Small Bowel Grafts Research Articles

Synchronous Abdominal Wall and Small Bowel Transplantation: Critical Insights at 4-Year Follow-up

AbstractThis 4-year follow-up of synchronous abdominal wall vascular composite allotransplantation (AW-VCA) and small bowel transplantation reveals novel insights and innovations in abdominal wall VCA. The case, involving a 37-year-old male Army veteran, showcases the benefits of AW-VCA in addressing loss of abdominal domain in intestinal transplantation (ITx). The events leading to ultimate rejection of both the AW-VCA and small bowel graft at 4 years highlights the complex interplay between graft survival, patient compliance, and immunosuppressive management. Notably, a significant discordance between AW-VCA and ITx rejection patterns was identified, questioning the reliability of skin components in AW-VCA as early indicators of ITx rejection. Furthermore, the behavior of the vascularized abdominal fascia, observed postexcision of the small bowel graft, offers new understanding of the immunologic response to fascia-only grafts. This follow-up emphasizes the complexities of graft survival, patient compliance, and immunosuppressive management, underscoring the need for ongoing research and innovation in the field.

126: Decoding donor and recipient cell dynamics in the small bowel graft within six months post-transplantation

126: Decoding donor and recipient cell dynamics in the small bowel graft within six months post-transplantation

S3358 Exploring Probe-Based Confocal Laser Endomicroscopy as a Novel Tool in Graft Monitoring After Small Bowel Transplantation

Introduction: The most common and severe complication early in Small Bowel Transplant (SBT) is graft rejection making timely detection key to graft preservation. Endoscopic surveillance with protocol biopsy is the gold standard for graft monitoring. Confocal Laser Endomicroscopy (CLE) has emerged as a modality for real-time diagnosis at a histological scale. However, its role in SBT is not known. Herein, we report 3 cases of SBT patients and compare CLE results with standard protocols. Case Description/Methods: Case 1: A 73-year-old man underwent SBT for sclerosing mesenteritis and total enterectomy. CLE and ileoscopy was performed 15 times post-transplant without findings of acute cellular rejection (ACR). Patient expired of sepsis on day 30 post-transplant. Case 2: A 17-year-old male with familial adenomatous polyposis complicated by total colectomy, hepatoblastoma s/p resection and chemotherapy underwent SBT for large desmoid tumor requiring total enterectomy. CLE and ileoscopy was performed 14 times post-transplant without findings of ACR. Case 3: A 23-year-old female underwent SBT for intestinal neuronal dysplasia after chronic rejection from 1st transplant 10 years ago. Ileoscopy done at 20 days post-transplant showed congested and ulcerated mucosa in the proximal ileum. CLE images and histopathology showed findings consistent with ACR. Immunosuppression was increased and reassessment with CLE and ileoscopy done. Discussion: Cases 1 and 2 show normal CLE assessment. Normal villus architecture, non-edematous, and adequate microcirculation suggesting low suspicion for ACR. This correlated with normal pathology characterized by less than 6 apoptotic bodies per 10 crypts, no intravascular neutrophils, and negative viral cytopathology. However, in case 3, CLE images showed significant villus congestion and decreased microcirculation (Figure) indicative of ACR. Biopsies confirmed ACR. Rejection protocols were rapidly initiated.Repeat CLE and ileoscopy showed recovery of mucosal congestion and return of microcirculation. This correlated with complete resolution of ACR on pathology. In the absence of endoscopic criteria for small bowel graft rejection, biopsies are the gold standard. Enhanced technology for in vivo visualization of grafted bowel is needed and would allow for examination of a greater surface area of the bowel than limited biopsies. CLE is a promising tool that could significantly improve early transplant graft monitoring. Further data and prospective studies are needed.Figure 1.: CLE images showing significant villus congestion, and decreased microcirculation.

The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation.

Attenuating the rheological and structural consequences of intestinal ischemia-reperfusion-injury (IRI) is important in transplant proceedings. Preconditioning is an often-proposed remedy. This technique uses physical or pharmacological methods to manipulate key ischemia pathways, such as oxidation, inflammation, and autophagy, prior to ischemia. This study determined the time-dependent effects of Rapamycin preconditioning on small-bowel grafts undergoing cold ischemia perfusion and preservation. Our main parameters were mucosa and cell injury and autophagy. A total of 30 male Wistar rats were divided into 5 groups: sham, preservation-control, and 3 treated groups (Rapamycin administered either 0, 30, or 60 min prior to perfusion). After perfusion, the intestines were placed in chilled IGL-1 solution for 12 h. Thereafter, they were reperfused. Histology and bioanalysis (LDH and lactate) were used to ascertain intestinal injury while immunohistochemistry was used for measuring changes in autophagy markers (Beclin-1, LC3B, and p62 proteins). The results show no significant difference amongst the groups after vascular perfusion. However, intestinal injury findings and autophagy changes demonstrate that administering Rapamycin 30 min or 60 min prior was protective against adverse cold ischemia and reperfusion of the intestinal graft. These findings show that Rapamycin is protective against cold ischemia of the small intestine, especially when administered 30 min before the onset.

Isolated vascularized gastric tube biliary enteric drainage: a paediatric case series experience

BackgroundDespite the enormous surgical advancements in the last century, access to the biliary system is lost when a Roux-en-Y (RY) biliary drainage procedure is performed. Attempts have been made to overcome this inconvenient sequel using variations in the RY anastomosis, small bowel grafts and vascular grafts. These have been predominantly unsuccessful. An isolated vascularized gastric tube (IVGT) graft has been reported in the literature, which was successfully used for adult patients with common bile duct injuries. We have adopted the technique of using an IVGT graft for bile duct reconstruction in the paediatric patients at our institution. We reviewed our experience at our institution between January 2015 and October 2019. This was a retrospective review of all paediatric patients undergoing an IVGT graft procedure for biliary tract anatomical obstruction in the past 5 years. We looked at the indications for surgery, the demographic profile of the patients and outcomes following surgery and outlined the surgical technique used.ResultsIVGT bile duct reconstruction was performed on eight patients. Patients ranged from 2 months to 7 years, and there was an equal number of males and females. The diagnosis was made on clinical suspicion and confirmed with ultrasound (U/S) and magnetic resonance cholangiopancreatography (MRCP). There was an 87.5% resolution of biliary obstruction, and two patients who had bile leaks postoperatively were managed conservatively. Unfortunately, one patient died in the early postoperative period from sepsis due to pneumonia. Follow-up was for a minimum of 6 months and up to 5 years.ConclusionIVGT biliary enteric drainage is a safe, reproducible procedure that allows access to the biliary tree if required in the future. Thus, this procedure serves as an alternative, especially in limited-resource areas where interventional radiology is not available for future interventions.

Multiple rare‐earth magnet bead ingestion in a pediatric liver‐small bowel‐pancreas transplant recipient: A case report and lessons learned

Ingestion of rare-earth magnet beads in children has been a public health concern. The potential risk of swallowing multiple magnets is related to magnet attraction to each other, resulting in serious gastrointestinal complications, such as entero-enteric fistula formation, peritonitis, bowel ischemia or necrosis, bowel perforation, and potentially death. We describe the clinical outcome of a 10-year-old child with a liver-small bowel-pancreas transplant who swallowed 26 rare-earth magnetic beads. The patient presented with fever and abdominal pain. Due to difficulty locating the magnets and post-surgical anatomy changes, only 25 magnets were removed endoscopically. After the procedure, she continued to have abdominal distention and fever, leading to further investigation and subsequently an exploratory laparotomy, which confirmed a walled-off perforation. She was treated conservatively with bowel rest and antibiotics, without the need for small bowel graft resection. She recovered well and was eventually discharged on her home enteral feeding regimen. This case emphasizes the importance of taking a good history and having a high index of suspicion to diagnose this dangerous clinical condition, especially in children with an associated predisposing condition for foreign body ingestion, such as developmental delay. Early diagnosis of multiple magnet bead ingestion and prompt detection of its complications in pediatric intestinal transplant recipients could help initiate appropriate intervention and prevent intestinal graft loss.

Normothermic extracorporeal membrane oxygenation support: Improving the function of intestinal grafts obtained from cardiac death donors.

Extracorporeal membrane oxygenation (ECMO) could ameliorate the energy status and viability of bowel grafts from cardiac death donors. However, the function of these grafts after transplantation is not clear. The purpose of the study was to evaluate the early function of intestinal grafts after transplantation from expected cardiac death donors supported with normothermic extracorporeal support using a porcine allogeneic orthotopic segmental small bowel transplantation model. Eighteen domestic crossbred donor pigs were assigned to living donation (LD), donation after cardiac death (DCD), and ECMO groups. In the LD group, small bowels were harvested and preserved immediately in cold storage. In the other two groups, the donor pigs received conventional rapid recovery treatment or 1-hour normothermic extracorporeal support after 10-minutes expected cardiac arrest. Subsequently, the small bowels were removed and preserved in cold storage. After 5-6hours of preservation, small bowel grafts were transplanted into the recipient pigs that underwent enterectomy. The pathology and electron microscopy results, cell apoptosis rate, tight junction protein expression level in the intestinal mucosa, and plasma endotoxin level were evaluated after transplantation. All grafts functioned on the basis of the maltose absorption test results at day 7 after transplantation. There were no significant differences in the morphological changes in the intestinal mucosa among the three groups at day 7 after transplantation. The cell apoptosis rate and plasma endotoxin level in the ECMO group did not differ significantly than those in the LD group, but were evidently lower than those in the DCD group (P<.001). The intestinal absorptive function improved significantly in the ECMO group in contrast with that in the DCD group (P<.001). Short-term ECMO intervention can alleviate ischemia-reperfusion injuries in intestinal grafts and improve intestinal absorptive function in the early stage after transplantation. Reducing caspase-3 protein expression and cell apoptosis in the intestinal mucosa may be one of the protective mechanisms of ECMO intervention.

A novel histidine-tryptophan-ketoglutarate formulation ameliorates intestinal injury in a cold storage and ex vivo warm oxygenated reperfusion model in rats.

The present study aims to evaluate protective effects of a novel histidine-tryptophan-ketoglutarate solution (HTK-N) and to investigate positive impacts of an additional luminal preservation route in cold storage-induced injury on rat small bowels. Male Lewis rats were utilized as donors of small bowel grafts. Vascular or vascular plus luminal preservation were conducted with HTK or HTK-N and grafts were stored at 4°C for 8 h followed by ex vivo warm oxygenated reperfusion with Krebs-Henseleit buffer for 30 min. Afterwards, intestinal tissue and portal vein effluent samples were collected for evaluation of morphological alterations, mucosal permeability and graft vitality. The novel HTK-N decreased ultrastructural alterations but otherwise presented limited effect on protecting small bowel from ischemia-reperfusion injury in vascular route. However, the additional luminal preservation led to positive impacts on the integrity of intestinal mucosa and vitality of goblet cells. In addition, vascular plus luminal preservation route with HTK significantly protected the intestinal tissue from edema. HTK-N protected the intestinal mucosal structure and graft vitality as a luminal preservation solution. Additional luminal preservation route in cold storage was shown to be promising.

Beyond 10years, with or without an intestinal graft: Present and future?

Long-term outcomes in children undergoing intestinal transplantation remain unclear. Seventy-one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10-year posttransplant outcomes with (group 1, n=26) and without (group 2, n=9) a functional graft. Ten-year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87mL/min/1.73m2 . Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3-drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.

Quality of life after reconstructive procedures for esophageal strictures

To study the long-term results of reconstructive procedures for esophageal strictures and evaluate quality life after each type of esophageal repair using own criteria. The study was conducted among patients who underwent esophageal repair with gastric transplant (172), colonic transplant (25), intestinal transplant (14) and repair of short cervical strictures (7). The age of patients ranged from 5 to 60 years. All patients underwent X-ray and endoscopic examination. Survey also included external respiration function and cardiac function, digestive function, measurement of height and weight, analysis of social aspects (work, study), female genital function. Five-score scale for quality of life assessment was developed. Long-term results were studied in 218 patients for the period from 3 months to 31 years (2002-2017). Excellent and good results were obtained in 180 patients. The best results were obtained after repair of short cervical strictures (4.42 scores), good results - after esophageal repair with gastric (4.14 scores) and intestinal (4.07 scores) transplants. Colonic repair was followed by satisfactory outcome (3.16 scores). Gastric and small bowel grafts are preferred for total esophageal repair due to better quality of life in long-term postoperative period.

P4.07: Does our current dietetic input meet the long term needs of our post transplant patient population?

Introduction: As a super-regional centre with patients from all over the UK frequent face to face contact is not feasible, therefore telephone or email dietetic consultations are necessary. Current dietetic review practice is to personally see patients at their annual review and outpatient appointments to provide assessment of nutritional parameters, intake and matching this to need. Telephone consultations are more ad hoc but are amenable to be standardised so to provide a robust dietetic follow up. We therefore report on current practise and recommendations for future standards of care. Aim: To review our current practise of dietetic input and provide recommendations for future standards of care. Methods: Dietetic notes of all patients who have a small bowel containing graft throughout 2018 who are cared for at Birmingham Children’s Hospital, were retrospectively reviewed to identify all patient contact during the study year. We then looked at the intensity of nutritional support and dietetic needs. Of note, some patients will also have local dietetic intervention. Results: 32 patients were under review throughout 2018. Table 1 shows the dietetic input required and table 2 the median number of reviews each group received. As expected the patients requiring the most intense dietetic intervention have received the most input. It is vital however to consider individual patient need as some patients on less intense intervention required more frequent review demonstrated in the range of patient contacts. 6 patients also had local dietetic input. Conclusion: Dietetic input into small bowel graft patients in imperative. Rationalisation of resources means that those at high risk or high supplemental needs should be prioritised and a standard of care developed. We propose the following standard:- Develop care pathway for each group highlighting frequency of follow up and method to escalate concerns to consultant. Written information for families regarding review process to ensure early reporting of concerns. Referral to local Dietitian where appropriate. Telephone proforma to ensure consistency.

P2.40: Visceral Transplantation in Pediatric Patients with Intestinal Failure: Report from a Large Academic Transplant Program

Objective:Visceral transplantation (VT) is indicated in patients who have failed intestinal rehabilitation and have complications related to parenteral therapy. VT outcomes from an academic center over a 20-year period were studied. Methods:Between 1/1996 and 12/2015, 212 pediatric patients underwent 235 VT. There were 23 re-transplants. Index VT included isolated small bowel (SB n=90); liver, pancreas, small bowel (L+SB n=86); liver, stomach, pancreas, small bowel (multivisceral MVT n= 28); or stomach, pancreas, small bowel (modified multivisceral MMVT n=7) with or without colon. M/F ratio was 125/87. Immunosuppression was antibody induction, tacrolimus and steroids. VT indications were gastroschisis (n=52), intestinal atresia (n=21), volvulus (n=49), necrotizing enterocolitis (n=24), pseudo-obstruction (n=27), Hirschsprung’s disease (n=17), microvillous inclusion disease (n=12), others (n=11). Results:140 patients are alive between 2 and 23 years after transplant (mean 12.8 years). 31 of these underwent allograft enterectomy for rejection (n=26), technical (n=3), primary nonfunction (n=1), PTLD (n=1), and are on parenteral nutrition. 11 in this group were re-transplanted. 77 patients died between 4 days and 20.5 years following visceral transplant (mean 44.5 months). Infection and multisystem organ failure was the leading cause of death (n=26, 31%). Maximum 10 and 15-year graft and patient survival were observed in LB recipients confirming liver’s protective role in sustaining small bowel grafts (table and graph; p=0.009). Conclusions:Visceral transplantation is a viable option for patients with intestinal failure and offers long-term benefit and freedom from parenteral nutrition. Infection continues to be a major factor responsible for graft loss. With careful patient selection and comprehensive management by multidisciplinary team prolonged nutritional autonomy can be restored.

New reconstructive surgery for radical surgical treatment of colon non-tumorous diseases

The aim — to develop new methods of reconstructive operations after radical surgery of colon non­neoplastic diseases in patients with atypical small intestine and superior mesenteric artery anatomy, as well as atypical anatomical relationship between the ileal segments and the demucosal surgical anal canal, in the presence of irritable bowel syndrome.Materials and methods. New methods of reconstructive surgery after radical surgical treatment of patients with non­neoplastic diseases of the large intestine (small bowel reservoir, ileoendoanal anastomosis method, methods of mobilization and dislocation of the small bowel graft into the pelvic cavity) have been developed. These techniques were used in 32 patients from 2008 to 2017.Results and discussion. Postoperative complications due to the implementation of reconstructive­restoration stage of surgical intervention arose in 3 (9.4 %) operated patients. Favorable functional results were obtained, in particular, the absence of diarrhea syndrome and anal incontinence syndrome in 28 (93.3 %) patients. The presence of postcollectomic syndrome I (mild) degree in 26 (86.7 %) operated patients, II (moderate) degree — in 4 (13.3 %).Conclusions. Developed methods of new reconstructive operations in the radical surgical treatment of patients with non­tumor colon diseases contributed to the uncomplicated flow of healing ileo­endoanal anastomosis, the postoperative complications frequency reduction, physiological retardation of the small intestine contents, intestinal digestion improvement, absorption, and anal hold.

Autologous Fibroblast-Seeded Amnion for Reconstruction of Neo-vagina in Male-to-Female Reassignment Surgery.

Plastic surgeons have used several methods for the construction of neo-vaginas, including the utilization of penile skin, free skin grafts, small bowel or recto-sigmoid grafts, an amnion graft, and cultured cells. The aim of this study is to compare the results of amnion grafts with amnion seeded with autograft fibroblasts. Over 8years, we compared the results of 24 male-to-female transsexual patients retrospectively based on their complications and levels of satisfaction. Sixteen patients in group A received amnion grafts with fibroblasts, and the patients in group B received only amnion grafts without any additional cellular lining. The depths, sizes, secretions, and sensations of the vaginas were evaluated. The patients were monitored for any complications, including over-secretion, stenosis, stricture, fistula formation, infection, and bleeding. The mean age of group A was 28±4years and group B was 32±3years. Patients were followed up from 30 months to 8 years, (mean 36±4) after surgery. The depth of the vaginas for group A was 14-16 and 13-16cm for group B. There was no stenosis in neither group. The diameter of the vaginal opening was 34-38mm in group A and 33-38cm in group B. We only had two cases of stricture in the neo-vagina in group B, but no stricture was recorded for group A. All of the patients had good and acceptable sensation in the neo-vagina. Seventy-five percent of patients had sexual experience and of those, 93.7% in group A and 87.5% in group B expressed satisfaction. The creation of a neo-vaginal canal and its lining with allograft amnion and seeded autologous fibroblasts is an effective method for imitating a normal vagina. The size of neo-vagina, secretion, sensation, and orgasm was good and proper. More than 93.7% of patients had satisfaction with sexual intercourse. Amnion seeded with fibroblasts extracted from the patient's own cells will result in a vagina with the proper size and moisture that can eliminate the need for long-term dilatation. The constructed vagina has a two-layer structure and is much more resistant to trauma and laceration. No cases of stenosis or stricture were recorded. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PTLD Involving the Colon Graft in Small Bowel Transplant Recipient

Intestinal transplant is indicated in those who have intestinal failure with resultant life-threatening complications. Complications from intestinal transplant include surgical complications eg. graft thrombosis, rejection and complications due to a high immunosuppressive requirement eg. atypical viral/fungal infections and PTLD. We present a 23-year-old white female with combined small bowel and colonic transplant 11 months ago due to intestinal failure from small bowel volvulus. She was diagnosed with PTLD with diffuse large B-cell lymphoma 1 month ago after presenting with painless LAD. She was on tacrolimus 4 mg BID, 2000 mg/day MMF, and 5 mg/day prednisone. Her EBV DNA was > 2 million copies/ml at the time of diagnosis. She underwent reduction in immunosuppression followed by 1 cycle of R-CHOP and presented with new-onset GI bleeding. EGD to jejuno-jejunal anastomosis was unremarkable but colonoscopy showed a large amount of fresh blood in the colon and ileum. The visualization of colonic mucosa was limited but CTA showed positive luminal extravasation just beyond jejuno-jejunal anastomosis which was successfully treated with embolization. Follow-up colonoscopy to evaluate for small bowel and colonic graft rejection showed normal small bowel and colonic allograft and multiple non-bleeding discreet raised yellowish black-crusted sub-epithelial nodules obliterating nearby normal colonic vasculature in native colon. Pathology showed an atypical lymphoid infiltrate with necrosis in the native colon confirmed to be monomorphic PTLD (positive for CD79a, Pax5, Mum-1, CD 20, EBV-LMP, negative CD3, Ki-67 of 70%). Her abdominal CT scan showed progressive disease burden with extensive liver metastasis. Despite treatment, her hospital course was complicated by neutropenic fever, septic shock, malignant ascites, and spontaneous intracranial hemorrhage from CNS involvement of PTLD. Therefore, no escalation of treatment was discussed and she was made comfort care. The risk of PTLD is high in intestinal transplant recipients due to high immunosuppression requirement (tacrolimus and MMF) and occur in 15% of adults and 20% of children. Colonic involvement of PTLD may portend the aggressive nature of PTLD and be seen more in disseminated or multiple organs involvement. This case highlights a variety of symptoms of PTD in an intestinal transplant recipient from initial presentation with painless LAD followed by an obscure overt GI bleeding due to colonic PTLD

Comparative Study of Small Bowel and Colonic Biopsies with Acute Cellular Rejection in Intestinal Transplantation

Aim: Many centres now include a segment of transplanted colon with an intestinal graft as International Registry data show this is associated with less dependence on parenteral support and improved graft survival.[1] We here compare the diagnosis of acute cellular rejection (ACR) based on biopsies (Bx) performed simultaneously in the small bowel (SB) and colonic grafts (paired Bx) after intestinal transplantation (ITx). Method: We undertook a retrospective review of patients with Intestinal containing grafts at Addenbrooke’s hospital from 2007 to 2016 who developed ACR. Paired bx were reviewed before and after the ACR by an experienced GI pathologist and were graded based on the VIII International Small Bowel Transplant Symposium Consensus criteria with minor modifications for evaluation of colon biopsies. Each Bx was graded either negative or positive for ACR. If the histology suggested borderline paired with normal, this was counted as normal as it was likely not to be clinically relevant. However, if borderline was paired with mild this was included as a discordance as it was considered clinically relevant. Results: During the study a total of 71 ITx were performed in 65 patients. Of these, there were 32 cases of ACR in 30 patients, 18 of which had colon containing grafts. There were a total of 221 paired Bx included in the analysis. Of the 221 paired Bx, the number of concordant normal Bx was 153 (69%) & concordant abnormal Bx was 34 (16%). The total number of discordant Bx was 33 (15%). Among these discordant Bx, the number demonstrating ACR in the small bowel but not the large bowel was 19 and the converse was true in 14 cases. The overall concordance rate was 82.25%. The rate of discordance in ACR was 17%. If the large bowel demonstrated rejection there was a 71% positive predictive value of the small bowel also demonstrating rejection. If the large bowel was normal then the negative predictive value for the small bowel also being normal was 89%. If the small bowel demonstrated rejection then the positive predictive value of the large bowel demonstrating rejection was 64%. If the small bowel was normal then there is a 92% negative predictor value for the large bowel also being normal. Conclusion: Paired Bx in the SB and the colon are usually in agreement regarding the presence or the absence of ACR. However, colonic Bx alone may not suffice to exclude ACR following ITx. Reference: 1. Grant et al. Intestinal Transplant Registry Report: Global Activity and Trends American Journal of Transplantation 2015;15:210–219

Luminal Preservation of the Human Small Bowel Graft Reduces Mucosal Damage During Cold Storage

Luminal Preservation of the Human Small Bowel Graft Reduces Mucosal Damage During Cold Storage

A single-centre experience of Roux-en-Y enteric drainage for pancreas transplantation.

Exocrine drainage following pancreas transplantation can be achieved by drainage into the bladder or bowel, the latter typically by direct duodeno-jejunostomy; the use of Roux-en-Y enteric drainage is uncommon. We report a retrospective analysis of a single-centre experience of Roux-en-Y enteric drainage following pancreas transplantation. Over a 14-year period (2001-2015), 204 consecutive adult pancreas transplants were performed (96.6% simultaneous pancreas and kidney transplants), of which 26.0% were from donors after circulatory death (DCD). During a median follow-up of 67 months (range 13-183 months), 14 (6.9%) recipients experienced complications related to their enteric drainage. Complications during follow-up included early enteric anastomotic haemorrhage (five patients), non-anastomotic enteric bleeding (one patient), small bowel obstruction (four patients) and graft duodenal perforation (two within 6 weeks, five beyond 12 months). No recipient lost their graft as a direct result of complications related to enteric drainage. Patient and pancreas graft survival at 1 year was 99.0% and 94.0% and at 5 years 91.3% and 84.9%, respectively. We conclude that Roux-en-Y enteric drainage following pancreas transplantation is a safe and effective procedure and facilitates graft salvage in the event of graft duodenal perforation.

The Long and Short of It: A Case of Long-term Teduglutide for the Treatment of Intestinal Rejection in Small Bowel Transplant: 2016 ACG Presidential Poster Award

Small bowel transplantation (SBT) is a therapeutic option for those patients who suffer from short bowel syndrome, intestinal failure, and life-threatening complications related to total parental nutrition (TPN). Post-small bowel transplant rejection continues to be a major cause of morbidity and mortality. Endoscopically, graft rejection is characterized by hemorrhage, blunting, and sloughing of the intestinal villi while histologically, it is characterized by increased apoptotic bodies and decreased mitotic bodies per crypt. Teduglutide, a glucagon-like peptide 2 analogue, has been shown to improve intestinal absorption by promoting villous hypertrophy and crypt proliferation. We hypothesized that teduglutide 5 mg subcutaneously daily can promote small bowel villous growth and attenuate small bowel transplant rejection by increasing crypt division while decreasing the apoptotic rate. This novel application of teduglutide may facilitate recovery from rejection and improve nutritional absorption. We present an interesting case of a 22-year-old woman with a myofibroblastic tumor of the mesentery who underwent extensive small bowel resection and subsequent living related small bowel transplantation. She presented with fever and abdominal pain post-operative day 14 after SBT. She underwent ileoscopy revealing ulcerated and extensively denuded intestinal mucosal villi. Histology demonstrated inflammatory changes extending through the muscularis mucosa that was consistent with severe acute graft rejection. She was subsequently placed on teduglutide while continuing immunosuppressive therapy and underwent serial endoscopic evaluations with random small bowel biopsies. Endoscopically, there was serial improvement in the health of the small bowel graft, as histologically demonstrated by an increase in villous growth, overall decrease in the apoptotic rate, and overall increase mitotic rate over 9 months. Furthermore, we conducted novel fluorescent in-situ hybridization (FISH) analysis which confirmed an XY karyotype in the regenerating stem cells of the small bowel graft, indicating that her father's stem cells from the donated small bowel were indeed regenerating. In conclusion, we present a novel application of teduglutide to mitigate small bowel transplant rejection and promote villous growth. Teduglutide should be considered in these patients to help improve nutritional status, allow them to wean off TPN, and ultimately improve quality of life.

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%), Crohn's 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 to our United Kingdom center are increasing, and the indications for transplant are becoming more diverse. Our patient survival rates remain comparable with figures reported worldwide.