Introduction

Total colonic aganglionosis (TCA) is a severe form of Hirschsprung’s disease (HD) characterised by the absence of ganglion cells in the entire colon extending into the terminal ileum. This relatively rare condition occurs in less than 10 % of the HD cases [1, 2]. Despite recent advances in surgical techniques and meticulous pre- and post-operative management, TCA remains a challenging surgical condition. For a long time, it has been thought that the length of aganglionosis in HD negatively impacts the long-term functional outcome [3] and that results of pull-through (PT) surgery for TCA are inferior to those in patients with recto-sigmoid HD [4, 5]. Few studies have evaluated the long-term clinical outcome and bowel function in patients with TCA. Even in large centres, only a few patients with TCA may be treated over the course of a year, and therefore, only studies with limited numbers of patients are reported in the literature. The lack of large multi-centre studies for TCA has resulted in conflicting reports regarding the long-term results of surgery. The aim of this study was to investigate the long-term clinical outcome of patients with TCA based on the meta-analysis of the published literature.

Methods

A systematic literature search was performed to identify articles that reported the outcomes of patients with TCA. MEDLINE®(1966–present) and EMBASE®(1980–present) electronic databases were searched in April 2012 using a combination of the following terms: “Hirschsprung’s disease”, “Total colonic aganglionosis” AND “Outcome”. References lists of identified articles were screened for additional publications of interest. All identified articles were independently assessed by each of the three authors. Only retrospective or prospective studies published between 1980 and 2011 with a minimum mean follow-up of 4 years from the time of PT surgery were eligible for inclusion. Series referring to results of already selected cohorts were excluded. Reports on patients selected for specific complications or anomalies were excluded to avoid selection bias and confounding towards a poorer outcome.

Detailed data regarding study design, patient characteristics, procedure type and outcomes were extracted into an electronic datasheet in a standardised manner. Outcome parameters of patients with TCA included mortality rates, post-operative morbidities (immediate and late complications) and long-term outcomes. Patients were considered to have a good long-term outcome when their bowel function was described as “normal”, “satisfactory” or “continent” without soiling or need for washouts/dilations to achieve stooling. Conversely, patients with soiling, incontinence or permanent stoma were considered to have a poor functional outcome along with patients who required long-term medications, washouts/dilations or had a high frequency of bowel motions (>5/day). Data for each outcome category were not available in every paper. Outcome incidence is given per total number of patients reported on in that category.

Statistical analysis of contingency tables comparing outcomes between two groups formed on the basis of publication date, and comparing outcomes for three groups with different follow-up lengths, was performed with Fisher’s exact test using GraphPad Prism 5.0 (GraphPad Software Inc., La Jolla, USA). A p value <0.05 was considered as statistically significant.

Results

The literature search produced 225 articles, of which 189 were excluded because they did not fulfil the inclusion criteria (Fig. 1). Ultimately 36 articles, published between 1982 and 2011, were included in this analysis [3, 6–41]. Data from 969 individual cases of TCA from 37 different centres worldwide was collected. In 27 articles, 804 cases of TCA were reported from a total of 8,818 patients with HD; therefore, the incidence of HD in which TCA was present was 9.1 %. Gender was reported in 859 cases, 559 were male and 300 females, determining a male-to-female ratio of 1.86:1. The mean follow-up period for all studies was 9.6 years. The earliest study commenced in 1954 and the longest study period was 35 years. The three largest cohorts all originated from Japan and employed national surveys of surgeons [8, 26, 32]. All other studies used retrospective methodology with some employing postal questionnaires, clinical review or interview to generate follow-up data. The largest study reporting long-term functional outcome involved 58 patients with TCA from Ireland and Italy [9]. A comprehensive list of the articles is given in Table 1. Details of the type of PT surgery performed were available in 722 patients. The most common operation for TCA was Martins’ procedure in 230 cases closely followed by Duhamel procedure in 229 cases. Straight ileo-anal anastomosis was performed in 197 cases (Soave in 113, Swenson in 41 and not defined in 43). In 66 patients, other procedures performed included Rehbein, Kimura and various patch graft procedures.

Fig. 1
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Literature search flow chart

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Table 1 Articles in order of year of publication
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The overall mortality rate was 193/969 (19.9 %). The pre-PT mortality rate was 152/969 (15.7 %), and of those who had PT, 42/739 (5.7 %) died postoperatively (excluding 3 unrelated deaths). A total of 543 complications occurred after PT, the most frequent being enterocolitis arising in 42 % of the patients (248/592). Table 2 presents a breakdown of morbidity rates post-PT. Data on long-term functional outcome were reported in a total of 396 patients post-definitive surgery for TCA. A patient distribution flowchart is given in Fig. 2 showing long-term outcomes. Between two publication periods, there was a significant decrease in overall mortality and the number of patients undergoing PT increased, but long-term functional outcome was not significantly different (Table 3 ). However, a significant improvement in the long-term functional outcome was detected between groups followed-up at 4–7.9 and 8–11.9 years (Fig. 3).

Table 2 Post-PT complications
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Fig. 2
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Patient distribution flowchart showing long-term outcomes

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Table 3 Comparison of two patient groups based on the publication period
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Fig. 3
figure 3

Comparison of long-term functional outcome by follow-up period

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Discussion

In the present study, we found a TCA incidence of 9.1 % of the total HD cases, which is comparable to previous studies [2]. For the first time, the gender distribution in a large group of TCA patients is shown. HD has a male preponderance of approximately 4:1 [42]; however, our results confirm that TCA differs from recto-sigmoid HD for gender ratio supporting previous evidence that in TCA the male-to-female ratio approaches 2:1 [32].

Mortality rates for TCA are high both pre- and post-definitive PT surgery. In a 40-year multi-centre follow-up of 2,430 HD patients post-Duhamel surgery, an overall mortality rate of 1.6 % was found [43]. The post-PT mortality rate in TCA in the present study was higher at 5.7 %. The overall mortality rates have improved significantly for TCA between an early and a more recent group of cases. Several factors are likely to influence this trend. In the early group, many patients were treated prior to the era of intravenous nutritional support, when PT surgery was in its infancy [11, 15, 44]. The first successful surgical procedure for TCA was described by Sandegard in 1953 [45]. The earliest cases included herein date from this time period. Total parenteral nutrition came into use during the 1970s and, with improvements in intensive care for neonates, has had a diminishing effect on mortality in TCA.

Good functional outcome in recto-sigmoid HD varies depending on the procedure, but can be expected in approximately 90 % of the cases [46, 47]. Long-term bowel function following PT operation in patients with TCA only achieves a good outcome in 60 % of the cases. Faecal incontinence and soiling severely impact the quality of life [48, 49], and are seen in 25 % of the patients at long-term follow-up. This rate did not show significant improvement over time. Faecal continence rates are more satisfactory for HD as compared to TCA. In a large survey of the members of the surgical section of the American Academy of Paediatrics examining the outcomes of 1,196 operated HD patients, a long-term soiling rate of 7.5 % was reported [37]. The incidence of TCA patients suffering from long-term soiling or incontinence reported in the articles included in the present study varied from 6 to 86 % [3, 7, 12]. The overall rate of poor bowel function in operated TCA cases is 40 % when other outcomes such as conversion to permanent stoma, high stool frequency and dependence on medications, rectal washouts or dilations are factored in. Sherman et al. [50] reported that 10 (1.3 %) of 797 patients with HD had undergone conversion to a permanent stoma for post-operative complications. In the present study, the incidence of patients with TCA who opted for a permanent stoma for complications after PT operation is much higher at 6.5 %. This figure excludes 22 surviving patients who did not undergo PT and were given a long-term stoma as management and an additional 11 patients who were reported to have a temporary or diverting stoma at long-term review. Several investigators have shown that continence post-PT improves over time [5, 50–52]. We have found that outcome is significantly better in patients at a mean follow-up of 8–11.9 years when compared to a group at 4–7.9 years. This trend did not persist in the group followed-up for longer than 12 years and was in fact reversed. The earliest cases included in this study were managed in the 1950s and 1960s, during a time of rapid development in the field of HD surgery, we therefore feel that the older group of patients reported here may not have had the advantages of modern surgical techniques and bowel management programs.

Many patients underwent Martins’ modification of the Duhamel operation for TCA, however 85% of these cases dated pre-1996. This procedure was designed to increase absorption using a long side-to-side anastomosis of the ganglionic ileum to aganglionic colon. Most surgeons have had less satisfactory outcomes with the Martin long Duhamel operation and have abandoned this procedure in recent years in favour of the standard modified Duhamel operation [20].

Enterocolitis after PT procedure was the most common post-operative complication occurring in 42 % of the patients. Many authors have reported that an increasing length of aganglionosis is associated with higher risk of enterocolitis [53, 54] and our results would concur with this. In a literature review, Little and Synder [55] found an incidence of enterocolitis of 10.6 % in 10,381 patients with HD and TCA outcomes compare poorly with this.

In conclusion, this meta-analysis reveals that a large number of patients with TCA have long-term problems with bowel control. Although some improvements have been seen at a longer duration of follow-up, continence rates have not improved over the last 3 decades and many patients with TCA have poor long-term functional results following PT.