Intra-Operative Contrast Cholangiography in Living Donor Liver Transplantation: The ISMETT Experience.

BACKGROUND: We evaluated the clinical impact of donor biliary anatomy discrepancies (DBAD) achieved by comparing pre-operative evaluation obtained with magnetic resonance (MR)/magnetic resonance cholangiopancreatography (MRCP) imaging, with intra-operative cholangiography (IOC) on the living related liver donor (LDLT) and recipient. METHODS: This single-center, retrospective study included 97 consecutive adult-to-adult (A2A) LDLT performed in our hospital in the last 12 years. Donor sex and age, living donors with biliary and/or vascular anomalies, recipient age, sex, primary etiology, re-transplantation, Model of End-Stage Liver Disease score, co-morbidities, arterial and biliary recipient complications assessed on the basis of clinical follow-up were collected and analyzed for significance through the use of a multivariate linear regression model. RESULTS: Biliary complications in the donor (DBC) were detected in 8 (8.2%) cases. Biliary complications in the recipients (RBC) were detected in 38 (39%) cases. DBADs were found in 32 (33%) cases and resulted strictly related to RBC (P = .05). CONCLUSIONS: After adjusting for co-variables, results of the linear regression analysis confirmed that DBAD is an independent predictor of RBC, but it is not significantly associated with vascular complications or patient survival. We showed that RBCs after LDLT were influenced by DBAD.

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.

In vivo multiclonal transfer of bla(KPC-3) from Klebsiella pneumoniae to Escherichia coli in surgery patients.

During active surveillance at the Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT, Palermo, Italy) with the CARBA screening medium, five pairs of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae and Escherichia coli strains were isolated in each of five colonized patients. In each patient, lateral gene transfer was demonstrated by comparing K. pneumoniae and E. coli strains, both possessing KPC-3, Tn4401a and pKpQIL-IT elements. The isolates were found to be multiclonal by multilocus sequence typing (sequence type (ST) 512 related to ST258, and ST307 belonging to a clonal complex different from the habitual sequence clone ST258 isolated in Italy) and pulsed-field gel electrophoresis. The results of our study highlight the easy transfer of KPC among Enterobacteriaceae colonizing the human intestine, and the active and careful surveillance required to identify and prevent the spread of these multidrug-resistant microorganisms.

Recipient-donor age matching in liver transplantation: a single-center experience.

OBJECTIVE: The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching. METHODS: We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009. RESULTS: Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02-15.47; P = .046). CONCLUSIONS: The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients.

Two brothers with renal and hepatic polycystic disease treated with combined liver and kidney transplantation: a case report.

We report two brothers with renal and hepatic polycystic disease who developed end-stage renal failure, requiring hemodialysis, and organomegaly syndrome related to the gigantic size of the liver and both kidneys. Although there was no liver failure, combined liver and kidney transplantation was performed owing to worsening of the clinical condition. In both cases, successful transplantation was accomplished with intra-abdominal engraftment of the liver and kidneys through the same abdominal incision.

Marrow-derived mesenchymal stem cells restore biochemical markers of acute liver injury in experimental model.

Bone marrow-derived mesenchymal stem cells were investigated as prompters of liver regeneration in an experimental model of acute hepatic injury. A model was created in Wistar rats through intraperitoneal injection of carbon tetrachloride (CCl4). Bone marrow-derived mesenchymal stem cells collected from the long bones of 10 Wistar rats were intravenously infused 24 hours after induction of acute liver failure in 16 rats, group A. In group B, the control group, 16 rats received a peritoneal injection of CCl4, and an intravenous infusion of normal saline solution. All rats were sacrificed at 2, 3, 4, and 7 days post-CCl4 injection to examined biochemical markers and pathological appearances. The platelet counts were higher in group A versus group B on post-CCl4 infusion days 2 (P = .02) and 3 (P = .001), as were the transaminase trends in glutamic oxaloacetic (P = .002), and glutamic-pyruvic transaminases (P < .0001). Pathological examination showed a greater grade of hepatocellular necrosis with neutrophilic infiltration in group B (P = .02). In conclusion, infusion of bone marrow-derived mesenchymal stem cell resulted in a less aggressive picture of hepatic damage.

Development of a standardized model for liver failure in pigs: anatomopathophysiologic findings after extended liver resection.

Eighteen pigs weighing a mean 19 ± 4 kg, were divided into group 1 (n = 2), that underwent resection of the left lateral lobe, group 2 (n = 2), resection of the left median and right median lobes; and group 3 (n = 18), resection of the left lateral, left median, right median, and right lateral lobes. All animals were followed for 5 days. Liver failure (n = 8) leading to animal death within 3 days after surgery was observed in 65% of group 3, whereas no group 1 or 2 animal experienced liver insufficiency. Multivariate analysis revealed that the extent of liver resection expressed as a percentage of total body weight <2.3%, international normalized ratio > 1.6 as postoperative day 2, serum bilirubin > 4.2 on postoperative day 2, and serum lactates > 9 mmol/L after resection were independent predictors of liver failure (P < .05). The number of resected liver lobes was not a good predictor of liver failure in swine, whereas the extent of resection expressed as a percentage of total body weight was an independent predictor of early liver failure. A resected liver-to-body weight ratio >2.3% was associated with a 65% probability of developing liver insufficiency. This parameter may be useful when developing a model of liver failure after extended liver resection in swine.

Laparoscopic approach for an intra-abdominal kidney allograft nephrectomy after pediatric transplantation: a case report.

We report a case of minimally invasive nephrectomy of a kidney transplanted into the abdominal cavity in a child. A 15-year-old girl underwent transplantation with a cadaveric donor kidney due to congenital pyelonephritis, vesicoureteral reflux, and secondary bladder atrophy. The transplant was complicated by hyperacute rejection, cytomegalovirus infection, and anastomotic stenosis of the Bricker neobladder. After recurrent urinary tract infections, the patient was reintroduced to hemodialysis in 2010. After pneumo-peritoneum, we placed 2 10-mm trocars in the hypochondrium and left side and 2 5-mm in the left iliac fossa and right upper quadrant. The transplanted kidney was skeletonized, the artery and vein were cut to the end-to-side anastomoses to the juxta-renal aorta and cava using an automatic 35-mm, stapler, and the ureter was dissected and closed with clips. Via a Pfannestiel minilaparotomy we extracted the allograft. The patient was discharged on the third postoperative day. After 4 months of follow-up, she is alive an on dialysis. Laparoscopic nephrectomy of a kidney transplanted into the abdominal cavity is feasible and safe in centers with skilled minimally invasive techniques.

The Charlson comorbidity index as a predictor of outcomes in liver transplantation: single-center experience.

Several comorbidity indices, such as the Child-Turcotte-Pugh (CTP) score and the Model for End-Stage Liver Disease (MELD) score, have been used to optimize available organ resources and adjust priorities in diagnosis and allocation of grafts for patients who are candidates for liver transplantation. There have also been various attempts to create instruments to accurately predict outcomes after liver transplantation, but none has proved to be truly applicable, with the exception of the Charlson comorbidity index (CCI). We retrospectively reviewed data of 221 liver recipients, including living-related liver transplantation and multiple organ transplantation performed between January 2006 and September 2009. Survival analysis revealed a significant association of the CCI with decreased posttransplantation patient survival (P = .003). Furthermore, Kaplan-Meier plots and log-rank test showed a significant association between graft survival and the score (P = .039). Our data suggest that the CCI is a simple tool for the evaluation of comorbidity and that increased preoperative patient comorbidity increases the risk of graft loss and patient death after liver transplantation. The CCI should be considered an important tool for improving patient care because of its potential applications for patient management.

The first report of orthotopic liver transplantation in the Western world.

Until the present time, the first experimental liver transplant which led to the development of human liver transplantation is attributed to C. Stuart Welch who performed a heterotopic transplant in the canine species in 1955. In 1956, Jack Cannon is credited with the first animal orthotopic liver transplant although the species was not disclosed. This report is intended to set the historical record straight by acknowledging that Vittorio Staudacher in 1952 was the first to perform a liver transplant in a large animal model.

Fully covered metallic stents in biliary stenosis after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: Data from a preliminary study suggested that the placement of a fully covered metal stent may be a valid alternative to surgery in patients who do not respond to standard endoscopic treatment. The aims of the current study were to evaluate the clinical success of self-expandable metallic stents (SEMS) in a large cohort of patients and with a long followup,and the effectiveness of SEMS placement as a first-line procedure. MATERIALS AND METHODS: Between January 2008 and August 2010, 54 consecutive patients with biliary complications following orthotopic liver transplantation were treated with SEMS placement:39 after failure of conventional endoscopic therapy (Group I), and 15 with no previous endoscopic treatment who were undergoing SEMS placement as first-line treatment for complications(Group II). RESULTS: In Group I, resolution after SEMS removal was observed in 71.8% of patients. Mean followup after resolution was 22.1 ±10 months. Recurrence of the complication was observed in 14.3%of patients after a mean of 8.5 months and SEMS migration was observed in 33.3% of patients. In Group II, resolution was observed in 53.3% of patients.Mean follow-up after resolution was 14.4±2.2 months. Recurrence was observed in 25% of patients and SEMS migration was observed in 46.7 %. CONCLUSIONS: For endotherapy of biliary complications after orthotopic liver transplantation, metallic stents should not be used as the primary modality. In patients in whom the standard approach fails, treatment with temporary SEMS placement can solve biliary complications in almost three-quarters of cases; however stent migration(33 %) remains a problem.

Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study.

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

Unusual presentation of left hepatic vein in deceased donor: case report.

An anomaly of the left hepatic vein was discovered in a deceased donor for whole liver transplantation. This vein was attached by a thin bridge of tissue to the suprahepatic inferior vena cava cuff, which received the right and middle hepatic vein in a common trunk. The left hepatic vein and the common trunk drained together into the right atrium. The thin bridge of tissue connecting the 2 independent vessels was severed, and ex situ reduction of the left lateral segments was using a harmonic scalpel. Although a graft with reduced size is not ideal, ex situ reduction should be considered a valuable option when viability of the left lateral segments is uncertain in the donor or at the back table.

Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants: clinical relevance.

A lack of deceased human donor livers leads to a significant mortality in patients with acute-on-chronic or acute (fulminant) liver failure or with primary nonfunction of an allograft. Genetically engineered pigs could provide livers that might bridge the patient to allotransplantation. Orthotopic liver transplantation in baboons using livers from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs (n = 2) or from GTKO pigs transgenic for CD46 (n = 8) were carried out with a clinically acceptable immunosuppressive regimen. Six of 10 baboons survived for 4-7 days. In all cases, liver function was adequate, as evidenced by tests of detoxification, protein synthesis, complement activity and coagulation parameters. The major problem that prevented more prolonged survival beyond 7 days was a profound thrombocytopenia that developed within 1 h after reperfusion, ultimately resulting in spontaneous hemorrhage at various sites. We postulate that this is associated with the expression of tissue factor on platelets after contact with pig endothelium, resulting in platelet and platelet-peripheral blood mononuclear cell(s) aggregation and deposition of aggregates in the liver graft, though we were unable to confirm this conclusively. If this problem can be resolved, we would anticipate that a pig liver could provide a period during which a patient in liver failure could be successfully bridged to allotransplantation.

Successful lung transplantation in an HIV- and HBV-positive patient with cystic fibrosis.

Prior to the advent of highly active antiretroviral therapy (HAART), HIV-infected patients were usually not considered as transplant candidates because of the poor prognosis of their underlying disease and concerns regarding the potential detrimental effects of immunosuppression on viral load and immune status. However, with the significant HAART-associated improvements in morbidity and mortality, good short-term outcomes after liver and kidney transplantation for patients with HIV infection have been reported. Nevertheless, HIV infection is currently considered a contraindication to lung transplantation in most transplant centers worldwide. The results of a double lung transplant performed in an HIV and HBV co-infected patient with cystic fibrosis (CF) and end-stage respiratory failure (ESRF) are presented after a 2-year follow-up. Approval of and recommendations for the management of this patient were obtained from the Italian National Center for Transplantation as an extension of the ongoing Italian protocol for liver and kidney transplantation in HIV-infected individuals. The operation was successful and the patient recovered rapidly after surgery. A cautious infectious and immunosuppressive management allowed so far the avoidance of major infectious complications and rejection. To the best of our knowledge, this is the first report of lung transplantation in an HIV and HBV co-infected patient.

Clinical burden of screening asymptomatic patients for coronary artery disease prior to liver transplantation.

The aim of this study is to assess the clinical burden of silent coronary artery disease (CAD) in cirrhotic candidates for liver transplantation (LT), and to evaluate the usefulness of a CAD screening approach. Between July 1999 and January 2006, we evaluated 627 LT candidates. All of them underwent a detailed clinical history. Sixteen had a previous diagnosis of CAD or symptoms suggestive (2.5%). The remaining 611 underwent further tests according to a predefined protocol, including EKG, echocardiogram and, on the basis of CAD risk factors, heart stress tests. Selective coronary angiography (SCA) was performed in the 30 patients with positive heart stress test: in only 2 did SCA show any CAD, and in both it was subcritical disease requiring neither intervention nor contraindicating LT. The 611 screened patients continued their follow-up until study closure or death. No coronary events occurred in the study population in a mean follow-up of 32.50 months (+/- 23.67 DS). No perioperative mortality related to CAD occurred in the 233 transplanted patients. In conclusion, no prognostic advantage was achieved by following a strict CAD screening protocol, leading us to believe that the cost-effectiveness of a similar screening can be unacceptably high in our setting.

Technical aspects of living-related liver donation: single-center experience.

Living-related donor liver transplantation is the newest and both technically and ethically most challenging evolution in liver transplantation and has contributed to reduction in donor shortage. We briefly report the technical aspects of surgical procedures performed to achieve a partial graft from a live donor. Eighty-four adult and two pediatric recipients underwent living-related donor liver transplantation at our center. There were no donor deaths, and all patients returned to their normal activities after the perioperative period. This single-center experience may contribute to refinement of the surgical technique required to improve the outcome of these complex operations.