Biomedical subjects

Ronald W Busuttil

Publications and source records attributed to Ronald W Busuttil.

At least 55 records · Page 3Linked to original sources

PubMed2005

Ischemic cholangiopathy after liver transplantation.

Orthotopic liver transplantation (OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastomotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or "ischemic cholangiopathy" in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.

Animals↗

PubMed2004

Cutting edge: TLR4 activation mediates liver ischemia/reperfusion inflammatory response via IFN regulatory factor 3-dependent MyD88-independent pathway.

The triggering molecular mechanism of ischemia-reperfusion injury (IRI), which in clinical settings results in excessive and detrimental inflammatory responses, remains unclear. This study analyzes the role of the TLR system in an established murine model of liver warm ischemia followed by reperfusion. By contrasting in parallel TLR knockout mice with their wild-type counterparts, we found that TLR4, but not TLR2, was specifically required in initiating the IRI cascade, as manifested by liver function (serum alanine aminotransferase levels), pathology, and local induction of proinflammatory cytokines/chemokines (TNF-alpha, IL-6, IFN-inducible protein 10). We then investigated the downstream signaling pathway of TLR4 activation. Our results show that IFN regulatory factor 3, but not MyD88, mediated IRI-induced TLR4 activation leading to liver inflammation and hepatocellular damage. This study documents the selective usage of TLR in a clinically relevant noninfectious disease model, and identifies a triggering molecular mechanism in the pathophysiology of liver IRI.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Role of tacrolimus in the evolution of liver transplantation.

Once regarded as a last-resort therapy for patients with end-stage liver disease, liver transplantation has become a viable therapeutic option because of sweeping improvements in surgical techniques and the development of more powerful immunosuppressive agents. The addition of tacrolimus to the immunosuppression regimen represents a highly potent therapy and a powerful defense against acute rejection. In the decade since tacrolimus was approved for use in the United States, it has become a widely used immunosuppressant in the field of liver transplantation.

Diabetes Mellitus↗

PubMed2004

Randomized controlled trial of sequential intravenous and oral ganciclovir versus prolonged intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in high-risk cytomegalovirus-seronegative liver transplant recipients with cytomegalovirus-seropositive donors.

Cytomegalovirus (CMV)-seronegative liver transplant recipients with CMV-seropositive donors have the greatest risk for CMV disease. We performed a randomized, controlled trial comparing sequential intravenous (IV) and oral ganciclovir with prolonged IV ganciclovir for long-term prophylaxis of CMV disease in these high-risk patients. Patients were initially given IV ganciclovir at a dose of 6 mg/kg per day from days 1 to 14 after transplantation. Patients then either received oral ganciclovir (1 g every 8 hr) or continued IV ganciclovir (6 mg/kg once per day on Monday-Friday of each week) from days 15 to 100 after transplantation. CMV disease occurred in 3 of 32 patients (9.3%) receiving oral ganciclovir and in 4 of 32 patients (12.5%) receiving IV ganciclovir within the first year after transplantation (P>0.2). All cases of CMV disease occurred more than 90 days after transplantation (median time of onset day +137 for oral ganciclovir and day +135 for IV ganciclovir). There were no deaths from CMV in either study group. Both oral and IV ganciclovir were generally well tolerated. These results indicate that, after induction with 14 days of IV ganciclovir, oral ganciclovir can be as effective as IV ganciclovir for long-term prophylaxis of CMV disease in high-risk CMV-seronegative liver transplant recipients with CMV-seropositive donors and eliminates the need for prolonged IV access.

Administration, Oral↗

PubMed2004

Giant cavernous liver hemangiomas: effect of operative approach on outcome.

HYPOTHESIS: The choice of operative technique for resection of giant cavernous hepatic hemangiomas has an effect on outcome. DESIGN: Case series. SETTING: Tertiary hepatobiliary surgery-liver transplantation service. PATIENTS AND INTERVENTIONS: Fifty-two adult patients who underwent resection of symptomatic hepatic hemangiomas (38 [73%] in the right lobe; average diameter, 10.9 cm) by means of lobectomy or enucleation, with or without Pringle inflow occlusion. MAIN OUTCOME MEASURES: Blood transfusion, morbidity, mortality, and length of hospitalization. RESULTS: Patient age and sex and the size of hemangiomas were similar for patients who underwent lobectomy and enucleation. Right-lobe lesions were more often treated by enucleation, and inflow occlusion was used more frequently; transfusion requirements and length of hospitalization were similar for both techniques. Complications were more frequent after lobectomy. There were no deaths. In the latter years of the series, enucleation was used in 22 (63%) and inflow occlusion in 24 (69%) of 35 patients. CONCLUSIONS: Outcome is related to the operative approach used for resection of giant cavernous liver hemangiomas. Although lobectomy and enucleation are curative, enucleation offers greater preservation of normal hepatic parenchyma and fewer complications and is the preferred technique for suitable lesions.

Adult↗

PubMed2004

Biliverdin therapy protects rat livers from ischemia and reperfusion injury.

Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative stress and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV). The role of BV and its potential use in preventing ischemia/reperfusion injury (IRI) had never been studied. This study was designed to explore putative cytoprotective functions of BV during hepatic IRI in rat liver models of ex vivo perfusion and orthotopic liver transplantation (OLT) after prolonged periods of cold ischemia. In an ex vivo hepatic IRI model, adjunctive BV improved portal venous blood flow, increased bile production, and decreased hepatocellular damage. These findings were correlated with amelioration of histological features of IRI, as assessed by Suzuki's criteria. Following cold ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in untreated controls to 90% to 100%. This effect correlated with improved liver function and preserved hepatic architecture. Additionally, BV adjuvant after OLT decreased endothelial expression of cellular adhesion molecules (P-selectin and intracellular adhesion molecule 1), and decreased the extent of infiltration by neutrophils and inflammatory macrophages. BV also inhibited expression of inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1beta, tumor necrosis factor alpha, and interleukin 6) in OLTs. Finally, BV therapy promoted an increased expression of antiapoptotic molecules independently of HO-1 expression, consistent with BV being an important mediator through which HO-1 prevents cell death. In conclusion, this study documents and dissects potent cytoprotective effects of BV in well-established rat models of hepatic IRI. Our results provide the rationale for a novel therapeutic approach using BV to maximize the function and thus the availability of donor organs.

Animals↗

PubMed2004

The utility of MRCP in preoperative mapping of biliary anatomy in adult-to-adult living related liver transplant donors.

PURPOSE: To assess the utility of magnetic resonance cholangiopancreatography (MRCP) in preoperative mapping of biliary anatomy in adult-to-adult living related liver transplant (LRLT) donors. MATERIALS AND METHODS: From 57 potential donors with preoperative MRCP, 27 cases (16 men, 11 women, age range 22-51 years, mean 37.2 years) underwent right lobe resection and had intraoperative cholangiography (IOC) for comparison. The MRCP and IOC reports were retrospectively reviewed in all 27 cases. The MRCP was performed on 1.5 Tesla MR magnets using breath-hold heavily T2-weighted sequences in axial/coronal thin sections, and variable-thickness rotating slabs. The accuracy of preoperative MRCP for biliary mapping in potential LRLT donors was analyzed compared to the IOC findings. RESULTS: Of 27 donors, 26 (96.3%) had MRCP which showed adequate information of central intrahepatic biliary anatomy. Of these, 19 had normal bifurcation confirmed by IOC, and single biliary anastomosis was created in the recipient at transplantation. MRCP correctly predicted 17 of 19 normal cases (sensitivity for normals: 89.5%). In seven donors with variant biliary anatomy, two separate biliary anastomoses were performed in the recipient. MRCP correctly predicted five of seven variants (sensitivity for variants: 71.4%). Overall, MRCP had an accuracy 84.6% (22/26). CONCLUSIONS: MRCP has potential in the preoperative assessment of nondilated bile ducts in LRLT donors, however further improvements are desired to increase its quality and accuracy.

Adult↗

PubMed2004

Outcomes of acute rejection after interferon therapy in liver transplant recipients.

Interferon alfa has been increasingly used against recurrent hepatitis C (HCV) disease in post-liver transplant (LT) recipients. A serious potential adverse effect is acute rejection. We reviewed our experience using interferon-based therapy (interferon or pegylated interferon with or without ribavirin) for treating recurrent HCV in LT recipients. Forty-four LT recipients were treated with interferon for recurrent HCV. Five of the 44 patients developed acute rejection during interferon-based therapy. These 5 patients started treatment of 42.4 +/- 33.89 months (mean +/- SD) after LT. Mean (+/- SD) histological activity index and fibrosis scores before initiating antiviral therapy were 8.8 (+/- 1.92) and 2.6 (+/- 0.55), respectively. Patients were treated for 3.3 +/- 2.28 months (mean +/- SD) prior to rejection. At the time of rejection, HCV load was not detectable in 4 of the 5 recipients. All 5 patients had tolerated interferon therapy, and none had stopped therapy because of adverse effects. The rejection was successfully treated in 3 patients. In 2 of those 3 patients, cirrhosis eventually developed. In the 2 patients who did not respond to rejection treatment, immediate graft failure occurred, leading to re-LT in 1 patient and death from sepsis in the other. In conclusion, the results indicate that further studies are needed to assess the safety of interferon in LT recipients. Interferon-based therapy may lead to acute rejection and subsequent graft loss and should therefore be used with caution. Treated recipients may also develop progressive cirrhosis despite achieving a sustained virological response.

Adult↗

PubMed2004

Impact of tacrolimus versus cyclosporine in hepatitis C virus-infected liver transplant recipients on recurrent hepatitis: a prospective, randomized trial.

Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation, but HCV recurrence is nearly universal and may worsen patient / graft outcomes. The frequency and severity of HCV recurrence has apparently increased in recent years, raising concern about a possible role for newer immunosuppression regimens in this increase, including potentially tacrolimus. We randomized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation. A pathologist blinded to treatment reviewed serial liver biopsies. Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 (P = .19) and failure / death were .25 and .28, respectively (P = .789). Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels (months 1, 6, and 12), no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates. In conclusion, choice of calcineurin inhibitors does not impact severity of recurrent HCV.

Adult↗

PubMed2004

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.

Adult↗

PubMed2004

Surgical advances in liver and bowel transplantation.

Liver and intestinal transplantation are currently the treatments of choice for life-threatening hepatic and gastrointestinal failure. These technologies have evolved through contributions from the fields of immunology, anatomy, physiology, surgery, anesthesiology, critical care, ethics, epidemiology, and public health. Transplantation now accounts for the treatment of over 5,000 recipients per year who are in a state of organ failure. The available donor population, however, is not increasing to meet the demands of the faster growing recipient population. This discrepancy has led to the rapid development of novel strategies that require critical evaluation to build on the success rates in recent years. This article presents the most salient advances in liver and intestinal transplantation in the last 15 years.

Humans↗

PubMed2004

Gene therapy for liver transplantation using adenoviral vectors: CD40-CD154 blockade by gene transfer of CD40Ig protects rat livers from cold ischemia and reperfusion injury.

Liver injury induced by ischemia/reperfusion (I/R) is the prime factor in delayed or loss graft function following transplantation. CD4+ T lymphocytes are key cellular mediators of antigen-independent inflammatory response triggered by I/R. We attempted to modulate rat liver I/R injury by targeted gene therapy with CD40Ig, which blocks the CD40-CD154 costimulation pathway. One hundred percent of Ad-CD40Ig-pretreated orthotopic liver transplants (OLTs) subjected to 24 h of cold (4 degrees C) ischemia survived > 14 days (vs 50% in untreated/Ad-beta-gal groups). Ad-CD40Ig treatment decreased sGOT levels and depressed neutrophil infiltration, compared with controls. These functional data correlated with histological Suzuki's grading of hepatic injury, which in untreated/Ad-beta-gal groups showed severe necrosis (> 60%) and moderate to severe sinusoidal congestion; the Ad-CD40Ig-pretreated group revealed minimal sinusoidal congestion/necrosis. Unlike in controls, OLT expression of mRNA coding for IL-2/IFN-gamma remained depressed, whereas that of IL-4/IL-13 reciprocally increased in the Ad-CD40Ig group. Ad-CD40Ig reduced frequency of TUNEL+ cells and pro-apoptotic Caspase-3, but enhanced antioxidant HO-1 and anti-apoptotic Bcl-2/Bcl-xl expression. Thus, prolonged blockade of CD40-CD154 by CD40Ig exerts potent cytoprotection against hepatic I/R injury. These results provide the rationale for a novel gene therapy approach to maximize the organ donor pool through the safer use of liver transplants exposed to prolonged cold ischemia.

Adenoviridae↗

PubMed2004

Interleukin 13 gene transfer in liver ischemia and reperfusion injury: role of Stat6 and TLR4 pathways in cytoprotection.

Ischemia and reperfusion injury (IRI) represents the major problem in clinical liver transplantation. We have shown that transcription of signal transducer and activator of transcription 4 (Stat4) plays a key role in the mechanism of hepatic IRI, whereas local induction of interleukin 13 (IL-13) is cytoprotective. The disruption of innate Toll-like receptor 4 (TLR4) signaling prevents mouse livers from undergoing fulminant IRI. This study analyzes in vivo interplay between innate (TLR4) and adaptive (Stat6) immunity in Ad-IL-13 (recombinant adenovirus encoding IL-13) cytoprotection in hepatic IRI. Using a partial 90-min lobar warm ischemia model, groups of wild-type and Stat6-deficient knockout mice were assessed for the severity of hepatocellular damage at 6 hr postreperfusion. Unlike in wild-type mice, treatment of Stat6 knockout recipients with Ad-IL-13 failed to improve hepatic function/histology. The expression of mRNAs encoding tumor necrosis factor alpha/IL-1 beta and IL-2/interferon gamma remained depressed in the wild-type plus Ad-IL-13 group, but not in the Stat6 knockout plus Ad-IL-13 group. Ad-IL-13 increased antioxidant heme oxygenase 1 (HO-1) expression and prevented TLR4 activation in livers of Stat6-competent (wild-type) mice. In contrast, low HO-1 expression and enhanced TLR4 expression were recorded in Stat6 knockout recipients despite Ad-IL-13 therapy. Thus (1) Stat6 is required for Ad-IL-13 to prevent IRI, and (2) depression of TLR4 activation is Stat6 dependent. In conclusion, the Stat6 pathway operates as a key negative regulator in the hepatic inflammatory ischemia-reperfusion response. This study outlines requirements for Ad-IL-13 use to maximize the organ donor pool through the use of liver transplants despite prolonged ischemia.

Animals↗

PubMed2004

Split-liver transplantation in the United States: outcomes of a national survey.

OBJECTIVE: Assess application and outcomes of split-liver transplantation within the United States. SUMMARY BACKGROUND DATA: While a theoretically attractive mechanism to increase cadaver organ supply, split-liver transplantation has been infrequently applied. The American Society of Transplant Surgeons, in an attempt to gather preliminary data on split-liver transplantation, performed a data protected survey of transplant centers participating in the U.S. Scientific Registry for Transplant Recipients. METHODS: Between April 2000 and May 2001, 89 surgical teams were surveyed. Elicited data included graft type, recipient status, procurement method, graft sharing, graft outcomes, recipient outcomes, and experience with cadaver, whole-organ transplantation. RESULTS: Eighty-three surgical teams reported data on 207 left lateral segment, 152 right trisegment, 15 left lobe, and 13 right lobe grafts. The split procedure was performed ex vivo in 54% and in situ in 46% of grafts. Complications were frequent in all graft types with biliary and vascular complications equally distributed between grafts procured by either technique. Primary nonfunction, graft failure, and recipient death correlated with transplant status. CONCLUSIONS: Split-liver transplantation has been principally applied to adult-child pairs with at least one recipient critically ill. Biliary and vascular complications account for the majority of morbidity in grafts procured by either split technique with graft failure and recipient death observed more frequently in critically ill recipients. Enhanced utilization and improved results may be possible through improved information sharing and modification of allocation criteria.

Adult↗

PubMed2004

Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure.

OBJECTIVE: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. METHODS: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. RESULTS: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). CONCLUSIONS: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Adolescent↗

PubMed2004

Fulminant liver failure due to usnic acid for weight loss.

The use of complementary and alternative medicine (CAM) in developed countries has increased significantly over the years. Among the most popular are the weight loss supplements or "fat burners." Liver failure due to these popular remedies has been widely recognized. Usnic acid has been an ingredient of dietary supplements that cause liver failure. Its hepatotoxicity has not been recognized because it is usually mixed with other ingredients that are presumably hepatotoxic. We describe a case of a 28-yr-old woman who presented with fulminant liver failure requiring orthotopic liver transplantation, after taking pure usnic acid for weight loss. This is the first report on fulminant liver failure associated with the ingestion of pure usnic acid. A discussion about hepatotoxicity of the different compounds of dietary supplements is presented. This is a reminder for the clinicians about the potential side effects of CAM.

Adult↗

PubMed2004

Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings.

PURPOSE: To assess degree of macrovesicular steatosis with unenhanced computed tomography (CT) and correlate it with histologic findings in potential donors for living related liver transplantation. MATERIALS AND METHODS: Forty-two candidates underwent unenhanced CT within 4 weeks of core liver biopsy. An experienced liver pathologist, blinded to both CT and surgical findings, retrospectively reviewed biopsy specimens and determined degree of macrovesicular steatosis. A radiologist blinded to histologic grading calculated mean hepatic attenuation in each donor liver by averaging 25 region-of-interest (ROI) measurements on five sections (five ROIs per section). Mean splenic attenuation was calculated with three separate ROI measurements. Liver attenuation index (LAI) was derived and defined as the difference between mean hepatic and mean splenic attenuation. Body mass index (BMI) was determined for each patient. Linear regression analysis was used to correlate degree of macrovesicular steatosis with both LAI and BMI. RESULTS: LAI correctly predicted degree of macrovesicular steatosis in 38 (90%) of 42 cases. In four of four livers, LAI below -10 HU correlated with greater than 30% macrovesicular steatosis (unacceptable for liver transplantation). In nine of 11 livers, LAI was between -10 and 5 HU and correctly predicted 6%-30% steatosis (relative contraindication). In two of 11 cases, LAI overestimated degree of hepatic steatosis. LAI above 5 HU correctly predicted 0%-5% steatosis in 25 of 27 livers. In two of 27 cases, parenchymal hemosiderin deposition led to an increase in LAI into the normal range, despite mild histologically confirmed steatosis. Degree of histologic macrovesicular steatosis correlated well with LAI (r = 0.92) and marginally with BMI (r = 0.45). Of 27 potential donors with normal livers at CT and acceptable LAI levels, four (15%) were deemed poor donor candidates because core biopsy revealed subtle hepatic necrosis and nonspecific hepatitis. CONCLUSION: Although unenhanced CT quantifies the degree of macrovesicular steatosis relatively well, it may preclude a liver biopsy only in a small percentage of potential donors with low LAI (unacceptable degree of steatosis). Core liver biopsy is still necessary in the majority of donors with normal LAI to identify those with both fatty liver and coexistent hemosiderin deposition or radiologically occult diffuse liver diseases.

Adult↗

PubMed2004

Surgery for hepatocellular carcinoma: does it improve survival?

BACKGROUND: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing in the United States. Whether surgery is associated with improved survival at the population level is relatively unknown. To address this question, we used a population-based cancer registry to compare survival outcomes between patients receiving and not receiving surgery with similar tumor sizes and health status. METHODS: By using the Surveillance, Epidemiology, and End Results database, we identified HCC patients who had surgically resectable disease as defined by published expert guidelines. After excluding patients with contraindications to surgery, we performed both survival analysis and Cox regression to identify predictors of improved survival. RESULTS: Of the 4008 patients diagnosed with HCC between 1988 and 1998, 417 were candidates for surgical resection. The mean age was 63.6 years; mean tumor size was 3.3 cm. The 5-year overall survival with surgery was 33% with a mean of 47.1 months; without surgery, the 5-year overall survival was 7% with a mean of 17.9 months (P <.001). In the multivariate Cox regression, surgery was significantly associated with improved survival (P <.001). Specifically, patients who received surgery had a 55% decreased rate of death compared with patients who did not have surgery, even after controlling for tumor size, age, sex, and race. CONCLUSIONS: This study shows that surgical therapy is associated with improved survival in patients with unifocal, nonmetastatic HCC tumors <5 cm. If this is confirmed in future studies, efforts should be made to ensure that appropriate patients with resectable HCC receive high-quality care, as well as the opportunity for potentially curative surgery.

Aged↗