Claudia Boesmueller

Local administration of cidofovir for human papilloma virus associated skin lesions in transplant recipients

Human papilloma virus (HPV)‐associated diseases are increasingly diagnosed in solid organ recipients. Cidofovir (CDV) is a broad‐spectrum antiviral agent with activity against all human herpes viruses and HPV. From 2000–2004, a total of 1303 solid organ transplants (SOT) were performed at our center. Six transplant recipients were treated with topical CDV for HPV‐associated lesions. One cardiac recipient responded to a single injection of CDV into his recurrent anal condylomata. In a renal recipient with recurrent penile condylomata CDV was injected into the lesions four times (2 week interval) until lesions regressed. One renal recipient developed multiple vaginal and anal intradermal neoplasias, which relapsed after laser ablation. The lesions were repeatedly injected with CDV and completely disappeared. Two renal recipients with widespread verrucae vulgares were treated with CDV gel, which resulted in regression of the lesions. One patient developed donor derived verrucae vulgares on both transplanted hands, which responded to CDV gel. Four of the six patients were switched from calcineurin inhibitors (CNIs) to Sirolimus (SIR). CDV was found effective in the treatment of HPV‐associated skin lesions in SOT recipients. It needs to be determined whether switch from CNIs to SIR might have contributed to the beneficial effect of CDV.

Malignancies of the colorectum and anus in solid organ recipients.

Patients undergoing solid organ transplantation (SOT) are at increased risk for developing malignancies due to the long term immunosuppression. Data on malignancies of the large intestine after various types of SOT are rare. A total of 3595 SOTs were performed between 1986 and 2005 at our center and retrospectively analyzed with regard to the incidence and course of malignancies of the colon, rectum, and anus. Standard immunosuppression consisted of calcineurin inhibitors in combination with azathioprine or mycophenolate mofetil and steroids with or without antithymocyte globulin or IL‐2 receptor antagonist induction. A total of 206 patients (5.7%) developed malignancies. Colorectal adenocarcinoma was diagnosed in nine patients (0.25%; mean age at diagnosis 65 years) at a mean of 5.3 years after transplantation. Five patients (55%) died 7.2 years post‐transplant due to cardiovascular disease (n = 4) and tumor progression (n = 1). Four patients developed anal neoplasia (0.11%) 7 years post‐transplant with 100% 1‐year survival. Five patients showed post‐transplant lymphoproliferative disorders (PTLD) with intestinal involvement. The incidence of anal but not of colorectal cancers in our transplant recipients differed from that of immunocompetent individuals of corresponding age (0.11% vs. 0.002% and 0.25% vs. 0.3%). PTLD may involve the colon.

Listeria meningitis in transplant recipients.

SummaryINTRODUCTION: Meningitis is a rare complication following organ and stem-cell transplantation and can be caused by a variety of microorganisms. AIM: To retrospectively review the clinical course and outcome of five cases of listeriosis in four organ recipients and one stem-cell recipient during a seven-year period. PATIENTS AND METHODS: Patient records for more than 3500 patients undergoing organ or stem-cell transplantation at the university hospital of Innsbruck during a 27-year period were evaluated. Standard immunosuppression consisted of calcineurin inhibitor-based triple drug therapy with or without ATG or IL2 receptor antagonist induction. RESULTS: The first case affected a 35-year-old woman who received an allogenic bone marrow transplant for advanced breast cancer. Cases two and three related to two male heart recipients. Cases four and five were diagnosed in one male and one female renal recipient. Listeria monocytogenes was isolated from blood in two cases and from cerebrospinal fluid in three. Treatment consisted of ampicillin in all cases with the addition of tobramycin (1), TMPS (1), meropenem (2) or imipenem/cilastatin (1). The deaths of two patients were directly related to L. monocytogenes. CONCLUSIONS: Although listeriosis is a rare complication following transplantation, this infection should be ruled out in individuals presenting with neurological symptoms and fever.ZusammenfassungEINLEITUNG: Meningitis ist eine seltene Komplikation nach Organ- bzw. Stammzelltransplantation und kann durch eine Vielzahl von Mikroorganismen verursacht werden. Ziel dieser Studie war eine retrospektive Analyse über klinischen Verlauf und Outcome bei fünf Transplantationspatienten, die an einer Listerienmeningits erkrankt sind. PATIENTEN UND METHODEN: Die Studienpopulation dieser Arbeit umfasst mehr als 3500 Organ- bzw. Stammzelltransplantationen, die an der Universiätsklinik in Innsbruck während eines Zeitraumes von 26 Jahren durchgeführt wurden. Die Standardimmunosuppression umfasste eine Calcineurininhibitor-basierte Dreifachtherapie, zum Teil unter Verwendung einer Induktionstherapie mit ATG oder eines IL2-Rezeptor-Antagonisten. ERGEBNISSE: Alle Patienten zeigten Zeichen der Meningitis und hatten hohes Fieber sowie eine Erhöhung der Entzündungsparameter. Bei zwei Fällen handelte es sich um eine nosokomiale Erkrankung innerhalb der ersten beiden Wochen nach Transplantation. Beim ersten Fall handelte es sich um eine 35-jährige Frau, die sich aufgrund eines fortgeschrittenen Mamma-Karzinoms einer allogenen Stammzelltransplantation unterziehen musste. Die übrigen vier Betroffenen waren zwei Herz- und zwei Nierenempfänger. Listeria monocytogenes wurde bei zwei Patienten im Blut und bei drei Patienten im Liquor nachgewiesen. Die Behandlung erfolgte in allen Fällen mit Ampicillin. Zusätzlich wurden Tobramycin (n = 1), Meropenem (n = 2) und Imipenem/Cilastatin (n = 1) verabreicht. Zwei Patienten verstarben unmittelbar an den Folgen der Listeriose. SCHLUSSFOLGERUNG: Obwohl die Listerienmeningitis eine seltene Komplikation nach Transplantation darstellt, sollte sie doch bei allen Organempfängern mit hohem Fieber in Erwägung gezogen werden, die eine neurologische Symptomatik entwickeln.

Long-term outcome in kidney transplant recipients over 70 years in the Eurotransplant Senior Kidney Transplant Program: a single center experience.

Background. Kidney transplantation in the elderly is complicated by comorbidities and a higher incidence of death. The Eurotransplant Senior Program (ESP) has been established to allocate kidneys from older donors to the increasing number of older recipients. In this retrospective, single center data analysis, we compare the outcome of recipients older than 70 years with younger recipients transplanted under the ESP protocol. Methods. Between 1999 and 2009, a total of 83 kidneys were transplanted under the ESP protocol in Innsbruck and 19 of the recipients were older than 70 years (mean, 72.7 years). Cold ischemia time was kept short in both groups by giving preference to regional donor organs. Results. Patient survival at 1 and 5 years were 95% and 67% in the 70+ group and 94.4% and 82.6% in the 70− group. Graft survival was 95% and 52% at 1 and 5 years in the 70+ group and 94.4% and 79.0% in the 70− group. When censored for death, graft survival at year 1 and 5 were 100% and 82% in the 70+ group and 98.1% and 92.7% in the 70− group. The delayed graft function rate was high in both groups (36.8% and 41.1%, respectively). Morbidities were largely related to hemodynamic, oncologic, and infectious events. Cardiac failure was the major cause of death. Conclusion. Relatively good results can be achieved with renal transplantation in patients older than 70 years under careful pretransplant evaluation and postoperative management of comorbidities.

Alemtuzumab in solid organ transplantation and in composite tissue allotransplantation

Alemtuzumab (Campath®, Genzyme Corporation, MA, USA) is a potent monoclonal antilymphocyte, anti-CD52 antibody. Since the 1980s, alemtuzumab has been used extensively in organ transplantation as an induction agent - also with the aim of avoiding or reducing maintenance immunosuppression. We herein review the literature on alemtuzumab in solid organ and composite tissue allotransplantation with an emphasis on clinical and mechanistic aspects of alemtuzumab. In summary, the use of alemtuzumab in solid organ and composite tissue allotransplantation shows excellent early results and holds potential for wider use in conjunction with immunosuppression minimization protocols.

Hemolytic uremic syndrome following Campath-1H induction

Hemolytic uremic syndrome (HUS) is a rare complication following solid organ transplantation. We report on a patient who underwent renal transplantation using Campath‐1H induction and tacrolimus maintenance therapy who developed HUS, which was managed by plasma exchange and switch to Rapamycin. However, graft function could not be restored.

Single shot of alemtuzumab as induction therapy after kidney transplantation is sufficient

In an earlier study, we were able to show that Tac monotherapy following 2 × 20 mg alemtuzumab induction is at least as effective as Tac‐based triple‐drug immunosuppression in cadaveric renal transplantation. We were interested to learn whether 1 × 30 mg of alemtuzumab is as effective as 2 × 20 mg. Patients of the initial study group (group A) received 20 mg alemtuzumab on days 0 and 2, and tac monotherapy from day 2 on. This group acted as control group for the new arm (group C), where patients were given only 1 × 30 mg alemtuzumab on day 0 followed by Tac monotherapy from day 2 on with the same target levels as in the control group. Frequency of rejection at 6 months was 15% in the control group compared to 6% in the study group and 20% at 12 months in group A versus 6% in group C (P = 0.034). Time to rejection was 4.9 months in group A and 0.8 in group C. One‐year patient survival was 98.5% in both groups, graft survival 96.9% in group A, and 98.5% in group C. Safety profile was similar in both groups apart from more viral and bacterial infections in group C. Single shot alemtuzumab induction of 30 mg is as effective as 2 × 20 mg in cadaveric renal transplantation.

Liver Transplantation for Nonalcoholic Steatohepatitis. Organ Waste or Successful Treatment of the New Epidemic? A Single Center Experience.: Abstract# 1500

1500 Liver Transplantation for Nonalcoholic Steatohepatitis. Organ Waste or Successful Treatment of the New Epidemic? A Single Center Experience. B. Kern,1 R. Sucher,1 J. Fritz,2 B. Feurstein,1 C. Fabritius,1 C. Boesmueller,1 R. Oellinger,1 J. Pratschke,1 S. Schneeberger.1 1Visceral-, Transplant-, Thoracic Surgery, Medical University, Innsbruck, Austria; 2Statistics and Informatics, Medical University, Innsbruck, Austria. Background: Nonalcoholic steatohepatitis (NASH) may become the leading indication for orthotopic liver transplantation (OLT). The aim of this study was to describe the clinical outcome of NASH patients compared to patients with other common indications for OLT. Methods: This is a retrospective analysis of 515 patients who underwent deceased-donor OLT between 2002 and 2012. Results: The incidence of NASH was 14,4% (74/515). Study population included 116 (22,5%) women and 399 (77,5%) men. NASH cohort compared to the nonNASH cohort showed no signifi cance on patient survival (p=0,109). Patients with a malignancy displayed a shorter overall survival (p=0,009). Average MELD score was 21,0, average BMI 25,3. Patients with a lower MELD at time of transplantation were associated with a signifi cantly better overall survival (p=0,043). BMI greater than 30kg/m2 had no impact on survival rates. Diabetes was diagnosed in 124 patients, compared to the patients with no evidence of diabetes overall survival was signifi cantly shorter (p=0,006). NASH patients with diabetes had similar overall survival and complications when compared to NASH patients without diabetes (p=0,242; p=0.112 respectively). Donor data such as BMI over 30 kg/m2, sever steatosis, age over 55 years and cold ischemic time over 14 hours had no impact on patient survival. Infection rate was signifi cantly higher in the NASH cohort (p=0,04). NASH patients with HCC were associated with a signifi cantly shorter overall survival compared to HCC patients with no evidence of NASH (p=0,02; see fi gure 1). Conclusion: Metabolic comorbidities such as diabetes signifi cantly impact on patient survival. NASH predicts an inferior outcome in patients with HCC compared to other liver diseases. Accurate preoperative treatment of metabolic disorders and intensifi ed infection prophylaxis should be considered in patients with NASH undergoing OLT. Criteria for OLT in patients with HCC and NASH should be revisited. Abstract# 1501 The Negative Predictive Value of Preoperative Stress Testing for NonFatal Cardiac Events After Orthotopic Liver Transplantation in the Modern Era. F. Niyazi, R. Patel, Y. Nasr, J. Perez, S. Mawri, M. Njeim, A. Yoshida, D. Moonka, S. Jafri, J. Schairer, K. Abdul-Nour. Internal Medicine, Henry Ford Health System, Detroit, MI. Aim: Studies evaluating functional stress testing as the means of preoperative cardiac clearance in patients awaiting orthotopic liver transplantation (OLT) have shown signifi cant variability in the prediction of major adverse cardiovascular events (MACE). Given increased co-morbid cardiac risk factors in our current era of transplant we evaluated the negative predictive value (NPV) of stress echocardiography (SE) for post-OLT survival and MACE in the modern era. Methods: We performed a retrospective review on 384 consecutive patients who received an OLT between 2007 and 2011. Data was collected on demographic characteristics, pertinent pre-operative laboratory results, echocardiographic studies and post-operative events. Mortality was confi rmed by public documents available via the Social Security Death Index. MACE was defi ned as a combined outcome of cardiac death, new onset congestive heart failure, nonfatal myocardial infarction, stroke or need for coronary revascularization. The NPV of SE for cardiac mortality and MACE were calculated using the subgroup of patients that achieved an adequate level of cardiac stress while undergoing testing. A SE was considered abnormal if there were wall motion abnormalities or drop in ejection fraction greater than 5%. Results: 384 consecutive patients received an OLT between January 2007 and November 2011. Over a 3 year post-operative follow-up period there were 82 total deaths, 17 cardiac deaths, 12 nonfatal myocardial infarctions, 15 new onset heart failure and 5 coronary revascularizations. 276 (72%) patients were evaluated by SE. Within the stress testing cohort of patients, 189 (68%) reached target heart rate for optimal stress testing. Hypertension (34%) and diabetes mellitus (25%) were prevalent in this group. A normal SE had a 98.4% NPV for cardiac mortality at 3 years of postoperative follow-up and a 92.51% NPV for MACE. Survival rate at 3 years postoperatively was 78.6%. Conclusion: The overall survival rate of liver transplant patients in our highly morbid recent liver transplant population is comparable to the national survival rates. The unadjusted NPV of SE was very strong for prediction of cardiac events. Well-thought evidence based strategies that incorporate other clinical predictors in the modern transplant population are still needed. Abstract# 1502 Post Liver Transplant Biliary Complications in Deceased Donor Liver Grafts: Analysis of Preservation Solution. R. Mangus, R. Chihara, T. Borup, A. Marshall, J. Fridell, C. Kubal, A. Tector. Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. 1502 Post Liver Transplant Biliary Complications in Deceased Donor Liver Grafts: Analysis of Preservation Solution. R. Mangus, R. Chihara, T. Borup, A. Marshall, J. Fridell, C. Kubal, A. Tector. Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Objective: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions are the two solutions used primarily in abdominal organ procurement in the U.S. Bile duct complications are common in the post liver transplant (LT) period and may be related to the arterial blood supply for the biliary system. Because HTK is much less viscous than UW, it has been hypothesized that this solution provides a better fl ush of the biliary microcirculation. Improved blood clearance from these small vessels may lower the risk for thrombus formation and improve post-transplant biliary perfusion leading to a lower risk of biliary complications. This study reviews the biliary complications in a large number of deceased donor LTs and compares outcomes for HTK and UW. Methods: Data were extracted using a retrospective review of all liver transplants between 2001 and 2013, with an extensive review of all endoscopic and percutaneous biliary imaging and post-transplant liver function enzymes. Our center uses doppler ultrasound and biliary imaging as fi rst evaluation for elevated liver enzymes, prior to biopsy, resulting in a large number of imaging studies. Primary outcomes included need for imaging, any leak, and stricture formation.