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ORIGINAL ARTICLE
Year : 2014  |  Volume : 19  |  Issue : 2  |  Page : 85-89
 

Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship


1 Department of Pediatric Surgery, Children's Hospital of New Jersey and Beth Israel Medical Center, Newark, USA
2 Medical Student, The University of Medicine and Dentistry of New Jersey, NJ, USA

Date of Web Publication29-Mar-2014

Correspondence Address:
Sathyaprasad Burjonrappa
Attending Pediatric Surgeon, Department of Pediatric Surgery, Newark Beth Israel Medical Center, Clinical Assistant Professor of Surgery, 2130 Millburn Avenue, Maplewood, New Jersey - 07040
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9261.129601

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   Abstract 

Introduction: Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. Materials and Methods: The temporal relationship between age at Meckel's diverticulectomy and the presence of ectopic epithelium was evaluated in our series. A meta-analysis of all reported recent literature on this condition was subsequently performed to evaluate the strength of the relationship between ectopic epithelium and symptomatic Meckel's diverticulum. Results: There was a paucity of ectopic epithelium in Meckel's diverticulectomy specimens in infants operated on at less than 1 year of age. Having two or more ectopic epithelia in a diverticulum does not appear to carry an additive risk for complications. The meta-analysis confirmed that ectopic epithelium was the most significant factor that influenced surgical intervention in all series of Meckel's diverticulum. Conclusion: The relationship between ectopic epithelium and the development of symptomatic Meckel's diverticulum is complex. Further understanding of the development of ectopic rests in the diverticulum will facilitate elucidating the pathophysiology in symptomatic cases.


Keywords: Ectopic epithelium, meta-analysis, meckel′s diverticulum, surgical indications


How to cite this article:
Burjonrappa S, Khaing P. Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship. J Indian Assoc Pediatr Surg 2014;19:85-9

How to cite this URL:
Burjonrappa S, Khaing P. Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship. J Indian Assoc Pediatr Surg [serial online] 2014 [cited 2019 Oct 17];19:85-9. Available from: http://www.jiaps.com/text.asp?2014/19/2/85/129601



   Introduction Top


Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract with an incidence of approximately 2% in the population. [1] Most cases are asymptomatic, with an overall lifetime risk of complications being reported at around 6.4%. [2] The most common clinical finding in symptomatic cases is gastrointestinal bleeding, although obstruction, diverticulitis and intussusception are also commonly seen. [1] Obstructive symptoms due to congenital bands manifest earlier in life while inflammatory presentations usually manifest later. It is generally agreed upon that this temporal distribution of symptoms is due to the time taken to develop inflammation and ulceration in Meckel's with ectopic mucosa. The combined presence of multiple ectopic tissues within one Meckel's diverticulum is relatively rare, and its occurrence is not well established in the literature. [3],[4],[5] Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. Herein, we report 22 cases of Meckel's diverticulum in pediatric patients treated at our institution between 2007 and 2012. We also performed a meta-analysis of studies reporting on this topic. The objectives of the study were three-fold: (1) to assess the temporal relationship between patient age and development of a symptomatic diverticulum, (2) to determine the surgical implication of the pathological finding of multiple ectopic epithelium in a Meckel's diverticulum and lastly (3) to reconfirm by a meta-analysis, and offer higher level scientific evidence, the well known association between ectopic epithelium and symptomatic Meckel's diverticulum.


   Materials and Methods Top


We obtained de-identified patient records of Meckel's diverticulectomy performed at our institution over a 5-year period and evaluated the pathology reports for the presence or absence of ectopic epithelium. Demographic data of the patients were noted. Patients were classified as having had surgery performed for symptomatic or asymptomatic Meckel's diverticulum. Pathology reports were evaluated to assess for the presence of and the nature of ectopic epithelium. The temporal relationship between the age of Meckel's diverticulectomy and the presence of ectopic epithelium and development of inflammatory changes was analyzed. Further we evaluated if there was an increased incidence of symptomatic Meckel's in those patients with a pathological finding of more than one ectopic epithelium.

As the second part of the study we conducted a search on Medline for articles containing the keywords "Meckel's diverticulum" and "ectopic" or "heterotopic epithelium" from February 1993 to February 2013. The inclusion criteria for an article in the meta-analysis were a clear description of the nature of the ectopic epithelium in the results. The exclusion criteria omitted those articles that did not clarify whether the ectopic tissue was found in a symptomatic or asymptomatic diverticulum. Articles that met both criteria were individually reviewed to extract the numbers of symptomatic cases (all cases where surgical intervention was primarily performed for a Meckel's diverticulum related issue) and the number of total cases for each category of normal epithelium, single ectopic tissue, or multiple ectopic tissues. A meta-analysis was performed using a random effects model. The purpose of the meta-analysis was to offer a higher level of scientific evidence to the association between symptomatic Meckel's diverticulum and ectopic epithelium. The secondary goals of the meta-analysis were to identify if the presence of multiple ectopic elements additively increased the risk of symptomatic presentations of Meckel's. Descriptive statistics were performed on collected data. The Fisher exact test was used to determine significance of categorical data.


   Results Top


Twenty-two (22) patients underwent Meckel's diverticulectomy over the study period [Table 1]. There were 16 males (73%) and 6 females (27%). Seven patients (33%) presented with symptoms secondary to the local effects of the ectopic epithelium (bleeding, diverticulitis, perforation). Seven patients (33%) presented with bowel obstruction and four had ectopic epithelium in the diverticulum. Six patients (30%) were asymptomatic and had the Meckel's diverticulectomy concomitant with another abdominal procedure and none of them had an ectopic epithelium. Two neonates underwent surgery for a patent omphalomesenteric duct and they did not have any ectopic epithelium. The average age of patients in the study was 4.7 years (Range: 1 day-16 years; Median: 2 years). The average age of patients with ectopic epithelium was 6.3 years (Range: 1 year-16 years; Median: 4 years). The average age of patients with no ectopic epithelium was 3.125 years (Range: 1 day-13 years; Median: 1.5 months) (P = 0.075). No ectopic epithelium was identified in any patient who underwent Meckel's diverticulectomy before the age of 1 year (P < 0.006). Gastric (11/11) and pancreatic (3/11) ectopic epithelium were encountered most frequently. There were three patients who had both gastric and pancreatic ectopic epithelium.
Table 1: Cases of Meckel's diverticulum treated at our institution between 2007 and 2012

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A total of nine eligible case series were identified from the literature based on our criteria. [6],[7],[8],[9],[10],[11],[12],[13],[14] None out of these nine studies contained cases of multiple ectopic tissues. The meta-analysis shown in [Figure 1] includes data from these nine case series plus the data from our own case series.
Figure 1: Meta-analysis by random effects model confirms the well known finding of ectopic epithelium causing symptomatic Meckel's diverticulum

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Of the ten total case series, five showed statistically significant higher odds ratios for symptomatic complications with single ectopic tissue as compared to normal epithelium in a Meckel's diverticulum. The combined odds ratio for all ten studies also showed a statistically significant higher odds ratio for symptomatic complications with single ectopic tissue [Figure 1].


   Discussion Top


As the fetal intestines separate from the yolk sac during early embryogenesis, the omphalomesenteric duct forms and subsequently obliterates by the fifth to seventh week of fetal life. Failure of the omphalomesenteric duct to obliterate completely can lead to many congenital anomalies of the small intestines. Of these, Meckel's diverticulum is the most common. [15]

The presence of ectopic tissues within Meckel's diverticulum has been noted since the early 1900s, and historically, many hypotheses have been proposed to explain their presence. [5],[16] The now widely-accepted theory purport that the pluripotent cells that once lined the omphalomesenteric duct are responsible for giving rise to the various ectopic tissues within the Meckel's diverticulum. [17],[18],[19] This theory, however, fails to explain the strong preponderance for finding ectopic gastric or ectopic pancreatic tissues with Meckel's diverticula. Case reports of less common ectopic tissues, such as colonic, duodenal, jejunal, hepatic, and endometrial, are very few in numbers. It is unknown why the pluripotent cells of the omphalomesenteric duct would more commonly differentiate into one type of tissue over another. It has been proposed that ectopic pancreatic tissue may be misplaced tissue from migration and fusion of the ventral and dorsal pancreatic buds during embryology. [20] It has also been suggested that improper molecular signaling throughout the GI tract with loss of the sonic hedgehog gene might be responsible ectopic pancreatic tissue. [21] Our personal series raises the intriguing question as to whether the ectopic tissue in Meckel's diverticulum is an early post-natal development as not one of our patients less than 1 year of age had ectopic epithelium in the Meckel's. Perhaps variable phenotypic expression of pluripotent cells in the diverticulum is based on the exposure to gastrointestinal nutrients and growth factors. This might be a different explanation to the currently understood pathophysiology of symptomatic inflammatory Meckel's occurring later in life. However as this is a small series, larger studies are needed to answer this question satisfactorily.

The presence of ectopic tissue is associated with higher incidences of complications from Meckel's diverticulum. [1],[10],[22] It is estimated that the incidence of symptoms in a Meckel's diverticulum with ectopic tissue is as high as 50-60%, whereas the incidence of symptoms in all Meckel's diverticula is around 6% as previously stated. [1] Results from this meta-analysis support these conclusions, and to the best of our knowledge, ours is the first study to combine multiple studies on this topic into a statistically informative meta-analysis.

Unfortunately, we failed to answer the question of whether the presence of multiple ectopic tissues increases the incidence of complications in a Meckel's diverticulum. Based on our case series from our institution alone, it seems that the odds ratio of complications is not statistically significantly higher for multiple ectopic tissues as compared to normal epithelium.

In this study, we have shown a statistically significant higher odds ratio for developing symptomatic complications in Meckel's diverticula with (at least) single ectopic tissue across multiple studies in the last two decades of literature. However, currently there exists no effective way to establish the presence ectopic tissue prior to surgical pathologic examination in an incidentally discovered Meckel's diverticulum. A consideration of factors, such as the age and sex of the patient, or the length, location, and diameter of the diverticulum, as well as palpation of the diverticulum during surgery, has proven to be imprecise and ineffective in predicting whether a diverticulum would subsequently develop complications and whether a prophylactic diverticulectomy is warranted. [23] The finding of male preponderance in our series in the overall and symptomatic groups has however not been substantiated in other studies where sex was not a discriminatory factor. The most useful method in existence for detecting ectopic gastric mucosa, the technetium-99m pertechnate scan, has extremely poor utility. It has been shown that this scan has a sensitivity and specificity of 85% and 95% percent, respectively in children, and of 62.5 and 9%, respectively in adults. [24],[25] Understanding the pathogenesis of ectopic epithelium development may enable development of surgical algorithms to accurately predict who would benefit from Meckel's diverticulectomy in the incidental presentation.

 
   References Top

1.Schropp KP, Garey CL. Meckel's diverticulum. In: Ashcraft's Pediatric Surgery. Editors: Holcomb & Murphy. 5 th Edition W.B. Saunders, Philadelphia, PA; 2010. p. 526-31.  Back to cited text no. 1
    
2.Cullen JJ, Kelly KA, Moir CR, Hodge DO, Zinsmeister AR, Melton LJ 3 rd . Surgical management of Meckel's diverticulum. An epidemiologic, population-based study. Ann Surg 1994;220:564-8; discussion 568-9.  Back to cited text no. 2
    
3.Zarand A, Bajtai A, Baranyai Z, Dede K, Jakab F. Inflammation of ectopic pancreatic tissue in a Meckel's diverticulum causing acute abdominal symptoms: A case report and review of the literature. Int J Surg Pathol 2011;19:359-63.  Back to cited text no. 3
    
4.Al-Zahem A, Arbuckle S, Cohen R. Combined ileal heterotopic pancreatic and gastric tissues causing ileocolic intussusception in an infant. Pediatr Surg Int 2006;22:297-9.  Back to cited text no. 4
    
5.Soderlund S. Meckel's diverticulum. A clinical and histologic study. Acta Chir Scand Suppl 1959; 248(Suppl):1-233.  Back to cited text no. 5
    
6.Ackerman Z, Peston D, Cohen P. Role of Helicobacter pylori infection in complications from Meckel's diverticulum. Dig Dis Sci 2003;48:1068-72.  Back to cited text no. 6
    
7.Bani-Hani KE, Shatnawi NJ. Meckel's diverticulum: Comparison of incidental and symptomatic cases. World J Surg 2004;28:917-20.  Back to cited text no. 7
    
8.Chiengkriwate P, Patrapinyokul S, Sangkhathat S, Chowchuvech V. Circumumbilicus incision for bleeding Meckel's diverticulectomy. J Med Assoc Thai 2007;90:931-5.  Back to cited text no. 8
    
9.McKay R. High incidence of symptomatic Meckel's diverticulum in patients less than fifty years of age: An indication for resection. Am Surg 2007;73:271-5.  Back to cited text no. 9
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10.Park JJ, Wolff BG, Tollefson MK, Walsh EE, Larson DR. Meckel diverticulum: The Mayo Clinic experience with 1476 patients (1950-2002). Ann Surg 2005;241:529-33.  Back to cited text no. 10
    
11.Shalaby RY, Soliman SM, Fawy M, Samaha A. Laparoscopic management of Meckel's diverticulum in children. J Pediatr Surg 2005;40:562-7.  Back to cited text no. 11
    
12.Arnold JF, Pellicane JV. Meckel's diverticulum: A ten-year experience. Am Surg 1997;63:354-5.  Back to cited text no. 12
    
13.Bemelman WA, Hugenholtz E, Heij HA, Wiersma PH, Obertop H. Meckel's diverticulum in Amsterdam: Experience in 136 patients. World J Surg 1995;19:734-7.  Back to cited text no. 13
    
14.Piñero A, Martinez-Barba E, Canteras M, Rodrigues JM, Castellanos G, Parrilla P. Surgical management and complications of Meckel's diverticulum in 90 patients. Eur J Surg 2002;168:8-12.  Back to cited text no. 14
    
15.Snyder CL. Meckel diverticulum. Pediatric Surgery 2012; In Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA editor. Pediatric surgery. 7th ed.. Philadelphia, PA: Elsevier Saunders; 2012;p.1085-92.  Back to cited text no. 15
    
16.Bigelow R, Clark DE. Heterotopic pancreatic tissue and gastric mucosa in Meckel's diverticulum. Arch Surg 1950;60:157-63.  Back to cited text no. 16
[PUBMED]    
17.Sharma RK, Jain VK. Emergency surgery for Meckel's diverticulum. World J Emerg Surg 2008;3:27.  Back to cited text no. 17
    
18.Varcoe RL, Wong SW, Taylor CF, Newstead GL. Diverticulectomy is inadequate treatment for short Meckel's diverticulum with heterotopic mucosa. ANZ J Surg 2004;74:869-72.  Back to cited text no. 18
    
19.Mukai M, Takamatsu H, Noguchi H, Fukushige T, Tahara H, Kaji T. Does the external appearance of a Meckel's diverticulum assist in choice of the laparoscopic procedure? Pediatr Surg Int 2002;18:231-3.  Back to cited text no. 19
    
20.Bromberg SH, Camilo Neto C, Borges AF, Franco MI, França LC, Yamaguchi N. Pancreatic heterotopias: Clinicopathological analysis of 18 patients. Rev Col Bras Cir 2010;37:413-9.  Back to cited text no. 20
    
21.Baysoy G, Balamtekin N, Uslu N, Karavelioðlu A, Talim B, Ozen H. Double heterotopic pancreas and Meckel's diverticulum in a child: Do they have a common origin? Turk J Pediatr 2010;52:336-8.  Back to cited text no. 21
    
22.Artigas V, Calabuig R, Badia F, Rius X, Allende L, Jover J. Meckel's diverticulum: Value of ectopic tissue. Am J Surg 1986;151:631-4.  Back to cited text no. 22
[PUBMED]    
23.Martin JP, Connor PD, Charles K. Meckel's diverticulum. Am Fam Physician 2000;61:1037-44.  Back to cited text no. 23
    
24.Daneman A, Lobo E, Alton DJ, Shuckett B. The value of sonography, CT and air enema for detection of complicated Meckel diverticulum in children with nonspecific clinical presentation. Pediatr Radiol 1998;28:928-32.  Back to cited text no. 24
    
25.Schwartz MJ, Lewis JH. Meckel's diverticulum: Pitfalls in scintigraphic detection in the adult. Am J Gastroenterol 1984;79:611-8.  Back to cited text no. 25
[PUBMED]    


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