- Email: [email protected]
Surgical treatment of ulcerative colitis
PEDIATRIC SURGERY
Surgical treatment of ulcerative colitis
or because of a lack of efficacy of therapy, patients affected by the severe adverse effects of corticosteroids, those with growth retardation or delayed sexual maturation, and patients who are severely limited in their activities and who have an unacceptable quality of life. Complete proctocolectomy with permanent ileostomy is curative for UC and is carried out as a one-stage operation. It has been used for many years, with low morbidity and mortality rates. However, a major concern of patients, particularly children, is the required lifetime ileostomy appliance. The presence of a stoma, particularly in a child, often creates embarrassment during physical and social activities. Classically, the surgical options proposed for children affected by UC include endorectal mucosectomy followed by an ileo-anal anastomosis with (ileal poucheanal anastomosis [IPAA]) or without (endorectal pull-through [ERPT]) the creation of a pouch. The ileo-anal anastomosis can be performed as a handsewn or a mechanical procedure (endorectal dissection and double-stapled anastomosis [ERDS]) or, as second option, as colectomy with subtotal mucosectomy and ileorectal anastomosis by means of a mechanical stapler, according to the KnighteGriffen technique (Figure 1). Inasmuch as UC is primarily a disease of the mucosa, a modification of the rectal mucosal stripping procedure (ERPT) proposed by Ravitch and Sabiston in 1951,1 popularised by Soave in 1963 for treatment of Hirschsprung’s disease,2 and modified by Coran in 1976,3 has become the treatment of choice for both children and adults. Removal of the entire rectal mucosa down to the dentate line does not appreciably interfere with anorectal sphincter function or the ability to discriminate between gas and liquid or solid contents. This procedure is now generally accepted as a desirable option for the surgical treatment of UC and familial polyposis. Appealing features of this operation include the absence of a permanent stoma and the development of a near-normal pattern of defecation. The advantages of ERPT are a limited extrarectal dissection and a reduced risk of injury to the sphincter muscles and surrounding deep pelvic nerves. Despite these advantages, patients’ expectations need to be addressed preoperatively. Stooling frequency is typically quite high initially regardless of whether or not a pouch is utilised. Another problem is nocturnal incontinence. This latter problem is particularly prevalent in younger children, with the process resolving as the child matures. The main advantages of the creation of an ileal reservoir, as in the IPAA technique, are to increase rectal capacity and reduce the frequency of bowel movements. Four basic reservoir types have been used clinically: the S-shaped reservoir, the J reservoir, the lateral isoperistaltic reservoir and the W-shaped reservoir (Figure 2). The J-shaped reservoir, currently the most commonly used pouch, is usually constructed with a stapling instrument and followed by a hand-sewn ileal poucheanal anastomosis. In certain cases (tall, short or overweight patients), a hand-sewn anastomosis can be technically difficult. This has led to the development of a new technique that combines endorectal mucosectomy with a double-stapled ileo-anal anastomosis.4 In this procedure, an ileal J-pouch is constructed after colectomy. The head of the circular stapler is placed in the apex of the
Emanuela Ceriati Francesco De Peppo Massimo Rivosecchi
Abstract Ulcerative colitis is primarily a disease of the rectal and colonic mucosa. The disease begins in 4% of patients before the age of 10, and in 18% between the ages of 10 and 20. The disease is more severe in children than in adults and is often associated with more overt symptoms. Ulcerative colitis can be cured by surgically removing the diseased colon and rectum. The aims of surgical treatment are: to remove the diseased bowel and to return the patient to health; to preserve the anus for defecation; to maintain continence; to obviate the need for a permanent ileostomy; and to lessen the risk of complications. The surgical options proposed for children affected by ulcerative colitis include endorectal mucosectomy followed by an ileo-anal anastomosis with (ileal pouche anal anastomosis [IPAA]) or without (endorectal pull-through [ERPT]) creation of a pouch. If ERPT represents a good choice for treating severe ulcerative colitis in paediatric patients, IPAA seems to show better results. Both these procedures are illustrated, with an analysis of related advantages and complications, considering also an evaluation of the quality of life of patients who have undergone this kind of surgery.
Keywords paediatrics; pouchitis; quality of life; surgery; ulcerative colitis
Surgical strategies Surgery in children who suffer with ulcerative colitis (UC) can be an elective or an emergency procedure. Emergency indications for operation include extensive rectal bleeding, fulminant disease refractory to medical therapy, toxic megacolon and perforation. However, careful monitoring and the use of steroids have reduced the number of operations undertaken in an emergency setting. Elective surgery is performed in patients with chronic disease who continue to experience symptoms despite medical therapy
Emanuela Ceriati Dr. is a Pediatric Surgeons at the Department of Paediatric Surgery, IRCCS, Bambino Gesu` Children’s Hospital, Palidoro, Rome, Italy. Francesco De Peppo Dr. is a Pediatric Surgeons at the Department of Paediatric Surgery, IRCCS, Bambino Gesu` Children’s Hospital, Palidoro, Rome, Italy. Massimo Rivosecchi Dr. is a Head of Peadiatric Surgery Department, IRCCS at the Department of Paediatric Surgery, IRCCS, Bambino Gesu` Children’s Hospital, Palidoro, Rome, Italy.
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The discrepancy in the reported cumulative frequencies from different institutions probably results from the diagnostic criteria used (e.g. diagnosis made based on symptom assessment alone or on a combined assessment of symptoms and endoscopy, with or without histology), the intensity of follow-up with pouch endoscopy, and the inclusion or exclusion of other inflammatory or functional disorders of the pouch and surgery-related conditions (such as abscess, fistula and sinus of the pouch). Because we still know so little about the pathophysiology of chronic UC, the events leading to pouchitis are very sketchy. We can speculate that whatever it is that predisposes to UC is still present once the ileal mucosa has adapted into a colonic epithelium, although recent elegant epithelial studies seem to suggest a different character of the ileal mucosa in patients with pouchitis compared with the mucosa in patients with UC. Pouchitis almost exclusively occurs in patients with underlying UC and is rarely seen in patients with familial adenomatous polyposis.8,9 Although the aetiology and pathogenesis of pouchitis are not entirely clear, the bulk of evidence points towards an abnormal mucosal immune response (innate and adaptive) to altered microflora in the pouch, leading to acute and/or chronic inflammation.10e15 The prevailing theory holds that pouchitis results from an overgrowth of certain commensal bacteria.11,12,16,17 In fact, pouchitis only develops after closure of the ileostomy, i.e. when the pouch mucosa begins to be exposed to the faecal stream. The manipulation of microflora with antibiotic or probiotic therapy, resulting in an improvement in patients with pouchitis, provides additional evidence of the involvement of microflora in the pathogenesis of pouchitis. Immune mechanisms in pouchitis have been extensively studied in a fashion similar to that for inflammatory bowel disease. There are overlaps in tissue cytokine profiles between pouchitis and UC. However, pouchitis is not simply a duplication of the disease process seen in UC.
1. Total colectomy + mucosectomy + endorectal ileal-anal anastomosis
Straight (ERPT)
Pouch (IPAA)
Hand-sewn
Stapler (ERDS)
2. Total colectomy + stapled straight ileal-anal anastomosis (extrarectal dissection – Knight-Griffen procedure)
Figure 1 Surgical procedures for the treatment of ulcerative colitis in children. See text for abbreviations.
pouch and secured. An endorectal mucosectomy is performed from the abdomen to approximately 1.5 cm above the dentate line. The rectal mucosal/submucosal tube is then everted onto the perineum. A transverse stapler is positioned 1.5 cm above the dentate line on the perineum and fired. The circular stapler is inserted transanally, and the trocar is advanced through the transverse staple line until the head and anvil are mated and then fired.
Pouchitis Pouchitis remains a common problem. The reported rate of prevalence of pouchitis in patients operated on for UC varies depending on the series. In adults, the reported cumulative frequency rates of pouchitis 10e11 years after IPAA surgery range from 23% to 46%.5,6 It is estimated that approximately 50% of patients undergoing IPAA surgery for UC will develop at least one episode of pouchitis.7
The four basic reservoir types: (A) J shaped, (B) S shaped, (C) lateral isoperistaltic, and (D) W shaped. Figure 2
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The role of T-cell-mediated intestinal immunity in the pathogenesis of pouchitis is not entirely clear and probably occurs secondary to alterations in pouch microflora. Alterations in the macrophage and T-cell subpopulations have been postulated in the process of pouchitis.18e20 Increased T-cell activation and proliferation have been demonstrated in pouchitis, as evidenced by an increased expression of activation markers such as CD25, CD30 and CD27.20 As a result of the activation of T cells and other immune cells, the production of cytokines is upregulated. Abnormal cytokine profiles have been reported in pouchitis, including a deregulated production of proinflammatory and immunoregulatory cytokines.21 Proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-a), are released to a great extent in the inflamed mucosa by macrophages and monocytes, leading to tissue injury, and are considered to be involved in pouchitis as a secondary pathophysiological mechanism.21 As in UC, there is also an increased production of other inflammatory mediators, including cytokines (such as interleukin-1b [IL-1b], IL-6 and IL-8), cell adhesion molecules, platelet-activating factor, lipoxygenase products of arachidonic acids (leukotriene B4 and prostaglandin E2), proinflammatory neuropeptides, macrophage inflammatory protein 2a, matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-9, myeloid-related protein-14 (MRP-14), and inducible nitric oxide. Abnormalities in immunoregulatory cytokines such as IL-2, and interferon-g, IL-4 and IL-10, are also seen in pouchitis. An imbalance between proinflammatory and immunoregulatory cytokines has been described in patients with pouchitis. Abnormalities of T cells and other immune cells may not, however, explain the whole mechanism of pouchitis. It is likely that such abnormalities are non-specific and secondary in nature. Inconsistent results in studies of immune cells and inflammatory mediators in pouchitis reflect the complexity of the pathogenesis of this disease.22 One of the most intriguing aspects of pouchitis is that it occurs almost exclusively in patients with underlying UC. Interestingly, there are similarities in terms of clinical presentations and immunological abnormalities between pouchitis and UC, suggesting that a subset of pouchitis may actually represent the recurrence of a UC-like disease in the ileal pouch. The theory of recurrent UC is supported by several lines of evidence. With the presence of stasis in the pouch, exposure to faecal contents and an increased microbial load could be the cause of inflammatory changes leading to morphological alterations in the ileal pouch mucosa mimicking those of colonic epithelia in UC. Colonic metaplasia of the pouch mucosa seems to be a non-specific adaptive response to the new luminal environment. Colonic metaplasia characterised by villous blunting, crypt cell hyperplasia and colonic epithelium-specific antigens such as human tropomyosin-5 may increase the risk of pouchitis. A similar alteration in mucin glycoproteins occurs in both pouchitis and UC. It is possible that the altered glycoproteins are more susceptible to enzymatic degradation by bacteria, making the mucous barrier less resistant. Anal stenosis or a large pouch, factors that would allow stasis, are predisposing elements, whereas previous backwash ileitis or faecal concentrations of bile acids in the pouch have not been associated with an increased incidence. Symptoms that indicate pouchitis include looser and more frequent stools, with or
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without blood, and associated with cramps or tenesmus. The symptoms usually present after more than 6 months have passed since the closure of the temporary ileostomy. The patient will notice a change in the character (more loose to watery) and frequency (often doubling in number) of the stools, with more urgency, cramps (if not incontinence) and the appearance of blood. Extraintestinal manifestations are common: fever, arthralgia and arthritis, and skin manifestations. Patients with primary sclerosing cholangitis have an increased tendency to develop pouchitis, and this tendency persists even after liver transplantation. The symptoms usually progress over a course of a few days to a few weeks. Recurrence may appear a few weeks, months or years later, whereas chronicity is suggested by symptoms continuing once the medication programme has finished, or persisting throughout the treatment programme. At endoscopy, the pouch shows localised or diffuse oedema, erythema, granularity, friability and even ulcerations. At biopsy, one sees neutrophilic infiltration and ulceration in addition to the chronic inflammatory changes ordinarily seen in an otherwise normal pouch (see previous discussion). Ideally, the diagnosis of pouchitis incorporates the clinical symptoms, endoscopic findings and histopathological features (Table 1). Many patients may have clinical symptoms but not endoscopic or histopathological findings, and a diagnosis of pouchitis in this instance is not warranted. For acute pouchitis, metronidazole for 7e10 days is the antibiotic of choice; ciprofloxacin or amoxicillin and clavulanic acid are appropriate alternatives for patients resistant to metronidazole. Chronic pouchitis is more difficult to treat. These patients are now persistently symptomatic and fear that the original problem for which they had major surgery has returned. It is important to review the clinical situation in detail; resection is rarely needed, although surgical revision of the pouch or dilation of a strictured distal anastomosis is sometimes indicated. The most interesting compounds recently advocated are the prebiotics and probiotics. Their propensity to treat or protect the patient from various diarrhoeal disorders has been well described. They have since been used quite effectively in different animal models and in human colitis, although the exact mechanisms of action remain to be determined. Some of the inflammatory response might result from an imbalance in the
Histopathologic changes in the ileal pouch after colectomy, ileal pouch-anal anastomosis and reanastomosis Anatomic feature
Without pouchitis
With pouchitis
Villi
Variable atrophy
Subtotal atrophy
Crypts
Hyperplastic
Hyperplastic, some crypt abscesses
Cell infiltrates
Lymphocytes, histiocytes, eosinophils, plasma cells
Polymorphonuclear neutrophil
Information from references 41,42.
Table 1
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proportion of ‘aggressive’ and ‘protective’ bacteria, which might in turn affect the intestinal integrity, either because of the stimulation of inflammatory cytokine production or because of a change in mucosal permeability. All probiotics are not alike, and one has to be sure to identify correctly the compound used in the different studies and what is readily available. Friedman and George observed a good response in 10 patients with chronic pouchitis using Lactobacillus rhamnosus GG and fructo-oligosaccharide (a prebiotic) in an open trial study23; all 10 patients experienced a clinical response and normalisation of the endoscopic picture after 4 weeks of treatment. Gionchetti et al.13 used an experimental preparation (VSL#3) composed of four strains of Lactobacillus, three strains of Bifidobacterium and one strain of Streptococcus, compared with a placebo. During the 9 months of treatment, the 20 patients taking the placebo relapsed, compared with only three (15%) of those receiving the treatment ( p < 0.001); however, all the treated patients relapsed 4 months after stopping treatment. While on treatment, the stools showed increased concentrations ( p < 0.001) of the strains given orally, which all returned to baseline levels within 1 month after therapy. These researchers expanded their study to examine the levels of cytokines in biopsy material from the inflamed pouches in seven patients with pouchitis, compared with five control patients with normal pouches.24 Tissue levels of TNF-a, interferon-g and IL-1b were all significantly decreased in patients with pouchitis after treatment with both antibiotics and probiotics, but only the probiotic preparation significantly increased ( p < 0.05) the levels of the anti-inflammatory cytokine IL-10.24 Furthermore, the risk of dysplasia of the mucosal pouch is unknown. Concern about the risk of pouch neoplasia was raised 10 years ago after a combination of colonic metaplasia and chronic inflammation was observed in pouches.25 Seven cases have been reported in the literature in which an adenocarcinoma has arisen in or adjacent to ileal pouch mucosa when a pouch formation has been performed in adult patients with UC.26e32 To our knowledge, no cases have been reported to date of adenocarcinoma in ileal pouches performed in paediatric patients. In the KnighteGriffen procedure,33 the entire rectum is dissected (with no endorectal mucosectomy), closed and resected using a linear stapler as deep as possible in the pelvis. The body of the circular stapler is inserted through the anus, and the distal rectal stump is perforated by the trocar of this instrument. The anastomosis is performed between the ileum and the anal canal proximally to the sphincter muscle plane. The advantages of using the mechanical stapler in children are significant e easier and safer suturing with a decreased time need to perform the anastomosis e but as no mucosectomy is performed, residual mucosa is left in place (about 2.5 cm), with a high risk of disease recurrence. The distance from the dentate line to the anastomosis has been reported to be 1e3 cm in most series. However, in patients with difficult body habitus, it is easy to come across the rectum too high and, in the process, to construct an ileo-rectostomy rather than an ileo-anal anastomosis, which could increase the risk of cancer or pouchitis.16e19 Surgical experience with pull-through operations (both straight ERPT and IPAA procedures) indicate that it is advisable to have a completely divertive, protective ileostomy for approximately 2 months to minimise the risk of pelvic infection. Children with
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chronic UC who receive long-term steroids are often malnourished and frequently have a suppressed immune response, which increases the risk of anastomotic leak. In fact, the risk of such a leak has been found in approximately 10e15% of patients, and has the attendant risk of leading to anal stricturing.
Experience at Bambino Gesu Children’s Hospital In 2004, we published our experience and 10-year follow-up results of 28 patients who underwent ERPT as surgical treatment for UC, with special regard to surgical complications, stooling patterns (frequency of defecation, stool consistency and urgency period), faecal incontinence and quality of life. In this paper, a retrospective chart review of these patients was performed to evaluate age at colectomy, indication for surgical treatment, operative procedures, technical details and early or late complications.34 Frequency of defecation was less than twice per day in 2 patients, between three and five times per day in 9 patients, and more than six times per day in 10 patients. Stool consistency was normal in 14 patients, loose in 5 and liquid in only 2 cases. Urgency period was normal (minutes) in 14 patients, short (seconds) in 4 and absent in 3. Ten patients (47%) had perfect or good faecal continence, whereas 11 (52%) patients presented with moderate-to-total incontinence. Self-reported emotional health was good in most of the patients. A large number were progressing well at school and coping with their operations. In our experience of evaluation of quality of life, it is relevant to point out that most of the patients experienced a satisfactory lifestyle even if faecal incontinence and a high frequency of defecation were probably the main factors compromising quality of life. We concluded that studies on the quality of life of UC patients who underwent surgical treatment in childhood or adolescence, including a comparison of results according to the surgical technique used, should be encouraged. Starting in 2002, we adopted the IPAA technique, mainly because of the high frequency of bowel movements and the rate of faecal incontinence in our ERPT series. We first perform the rectal mucosectomy (Figure 3) and then create a J-shaped ileal
Figure 3 Rectal mucosectomy.
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pouch (of approximately 5e7 cm) using a linear stapling device (Figure 4). We next make a section of the posterior muscular cuff, and finally a hand-sewn IPAA is created. Between March 2002 and December 2006, all patients affected by UC for whom a surgical procedure was necessary underwent IPAA. The series included four males and three females, with ages ranging from 3 to 16 (mean 10) years at the time of operation. In all cases, a pancolitis was documented. One patient underwent urgent subtotal colectomy with a delayed IPAA anastomosis because of severe rectal bleeding. The other six patients had an elective operative procedure for poor response to medical therapy; in all cases a J-shaped pouch was constructed with a temporary ileostomy. About 4 months after surgery, all children underwent ileostomy closure. No deaths were observed. There were no intraoperative complications or early septic complications in any of the patients. Minor complications occurred in three cases (one mucosal prolapse, one extraperitoneal haemorrhage and one acute pouchitis). These patients had a mean follow-up period of 23 months, with a mean 24-hour stool frequency of four. The median nighttime frequency for these patients was 1 (range 0 to 2). There was no incontinence. Stool consistency was normal in all patients, as was evaluation of urgency period. It is, of course, impossible to compare the results of our experiences with ERPT and with IPAA (because of differences in cases/ series and length of follow-up), but it would seem reasonable to expect to achieve, in the future, better results with IPAA.
Although each has its proponents, evidence directly comparing the ERPT and IPAA is sparse, with the obvious difficulties of performing a randomised trial in young patients when the number undergoing such surgery is relatively small. Regardless of the type of pull-through, stool frequency and continence are quite similar in large series of patients followed for a number of years. The choice between ERPT and IPAA is still a matter of debate. On the one hand, pouch procedures have been associated with an increased risk of anastomotic strictures, faecal stasis and recurrent inflammation of the neorectum/pouchitis, and have been perceived as having a higher incidence of perioperative complications.35 On the other hand, the functional outcome of pouch procedures is superior to that of straight anastomoses.38,39 The small number of studies comparing complications and functional outcomes, the relatively small number of children involved and the lack of any randomised controlled trials make it difficult to assess the relative advantages and disadvantages of the two types of procedure. Most published accounts are retrospective, and there is a substantial amount of repeat publication from large centres updating their series outcomes and numbers, rather than publishing the results of surgery in new groups of patients. Recently a meta-analysis was performed and studies comparing outcomes from IPAA and straight ileo-anal anastomosis (ERPT) were identified by searching Medline, Ovid and Embase.40 To enter the analysis, studies had to: report the operative results of restorative proctocolectomy in children or adolescents; compare IPAA and EPT operations; report on at least one of the following outcome measures: failure of reconstruction (primary end-point), need for abdominal salvage procedures, anastomotic stricture, inflammation of the neorectum, rates of perianal sepsis, enterovaginal fistula, small bowel obstruction, anastomotic leaks, bowel frequency per 24 hours, nocturnal defecation
Results Complications are multiple, and children need long-term followup and care to attend to these problems. Long-term follow-up must include an endoscopic check of the ileal loop (pouch) and of the retained rectal cuff every 1e3 years with biopsies to rule out malignancy. Reported results in paediatric patients with either a straight pull-through or a pouch have been satisfactory and comparable to those reported from adult centres.35e37
Creation of the J-shaped pouch. Figure 4
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4 Geiger JD, Teitelbaum DH, Hirschl RB, Coran AG. A new operative technique for restorative proctocolectomy: the endorectal pullthrough combined with a double-stapled ileo-anal anastomosis. Surgery 2003; 134: 492e5. 5 Penna C, Dozois R, Tremaine W, et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut 1996; 38: 234e9. 6 Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg 1995; 222: 120e7. 7 Stocchi L, Pemberton JH. Pouch and pouchitis. Gastroenterol Clin North Am 2001; 30: 223e41. 8 Penna C, Tiret E, Kartheuser A, Hannoun L, Nordlinger B, Parc R. Function of ileal J pouch-anal anastomosis in patients with familial adenomatous polyposis. Br J Surg 1993; 80: 765e7. 9 Tjandra JJ, Fazio VW, Church JM, Oakley JR, Milsom JW, Lavery IC. Similar functional results after restorative proctocolectomy in patients with familial adenomatous polyposis and mucosal ulcerative colitis. Am J Surg 1993; 165: 322e5. 10 Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003; 124: 1202e9. 11 Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology 1994; 107: 1856e60. 12 Gosselink MP, Schouten WR, van Lieshout LM, et al. Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus GG. Dis Colon Rectum 2004; 47: 876e84. 13 Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119: 305e9. 14 Mimura T, Rizzello F, Helwig U, et al. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 2004; 53: 108e14. 15 Komanduri S, Gillevet PM, Sikaroodi M, Mutlu E, Keshavarzian A. Dysbiosis in pouchitis: evidence of unique microfloral patterns in pouch inflammation. Clin Gastroenterol Hepatol 2007; 5: 352e60. 16 Duffy M, O’Mahony L, Coffey JC, et al. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis. Dis Colon Rectum 2002; 45: 384e8. 17 Nasmyth DG, Godwin PG, Dixon MF, Williams NS, Johnston D. Ileal ecology after pouch-anal anastomosis or ileostomy. A study of mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationship. Gastroenterology 1989; 96: 817e84. 18 de Silva HJ, Jones M, Prince C, Kettlewell M, Mortensen NJ, Jewell DP. Lymphocyte and macrophage subpopulations in pelvic ileal pouches. Gut 1991; 32: 1160e5. 19 Hirata I, Austin LL, Blackwell WH, Weber JR, Dobbins 3rd WO. Immunoelectron microscopic localization of HLA-DR antigen in control small intestine and colon and in inflammatory bowel disease. Dig Dis Sci 1986; 31: 1317e30. 20 Stallmach A, Schafer F, Hoffmann S, et al. Increased state of activation of CD4 positive T cells and elevated interferon gamma production in pouchitis. Gut 1998; 43: 499e505. 21 Goldberg PA, Herbst F, Beckett CG, et al. Leucocyte typing, cytokine expression, and epithelial turnover in the ileal pouch in patients with ulcerative colitis and familial adenomatous polyposis. Gut 1996; 38: 549e55.
and nocturnal seepage of faeces; contain a previously unreported group; when two studies were reported by the same institution, include in the analysis either the one of better quality or the most recent publication. Of 13 studies identified by literature search, five satisfied the inclusion criteria. These studies comprised a total of 306 patients, 86 of whom (28.1%) underwent ERPT and the remainder IPAA. Pouch failure was more common in the ERPT group (odds ratio 3.21, confidence interval 1.24e8.34), as were abdominal salvage procedures (odds ratio 9.5, confidence interval, 3.14e28.77). Short-term adverse events were similar between the two groups, with the exception of perianal sepsis, the higher frequency of which in ERPT just reached statistical significance. Bowel frequency was lower in the patients who had undergone IPAA, although few studies presented functional data in a comparable form. The authors of this meta-analysis concluded that there were few good-quality studies comparing the outcomes from ERPT and from IPAA, and that caution should be exercised concerning the generalisation of these results (which suggest an advantage for pouch procedures in terms of reconstruction survival and functional outcome). Evaluation of the child’s condition should be made periodically during the course of illness and therapy by the surgeon as well as by the gastroenterologist to consider alternatives to long-term medical therapy.
Conclusion Even if ERPT represents a good choice for treating severe UC in paediatric patients, with this option faecal incontinence and a high frequency of defecation are the main factors compromising quality of life. IPAA seems to show better results. We think that studies of quality of life in patients affected by UC who underwent surgical treatment as children or adolescents, also comparing results according to the surgical techniques used (with special regard to ERPT or IPAA) and evaluating differences before and after surgery, must be encouraged in order to provide patients and their families with information not only about potential surgical complications, but also about reasonable expectations concerning quality of life after surgery. The question ‘What is the quality of life for patients living with UC compared with the quality of life they can expect after an ERPT or IPAA?’ still needs to be answered.
Conflict of interest None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper. A
REFERENCES 1 Ravitch MM, Sabiston DC. Anal ileostomy with preservation of the sphincter. Surg Gynecol Obstet 1951; 98: 87e90. 2 Soave F. A new surgical technique for the treatment of Hirschsprung’s disease. Surgery 1963; 56: 1007e14. 3 Coran AG, Weintraub WH. Modification of the endorectal procedure for Hirschsprung’s disease. Surg Gynecol Obstet 1976; 143: 277e82.
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22 Yu E-D, Shao Z, Shen B. Pouchitis. World J Gastroenterol 2007; 13: 5598e604. 23 Friedman G. Treatment of refractory ‘‘pouchitis’’ with prebiotic and probiotic therapy [abstract]. Gastroenterology 2000; 118: A778. 24 Ulisse S, Gionchetti D, D’Alo` S, et al. Expression of cytokines, inducible nitric oxide synthase and matrix metalloproteinases in pouchitis: effects of probiotic treatment. Am J Gastroenterol 2001; 96: 2691e9. 25 Shepherd NA. The pelvic ileal reservoir: apocalypse later? BMJ 1990; 301: 886e7. 26 Stern H, Walsh S, Mullen B, et al. Cancer in an ileo-anal reservoir: a new complication? Gut 1990; 31: 473e5. 27 Rodriguez-Sanjuan J, Polavieja M, Naranjo A, et al. Adenocarcinoma in an ileal pouch for ulcerative colitis [letter]. Dis Colon Rectum 1996; 38: 779e80. 28 Sequens R. Cancer in the anal canal (transitional zone) after restorative proctocolectomy with stapled ileal pouch-anal anastomosis. Int J Colorectal Dis 1997; 12: 254e5. 29 Ravitch MM. The reception of new operations. Ann Surg 1984; 200: 231e46. 30 Puthu D, Rajan N, Rao R, et al. Carcinoma of the rectal pouch following restorative proctocolectomy: report of a case. Dis Colon Rectum 1992; 35: 257e60. 31 Vieth M, Grunewald M, Niemeyer C. Adenocarcinoma in an ileal pouch after prior colectomy for carcinoma in a patient with ulcerative pancolitis. Virchows Arch 1998; 433: 281e4. 32 Bell S, Parry B, Neill M. Adenocarcinoma in the anal transitional zone after ileal pouch for ulcerative colitis: report of a case. Dis Colon Rectum 2003; 46: 1134e7.
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33 Knight CD, Griffen FD. An improved technique for low anterior resection of the rectum using the EEA stapler. Surgery 1980; 88: 710e4. 34 Ceriati E, Deganello F, De Peppo F, Rivosecchi M. Surgery for ulcerative colitis in pediatric patients: functional results of 10-year follow-up with straight endorectal pull-through. Pediatr Surg Int 2004; 20: 573e8. 35 Coran AG. A personal experience with 100 consecutive total colectomies and straight ileoanal endorectal pull-throughs for benign disease of the colon and rectum in children and adults. Ann Surg 1990; 212: 242. 36 Fonkalsrud EW, Thakur A, Beanes S. Ileoanal pouch procedures in children. J Pediatr Surg 2001; 36: 1689e92. 37 Shamberger RC, Masek BJ, Leichtner AM, Winter HS, Lillehei CW. Qualityof-life assessment after ileoanal pullthrough for ulcerative colitis and familial adenomatous polyposis. J Pediatr Surg 1999; 34: 163e6. 38 Durno C, Sherman P, Harris K, et al. Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis. J Pediatr Gastroenterol Nutr 1998; 27: 501e7. 39 Rintala RJ, Lindahl H. Restorative proctocolectomy for ulcerative colitis in childrendis the J-pouch better than straight pullethrough? J Pediatr Surg 1996; 31: 530e3. 40 Tilney HS, Constantinides V, Ioannides AS, Tekkis PP, Darzi AW, Haddad MJ. Pouch-anal anastomosis vs straight ileoanal anastomosis in pediatric patients: a meta-analysis. J Pediatr Surg 2006; 41: 1799. 41 De Silva HJ, Millard PR, Kettlewell M, et al. Mucosal characteristics of pelvic ileal pouches. Gut 1991; 32: 61e5. 42 Shepherd NA, Jass JR, Duval I, Moskowitz RL, Nicholls RJ, Morson BC. Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens. J Clin Pathol 1987; 40: 601e7.
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or because of a lack of efficacy of therapy, patients affected by the severe adverse effects of corticosteroids, those with growth retardation or delayed sexual maturation, and patients who are severely limited in their activities and who have an unacceptable quality of life. Complete proctocolectomy with permanent ileostomy is curative for UC and is carried out as a one-stage operation. It has been used for many years, with low morbidity and mortality rates. However, a major concern of patients, particularly children, is the required lifetime ileostomy appliance. The presence of a stoma, particularly in a child, often creates embarrassment during physical and social activities. Classically, the surgical options proposed for children affected by UC include endorectal mucosectomy followed by an ileo-anal anastomosis with (ileal poucheanal anastomosis [IPAA]) or without (endorectal pull-through [ERPT]) the creation of a pouch. The ileo-anal anastomosis can be performed as a handsewn or a mechanical procedure (endorectal dissection and double-stapled anastomosis [ERDS]) or, as second option, as colectomy with subtotal mucosectomy and ileorectal anastomosis by means of a mechanical stapler, according to the KnighteGriffen technique (Figure 1). Inasmuch as UC is primarily a disease of the mucosa, a modification of the rectal mucosal stripping procedure (ERPT) proposed by Ravitch and Sabiston in 1951,1 popularised by Soave in 1963 for treatment of Hirschsprung’s disease,2 and modified by Coran in 1976,3 has become the treatment of choice for both children and adults. Removal of the entire rectal mucosa down to the dentate line does not appreciably interfere with anorectal sphincter function or the ability to discriminate between gas and liquid or solid contents. This procedure is now generally accepted as a desirable option for the surgical treatment of UC and familial polyposis. Appealing features of this operation include the absence of a permanent stoma and the development of a near-normal pattern of defecation. The advantages of ERPT are a limited extrarectal dissection and a reduced risk of injury to the sphincter muscles and surrounding deep pelvic nerves. Despite these advantages, patients’ expectations need to be addressed preoperatively. Stooling frequency is typically quite high initially regardless of whether or not a pouch is utilised. Another problem is nocturnal incontinence. This latter problem is particularly prevalent in younger children, with the process resolving as the child matures. The main advantages of the creation of an ileal reservoir, as in the IPAA technique, are to increase rectal capacity and reduce the frequency of bowel movements. Four basic reservoir types have been used clinically: the S-shaped reservoir, the J reservoir, the lateral isoperistaltic reservoir and the W-shaped reservoir (Figure 2). The J-shaped reservoir, currently the most commonly used pouch, is usually constructed with a stapling instrument and followed by a hand-sewn ileal poucheanal anastomosis. In certain cases (tall, short or overweight patients), a hand-sewn anastomosis can be technically difficult. This has led to the development of a new technique that combines endorectal mucosectomy with a double-stapled ileo-anal anastomosis.4 In this procedure, an ileal J-pouch is constructed after colectomy. The head of the circular stapler is placed in the apex of the
Emanuela Ceriati Francesco De Peppo Massimo Rivosecchi
Abstract Ulcerative colitis is primarily a disease of the rectal and colonic mucosa. The disease begins in 4% of patients before the age of 10, and in 18% between the ages of 10 and 20. The disease is more severe in children than in adults and is often associated with more overt symptoms. Ulcerative colitis can be cured by surgically removing the diseased colon and rectum. The aims of surgical treatment are: to remove the diseased bowel and to return the patient to health; to preserve the anus for defecation; to maintain continence; to obviate the need for a permanent ileostomy; and to lessen the risk of complications. The surgical options proposed for children affected by ulcerative colitis include endorectal mucosectomy followed by an ileo-anal anastomosis with (ileal pouche anal anastomosis [IPAA]) or without (endorectal pull-through [ERPT]) creation of a pouch. If ERPT represents a good choice for treating severe ulcerative colitis in paediatric patients, IPAA seems to show better results. Both these procedures are illustrated, with an analysis of related advantages and complications, considering also an evaluation of the quality of life of patients who have undergone this kind of surgery.
Keywords paediatrics; pouchitis; quality of life; surgery; ulcerative colitis
Surgical strategies Surgery in children who suffer with ulcerative colitis (UC) can be an elective or an emergency procedure. Emergency indications for operation include extensive rectal bleeding, fulminant disease refractory to medical therapy, toxic megacolon and perforation. However, careful monitoring and the use of steroids have reduced the number of operations undertaken in an emergency setting. Elective surgery is performed in patients with chronic disease who continue to experience symptoms despite medical therapy
Emanuela Ceriati Dr. is a Pediatric Surgeons at the Department of Paediatric Surgery, IRCCS, Bambino Gesu` Children’s Hospital, Palidoro, Rome, Italy. Francesco De Peppo Dr. is a Pediatric Surgeons at the Department of Paediatric Surgery, IRCCS, Bambino Gesu` Children’s Hospital, Palidoro, Rome, Italy. Massimo Rivosecchi Dr. is a Head of Peadiatric Surgery Department, IRCCS at the Department of Paediatric Surgery, IRCCS, Bambino Gesu` Children’s Hospital, Palidoro, Rome, Italy.
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The discrepancy in the reported cumulative frequencies from different institutions probably results from the diagnostic criteria used (e.g. diagnosis made based on symptom assessment alone or on a combined assessment of symptoms and endoscopy, with or without histology), the intensity of follow-up with pouch endoscopy, and the inclusion or exclusion of other inflammatory or functional disorders of the pouch and surgery-related conditions (such as abscess, fistula and sinus of the pouch). Because we still know so little about the pathophysiology of chronic UC, the events leading to pouchitis are very sketchy. We can speculate that whatever it is that predisposes to UC is still present once the ileal mucosa has adapted into a colonic epithelium, although recent elegant epithelial studies seem to suggest a different character of the ileal mucosa in patients with pouchitis compared with the mucosa in patients with UC. Pouchitis almost exclusively occurs in patients with underlying UC and is rarely seen in patients with familial adenomatous polyposis.8,9 Although the aetiology and pathogenesis of pouchitis are not entirely clear, the bulk of evidence points towards an abnormal mucosal immune response (innate and adaptive) to altered microflora in the pouch, leading to acute and/or chronic inflammation.10e15 The prevailing theory holds that pouchitis results from an overgrowth of certain commensal bacteria.11,12,16,17 In fact, pouchitis only develops after closure of the ileostomy, i.e. when the pouch mucosa begins to be exposed to the faecal stream. The manipulation of microflora with antibiotic or probiotic therapy, resulting in an improvement in patients with pouchitis, provides additional evidence of the involvement of microflora in the pathogenesis of pouchitis. Immune mechanisms in pouchitis have been extensively studied in a fashion similar to that for inflammatory bowel disease. There are overlaps in tissue cytokine profiles between pouchitis and UC. However, pouchitis is not simply a duplication of the disease process seen in UC.
1. Total colectomy + mucosectomy + endorectal ileal-anal anastomosis
Straight (ERPT)
Pouch (IPAA)
Hand-sewn
Stapler (ERDS)
2. Total colectomy + stapled straight ileal-anal anastomosis (extrarectal dissection – Knight-Griffen procedure)
Figure 1 Surgical procedures for the treatment of ulcerative colitis in children. See text for abbreviations.
pouch and secured. An endorectal mucosectomy is performed from the abdomen to approximately 1.5 cm above the dentate line. The rectal mucosal/submucosal tube is then everted onto the perineum. A transverse stapler is positioned 1.5 cm above the dentate line on the perineum and fired. The circular stapler is inserted transanally, and the trocar is advanced through the transverse staple line until the head and anvil are mated and then fired.
Pouchitis Pouchitis remains a common problem. The reported rate of prevalence of pouchitis in patients operated on for UC varies depending on the series. In adults, the reported cumulative frequency rates of pouchitis 10e11 years after IPAA surgery range from 23% to 46%.5,6 It is estimated that approximately 50% of patients undergoing IPAA surgery for UC will develop at least one episode of pouchitis.7
The four basic reservoir types: (A) J shaped, (B) S shaped, (C) lateral isoperistaltic, and (D) W shaped. Figure 2
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The role of T-cell-mediated intestinal immunity in the pathogenesis of pouchitis is not entirely clear and probably occurs secondary to alterations in pouch microflora. Alterations in the macrophage and T-cell subpopulations have been postulated in the process of pouchitis.18e20 Increased T-cell activation and proliferation have been demonstrated in pouchitis, as evidenced by an increased expression of activation markers such as CD25, CD30 and CD27.20 As a result of the activation of T cells and other immune cells, the production of cytokines is upregulated. Abnormal cytokine profiles have been reported in pouchitis, including a deregulated production of proinflammatory and immunoregulatory cytokines.21 Proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-a), are released to a great extent in the inflamed mucosa by macrophages and monocytes, leading to tissue injury, and are considered to be involved in pouchitis as a secondary pathophysiological mechanism.21 As in UC, there is also an increased production of other inflammatory mediators, including cytokines (such as interleukin-1b [IL-1b], IL-6 and IL-8), cell adhesion molecules, platelet-activating factor, lipoxygenase products of arachidonic acids (leukotriene B4 and prostaglandin E2), proinflammatory neuropeptides, macrophage inflammatory protein 2a, matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-9, myeloid-related protein-14 (MRP-14), and inducible nitric oxide. Abnormalities in immunoregulatory cytokines such as IL-2, and interferon-g, IL-4 and IL-10, are also seen in pouchitis. An imbalance between proinflammatory and immunoregulatory cytokines has been described in patients with pouchitis. Abnormalities of T cells and other immune cells may not, however, explain the whole mechanism of pouchitis. It is likely that such abnormalities are non-specific and secondary in nature. Inconsistent results in studies of immune cells and inflammatory mediators in pouchitis reflect the complexity of the pathogenesis of this disease.22 One of the most intriguing aspects of pouchitis is that it occurs almost exclusively in patients with underlying UC. Interestingly, there are similarities in terms of clinical presentations and immunological abnormalities between pouchitis and UC, suggesting that a subset of pouchitis may actually represent the recurrence of a UC-like disease in the ileal pouch. The theory of recurrent UC is supported by several lines of evidence. With the presence of stasis in the pouch, exposure to faecal contents and an increased microbial load could be the cause of inflammatory changes leading to morphological alterations in the ileal pouch mucosa mimicking those of colonic epithelia in UC. Colonic metaplasia of the pouch mucosa seems to be a non-specific adaptive response to the new luminal environment. Colonic metaplasia characterised by villous blunting, crypt cell hyperplasia and colonic epithelium-specific antigens such as human tropomyosin-5 may increase the risk of pouchitis. A similar alteration in mucin glycoproteins occurs in both pouchitis and UC. It is possible that the altered glycoproteins are more susceptible to enzymatic degradation by bacteria, making the mucous barrier less resistant. Anal stenosis or a large pouch, factors that would allow stasis, are predisposing elements, whereas previous backwash ileitis or faecal concentrations of bile acids in the pouch have not been associated with an increased incidence. Symptoms that indicate pouchitis include looser and more frequent stools, with or
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without blood, and associated with cramps or tenesmus. The symptoms usually present after more than 6 months have passed since the closure of the temporary ileostomy. The patient will notice a change in the character (more loose to watery) and frequency (often doubling in number) of the stools, with more urgency, cramps (if not incontinence) and the appearance of blood. Extraintestinal manifestations are common: fever, arthralgia and arthritis, and skin manifestations. Patients with primary sclerosing cholangitis have an increased tendency to develop pouchitis, and this tendency persists even after liver transplantation. The symptoms usually progress over a course of a few days to a few weeks. Recurrence may appear a few weeks, months or years later, whereas chronicity is suggested by symptoms continuing once the medication programme has finished, or persisting throughout the treatment programme. At endoscopy, the pouch shows localised or diffuse oedema, erythema, granularity, friability and even ulcerations. At biopsy, one sees neutrophilic infiltration and ulceration in addition to the chronic inflammatory changes ordinarily seen in an otherwise normal pouch (see previous discussion). Ideally, the diagnosis of pouchitis incorporates the clinical symptoms, endoscopic findings and histopathological features (Table 1). Many patients may have clinical symptoms but not endoscopic or histopathological findings, and a diagnosis of pouchitis in this instance is not warranted. For acute pouchitis, metronidazole for 7e10 days is the antibiotic of choice; ciprofloxacin or amoxicillin and clavulanic acid are appropriate alternatives for patients resistant to metronidazole. Chronic pouchitis is more difficult to treat. These patients are now persistently symptomatic and fear that the original problem for which they had major surgery has returned. It is important to review the clinical situation in detail; resection is rarely needed, although surgical revision of the pouch or dilation of a strictured distal anastomosis is sometimes indicated. The most interesting compounds recently advocated are the prebiotics and probiotics. Their propensity to treat or protect the patient from various diarrhoeal disorders has been well described. They have since been used quite effectively in different animal models and in human colitis, although the exact mechanisms of action remain to be determined. Some of the inflammatory response might result from an imbalance in the
Histopathologic changes in the ileal pouch after colectomy, ileal pouch-anal anastomosis and reanastomosis Anatomic feature
Without pouchitis
With pouchitis
Villi
Variable atrophy
Subtotal atrophy
Crypts
Hyperplastic
Hyperplastic, some crypt abscesses
Cell infiltrates
Lymphocytes, histiocytes, eosinophils, plasma cells
Polymorphonuclear neutrophil
Information from references 41,42.
Table 1
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proportion of ‘aggressive’ and ‘protective’ bacteria, which might in turn affect the intestinal integrity, either because of the stimulation of inflammatory cytokine production or because of a change in mucosal permeability. All probiotics are not alike, and one has to be sure to identify correctly the compound used in the different studies and what is readily available. Friedman and George observed a good response in 10 patients with chronic pouchitis using Lactobacillus rhamnosus GG and fructo-oligosaccharide (a prebiotic) in an open trial study23; all 10 patients experienced a clinical response and normalisation of the endoscopic picture after 4 weeks of treatment. Gionchetti et al.13 used an experimental preparation (VSL#3) composed of four strains of Lactobacillus, three strains of Bifidobacterium and one strain of Streptococcus, compared with a placebo. During the 9 months of treatment, the 20 patients taking the placebo relapsed, compared with only three (15%) of those receiving the treatment ( p < 0.001); however, all the treated patients relapsed 4 months after stopping treatment. While on treatment, the stools showed increased concentrations ( p < 0.001) of the strains given orally, which all returned to baseline levels within 1 month after therapy. These researchers expanded their study to examine the levels of cytokines in biopsy material from the inflamed pouches in seven patients with pouchitis, compared with five control patients with normal pouches.24 Tissue levels of TNF-a, interferon-g and IL-1b were all significantly decreased in patients with pouchitis after treatment with both antibiotics and probiotics, but only the probiotic preparation significantly increased ( p < 0.05) the levels of the anti-inflammatory cytokine IL-10.24 Furthermore, the risk of dysplasia of the mucosal pouch is unknown. Concern about the risk of pouch neoplasia was raised 10 years ago after a combination of colonic metaplasia and chronic inflammation was observed in pouches.25 Seven cases have been reported in the literature in which an adenocarcinoma has arisen in or adjacent to ileal pouch mucosa when a pouch formation has been performed in adult patients with UC.26e32 To our knowledge, no cases have been reported to date of adenocarcinoma in ileal pouches performed in paediatric patients. In the KnighteGriffen procedure,33 the entire rectum is dissected (with no endorectal mucosectomy), closed and resected using a linear stapler as deep as possible in the pelvis. The body of the circular stapler is inserted through the anus, and the distal rectal stump is perforated by the trocar of this instrument. The anastomosis is performed between the ileum and the anal canal proximally to the sphincter muscle plane. The advantages of using the mechanical stapler in children are significant e easier and safer suturing with a decreased time need to perform the anastomosis e but as no mucosectomy is performed, residual mucosa is left in place (about 2.5 cm), with a high risk of disease recurrence. The distance from the dentate line to the anastomosis has been reported to be 1e3 cm in most series. However, in patients with difficult body habitus, it is easy to come across the rectum too high and, in the process, to construct an ileo-rectostomy rather than an ileo-anal anastomosis, which could increase the risk of cancer or pouchitis.16e19 Surgical experience with pull-through operations (both straight ERPT and IPAA procedures) indicate that it is advisable to have a completely divertive, protective ileostomy for approximately 2 months to minimise the risk of pelvic infection. Children with
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chronic UC who receive long-term steroids are often malnourished and frequently have a suppressed immune response, which increases the risk of anastomotic leak. In fact, the risk of such a leak has been found in approximately 10e15% of patients, and has the attendant risk of leading to anal stricturing.
Experience at Bambino Gesu Children’s Hospital In 2004, we published our experience and 10-year follow-up results of 28 patients who underwent ERPT as surgical treatment for UC, with special regard to surgical complications, stooling patterns (frequency of defecation, stool consistency and urgency period), faecal incontinence and quality of life. In this paper, a retrospective chart review of these patients was performed to evaluate age at colectomy, indication for surgical treatment, operative procedures, technical details and early or late complications.34 Frequency of defecation was less than twice per day in 2 patients, between three and five times per day in 9 patients, and more than six times per day in 10 patients. Stool consistency was normal in 14 patients, loose in 5 and liquid in only 2 cases. Urgency period was normal (minutes) in 14 patients, short (seconds) in 4 and absent in 3. Ten patients (47%) had perfect or good faecal continence, whereas 11 (52%) patients presented with moderate-to-total incontinence. Self-reported emotional health was good in most of the patients. A large number were progressing well at school and coping with their operations. In our experience of evaluation of quality of life, it is relevant to point out that most of the patients experienced a satisfactory lifestyle even if faecal incontinence and a high frequency of defecation were probably the main factors compromising quality of life. We concluded that studies on the quality of life of UC patients who underwent surgical treatment in childhood or adolescence, including a comparison of results according to the surgical technique used, should be encouraged. Starting in 2002, we adopted the IPAA technique, mainly because of the high frequency of bowel movements and the rate of faecal incontinence in our ERPT series. We first perform the rectal mucosectomy (Figure 3) and then create a J-shaped ileal
Figure 3 Rectal mucosectomy.
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pouch (of approximately 5e7 cm) using a linear stapling device (Figure 4). We next make a section of the posterior muscular cuff, and finally a hand-sewn IPAA is created. Between March 2002 and December 2006, all patients affected by UC for whom a surgical procedure was necessary underwent IPAA. The series included four males and three females, with ages ranging from 3 to 16 (mean 10) years at the time of operation. In all cases, a pancolitis was documented. One patient underwent urgent subtotal colectomy with a delayed IPAA anastomosis because of severe rectal bleeding. The other six patients had an elective operative procedure for poor response to medical therapy; in all cases a J-shaped pouch was constructed with a temporary ileostomy. About 4 months after surgery, all children underwent ileostomy closure. No deaths were observed. There were no intraoperative complications or early septic complications in any of the patients. Minor complications occurred in three cases (one mucosal prolapse, one extraperitoneal haemorrhage and one acute pouchitis). These patients had a mean follow-up period of 23 months, with a mean 24-hour stool frequency of four. The median nighttime frequency for these patients was 1 (range 0 to 2). There was no incontinence. Stool consistency was normal in all patients, as was evaluation of urgency period. It is, of course, impossible to compare the results of our experiences with ERPT and with IPAA (because of differences in cases/ series and length of follow-up), but it would seem reasonable to expect to achieve, in the future, better results with IPAA.
Although each has its proponents, evidence directly comparing the ERPT and IPAA is sparse, with the obvious difficulties of performing a randomised trial in young patients when the number undergoing such surgery is relatively small. Regardless of the type of pull-through, stool frequency and continence are quite similar in large series of patients followed for a number of years. The choice between ERPT and IPAA is still a matter of debate. On the one hand, pouch procedures have been associated with an increased risk of anastomotic strictures, faecal stasis and recurrent inflammation of the neorectum/pouchitis, and have been perceived as having a higher incidence of perioperative complications.35 On the other hand, the functional outcome of pouch procedures is superior to that of straight anastomoses.38,39 The small number of studies comparing complications and functional outcomes, the relatively small number of children involved and the lack of any randomised controlled trials make it difficult to assess the relative advantages and disadvantages of the two types of procedure. Most published accounts are retrospective, and there is a substantial amount of repeat publication from large centres updating their series outcomes and numbers, rather than publishing the results of surgery in new groups of patients. Recently a meta-analysis was performed and studies comparing outcomes from IPAA and straight ileo-anal anastomosis (ERPT) were identified by searching Medline, Ovid and Embase.40 To enter the analysis, studies had to: report the operative results of restorative proctocolectomy in children or adolescents; compare IPAA and EPT operations; report on at least one of the following outcome measures: failure of reconstruction (primary end-point), need for abdominal salvage procedures, anastomotic stricture, inflammation of the neorectum, rates of perianal sepsis, enterovaginal fistula, small bowel obstruction, anastomotic leaks, bowel frequency per 24 hours, nocturnal defecation
Results Complications are multiple, and children need long-term followup and care to attend to these problems. Long-term follow-up must include an endoscopic check of the ileal loop (pouch) and of the retained rectal cuff every 1e3 years with biopsies to rule out malignancy. Reported results in paediatric patients with either a straight pull-through or a pouch have been satisfactory and comparable to those reported from adult centres.35e37
Creation of the J-shaped pouch. Figure 4
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4 Geiger JD, Teitelbaum DH, Hirschl RB, Coran AG. A new operative technique for restorative proctocolectomy: the endorectal pullthrough combined with a double-stapled ileo-anal anastomosis. Surgery 2003; 134: 492e5. 5 Penna C, Dozois R, Tremaine W, et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut 1996; 38: 234e9. 6 Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg 1995; 222: 120e7. 7 Stocchi L, Pemberton JH. Pouch and pouchitis. Gastroenterol Clin North Am 2001; 30: 223e41. 8 Penna C, Tiret E, Kartheuser A, Hannoun L, Nordlinger B, Parc R. Function of ileal J pouch-anal anastomosis in patients with familial adenomatous polyposis. Br J Surg 1993; 80: 765e7. 9 Tjandra JJ, Fazio VW, Church JM, Oakley JR, Milsom JW, Lavery IC. Similar functional results after restorative proctocolectomy in patients with familial adenomatous polyposis and mucosal ulcerative colitis. Am J Surg 1993; 165: 322e5. 10 Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003; 124: 1202e9. 11 Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology 1994; 107: 1856e60. 12 Gosselink MP, Schouten WR, van Lieshout LM, et al. Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus GG. Dis Colon Rectum 2004; 47: 876e84. 13 Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119: 305e9. 14 Mimura T, Rizzello F, Helwig U, et al. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 2004; 53: 108e14. 15 Komanduri S, Gillevet PM, Sikaroodi M, Mutlu E, Keshavarzian A. Dysbiosis in pouchitis: evidence of unique microfloral patterns in pouch inflammation. Clin Gastroenterol Hepatol 2007; 5: 352e60. 16 Duffy M, O’Mahony L, Coffey JC, et al. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis. Dis Colon Rectum 2002; 45: 384e8. 17 Nasmyth DG, Godwin PG, Dixon MF, Williams NS, Johnston D. Ileal ecology after pouch-anal anastomosis or ileostomy. A study of mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationship. Gastroenterology 1989; 96: 817e84. 18 de Silva HJ, Jones M, Prince C, Kettlewell M, Mortensen NJ, Jewell DP. Lymphocyte and macrophage subpopulations in pelvic ileal pouches. Gut 1991; 32: 1160e5. 19 Hirata I, Austin LL, Blackwell WH, Weber JR, Dobbins 3rd WO. Immunoelectron microscopic localization of HLA-DR antigen in control small intestine and colon and in inflammatory bowel disease. Dig Dis Sci 1986; 31: 1317e30. 20 Stallmach A, Schafer F, Hoffmann S, et al. Increased state of activation of CD4 positive T cells and elevated interferon gamma production in pouchitis. Gut 1998; 43: 499e505. 21 Goldberg PA, Herbst F, Beckett CG, et al. Leucocyte typing, cytokine expression, and epithelial turnover in the ileal pouch in patients with ulcerative colitis and familial adenomatous polyposis. Gut 1996; 38: 549e55.
and nocturnal seepage of faeces; contain a previously unreported group; when two studies were reported by the same institution, include in the analysis either the one of better quality or the most recent publication. Of 13 studies identified by literature search, five satisfied the inclusion criteria. These studies comprised a total of 306 patients, 86 of whom (28.1%) underwent ERPT and the remainder IPAA. Pouch failure was more common in the ERPT group (odds ratio 3.21, confidence interval 1.24e8.34), as were abdominal salvage procedures (odds ratio 9.5, confidence interval, 3.14e28.77). Short-term adverse events were similar between the two groups, with the exception of perianal sepsis, the higher frequency of which in ERPT just reached statistical significance. Bowel frequency was lower in the patients who had undergone IPAA, although few studies presented functional data in a comparable form. The authors of this meta-analysis concluded that there were few good-quality studies comparing the outcomes from ERPT and from IPAA, and that caution should be exercised concerning the generalisation of these results (which suggest an advantage for pouch procedures in terms of reconstruction survival and functional outcome). Evaluation of the child’s condition should be made periodically during the course of illness and therapy by the surgeon as well as by the gastroenterologist to consider alternatives to long-term medical therapy.
Conclusion Even if ERPT represents a good choice for treating severe UC in paediatric patients, with this option faecal incontinence and a high frequency of defecation are the main factors compromising quality of life. IPAA seems to show better results. We think that studies of quality of life in patients affected by UC who underwent surgical treatment as children or adolescents, also comparing results according to the surgical techniques used (with special regard to ERPT or IPAA) and evaluating differences before and after surgery, must be encouraged in order to provide patients and their families with information not only about potential surgical complications, but also about reasonable expectations concerning quality of life after surgery. The question ‘What is the quality of life for patients living with UC compared with the quality of life they can expect after an ERPT or IPAA?’ still needs to be answered.
Conflict of interest None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper. A
REFERENCES 1 Ravitch MM, Sabiston DC. Anal ileostomy with preservation of the sphincter. Surg Gynecol Obstet 1951; 98: 87e90. 2 Soave F. A new surgical technique for the treatment of Hirschsprung’s disease. Surgery 1963; 56: 1007e14. 3 Coran AG, Weintraub WH. Modification of the endorectal procedure for Hirschsprung’s disease. Surg Gynecol Obstet 1976; 143: 277e82.
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PEDIATRIC SURGERY
22 Yu E-D, Shao Z, Shen B. Pouchitis. World J Gastroenterol 2007; 13: 5598e604. 23 Friedman G. Treatment of refractory ‘‘pouchitis’’ with prebiotic and probiotic therapy [abstract]. Gastroenterology 2000; 118: A778. 24 Ulisse S, Gionchetti D, D’Alo` S, et al. Expression of cytokines, inducible nitric oxide synthase and matrix metalloproteinases in pouchitis: effects of probiotic treatment. Am J Gastroenterol 2001; 96: 2691e9. 25 Shepherd NA. The pelvic ileal reservoir: apocalypse later? BMJ 1990; 301: 886e7. 26 Stern H, Walsh S, Mullen B, et al. Cancer in an ileo-anal reservoir: a new complication? Gut 1990; 31: 473e5. 27 Rodriguez-Sanjuan J, Polavieja M, Naranjo A, et al. Adenocarcinoma in an ileal pouch for ulcerative colitis [letter]. Dis Colon Rectum 1996; 38: 779e80. 28 Sequens R. Cancer in the anal canal (transitional zone) after restorative proctocolectomy with stapled ileal pouch-anal anastomosis. Int J Colorectal Dis 1997; 12: 254e5. 29 Ravitch MM. The reception of new operations. Ann Surg 1984; 200: 231e46. 30 Puthu D, Rajan N, Rao R, et al. Carcinoma of the rectal pouch following restorative proctocolectomy: report of a case. Dis Colon Rectum 1992; 35: 257e60. 31 Vieth M, Grunewald M, Niemeyer C. Adenocarcinoma in an ileal pouch after prior colectomy for carcinoma in a patient with ulcerative pancolitis. Virchows Arch 1998; 433: 281e4. 32 Bell S, Parry B, Neill M. Adenocarcinoma in the anal transitional zone after ileal pouch for ulcerative colitis: report of a case. Dis Colon Rectum 2003; 46: 1134e7.
PAEDIATRICS AND CHILD HEALTH 19:S1
33 Knight CD, Griffen FD. An improved technique for low anterior resection of the rectum using the EEA stapler. Surgery 1980; 88: 710e4. 34 Ceriati E, Deganello F, De Peppo F, Rivosecchi M. Surgery for ulcerative colitis in pediatric patients: functional results of 10-year follow-up with straight endorectal pull-through. Pediatr Surg Int 2004; 20: 573e8. 35 Coran AG. A personal experience with 100 consecutive total colectomies and straight ileoanal endorectal pull-throughs for benign disease of the colon and rectum in children and adults. Ann Surg 1990; 212: 242. 36 Fonkalsrud EW, Thakur A, Beanes S. Ileoanal pouch procedures in children. J Pediatr Surg 2001; 36: 1689e92. 37 Shamberger RC, Masek BJ, Leichtner AM, Winter HS, Lillehei CW. Qualityof-life assessment after ileoanal pullthrough for ulcerative colitis and familial adenomatous polyposis. J Pediatr Surg 1999; 34: 163e6. 38 Durno C, Sherman P, Harris K, et al. Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis. J Pediatr Gastroenterol Nutr 1998; 27: 501e7. 39 Rintala RJ, Lindahl H. Restorative proctocolectomy for ulcerative colitis in childrendis the J-pouch better than straight pullethrough? J Pediatr Surg 1996; 31: 530e3. 40 Tilney HS, Constantinides V, Ioannides AS, Tekkis PP, Darzi AW, Haddad MJ. Pouch-anal anastomosis vs straight ileoanal anastomosis in pediatric patients: a meta-analysis. J Pediatr Surg 2006; 41: 1799. 41 De Silva HJ, Millard PR, Kettlewell M, et al. Mucosal characteristics of pelvic ileal pouches. Gut 1991; 32: 61e5. 42 Shepherd NA, Jass JR, Duval I, Moskowitz RL, Nicholls RJ, Morson BC. Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens. J Clin Pathol 1987; 40: 601e7.
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