Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors.

The use of donation after cardiac death (DCD) donor hepatic allografts is becoming more widespread; however, there have been published reports of increased graft failure from specific complications associated with this type of allograft. The complication of ischemic cholangiopathy (IC) has been reported to occur more frequently after the use of DCD hepatic allografts. We report the results of 52 liver transplants from DCD donors and the factors that influenced the development of IC. We conducted a retrospective review of all DCD and donation after brain death (DBD) donor liver recipients from September 2003 through December 2006 at a single institution. Survival and complication rates were compared between the 2 groups. The Cox proportional hazards model was then used to identify recipient and donor factors that predict the development of IC in the DCD group. There was no difference in 1-year patient or graft survival rates between the 2 groups. There was no incidence of primary nonfunction from the DCD allografts. Hepatic artery complications and anastomotic bile duct complications were comparable in the 2 groups. There was, however, an increased risk for the development of IC in the DCD group (13.7% versus 1%, P = 0.001). Donor weight >100 kg and total ischemia times > or =9 hours, in donors older than 50 years of age, predicted the development of IC in the DCD group. In conclusion, there is a higher incidence of IC in recipients receiving DCD donor livers; however, patient and graft outcomes with DCD donors remain comparable to those with DBD donors. Careful donor selection may improve utilization of these grafts.

Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: implications for surveillance studies and new adjuvant therapies.

The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We conducted a retrospective review of 834 consecutive liver transplants from 1/1/1996 to 12/31/2005 (mean follow-up 1303 +/- 1069 days) at one institution and 352 consecutive transplants from 1/2/2002 to 12/31/2005 (mean follow-up 836 +/- 402 days) at a second institution. The test cohort comprised patients identified with HCC in their explanted livers from 1/1/2001 to 12/31/2005 at the first institution. Explant pathology and donor and recipient characteristics were reviewed to determine factors associated with HCC recurrence. These predictors were validated in the remaining liver transplant recipients. The test cohort had 116 patients with findings of HCC in their explanted livers. Twelve patients developed recurrent HCC. Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (>4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well-differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from -3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. In conclusion, patients transplanted for HCC with a PCRS of < or =0 have a low risk of recurrence. Patients with a PCRS of 1 or 2 have a moderate risk of recurrence, and those with a PCRS of > or =3 have a high risk for recurrence.

Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis.

BACKGROUND: Antiviral prophylaxis has been shown to decrease the incidence of cytomegalovirus (CMV) disease in organ transplant recipients, but whether CMV disease that occurs despite prophylaxis is associated with mortality remains unknown. METHODS: The clinical features and risk factors for CMV disease in a cohort of liver transplant recipients who received antiviral prophylaxis were assessed retrospectively. Cox proportional hazard regression was used to assess the relationship of CMV to mortality during the first posttransplant year. RESULTS: CMV disease developed in 37 of 437 (8.5%) recipients at a median of 4.5 (range, 2.5 to 12) months posttransplant and was associated only with donor-seropositive/recipient-seronegative serostatus in multivariate analysis (P<0.0001). Mortality at 1 year was 12% (51 of 437) and was infection-associated in 49% of cases. In multivariate analysis, CMV disease was independently associated with overall mortality at 1 year (HR, 5.1, P=0.002) and even more strongly with infection-associated mortality (HR 11, P=0.002). There was no association of CMV with noninfection-associated mortality (P>0.05). CONCLUSIONS: Late CMV disease is an important clinical problem in liver transplant recipients who receive antiviral prophylaxis, and is strongly and independently associated with mortality. Strategies to prevent late CMV disease are warranted.

Transiently altered acetaminophen metabolism after liver transplantation.

BACKGROUND AND OBJECTIVES: Acetaminophen (INN, paracetamol) is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), a hepatotoxic metabolite, predominantly by cytochrome P450 (CYP) 2E1. Alterations in drug metabolism occur after organ transplantation. This study was designed to characterize acetaminophen disposition during the first 6 months after liver transplantation. METHODS: Thirteen liver transplant patients received an oral dose of acetaminophen (500 mg) on days 2, 10, 90, and 180 after transplantation. Serial blood samples were collected for 8 hours, and urine was collected for 24 hours. Liver biopsy specimens were obtained from the donor liver during transplantation (day 0) and on days 10, 90, and 180 after transplantation. RESULTS: There were significant time-dependent changes in acetaminophen metabolism after liver transplantation. When day 2 and day 10 were compared with day 180, the respective mean urinary recovery was 137% and 81% higher for thioether conjugates derived from NAPQI (P =.0002 and P =.01, respectively); 31% and 22% lower for acetaminophen sulfate (P =.0006 and P =.008, respectively); and 22% and 27% lower for acetaminophen glucuronide (P =.05 and P =.004, respectively). Metabolite formation clearances changed in concordance with the fractional urinary recovery. It was surprising that hepatic CYP2E1 content on day 10 after transplantation was only 20% higher, on average, than that found on day 180 (not significant). In contrast, hepatic CYP3A4 content was 984% higher, on average, when tissue from days 10 and 180 was compared after transplantation (P =.007). CONCLUSIONS: Increased recovery of acetaminophen thioether conjugates during the first 10 days after liver transplantation was a result of impaired glucuronidation and sulfation and enhanced NAPQI formation.

The role of tumor ablation in bridging patients to liver transplantation.

HYPOTHESIS: Treatment of hepatocellular carcinoma before liver transplantation can curb local tumor progression and thereby prolong patients' transplantation eligibility. DESIGN: Retrospective case-control pilot study. Twelve of 39 patients receiving liver transplantation for hepatocellular carcinoma had treatment before transplantation. Pretreatment included radiofrequency ablation (n = 8), percutaneous ethanol injection (n = 2), both modalities (n = 1), and tumor resection (n = 1). Twelve control subjects without pretreatment who were age-, sex-, and score-matched on the Model for End-stage Liver Disease and Child-Turcotte-Pugh classification were selected. The primary outcome measure was the waiting period for transplantation. RESULTS: Patients with pretreatment waited on the transplant list significantly longer than their counterparts without pretreatment (median, 484 vs 253 days; P =.03). CONCLUSIONS: Treatment before transplantation with tumor ablation or resection is associated with a longer waiting period on the transplant list. This enables patients who might otherwise be removed from the list because of tumor progression to receive transplantation.

Acquiring basic surgical skills: is a faculty mentor really needed?

BACKGROUND: We evaluated the impact of expert instruction during laboratory-based basic surgical skills training on subsequent performance of more complex surgical tasks. METHODS: Forty-five junior residents were randomized to learn basic surgical skills in either a self-directed or faculty-directed fashion. Residents returned to the laboratory 2 days later and were evaluated while performing 2 tasks: skin closure and bowel anastomosis. Outcome measures included Objective Structured Assessment of Technical Skill, time to completion, final product quality, and resident perceptions. RESULTS: Objective Structured Assessment of Technical Skill, time to completion, and skin esthetic ratings were not better in the faculty-directed group, although isolated improvement in anastomotic leak pressure was seen. Residents perceived faculty-directed training to be superior. CONCLUSIONS: Our data provided minimal objective evidence that faculty-directed training improved transfer of learned skills to more complex tasks. Residents perceived that there was a benefit of faculty mentoring. Curriculum factors related to training of basic skills and subsequent transfer to more complex tasks may explain these contrasting results.

Laboratory-based instruction for skin closure and bowel anastomosis for surgical residents.

HYPOTHESIS: Multimedia delivery of cognitive content paired with faculty-supervised partial task simulation for both excision of a simulated skin lesion with subsequent wound closure and hand-sewn bowel anastomosis would be an effective method for developing appropriate procedural skills among junior residents. DESIGN: Prospective cohort study. SETTING: University-based surgical residency. PARTICIPANTS: First- and second-year surgical residents (n = 45). INTERVENTIONS: Surgical residents were given comprehensive instructional materials, including structured curricula with goals and objectives, text, figures, and narrated expert digital video, before the training session. A 4-hour, standardized, laboratory-based instruction session was then performed in small groups, which emphasized faculty-supervised practice. Residents were asked to (1) excise a skin lesion and close the wound and (2) perform hand-sewn bowel anastomosis. These 2 tasks were assessed before and after supervised practice. Performances were video recorded. Residents were surveyed before and after training. MAIN OUTCOME MEASURES: Time to completion and Objective Structured Assessment of Technical Skill global rating scale score based on video recordings were evaluated by blinded reviewers. Final product quality was measured by anastomotic leak pressure and by wound closure aesthetic quality. RESULTS: Residents perceived the laboratory training to be equal to training in the operating room for skin closure and superior to training in the operating room for bowel anastomosis. Residents perceived time spent on both tasks to be "perfect." Mean objective scores improved significantly on 5 of 6 outcome measures. CONCLUSIONS: Junior resident surgical performance improved substantially with 4 hours of laboratory-based, faculty-supervised practice. Both first- and second-year residents benefited from this training. These data show that curriculum-driven, faculty-supervised instruction in a laboratory setting is beneficial in the training of junior surgical residents.

Using root cause analysis to improve survival in a liver transplant program.

BACKGROUND: With the advent of programs such as the American College of Surgeons-National Surgical Quality Improvement Program, surgical services will be compared with their peers across the United States. At times, many programs will experience lower-than-expected outcomes. During July 1, 1998, to June 30, 2000 our 1-year graft (76.86%, P = 0.23) and patient (80.61%, P = 0.016) survivals after liver transplantation were lower than our expected rates (graft 81.89% and patient 88.3%), according to the U.S. Scientific Registry of Transplant Recipients (SRTR). METHODS: We used aggregate root cause analysis to determine underlying reasons for our patient deaths. Two of our surgeons performed a systematic review of all our center's liver transplant patient deaths from January 1, 1995, to December 31, 2000. Each phase of the transplant process was reviewed. RESULTS: Of 355 patients receiving their first transplant, there were 90 deaths, with 188 root causes identified. The apportionment according to phase of the transplant process was patient selection, 50%; transplant procedure, 17%; donor selection, 15%; post-transplant care, 8%, and psychosocial issues, 10%. Risk reduction action plans were developed, and several important changes made in our care protocol. In April 2004, SRTR data revealed that for patients transplanted between January 1, 2001 and June 30, 2003, our 1-year liver graft survival of 90.73% (P = 0.018) was significantly higher than the national expected rate of 84.48%. Our 1-year patient survival rate of 92.66% (P = 0.285) was higher than the expected rate of 89.29%. CONCLUSIONS: Lower-than-expected outcomes can provide an impetus for improving patient care and raising the quality of a surgical service. Aggregate root cause analysis of adverse events is a valuable method for program improvement.