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478 Nightingale

8 Van Doorn L, Figueiredo C, Sanna R, et al. Clinical relevance of the cagA, 10 Yamaoka Y, Kodama T, Kashima K, et al. Variants of the 3' region of the vacA and iceA status of Helicobacter pylori. Gastroenterology 1998;115:58–66. cagA gene in Helicobacter pylori isolates from patients with diVerent H. 9 Rudi J, Kolb C, Maiwald M, et al. Diversity of Helicobacter pylori vacA and pylori-associated diseases. J Clin Microbiol 1998;36:2258–63. cagA genes and relationship to VacA and CagA protein expression, 11 Blaser MJ. Helicobacters are indigenous to the human : duodenal cytotoxin production and associated diseases. J Clin Microbiol 1998;36: ulceration is due to changes in gastric microecology in the modern era. Gut 944–8. 1998;43:721–7.

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Short bowel, short answer? from their .14 This is because of loss of normal daily intestinal secretions (about 4 litres/24 hours), rapid gastric emptying and rapid small bowel transit.15 If a patient has less than 100 cm remaining and a stoma he/she is The paper by Jeppsen et al (see page 559) shows that likely, as a minimum, to need long term parenteral saline.14 glucagon-like peptide-2 (GLP-2) concentrations are low in This requirement does not reduce with time.3 Patients patients lacking an ileum and colon. This is not an with a retained colon do not have these problems and, unexpected finding as the L cells that produce GLP-2 are owing to functional adaptation, nutrient absorption situated in the ileum and colon. GLP-2 is an enterocyte usually improves with time. To explain the diVerences specific growth hormone that in mice causes small and between the two types of patient, measurements of various large bowel villus/crypt growth and increases small and gastrointestinal hormones have been made with interest large bowel length and weight. In mice it also reduces body focusing upon those produced by the ileum and colon. weight loss and restores mucosal integrity after dextran Peptide YY, which like GLP-2 is produced by the L cells induced colitis. In pigs it reduces gastric antral motility.1 of the ileum and colon, slows gastric emptying and small The deficiency of GLP-2 in patients with a jejunostomy bowel transit and may be responsible for the “ileal” and may explain why these patients show no evidence of struc- “colonic” brakes. Peptide YY serum values are high in 2–4 patients with a retained colon and low in patients with a tural or functional intestinal adaptation over time. 16 A distal ileal/colonic peptide with glucagon-like immu- jejunostomy. Thus peptide YY may be responsible for noreactivity has been recognised for many years and part of the functional adaptation that occurs in patients with a retained colon; however, it is unlikely to induce termed enteroglucagon. However, the molecular structure 17 of enteroglucagon was originally unknown and serum structural changes. concentrations were derived by subtracting pancreatic Data are not yet available about GLP-2 values in patients glucagon concentrations from total glucagon-like with a jejuno-colic anastomosis. If high, this may represent immunoreactivity.5 Enteroglucagon producing tumours an adaptive mechanism by which GLP-2 increases intesti- were associated with mucosal hyperplasia67and enteroglu- nal growth and slows gastric emptying. Thus GLP-2 serum cagon was thought to be responsible for the ileal adaptation values could become a useful measure of the amount of intestinal adaptation. If GLP-2 values are low, then it will that occurred after a jejunal resection. GLP-2 is likely to be 8 be important to study the therapeutic eVects of administer- the most important mucosal growth stimulating hormone. ing it. There may even be a congenital defect in absorption Its consists of 33 amino acids and its structure is highly related to a deficiency of GLP-2. conserved throughout all mammalian species (only one The importance of GLP-2 is just starting to be amino acid diVerent in the rat). It has been synthesised and recognised. Its role in promoting intestinal growth makes it its receptor characterised.1 As it stimulates mucosal growth a potentially useful treatment for patients with a short or there is the possibility of giving it to patients with a short damaged bowel. The role of GLP-2 (and peptide YY) in bowel to promote adaptation, or to adults or children with inducing jejunal structural and functional adaptation will intestinal damage (e.g. from ischaemia, irradiation, chemo- only become clearer after they (or analogues) have been therapy, severe coeliac disease, necrotising enterocolitis or infused/injected into patients with a short bowel, and the congenital microvillus atrophy). short and long term eVects documented. When the jejunum is resected, the remaining ileum undergoes both structural and functional adaptation. J NIGHTINGALE Department of Gastroenterology, Structural adaptation is apparent as the bowel increases in Leicester Royal Infirmary, width, its villi become longer and crypts deeper. Leicester LE1 5WW,UK Functional adaptation is shown by measuring increases (with time or compared with normal subjects) in the absorption of macro- and/or micronutrients over a given length of bowel. Functional adaptation may be the result 1 Druker DJ. Glucagon-like peptide 2. Trends in Endocrinology and Metabolism of structural changes, a slowing of transit rate or 1999;10:153–6. 2 Hill GL, Mair WSJ, Goligher JC. Impairment of ‘ adaptation’ in intracellular molecular events (e.g. increased transport patients after ileal resection. Gut 1974;15:982–7. and/or enzyme activity).9 Patients with a short bowel com- 3 Nightingale JMD, Lennard-Jones JE, Gertner DJ, et al. Colonic preservation reduces the need for parenteral therapy, increases the incidence of renal monly encountered in clinical practice do not have a stones but does not change the high prevalence of gallstones in patients retained ileum; they have either a jejuno-colic anastomosis with a short bowel. Gut 1992;33:1493–7. 3 4 O’Keefe SJD, Haymond MW, Bennet WM, et al. Long-acting somatostatin or a jejunostomy. There is no convincing evidence in analogue therapy and protein metabolism in patients with jejunostomies. humans that the remaining jejunal mucosa can adapt Gastroenterology 1994;107:379–88. 410 5 Bloom SR, Long RG. Radioimmunoassay of gut regulatory peptides. London: structurally in either of these situations ; however, WB Saunders, 1982. 6 Gleeson MH, Bloom SR, Polak JM, et al. Endocrine tumour in kidney patients with a retained colon do show evidence of Gut 11–13 aVecting small bowel structure, motility, and absorptive function. function adaptation. 1971;12:773–82. 7 Stevens FM, Flanagan RW, O’Gorman D, et al. Glucagonoma syndrome The clinical problems experienced by the two types of demonstrating giant duodenal villi. Gut 1984;25:784–91. patient with a short bowel are diVerent. Both have 8 Dunphy JL, Fuller PJ. Enteroglucagon, bowel growth and GLP-2. Mol Cell Endocrinol 1997;132:7–11. problems with nutrient absorption; however, patients with 9 Williamson RCN, Chir M. Intestinal Adaptation. N Engl J Med a jejunostomy also lose large amounts of water and sodium 1978;298:1393–402; 1444–50. Pseudo-obstruction in children 479

10 De Francesco A, Malfi G, Delsedime L, et al. Histological findings regarding 14 Nightingale JMD, Lennard-Jones JE, Walker ER, et al. Jejunal eZux in short jejunal mucosa in . Transplant Proc 1994;26:1455–6. bowel syndrome. Lancet 1990;336:765–8. 11 Dowling RH, Booth CC. Functional compensation after small bowel 15 Nightingale JMD, Kamm MA, van der Sijp JRM, et al. Disturbed gastric resection in man: Demonstration by direct measurement. Lancet emptying in the short bowel syndrome. Evidence for a “colonic brake”. Gut 1966;ii:146–7. 1993;34:1171–6. 12 Gouttebel MC, Saint Aubert B, Colette C, et al. Intestinal adaptation in 16 Nightingale JMD, Kamm MA, van der Sijp JRM, et al. Gastrointestinal hor- patients with short bowel syndrome. Measurement by calcium absorption. mones in the short bowel syndrome. PYY may be the ‘colonic brake’ to Dig Dis Sci 1989;34:709–15. gastric emptying. Gut 1996;39:267–72. 13 Cosnes J, Carbonnel F, Beaugerie L, et al. Functional adaptation after 17 Savage AP, Gornacz GE, Adrian TE, et al. Is raised plasma peptide YY after extensive small in humans. Eur J Gastroenterol Hepatol intestinal resection in the rat responsible for the trophic response? Gut 1994;6:197–202. 1985;26:1353–8.

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Pseudo-obstruction in children: This is of course a result of the current shortage of donors but also reflects the poor clinical condition of the patients at transplant or wait? the time of registration. Poor clinical condition and pre-existing complications are clearly related to an increased risk of death.3–5 Moreover, worsening of the clinical condition while on the waiting list leads to increased With advances in immunosuppression intestinal transplan- post-transplant morbidity and a higher death rate.3–5 tation has emerged as a viable option for patients with Taking into account that the long term results of chronic intestinal failure and life threatening complica- transplants are still not as good as those for long term tions. With a one year graft survival rate of around 60% , the timing of referral and the criteria over the past few years, the current situation compares for small bowel transplantation continue to be debated. favourably with the pre-1990 results when 30% survival The current general indication for bowel replacement is rates were achieved (data from the Intestinal Transplant still the development of life threatening problems in the Registry: www.lhsc.on.ca/itr). At the 7th Meeting of the context of gut failure (mostly progressive disease European Intestinal Transplantation Study Group (Brus- and/or central venous access problems). Sigurdsson et al sels, 1998), one year survival rates up to 80–90% were propose a reasonable approach—patients who do not reported by some very experienced centres. present with cholestasis or hepatic dysfunction should be In children, chronic intestinal pseudo-obstruction is managed conservatively. These patients should benefit often a primary disorder, either congenital or acquired. from the best appropriate care, minimising the risk of pro- Secondary pseudo-obstruction is related to various sys- gressive liver disease and preventing line infections.6 This temic diseases and is more common in older patients. strategy adheres to the current consensus guidelines: According to the pathological findings, the primary disease transplantation should be avoid by adequate medical man- is classified as neuropathic, myopathic, or idiopathic if no agement but patients who develop complications specific pattern is recognised. The disease always involves (cholestasis, , vascular access prob- the small bowel and may occur in any other (or all) regions lems) should be referred for transplantation. of the digestive tract. Signs and symptoms of obstruction, Earlier referral and thus registration of patients while still but without anatomical obstruction being evident on con- in reasonable health may help to decrease both pre- and ventional imaging, dominate the clinical picture. The first post-transplant risks. In a recent study, early referral for symptoms may appear as early as the neonatal period or led to better results which in turn had later in life and range from occlusion and complete intoler- a positive eVect on patient selection.7 ance to food to recurrent abdominal pain and constipation. Bueno et al reported that a bilirubin concentration above Chronic bacterial intestinal overgrowth and chronic central 3 mg/l, a prothrombin time of more than 15 seconds or venous access for parenteral nutrition can be associated bridging fibrosis at were significantly related to with infectious episodes, which in turn can result in evolu- poor outcome.3 Also, 80% of the children under 1 year of age tion towards liver fibrosis/cirrhosis and cholestasis.12Little when referred for transplant assessment died within two has been reported on the long term outcome of children years.3 Thus, patients should be referred to transplant with primary intestinal pseudo-obstruction, especially centres as early as possible before liver dysfunction or portal those presenting with severe disease early in life. Because hypertension has developed, or at least before complications the disease is uncommon and because it usually progress occur. Then, after a full evaluation of the patient’s condition, slowly, the poor long term prognosis has probably been the appropriate management strategy should be discussed underestimated in the past. with the referring team, including the option for possible Sigurdsson et al’s experience with 27 young patients future transplantation and its ideal timing. (1–19 years old) (see page 570) is of major importance for Early referral and early interactive management between several reasons. As the patients were referred for local and transplant centres is essential if the general transplant, this group is probably not representative of the outcome of patients in potential need of bowel replacement general population but confirms, however, that severe is to be improved. complications can occur during childhood. Multidiscipli- nary, perioperative management is mandatory and J DE VILLE DE GOYET Liver Unit, must be tailored to each individual because the disease can Birmingham Children’s Hospital, aVect other portions of the digestive system and other Steelhouse Lane, organ systems.1 With expert care, good results can be Birmingham B4 6NH, UK achieved in this diYcult group of patients, as illustrated in this series. 1 Kocoshis S, Reyes J, Todo S, et al. Small intestinal transplantation for irre- Of more concern is that of the 22 patients registered for versible intestinal failure in children. Dig Dis Sci 1997;42:1997–2008. 2 Rudolph CD, Hyman PE, Altschuler SM, et al. Diagnosis and treatment of transplantation, eight were transplanted, eight died before a chronic intestinal pseudo-obstruction in children: report of consensus graft became available and six were still awaiting transplant. workshop. J Pediatr Gastroenterol Nutr 1997;24:102–12.