Journal of Pediatric Surgery 49 (2014) 280–283
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Gastrointestinal surgery in cystic fibrosis: A 20-year review Paul J. Farrelly a, Caroline Charlesworth a, Sophie Lee a, Kevin W. Southern b, Colin T. Baillie a,⁎ a b
Department of Paediatric Surgery, Alder Hey Children’s NHS Foundation Trust, West Derby, Liverpool, L12 2AP, United Kingdom Institute of Child Health, Alder Hey Children’s NHS Foundation Trust, West Derby, Liverpool, L12 2AP, United Kingdom
a r t i c l e
i n f o
Article history: Received 31 October 2013 Accepted 10 November 2013 Key words: Cystic fibrosis Meconium ileus Distal intestinal obstruction syndrome Surgery
a b s t r a c t Objectives: The purpose of this study was to evaluate outcomes of the surgical management for meconium ileus (MI) and Distal Intestinal Obstruction Syndrome (DIOS) in Cystic Fibrosis (CF). Methods: Children born between 1990 and 2010 were identified using a regional CF database. Retrospective case note analysis was performed. Outcome measures for MI were mortality, relaparotomy rate, length of stay (LOS), time on parental nutrition (TP), and time to full feeds (TFF). Outcome measures for DIOS were: age of onset, number of episodes, and need for laparotomy. Results: Seventy-five of 376 neonates presented with MI. Fifty-four (92%) required laparotomy. Contrast enema decompression was attempted in nineteen. There were no post-operative deaths. Thirty-nine (72%) neonates with MI were managed with stomas. LOS was longer in those managed with stomas (p = 0.001) and in complex MI (p = 0.002). Thirty-five patients were treated for DIOS. Twenty-five patients were managed with gastrograffin. Ten patients underwent surgical management of DIOS. Overall, MI did not predispose to later development of DIOS. There was a significantly greater incidence of laparotomy for DIOS in children who had MI. Conclusion: The proportion of neonates with complex meconium ileus was high (49%) and may explain the infrequent utilisation of radiological decompression. Complex MI or management with stomas both significantly increase LOS. Re-laparotomy rate is high (22%) in MI irrespective of the type of management. DIOS is not a benign condition, particularly when the child has had previous abdominal surgery. Early referral to a surgical team is essential in these children. © 2014 Elsevier Inc. All rights reserved.
Meconium ileus (MI) may be the presenting feature in 10%–15% of patients with cystic fibrosis (CF) [1,2] and can be classified as simple or complex. Simple MI is an uncomplicated intraluminal distal small bowel obstruction due to abnormally viscid meconium. Complex MI additionally can be characterized by complications such as meconium peritonitis, pseudocyst formation, volvulus or intestinal atresia. A variety of operative strategies have been utilized in the management of both simple and complicated MI [1–4,6], the ultimate aim being to decompress the bowel and relieve obstruction by clearing the abnormal meconium. Strategies can be broadly classified as those employing the formation of a stoma (e.g. divided, Bishop– Koop or Santulli), and those where bowel continuity is maintained (e.g. enterotomy and washout, with or without intestinal resection and primary anastomosis). There is no consensus in the current literature as to what constitutes the preferred surgical strategy for the management of MI. Partial or complete small bowel obstruction attributed to CF has also been described since 1945 in older children [8]. This was initially termed ⁎ Corresponding author at: Department of Paediatric Surgery; Alder Hey Children’s NHS Foundation Trust; Eaton Road; West Derby; Liverpool, L12 2AP, United Kingdom. Tel.:+44 0151 228 4811; fax:+44 0151 228 0328. E-mail address: [email protected] (C.T. Baillie). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.11.038
meconium ileus equivalent (MIE) but more recently the term distal intestinal obstruction syndrome (DIOS) has become commonplace. The term DIOS came to encompass a variety of intestinal symptoms and signs, possibly including recalcitrant constipation. The varied definitions have made it difficult to estimate the true incidence and morbidity associated with DIOS [5,7–9]. However, in 2010 the ESPGHAN CF Working group introduced a clear and specific definition for the term DIOS [8] (Table 1). Since then there has been very little contemporary literature on the morbidity and surgical management of DIOS [7]. Our aim was to evaluate the success of managing meconium ileus and DIOS using different surgical strategies over a 20-year period at a single institution. We were specifically interested as to whether infants with MI managed with stomas were comparable to those where intestinal continuity was maintained. The utilization and outcome of radiological decompression in MI were also investigated. For the group with DIOS the principle aim was to test the hypothesis that MI predisposes to the later development of DIOS overall and for DIOS requiring surgery. 1. Methods Patients were retrospectively identified using the regional CF database. All patients under the care of the Alder Hey Children’s NHS
P.J. Farrelly et al. / Journal of Pediatric Surgery 49 (2014) 280–283 Table 1 ESPGHAN CF Working Group definition for DIOS in cystic fibrosis [8]. Criteria Explanation 1
Complete intestinal obstruction as evidenced by vomiting of bilious material and/or fluid levels in smallintestine on an abdominal radiography 2 Faecal mass in ileo-caecum 3 Abdominal pain and/or distension Complete DIOS: 1 and 2 and 3 Incomplete/Impending DIOS: 2 and 3 only
Foundation Trust with CF who were born between 1990 and 2010 were eligible for inclusion. Patients requiring management of MI or DIOS were identified from the CF database and their hospital case notes retrieved. Data were collected for each patient with MI with regard to; conservative versus operative management and stoma versus other operative procedure. Outcome measures included mortality, relaparotomy (excluding restoration of continuity), time to restoration of continuity, length of stay (LOS), time on parenteral nutrition (TP) and time to full feeds (TFF). DIOS was defined using ESPGHAN criteria of abdominal pain +/− distension and ileocaecal mass with evidence of obstruction (Table 1) [8]. Case notes and radiological investigations were rigorously reviewed and children were only included when they met all the criteria for the contemporary definition of “complete DIOS”. Data for this group included age of onset, number of episodes, history and type of preceding MI, and need for previous surgery. Data are quoted as median (range). The Mann–Whitney U-test and the Fisher exact 2-tailed test were used for statistical analysis. P values of b 0.05 were considered significant. 2. Results The regional database identified 376 children with CF born between Jan. 1990 and Dec. 2010. However complete data were only available for the 146 patients that were managed and followedup at Alder Hey Children’s NHS Foundation Trust. The remaining patients predominantly attended district general hospitals for the subsequent management of their CF. Seventy-five (19.9%) of 376 children presented as infants with MI. Complete data sets were available for only 59 as 16 were subsequently transferred back to a more local specialist centre as infants or relocated later and were not followed up at Alder Hey hospital. These were excluded from this analysis. Thirty (51%) infants were regarded as having simple MI and 29 (49%) had complicated MI. Gastrograffin© enemas were attempted initially in 19 (32%) infants but in only 5 (9%) was this successful and the remaining 54 (91%) required laparotomy. Of the 54 patients requiring laparotomy 39 (72%) had divided stomas formed, 7 (13%) were managed with enterotomy and washout, and 8 (15%) with resection and primary anastomosis. The
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time to closure for patients managed with stomas was 47 days (4– 202). All neonates with meconium ileus were given N-acetyl cysteine in the post-operative period. It is administered through the feeding tube or by lavage of the proximal stoma to aid resolution of obstructive symptoms. Once enteral feeding is established the N-acetyl cysteine is replaced by pancreatic enzyme replacement therapy. Enzyme replacement therapy is initiated once infants have reached a volume of 30 ml per feed. There was a significant difference in LOS after MI between operative patients managed with and without stomas: 49 days (19– 390) and 23 days (15–60) respectively. Table 2 shows that those managed with stomas tended to take longer to reach full feeds compared with neonates where bowel continuity was maintained after laparotomy (25 days (7–148) versus 9 days (5–49)), however the difference failed to reach statistical significance (p = 0.067). There was also a trend towards a reduced duration of parental nutrition in the group managed without stomas (18 days (5–104) versus 37 days (1–148)) that failed to reach statistical significance (p0.062). Infants tended to stay on supplemental parenteral nutrition for a period of time after establishing appropriate full volume enteral feeds. Parenteral nutrition was discontinued once it was demonstrated that growth was adequate on serial weight measurements. Infants with complex MI had a longer LOS than those with simple MI [26.5 (6–390) days versus 52 (15–151) days; P b 0.002)] (Table 2). There was no difference in the re-laparotomy rate between infants managed with or without stomas [8 of 36 (22%) versus 3 of 13 (23%); P = 1.00]. Data regarding re-laparotomy were incomplete for 5 patients. Although surgical management with stomas increased length of stay [49 (19–390) days vs 23.5 (15–60) days: P = 0.001], it did not increase re-laparotomy rates [22% versus 23%; P =1.00]. Median follow-up in this group was 118 (12–225) months. There were no deaths in the post-operative neonatal period. There were 3 late deaths due to non-gastrointestinal manifestations of CF. The number of CF patients treated for DIOS was 35 (24%). The age of onset of the first episode of DIOS was 7.7 (0.9–16.7) years. Of these, 22 (62%) were managed with oral Gastrograffin and 3 (9%) with Gastrograffin enemas. The other 10 (29%) had DIOS requiring laparotomy. In total there were 80 separate episodes of “complete DIOS” in these patients. Presentation with MI did not predispose to later development of DIOS [n = 20 (29%) versus n = 15(19%); P = 0.24] (Table 3). However, there was a greater incidence of surgical management of DIOS in children who had had MI [n = 10 (50%) versus n = 0 (0%); P = 0.002]. Laparotomy was never required for the management of DIOS in children who had not previously had MI (Table 3). Subgroup analysis showed that neither complex MI (P = 1) nor management with stomas (P = 0.35) predisposed to surgical management of DIOS. Of the children that required laparotomy for DIOS, 5 (50%) had simple meconium ileus and 5 (50%) had complex meconium ileus (Table 3).
Table 2 Outcomes in Meconium Ileus (MI). Type of Surgery
LOS (days) TP (days) TFF (days)
Type of MI
Stoma n = 39
No Stoma n = 15
P value
Simple MI n = 30
Complex MI n = 29
P value
49a (19–390) 37 (1–148) 25 (7–148)
23.5 (15–60) 18 (5–104) 9 (5–49)
0.001
26.5 (6–390) 19.5 (5–75) 19 (5–75)
52 (15–151) 32.5 (1–148) 21 (5–148)
0.002
LOS: length of stay, TP: time on parenteral nutrition, TFF: time to full enteral feeds. a All values are median (range)
0.062 0.067
0.14 0.34
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P.J. Farrelly et al. / Journal of Pediatric Surgery 49 (2014) 280–283
Table 3 Predisposing factors for DIOS. Development of DIOS after MI Subsequent DIOS (n = 35) No DIOS (n = 111) Fisher exact 2-tailed test, P = 0.24
MI (n = 69) 20 49
No MI (n = 77) 15 62
MI (n = 20) 10 10
No MI (n = 15) 0 15
MI Managed with stomas (n = 13) 8 5
MI managed without stomas (n = 7) 2 5
Simple MI (n = 10) 5 5
Complicated MI (n = 10) 5 5
Requirement for laparotomy for DIOS after MI Surgically managed DIOS (n = 10) Medically managed DIOS (n = 25) Fisher exact 2-tailed test, P = 0.0016 Requirement for laparotomy according to surgical treatment of MI Surgically managed DIOS (n = 10) Medically managed DIOS (n = 10) Fisher exact 2-tailed test, P = 0.35 Requirement for laparotomy according to type of MI Surgically managed DIOS (n = 10) Medically managed DIOS (n = 10) Fisher exact 2-tailed test, P = 1
Children who had a laparotomy for DIOS had a younger age of onset of DIOS [0.3 (0.1–6.7) years versus 6.51 (0.1–15.4) years; P b 0.001). At laparotomy for DIOS all children were found to have significant adhesions. In addition, we could define actual intestinal stricture (n = 2) and volvulus (n = 1) (Table 4). Procedures included ileostomy formation (n = 8) and bowel resection (n = 7). Recurrent episodes of DIOS did not predispose to later need for surgery [5/15 (33%) recurrent episodes versus 5/20 (25%) single episode; P = 0.24].
3. Discussion This is the largest UK surgical series investigating the surgical management of MI and appears to be the largest surgical series worldwide of DIOS [9]. Larger series of MI have been reported by centres in North America but encompass a time period when neonatal survival after MI improved from approximately 33% in the 1960s to 77% in the 1980s [10]. Contemporary series report survival for infants with MI in of N 90% [6,7].
Table 4 Surgical management of DIOS (n = 10). Type of MI
Episode of DIOS
Age (Yrs)
Simple Simple Simple
1 18 1
0.2 3.3 0.4
Simple
1
0.5
Simple
3 5
1.4 2.5
8
3.0
Complex Complex Complex
9 1 1 1
3.5 6.7 0.1 0.2
Complex
1
0.2
Complex
1 5
1.1 10.7
Surgical management Adhesiolysis Right hemicolectomy Adhesiolysis, ileal resection and formation of ileostomy Adhesiolysis, ileal resection and formation of ileostomy Adhesiolysis, enterotomy and washout Adhesiolysis, small bowel resection and primary anastomosis Adhesiolysis, ileal resection and formation of ileostomy Bowel resection, refashioning of stoma Adhesiolysis, enterotomy and washout Adhesiolysis, enterotomy and washout Adhesiolysis, small bowel resection and primary anastomosis Adhesiolysis, small bowel resection and primary anastomosis Adhesiolysis Adhesiolysis, small bowel resection and primary anastomosis
The overall incidence of MI as a proportion of all infants proven later to have CF in this series appears to be relatively high (20%), although not outside the range of previously published series (10%– 20%) [1,2,11–13]. The incidence of MI in our series may have been artificially inflated by infants with neonatal intestinal obstruction due to MI being transferred in to Alder Hey from outside of the region for surgical care if their local surgical unit was unable to accommodate them. There were no deaths in the post-operative or neonatal period despite the high incidence of complex MI. One of our challenges of this series should therefore be to reduce morbidity and other indices of surgical outcome. The most appropriate surgical intervention for the management of MI remains a contentious issue. Strategies can be broadly classified as those employing the formation of a stoma and those where bowel continuity is maintained although other strategies have been described. Mak et al. reported their experience of T-tube enterostomy in uncomplicated MI. Twenty of 23 (87%) infants had successful management of their MI using T-tube irrigation with n-acetylcysteine or enzyme replacement [9]. Those who advocate management with a stoma or T-tube argue that this strategy allows access to the bowel for irrigation in an effort to prevent the re-accumulation of the tenacious stool that causes intra-luminal obstruction. Complex MI or operative management with stomas both significantly increases length of stay. Neonates with complex MI are likely to present with greater derangement of their physiology and require more extensive bowel resection than those with simple MI [13]. The presence of a stoma in itself may lead to difficulties with high stoma output and consequently poor nutritional status. The ongoing presence of viscid intra-luminal content after surgery can delay adequate emptying and prolong the time to establishing full feeds. Achieving a satisfactory nutritional state in neonates with CF has been shown to effect longer-term, extra-intestinal prognosis [14–16]. Adequate weight gain may not be achieved without parenteral nutrition until bowel continuity is restored as the calorific requirement of these neonates is high. This series confirms that MI can be appropriately managed without stoma formation in selected cases and is associated with reduced length of stay. Mushtaq et al. has previously reported that primary anastomosis in MI was safe and associated with a reduced length of stay in a large UK series of 51 infants born in 1976 to 1995 [10]. There was a high re-laparotomy (22%) rate in our series of neonates with MI irrespective of the type of operative management compared to published re-laparotomy rates for other causes of
P.J. Farrelly et al. / Journal of Pediatric Surgery 49 (2014) 280–283
neonatal intestinal obstruction [17]. Jawaheer et al. has reported a surgical complication rate requiring re-laparotomy of 31% in patients with complex MI managed without stomas. Complications included anastomotic strictures and adhesive bowel obstruction [3]. This high reoperation rate is likely to be multi-factorial. Whilst the bowel may be completely decompressed at initial laparotomy the underlying pathophysiology of MI remains resulting in the continued production of tenacious gastrointestinal contents and obstruction requiring secondary intervention. Adhesive obstruction is more common after surgery for MI than for other conditions requiring neonatal laparotomy [17]. The adhesions encountered at subsequent laparotomy are often dense and extensive suggesting that there may be a more pronounced inflammatory reaction after MI. DIOS presents as a spectrum of severity from partial to complete obstruction. There have been no studies addressing the management of DIOS since the introduction of the ESPGHAN criteria and ours appears to be the first. The definition of ‘complete DIOS’ needs to be used with care as it might imply a requirement for surgical intervention. In our series, the rate of surgical intervention in such children was 12.5% (10 of 80 episodes). Most episodes of ‘complete DIOS’ were relieved with a regime including use of oral Gastrograffin©. Laparotomy was required for failure of medical management and typical findings at surgery were dense adhesions, stricture, volvulus or bowel ischaemia. Whilst MI does not predispose to DIOS per se, we have demonstrated that CF children who presented with MI had a predisposition to develop a more severe/complex form of DIOS necessitating surgery. It is possible that the intra-abdominal adhesions that form after neonatal laparotomy compound the pathophysiological processes found in DIOS and result in complications that mandate surgical intervention. Eighty percent of laparotomies performed for DIOS were complicated by the presence of significant adhesions and in 70% of cases bowel resection was required. In conclusion, maintaining bowel continuity at initial laparotomy for MI compared to management with stomas appears to be safe, associated with reduced lengths of stay, and doesn’t increase the rate of unplanned re-laparotomy. Clinicians involved in the management of children with CF need to be aware that ‘Complete DIOS’ is far from
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being a benign condition, particularly when the child has had previous abdominal surgery and early referral to a surgical team is essential in these children.
References [1] Burke MS, Ragi JM, Karamanoukian HL, et al. New strategies in nonoperative management of meconium ileus. J Pediatr Surg 2002;37:60–764. [2] Chaudry G, Navarro OM, Levine DS, et al. Abdominal manifestations of cystic fibrosis in children. Pediatr Radiol 2006;36:233–40. [3] Jawaheer J, Khalil B, Plummer T, et al. Primary resection and anastomosis for complicated meconium ileus: a safe procedure? Pediatr Surg Int 2007;23:1091–3. [4] Copeland DR, St Peter SD, Sharp SW, et al. Diminishing role of contrast enema in simple meconium ileus. J Pediatr Surg 2009;44:2130–2. [5] van der Doef HP, Kokke FT, van der Ent CK, et al. Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal intestinal obstruction syndrome, and constipation. Curr Gastroenterol Rep 2011;13:265–70. [6] Karimi A, Gorter RR, Sleeboom C, et al. Issues in the management of simple and complex meconium ileus. Pediatr Surg Int 2011;27:963–8. [7] Escobar MA, Grosfeld JL, Burdick JJ, et al. Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes. Surgery 2005;138:560–72. [8] Houwen RH, van der Doef HP, Sermet I, et al. Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr 2005;50:38–42. [9] Mak GZ, Harberg FJ, Hiatt P, et al. T-tube ileostomy for meconium ileus: four decades of experience. J Pediatr Surg 2000;35:349–52. [10] Mushtaq I, Wright VM, Drake DP, et al. Meconium ileus secondary to cystic fibrosis. The East London experience. Pediatr Surg Int 1998;13:365–9. [11] Del Pin CA, Czyrko C, Ziegler MM, et al. Management and survival of meconium ileus. A 30-year review. Ann Surg 1992;215:179–85. [12] Colombo C, Ellemunter H, Houwen R, et al. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros 2011;10:S24–8. [13] Carlyle BE, Borowitz DS, Glick PL. A review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon. J Pediatr Surg 2012;47:772–81. [14] Sawicki GS, Rasouliyan L, McMullen AH, et al. Longitudinal assessment of healthrelated quality of life in an observational cohort of patients with cystic fibrosis. Pediatr Pulmonol 2011;46:36–41. [15] Dijk FN, McKay K, Barzi F, et al. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 2011;96:1118–23. [16] Salvatore D, Buzzetti R, Baldo E, et al. An overview of international literature from cystic fibrosis registries 2. Neonatal screening and nutrition/growth. J Cyst Fibros 2010;9:75–83. [17] Choudhry MS, Grant HW. Small bowel obstruction due to adhesions following neonatal laparotomy. Pediatr Surg Int 2006;22:729–32.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Gastrointestinal surgery in cystic fibrosis: A 20-year review Paul J. Farrelly a, Caroline Charlesworth a, Sophie Lee a, Kevin W. Southern b, Colin T. Baillie a,⁎ a b
Department of Paediatric Surgery, Alder Hey Children’s NHS Foundation Trust, West Derby, Liverpool, L12 2AP, United Kingdom Institute of Child Health, Alder Hey Children’s NHS Foundation Trust, West Derby, Liverpool, L12 2AP, United Kingdom
a r t i c l e
i n f o
Article history: Received 31 October 2013 Accepted 10 November 2013 Key words: Cystic fibrosis Meconium ileus Distal intestinal obstruction syndrome Surgery
a b s t r a c t Objectives: The purpose of this study was to evaluate outcomes of the surgical management for meconium ileus (MI) and Distal Intestinal Obstruction Syndrome (DIOS) in Cystic Fibrosis (CF). Methods: Children born between 1990 and 2010 were identified using a regional CF database. Retrospective case note analysis was performed. Outcome measures for MI were mortality, relaparotomy rate, length of stay (LOS), time on parental nutrition (TP), and time to full feeds (TFF). Outcome measures for DIOS were: age of onset, number of episodes, and need for laparotomy. Results: Seventy-five of 376 neonates presented with MI. Fifty-four (92%) required laparotomy. Contrast enema decompression was attempted in nineteen. There were no post-operative deaths. Thirty-nine (72%) neonates with MI were managed with stomas. LOS was longer in those managed with stomas (p = 0.001) and in complex MI (p = 0.002). Thirty-five patients were treated for DIOS. Twenty-five patients were managed with gastrograffin. Ten patients underwent surgical management of DIOS. Overall, MI did not predispose to later development of DIOS. There was a significantly greater incidence of laparotomy for DIOS in children who had MI. Conclusion: The proportion of neonates with complex meconium ileus was high (49%) and may explain the infrequent utilisation of radiological decompression. Complex MI or management with stomas both significantly increase LOS. Re-laparotomy rate is high (22%) in MI irrespective of the type of management. DIOS is not a benign condition, particularly when the child has had previous abdominal surgery. Early referral to a surgical team is essential in these children. © 2014 Elsevier Inc. All rights reserved.
Meconium ileus (MI) may be the presenting feature in 10%–15% of patients with cystic fibrosis (CF) [1,2] and can be classified as simple or complex. Simple MI is an uncomplicated intraluminal distal small bowel obstruction due to abnormally viscid meconium. Complex MI additionally can be characterized by complications such as meconium peritonitis, pseudocyst formation, volvulus or intestinal atresia. A variety of operative strategies have been utilized in the management of both simple and complicated MI [1–4,6], the ultimate aim being to decompress the bowel and relieve obstruction by clearing the abnormal meconium. Strategies can be broadly classified as those employing the formation of a stoma (e.g. divided, Bishop– Koop or Santulli), and those where bowel continuity is maintained (e.g. enterotomy and washout, with or without intestinal resection and primary anastomosis). There is no consensus in the current literature as to what constitutes the preferred surgical strategy for the management of MI. Partial or complete small bowel obstruction attributed to CF has also been described since 1945 in older children [8]. This was initially termed ⁎ Corresponding author at: Department of Paediatric Surgery; Alder Hey Children’s NHS Foundation Trust; Eaton Road; West Derby; Liverpool, L12 2AP, United Kingdom. Tel.:+44 0151 228 4811; fax:+44 0151 228 0328. E-mail address: [email protected] (C.T. Baillie). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.11.038
meconium ileus equivalent (MIE) but more recently the term distal intestinal obstruction syndrome (DIOS) has become commonplace. The term DIOS came to encompass a variety of intestinal symptoms and signs, possibly including recalcitrant constipation. The varied definitions have made it difficult to estimate the true incidence and morbidity associated with DIOS [5,7–9]. However, in 2010 the ESPGHAN CF Working group introduced a clear and specific definition for the term DIOS [8] (Table 1). Since then there has been very little contemporary literature on the morbidity and surgical management of DIOS [7]. Our aim was to evaluate the success of managing meconium ileus and DIOS using different surgical strategies over a 20-year period at a single institution. We were specifically interested as to whether infants with MI managed with stomas were comparable to those where intestinal continuity was maintained. The utilization and outcome of radiological decompression in MI were also investigated. For the group with DIOS the principle aim was to test the hypothesis that MI predisposes to the later development of DIOS overall and for DIOS requiring surgery. 1. Methods Patients were retrospectively identified using the regional CF database. All patients under the care of the Alder Hey Children’s NHS
P.J. Farrelly et al. / Journal of Pediatric Surgery 49 (2014) 280–283 Table 1 ESPGHAN CF Working Group definition for DIOS in cystic fibrosis [8]. Criteria Explanation 1
Complete intestinal obstruction as evidenced by vomiting of bilious material and/or fluid levels in smallintestine on an abdominal radiography 2 Faecal mass in ileo-caecum 3 Abdominal pain and/or distension Complete DIOS: 1 and 2 and 3 Incomplete/Impending DIOS: 2 and 3 only
Foundation Trust with CF who were born between 1990 and 2010 were eligible for inclusion. Patients requiring management of MI or DIOS were identified from the CF database and their hospital case notes retrieved. Data were collected for each patient with MI with regard to; conservative versus operative management and stoma versus other operative procedure. Outcome measures included mortality, relaparotomy (excluding restoration of continuity), time to restoration of continuity, length of stay (LOS), time on parenteral nutrition (TP) and time to full feeds (TFF). DIOS was defined using ESPGHAN criteria of abdominal pain +/− distension and ileocaecal mass with evidence of obstruction (Table 1) [8]. Case notes and radiological investigations were rigorously reviewed and children were only included when they met all the criteria for the contemporary definition of “complete DIOS”. Data for this group included age of onset, number of episodes, history and type of preceding MI, and need for previous surgery. Data are quoted as median (range). The Mann–Whitney U-test and the Fisher exact 2-tailed test were used for statistical analysis. P values of b 0.05 were considered significant. 2. Results The regional database identified 376 children with CF born between Jan. 1990 and Dec. 2010. However complete data were only available for the 146 patients that were managed and followedup at Alder Hey Children’s NHS Foundation Trust. The remaining patients predominantly attended district general hospitals for the subsequent management of their CF. Seventy-five (19.9%) of 376 children presented as infants with MI. Complete data sets were available for only 59 as 16 were subsequently transferred back to a more local specialist centre as infants or relocated later and were not followed up at Alder Hey hospital. These were excluded from this analysis. Thirty (51%) infants were regarded as having simple MI and 29 (49%) had complicated MI. Gastrograffin© enemas were attempted initially in 19 (32%) infants but in only 5 (9%) was this successful and the remaining 54 (91%) required laparotomy. Of the 54 patients requiring laparotomy 39 (72%) had divided stomas formed, 7 (13%) were managed with enterotomy and washout, and 8 (15%) with resection and primary anastomosis. The
281
time to closure for patients managed with stomas was 47 days (4– 202). All neonates with meconium ileus were given N-acetyl cysteine in the post-operative period. It is administered through the feeding tube or by lavage of the proximal stoma to aid resolution of obstructive symptoms. Once enteral feeding is established the N-acetyl cysteine is replaced by pancreatic enzyme replacement therapy. Enzyme replacement therapy is initiated once infants have reached a volume of 30 ml per feed. There was a significant difference in LOS after MI between operative patients managed with and without stomas: 49 days (19– 390) and 23 days (15–60) respectively. Table 2 shows that those managed with stomas tended to take longer to reach full feeds compared with neonates where bowel continuity was maintained after laparotomy (25 days (7–148) versus 9 days (5–49)), however the difference failed to reach statistical significance (p = 0.067). There was also a trend towards a reduced duration of parental nutrition in the group managed without stomas (18 days (5–104) versus 37 days (1–148)) that failed to reach statistical significance (p0.062). Infants tended to stay on supplemental parenteral nutrition for a period of time after establishing appropriate full volume enteral feeds. Parenteral nutrition was discontinued once it was demonstrated that growth was adequate on serial weight measurements. Infants with complex MI had a longer LOS than those with simple MI [26.5 (6–390) days versus 52 (15–151) days; P b 0.002)] (Table 2). There was no difference in the re-laparotomy rate between infants managed with or without stomas [8 of 36 (22%) versus 3 of 13 (23%); P = 1.00]. Data regarding re-laparotomy were incomplete for 5 patients. Although surgical management with stomas increased length of stay [49 (19–390) days vs 23.5 (15–60) days: P = 0.001], it did not increase re-laparotomy rates [22% versus 23%; P =1.00]. Median follow-up in this group was 118 (12–225) months. There were no deaths in the post-operative neonatal period. There were 3 late deaths due to non-gastrointestinal manifestations of CF. The number of CF patients treated for DIOS was 35 (24%). The age of onset of the first episode of DIOS was 7.7 (0.9–16.7) years. Of these, 22 (62%) were managed with oral Gastrograffin and 3 (9%) with Gastrograffin enemas. The other 10 (29%) had DIOS requiring laparotomy. In total there were 80 separate episodes of “complete DIOS” in these patients. Presentation with MI did not predispose to later development of DIOS [n = 20 (29%) versus n = 15(19%); P = 0.24] (Table 3). However, there was a greater incidence of surgical management of DIOS in children who had had MI [n = 10 (50%) versus n = 0 (0%); P = 0.002]. Laparotomy was never required for the management of DIOS in children who had not previously had MI (Table 3). Subgroup analysis showed that neither complex MI (P = 1) nor management with stomas (P = 0.35) predisposed to surgical management of DIOS. Of the children that required laparotomy for DIOS, 5 (50%) had simple meconium ileus and 5 (50%) had complex meconium ileus (Table 3).
Table 2 Outcomes in Meconium Ileus (MI). Type of Surgery
LOS (days) TP (days) TFF (days)
Type of MI
Stoma n = 39
No Stoma n = 15
P value
Simple MI n = 30
Complex MI n = 29
P value
49a (19–390) 37 (1–148) 25 (7–148)
23.5 (15–60) 18 (5–104) 9 (5–49)
0.001
26.5 (6–390) 19.5 (5–75) 19 (5–75)
52 (15–151) 32.5 (1–148) 21 (5–148)
0.002
LOS: length of stay, TP: time on parenteral nutrition, TFF: time to full enteral feeds. a All values are median (range)
0.062 0.067
0.14 0.34
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Table 3 Predisposing factors for DIOS. Development of DIOS after MI Subsequent DIOS (n = 35) No DIOS (n = 111) Fisher exact 2-tailed test, P = 0.24
MI (n = 69) 20 49
No MI (n = 77) 15 62
MI (n = 20) 10 10
No MI (n = 15) 0 15
MI Managed with stomas (n = 13) 8 5
MI managed without stomas (n = 7) 2 5
Simple MI (n = 10) 5 5
Complicated MI (n = 10) 5 5
Requirement for laparotomy for DIOS after MI Surgically managed DIOS (n = 10) Medically managed DIOS (n = 25) Fisher exact 2-tailed test, P = 0.0016 Requirement for laparotomy according to surgical treatment of MI Surgically managed DIOS (n = 10) Medically managed DIOS (n = 10) Fisher exact 2-tailed test, P = 0.35 Requirement for laparotomy according to type of MI Surgically managed DIOS (n = 10) Medically managed DIOS (n = 10) Fisher exact 2-tailed test, P = 1
Children who had a laparotomy for DIOS had a younger age of onset of DIOS [0.3 (0.1–6.7) years versus 6.51 (0.1–15.4) years; P b 0.001). At laparotomy for DIOS all children were found to have significant adhesions. In addition, we could define actual intestinal stricture (n = 2) and volvulus (n = 1) (Table 4). Procedures included ileostomy formation (n = 8) and bowel resection (n = 7). Recurrent episodes of DIOS did not predispose to later need for surgery [5/15 (33%) recurrent episodes versus 5/20 (25%) single episode; P = 0.24].
3. Discussion This is the largest UK surgical series investigating the surgical management of MI and appears to be the largest surgical series worldwide of DIOS [9]. Larger series of MI have been reported by centres in North America but encompass a time period when neonatal survival after MI improved from approximately 33% in the 1960s to 77% in the 1980s [10]. Contemporary series report survival for infants with MI in of N 90% [6,7].
Table 4 Surgical management of DIOS (n = 10). Type of MI
Episode of DIOS
Age (Yrs)
Simple Simple Simple
1 18 1
0.2 3.3 0.4
Simple
1
0.5
Simple
3 5
1.4 2.5
8
3.0
Complex Complex Complex
9 1 1 1
3.5 6.7 0.1 0.2
Complex
1
0.2
Complex
1 5
1.1 10.7
Surgical management Adhesiolysis Right hemicolectomy Adhesiolysis, ileal resection and formation of ileostomy Adhesiolysis, ileal resection and formation of ileostomy Adhesiolysis, enterotomy and washout Adhesiolysis, small bowel resection and primary anastomosis Adhesiolysis, ileal resection and formation of ileostomy Bowel resection, refashioning of stoma Adhesiolysis, enterotomy and washout Adhesiolysis, enterotomy and washout Adhesiolysis, small bowel resection and primary anastomosis Adhesiolysis, small bowel resection and primary anastomosis Adhesiolysis Adhesiolysis, small bowel resection and primary anastomosis
The overall incidence of MI as a proportion of all infants proven later to have CF in this series appears to be relatively high (20%), although not outside the range of previously published series (10%– 20%) [1,2,11–13]. The incidence of MI in our series may have been artificially inflated by infants with neonatal intestinal obstruction due to MI being transferred in to Alder Hey from outside of the region for surgical care if their local surgical unit was unable to accommodate them. There were no deaths in the post-operative or neonatal period despite the high incidence of complex MI. One of our challenges of this series should therefore be to reduce morbidity and other indices of surgical outcome. The most appropriate surgical intervention for the management of MI remains a contentious issue. Strategies can be broadly classified as those employing the formation of a stoma and those where bowel continuity is maintained although other strategies have been described. Mak et al. reported their experience of T-tube enterostomy in uncomplicated MI. Twenty of 23 (87%) infants had successful management of their MI using T-tube irrigation with n-acetylcysteine or enzyme replacement [9]. Those who advocate management with a stoma or T-tube argue that this strategy allows access to the bowel for irrigation in an effort to prevent the re-accumulation of the tenacious stool that causes intra-luminal obstruction. Complex MI or operative management with stomas both significantly increases length of stay. Neonates with complex MI are likely to present with greater derangement of their physiology and require more extensive bowel resection than those with simple MI [13]. The presence of a stoma in itself may lead to difficulties with high stoma output and consequently poor nutritional status. The ongoing presence of viscid intra-luminal content after surgery can delay adequate emptying and prolong the time to establishing full feeds. Achieving a satisfactory nutritional state in neonates with CF has been shown to effect longer-term, extra-intestinal prognosis [14–16]. Adequate weight gain may not be achieved without parenteral nutrition until bowel continuity is restored as the calorific requirement of these neonates is high. This series confirms that MI can be appropriately managed without stoma formation in selected cases and is associated with reduced length of stay. Mushtaq et al. has previously reported that primary anastomosis in MI was safe and associated with a reduced length of stay in a large UK series of 51 infants born in 1976 to 1995 [10]. There was a high re-laparotomy (22%) rate in our series of neonates with MI irrespective of the type of operative management compared to published re-laparotomy rates for other causes of
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neonatal intestinal obstruction [17]. Jawaheer et al. has reported a surgical complication rate requiring re-laparotomy of 31% in patients with complex MI managed without stomas. Complications included anastomotic strictures and adhesive bowel obstruction [3]. This high reoperation rate is likely to be multi-factorial. Whilst the bowel may be completely decompressed at initial laparotomy the underlying pathophysiology of MI remains resulting in the continued production of tenacious gastrointestinal contents and obstruction requiring secondary intervention. Adhesive obstruction is more common after surgery for MI than for other conditions requiring neonatal laparotomy [17]. The adhesions encountered at subsequent laparotomy are often dense and extensive suggesting that there may be a more pronounced inflammatory reaction after MI. DIOS presents as a spectrum of severity from partial to complete obstruction. There have been no studies addressing the management of DIOS since the introduction of the ESPGHAN criteria and ours appears to be the first. The definition of ‘complete DIOS’ needs to be used with care as it might imply a requirement for surgical intervention. In our series, the rate of surgical intervention in such children was 12.5% (10 of 80 episodes). Most episodes of ‘complete DIOS’ were relieved with a regime including use of oral Gastrograffin©. Laparotomy was required for failure of medical management and typical findings at surgery were dense adhesions, stricture, volvulus or bowel ischaemia. Whilst MI does not predispose to DIOS per se, we have demonstrated that CF children who presented with MI had a predisposition to develop a more severe/complex form of DIOS necessitating surgery. It is possible that the intra-abdominal adhesions that form after neonatal laparotomy compound the pathophysiological processes found in DIOS and result in complications that mandate surgical intervention. Eighty percent of laparotomies performed for DIOS were complicated by the presence of significant adhesions and in 70% of cases bowel resection was required. In conclusion, maintaining bowel continuity at initial laparotomy for MI compared to management with stomas appears to be safe, associated with reduced lengths of stay, and doesn’t increase the rate of unplanned re-laparotomy. Clinicians involved in the management of children with CF need to be aware that ‘Complete DIOS’ is far from
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being a benign condition, particularly when the child has had previous abdominal surgery and early referral to a surgical team is essential in these children.
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