S Middleton

Adult Intestinal and Multivisceral Transplantation: Experience From a Single Center in the United Kingdom

Cambridge is one of two designated adult intestinal transplant centers in the United Kingdom and has performed 60 transplants on 54 patients since 2007; 52% of these were undertaken in the last 3 years. This increasing trend is in contrast with that reported worldwide; 27% were small bowel grafts (SBT), 15% modified multivisceral (MMVT), and 58% multivisceral (MVT). Median recipient age was 47 years; the female-to-male ratio was 27/33. Primary diseases included visceral arterial thromboses (17%), Crohns disease (17%), motility disorders (12%), visceral venous thromboses (12%), familial adenomatous polyposis (FAP)/desmoids (8%), alcoholic cirrhosis (3%), nonalcoholic fatty liver disease (3%), ulcerative colitis (2%), and other (15%). Indications for transplant included intestinal failure-associated liver disease (IFALD) (27%), loss of central venous access (17%), FAP/desmoid disease (5%), extensive portomesenteric venous thrombosis (PMVT) (20%), widespread mesenteric arterial ischemia (WMAI) (13%), re-transplant (8%), and other (10%). Overall 1-year/5-year patient survival rates were 77%/62%. One-year/5-year patient survival rates were 92%/83%, 85%/65%, and 71%/33% for SBT, MMVT, and MVT. One-year/5-year survival rates for patients with IFALD, PMVT, and other indications who underwent MVT were 80%/20%, 65%/55%, and 55%/35%. The greatest proportion of patient deaths occurred during the first year after transplant (50% in year 1, 23% in year 2, 9% in year 3, 5% in year 4, and 14% in year 5), particularly in the MVT group. Referrals toxa0our United Kingdom center are increasing, and the indications for transplant are becoming more diverse. Our patient survival rates remain comparable with figures reported worldwide.

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.

Urgent Multivisceral Transplantation for Widespread Splanchnic Ischemia

BACKGROUNDnMultivisceral transplantation (transplantation of the stomach, intestine, liver, and pancreas) is usually undertaken as a semi-elective procedure after thorough assessment in patients who have intestinal failure with cirrhosis, cirrhosis with portomesenteric venous thrombosis, or tumors such as desmoids involving the liver and mesentery.nnnSTUDY DESIGNnData were collected prospectively from the time of referral and held in a central database. We used it to report the first cases of urgent multivisceral transplantation (MVT) in patients with widespread splanchnic ischemia (occlusion of the celiac axis and superior mesenteric artery) resulting in small bowel infarction and hepatic failure.nnnRESULTSnThree women (ages 33, 48, and 50 years) were referred to our center with superior mesenteric artery and celiac axis occlusion. All other modes of treatment had been considered and/or attempted. After transfer to our institution, all patients were assessed, urgently listed, and underwent transplantation in 10, 7, and 5 days. Two patients are still alive after 2 years and 1 died at 8 months from multiorgan failure due to infections and graft vs host disease.nnnCONCLUSIONSnTreatment options for patients presenting with widespread splanchnic ischemia with hepatic and intestinal failure/infarction were previously limited to salvage surgery and attempted revascularization. In situations in which these failed, the only previous option would have been palliation. In selected cases, we propose that urgent multivisceral transplantation should be considered as a life-saving treatment. This represents a previously unreported indication for MVT.

Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving micafungin: Case report and literature review

Introduction Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. Presentation of case A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. Discussion Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. Conclusion A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor.

Graft versus host disease after multivisceral transplantation: A UK center experience and update on management

Graft versus host disease (GVHD) following transplantation of an intestine‐containing graft occurs more frequently than with other solid organ transplants and is known to have a poor outcome. The presentation differs from other solid organ transplants, as the gastrointestinal tract is not involved following intestinal transplant. Diagnosis is based on clinical symptoms arising due to native tissue damage and the detection of donor T lymphocytes in circulating blood (T‐cell chimerism). The ideal treatment strategy has not been defined, with advocates for both increased and decreased immunosuppression. We reviewed all cases of GVHD in an adult intestinal transplant center in the United Kingdom and report on management strategies of five cases and methods of detecting T‐cell chimerism. The practice in our center has evolved with experience. The first two patients received an increase in immunosuppression, which was only successful in one case. Subsequently, reducing immunosuppression has been more effective. However, patients with bone marrow involvement have a poorer prognosis. We demonstrate successful treatment of GVHD after multivisceral transplant with a reduction in immunosuppression. This should be followed by vigilant graft surveillance and serial monitoring of the level of T‐cell chimerism, with reintroduction of immunosuppression at the earliest sign of graft dysfunction.

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)

Occult invasive aspergillosis infection following multivisceral transplantation

Patients undergoing multivisceral transplantation are particularly susceptible to post-operative infections due to immunosuppression and the inclusion of bowel in the transplanted graft. These patients typically receive broad-spectrum antimicrobial and antifungal agents as prophylaxis and treatment. However, evidence for this is limited due to the small number of patients undergoing the procedure. We present a case of occult disseminated invasive aspergillosis infection in a patient who underwent multivisceral transplantation.

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.