undergo a chest x-ray at each visit, as surveillance for CDH recurrence. Clinical, operative, and outcomes data were tabulated for subgroup comparison. Specifically, the timing and clinical features of all surgical complications were documented including hernia recurrence requiring operative repair, small bowel obstruction (SBO) requiring laparotomy, major chest
T. Jancelewicz et al. wall deformity (defect sufficient to plan referral for eventual treatment), and scoliosis as assessed by physical exam and sequential imaging.
1.2. Operative repair Prior to 2005, patients underwent open repair with primary closure, muscular flap closure using the method of Simpson as previously reported [18,19], or patch closure using polytetrafluoroethylene (PTFE, Gore-Tex® or Gore® Dualmesh®, W. L. Gore and Associates, Flagstaff, AZ) or Surgisis® (SIS, Cook Medical, Bloomington, IN). After 2005, minimally invasive (MIS) repair (usually thoracoscopic) was employed in select patients without pulmonary hypertension, and the Simpson flap was no longer used due to abdominal wall deformity. Currently, patch repair is performed using PTFE at our institution due to published reports and our own observations of higher recurrence rates with bioabsorbable mesh [3].
1.3. Statistical analysis Group comparison was made using Fisher's exact test for categorical variables, and Student's t test for continuous variables, with a P b 0.05 considered significant. Since CDH recurrence can occur at any time post-repair, Kaplan–Meier survival analysis was used to assess and visually demonstrate the chronology of CDH recurrence in the CDH cohort.
2. Results 2.1. Study cohort From January 2000 to September 2011, 187 patients were treated for CDH at our institution, with 160 surviving to discharge (86%). There have been no post-discharge deaths in the cohort. Three patients were excluded due to lack of followup, leaving a study cohort of 157 patients. Of these, 115 (73%) underwent primary repair, and 42 (27%) had a patch repair. Clinical characteristics are shown in Table 1, with comparison between patch and primary repair subgroups.
2.2. Recurrence data A total of 23 patients had a CDH recurrence requiring operation for repair, yielding an overall recurrence rate of 15%. Recurrence rates stratified by repair type are presented in Table 2. The MIS group had a higher recurrence rate (32%) than patients with open repairs (11%); excluding all MIS repairs, the cohort recurrence rate was 4% for primary repairs and 27% for patch repairs. CDH recurrences were sometimes seen on surveillance xray at clinic in asymptomatic or minimally symptomatic patients, leading to elective repair; this was the case in 15
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Table 1 Cohort characteristics, comparing primary and patch repair subgroups. Primary repairs, Non-primary P n = 115 repairs, n = 42 (% or range) (% or range) Male gender Left-sided CDH Median GA birth (weeks) Mean birth weight (kg) Median age at repair (days) Median follow-up time (years) ECMO HFOV MIS repair
66 (57) 105 (91) 38 (28–40)
28 (67) 35 (83) 38 (31–40)
0.29 0.22 0.25
3.2 ± 0.7 3 (0–1452)
3.1 ± 0.7 4 (1–4151)
0.63 0.8
5.7 (0.7–12.3)
6.8 (1.2–12.0) 0.59
1 (1) 27 (23) 23 (20)
3 (7) 20 (48) 5 (12)
0.06 0.09 0.35
GA, gestational age; ECMO, extracorporeal membrane oxygenation; HFOV, high-frequency oscillatory ventilation; MIS, minimally invasive surgery.
(65%) of 23 patients with recurrence. In the other 8 patients with CDH recurrence (35%), presentation was to clinic or emergency room with significant clinical signs or symptoms leading to further imaging or immediate re-operation. Fig. 1 demonstrates the variable findings seen on imaging studies in patients from our cohort with hernia recurrence, reflecting the variability of findings that can make hernia recurrence difficult to detect. The median time to recurrence was 0.7 (range 0–8.5) years. Although 16 (70%) of 23 recurrences occurred within 2 years following repair, nearly a third of recurrences occurred beyond 2 years, and four patients (17%) had a recurrence 4 years or more post-repair. The latest recurrences were seen among PTFE repairs. There was a significant difference in recurrence rates between primary and patch repaired CDH patients (Table 3). Time to CDH recurrence was also variable and dependent on the type of CDH repair (Fig. 2). Of note, most recurrences among SIS repairs occurred early, and PTFE recurrences occurred over a
Table 2
Recurrences rates stratified by repair type.
Type of repair
Number of repairs (% of cohort)
Number with recurrence (%)
All Open (primary + patch) Open primary MIS (primary + patch) PTFE SIS Simpson flap
157 (100) 129 (82) 92 (59) 28 (18) 19 (12) 14 (9) 10 (6)
23 (15) 14 (11) 4 (4) 9 (32) 4 (21) 7 (50) 1 (10)
PTFE, polytetrafluoroethylene; MIS, minimally invasive surgery; SIS, Surgisis.
broad range of time. For the six patients with multiple recurrences, four (66%) had an initial SIS repair; the median time to second recurrence was 0.7 (range 0.2–0.9) years. Early recurrence (before 6 months after repair) was also seen in 11 patients (7%), with 5 of these patients having had MIS repairs. The rest were evenly distributed among muscle flap, patch, and primary repairs. Early recurrence (before 6 months after repair) was seen in 11 patients (7%), but 5 of these were MIS repairs. The rest were evenly distributed among flap, patch, and primary repairs. Thoracoscopic MIS repair was associated with a recurrence rate of 39% (n = 9/23) with exclusion of non-neonatal repairs (n = 4, no recurrences) and laparoscopic repairs (n = 1, no recurrence). Seven of 17 primary MIS repairs (41%) and 2 (40%) of 5 patch MIS repairs had a recurrence, at a median time of 162 (range: 8–447) days after initial repair (both recurrences were SIS patch repairs, and the other 3 patch repairs were PTFE). In an attempt to decrease recurrence rates, a quality improvement initiative was implemented at our institution in 2007 that involved protocolized surgical technique (use of pledgets and an extracorporeal corner stitch, more liberal use of PTFE patch repair, and lower intrathoracic pressures; also, performance of TR was restricted to two experienced surgeons). This resulted in a reduction in overall recurrence rates to 25% from 50% in patients undergoing primary thoracoscopic repair [20].
2.3. Other outcomes Other long-term surgical complications for CDH patients with primary and patch repairs include SBO, major chest deformity, and scoliosis (Table 3). SBO requiring laparotomy in the absence of CDH recurrence occurred in 12 patients (8%) at a median time of 0.7 (range 0.2–7.2) years after CDH repair. This was not significantly different between non-primary repairs (n = 5) and primary repairs (n = 7). One patient who underwent thoracoscopic primary repair suffered a CDH recurrence involving gastric herniation with volvulus and ischemia, requiring laparotomy, gastric resection and gastroduodenostomy. However, no patient with an MIS repair has had an SBO independent of recurrence. Mild chest deformity was extremely common in the cohort at all ages (data not shown), but major deformity with progression prompting referral for eventual treatment occurred in 13 patients (8%) at a median age of 5 (range 1.1–6.8) years. Although no patient with an initial MIS repair has developed a major chest deformity, the number of patients is too small and the follow-up time is too short in that subgroup to currently assess for statistical significant differences. Scoliosis was not commonly observed, but occurred exclusively in patients who underwent SIS patch (n = 2) or Simpson flap (n = 2) repair (3% of total cohort). This
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Fig. 1 Examples of imaging findings in patients with CDH recurrence. Recurrence can be obvious (1), or more subtle as in (2) and (3) with simple absence of normal diaphragmatic contour. Images 4a–c show a 5-year-old patient with a history of right CDH repair, who presented to clinic with occasional right chest pain and growth delay; diaphragmatic irregularity seen on x-ray combined with mild symptoms led to a computed tomography scan that revealed an occult hernia recurrence posterior to the liver. Note that the PTFE patch is completely separated from the chest wall on sagittal image (4c).
represents 10% of non-primary repair patients. Mild to moderate scoliosis may be under-reported in our cohort since measurement of spinal curvature with spine x-ray was not performed and recorded unless the deformity was obvious on clinical exam and/or CXR. Referral for treatment was made when spine x-ray demonstrated progressive increased curvature on two sequential imaging studies. For the four patients referred in our cohort, the mean Cobb angle at referral was 57° (range 50°–73°) and median age at referral was 3 (range 0.6–5) years.
3. Discussion Because postnatal management of CDH has improved, there are increasing numbers of survivors who are growing into childhood and adolescence, and the prevalence of related morbidity is also increasing in these patients. In keeping with previous reports regarding long-term outcomes in CDH [1–3,5,6,8,10], we found a significant
burden of surgical complications in our cohort of patients, including an overall 15% hernia recurrence rate (4% in open primary repairs, 27% in non-primary repairs, and 32% in MIS repairs), an 8% incidence of SBO and chest wall deformity, and a 3% scoliosis rate. The median length of follow-up of nearly 7 years in this series exceeds many other reports including our own prior studies [1–3,8]; as a direct result, we found a high incidence of late complications in our cohort and, in total, these data support the concept of diligent long-term surveillance of CDH patients by surgeons with routine imaging to at least 10 years of age. Our protocol is to follow CDH patients through our out-patient clinic until age 17 (Table 4), when their care is then transitioned to an adult center. Hernia recurrence may be a particularly insidious longterm problem that is difficult to detect in some patients. Twothirds of our patients with CDH recurrence were asymptomatic at time of diagnosis, and x-ray surveillance at clinic may have made a significant difference in their outcome. We have observed presentations of patients with reherniation that
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Table 3 Surgical outcomes comparisons between primary and non-primary repairs. Primary repairs, Non-primary P n = 115 repairs, n = 2 (% or range) (% or range) Operation for CDH 11 (10) recurrence—all patients 4 (4) Operation for CDH recurrence— excluding MIS repairs Median time to 0.4 (0.0-5.1) recurrence (years) 7 (6) Early recurrence (b 6 months after first repair) Multiple recurrences 0 (0) Major chest deformity 7 (6) Operation for bowel 7 (6) obstruction Scoliosis 0 (0)
12 (29)
b 0.01
10 (27)
b 0.01
1.4 (0.0-8.5) 4 (9)
0.12 0.50
6 (14) 6 (14) 5 (12)
b 0.01 0.17 0.30
4 (10)
b 0.01
MIS, minimally invasive surgery.
varied from asymptomatic to mild chest pain to frank respiratory failure or sepsis from bowel obstruction. Plain film imaging is suggestive but may not be entirely reliable, and CT, ultrasound or upper gastrointestinal contrast studies may be warranted for some patients. Because of the potential adverse consequences of delayed repair of recurrences, we
Table 4
Hospital for Sick Children CDH Clinic Protocol.
Timeline Pre-discharge 4 weeks postdischarge 4 months of age
8 months of age
12 months of age
18 months of age
2 years of age
3 years of age
5 years of age
7 years of age
10 years of age
17 years of age
Fig. 2 Kaplan–Meier survival analysis depicting proportion of patients without hernia recurrence over number of years post-repair, stratified by repair type. (A) Primary versus non-primary repairs. (B) All repair type subgroups. “MIS primary” includes thoracoscopic and laparoscopic primary repairs (MIS, minimally invasive surgery; SIS, Surgisis; PTFE, polytetrafluoroethylene).
Follow-up Assessments ECHO, infant hearing test General surgery clinic with CXR CDH clinic (including a pediatric surgeon) with CXR Neonatal follow-up (AIMS, PFMA-I) Infant hearing test (if not already done) CDH clinic with CXR Neonatal follow-up (AIMS, PFMA-I, CSBS if concerns) Cardiology if PHTN/PDA/PFO at first assessment post-discharge (ECHO, ECG) CDH clinic with CXR Neonatal follow-up (AIMS, PFMA-I, CSBS), infant hearing test CDH clinic with CXR Neonatal follow-up (Bayley III, M-CHAT, REEL-III) CDH clinic with CXR Cardiology: if no PHTN/PDA/PFO at first assessment, ECHO, ECG, LPS) CDH/General surgery clinic with CXR Neonatal follow-up (Bayley III, BRIEF-P, CBCL, Vineland II) CDH clinic with CXR, PFT (spirometry) Cardiology: ECHO, ECG Neonatal follow-up clinic a CDH clinic with CXR, PFT (spirometry and lung volumes) Neonatal follow-up clinic a CDH clinic with CXR, PFT (complete with MIPS/MEPS) Cardiology: ECHO, ECG, CT scan, VO2 exercise test CDH clinic with CXR Cardiology: ECHO, ECG
Abbreviations: AIMS, Alberta Infant Motor Score; BRIEF-P, Behavior Rating Inventory of Executive Function–Pre-school version; CSBS, Communication and Symbolic Behavior Scale; CBCL, Child Behavior Check List; CT, computed tomography; CXR, chest x-ray; ECG, electrocardiogram; ECHO, echocardiogram; LPS, lung perfusion scan; M-CHAT, Modified Checklist for Autism in Toddlers; MIPS/MEPS, maximal inspiratory/expiratory pressures; PFMA-I, Posture and Fine Movement Assessment 1st edition; PFT, pulmonary function test; PHTN, pulmonary hypertension; PDA, patent ductus arteriosus; PFO, patent foramen ovale; REEL-III, Receptive Expressive Emergent Language Test 3rd edition; Vineland II, Vineland Adaptive Behavior Scales 2nd edition; VO2 exercise test, oxygen uptake exercise test. a To be determined if there will be 7-year follow-up replacing 5-year visit.
940 advocate thorough evaluation and either immediate repair of obvious recurrences, or else very close surveillance of small, asymptomatic recurrences, which has been described but is controversial [8]. Our data suggest that as somatic growth progresses, patch repair of CDH, such as those using PTFE, may become more vulnerable to recurrence as musculoskeletal tension increases. These initial recurrences may involve small defects at high risk for hernia incarceration, and early intervention may be warranted if a recurrence is suspected. Nearly onefifth of patients with recurrence in our cohort presented more than 4 years after repair. The durable nature of PTFE may simply delay inevitable recurrence until later in childhood, suggesting that use of a domed or cone-shaped patch with redundant material could help reduce the late recurrence rate [8,21]. However, long-term data and large series with this technique are lacking. Our experience with Surgisis bioabsorbable material for patch repair of CDH demonstrates an unacceptably high recurrence rate of 50% (compared with 21% for PTFE), as well as a high frequency of multiple recurrences in these patients. A number of other studies have reported this concern in relation to Surgisis but there is still some support for its use [7,9]. Based on our data we strongly recommend against use of Surgisis or other bioabsorbable material, and advocate use of PTFE or a composite mesh as has been suggested [10]. Neonatal MIS repair of CDH remains a controversial approach due to data suggesting a higher recurrence rate than seen with open repair [22,23]. At our institution, we have observed a very high recurrence rate for neonatal MIS repair, which made up nearly 40% of our CDH recurrences overall. Since 2008 our results have improved somewhat with a quality improvement initiative [23]. Currently, we rarely perform this technique and only after careful discussion of risks and benefits with families. More studies are required to verify the causes of high recurrence rates after MIS CDH repair, and we support a prospective registry to evaluate long-term outcomes data in these patients. Chest wall deformity and scoliosis are also late-onset complications for CDH patients, and our study correlates with previous findings. We advocate surveillance and referral as necessary for these conditions. Adverse medical or physiologic outcomes that may occur in CDH survivors include long-standing respiratory, nutritional, and neurodevelopmental problems, and these conditions necessitate appropriate monitoring along with protracted vigilance for the surgical or anatomic complications studied in this report [1,5]. Surveillance imaging and examination by a pediatric surgeon are only a part of the necessary multidisciplinary follow-up regimen for these patients. Based on our cohort and on previously published data, we have designed the Toronto CDH clinic follow-up protocol that is presented in Table 4. At centers where a multidisciplinary clinic is not available, a tailored follow-
T. Jancelewicz et al. up schedule can be designed for individual patients such that a primary care physician can conduct the majority of the required tests with referral to specialists as needed. Alternatively, telemedicine may play a valuable role for the surveillance by specialists of patients in remote locations. In summary, the high incidence of late surgical morbidity in our cohort of CDH survivors underscores the essential role of the pediatric surgeon in the long-term surveillance and management of these patients. Ideally, the development of an international, multicenter long-term outcomes registry, which we strongly advocate, will help better define the incidence patterns of surgical disease and other morbidity in children and young adults with CDH, ultimately facilitating improved treatment and better outcomes.
References [1] Chiu P, Hedrick HL. Postnatal management and long-term outcome for survivors with congenital diaphragmatic hernia. Prenat Diagn 2008;28:592-603. [2] Chiu PP, Sauer C, Mihailovic A, et al. The price of success in the management of congenital diaphragmatic hernia: is improved survival accompanied by an increase in long-term morbidity? J Pediatr Surg 2006;41:888-92. [3] Jancelewicz T, Vu LT, Keller RL, et al. Long-term surgical outcomes in congenital diaphragmatic hernia: observations from a single institution. J Pediatr Surg 2010;45:155-60. [4] Danzer E, Hedrick HL. Neurodevelopmental and neurofunctional outcomes in children with congenital diaphragmatic hernia. Early Hum Dev 2007;87:625-32. [5] Lally KP, Engle W. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics 2008;121:627-32. [6] Safavi A, Synnes AR, O'Brien K, et al. Multi-institutional follow-up of patients with congenital diaphragmatic hernia reveals severe disability and variations in practice. J Pediatr Surg 2012;47:836-41. [7] Valfre L, Braguglia A, Conforti A, et al. Long term follow-up in highrisk congenital diaphragmatic hernia survivors: patching the diaphragm affects the outcome. J Pediatr Surg 2011;46:52-6. [8] Tsai J, Sulkowski J, Adzick NS, et al. Patch repair for congenital diaphragmatic hernia: is it really a problem? J Pediatr Surg 2012;47: 637-41. [9] Riehle KJ, Magnuson DK, Waldhausen JH. Low recurrence rate after Gore-Tex/Marlex composite patch repair for posterolateral congenital diaphragmatic hernia. J Pediatr Surg 2007;42:1841-4. [10] St Peter SD, Valusek PA, Tsao K, et al. Abdominal complications related to type of repair for congenital diaphragmatic hernia. J Surg Res 2007;140:234-6. [11] Vanamo K, Rintala R, Sovijarvi A, et al. Long-term pulmonary sequelae in survivors of congenital diaphragmatic defects. J Pediatr Surg 1996;31:1096-9. [12] Vanamo K, Peltonen J, Rintala R, et al. Chest wall and spinal deformities in adults with congenital diaphragmatic defects. J Pediatr Surg 1996;31:851-4. [13] Vanamo K, Rintala RJ, Lindahl H, et al. Long-term gastrointestinal morbidity in patients with congenital diaphragmatic defects. J Pediatr Surg 1996;31:551-4. [14] Muratore CS, Utter S, Jaksic T, et al. Nutritional morbidity in survivors of congenital diaphragmatic hernia. J Pediatr Surg 2001; 36:1171-6. [15] Muratore CS, Kharasch V, Lund DP, et al. Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic. J Pediatr Surg 2001;36:133-40.
Late surgical outcome among CDH patients [16] Nobuhara KK, Lund DP, Mitchell J, et al. Long-term outlook for survivors of congenital diaphragmatic hernia. Clin Perinatol 1996;23: 873-87. [17] Lund DP, Mitchell J, Kharasch V, et al. Congenital diaphragmatic hernia: the hidden morbidity. J Pediatr Surg 1994;29:258-62. [18] Simpson JS, Gossage JD. Use of abdominal wall muscle flap in repair of large congenital diaphragmatic hernia. J Pediatr Surg 1971;6:42-4. [19] Nasr A, Struijs MC, Ein SH, et al. Outcomes after muscle flap vs prosthetic patch repair for large congenital diaphragmatic hernias. J Pediatr Surg 2010;45:151-4. [20] Jancelewicz T, Langer JC, Chiang M, et al. Thoracoscopic repair of neonatal congenital diaphragmatic hernia (CDH): outcomes after a
941 systematic quality improvement process. J Pediatr Surg 2013;48: 321-5. [21] Loff S, Wirth H, Jester I, et al. Implantation of a cone-shaped doublefixed patch increases abdominal space and prevents recurrence of large defects in congenital diaphragmatic hernia. J Pediatr Surg 2005;40: 1701-5. [22] Gander JW, Fisher JC, Gross ER, et al. Early recurrence of congenital diaphragmatic hernia is higher after thoracoscopic than open repair: a single institutional study. J Pediatr Surg 2011;46:1303-8. [23] Lansdale N, Alam S, Losty PD, et al. Neonatal endosurgical congenital diaphragmatic hernia repair: a systematic review and meta-analysis. Ann Surg 2010;252:20-6.