Multivisceral Transplantation Research Articles

Prikaz slučaja 30-godišnjeg muškarca sa megacistis-mikrokolon-intestinalnim hipoperistaltičkim sindromom sa de novo mutacijom gena ACTG2

Introduction: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a very rare genetic disorder of visceral motility of the gastrointestinal and genitourinary system. According to our knowledge, so far there has been no description of a patient with megacystis-microcolon-intestinal hypoperistalsis syndrome and chronic secretory diarrhea. Case report: We have presented a case report of a 30-year-old male with a genetically verified novel (de novo) mutation p.R257H in the smooth muscle actin (ACTG2) gene. At 8 months of age he was diagnosed with suspected Hirschsprung's disease, partial resection of the colon was performed. During the first year of his life, subtotal colectomy with cecorectal anastomosis was performed and, simultaneously, deteriorated emptying of the urinary bladder was confirmed. The patient was subjected to several unsuccessful abdominal and urological operations. At age of 18, the differential diagnosis was narrowed to micro-villus inclusion disease and congenital chloride diarrhea. The patient was tolerant to oral feeding all the time, where intermittent parenteral nutrition started only in adolescence. At the age of 26, due to urethral stenosis, perineal urethrostomy was performed. Since the age of 29, due to complications of the underlying disease the patient was administered chronic dialysis treatment, and a year later, genetic testing provided the definitive diagnosis of MMIHS. Therefore, combined kidney and intestinal transplantation was proposed. The patient continued the treatment with daily fluid and electrolyte compensation along with adequate parenteral nutrition through a triple-lumen central catheter. Conclusion: Timely genetic testing leads to avoiding repeated surgical interventions and numerous complications. Multivisceral transplantation represents a significant improvement in the treatment of patients with this syndrome.

First Report With Medium-term Follow-up of Intestinal Transplantation for Advanced and Recurrent Nonresectable Pseudomyxoma Peritonei.

To report our experience with the combination of radical surgical excision and intestinal transplantation in patients with recurrent pseudomyxoma peritonei (PMP) not amenable to further cytoreductive surgery (CRS). CRS and heated intraoperative peritoneal chemotherapy are effective treatments for many patients with PMP. In patients with extensive small bowel involvement or nonresectable recurrence, disease progression results in small bowel obstruction, nutritional failure, and fistulation, with resulting abdominal wall failure. Between 2013 and 2022, patients with PMP who had a nutritional failure and were not suitable for further CRS underwent radical debulking and intestinal transplantation at our centre. Fifteen patients underwent radical exenteration of affected intra-abdominal organs and transplantation adapted according to the individual case. Eight patients had isolated small bowel transplantation and 7 patients underwent modified multivisceral transplantation. In addition, in 7 patients with significant abdominal wall tumor involvement, a full-thickness vascularized abdominal wall transplant was performed. Two of the 15 patients died within 90 days due to surgically related complications. Actuarial 1-year and 5-year patient survivals were 79% and 55%, respectively. The majority of the patients had significant improvement in quality of life after transplantation. Progression/recurrence of disease was detected in 91% of patients followed up for more than 6 months. Intestinal/multivisceral transplantation enables a more radical approach to the management of PMP than can be achieved with conventional surgical methods and is suitable for patients for whom there is no conventional surgical option. This complex surgical intervention requires the combined skills of both peritoneal malignancy and transplant teams.

A case of delayed primary-CNS post-transplant lymphoproliferative disorder in a patient with concurrent metastatic colorectal malignancy

Introduction: Post-transplant lymphoproliferative disorders (PTLD) are a complication of immunosuppression following organ transplantation. Due to their heterogeneous presentation, diagnosis of PTLD can be challenging. Case Report: In this case report, we present a patient with metastatic colon cancer, with remote history of multivisceral organ transplant 20-years prior, who presented with altered mental status and was diagnosed with primary central nervous system PTLD. Conclusion: This case illustrates the importance of continued suspicion of PTLD long after transplantation in solid-organ transplant recipients, even in the setting of multiple comorbidities.

Epstein-Barr Virus DNAemia and post-transplant lymphoproliferative disorder in pediatric solid organ transplant recipients.

Pediatric solid organ transplant (SOT) recipients commonly have Epstein-Barr virus (EBV) DNAemia and are at risk of developing post-transplant lymphoproliferative disorder (PTLD). EBV DNAemia has not been analyzed on a continuous scale in this population. All children ≤ 18 years of age who underwent SOT at a single center between January 1, 2007 and July 31, 2018 were included in this retrospective study. Transplant episodes in which PTLD occurred were compared to transplant episodes without PTLD. Multivariable logistic regression was used to identify factors associated with the development of EBV DNAemia and maximum height of EBV DNAemia. A Cox proportional hazards model was used to calculate hazard ratios for time to PTLD. Of 275 total transplant recipients and 294 transplant episodes, there were 14 episodes of PTLD. Intestinal and multivisceral transplant were strongly associated with PTLD (p = 0.002). Risk factors for the development of EBV DNAemia include donor and recipient positive EBV serologies (p = 0.001) and older age (p = 0.001). Maximum level of EBV DNAemia was significantly associated with development of PTLD (p<0.0001). Every one log (log10) increase in the maximum level of EBV DNAemia was associated with a more than doubling of the hazard on developing PTLD (HR: 2.18, 95% CI 1.19-3.99). Transplant type was strongly associated with development of PTLD in pediatric SOT recipients. EBV serologies and age were associated with the development of EBV DNAemia and height of DNAemia. High levels of EBV DNAemia were strongly associated with an increased hazard for PTLD.

S2992 Extensive Portomesenteric Venous Thrombosis Due to JAK2 V617F Mutation as an Indication for Multivisceral Transplantation

Introduction: Cavernous transformation of the portal vein (CTPV) involving periportal or intrahepatic venous collateral network is a sequelae of chronic portal vein thrombosis (PVT). This adaptation increases the risk of complications and poor outcomes from revascularization procedures. In cases with diffuse portomesenteric venous thrombosis, multivisceral transplantation (MT) may be indicated. Case Description/Methods: An otherwise healthy female was diagnosed with Janus kinase 2 V617F (JAK2) mutation at age 43 during work up for PVT of unknown etiology. Her disease progressed with bleeding esophageal varices, portal hypertensive gastropathy, and splenomegaly. Liver biopsy was negative for cirrhosis. Bone marrow biopsy was negative for leukemia or fibrosis. She developed mesenteric vein thrombosis (MVT) at age 45 and was started on rivaroxaban, but then transitioned to high dose enoxaparin due to worsening thrombus progression. At age 47 she underwent thrombolysis for new MVT. Four months later, on current presentation, she endorsed worsening abdominal pain. Physical exam demonstrated ascites and pitting lower extremity edema. Abdominal ultrasound with venous duplex demonstrated absent flow in the portal vein. Computed tomography angiography (CTA) revealed progressive portal, superior mesenteric, and splenic vein thromboses despite anticoagulation (AC) compliance. Transjugular intrahepatic portosystemic shunt (TIPS) procedure was unsuccessful. Post-procedure CTA demonstrated an enlarging hepatic hematoma treated by embolization (figure 1). AC was discontinued resulting in worsening clot burden and hepatic ischemia. Given the extent of clot burden, the patient was transferred to another facility for a MT. Discussion: Presented is a rare case of chronic PVT in a patient with JAK2 mutation leading to CTPV refractory to anticoagulation or endovascular intervention, eventually requiring MT. Though JAK2 is associated with myeloproliferative disorders, it is an independent risk factor for the development of PVT. With worsening thrombus chronicity and burden, cavernous transformation may occur which decreases the chance of successful TIPS. When organ ischemia develops due to extensive portomesenteric venous thrombosis, orthotopic liver transplantation is no longer an option. Multivisceral transplantation replaces the liver, small bowel, and other abdominal organs. Replacement of the thrombosed portomesenteric system may be the only recourse to reverse portal hypertension and address the primary disease.Figure 1.: Computed tomography angiography of hematoma in liver segments VII and VIII, demarcated by green lines. A complication from attempted portal vein access.

Intestinal Transplantation in a Country Without Home Parenteral Nutrition: The Largest Report from the Middle East.

Background:Many regions of the world, especially middle- and low-income countries, lack facilities for home parenteral nutrition and thus cannot follow existing guidelines for intestinal transplantation. Herein, we report our experiences with treatment protocols, intraoperative management, and early postoperative outcomes among patients undergoing either isolated intestinal transplantation or multivisceral transplantation in our center.Methods:During a 1-year period from March 2019 to March 2020, a total of 9 intestinal transplantations including 6 isolated intestinal transplantations and 3 multivisceral transplantations were performed in our center. We reported on donor selection strategies, surgical treatment, anesthesiology care and protocols for total parenteral nutrition, immunosuppression regimen, and pathology evaluation.Results:Mean (standard deviation) age of patients was 37.5 ± 12.5 years. The majority of patients were females (7/9). The median (interquartile range) waiting time for patients from diagnosis to transplantation was 79 (34, 164) days. Our 7-day survey of the amount of fluid therapy after transplantation revealed that the greatest need for fluid therapy was seen on the second postoperative day. After transplantation, 2 patients showed a total of 3 episodes of severe rejection, 1 of which was antibody-mediated. The 1-year survival was 66.6% and the 2-year survival was 44.5% in our study population. The median (interquartile range) time to death was 157 (26.5, 382) days. The most common cause of death was sepsis in our series (3/5).Conclusion:Acceptable outcomes can be obtained with intestinal transplantation in countries without home parenteral nutrition by application of specific treatment protocols.

P7.01: Selecting Candidates for Multi-Visceral Transplantation in Neuroendocrine Tumors (NET) of the Gastrointestinal Tract: A Review of Two Cases

Introduction: Neuroendocrine tumors (NETs) are rare neoplasms arising neurologic or endocrine tissues. These tumors can be seen in nearly any organ system, though they mostly would be present in the gastrointestinal and respiratory systems. In this study, we report two cases of multi-visceral transplantations (MVT) in NET and discuss our indications for MVT among NET patients. Methods and Results: Case 1: A 44-year-old lady referred with a complaint of acute abdominal pain and small bowel obstruction symptoms in June 2018. In laparotomy, an obstructive jejunal mass, a huge retroperitoneal lesion involving the mesentery and liver, was found. A partial resection of the jejunal mass and palliative anastomosis of the bowel was performed. Histopathologic examinations revealed a well-differentiated NET [G1 (ki67:1%)]. The patient underwent MVT. She developed an entero-cutaneous fistula ten days after the surgery which was managed. After which the patient was relatively well till February 2021, when she was admitted with severe watery diarrhea. Severe mucosal ulcerations were seen in endoscopy, and rejection was confirmed through pathologic assessments. The patient died despite our efforts. Case 2: A 46-year-old man who had been suffering from vague abdominal pain and dyspepsia was referred to our clinic in February 2021. He gave a history of 5 kilograms weight loss in the preceding six months. Computed tomography (CT) showed a large lobulated heterogeneously enhancing mass about 150*90 mm in the pancreas with extension to the liver hilum and involvement of spleen and stomach, and signs of partial port vein thrombosis. The pathologist reported a well-differentiated NET (G2, ki67<15%, mitosis 1-2/10 HPF). Exploratory laparotomy, performed in May 2021, showed locally advanced pancreatic NET with celiac encasement and involvement of stomach and colon and portal vein thrombosis with varicose veins and portal hypertension, but no evidence of hepatic metastases. MVT was performed in June 2021. The grafts, including stomach, duodenum, liver, pancreas, and small bowel, were implanted. One month later, the patient complained of diarrhea, 3rd-grade acute T-cell rejection, in a small bowl biopsy was reported. However, the liver biopsy was insignificant. Favorably the patient responded well to the treatment, and after six months, closure of ostomy was performed. The patient is alive and well to this day. Conclusion: We propose the following criteria for MVTx in NETs: Well-differentiated NETs; absence of progression in the last six months; extensive porto-mesenteric thrombosis; intestinal failure with liver metastases; Both superior mesenteric artery and celiac trunk involvement; absence of extra-abdominal involvement that is confirmed by Ga-68 dotatate scan. We should note that this was a case report and larger series are required to support our conclusion.

427.6: Transplant of the Abdominal Rectus Fascia in Rodents, First Report of the Microsurgical Procedure, and Initial Results

Introduction: After intestinal or multivisceral transplants, the proper management and closure of the abdominal wall becomes a challenge. The enterocutaneous fistulas, ostomies, skin scars secondary to multiple previous surgeries or frozen abdomen syndrome are some of the predisposing factors. Synthetic meshes usually produce complications associated with infections and fistulas when used in unfavorable environments, in addition to high costs. Some previous clinical studies have shown benefits applying wall reconstruction techniques including the variant of using a non-vascularized fascia of the abdominal rectus muscle, described by our team. The need to better understand immunological aspects of this procedure we have conceived the concept of performing a murine model. Methods: The procedures were approved by the internal review board and ethics committee for the care and use of laboratory animals (CICUAL UF 2021-016, #PICT 2016-3677). Technical aspects were done reproducing the technique for humans, details and pitfalls are described as part of the results. Engraftment observations were made on days 7, 11, and 30 post-transplantation for each animal strain. At day 30, each recipient was sacrificed, serum and tissue samples were obtained (from the sheath, and the adjacent muscle tissue). Histological studies of the graft were performed. Results: 6 transplants of the abdominal rectus fascia (TxARF) were performed. All donors were female Sprague Dawley rats, while the recipients were 3 Sprague Dawley (3 isogenic TxARF) and 3 Wistar females (allogeneic TxARF). The skin was separated, and the abdominal muscle wall was completely removed to then perform the dissection under a microscope (Fig. 1). TxARF was done utilizing a continuous suture kind Surget with 6-0 Prolene, after removing the ARF and muscle of the recipient (Fig. 2), the skin is closed over the fascia. Once the Tx was finish a strict clinical follow-up of each rat was carried out providing initial treatment with Tramadol and Ceftriaxone; 30th day survival was 100%, 2 recipients developed seromas on days 5 and 11, both isogenic ARF. The visual observation of the grafts showed absence of tissue stiffness and the presence of macroscopic neovascularization (Fig. 3) None of the grafts presented visceral adhesions at the end of the observation period. On histological inspection, the grafts showed, no presence of leukocytes or apoptosic cells, the adjacent native muscle tissue did not present particularities. Conclusion: This first report of the TxARF in rodents, proofs the feasibility of these experimental and translational model. Likewise, it shows similar results to the published in the clinical field, there was absence rejection and abdominal adhesions in the short term under a model without immunosuppression. Further studies will be done to evaluate the immunogenicity, the loss of strength and elasticity as well as the long term results of transplanting the ARF.

317.1: Personalized Approach to Risk-Stratified Desensitization in Modified Multivisceral Transplantation

Introduction: Human leukocyte antigen (HLA) allosensitization prolongs waitlist times and can increase the risk of rejection and both graft and patient loss for intestinal transplant candidates. Desensitization offers a potential therapeutic option to facilitate transplantation with a more compatible donor however there is paucity of evidence on the field. We aim to describe a case of personalized approach to risk-stratified desensitization in a modified non-liver multivisceral transplant (MVT) candidate with cPRA of 100%. Method: A 45 y.o female with history of multiple severe gastroparesis and pseudoobstruction on chronic parenteral nutrition, sensitized via multiple blood transfusions and pregnancy x 2 actively listed for modified MVT was prospectively follow up to determined risk stratification desensitization based on HLA and C1q antibodies (Ab) tests. She underwent desensitization with Rituximab 375 mg/m2 x 1, therapeutic plasma exchange (TPE) x 5 sessions in March 2021 followed by 2 g/k monthly IVIG x 6. We report her follow up at 12 months since the therapy. Results: Before starting desensitization strategies, she tested positive for T and B cell virtual cross match (VCM) with all her donor offers. Her cPRA was 100 % with 54% for Class I (dominant HLA Ab: B7: 22775 MFI) and 63 % of class II (dominant HLA Ab: DR17: 21021 MFI). Following desensitization strategy, we identify using C1q test her dominants HLA Ab as B7, B81 and DR4 with 17321, 8619 and 3133 MFIs respectively; therefore, they were classified as unacceptable antigens. A donor’s offer was accepted when her HLA ab were deemed appropriate in the context of T cell VXM negative and the expected B cell VXM positive (6. 48 ratio) by flow cytometry. She underwent modified MVT in August 2021. The patient received induction immunosuppression with Methylprednisolone taper, Rituximab 150 mg/m2, anti-thymoglobulin 2 mg/kg x 5 doses, TPE x 5 sessions, Vedolizumab 300 mg IV 10, 30 and 60 days posttransplant. Her current maintenance immunosuppression is with tacrolimus (target trough level: 8-10 ng/ml now 7 months post transplant), mophetil mycophenolate 500 mg twice daily and prednisone taper to 5 mg daily. Her dominant donor specific antibody (DSA) was DR 7, which decreased on pre-transplant sample from 13982 to 3053 MFI post induction treatment a week after finishing TPE. The patient’s protocol biopsies showed no evidence of rejection. At 7 months post -transplant her DR7 DSA remains low at 1576 MFI and there is no evidence of de novo DSA. Conclusion: We described the use of personalized approach to risk-stratified desensitization that lead to accept an organ offer based on HLA and C1q antibodies test follow by tailored immunosuppression strategies with early successful results. Further studies are needed to reproduce our outcomes.

407.1: Experimental Assay of Intestinal Graft Viability and Function After Regional Abdominal Normothermic Perfusion

Introduction: DCD has not been considered as a valid alternative for intestinal transplantation (IT). However, normothermia has recently improved the results of the classic cold perfusion in other organs. Our aim was double: to test the viability and function of the intestinal grafts using normothermic regional perfusion (NRP) in an experimental porcine model and to assess ischemic-reperfusion injury (IRI) of the small bowel in human DCD. Method: We used 8 donor-recipient pairs (25.5 ± 2.5 kg), supporting donors with an abdominal NRP. Their small intestine was heterotopically transplanted into the recipients. Blood and intestinal samples were obtained repeatedly throughout the procedure and 1, 2, 7 and 14 days after. IRI was evaluated using Park-Chiu score (PCS) in samples taken during NRP and up to 48 hours after IT. Samples from 7 and 14 days were analyzed to assess graft rejection and GVHD. The gene expression for TJP1, EPCAM, MUC2, LYZ, IL-6, and TNF was measured in all samples. The absorptive function of the grafts was tested at the endpoint. Glycemia from the draining veins of the graft was compared with that from the native small bowel and peripheral blood 15, 30 and 60 minutes after intra-graft glucose administration. The small intestines from eight human DCDs were also sampled for histological analysis while other organs were procured for transplantation. Results: All the intestines were successfully procured. One case was excluded due to venous stenosis. 6 animals (86%) reached the endpoint in good conditions. Grafts conserved architecture during NRP. The highest PCS was observed 1 hour after reperfusion, with denuded villi (PCS-4) in 3 samples (43%). All grafts recovered, with no or very subtle alterations after 48 hours. Five recipients (71%) did not show rejection signs at any time. 2 cases expressed mild rejection (29%) after 7 days. At the endpoint, one of them had recovered but the other had progressed to severe acute cellular rejection (14%). TNF-α, TJP-1 and IL-6 showed maximum levels at the endpoint. Grafts’ glycemia reached its maximum 30 minutes after glucose administration, demostrating their absorption capacity. Human samples did not show any IRI in 80% of the cases. Conclusion: This experimental model postulate DCD with NRP as an alternative source of organs to address the mismatch between the waiting list for IT and the scarcity of donors. Its clinical and functional results appear to be comparable to those of other procurement techniques. The analysis of the human samples suggests that this approach could be successfully translated to the clinical setting. The authors thank NUPA (Spanish Association of Help to Children and Adults with Intestinal Failure, Parenteral Nutrition and Multivisceral Transplant) and Fundación Mutua Madrileña for their support of the present research.

407.9: Treatment of Complex Desmoid Tumours by Intestinal Transplantation

Introduction: Desmoid tumours are rare, locally aggressive tumours which often have an unpredictable and variable clinical course. Although most desmoids (80%) are sporadic, 20% are associated with Familial Adenomatous Polyposis (FAP) which tend to be multi-focal and more aggressive. While the majority of desmoids can be managed by watchful waiting, systemic therapy or radiotherapy, some will require surgical excision. It is recommended in these cases to perform a total resection to reduce the chance of recurrence. In the most extreme cases (multiple segments of bowel, complex fistulating disease, invasion into the abdominal wall, ureteric encasement), the most radical option is to perform a total enterectomy and Intestinal Transplant (ITx). The decision if and when to refer a desmoid patient for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous vs sequential exenteration + delayed listing for ITx). In this study, we present our centre’s experience of managing complex, desmoid tumours with ITx. Method: We performed a retrospective case review of our prospectively collected database between 2007 and 2022. All patients receiving an ITx for desmoids were identified. Results: Between 10/2007 and 03/2022, 126 ITx in 119 patients were performed at our centre. Of these, 14 patients (12%) were for desmoid disease (6 Modified Multivisceral Transplants (MMVT), 5 Isolated ITx and 3 Liver-Small bowel Transplant. Median follow was 43 months (7-104). 9 out of 14 patients are alive (64%) without GI recurrence. None of the patients died from desmoid recurrence. The management of this cohort presented us with several complex technical issues that needed to be overcome such as loss of abdominal domain (6/14), retroperitoneal involvement (6/14), pouch related issues (2/14) and the need for a gastrectomy/duodenectomy due to dysplastic disease (6/14). Loss of abdominal domain and invasion/destruction by the desmoid disease was addressed by using non-vascularised rectus fascia (NVRF), either on its own (4/6) or in combination of vascularized muscle flaps (2/6).Retroperitoneal involvement of the vena cava/iliac vessels and the ureters. Two of these patients required a renal auto-transplantation into the iliac fossa while one patient had a ureteric re-implantation from right to left. The decision to also remove stomach and/or duodenum at the time of ITx depends on the risk of polyp malignancy. Pre-operative polyp surveillance, histology and the Spiegleman score help us to determine the need for a MMVT. Conclusion: Intestinal Transplantation is a viable treatment option in selected patients with extensive desmoid disease. Deciding which patients would benefit from ITx is important to ensure timely referral. Delays in this process can result in additional disease burden such as secondary liver disease or invasion of adjacent structures, requiring further reconstructions.

SARS-CoV-2 Infection in Pediatric Solid Organ Transplant Recipients: A Single Center Observation.

Objectives:This is a descriptive study to characterize rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in pediatric SOT recipients.Methods:We queried Organ Transplant Tracking Record (OTTR) for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 and June 30, 2021. Patients were tested by polymerase chain reaction (PCR): prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (1) acute infection versus convalescence; (2) acute infection versus SOT recipients without infection (called healthy controls); (3) liver transplant (LT) versus small bowel (SB)/multivisceral transplant (MVT); (4) positive versus negative test result.Results:Of 257 LT recipients, 99 were tested: 6 were PCR positive, 13 were antibody positive. Of 150 SB/MVT recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs 10.0 years; P = 0.017). We observed a rapid decline in viral load within 96 hours without a change in immunosuppression. Antibody lasted >8 months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 TEM cell frequency (P = 0.04, P = 0.03, respectively), decreased interferon (IFN)-γ production from T-cells (2.8% vs 11.3%; P = 0.006), and decreased CD8 TEMRA frequency (4.56% vs 11.70%; P = 0.006).Conclusions:Early in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed.

Multivisceral Transplant in a Patient With Portopulmonary Hypertension: A Case Report

Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was <30 mm Hg with a pulmonary vascular resistance of <300 dynes.s/cm5 on oral sildenafil and intravenous epoprostenol. Intraoperatively, management required comprehensive transfusion protocols, a careful balance between correcting blood loss and preventing thrombosis. Intravenous epoprostenol, sildenafil, milrinone, and inhaled nitric oxide were used to reduce elevated mean pulmonary artery pressure and right ventricular strain associated with vascular clamping, reperfusion, and massive fluid shifts. Nitric oxide and epoprostenol use unleashed antiplatelet effects on a patient already susceptible to coagulopathy. A multimodal and multidisciplinary approach continued throughout the surgery and in the postoperative period, which led to a successful outcome.

Shear wave elastography-based liver fibrosis assessment in patients with chronic hepatitis E displays elevated liver stiffness regardless of previous antiviral therapy.

Hepatitis E virus (HEV) infection especially in immunocompromised individuals can lead to chronic hepatitis. Aggressive courses of chronic hepatitis E leading to liver cirrhosis in a short period of time have been described, but evidence on the degree of liver involvement in chronic hepatitis E is rare. We therefore aimed to quantify liver fibrosis in patients with chronic active hepatitis E compared to patients with sustained virological response after ribavirin (RBV) treatment using 2D-shear wave elastography (2D-SWE) to measure liver stiffness. Patients with chronic hepatitis E underwent 2D-SWE, B-mode and Doppler ultrasound and laboratory testing in order to assess severity of liver involvement. In this cross-sectional study, we included 14 patients of whom 8 had ongoing chronic hepatitis E and 6 patients had been successfully treated for chronic hepatitis E. The most frequent cause for immunosuppression was prior kidney transplantation (n=12), one patient was a multivisceral transplant recipient, one had been treated for lymphoma. Five patients cleared HEV after RBV therapy, one patient reached viral clearance after reduction of his immunosuppressive medication. Using 2D-SWE measurement, 71.4% displayed increased stiffness indicative of liver fibrosis: 57.1% classified as significant fibrosis and 14.3% as severe fibrosis. Liver stiffness did not differ between patients with active chronic hepatitis E and in patients who had cleared HEV (1.59 and 1.54 m/s respectively). Compared with a control group of kidney transplant recipients without hepatitis E (1.44 m/s), the patients with a history of hepatitis E displayed a significantly higher liver stiffness (P=0.04). In our cohort of chronic hepatitis E patients, elevated liver stiffness indicating liver fibrosis was common and significantly higher than in controls. This is consistent with prior sparse reports of the presence of liver fibrosis or cirrhosis in chronic hepatitis E and emphasizes the need for HEV testing, therapy and research on new therapeutic options. As elevated liver stiffness was also present in patients after HEV treatment, continuous liver surveillance including elastography and ultrasound should be considered.

The Effect of the COVID-19 Pandemic in Intestinal Rehabilitation and Transplant Patients: Initial Results of the Intestinal Rehabilitation and Transplant Association's International Survey.

The Effect of the COVID-19 Pandemic in Intestinal Rehabilitation and Transplant Patients: Initial Results of the Intestinal Rehabilitation and Transplant Association's International Survey.

#10 Variation in Antibiotic Use and Incidence of Surgical Site Infections in Pediatric Liver Transplant Recipients

Abstract Background Surgical site infections (SSIs) are an important source of early complication after liver transplantation (LT). Peri-operative antibiotics to prevent SSI is considered standard of care, yet there are limited data on the frequency of SSI and no consensus on a standardized regimen. A major barrier is the lack of a large cohort of pediatric LT recipients. Leveraging merged data from the Pediatric Health Information System (PHIS) and the United Network for Organ Sharing (UNOS) we assembled a large cohort of pediatric LT patients to describe the frequency of SSI, variation in antibiotic prophylaxis practices and associated factors. Method The source cohort included all patients under 18 years in the UNOS database who received a LT at a PHIS-participating institution between January 1st 2006 to August 6th, 2017. We excluded those undergoing multi-visceral transplantation and/or re-transplantation. Patient data were merged using a probabilistic merge algorithm using the following present in both datasets: transplant center, date of birth, gender and date of transplant. Our primary outcome was any SSI present during the first 30 days of the hospitalization in which the LT was performed. SSI was defined using ICD 9 and ICD-10 diagnosis codes for post-operative surgical site infection, in addition to procedure codes for incision and drainage or return to the operating room. Peri-operative prophylaxis regimens were inclusive of antibiotic(s) received on the day of or day after LT. After all unique antibiotic regimens were identified, we further categorized into 6 levels of clinically relevant antibiotic combinations ranging from narrowest (Level 1 was cefazolin) to broadest spectrum (Level 6 was carbapenems). Patients receiving agents from more than one category defaulted to the broadest spectrum group. Vancomycin/linezolid administration was collected as a distinct covariate. Data collected on baseline factors included age at LT, sex, race, specifics of the LT type, and severity of illness (SOI) defined as receiving ICU level care on at least one day in the week prior to LT. Results Data from PHIS was successfully merged to 3055 (94%) of patients in the UNOS cohort. We excluded 264 multi-visceral transplants and/or re-transplants and 205 LT recipients without a categorizable antibiotic regimen with a final cohort of 2586 patients. This cohort was 50.8% female, 11.6% Black and 65% White with median age of 2 years (IQR of 0,9). 11.6% of patients required at least one ICU level of care day in the week prior to LT and the median hospital stay from day of transplant was 20 days (IQR: 13, 35). An SSI was identified during the hospital stay in 284 (11%) patients. As we discovered that patients less than 1-year of age at transplant were almost twice as likely to experience an SSI compared to patients over 1 year (16.2% versus 8.6%), the distribution of other covariates by antibiotic category was assessed after stratifying &amp;lt;1 year versus &amp;gt;=1 year (Table 1A and Table 1B).Category 5 was the most commonly represented antibiotic group.Significant differences in antibiotic regimen included donor type and type of liver transplanted , receipt of dialysis the week prior, and in those meeting SOI criteria. In older patients, differences in antibiotics administered were additionally noted within race category and if there was concern for donor infection. Conclusion SSI was common and varied by age, with children under one more likely to sustain an SSI. Antibiotic regimens administered varied withing each of these age groups. Factors associated broader-spectrum categories included receipt of a living donor LT, dialysis in the week prior to LT, and needing at least one ICU-level of care day in the week prior to LT. Additional multivariate analyses are warranted and will focus on investigating the degree to which center-specific differences are driving variation and will explore the comparative effectiveness of different antibiotic prophylaxis categories on SSI risk.

Investigation and follow up of patients under “hospital A” receiving home parenteral nutrition with liver function test (LFT) derangement

Investigations to help identify the cause of abnormal routine serum LFTs (Alkaline phosphatase (ALP), Alanine Transferase (ALT) and Bilirubin) may be sub-optimal in patients on home parenteral nutrition (HPN), despite the risk of patients developing intestinal failure associated liver disease.1 Suboptimal investigation and follow-up of patients may lead to a delay in multivisceral transplant referral and be associated with adverse outcomes.

Optimal Treatment for Patients With Cavernous Transformation of the Portal Vein.

Cavernous transformation of the portal vein (CTPV) is a sequela of extrahepatic and/or intrahepatic portal vein obstruction caused by a combination of local and risk factors. It was ever taken as a relatively rare disease due to its scant literature, which was mainly based on clinical series and case reports. CTPV often manifests as gastroesophageal variceal bleeding, splenomegaly, and portal biliopathy after the long-term insidious presentation. It is unable for CTPV to be recanalized with anticoagulation because it is a complete obstruction of the mesentericoportal axis. Endoscopic therapy is mainly used for temporary hemostasis in acute variceal bleeding. Meso-Rex shunting characterized by portal-flow-preserving shunts has been widely performed in children with CTPV. The multitude of complications associated with CTPV in adults can be effectively addressed by various interventional vascular therapies. With the ubiquity of radiological examinations, optimal treatment for patients with CTPV becomes important. Multivisceral transplantation, such as liver-small intestinal transplantation, may be lifesaving and should be considered for patients with diffuse mesenteric venous thrombosis.

Incidence and outcomes of post-transplant lymphoproliferative disease after 5365 solid-organ transplants over a 20-year period at two UK transplant centres.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of solid-organ transplantation (SOT). We present the incidence and outcomes of PTLD in a cohort of 5365 SOT recipients over a 20-year period at two UK transplant centres. With a median follow-up of 7.7years, 142 of 5365 patients have developed PTLD. Cumulative incidence was 18% at five years after multivisceral transplant and 1%-3% at five years following the other SOT types. Twenty-year cumulative incidence was 2%-3% following liver and heart transplantation and 10% following kidney transplantation. Median overall survival (OS) following SOT was 16years, which is significantly reduced compared with the age-adjusted UK population. There is relatively high early mortality following diagnosis of PTLD and only patients surviving two years regained a longer-term survival approaching the non-PTLD SOT cohort. Of 90 patients with monomorphic PTLD, diffuse large B-cell lymphoma, 66 were treated with first-line rituximab monotherapy and 24 received first-line rituximab plus chemotherapy. Up-front rituximab monotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes before and after treatment remains high with both treatment approaches. Multivariate analysis of all 90 monomorphic PTLD patients identified an International Prognostic Index (IPI) of 3+ as the strongest pretreatment variable associating with inferior one-year OS.

A226 SEX-BASED DISPARITY COMPLICATIONS FOLLOWING LIVER TRANSPLANTATION

BackgroundSex-based disparity exists in liver transplantation (LT) with women being disadvantaged at every stage of the process starting from assessment to post transplantation (Bryce et al., 2009). The reasons for this are multifactorial and include biological disparities, psychosocial, and allocation inequalities (Burra et al., 2013).AimsThe purpose of this study was to identify differences in immediate or long-term complications post-LT by sex.MethodsWe analyzed 702 patients who underwent LT at the University of Alberta from 2002 to 2015. Patients aged < 18 years or requiring a repeat or multivisceral transplant were excluded. Renal dysfunction was defined according to the KDIGO criteria. Cardiovascular disease (CVD) was defined as hospitalization for or death from coronary artery disease, cardiac arrest or cerebrovascular disease.ResultsMale patients comprised 69% of the population. Time on the waitlist was similar for men (9.3 ± 11.7 months) and women (9.9 ± 12.3 months; p=0.57). Both sexes were comparable in age (males: 53 ± 10 years; females: 52 ± 11 years; p=0.19), MELD (males: 18 ± 9; females: 19 ± 10; p=0.16) and BMI (males: 27.7 ± 5.7 kg/m2; females: 27.3 ± 6.6 kg/m2; p=0.58). Women had lower creatinine pre-LT (males: 1.1 ± 0.60 mg/dL; females 0.96 ± 0.51 mg/dL; p<0.01). There were no differences in donor age, sex or BMI. Women had significantly longer hospital length of stay (males: 18 days [IQR: 11, 32]; females: 25 days [IQR: 14, 43]; p <0.001). There was no difference in risk of acute kidney injury (OR 1.4 [95% CI: 0.98, 2.1]; p=0.06), infection (OR 1.1 [95% CI: 0.8, 1.5]; p=0.52) or rejection episodes (OR 1.1 [95% CI: 0.8, 1.5]; p=0.74) following LT. Women had a higher risk of CKD post-LT (OR 2.3 [95% CI: 1.6, 3.2]; p<0.0001). There was no difference in de-novo diabetes (males: 22%; females: 16%; p=0.10), hypertension (males: 45%; females: 48%; p=0.41), dyslipidemia (males: 37%; females: 39%; p=0.67) and CVD (males: 20%; females: 19%; p=0.84) post-LT. Graft (males: 11.4 ± 0.4 years; females: 11.8 ± 0.5 years; p=0.32) and patient survival (males: 11.8 ± 0.4 years; females: 12.4 ± 0.5 years; p=0.18) were similar over a median follow up of 6.3 years [IQR: 3.5, 9.9].ConclusionsWomen spend a longer time in hospital and are at an increased risk of CKD following LT. Despite these differences, overall graft and patient survival are comparable. Our data suggest the disparity between sexes likely exists pre-LT and females that undergo LT have similar outcomes to their male counterparts. Funding AgenciesNone