Andreas Tzakis

When and why portal vein thrombosis matters in liver transplantation: A critical audit of 174 cases

Objective:To identify complications associated with different techniques utilized to treat portal vein thrombosis (PVT) during primary liver transplantation and their impact on survival. Background:PVT remains an intricate problem in liver transplantation, and the long-term outcomes of patients with PVT who undergo transplantation are not well defined. Methods:We performed a retrospective cohort analysis of all consecutive adult patients who underwent primary isolated liver transplantation from 1998 to 2009 (median follow-up period, 89 months). The outcomes of patients with PVT were compared with those without PVT. Results:Among 1379 recipients, 174 (12.6%) had PVT at the time of transplantation [83 (48%) complete and 91 (52%) partial]. Among PVT patients with reestablished physiological portal inflow (PVT: physiological group; n = 149), 123 underwent thrombectomies, 16 received interpositional vein grafts, and 10 received mesoportal jump grafts. In 25 patients, physiological portomesenteric venous circulation was not reconstituted (PVT: nonphysiological group; 18 underwent cavoportal hemitranspositions, 6 renoportal anastomoses, and 1 arterialization). The PVT: nonphysiological group suffered a significantly increased incidence of rethrombosis of the portomesenteric veins and gastrointestinal bleeding, with a marginal 10-year overall survival rate of 42% (no PVT, 61%; P = 0.002 and PVT: physiological, 55%; P = 0.043). The PVT: physiological and no PVT groups exhibited comparable survival rates (P = 0.13). No significant differences in survival were observed between complete and partial PVT as long as physiological portal flow was reestablished. Conclusions:The subset of PVT patients requiring nonphysiological portal vein reconstruction was associated with higher complication rates and suffered diminished long-term prognoses. For the most severe PVT cases, a comprehensive approach is critical to further improve outcomes.

Refractory ascites after liver transplantation: an analysis of 1058 liver transplant patients at a single center.

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty‐two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.

Allogeneic uterus transplantation in baboons: surgical technique and challenges to long-term graft survival.

The authos declare no funding or conflicts of interest. Address correspondence to: James Fernandez, M.D., Ph.D., Department of Allergy and Clinical Immunology, Cleveland Clinic Foundation, Cleveland OH, 9500 Euclid Ave, A90, Cleveland, OH, 44195. E-mail: fernandezj2@ccf.org Received 21 May 2014. Accepted 22 May 2014. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9805-e50 DOI: 10.1097/TP.0000000000000320

Eculizumab Salvage Therapy for Antibody-Mediated Rejection in a Desensitization-Resistant Intestinal Re-Transplant Patient

The presence of elevated calculated panel reactive antibody (cPRA) and anti‐HLA donor specific antibodies (DSA) are high risk factors for acute antibody‐mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization‐resistant intestinal re‐transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18u2009000 MFI (mean fluorescent intensity) to below the positive cut‐off value of 3000 MFI and remains rejection free with a 2‐year follow‐up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization‐resistant patients.

Deceased Donor Uterine Transplantation: Innovation and Adaptation.

This commentary endeavors to share our practical experience in developing and implementing the first uterine transplant clinical trial in the United States. Uterine transplant is a promising novel treatment for uterine factor infertility. After reported successful live births after uterine transplant in Sweden, research teams around the world are either embarking on or are considering the development of uterine transplant protocols. Our observations on the applied rather than theoretical aspects of uterine transplantation research in human subjects are detailed in this article. Important among these considerations are composing a broad and experienced multidisciplinary team as well as performing adequate preclinical preparations, including ideally animal studies and practice organ procurements. Ethical preparation is tantamount to clinical preparation for the complexities inherent in uterine transplant, and our suggestions for updating the current ethical criteria for uterine transplant are outlined here. We also describe our perspectives on the strengths and weaknesses of living compared with deceased donor models. Finally, we describe how a strong program can recover and adapt in the face of setbacks to continue a path toward innovation.

Organ Shortage: The Greatest Challenge Facing Transplant Medicine

The success of organ transplantation as a treatment for end-stage organ disease has yielded a series of ethical quandaries originating from the issue of organ shortage. Scarcity of organs for transplantation necessitates formulation of just and fair allocation policies as well as ethically viable solutions to bridging the vast gap between organ supply and demand. The concept of “triage” provides a useful paradigm in which to contextualize the organ shortage issue. This entails subjugating the welfare of the individual patient for the benefit of the wider community as an ethically justified response to the challenge of scarcity.

Deceased donor uterine transplantation

OBJECTIVEnTo share our experience in performing the first-ever deceased-donor uterine transplant in the United States.nnnDESIGNnThis video uses an animation and footage from a uterine transplantation procedure to review the steps and techniques involved in performing a uterine transplant.nnnSETTINGnAcademic, multisite medical center.nnnPATIENT(S)nA reproductive-age patient with Mayer-Rokitansky-Kuster-Hauser syndrome.nnnINTERVENTION(S)nTransplantation of a viable uterus from a deceased donor.nnnMAIN OUTCOME MEASURE(S)nAssessment of posttransplantation uterine graft viability.nnnRESULT(S)nThis video article describes the essential steps in the uterine transplant process, including selecting an appropriate donor with no history of infertility or uterine malformations. Furthermore, a deceased donor should exhibit brain death but not cardiac death. We also review our inclusion criteria for suitable recipients. In this video we outline the key steps in a uterine transplantation procedure and demonstrate footage from an actual transplant procedure. These steps include establishing bilateral end-to-side vascular anastomoses between the donor uterine artery and vein and the recipients external iliac vessels. Once this has been completed and reperfusion noted of the donor uterus, connection to the recipient vaginal cuff is then performed.nnnCONCLUSION(S)nUterine transplantation, although currently experimental, has gained the potential to become the first true treatment for uterine factor infertility. This procedure can become a promising option for the approximately 1.5 million women worldwide for whom pregnancy is not possible because of the absence of the uterus or presence of a nonfunctional uterus. Deceased donor uterine transplantation will further serve to broaden accessibility for this procedure.

Partial bladder transplantation with en bloc kidney transplant - The first case report of a 'bladder patch technique' in a human

Transplantation of the urinary bladder has not been reported in humans. We transplanted a portion of the donor bladder with an en bloc kidney graft in a 12‐month‐old girl. The child had a congenital hypoplastic single kidney with an ectopic ureteral opening into the vagina. Her native bladder was extremely small. Bilateral kidneys were transplanted en bloc with their ureters connected to a patch of the donor bladder, which encompassed the bilateral ureterovesical junctions (UVJs) (bladder patch technique). Approximately one‐third of the donor bladder wall was used. The bladder patch reperfused well via blood supply from the ureters. Posttransplant cystoscopy with retrograde cystogram revealed a viable transplanted bladder with normal emptying of transplanted ureters. No reflux across the donor UVJs was seen in a voiding cystourethrogram. The child is doing well with normal renal function at 18‐month follow‐up.

Longterm outcomes of auxiliary partial orthotopic liver transplantation in preadolescent children with fulminant hepatic failure

By preserving part of the native liver, auxiliary partial orthotopic liver transplantation (APOLT) provides the advantage of potential immunosuppression (ISP) withdrawal if the native liver recovers but has had limited acceptance, especially in the United States, due to technical complications and low rates of native liver regeneration. No previous study has evaluated APOLT specifically for preadolescent children with fulminant hepatic failure (FHF). This population might benefit especially based on greater capacity for liver regeneration. Data from 13 preadolescent children who underwent APOLT were compared to 13 matched controls who underwent orthotopic liver transplantation (OLT) for FHF from 1996 to 2013. There were no significant differences in patient demographics or survival between the 2 groups. However, all surviving OLT recipients (10/13) remain on ISP, while all but 1 surviving APOLT recipient (12/13) showed native liver regeneration, and the first 10 recipients (76.9%) are currently off ISP with 2 additional patients currently weaning. In our experience, APOLT produced excellent survival and high rates of native liver regeneration in preadolescent children with FHF. This represents the largest series to date to report such outcomes. Liberating these children from lifelong ISP without the downside of increased surgical morbidity makes APOLT an attractive alternative. In conclusion, we therefore propose that, with the availability of technical expertise and with the technical modifications above, APOLT for FHF should be strongly considered for preteenage children with FHF. Liver Transplantation 22 485‐494 2016 AASLD

Uterine viability in the baboon after ligation of uterine vasculature: a pilot study to assess alternative perfusion and venous return for uterine transplantation

OBJECTIVEnTo assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively.nnnDESIGNnProspective, observational study.nnnSETTINGnBaboon breeding colony.nnnANIMAL(S)nSix naïve female Papio hamadryas baboons with indicators of normal reproductive function.nnnINTERVENTION(S)nThree baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals.nnnMAIN OUTCOME MEASURE(S)nPostoperative uterine and ovarian viability.nnnRESULT(S)nNear-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed.nnnCONCLUSION(S)nDisruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy.