An Improved Classification of Kidney Function Recovery Using Estimated Glomerular Filtration Rate Slope Post-transplantation.

BACKGROUND: The impact of renal function recovery on graft survival was examined using estimated glomerular filtration rate (eGFR) slope after kidney transplantation (GAP classification); this was compared to the conventional classification of immediate graft function (IGF), slow graft function (SGF), and delayed graft function (DGF). MATERIALS AND METHODS: Overall, 541 cases of cadaveric renal transplants were reviewed from a prospective transplant database. eGFR and its slope were measured using the harmonic mean over the first week post-transplantation. Next, 495 kidney transplant recipients from an independent institution were assessed to determine the prognostic value of graft function based on the eGFR slope. RESULTS: The main discrimination of eGFR slopes occurred within the first 7 days. Three groups in the GAP classification (Good graft function, Average graft function, Poor graft function) were defined based on eGFR slope tertiles: good graft function (GGF), average graft function (AGF), and poor graft function (PGF) were defined based on the ΔCrCL per day over the first 7 days: <1 mL/min, 1-4 mL/min, and >4 mL/min, respectively. When applied to the validation cohort, the 5-year graft failure was 20% for the PGF group, 4% for the AGF group, and 3% for the GGF group. Multivariable Cox regression analysis demonstrated better prediction of long-term graft function with the new classification (C statistic 0.49 [old)] vs 0.61 [new]). CONCLUSION: The new GAP criteria were better at predicting long-term graft survival and renal function compared to the conventional classification system, and deserve further consideration in future studies.

Evaluation of herpes simplex virus infection morbidity and mortality in pancreas and kidney-pancreas transplant recipients.

BACKGROUND: Infections remain a major cause of morbidity and mortality in solid organ transplant recipients. An increased risk of up to 50% of herpes simplex virus (HSV) reactivation in transplant recipients in the first months posttransplantation was well-documented during the pre-cytomegalovirus prophylaxis era. Previous reports suggest that these patients are likely to experience a more aggressive disease course and a higher rate of acyclovir-resistant HSV. No data currently exist regarding the course of HSV infection in pancreas or pancreas-kidney transplant (PKT) recipients. The goal of this study was to evaluate the incidence and severity of HSV infections in pancreas transplant and PKT recipients. STUDY DESIGN: We analyzed a transplant patient database of the Royal Victoria Hospital to identify 137 pancreas transplant or PKT performed between January 1999 and October 2010. A retrospective chart review was subsequently performed to evaluate the incidence and severity of herpetic infections post transplantation. RESULTS: Our findings show that the incidence of HSV infection in our patients was approximately 10% (10/98 cases). The majority of infections (80%) took place within the first 2 years after the transplantation. Most patients (90%) experienced a uniform, mild disease course and responded well to treatment. One patient died of an unrelated cause. Six patients were treated in hospital with a mean stay of 12.3 ± 6.35 days. The initial immunosuppressive regimen remained unchanged for half of the affected patients. None of our patients developed a drug-resistant HSV. CONCLUSION: These findings are intriguing and warrant a larger, multicenter, prospective study. Most important, they suggest that the new incidence of HSV reactivation is now much lower in the "cytomegalovirus prophylaxis era" and that with timely diagnosis and proper treatment most patients recover well from their HSV infections and respond to the current treatment regimens.

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy. METHODS: In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child-Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt. RESULTS: Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8-8.5 cm), which decreased with tace to 5.0 cm (range: 3.3-7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival. CONCLUSIONS: The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.

Evaluation of varicella zoster virus infection morbidity and mortality in pancreas and kidney-pancreas transplant recipients.

BACKGROUND: Solid organ transplant recipients are at increased risk of infection due to chronic immunosuppression. The incidence of varicella zoster virus (VZV) infection is known to be increased in these patients compared with the immunocompetent population. Previous reports suggested that these patients are likely to experience a morbid disease course. Few data currently exist on the course of VZV infections in pancreas or pancreas plus kidney (PK) transplant recipients. OBJECTIVE: The goal of this study was to evaluate the incidence and severity of VZV infections in pancreas or PK recipients. STUDY DESIGN: We analyzed the transplantation patient database of the Royal Victoria Hospital, identifying 137 pancreas or PK transplantation procedures performed between January 1999 and October 2010, among which we included 98 patients in the study. We subsequently performed a retrospective chart review to evaluate the incidence and severity of VZV infections posttransplantation. RESULTS: Our analysis revealed that 11/98 patients developed VZV infections. The majority of infections (~90.9%) occurred within the first 5 years. Most patients (63.6%) were treated on an outpatient basis, whereas only 4 (36.4%) were hospitalized with a mean hospital stay of 9.5 ± 8.42 days. The initial immunosuppressive regimen remained unchanged for the majority of patients. All patients experienced a mild disease course without intensive care unit admission or death. Only 3 patients (27.3%) developed postherpetic neuralgia. CONCLUSION: These findings suggest that with timely diagnosis and proper treatment, most patients recover well from a VZV infection.

Prolonged lymphopenia following anti-thymocyte globulin induction is associated with decreased long-term graft survival in liver transplant recipients.

BACKGROUND AND AIM: Induction with anti-thymocyte globulin (ATG) during solid organ transplantation is associated with an improved clinical course and leads to prolonged lymphopenia. This study aims to investigate whether prolonged lymphopenia, caused by ATG induction, has an impact on patient and graft survival following liver and kidney transplantation. PATIENTS AND METHODS: This was a single-center, retrospective study. A total of 292 liver and 417 kidney transplants were performed with ATG induction (6 mg/kgr, divided into four doses), and the transplant recipients were followed for at least three months. The average lymphocyte count for the first 30 days after the operation was calculated, and the cut-off value for defining lymphopenia was arbitrarily set to ≤ 500 cells/mm(3). RESULTS: There were 210 liver transplant recipients (71.9%) who achieved prolonged lymphopenia, whereas the remaining 82 recipients (28.1%) did not. The mean survival time of these patient groups was 10.27 and 12.71 years, respectively (p = 0.1217), and the mean graft survival time was 8.98 and 12.25 years, respectively (p = 0.0147). Of the kidney transplant patients, 330 (79.1%) recipients achieved prolonged lymphopenia, whereas the remaining 87 (20.9%) did not. The mean survival time of these patient groups was 13.94 and 14.59 years, respectively, (p = 0.4490), and the mean graft survival time was 11.84 and 11.54 years, respectively (p = 0.7410). CONCLUSION: The efficacy and safety of ATG induction partially depend on decreased total lymphocyte counts. Following ATG induction in liver transplant recipients, a reasonable average lymphocyte count during the first postoperative month would be above 500 cells/mm(3).

Allocation of renal grafts to older recipients does not result in loss of functioning graft-years.

BACKGROUND: Most deceased donor kidney allocation protocols are based on waiting time and do not take into account either recipient's life expectancy. This study investigates whether graft survival is affected by patient life expectancy. METHODS: A total of 640 adult kidney transplants were performed. Recipients were divided in group A (patients ≤ 50 years) and group B (patients > 50 years). The status of graft+recipient combination was characterized as: a) deceased recipient with functional graft, b) alive recipient with functional graft and c) deceased or alive recipient with nonfunctional graft. RESULTS: Mean kidney recipient survival was 15.15 (95% CI: 14.54, 15.77) and 12.40 (95% CI: 11.47, 13.33) years for groups A and B respectively (p < 0.0001). Mean graft survival was 13.62 (95% CI: 12.81, 14.43) and 12.42 (95% CI: 11.59, 13.25) years for groups A and B respectively (p=0.6516). Non-functional grafts were identified in 18.4% (n=57) and 16.4% (n=54) of group A and B respectively. CONCLUSIONS: Allocation of renal grafts to older patients does not result in significant loss of graft-years. Recipients' life expectancy has a small impact on graft survival. We should not deviate from the basic principles of equality, when kidney allocation systems are designed.

Transporting live donor kidneys for kidney paired donation: initial national results.

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.

Retroperitoneoscopic living donor nephrectomy: initial experience with a unique hand-assisted approach.

The retroperitoneoscopic (RP) approach to live donor nephrectomy (LDN) may be advantageous for the donor because it avoids mobilization of peritoneal organs and provides direct access to the renal vessels. Notwithstanding, this approach is not popular, likely because of the steeper learning curve. We feel that hand-assistance (HA) can reduce the learning curve and in this study, we present our experience with a novel hand-assist approach to retroperitoneoscopic live donor nephrectomy (HARP-LDN). Over a one-yr period, 10 consecutive patients underwent left HARP-LDN with a mean body mass index of 29 and three with prior left abdomen surgery. The surgical technique utilizes a 7 cm, muscle-sparing incision for the hand-port with two endoscopic ports. Operative time was an average of 155 min., with no open conversions. Mean blood loss was 68 mL, and warm ischemia time was 2.5 min. Hospital stay averaged 2.7 d with postoperative complications limited to one urinary retention. Our modified HARP approach to left LDN is safe, effective and can be performed expeditiously. Our promising initial results require a larger patient cohort to confirm the advantages of the hand-assisted retroperitoneal technique.

Re-vascularization may not increase graft survival after hepatic artery thrombosis in liver transplant recipients.

BACKGROUND AND AIM: Hepatic artery thrombosis (HAT) occurs in 3% to 11% of all liver transplantations. Some authors have reported good outcomes with early thrombectomy. To investgate the impact of re-vascularization on graft survival. METHODS: A total of 566 primary, cadaveric, single organ, adult liver transplants were performed. Hepatic arterial Doppler was performed routinely and patients with abnormal findings during the first two post-operative weeks were reexplored. Abnormal findings after this time-point were verified by non-invasive angiogram. The 47 patients that were diagnosed with arterial thrombosis, either intra-operatively or by angiogram, were divided into three groups. No further action was taken for group A, thrombectomy alone was performed for group B1, thrombectomy and anastomotic revision was employed for group B2. RESULTS: Arterial thrombosis was diagnosed in 47 (8.3%) patients. Mean patient survival was 42, 62 and 98 months for groups A, B1 and B2 respectively (p: 0.0629). Mean graft survival was 24, 29 and 60 months for groups A, B1 and B2 respectively (p: 0.3386). Re-transplant incidence was 8.7%, 40% and 28.6% for groups A, B1, and B2 respectively (p: 0.035). CONCLUSIONS: Early diagnosis of HAT by surveillance Doppler may lead to improved recipient survival secondary to earlier re-transplantation and not because of successful graft re-vascularization.

Lengthy cold ischemia time is a modifiable risk factor associated with low glomerular filtration rates in expanded criteria donor kidney transplant recipients.

The proportion of expanded criteria donor (ECD) kidneys transplanted in North America is steadily increasing. By definition, graft survival is shorter for ECD than standard criteria donor (SCD) kidneys. Seeking to identify factors associated with low posttransplant glomerular filtration rates (GFR), we retrospectively reviewed data on 390 consecutive patients transplanted in our center from January 1999 to December 2006 including 78% SCD and 22% ECD by UNOS criteria. We analyzed donor and patient characteristics, HLA mismatches, cold ischemia time (CIT) and delayed graft function (DGF). Pulsatile perfusion was not used. The average CIT was 14.6 hours for all SCD and ECD cases. All patients received thymoglobulin, a calcineurin inhibitor, mycophenolate mofetil, and steroids. The only factor associated with low estimated GFR in the entire ECD cohort was CIT. The average CIT for the ECD group was 18.3 hours, whereas it was only 13.6 hours for those in the SCD group (P < .001). We observed that at 6 months posttransplant, those in the ECD group are 2.2 times more likely (odds ratio, 2.23; 95% confidence interval, 1.065-4.654; P = .033) to have an estimated GFR < or =50 mL/min/1.73 m(2) compared with those in the SCD group for CIT up to 18 hours. The higher odds ratio for low estimated GFR was sustained at 3 years posttransplant. In our center, a lengthy CIT was an early risk factor associated with impaired renal function. We concluded that all efforts should be made to reduce CIT.

Recovery of graft function early posttransplant determines long-term graft survival in deceased donor renal transplants.

INTRODUCTION: Because kidneys show remarkable resilience and can recover function, we examined the impact on long-term graft survival in deceased donor renal transplants of both immediate graft function (IGF) and the rate of renal function recovery over the first 3 months after transplantation. METHODS: We included all cadaveric renal transplants from 1990 to 2007 (n = 583). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined by serum creatinine falls of <20% or >20% in the first 24 hours posttransplant respectively. Recovery of renal function was expressed as either the best creatinine clearance (CrCl) in the first 3 months post-renal transplantation (BCrCl-3mos) as calculated using the Cockcroft-Gault formula or as a percentage of actual versus expected value (as calculated from the donors' CrCl at procurement). RESULTS: There were 140 (23.6%) subjects who received extended criteria donor (ECD) organs. The overall graft survival at 1 and 5 years was 87.8% and 74%, respectively. The 5-year graft survivals for patients with IGF, SGF, and DGF were 85%, 76%, and 54%, respectively (P < .02). ECD kidneys showed twice the DGF rate (49% vs 23%, P < .001). BCrCl-3mos of <30 mL/min displayed a 5-year graft survival of 34%; 30 to 39 mL/min, 72%; 40 to 49 mL/min, 85%; and >50 mL/min, 82% (P < .001). Similarly, a recovery within 90% of expected CrCl in the first 3 months posttransplant correlated with 5-year graft survival of 81%; a recovery of 70% to 90%, with 65%; and a recovery of <70%, with 51% (P < .001). CONCLUSION: Early graft function in the first 3 months showed a significant impact on long-term graft survival after deceased donor renal transplantation.

Delayed graft function has an equally bad impact on deceased donor renal graft survival in both standard criteria donors and expanded criteria donors.

INTRODUCTION: The use of expanded criteria donors (ECDs) is still limited because of inferior graft survival compared to standard criteria donors (SCDs). We assessed the impact of immediate graft function (IGF) on renal graft survival among recipients of SCD and ECD grafts to determine whether these kidneys performed equally well under "ideal" conditions favoring IGF. METHODS: We included all cadaveric renal transplants performed from 1990 to 2002 (n = 335). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined as a serum creatinine fall by <20% versus >20% in the first 24 hours posttransplant, respectively. Non-death censored actual graft survivals are reported herein. RESULTS: Seventy-two of the 335 subjects (21.5%) received organs from ECDs and displayed IGF in 54.7%, SGF 16.2%, and DGF 29.1%. Among SCDs, the SGF and DGF rates were 15.3% and 23.4%, respectively. In ECD, the SGF and DGF rates were 19.4% and 50% (P < .02). Actual graft survivals at 1 and 5 years was 86.3% and 70.4%, respectively. Patients with IGF had higher actual graft survival at 5 years compared to SGF and DGF (83.5% vs 74.1% vs 45.4%). DGF had an equally bad impact on actual 5-year graft survival in SCDs and ECDs (42.6% vs 50%). CONCLUSION: DGF has a strong detrimental impact on 5-year graft survival. There is a higher rate of DGF in ECD versus SCD kidneys. The detrimental impact on 5-year actual graft survival is equal in SCD and ECD kidneys. Minimizing DGF should be our goal.

CD1d-mediated interaction between activated T cells and B cells is essential to B-cell proliferation and anti-alpha-Gal antibody production.

Antibody-mediated rejection is central to ABO-incompatible transplantation as well as to xenotransplantation. The carbohydrate structure of xenoantigen alpha-Gal is highly analogous to the human blood group antigens. Both require memory B-cell activation for antibody production. We hypothesized that B cells, reactive to the alpha-Gal xenoantigen, required the presence of fully activated T cells to survive and proliferate in vitro. This hypothesis was contrary to the traditional theory that the response of B cells to carbohydrate antigens is T cell independent (Wong and Arsequell: Immunobiology of Carbohydrates. New York: Kluwer; 2003). When we compared the capacity of B cells to proliferate, we observed that activated T cells were necessary for B-cell proliferation. However, this proliferation was independent of the presence of antigen. A relevant question was also to investigate the role of the specific class of T cells: the CD1d-restricted iNKT (iNKT) cells in the activation of alpha-Gal-reactive B cells. The iNKT cells are reactive to glycolipids and capable of producing both Th1 and Th2 cytokine responses. We therefore wanted to determine the role of the iNKT cells as mediators of a Th2-type response when B cells were exposed to a glycolipid antigen extracted from pig red blood cells, which express blockade of the alpha-Gal epitope. We observed that the interaction between B cells and iNKT cells prevents B-cell proliferation and anti-alpha-Gal antibody production.

Liver transplantation for metastases from a bile duct carcinoid.

BACKGROUND: A 29-year-old woman who presented with fatigue and jaundice was found to have an obstructing mass at the bifurcation of the bile duct. The patient underwent a successful left hepatectomy with resection of the bile duct bifurcation and a reconstruction with a right hepaticojejunostomy. Pathology revealed an atypical carcinoid tumour of the left extrahepatic bile duct, with perineural and lymphatic invasion. The patient subsequently developed multiple metastases in the remaining liver. METHODS: In the absence of extrahepatic disease, the patient underwent a successful liver transplant. RESULTS: Two years later she remains disease-free. DISCUSSION: To our knowledge this is the first report of a biliary carcinoid treated with hepatectomy and finally with liver transplantation, with excellent results. The biological behaviour of these rare tumours mandates aggressive surgical management.

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

Leukoreduction and acute rejection in liver transplantation: an interim analysis.

BACKGROUND: Little is known about the effect of blood transfusions and leukoreduction on acute rejection in liver transplantation. The purpose of this study was to assess the impact of leukoreduction on the occurrence of early rejection episodes in liver transplantation. METHODS: In 1999, mandatory leukoreduction was implemented in our program. Data from 339 consecutive liver transplant recipients were analyzed with attention to the time period as a proxy for leukoreduction, the number of transfusions, the wait list status, the hepatitis B or C status, the recipient age, and the type of immunosuppression. RESULTS: Using an early (6-month) rejection-free graft survival model, we observed that introduction of leukoreduction was independently associated with fewer rejection episodes (P =.001). Despite the lower rejection rate, due to a regimen of tacrolimus and antithymocyte globulin, the effect of implementation of leukoreduction remained significant (P =.021). CONCLUSION: The use of leukoreduction is associated with fewer early rejections, irrespective of the type of immunosuppression. These data support an exploration of the immunomodulatory effect of leukoreduction.

History of C2 monitoring in heart and liver transplant patients treated with cyclosporine microemulsion.

Therapeutic drug monitoring of CsA has evolved since the introduction of CsA microemulsion. The purpose of the present review is to summarize the history of CsA concentration 2 hours postdose (C2) monitoring in heart and liver transplantation. C2 has been shown to be the best single time point that correlates with the area-under-the-curve, with a correlation coefficient (r2) ranging between .83 and.93. C2 monitoring (300 to 600 ng/mL) has resulted in a significant clinical benefit in long-term heart and liver transplant patients compared to trough level (C0) monitoring. Moreover, a C2 range of 300 to 600 ng/mL resulted in a similar calcineurin inhibition compared to a C2 range of 700 to 1000 ng/mL or a C0 range of 100 to 200 ng/mL while being less injurious to renal function. In de novo liver transplant patients not receiving induction therapy, the achievement of a target C2 of 850 to 1400 ng/mL by postoperative day 3 has resulted in a low acute rejection rate. Furthermore, C2 monitoring has been associated with a lower rejection rate in hepatitis C virus (HCV)-negative patients and with an overall lesser severity of acute rejection compared to C0 monitoring. In de novo heart transplant patients who receive antithymocyte globulin induction, a lower C2 range may be sufficient to prevent rejection and renal dysfunction. Future studies should help to fine-tune the optimal C2 range in heart or liver transplant patients receiving induction therapy and different maintenance immunosuppressive combinations.

Ureteral implantation technique and urologic complications in adult kidney transplantion.

AIM: To assess the incidence of urological complications and hematuria after adult kidney transplantation using the Lich-Gregoire (LG) versus the Taguchi (T) ureteral implantation technique. METHODS: We performed a retrospective analysis of 212 consecutive kidney transplants from our institution using an access database. RESULTS: Sixty four patients underwent ureteral implantation using the T technique, and the other 148, the LG implantation. Both groups were matched for donor/recipient characteristics and for cold/warm ischemia times. There were 23 urological complications in 17 patients. Twenty-seven patients developed complicated hematuria. The rates of urinary leak and ureteral stones were not different. There was a higher incidence of permanent ureteral strictures using the LG technique (P =.05). T technique was associated more frequently with hematuria, but there was no difference in the length of stay. CONCLUSIONS: We identified an increased incidence of permanent strictures with the LG technique. The rate of hematuria was higher in the T group. Both techniques can be used interchangeably with acceptable rates of urological complications. The simplicity of the T technique has made it the technique of choice in our institution.

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine microemulsion in long-term liver-transplant patients with renal dysfunction.

BACKGROUND: Cyclosporine (CsA)-induced renal dysfunction is common after liver transplantation. We evaluated the efficacy of tapering CsA to a very low dose and introducing mycophenolate mofetil (MMF) in long-term liver-transplant recipients with renal dysfunction. In addition, we assessed the impact of this strategy on calcineurin inhibition and on transforming growth factor (TGF)-beta levels. METHODS: We prospectively enrolled 19 adult, long-term (>1 year) liver-transplant recipients with a decreased creatinine clearance greater than 25% compared with the first month posttransplant. MMF was introduced, and CsA was tapered to 25 mg twice daily. Calcineurin inhibition and TGF-beta were measured at baseline and 3 months thereafter. RESULTS: The CsA dose was tapered over 13+/-3 weeks. At 1-year follow-up, serum creatinine decreased from 141+/-24 to 105+/-22 micromol/L (P=0.002), creatinine clearance increased from 53+/-9 to 71+/-19 ml/min (P=0.02), and glomerular filtration rate increased from 40+/-13 to 64+/-18 mL/min (P=0.002). The incidence of acute rejection was 29%. Antihypertensive medications were discontinued in 71% of the patients. Although CsA levels decreased significantly, serum TGF-beta did not differ from normal controls, and calcineurin inhibition remained stable. The incidence of gastrointestinal side-effects and leukopenia was 18% and 24%, respectively. CONCLUSION: In long-term liver-transplant recipients with renal dysfunction, the introduction of MMF followed by tapering of CsA to a very low dose resulted in a significant improvement in renal function. However, this strategy maybe associated with a risk of acute rejection. The clinical pertinence of measuring serum TGF-beta levels and calcineurin inhibition remains to be determined.