C. Burcin Taner

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole‐to‐cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021‐1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368‐21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole‐to‐cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts. Liver Transpl 18:101–112, 2012.

Surgical treatment of gallbladder cancer

Gallbladder cancer is usually a fatal illness because early stages of this carcinoma cause no specific signs or symptoms. Although the best chance of cure for gallbladder cancer remains incidental discovery, radical resection of the gallbladder, with the adjacent liver, adherent structures, plus a regional lymphadenectomy, has been suggested to improve survival. We retrospectively analyzed all patients with gallbladder cancer who were treated surgically at Mayo Clinic (Rochester) between 1984 and 2000. There were 131 patients for whom complete survival information was available. Patients who underwent a radical cholecystectomy had a significantly longer median survival (24 months) than patients who had a simple cholecystectomy (6 months) or noncurative treatment (4 months) (P < 0.0001). The radical cholecystectomy group had significantly longer survival than the simple cholecystectomy group for all American Joint Committee on Cancer (AJCC) stages except stage I. Of the different variables tested in a univariate analysis (sex, surgical treatment modality, AJCC stage, tumor grade, jaundice, hyperbilirubinemia, and adjuvant therapy), all variables except sex, tumor grade, and adjuvant therapy were statistically significant predictors for the survival of patients with gallbladder cancer. AJCC stage and surgical treatment modality were the only significant predictors in a multivariate analysis. Our results support radical surgical resection for the treatment of gallbladder cancer to improve patient survival.

Asystole to cross‐clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole‐cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole‐cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole‐cross‐clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts.

Donor Safety and Remnant Liver Volume in Living Donor Liver Transplantation

Living donor liver transplantation is now a common practice in countries in which the availability of cadaveric organs is limited. The preoperative preparation, intraoperative surgical technique, and postoperative care of donors and recipients have evolved in recent years. We retrospectively compared 67 donors with a remnant liver volume equal to or more than 30% (group 1) with 14 donors who had less than 30% remnant liver volume (group 2) for donor outcomes. All the complications in donors were systematically classified. Donors with less than 30% remnant liver volume showed significantly higher peak aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and bilirubin levels. There were 6 complications in group 1 and 4 complications in group 2. The difference between the 2 groups in terms of donor complications did reach statistical significance (P = 0.043); donors with a remnant liver volume < 30% had a 4 times greater relative risk of morbidity. In conclusion, the use of donors with less than 30% remnant liver volume is highly debatable as donor safety should be of utmost importance in living donor liver transplantation. Liver Transpl 14:1174–1179, 2008.

Fixed-dose vasopressin compared with titrated dopamine and norepinephrine as initial vasopressor therapy for septic shock.

Study Objective. To investigate the early blood pressure effects of vasopressin compared with titrated catecholamines as initial drug therapy in patients with septic shock.

Excellent Renal Allograft Survival in Donor-Specific Antibody Positive Transplant Patients—Role of Intravenous Immunoglobulin and Rabbit Antithymocyte Globulin

Background. Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. Methods. A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. Results. Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. Conclusions. Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV+ patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV+ patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV+ recipients. Seventy‐seven HCV+ patients who received DCD liver grafts were compared to 77 matched HCV+ patients who received donation after brain death (DBD) liver grafts and 77 unmatched non‐HCV patients who received DCD liver grafts. There were no differences in 1‐, 3‐, and 5‐year patient or graft survival among the groups. Multivariate analysis showed that the Model for End‐Stage Liver Disease score [hazard ratio (HR) = 1.037, 95% confidence interval (CI) = 1.006‐1.069, P = 0.018] and posttransplant cytomegalovirus infection (HR = 3.367, 95% CI = 1.493‐7.593, P = 0.003) were significant factors for graft loss. A comparison of the HCV+ groups for fibrosis progression based on protocol biopsy samples up to 5 years post‐transplant did not show any difference; in multivariate analysis, HCV genotype 1 was the only factor that affected progression to stage 2 fibrosis (genotype 1 versus non‐1 genotypes: HR = 2.739, 95% CI = 1.047‐7.143, P = 0.040). In conclusion, this match‐controlled, retrospective analysis demonstrates that DCD liver graft utilization does not cause untoward effects on disease progression or patient and graft survival in comparison with DBD liver grafts in HCV+ patients. Liver Transpl 17:641‐649, 2011.

Comparison of kidney function between donation after cardiac death and donation after brain death kidney transplantation.

Backgroud Kidney graft survival is comparable between donation after cardiac death (DCD) and donation after brain death (DBD) kidney transplantation. However, data concerning kidney function after DCD kidney transplantation are lacking. Methods We retrospectively compared kidney function between 64 DCD and 248 DBD kidney transplant recipients. Graft function was assessed using iothalamate glomerular filtration rate at 1, 4, and 12 months, then annually. The primary endpoint was the composite of death-censored graft loss or two consecutive iothalamate glomerular filtration rates less than 50 mL/min/1.73 m2 occurring within 5 years from transplantation. Secondary endpoints included death and graft loss or death. Results Of the 312 patients, 102 (33%) experienced the primary endpoint, 78 (25%) experienced graft loss or death, and 44 (14%) died. In multivariable Cox regression analysis, there was no difference between DCD and DBD recipients regarding the primary endpoint (relative risk [RR], 1.16; P=0.59), death (RR, 0.97; P=0.94), or graft loss or death (RR, 1.09; P=0.79). In the subgroup of 64 DCD recipients, each 10-year increase in donor age was associated with increased risk of the primary endpoint (RR, 1.51; P=0.027) with the highest risk observed for donors older than 45 years (RR, 4.81; P=0.001). Delayed graft function affected 45% of the DCD recipients but had no impact on kidney function, graft survival, or patient survival. Conclusions Posttransplantation kidney function is comparable between DCD and DBD kidney transplantations. In the subgroup of DCD recipients, kidneys from donors older than 45 years may be associated with a higher risk of poor kidney function; however, this finding requires validation in a larger patient group.

Is a mandatory intensive care unit stay needed after liver transplantation? Feasibility of fast‐tracking to the surgical ward after liver transplantation

The continuation of hemodynamic, respiratory, and metabolic support for a variable period after liver transplantation (LT) in the intensive care unit (ICU) is considered routine by many transplant programs. However, some LT recipients may be liberated from mechanical ventilation shortly after the discontinuation of anesthesia. These patients might be appropriately discharged from the postanesthesia care unit (PACU) to the surgical ward and bypass the ICU entirely. In 2002, our program started a fast‐tracking program: select LT recipients are transferred from the operating room to the PACU for recovery and tracheal extubation with a subsequent transfer to the ward, and the ICU stay is completely eliminated. Between January 1, 2003 and December 31, 2007, 1045 patients underwent LT at our transplant program; 175 patients were excluded from the study. Five hundred twenty‐three of the remaining 870 patients (60.10%) were fast‐tracked to the surgical ward, and 347 (39.90%) were admitted to the ICU after LT. The failure rate after fast‐tracking to the surgical ward was 1.90%. The groups were significantly different with respect to the recipient age, the raw Model for End‐Stage Liver Disease (MELD) score at the time of LT, the recipient body mass index (BMI), the retransplantation status, the operative time, the warm ischemia time, and the intraoperative transfusion requirements. A multivariate logistic regression analysis revealed that the raw MELD score at the time of LT, the operative time, the intraoperative transfusion requirements, the recipient age, the recipient BMI, and the absence of hepatocellular cancer/cholangiocarcinoma were significant predictors of ICU admission. In conclusion, we are reporting the largest single‐center experience demonstrating the feasibility of bypassing an ICU stay after LT. Liver Transpl 18:361–369, 2012.

Utilization of elderly donors in living donor liver transplantation: When more is less?†

An accepted definition of donor exclusion criteria has not been established for living donor liver transplantation (LDLT). The use of elderly donors to expand the living donor pool raises ethical concerns about donor safety. The aims of this study were (1) the comparison of the postoperative outcomes of living liver donors by age (≥50 versus <50 years) and (2) the evaluation of the impact of the extent of right hepatectomy on donor outcomes. The study group included 150 donors who underwent donor right hepatectomy between October 2004 and April 2009. Extended criteria surgery (ECS) was defined as right hepatectomy with middle hepatic vein (MHV) harvesting or right hepatectomy resulting in an estimated remnant liver volume (RLV) less than 35%. The primary endpoints were donor outcomes in terms of donor complications graded according to the Clavien classification. Group 1 consisted of donors who were 50 years old or older (n = 28), and group 2 consisted of donors who were less than 50 years old (n = 122). At least 1 ECS criterion was present in 74% of donors: 57% had 1 criterion, and 17% had 2 criteria. None of the donors had grade 4 complications or died. The overall and major complication rates were similar in the 2 donor age groups [28.6% and 14.3% in group 1 and 32% and 8.2% in group 2 for the overall complication rates (P = 0.8) and the major complication rates (P = 0.2), respectively]. However, there was a significant correlation between the rate of major complications and the type of surgery in donors who were 50 years old or older. In LDLT, extending the limits of surgery comes at the price of more complications in elderly donors. Right hepatectomy with MHV harvesting and any procedure causing an RLV less than 35% should be avoided in living liver donors who are 50 years old or older. Liver Transpl 17:548–555, 2011.