Letters to the Editor

2014 Lippincott Williams & Wilkins

2 Department of Surgery Western General Hospital Edinburgh, Scotland

No external company was involved in the performance, analysis, or writing of this research, and financial support was received to undertake this project. Conflicts of interest: R.B. is the owner of researchactive.com Ltd, a company which provides smartphone apps, and is a medical advisor to Sermo and Ethicon. L.M. has no conflicts of interest to declare. K.C. and R.B. have previously published in the field of medical smartphone apps. R.B. is the founder of www.researchactive.com Ltd, a company which provides smartphone apps, and is a medical advisor to Worldone interactive and has previously received paid consultancy from Johnson and Johnson Medical Ltd. Address correspondence to Ms. Lorna Marson, Department of Transplantation, Royal Infirmary of Edinburgh, 56 Little France Crescent, Edinburgh, Scotland, EH16 4TJ. E-mail: [email protected] K.C. participated in analyzing the data, performing the research, and writing the article. R.B. participated in designing the research and writing the article. L.M. participated in performing the research and writing the article.

Received 16 September 2013. Accepted 22 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9703-e16 DOI: 10.1097/01.TP.0000438213.72960.e7

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Research2Guidance. Global smart phone application market report 2012, update 1st half year 2010. Research2Guidance 2010. Fisher J, Clayton M. Who gives a tweet: assessing patients’ interest in the use of social media for health care. Worldviews Evid Based Nurs 2012; 9: 2. L Type. The 41 Million Dollar Market for Mobile Phone Medical Apps: The Worldwide Market for Medical Apps. leaddiscovery.co.uk, 2010. (Pub ID: KLI2831262) Available at: http://www.kaloramainformation.com/ Worldwide-Mobile-Medical-2831262/. Accessed 11 June 2013. Alexander S, Hoy H, Maskey M, et al. Initiating collaboration among organ transplant professionals through web portals and mobile applications Online J Issues Nurs 2013; 18: 7. McGillicuddy JW, Weiland AK, Frenzel RM, et al. Patient attitudes toward mobile phone-based health monitoring: questionnaire

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study among kidney transplant recipients. J Med Internet Res 2013; 8: 15. Murphy C, Allen J. NHS Blood and Transplant Potential Donor Audit April 2011YMarch 2012. NHSBT Website, 2012. Available at: http:// www.organdonation.nhs.uk/statistics/potential_ donor_audit/pdf/pda_report_1112.pdf. Accessed 6th August 2013. Connor K, Brady RR, Tulloh B, et al. Smartphone applications (apps) for bariatric surgery. Obes Surg 2013; 23: 1669. Cameron A.M, Massie AB, Alexander CE, et al. Social media and organ donor registration: the Facebook effect. Am J Transplant 2013; 13: 2059. Barton A. The regulation of mobile health applications. BMC 171 Med, 2012;10: 46. Available at: http://www.biomedcentral.com/ 1721741-7015/10/46. Accessed August 2013. Singh I. Introducing the Health Apps Library. NHS England Website, 2013. Available at: http://www.england.nhs.uk/2013/03/13/healthapps-blog/. Accessed August 7, 2013. Schein R, Wilson K, Keelan J. Literature Review on Effectiveness of the Use of Social Media: A Report for Peel Public Health. Brampton, ON: Peel Public Health; 2011. Available at: http:// www.canadianopenlibrary.ca/SwfDocs/226/ 226272.pdf. Accessed August 6, 2013.

Sequential Split Liver Followed by Isolated Intestinal Transplant: The ‘‘Liver-First’’ Approach atients in need of a liver-containing multiorgan graft continue to experience high mortality rates in the waiting list. Several strategies have been implemented to decrease the mortality of these patients, including organ allocation policy changes, the use of reduced grafts (1, 2), and sequential organ transplantation (3). The latter approach, where the liver is transplanted first, is based on the observation that patients with combined liver and intestinal failure almost always die from liver failure (4). We report a case of adult sequential split liver and intestinal transplant in a patient with short bowel syndrome and intestinal failureY associated liver disease (IFALD), the first to our knowledge. A 47-year-old woman (49 kg) was referred to our Institution for a combined liver-intestine transplant evaluation. Her medical history was significant

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for fistulizing Crohn disease requiring multiple small bowel resections resulting in total parenteral nutritionYdependent short bowel syndrome. A liver biopsy showed cirrhosis secondary to IFALD. At the time of presentation, the patient had multiple intra-abdominal abscesses along with active Crohn disease involving only the gastrointestinal tract. At that time, her MELD score was 21 and she was listed for a combined liver-intestinal transplantation. Given her active intraabdominal infection, we decided to perform a near-total enterectomy first, with the intent to make her free from infection. An end jejunostomy was created 40 cm distal to the ligament of Treitz with preservation of the rectum and sigmoid colon and her abdomen was closed primarily. Because of her increasing waiting time, decision was made (about 9 mo after listing for the combined graft) to

perform a ‘‘liver first’’ sequential transplant. On waiting list day, 310 and 35 days after the enterectomy, a liver became available for a pediatric recipient from a brain-dead donor (a 15-year-old, 67-kg gil). The liver was split in situ, and a right trisegment graft (segments 1, 4, 5, 6, 7, and 8) was offered to our patient (Fig. 1). The graft included the retrohepatic vena cava, the main and right portal veins, the common and right bile ducts, and the right hepatic artery. The bile duct was reconstructed using an end-to-side choledoco-duodenostomy. Induction therapy consisted of two doses of 20 mg of basiliximab (postoperative day [POD] 1 and 4). Maintenance therapy consisted of tacrolimus and low-dose prednisone. The patient was discharged home on POD 18 with normal liver function test results. Thirty-nine days after the liver transplant (349 d after listing and 74 d after the enterectomy), our patient received an

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www.transplantjournal.com

Transplantation

& Volume 97, Number 3, February 15, 2014

FIGURE 1. Split liver transplantation followed by isolated intestinal transplantation.

isolated intestinal transplant (from a 8-year-old 33-kg boy). The graft was revascularized heterotopically on the aorta and vena cava by means of donor vascular iliac conduits. The gastrointestinal reconstruction consisted proximally of a jejuno-jejunostomy and an ileosigmoidostomy distally with a diverting loop ileostomy. Induction therapy consisted of 7.5 mg/kg thymoglobulin (five doses per week). HLA typing is shown in Table 1. Interestingly, the liver and intestinal donors shared one class II haplotype (DR17, DR52, or DQ2). The liver graft showed a negative T-cell and a weakly positive B-cell cross-match. The intestinal graft showed a weakly positive T- and B-cell cross-matches. At the time of

transplantation, donor-specific antibodies were negative for both grafts and remained negative during follow-up. Maintenance immunosuppression consisted of tacrolimus, sirolimus, and low-dose steroids. Total parenteral nutrition was discontinued on POD 18 when she was discharged home. The posttransplant course was uneventful until 3.5 years when she developed an episode of moderate acute

cellular rejection of the intestine that promptly responded to steroid pulse treatment. Organ allocation, recipient abdominal domain constraints, and malnutrition are often responsible for the increased mortality of small adults waiting for a liver-containing multiorgan graft. Our reported case offers several points for discussion; first, pretransplant recipient optimization is crucial to reduce perioperative infections and catastrophic outcomes. A near-total enterectomy allowed us to clear the intra-abdominal infection, a priority even in light of potential loss of abdominal domain (which was negligible in our patient likely because of the short period elapsing between the enterectomy and the intestinal transplant). The liver-alone approach and liver-first approach for combined intestinal failure and IFALD have been described before. A group at the university of Baylor (5) showed an overall 1- and 5-year survival of 72% and 52%, respectively, for the liver-alone approach. Two reports described the sequential liver-and-intestinal transplant approach in the pediatric population, showing acceptable outcomes (3, 6). The sequential approach allowed us to expand our options in terms of donor selection by allowing us to accept an adult-sized liver (pediatric-sized livers are almost always allocated to pediatric patients) followed by a pediatric isolated intestine (a much more abundant resource). It is likely that the patient blood type (B Rh+) along with our decision to accept a split liver allowed the patient to receive a liver transplant in a much shorter period compared to a whole graft. From an immunological standpoint, sequential transplant may carry the theoretical disadvantage of immunological ‘‘promiscuity,’’ where a third-party highly immunogenic organ is introduced after a liver transplant. It is unknown whether the liver may still confer protection from rejection to the unrelated intestinal graft. In both the aforementioned reports as well as our case, rejection did not represent a major

TABLE 1. HLA typing for recipient (R), liver donor (D1), and intestine donor (D2) R A24 B51 B8 Bw4 Bw6 Cw7 Cw15 DR17 DR4 DR52 DR53 DQ2 DQ7 D1 A1 A68 B44 B8 Bw4 Bw6 Cw7 Cw7 DR17 DR4 DR52 DR53 DQ2 DQ7 D2 A3 B53 B62 Bw4 Bw6 Cw9 Cw4 DR17 DR10 DR52 DQ2 DQ5

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Letters to the Editor

2014 Lippincott Williams & Wilkins

issue, and while chimeric studies where not performed, these could provide interesting information in future cases. Moreover, the presence of background immunosuppression related to the first transplant may create a favorable environment for intestinal engraftment on one hand and may increase the chance of early postoperative life-threatening infectious complications on the other, which represent a common cause of death in these patients. Lastly, from a regulatory perspective, the liver-first approach could potentially interfere with the current liver allocation algorithm and therefore require a more specific deliberation should this practice become more accepted. In conclusion, sequential split liver followed by isolated intestinal transplant was a safe and feasible approach in our experience and could represent a viable option when timing is crucial.

Ahmed Nassar1 Koji Hashimoto1 Christine Shay-Downer1

Jessica Bollinger2 Teresa Diago Uso1 Masato Fujiki1 Medhat Askar3 Ezra Steiger4 Bijan Eghtesad1 Kareem Abu-Elmagd1 Cristiano Quintini1

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1 Transplantation Center Department of General Surgery Cleveland Clinic Cleveland, OH 2 Department of Pharmacy Cleveland Clinic Cleveland, OH 3 Allogen Laboratories Transplantation Center Cleveland Clinic Cleveland, OH Department of General Surgery Cleveland Clinic Cleveland, OH

The authors declare no funding or conflicts of interest. Address correspondence to: Cristiano Quintini, M.D., Transplantation Center, Department of General Surgery, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195. E-mail: [email protected] Received 9 August 2013.

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Accepted 21 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9703-e17 DOI: 10.1097/01.TP.0000438201.61284.27

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Thomas N, Thomas G, Verran D, et al. Liver transplantation in children with hyper-reduced graftsVa single-center experience. Pediatr Transplant 2010; 14: 426. Oliverius M, Janousek L, Adamec M, et al. Liver transplantations in children using reduced grafts. Rozhl Chir 2010; 89: 411. Testa G, Holterman M, Abcarian H, et al. Simultaneous or sequential combined living donor-intestine transplantation in children. Transplantation 2008; 85: 713. Fryer J, Pellar S, Ormond D, et al. Mortality in candidates waiting for combined liverintestine transplants exceeds that for other candidates waiting for liver transplants. Liver Transpl 2003; 9: 748. Barshes NR, Carter BA, Karpen SJ, et al. Isolated orthotopic liver transplantation for parenteral nutritionYassociated liver injury. JPEN J Parenter Enteral Nutr 2006; 30: 526. Muiesan P, Dhawan A, Novelli M, et al. Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children. Transplantation 2000; 69: 2323.

No Progress in ABO Titer Measurement: Time to Aim for a Reference? ransplantation across antibody barriers has become routine in many centers, with increasingly improved short- to medium-term results. This has coincided with significant technical developments in testing for HLA-specific antibodies; extensive guidelines have been published on how to detect and characterize these antibodies and use this information clinically (1, 2). In contrast, there has been little corresponding development in ABO antibody testing. ABO-incompatible (ABOi) live donor kidney pairs are assessed according to risk based on antibody level, and high-risk patients (depending on local policy) are placed in paired exchange programs. However, group O recipients have a lower chance of matching in the current paired exchange program in the United Kingdom. The testing of ABO-specific antibody is not standardized between transplant centers. Currently, all centers use

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hemagglutination (HA) methods developed for pretransfusion compatibility testing. There is consensus in published data demonstrating significant variation in titers with different HA techniques between transplant centers (3). The UK National External Quality Assessment Scheme is currently conducting pilot studies across all centers performing ABO HA titration. HA assays determine an activityspecific (i.e. agglutination) rather than quantify-specific immunoglobulin and, in principle, may not be appropriate in the transplant setting where donorspecific antibody quantification is needed. Initial data associate ABO-specific IgG levels with poorer outcomes, but the different roles of isotypes and IgG subclasses have not been well described (4). Flow cytometric techniques are beginning to address these questions (5, 6). Synthetic antigen-binding assays have the potential to provide a more detailed

analysis of ABO antibodies but have yet to demonstrate sufficient specificity (7). There is no gold standard test; however, an HA reference technique and a standard reagent to compare each assay against are under development to improve reproducibility and precision between centers. The implications for not having a standardized assay include poor allograft outcome, listing for paired exchange programs unnecessarily, and excessive desensitization. The UK registry 3-year ABOi kidney allograft survival is lower than ABO-compatible (88% vs. 94%) and lower than internationally published single-center experience (88% vs. 92.9%) (8). Using non-standardized testing causes considerable variability in the ABO titer targets used for clinical decision making and may play a role in poorer allograft outcomes. The growth in the number of ABOi transplant centers in

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.