The precise staging of hepatocellular carcinoma (HCC) based on the size and number of lesions that predict recurrence after orthotopic liver transplantation (OLT) has not been clearly established. We therefore analyzed the outcome of 70 consecutive patients with cirrhosis and HCC who underwent OLT over a 12-year period at our institution. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified Tumor-Node-Metastases (TNM) Staging Classification. Tumor recurrence occurred in 11.4% of patients after OLT. The Kaplan-Meier survival rates at 1 and 5 years were 91.3% and 72.4%, respectively, for patients with pT1 or pT2 HCC; and 82.4% and 74.1%, respectively, for pT3 tumors (P ‫؍‬ .87). Patients with pT4 tumors, however, had a significantly worse 1-year survival of 33.3% (P ‫؍‬ .0001). An ␣-fetoprotein (AFP) level > 1,000 ng/mL, total tumor diameter > 8 cm, age > 55 years and poorly differentiated histologic grade were also significant predictors for reduced survival in univariate analysis. Only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis. Patients with HCC meeting the following criteria: solitary tumor < 6.5 cm, or < 3 nodules with the largest lesion < 4.5 cm and total tumor diameter < 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years, respectively, after OLT versus a 50% 1-year survival for patients with tumors exceeding these limits (P ‫؍‬ .0005). We conclude that the current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT. (HEPATOLOGY 2001;33:1394-1403.)Orthotopic liver transplantation (OLT) is a rational therapeutic option for patients with hepatocellular carcinoma (HCC), because it addresses the multifocal potential of HCC in many patients that limits the success and applicability of resection, and also treats the underlying liver disease. The early experience of OLT for HCC in unselected patients included those with extensive and bulky tumors, and was associated with a dismal outcome primarily as a result of aggressive tumor recurrence after OLT. 1,2 The observation that small HCC discovered incidentally at the time of pathologic examination of the explanted liver had a much lower recurrence rate after OLT 1,2 provided the impetus for subsequent studies evaluating OLT mainly for patients with small HCC. [3][4][5][6] In a study by Bismuth et al., 3 the subgroup of patients with no more than 3 tumor nodules and none greater than 3 cm in greatest diameter had a 3-year disease-free survival of 83% with OLT, compared with only 18% treated by resection. In a subsequent study by Mazzaferro et al., 5 35 patients with a solitary tumor not exceeding 5 cm or no more than 3 tumors with none greater than 3 cm had excellent overall and recurrence-free survival rates of 85% and 92%, respectively, at 4 years after OLT. In the report by Figueras et al.,6 the 5-year survival rate for OLT in 38 patients with small HCC not exceeding 5 cm in maximal diameter was 7...

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We previously reported encouraging results of down-staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2–5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer-term outcome data on HCC down-staging in a larger cohort of 61 patients with tumor stage exceedingT2criteriawhowere enrolled between June 2002 and January 2007. Eligibility criteria for down-staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down-staging was required before OLT. Tumor down-staging was successful in 43 patients (70.5%). Thirty-five patients (57.4%) had received OLT, including two who had undergone live-donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan-Meier intention-to-treat survival at 1 and 4 years after down-staging were 87.5% and 69.3%, respectively. The 1-year and 4-year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow-up of 25 months. The only factor predicting treatment failure was pretreatment alpha-fetoprotein > 1,000 ng/mL. Conclusion Successful down-staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome.

We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1-and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1-and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1-and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria.

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care.This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States. Key words: Deceased organ donation Received 25 July 2005, revised and accepted for publication 24 October 2005A national conference on organ donation after cardiac death (DCD) was convened in Philadelphia on April 7 and 8, 2005, to address the increasing experience of DCD and to affirm the ethical propriety of transplanting organs from such donors. Participants represented the broad spectrum of the medical community, including neuroscientists, critical care professionals and distinguished bioethicists (Appendix 1).Six work groups were assembled to address specific DCD issues and fulfill the conference objectives: (i) determining death by a cardiopulmonary criterion, (ii) assessing medical criteria that predict DCD candidacy following the withdrawal of life support, (iii) reviewing protocols for successful DCD organ recovery and subsequent transplantation, (iv) initiating DCD in donation service areas (DSAs), (v) discussing the allocation of DCD organs for transplantation and (vi) examining perceptions of DCD held by the media and the public. Work Group 1: Determining Death by a Cardiopulmonary CriterionA prospective organ donor's death may be determined by either cardiopulmonary (DCD) or neurologic criteria (donation after brain death [DBD]) (1). The term donation after cardiac death (DCD) clearly indicates that death precedes donation. Death determination in the DCD patient mandates the use of a cardiopulmonary criterion to prove the absence of circulation. The cardiopulmonary criterion may be used when the donor does not fulfill brain death criteria. The ethical axiom of organ donation necessitates adherence to the dead donor rule: the retrieval of organs for transplantation should not cause the death of a donor (2).In clinical situations that fulfill either brain death criteria ...

Fulminant hepatic failure (FHF) is defined by the appearance of severe liver injury with hepatic encephalopathy in a previously healthy person. There are an estimated 2,000 cases of FHF in the United States yearly, representing 0.1% of all deaths and, perhaps, 6% of liver-related deaths. The causes of FHF are many, the chief ones in the United States being hepatitis A; B; non-A, non-B and drug induced liver disease. There are no specific therapies for FHF, however, liver transplantation is recommended for situations in which spontaneous recovery appears unlikely. Factors that are valuable in assessing the likelihood of spontaneous recovery are static features such as patient age and etiology of FHF and dynamic features including encephalopathy grade, prothrombin time, and serum bilirubin. Presently, approximately 7% of all liver transplants are done for FHF and the 1-year patient survival rates average 63%, somewhat less than survival rates for nonfulminant liver disease, averaging 78%. The management of patients with FHF is challenging, particularly important being monitoring and early treatment of infections, hemodynamic abnormalities, and brain edema. Innovative approaches to management and therapy include use of cytoprotective or antiviral medications, hepatic support systems, extracorporeal liver support, hepatocyte transplantation, auxiliary liver transplantation, and xenotransplantation. None of these are of proven benefit, but many are promising as a means to support the patient with FHF until spontaneous recovery occurs or a suitable liver graft is available for transplantation.

A major obstacle for orthotopic liver transplantation (OLT) as treatment for hepatocellular carcinoma (HCC) is tumor growth resulting in dropout from the waiting list for OLT. There is a paucity of data on survival according to intention-to-treat analysis and the rate of dropout from the waiting list for OLT among patients with HCC. To further evaluate these issues, we analyzed the outcome of 46 consecutive patients with HCC listed for OLT between January 1998 and January 2001. Exclusion criteria for OLT were tumor size greater than 5 cm for one to three lesions or four lesions or greater of any size. Twenty-one patients underwent OLT. There were 11 dropouts because of tumor progression and six deaths, including three deaths after dropout. Kaplan-Meier 1-and 2-year intention-to-treat survival rates were 91.7% and 72.6%, respectively. Monthly dropout rates were 0% from 0 to 3 months, 1.5% from 3 to 6 months, 1.0% from 6 to 9 months, 4.9% from 9 to 12 months, and 5.6% from 12 to 15 months. One dropout occurred beyond 15 months among 4 patients remaining at risk. Cumulative probabilities for dropout at 6, 12, and 24 months were 7.3%, 25.3%, and 43.6%, respectively. Predictors for dropout included two or three tumor nodules or a solitary lesion greater than 3 cm at initial presentation and previous hepatic resection. Our results support recent changes in the scheme of organ allocation aimed at reducing the dropout rate and improving outcome for patients with HCC awaiting OLT. (Liver Transpl2002;8:873-883.)

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