Girish Gupte

Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients – BCSH and BTS Guidelines

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post‐transplant lymphoproliferative disorder (PTLD) in adult recipients of solid organ transplants. This review details the risk factors predisposing to development, initial features and diagnosis. It is important that the risk of developing PTLD is considered when using post transplant immunosuppression and that the appropriate investigations are carried out when there are suspicions of the diagnosis. These must include tissue for histology and computed tomography scan to assess the extent of disease. These recommendations have been made primarily for adult patients, there have been some comments made with regard to paediatric practice.

Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post‐transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi‐organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

Current issues in the management of intestinal failure

Successful long term parenteral nutrition has transformed the prognosis for children with irreversible intestinal failure in the last three decades, but has also highlighted the long term complications: intestinal failure associated liver disease; recurrent catheter sepsis; and impaired venous access. Recent advances in small bowel transplantation and non-transplant surgical techniques now offer hope of sustained survival in the future without parenteral nutrition.

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-associated liver disease: a position paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation.

ABSTRACT Intestinal failure–associated liver disease is the most prevalent complication affecting children with intestinal failure receiving long-term parenteral nutrition. This paper reviews the definition, diagnostic criteria, pathogenesis, and risk factors. The authors discuss the role of enteral nutrition, parenteral nutrition, and its components, especially lipid emulsions. The authors also discuss the surgical treatment, including intestinal transplantation, its indications, technique, and results, and emphasise the importance of specialised intestinal failure centres.

Neurologic Problems After Pediatric Liver Transplantation and Combined Liver and Bowel Transplantations: A Single Tertiary Centre Experience

Background. Neurologic problems postpediatric liver transplant have been reported in up to 46% of cases, and mortality is higher in the pediatric age group compared with adults. Methods. An internal audit was performed in all children undergoing solid organ transplant in the Liver unit at Birmingham Childrens Hospital to identify children with neurologic complications. Results. One hundred seventeen children underwent 127 pediatric liver transplant and combined liver and small bowel transplant episodes over a 4-year period. Neurologic problems were present after 31 of 127 (24.4%) transplant episodes involving 29 children. Seizures were the most common presentation (n=17; 54.8%), followed by encephalopathy (n=11; 35.4%) and posterior reversible leukoencephalopathy syndrome (n=6; 19.3%). Other complications noted were central nervous system infection (n=4; 12.9%), cerebrovascular accident (n=3; 9.6%), peripheral neuropathy (n=2; 6.4%) and tremor, transient blurring of vision, auditory hallucinations and choreoathetosis (n=1; 3.2%) each. There were 27 deaths (23%) in 117 children after transplantation, and the mortality rate in the group with neurologic problem was 13.3% (n=4) compared with 26.7% (n=23) in children without neurologic problem (odds ratio 0.45, 95% confidence interval 0.142–1.439). In contrast to other studies, our study showed that the mortality rate was not higher in children with neurologic problems. Conclusion. Neurologic problems were relatively common after pediatric liver transplantation and combined liver and bowel transplantations; however, the mortality was lower when compared with previously reported studies.

Staged abdominal closure after small bowel or multivisceral transplantation.

Sheth J, Sharif K, Lloyd C, Gupte G, Kelly D, de Ville de Goyet J, Millar AJ, Mirza DF, Chardot C. Staged abdominal closure after small bowel or multivisceral transplantation. 
Pediatr Transplantation 2012: 16: 36–40.

Impact of Change in the United Kingdom Pediatric Donor Organ Allocation Policy for Intestinal Transplantation

Background. Graft availability remains a problem in pediatric intestinal transplantation (IT), with most children waiting being less than 10 kg weight. In November 2004, wait-listed children in the United Kingdom were prioritized nationally to receive pediatric donor organs to improve donor availability for IT. We aimed to evaluate the impact of this change on the recipient population. Methods. Data regarding pediatric donor organ availability and allocation were accessed from the National Transplant database. Recipient demographics and outcomes were recorded from the Liver Unit database. Between 2001 and 2006, there were 228 pediatric donors in the United Kingdom (nonheart-beating donors were excluded), of which 39 livers were allocated to emergency super-urgent liver candidates. A total of six isolated intestine and 21 liver-intestine transplants (15 reduced size, six full grafts) were performed in the same period. Results. Since January 2001, there has been a progressive reduction in overall pediatric organ donation. Increasing awareness about IT has resulted in a significant increase in number of small bowel organs being offered (71.8% vs. 19.5%), although this has been associated with an increase in referrals for transplantation. Despite an increase in number of IT being performed (2.6 vs. 7.7 mean transplants per year), waiting list mortality still remains high in smaller children (<10 kg weight). No mortality was observed in larger children and in candidates for isolated IT. Conclusions. The new prioritization of the national pediatric donor allocation favoring IT has resulted in an increased number of procedures, without an impact on waiting list mortality for small children.

Update on intestinal rehabilitation after intestinal transplantation

Purpose of reviewThe past decade has seen improvements in patient selection and a greater range of surgical procedures available to patients with intestinal failure, and this, combined with more effective immunosuppressive regimens, has transformed survival after intestinal transplantation (ITx). Much more is known about optimizing rehabilitation of the engrafted intestine in the first 12 months after transplant, but it is also becoming apparent that there are some long-term health issues to consider. Recent findingsThe key issues in rehabilitation of ITx are the immunogenic nature of the intestinal graft, which means a higher risk of rejection and necessitates relatively high levels of immune suppression that promotes infections, including Epstein–Barr virus-driven lymphoma, viral gastroenteritis and renal impairment; and those related to the specifics of an intestinal allograft (nutritional support, chylous ascites, growth, food allergy, fat soluble vitamin deficiencies, metabolic bone disease). In this article, recent publications about approaches for establishing nutrition and methods for monitoring the health of the ITx patient are reviewed. SummaryITx appears to be cost-effective compared with parenteral nutrition, but ITx recipients continue to be vulnerable to infections, nutritional deficiencies and rejection over the long-term and, therefore, require support from and involvement of a multidisciplinary team for patients to become safely integrated with their local community.

The role of endoscopic ultrasound for evaluating portal hypertension in children being assessed for intestinal transplantation.

Intestinal transplant is an established treatment of irreversible intestinal failure, unless complicated by advanced intestinal failure-associated liver disease, when liver-bowel transplant may be necessary. Finding at least moderate hepatic fibrosis or gastroesophageal varices (GOV) at oesophago-gastroduodenoscopy (OGD) has been an indication for combined transplantation. Endoscopic ultrasound (EUS) is a sensitive method for detection of GOV. We hypothesized that EUS would detect early GOV and decrease the need for liver biopsy. Sixteen children, median age 13 months (range, 7-88), being assessed for intestinal transplant underwent simultaneous OGD and EUS. In 9 of 16 patients the results of OGD and EUS were concordant, that is, both positive (2) or both negative (7) for GOV. In seven patients, GOV were only identified by EUS. Liver biopsy was avoided in four of these cases. EUS is superior to OGD for detecting GOV in children with intestinal failure-associated liver disease and results in fewer liver biopsies being necessary.