[Show abstract][Hide abstract] ABSTRACT: The Joint Commission requires all hospitals have a policy regarding donation after cardiac death. To this date however, a quantitative analysis of adult hospital donation after cardiac death (DCD) policies and its impact on transplantation outcomes has not been reported. Specific characteristics for DCD polices were identified from 90 of the 164 (54.9%) hospitals within the New England Organ Bank's donor service area. Forty-five policies (50.0%) allow family members to be present during withdrawal of life-sustaining therapy (WLST) whereas eight (8.9%) prohibit this. Seventeen policies (18.9%) require WLST to occur in the operating room (OR); 20 (22.2%) specify a location outside of the OR. Fifty-six (62.2%) policies fail to state the method of determining death; however, some require arterial line (15 policies, 16.6%) and/or EKG (10 policies, 11.1%). These variables were not associated with organ recovery, utilization or donor ischemia time. Our regional analysis highlights the high degree of variability of hospital DCD policies, which may contribute to misunderstanding and confusion among providers and patients that may influence acceptance of this mode of donation.
American Journal of Transplantation 08/2011; 11(8):1719-26. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transplantation of donation after cardiac death (DCD) livers has higher rates of organ failure and complications, specifically ischemic biliary injuries. Reported large animal DCD models all employ active means to halt circulation, contrary to human DCD protocol. We report a DCD porcine model in which the animal passively progresses to cardiac death, thereby more closely mimicking human DCD scenario. Sixteen Yorkshire pigs (10 females, 6 males, 30-45 kg) had a mean time of 26:19 min ± 14:14 from withdrawal of ventilatory support (WVS) to circulatory arrest and 44:38 min ± 16:37 from WVS to electrical standstill. Cessation of hepatic flow (HF) occurred well before electrical standstill (22:15 min ± 10:09), previously not described in human or animal DCD. Histologically comparing livers from our DCD model demonstrated a dramatic increase in hepatocyte vacuolization, disorganization of endoplasmic reticulum, formation of mitochondrial inclusions and apoptosis compared with control specimens. Subtle changes were also evident in biliary epithelial cells (BEC). This results in severe cellular changes before reperfusion. Early histologic evidence suggests that there is severe hepatocyte and biliary cell disruption in our DCD model. Further research using this model may provide a deeper understanding of the pathophysiology of the DCD liver.
American Journal of Transplantation 06/2011; 11(6):1169-75. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Measuring medical students' experience on their surgical clerkship rotations to assess the adequacy of the breadth of exposure is essential for producing generalist clinicians.
A Surgical Clinical Checklist was developed by surveying the surgical faculty for those surgical problems and procedures that every generalist physician should experience. The checklist was then distributed to 48 consecutive third-year medical students for completion during their core clerkship in surgery.
Students reported encounters with surgical procedures more frequently than with surgical problems (64.3% of procedures versus 21.9% of problems were encountered by 80% of respondents). Students actively participated as often as they reported passive observation alone. Students assigned to two different teaching sites encountered similar numbers of items at each site although the distribution of individual items was different.
The Surgical Clinical Checklist provides a valuable measurement tool to assess student experiences on their surgical clerkship and can be used to direct future teaching initiatives.
The American Journal of Surgery 05/2001; 181(4):341-6. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P =.002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P =.10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P =.005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P =.04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.
[Show abstract][Hide abstract] ABSTRACT: Factors associated with the risk for mortality once placed on the liver transplant waiting list and how this risk relates to center-specific waiting time and transplant activity have not been adequately evaluated. We performed this study to determine the association between center-specific waiting time and waiting list mortality among liver transplant candidates stratified by medical urgency at the time of registration. A Cox proportional hazards model was used to calculate 2-year mortality risk for a cohort of 16, 414 registrants added to the United Network for Organ Sharing liver transplant waiting list between January 1, 1997, and December 31, 1997. After controlling for confounding variables, we calculated the mortality risk for centers, organ procurement organizations (OPOs), and states. The relation between center-specific waiting list mortality risk and median waiting time or transplant activity was determined by linear regression. In multivariate analyses, higher initial medical urgency status (relative risk [RR] = 12.8; P <.001), increasing age (P <.001), black ethnicity (RR = 1.29; P <.001), history of previous transplant (RR = 1.2; P =.009), certain liver diagnoses, and smaller center size (RR = 1.39; P =.008) were associated with significantly increased waiting list mortality. Candidates with blood type A (RR = 0.87; P <.001) and those with cholestatic cirrhosis as the primary diagnosis (RR = 0.73; P < 0. 001) had a reduced risk for dying. There were significant variations in 2-year waiting list mortality risk among centers, OPOs, and states. However, when stratified by medical urgency status at waiting list entry, center-specific waiting time and transplantation rates accounted for almost none of the center-specific waiting list mortality. Although there are variations in waiting list mortality risk among centers, OPOs, and states, there is very little relation between center-specific waiting list mortality and center-specific median waiting time or center-specific transplantation rates when stratified by medical urgency. Waiting time and center transplant rates should not influence liver allocation policy.
[Show abstract][Hide abstract] ABSTRACT: To study the outcomes of patients who underwent liver transplantation for the primary diagnosis of chronic active hepatitis secondary to hepatitis C virus (HCV).
Retrospective review within a university medical center.
Seventy-four adult recipients who received 78 orthotopic liver allografts for the primary diagnosis of chronic active hepatitis secondary to HCV between January 1990 and December 1994. Sixty-seven patients (91%) survived more than 2 months and were analyzed further for recurrent HCV infection.
Recurrence of HCV infection, hepatitis, or cirrhosis and survival rates for patients who were undergoing orthotopic liver transplantation for chronic active hepatitis secondary to HCV.
Actuarial survival rates for the entire group were 79.3%, 70.9%, and 64.5% at 1,2, and 3 years, respectively. Four patients (5% underwent retransplantation with an actuarial survival rate of 14.3% at 1 year (P<.05). Thirty-eight patients (57%) had evidence of posttransplant HCV infection, 31 patients (46%) showed histologic evidence of viral hepatitis, and 11 patients (16%) experienced portal fibrosis or cirrhosis. Seven (33%) of the deaths and all retransplantations were secondary to recurrent HCV infection. There were no significant differences in age, sex, United Network of Organ Sharing status, associated diagnoses, intraoperative packed red blood cell requirements, OKT3 use, or 1-, 2-, and 3-year survival rates in the recurrent vs nonrecurrent HCV infection groups. A higher incidence of posttransplant cirrhosis was observed in patients who were treated with tacrolimus (FK 506) (31.8% vs 8.9%, P<.05). Twenty-one patients (70%) received interferon alfa antiviral therapy with a significant benefit in the liver function test results during therapy (P<.01).
Despite recurrence of HCV infection in most patients after transplantation, survival following primary orthotopic liver transplantation for chronic active hepatitis secondary to HCV infection remains favorable, and these patients should continue to be candidates for liver transplantation. In contrast, survival following retransplantation for HCV infection is poor and should be reconsidered. There is an apparent association between the intensity of immunosuppression and recurrent HCV infection and cirrhosis that warrants continued evaluation. Interferon therapy appears to afford benefit to patients in whom recurrent HCV hepatitis develops after transplantation.
Archives of Surgery 03/1996; 131(3):284-91. · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The degree to which immunosuppression and/or rejection influences recurrent hepatitis C (HCV) after liver transplantation (LT) for end-stage HCV cirrhosis remains poorly defined. We quantified serum HCV-RNA in 84 serum samples from 28 anti-HCV-positive patients taken 223 days prior to and up to 1719 days after liver transplantation to determine if cumulative immunosuppression, rejection, or histologic recurrence correlated with HCV-RNA levels. Histologic, serum chemistry, cumulative steroid, and OKT3 and alpha-interferon (INF) dose data were collected at the time of HCV-RNA sampling. Eighteen of 24 evaluable patients (75%) had HCV-RNA detected in their sera after transplant. Eight patients had 14 rejection episodes, 9 patients received OKT3, and 5 were given INF for histologically moderate hepatitis. Five patients died - two of recurrent hepatitis C - and no retransplants were performed for recurrent hepatitis. Of the 23 survivors, 7 have histologic hepatitis - 2 with persistent ascites, and 2 with mild fibrosis. We could show no correlation between HCV-RNA levels and any of the variables examined although a trend toward increasing HCV-RNA levels with increasing numbers of rejection episodes was observed. In addition, histologic recurrence occurred more frequently for patients treated with OKT3. We conclude that the quantity of circulating viral genome is not influenced by immunosuppressive load and does not correlate with laboratory or histologic signs of recurrence. The roles that rejection, and possibly OKT3, play in the recurrence of HCV after liver transplant need further study.
[Show abstract][Hide abstract] ABSTRACT: Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly compromising patient survival. Retransplantation of the recipient with a chronically failing graft who deteriorates to the point of needing life-support is nearly futile, and in today's health care climate, not an optimal use of scarce donor livers.
[Show abstract][Hide abstract] ABSTRACT: To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization.
Retrospective cohort study.
Surgical intensive care unit in a tertiary care university hospital.
Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7).
We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death.
Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome.
Critical Care Medicine 03/1995; 23(3):466-73. · 6.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe the hemodynamic and oxygen transport patterns in survivors and nonsurvivors following liver transplantation (LT) and to assess their relationship to organ failure and mortality.
Surgical ICU in a tertiary care university teaching hospital.
Consecutive series of 113 adults undergoing LT between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or their records were incomplete (n = 7).
Preoperative severity of illness was assessed by the acute physiology and chronic health evaluation (APACHE) II scoring system. Hemodynamic and oxygen transport variables were recorded immediately preoperatively and sequentially every 12 h during the first 2 postoperative days. Organ failures (pulmonary, renal, cardiovascular, hepatic, and central nervous system) were assessed for patients in the postoperative period. Patients were grouped as survivors (n = 82) or nonsurvivors (n = 14) with a mortality rate of 15%. Preoperative APACHE II scores were significantly lower in survivors compared with nonsurvivors (7 +/- 0 vs 11 +/- 2; p = 0.029). Both preoperatively and postoperatively, survivors sustained a relatively higher mean arterial pressure, stroke volume index, left ventricular stroke work index, cardiac index, and oxygen delivery as compared with nonsurvivors (p < 0.01). The postoperative decline in systemic blood flow that was seen in both groups was particularly prominent in nonsurvivors during the first 12 h following LT (p < 0.03). Nonsurvivors sustained an approximately fivefold increase in the rate of organ failure (p < 0.0001); all patients (n = 6) with 4 or more organ failures died.
Nonsurvivors of LT have less cardiac reserve pretransplant; postoperatively, they demonstrate early myocardial depression and subsequently lower levels of cardiac index and oxygen delivery. Patients who develop these hemodynamic patterns are more prone to organ failure and death.
[Show abstract][Hide abstract] ABSTRACT: Recent reports document the efficacy of transjugular intrahepatic portocaval shunts (TIPS) for the prevention of portal hypertensive bleeding and have advocated its use as a bridge to liver transplantation. There are no reports, however, analyzing liver transplant results for patients with indwelling TIPS. We reviewed the records of all adult primary recipients with a history of portal hypertensive bleeding or unmanageable ascites transplanted since the TIPS procedure became available in our institution in July 1991. Seven of 20 recipients underwent TIPS before transplant. There were no significant differences between patients with or without TIPS in age, United Network for Organ Sharing status, Child-Pugh score, preoperative prothrombin time, operative time, operative blood product requirement, overall length of stay, and 6-month patient survival after transplant. We noted a trend toward less operative red cell (26.0 +/- 26.2 vs. 31.8 +/- 38.1 U, mean +/- SD) and autologous blood (4,762 +/- 3,335 vs. 13,355 [corrected] +/- 20,460 ml) transfusion and improved patient survival for those with a TIPS. Patients with a TIPS in place waited significantly longer for their transplant (282 +/- 113 vs. 149 +/- 113 days, P = 0.014). There were 2 technical complications related to the TIPS, 1 in a patient who died after rupture of the suprahepatic vena caval anastomosis where the device had traversed the caval/hepatic vein junction and weakened the tissues, and the other in a survivor in whom the device extended into the right atrium and was extracted during the transplant procedure. Three patients with TIPS in place died of sepsis while waiting for a donor organ. We conclude that while the TIPS offers benefits for the liver transplant recipient, placement of the device in small shrunken cirrhotic livers must be precise. Immediate benefits for the transplant candidate may be offset by increased waiting time and technical complications at the transplant operation.
[Show abstract][Hide abstract] ABSTRACT: Because of the almost universal recurrence of hepatitis B surface antigenemia (HBsAg) after liver transplantation, some centers have questioned whether these patients are appropriate allograft candidates. Since January 1984, 51 patients with hepatitis B (HBV) underwent OLT at our center. No therapy was given to prevent reinfection. Three patients underwent retransplantation. The indications for transplant included fulminant HBV (13 patients), chronic HBV (33 patients), and hepatocellular carcinoma (HCCA) in addition to HBV (5 patients). Incidental HCCA was found in 2 of the 33 patients thought to have only chronic HBV. Actuarial survival for the entire group was 57% at 1 year and 54% at 3 years. Of the 23 patients who died, only 4 deaths were attributable to recurrent HBV liver disease. Four patients survived less than 4 days due to primary graft nonfunction. Ten patients died in the first 3 months from sepsis. Although all patients who died beyond 30 days had recurrent HBsAg, only 4 deaths were attributable to recurrent HBV. The remaining 5 deaths were caused by portal vein thrombosis, bile leak, lymphoma, pancreatitis, and sepsis occurring at 15 months. Excluding the 4 patients who died from primary graft nonfunction, actuarial survival was 63% at 1 year and 60% at 3 years. Of the 28 survivors, 24 are HBsAg positive; however, only 5 have recurrent HBV liver disease. Multiple factors were evaluated to determine their influence on survival; i.e., HBV serology, United Network for Organ Sharing status, fulminant versus chronic HBV, incidence of rejection, immunosuppression, transfusion requirements, and presence of HCCA. Of these, only the presence of HCCA adversely affected outcome. Of the 7 patients with HCCA and HBV, 6 patients died within the first 6 months and 1 patient has recurrent HBV liver disease at 25 months. Actuarial survival excluding those patients with HCCA was 64% at 1 year and 61% at 3 years. Based on our results, patients with HBV and associated HCCA have a poorer prognosis and should probably be excluded from transplantation. Although the survival for patients with HBV undergoing liver transplantation is inferior to that expected in patients with some other diagnoses, long-term survival can be achieved in a majority of these patients despite recurrence of HBsAg. We believe that appropriately selected patients with a diagnosis of HBV alone should continue to be candidates for liver allografts.
[Show abstract][Hide abstract] ABSTRACT: Hepatic retransplantation (reTx) offers the only alternative to death for patients who have failed primary hepatic transplantation (PTx). Assuming a finite number of donor organs, reTx also denies the chance of survival for some patients awaiting PTx. The impact of reTx on overall survival (i.e., the survival of all candidates for transplantation) must therefore be clarified. Between 1983 and 1991, 651 patients from the New England Organ Bank underwent liver transplantation, and 73 reTx were performed in 71 patients (11% reTx rate). The 1-year actuarial survival for reTx (48%) was significantly less than for PTx (70%, P < 0.05). This survival varied, dependent on the interval of time following PTx in which the reTx was performed (0-3 days, 57% survival; 4-30 days, 24%; 30-365 days, 54%; and > 365 days, 83%). Patients on the regional waiting list had an 18% mortality rate while awaiting transplantation. These results were incorporated into a mathematical model describing survival as a function of reTx rate, assuming a limited supply of donor livers. ReTx improves the 1-year survival rate for patients undergoing PTx but decreases overall survival (survival of all candidates) for liver transplantation. In the current era of persistently insufficient donor numbers, strategies based on minimizing the use of reTx, especially in the case of patients in whom chances of success are minimal, will result in the best overall rate of patient survival.
[Show abstract][Hide abstract] ABSTRACT: Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this indication. Since the inception of the Boston Center for Liver Transplantation (BCLT) in 1983, 33 of 383 (8.6%) liver allograft recipients have undergone orthotopic transplantation as definitive treatment for otherwise unresectable cancer. Diagnoses included hepatocellular carcinoma (HCCA) in 24 patients (73%), and cholangiocarcinoma (CHCA) in 9 patients (27%). Actuarial survival rates for patients with hepatocellular carcinoma were 71%, 56%, and 42% at 1, 2, and 3 years, respectively. The actuarial survival rates for patients with cholangiocarcinoma were 89% at 6 months, and 56% at 1, 2, and 3 years. Of the nine patients with cholangiocarcinoma, 56% (5/9) developed recurrent disease. Although this recurrence rate is disheartening, because of the lack of other morbidity, long-term survival in these patients is comparable to patients with HCCA. In contrast, recurrent hepatocellular carcinoma developed in 25% of recipients (5/20) who survived longer than 3 months posttransplantation. Other causes of death in patients with hepatocellular carcinoma included perioperative complications, 16.6% (4/24); sepsis, 8.3% (2/24); coronary artery disease, 4.2% (1/24); and lymphoma, 4.2% (1/24). Favorable prognostic factors included: primary tumor less than 3 cm in size and absence of associated cirrhosis. These results emphasize that orthotopic liver transplantation can provide a long-term cure for approximately 50% of patients whose primary hepatic malignancy is unresectable by conventional procedures.
[Show abstract][Hide abstract] ABSTRACT: Previous studies of renal transplant recipients have demonstrated that allograft rejection is accompanied by an increase in plasma and urinary levels of interleukin 2 and its soluble receptor before the development of clinical symptoms. After measuring interleukin 2 and interleukin 2 receptor levels in the plasma, bile, and urine of liver transplant recipients, we found that rejection is preceded by elevation of plasma and biliary levels of both substances, that cyclosporine toxicity did not affect either of these levels, and that urinary levels of the substances are unaffected in either condition. Levels of interleukin 2 and interleukin 2 receptors increased in bile earlier than in plasma, and interleukin 2 levels did not overlap among stable patients and those experiencing rejection, whereas levels of interleukin 2 receptors did. Serial measurements of interleukin 2 levels, particularly in the product of the transplanted organ, provide a reliable assessment of the immunologic status of the allograft.
Archives of Surgery 07/1991; 126(6):717-9; discussion 719-20. · 4.30 Impact Factor