Improved outcome of referrals for intestinal transplantation in the UK

Aim

To describe the outcome of children with intestinal failure referred to Birmingham Children''s Hospital (BCH) for consideration of intestinal transplantation (ITx), to determine factors for an adverse outcome and to analyse the impact of post‐1998 strategies on survival.

Subjects and methods

A retrospective analysis was performed of children referred for ITx assessment from January 1989 to December 2003. Children were assessed by a multidisciplinary team and categorised into: (a) stable on parenteral nutrition; (b) unsuitable for transplantation (Tx); and (c) recommended for Tx. To analyse the impact of the post‐1998 strategies on survival, a comparison was made between the two eras (pre‐1998 and post‐1998).

Results

152 children with chronic intestinal failure were identified (63M:89F, median age 10 months (range 1–170)). After assessment, 69 children were considered stable on parenteral nutrition (5‐year survival 95%); 28 children were unsuitable for Tx (5‐year survival 4%); and 55 children were recommended for Tx (5‐year survival 35%, which includes 14 children who died waiting for size‐matched organs). Twenty three ITx and nine isolated liver transplants (iLTx) were performed. In a multivariate analysis, the following factors in combination had an adverse effect on survival: the presence of a primary mucosal disorder (p = 0.007, OR ratio 3.16, 95% CI 1.37 to 7.31); absence of involvement of a nutritional care team at the referring hospital (p = 0.001, OR ratio 2.55, 95% CI 1.44 to 4.52); and a serum bilirubin>100 µmol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 µmol/l in the post‐1998 era compared with 237 µmol/l in the pre‐1998 era, p = 0.001) may be a contributory factor to improved survival. The strategies of combined en bloc reduced liver/small bowel transplantation and iLTx resulted in fewer deaths on the waiting list in the post‐1998 era (2 deaths in post‐1998 era v 12 deaths in pre‐1998 era). The overall 3‐year survival in the post‐1998 era (69%) has improved compared with the pre‐1998 era (31%; p<0.001)

Conclusion

The changing characteristics at the time of referral, including earlier referral and innovative surgical strategies have resulted in improved long‐term survival of children referred for ITx.Intestinal failure is defined as a condition in which intestinal nutrient absorption is inadequate to sustain life and to support growth without intravenous nutritional supplementation.¹ The prevalence has increased from 2–3 per million to 5–6 per million of the population, as a result of improved survival in the newborn period.² There are three main causes of long‐term intestinal failure: (1) short bowel syndrome (SBS), usually occurring after extensive neonatal surgical resection for necrotising enterocolitis, small bowel atresia and gastroschisis; (2) motility disorders, for example Hirschprung''s disease, pseudo‐obstruction; and (3) primary mucosal disorders, for example microvillous inclusion disease, tufting enteropathy.From the 1970s successful developments in parenteral nutrition and in central venous catheter placement made it possible to maintain children with intestinal failure in a satisfactory nutritional state for many years.^3,4 However, the long‐term use of parenteral nutrition is associated with life‐threatening complications: liver disease, recurrent septicaemia, and thromboses resulting in difficult venous access.⁴ Intestinal transplantation has evolved from an innovative procedure in the late 1980s to a technically feasible option in the late 1990s⁵ and around 1300 intestinal transplants have now been performed worldwide.⁶ Moreover, non‐transplant surgery (for example, bowel lengthening or plication procedures) may be a treatment option in selected patients.⁷ In patients with SBS who develop severe liver disease, isolated liver transplantation may be an option if there is a realistic likelihood of eventual successful intestinal adaptation and recovery from intestinal failure.⁸ Thus, there are various possible treatment options for children with intestinal failure and choosing the best strategy for individual cases poses a major clinical challenge.Children who have developed complications associated with intestinal failure in the UK have been referred to the intestinal transplant program at Birmingham Children''s Hospital (BCH) since 1989, and the first intestinal transplant was performed in 1993. This centre was officially designated as the sole UK centre for paediatric small bowel transplantation in 1997. An earlier analysis of our experience between 1989 and 1997 indicated a poor survival rate (31%). At that time many referred patients were already seriously ill and many died awaiting transplantation (69%). For this reason, several new treatment strategies were implemented in 1998: combined reduced en bloc liver and small bowel transplantation; isolated liver transplantation for selected patients for short bowel syndrome; and non‐transplant surgery for selected patients of short bowel syndrome with dilated dysmotile loops of bowel. The aim of this study was to describe the outcome of children with intestinal failure referred to our centre, to determine risk factors for adverse outcome and analyse the impact of the new strategies implemented since 1998 onwards.     

Formalin-induced cataract in goat eyes as a surgical training model for phacoemulsification

We compared 2 techniques of inducing cataract in enucleated goat eyes as a training model for phacoemulsification. The cataract was induced using 0.2 to 0.5 mL of formalin 20%. In 10 eyes, formalin was injected through a clear corneal side port into the nucleus after capsulorhexis and in 10 eyes, through the pars plana before capsulorhexis. The pars plana technique achieved a cataract of different grades of nuclear hardness with the added advantage of anterior capsule elasticity closely simulating that of senile cataract but without compromising corneal clarity.     

Meniscofemoral ligaments revisited. Anatomical study,age correlation and clinical implications

The meniscofemoral ligaments were studied in 84 fresh-frozen knees from 49 cadavers. Combined anterior and posterior approaches were used to identify the ligaments. In total, 78 specimens (93%) contained at least one meniscofemoral ligament. The anterior meniscofemoral ligament (aMFL) was present in 62 specimens (74%), and the posterior meniscofemoral ligament (pMFL) in 58 (69%). The 42 specimens (50%) in which both ligaments were present were from a significantly younger population than that with one MFL or none (p < 0.05). Several anatomical variations were identified, including oblique fibres of the posterior cruciate ligament (PCL), which were seen in 16 specimens (19%). These were termed the 'false pMFL'. The high incidence of MFLs and their anatomical variations should be borne in mind during arthroscopic and radiological examination of the PCL. It is important to recognise the oblique fibres of the PCL on MRI in order to avoid wrongly identifying them as either a pMFL or a tear of the lateral meniscus. The increased incidence of MFLs in younger donors suggests that they degenerate with age.     

Changes in 'A' antigenic sites in haematological disorders. An immunoautoradiographic study

Using a quantitative immunoautoradiographic technique with simultaneously exposed internal standards, antigenic sites on A1, A1B, A2 and A2B erythrocytes were quantitated. The binding of purified radioiodinated rabbit anti-A antibodies was studied by the direct incubation technique. 61 normal individuals and 44 patients suffering from leukaemia and other haematological disorders such as polycythaemia vera (PV) and aplastic anaemia (Apl.A) were investigated. Among the normal volunteers, antigenic sites gradually increased up to 3 months of life, later on they were comparable with the values of adults. A reduction of more than 50% in the antigenic sites was observed in all cases of Apl.A. 50-70% of patients with various forms of leukaemia had a decrease in antigenicity. 1 patient suffering from acute unclassified leukaemia showed two populations of red cells. This case differed from natural O/A1 chimerism where A1 erythrocytes had normal antigenicity while in the patient, A1 antigens were depressed. 2 patients (1 with acute lymphoblastic leukaemia, 1 with Apl.A) who were investigated after allogenic bone marrow transplantation had a marked decrease in antigenic sites. Reasons for A antigenic variations in haematological disorders are discussed.