A Butler

Prothrombotic Disorders in a Cohort of 25 Patients Undergoing Transplantation: Investigation and Management Implications

BACKGROUNDnMany patients referred for intestinal transplantation have a history of thrombosis. We undertook an analysis of transplanted patients to describe the history and frequency of thrombosis, clinical course, and management strategies used.nnnRESULTSnTwenty-five patients underwent transplantation of intestine containing blocks between 2007 and 2012; 20 of 25 are still alive. Five of 25 patients were transplanted with history of portomesenteric thrombosis, 6 of 25 had experienced loss of venous access due to thrombosis, and 6 of 25 had history of mesenteric ischemia. Pretransplantation, 16 of 25 patients were anticoagulated. Thrombophilia screens identified 3 of 16 patients who were JAK2 positive, 1 of 25 who had antithrombin deficiency, and 1 of 25 who had a factor V Leiden heterozygote. Post-transplantation, of all 16 patients who were anticoagulated pretransplantation and continued postoperatively, 1 of 16 infarcted their small bowel graft and 4 of 16 developed a further venous thrombosis despite anticoagulation. Of the 9 without a previous history of thrombosis, 1 had a pulmonary embolus more than a decade after transplantation and another had an upper limb deep vein thrombosis associated with a line. Both were then anticoagulated. Seven of 25 are not anticoagulated, although they are administered antiplatelet prophylaxis. Postoperative bleeding complications of anticoagulation occurred in 3 patients. After a subarachnoid hemorrhage in 1 of those 3 patients, anticoagulation was stopped. The other 2 patients bled during ileal biopsy, and both remain on low molecular weight heparin treatment.nnnCONCLUSIONnThose with identifiable thrombophilic tendency and a history of venous or arterial thrombosis are considered to be at high risk for recurrent thrombosis. Those without such a history could be considered low risk. Our practice is to anticoagulate all high-risk individuals before and after transplantation and offer antiplatelet prophylaxis to low-risk patients as the risk of anticoagulation probably outweighs the risk of thrombosis for them. Early input from hematologists is vital in the management of high-risk patients, particularly those who thrombose when anticoagulated.

PWE-232 Indications for intestinal and multivisceral transplantation at addenbrooke–s hospital, cambridge

Introduction Small intestinal transplantation was first undertaken in Cambridge in 1991. All patients are discussed at the National Adult Intestinal Transplantation Forum (NASIT) and indications for transplantation agreed prior to listing. We present the indications for intestinal and multivisceral transplantation in patients referred to our unit over the last 8 years. Method A prospectively maintained database records the indications for all patients listed for intestinal and multivisceral transplantation. This database was used to identify indications for patients transplanted between January 2006 and December 2014. NASIT and International Transplant Registry indications were reviewed. Results 56 transplant procedures were performed on 50 patients - 27 (48%) multivisceral (MV); 6 (11%) liver/small intestine (LSB); 8 (14%) modified multivisceral and 15 (27%) small intestine. 6 patients were re-transplanted due to acute cellular rejection not amenable to medical therapy (n = 3), intestinal graft ischaemia (n = 2) and primary non-functioning liver graft (n = 1). The predominant NASIT indications for transplantation were intestinal failure associated liver disease (IFALD) (29%); need for multi-organ transplant (liver with portomesenteric venous thrombosis) (20%); loss of venous access for HPN (14%); widespread mesenteric arterial insufficiency (11%); FAP/desmoids (5%); catheter-related blood stream infections (5%) and acute cellular rejection (5%). 54% of patients had short bowel, the causes of which were ischaemia (57%), Crohn’s disease (27%), volvulus (3%), trauma (3%) and other (10%). Conclusion Cambridge is the only UK centre performing adult multivisceral transplants. IFALD remains the predominant indication for multivisceral transplantation but the number of referrals for this indication is not increasing year on year. This may reflect improved management of patients with Type 3 intestinal failure on home parenteral nutrition, with a focus on quality outcomes and reducing complications. We have observed an increase in patients referred with portomesenteric venous thrombosis which precludes an isolated liver graft. Subsequently we have performed more MV or LSB transplants over the last 2 years in a group of patients with multiple co-morbidities, whose management is more complex. Another emerging indication is widespread mesenteric arterial insufficiency, resulting in 5 urgent transplants during the last 2 years (6 in total). Treatment options for these patients have been very limited in the past and MV transplantation offers a potential new management strategy. Disclosure of interest None Declared.

OC-033 Outcomes following small intestinal and multivisceral transplantation at addenbrooke’s hospital, cambridge

Introduction Small intestinal transplantation was first undertaken in Cambridge in 1991 and with advances in immunosuppression agents, outcomes have improved. We present our survival figures from 2006 to 2014. Method A prospective database is used to record all patients who undergo small intestine (SB), liver/small intestine (LSB), modified multivisceral (MMVT – intestine and stomach) and multivisceral (MVT – intestine, stomach and liver) transplantation at Addenbrooke’s Hospital. All grafts may also contain pancreas, kidney and colon. The NHS Blood and Transplant service derived Kaplan-Meier survival curves for all patients undergoing their first transplant procedure between January 2006 and December 2014. Results 56 transplant procedures were performed on 50 patients (6 were re-transplanted, all are still alive). 1-year survival in patients transplanted is 92% (SB), 83% (MMVT), 67% (LSB) and 69% (MVT). 5-year survival is 92% (SB), 63% (MMVT) and 27% (MVT) – this data is not available for LSB transplants due to small numbers and follow-up duration of only 14 m. These data compare favourably with international transplant registry 5-year survival figures of 59% (SB) and 22% (MVT).1Overall 1-year survival for all patients transplanted in our unit is 76% and 5-year survival is 46%. Conclusion Cambridge is one of 2 UK centres performing intestinal transplantation in adults and we are undertaking an increasing number of procedures – 16 in 2013 and 10 in 2014. We are particularly encouraged by our 92% 5-year survival in patients undergoing isolated SB transplantation and would advocate early referral for assessment in patients with Type 3 intestinal failure who develop complications from home parenteral nutrition. Colon is routinely included in the graft to aid fluid balance and does not preclude regular endoscopic surveillance for rejection. We have performed continuity surgery in a number of patients post transplant (transplanted colon to native colon anastomosis) with good outcomes and no anastomotic leaks. Due to complications of the oesophagogastric anastomosis, gastroparesis and increased morbidity and mortality of MVT we are moving towards performing more LSB transplants and will monitor outcomes with interest. Detailed pre-operative assessment, individualised procedures, patient optimisation and an emphasis on the multidisciplinary team are essential when managing these complex patients. Disclosure of interest None Declared. Reference Intestinal Transplant Registry (ITR) – http://www.intestinaltransplant.org/itr/(Accessed May 2014)

PTH-123 Quality Of Life And Performance Status Scores Following Intestinal Transplantation Are Similar To Those Of Patients On Home Parenteral Nutrition In The Uk

Introduction Survival following Intestinal transplantation (ITX) has improved, approaching that of home parenteral nutrition (HPN) at 5 years. We describe quality of life (QOL) and performance status (PS) on uncomplicated HPN, those with criteria for ITX due to complicated HPN (CHPN) and those after ITX. Methods SF36 was used to assess QOL. Performance status was assessed by health related visual analogue scale (VAS), ECOG and Karnofsky performance score (KS). Results [Table – grouped data]. There was a trend for QOL and PS to be lower on CHPN than HPN and ITX (not significant, NS) Abstract PTH-123 Table 1 n VAS KS ECOG SF36Physical score SF36Mental health score HPN 21 43 (33,100) 60 (52,77) 1.5 (1,3) 30 (22,39) 47.3 (29.9,56.6) CHPN 23 37.5 (23,55) 70 (52.5,80) 2 (1,2.7) 28.4 (21.2,34.6) 37.5 (32,42) ITX 13live 50 (0,70) 70 (60,85) 1 (1,2) 30 (22,39) 43 (35,54) ITx 18all 45 (20,70) 60 (37.5,72.5) 1 (1.5,3.5) 30.2 (22.9,38.1) 43.2 (35.15,51.75) [Median (25th/75th%ile); VAS and KS: Best score100;ECOG: Best score 0] Paired data for SF36 pretransplant (CHPN) and post-transplant revealed “general health “was the only function to significantly improve (p < 0.05). Individual patients’ total scores improved in 4/11 with a statistically significant improvement in a further in 3/11(p < 0.05) and were worse in 3/11. PS showed a trend for improvement post ITX compared to CHPN and HPN [All Wilcoxon signed rank, NS]. Conclusion SF36 improves significantly in approximately 25%, but falls in 25% after ITX compared CHPN and trends suggest performance improvement after ITX. With more data effects of ITX on QOL and PS will emerge and if improvements are confirmed earlier transplantation for those dependent on HPN may be justifiable. Disclosure of Interest None Declared.

PTH-125 Survival Following Intestinal And Multivisceral Transplantation At Addenbrooke’s Hospital, Cambridge, Uk

Introduction Small intestinal transplantation (SBT) was first undertaken in the UK in Cambridge in 1991. Since the introduction of new immunosuppressive agents around the millenium, results have improved and we present our experience over the last 10 years. Since 2003, 47 tranplants have been performed on 43 patients. Grafts include small bowel or small bowel/colon (SBT), liver and small bowel (LSBT), modified multivisceral (MMVT – small bowel, stomach, pancreas, no liver) and multivisceral (MVT – intestine, stomach, pancreas and liver) transplantation. Cambridge is the only UK centre offering MVT in adults. Methods A review of all patients who underwent small intestine and multivsiceral transplantation at Addenbrooke’s Hospital between 2003 and 2013. Kaplan-Meier survival data are shown for each group of organs transplanted. Results Five year survival for all patients transplanted is 77%. Survival curves for each organ group transplanted is graphed below: Conclusion Five year survival in our patients transplanted since 2003 is 100% for SBT and LSBT and 65% for MVT, compared with international registry survival figures of 59% (SBT and LSBT combined) and 22% respectively. In recent years we have also experienced an increase in the number of urgent transplants performed and these patients are often critically unwell at the time of surgery. Our centre undertakes a relatively large number of procedures and this, coupled with a particular focus on multidisciplinary team working, may account in part for our favourable survival figures. Abstract PTH-125 Figure 1 Disclosure of Interest None Declared.

PTH-124 Changes In The Indications For Referral Of Adults For Intestinal And Multivisceral Transplantation

Introduction Small bowel transplantation (SBT) was first performed in the UK in Cambridge in 1991. Recipients mow undergo small bowel (SBT), liver and small bowel (LSBT), modified multivisceral (MMVT – small bowel, stomach, pancreas, no liver) and multivisceral (MVT – intestine, stomach, pancreas and liver) transplantation. Cambridge is the only UK centre offering MVT in adults. The main indications for referral to a transplant centre are: Irreversible intestinal failure plus life threatening complications of parenteral nutrition (PN). Extensive surgery requiring partial or complete evisceration. Methods Prospective data was collected from all patients who underwent intestinal and multivisceral transplantation at Addenbrooke’s Hospital between 2003 and 2013. All patients are discussed and indications for transplantation agreed prior to listing at NASIT (National Adult Small Intestinal Transplant forum). Results 47 transplants were performed on 43 patients; 4 procedures (9%) were re-transplantation for a primary non-functioning graft (2/4) or acute rejection (2/4). The indications for transplant are presented below: Abstract PTH-124 Table 1 Short bowel (%) Motility disorder (%) Re-transplant (%) Desmoids (%) Other (%) Total 2006 1 (100) 1 2007 1 (50) 1 (50) 2 2008 1 (30) 2 (70) 3 2009 3 (60) 1 (20) 1 (20) 5 2010 5 (83) 1 (17) 6 2011 6 (75) 2 (25) 8 2012 2 (33) 1 (17) 1 (17) 2 (33) 6 2013 8 (50) 3 (19) 1 (6) 1 (6) 3 (19) 16 Sixteen transplants were performed in 2013 - MVT (57%), SBT (31%), LSB (6%) and MMVT (6%). 50% of these were due to short bowel - arterial ischaemia (50%), Crohn’s (26%), venous ischaemia (12%) and other short bowel (12%). Colon is now routinely included in the graft to aid fluid balance and does not preclude endoscopic surveillance for rejection. Conclusion The number of small bowel and multivisceral transplants performed over the last 10 years has increased, and more than doubled in 2013. Short bowel remains the commonest indication for transplantation. Historically this was mainly due to Crohn’s disease however in 2013, it was mainly due to ischaemia; this trend was reflected worldwide. In our cohort, an increase in acute arterial thromboses causing coeliac/mesenteric ischaemia resulted in 3 recipients being listed urgently for MVT. There has also been an increase in the number of patients referred with portal vein thromboses extending into the superior mesenteric vein, precluding liver transplant alone. Disclosure of Interest None Declared.

PTU-149 Cambridge-Miami risk assessment for intestinal transplantation

Introduction The Cambridge-Miami (CaMi) preoperative risk assessment score has been previously validated in a small cohort and accurately predicted the survival after intestinal transplantation. We undertook a further validation in a larger cohort of patients. Methods Co-morbidity and lost venous access are used as putative preoperative risk factors, each scored 0–3 for severity. Patients (72 adults (M:F, 33:39) received an isolated intesinal graft (27), or a cluster graft including intestine (45). Results Mean (SD) survival was 1501 (1444)u2005days. The Kaplan–Meier analysis of survival revealed a significant inverse association between survival and CaMi score [logrank test for trend, p<0.0001]. Patients were grouped into CaMi scores of 0 and 1, 2 and 3, 4 and 5, 6 and above, and HR [95% CIs] for death (compared to group 0+1) was found to increase as the CaMi score increased; 1.945 [0.7622 to 5.816], 5.075 [3.314 to 36.17] and 13.77 [463.3 to 120100] respectively and was significantly greater than group 0+1 at group 4+5 (p<0.0001). Conclusion The ability to predict survival from the CaMi score might allow better patient selection, and identify patients for earlier transplantation. Competing interests None declared.

PTU-150 Quality of life before and after intestinal transplantation

Introduction Survival following intestinal transplantation has substantially improved over the last decade and if this trend continues quality of life (QOL) may be considered as a major indication for transplantation. It is important to establish if QOL can be enhanced by transplantation and whether some aspects are more inclined to improve than others. Methods QOL was assessed using Short form 36 (SF36) in a cohort of consecutive patients who had either been assessed for, undergone or, were awaiting transplantation. Data were scored using validated criteria for different QOL functions. The statistical package SPSS (IBM) was used to analyse the data. Results 62 data sets were available, 26 pre-transplant and 36 post-transplant. Grouped data showed significantly better physical function (p=0.03*), social functioning (p=0.01*), general health (p=0.006*) and emotional role limitation (p=0.02*) in the post-transplant group. Paired pre and post-operative data were available for eight patients: function scores improved significantly for general health (p0.04**). Improvements in physical function, social functioning, emotional role limitations, energy/fatigue, emotional well-being and pain were seen but this did not reach statistical significance. Physical role limitation was the only function to decline. Of the eight pairs, two patients had significantly better overall scores post transplant (p=0.02, p=0.01**) and four had improved overall scores not reaching statistical significance. *independent T test **Wilcoxon signed rank. Conclusion In this small experience there was an overall trend for better quality of life after transplantation, but certain QOL parameters appear to improve more than others. If quality of life is to be an indication for transplantation it will be important to select patients on the basis of quality of life parameters that are known to improve after transplantation. Longer term and larger studies are required. Competing interests None declared.

PP-016 Timing referral of patients with intestinal failure – accumulation of preoperative comorbidities adversely affects outcome of subsequent intestinal transplantation

Introduction The decision to refer patients for intestinal transplantation is often taken at a stage when patients are physically and psychologically weak due to an accumulation of multiple comorbidities which may impair their post operative survival. To assist with the assessment of these patients we have developed a scoring system which can be used to prospectively follow patients and avoid untimely referral. We have developed a preliminary preoperative scoring system for transplantation of the small intestine either alone or as a composite graft. Methods The score combines putative risk factors for survival. Factors included were loss of venous access, impairment of organs or systems not corrected by transplantation. Each factor was scored 0–3. A score of 3 indicated comorbidity approaching a contraindication for transplantation, that which might lead to but was not currently an adverse risk factor scored 1 and that presenting a definite but moderate increase in risk scored 2. The preoperative scores for 20 patients, who had either been followed up post operatively for at least 10u2005years or died, was compared to their survival. Results Post operative survival and CaMi score inversely correlated when analysed using (Spearmans test) r = -0.82 p = 0.0001. A score of <3 associated with survival ≥3u2005years (12/12 patients) and above 3 with survival of <6u2005months (4/4). Patient Km survival curves for patients grouped according to CaMi score became significantly different from group 0 at group 3. Using this as a threshold score patients were grouped as either >2 or below 3 and had significantly different survival rates, (logrank, p= 0.0001), Km median survival hazard ratio (HR) 6, rate of death Km HR of 5. Receiver – operator characteristics indicate a high degree of accuracy for prediction of death at 3u2005years, area under curve (C statistic): 0.98; 5u2005years: C statistic 0.82; 10u2005years: C statistic 0.65. Conclusion In this initial validation the preoperative CaMi score seems to predict postoperative survival and will now be applied to a larger population of patients for further validation and may be of use to physicians caring for patients with established intestinal failure as an additional guide to the timing of referral for transplantation.

PTH-102 Renal dysfunction is an early morbid event in intestinal transplantation

Introduction Renal dysfunction (RD) following intestinal transplantation (SBTx) contributes to significant morbidity and is associated with reduced patient survival. RD has been shown to occur within the first two postoperative years, but renal function in the early postoperative period is poorly described. Methods The study was performed in a single centre on patients who had a minimum survival of 6u2005months following small bowel/multivisceral transplantation. A total of 20 transplants were performed during the study period and 11 were eligible for this study. The data collected were recipient demographics, pre-transplant renal function, donor demographics, immunosuppressive therapy. Renal function (measured by serum creatinine and e-GFR), serum Tacrolimus levels were at 7, 14 and 21u2005days, 6, 12, 18 and 24u2005months and 3u2005years. In addition, number of admissions, acute rejection episodes, need for modulation of immunosuppressants and function of the allografts. The data were retrieved from a prospectively collected database. Results 8/11 patients had deterioration in the renal function with mean serum creatinines at Day 14, 21 of 172.4 and 161.2u2005μmol and at 3 and 6u2005months 163.1 and 143.9u2005μmol, respectively. The serum Tacrolimus levels were well controlled between 8.27 and 9.17u2005μg/l throughout the study period. The RD was treated by 3/8 patients being converted to m-TOR inhibitors and in the other 5/8 patients reduced Tacrolimus levels were used. The renal function for patients converted to MTOR inhibitors improved. The mean number of admissions in the first year after the transplant was 3.66 and 4.13 during 3u2005years. There was an association between the number of readmissions and renal dysfunction suggesting that these patients had a poorer outcome as previously observed by others. However, we did not find an association between RD and Tacrolimus levels which other have reported. Conclusion In our cohort, the renal dysfunction was noted in 73% (8/11) of patients and it occured within the first month of the SBTx. The association with readmission suggests it is related to impaired outcome, its cause remains speculative.