Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria. METHODS: Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary. RESULTS: Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053). CONCLUSIONS: Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.

Effects of Share 35 Policy on Liver Transplantation Outcomes for Patients With Nonalcoholic Steatohepatitis.

BACKGROUND: To examine the temporal variation and outcomes of liver transplantation between pre- and post-Share 35 eras for patients with nonalcoholic steatohepatitis. METHODS: A retrospective analysis was performed among 4380 patients with end-stage liver disease from the United Network for Organ Sharing database from 2009 to 2017 due to primary diagnosis of nonalcoholic steatohepatitis or cryptogenic cirrhosis with body mass index greater than 30. Cox regressions were used to model the effect of Share 35 policy on patient and graft survival comparing the first 3 years of Share 35 policy to an equivalent time period before. RESULTS: The number of nonalcoholic steatohepatitis-related transplants increased from 232 (14.1%) in 2009 to 266 (20.5%) in 2017. In post-Share 35 era, average waitlist time and cold ischemic time decreased, while Model for End-Stage Liver Disease (MELD) scores increased with higher proportion of recipients having MELD ≥35. No significant difference in average length of hospitalization or survival was found after Share 35. CONCLUSIONS: The Share 35 policy benefits patients with nonalcoholic steatohepatitis from reduced liver transplantation waiting time. It is also associated with comparable outcomes in 2 eras without increasing cold ischemic time or posttransplant length of hospitalization.

The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors: An Analysis of the United Network for Organ Sharing Registry.

INTRODUCTION: The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. RESEARCH QUESTION: To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. DESIGN: A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. RESULTS: Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. CONCLUSION: The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

Hepatocellular carcinoma: a review.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.

Efficacy and cost-effectiveness of voriconazole prophylaxis for prevention of invasive aspergillosis in high-risk liver transplant recipients.

Aspergillus infection remains a significant and deadly complication after liver transplantation (LT). We sought to determine whether the antifungal prophylactic use of voriconazole reduces the incidence of invasive aspergillosis (IA) in high-risk LT recipients without prohibitively increasing cost. During the study era (April 2008 to April 2014), 339 deceased donor LTs were performed. Of those patients, 174 high-risk recipients were administered antifungal prophylaxis with voriconazole. The median biological Model for End-Stage Liver Disease score at the time of LT was 33 (range, 18-49) with 56% requiring continuous renal replacement therapy and 50% requiring ventilatory support immediately before transplantation. Diagnosis of IA was stratified as proven, probable, or possible according to previously published definitions. No IA was documented in patients receiving voriconazole prophylaxis. At 90 days after LT, the institutional cost of prophylaxis was $5324 or 5.6% of the predicted cost associated with post-LT aspergillosis. There was no documentation of resistant strains isolated from any recipient who received voriconazole. In conclusion, these data suggest that voriconazole prophylaxis is safe, clinically effective, and cost-effective in high-risk LT recipients.

Conventional TACE and drug-eluting bead TACE as locoregional therapy before orthotopic liver transplantation: comparison of explant pathologic response.

BACKGROUND: Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality worldwide. Despite its increasing incidence, significant progress has been made in the clinical management of HCC. Transarterial chemoembolization (cTACE) has been shown to improve survival in patients with unresectable HCC; it has also been successfully used as bridging therapy before orthotopic liver transplantation (OLT) in efforts to delay tumor growth or to downstage HCC. TACE with drug-eluting beads (DEB-TACE), a novel drug delivery system that produces a slow and sustained release of chemotherapeutic agent, has recently been shown to have similar efficacy to conventional TACE (cTACE); it also exhibits fewer adverse effects resulting from reduced systemic drug concentrations. To date, the pathologic response rate to cTACE compared with DEB-TACE in patients undergoing OLT has not been well described. METHODS: A total of 111 consecutive patients with HCC who underwent cTACE (n=76) or DEB-TACE (n=35) before OLT at a single center between January 2005 and December 2010 were evaluated. RESULTS: Complete necrosis was achieved in 50.9% and 57.1% of cTACE and DEB-TACE patients, respectively; at least 50% necrosis was evident in approximately three fourths of patients in both groups. Rates of necrosis and tumor recurrence did not differ between groups. Dropout from the transplant list was equal in both groups. CONCLUSIONS: Either modality is an acceptable treatment to achieve tumor control for patients awaiting OLT and can be expected to result in excellent necrosis rates in the majority of patients.

Combined lung and liver transplantation: analysis of a single-center experience.

Patients with end-stage lung disease complicated by cirrhosis are not expected to survive lung transplantation alone. Such patients are potential candidates for combined lung-liver transplantation (CLLT), however few reports document the indications and outcomes after CLLT. This is a review of a large single-center CLLT series. Eight consecutive CLLT performed during 2009-2012 were retrospectively reviewed. One patient received a third simultaneous heart transplant. Mean age was 42.5 ± 11.5 years. Pulmonary indications included cystic fibrosis (CF) (n = 3), idiopathic pulmonary fibrosis (n = 2), α1-antitrypsin deficiency (AATD) (n = 1) and pulmonary hypertension (n = 2). Liver indications were CF (n = 3), hepatitis C (n = 2), AATD (n = 1), cryptogenic (n = 1), and cardiac/congestive (n = 1). Urgency was reflected by median lung allocation score (LAS) of 41 (36.0-89.0) and median predicted FEV1 of 25.7%. Median donor age was 25 (20-58) years with median cold ischemia times of 147 minutes and 6.1 hours for lung and liver, respectively. Overall patient survival at 30 days, 90 days and 1 year was 87.5%, 75.0% and 71.4% respectively. One patient had evidence of acute lung rejection, and no patients had liver allograft rejection. Early postoperative mortalities (90 days) were caused by sepsis in 2 recipients who exhibited the highest LAS of 69.9 and 89.0. The remaining recipients had a median LAS of 39.5 and 100% survival at 1-year. Median length of stay was 25 days (7-181). Complications requiring operative intervention included bile duct ischemia (n = 1) and bile leak (n = 1), ischemia of the bronchial anastomosis (n = 1), and necrotizing pancreatitis with duodenal perforation (n = 1). This series reflects a large single-center CLLT experience. Sepsis is the most common cause of death. The procedure should be considered for candidates with LAS < 50.

Pre-transplant utilization of sorafenib is not associated with increased complications after liver transplantation.

Hepatocellular carcinoma (HCC) is increasing in incidence, resulting in approximately 35% of orthotopic liver transplantation (OLT) performed each year. Sorafenib (SOR) is a multi-kinase inhibitor that is approved for the treatment of unresectable HCC. Concerns have been raised regarding the safety of SOR in patients undergoing major surgery. We retrospectively reviewed 79 consecutive patients with HCC receiving OLT. Patient data were compared for those who received SOR pre-OLT with those who did not. SOR was continued until time of transplant. During this time period, 15 patients received SOR pre-OLT and 64 did not. The two groups were similar with regards to demographic and clinical data. SOR patients were more likely to have larger tumors, more tumor nodules, and be outside of Milan criteria. The rate of recurrence of HCC was not different between the groups (13% in SOR group, 11% in no-SOR group). Surgical complications were not increased in patients receiving SOR prior to OLT. Survival rate was also similar between the two groups (median follow-up 19.7 months). In this small cohort of patients, use of SOR prior to liver transplantation does not confer an increased risk of surgical complications, even when continued until the day of surgery.

Liver transplantation for hepatocellular carcinoma: past, present, and future.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death globally. HCC is an aggressive disease with high fatality as reflected by the close numbers of annual deaths per year from HCC and annual incidence worldwide. In the United States, HCC incidence has increased substantially during the past two decades and is projected to continue to rise. Surgical resection remains the best treatment option for anatomically resectable tumors in patients with well-preserved liver function. For patients who are not resection candidates, liver transplantation offers treatment not only for HCC, but also for the cirrhotic liver. Liver transplantation for HCC is a rapidly evolving field. The results have dramatically improved with implementation of surveillance, careful selection of patients for transplantation, and pre-transplant tumor ablation. New promising tumor biomarkers, therapies for hepatitis C virus, molecular targeted therapies for HCC, and immunosuppression will ensure even better outcomes moving forward. This review discusses how liver transplant for HCC has changed over the many years, is currently improving, and how future research will shape better results.

Amphotericin B lipid complex versus liposomal amphotericin B monotherapy for invasive aspergillosis in patients with hematologic malignancy.

BACKGROUND: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with hematologic malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS: The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n=106) or ABLC (n=52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS: Risk factors for IA, such as underlying malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7-15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P<.001). CONCLUSIONS: Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting.

Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients.

The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Catheter-related Staphylococcus aureus bacteremia in cancer patients: high rate of complications with therapeutic implications.

Risk factors for complications of catheter-related Staphylococcus aureus bacteremia (CRSAB) have been studied in the general patient population but have not been well defined in cancer patients. We investigated potential risk factors for intravascular and extravascular complications in these patients. We retrospectively reviewed the records of patients with CRSAB hospitalized at our institution between January 2001 and December 2004. Demographic, clinical, laboratory, and microbiologic characteristics were extracted for the period of hospitalization and up to 3 months thereafter. Intravascular complications were defined as infective endocarditis and/or septic thrombosis. Extravascular complications included septic arthritis, deep tissue abscess, osteomyelitis, septic pulmonary emboli, septic shock, and CRSAB-related death. Ninety-one patients were included in the current study; 63% had solid tumors and the remainder had hematologic malignancies. The incidence of overall complications was 40% (n = 36); 19% (n = 17) were intravascular. On multivariate analysis, renal failure was associated with an increased risk of overall complications (odds ratio [OR], 12.78; 95% confidence interval [CI], 1.43-114.29; p = 0.0226). Patients with solid tumors were more likely to have intravascular complications (OR, 5.47; 95% CI, 1.11-27.01; p = 0.04369). Risk factors for extravascular complications included hematologic malignancy (OR, 9.56; 95% CI, 2.36-38.77; p = 0.0016) and female sex (OR, 5.25; 95% CI, 1.2-22.99; p = 0.0279). Renal failure is a risk factor for CRSAB complications in patients with cancer. Patients with solid tumors and CRSAB tend to develop intravascular complications, while patients with hematologic malignancies are prone to develop extravascular complications. Hence consideration should be given to extending the duration of therapy beyond 2 weeks.

Central venous catheter and Stenotrophomonas maltophilia bacteremia in cancer patients.

BACKGROUND: Stenotrophomonas maltophilia bacteremia is frequently found in cancer patients. This study attempted to determine how often the catheters were the source of this infection and the risk factors associated with catheter-related bacteremias. METHODS: The microbiology records were retrospectively reviewed of all cancer patients having S. maltophilia bacteremia and indwelling central venous catheters seen between January 1998 and January 2004. In a multivariate analysis the patients' clinical characteristics, antimicrobial therapy, outcome, and source of bacteremia that were significantly associated with definite catheter-related S. maltophilia bacteremia as opposed to secondary bacteremia were identified. RESULTS: A total of 217 bacteremias were identified in 207 patients: 159 (73%) were primary catheter-related (53 definite, 89 probable, and 17 possible), 11 (5%) were primary noncatheter-related, and 47 (22%) were secondary. Multivariate analysis showed the following factors to be independently associated with definite catheter-related bacteremias: 1) polymicrobial bacteremia (odds ratio [OR], 7.6; 95% confidence interval [95% CI], 1.3-45.5); 2) no prior intensive care unit admission (OR, 0.06; 95% CI, 0.005-0.578); and 3) nonneutropenic status at onset (OR, 0.07; 95% CI, 0.013-0.419). The response rate to appropriate antibiotics and catheter removal was 95% in the patients with definite catheter-related bloodstream infections, compared with only 56% in the patients with secondary bacteremias (P = .001). CONCLUSIONS: The majority of the S. maltophilia bacteremias occurring in cancer patients with indwelling central venous catheters appear to be catheter-related and are often polymicrobial. Catheter-related S. maltophilia bacteremias occurred more frequently in noncritically ill, nonneutropenic patients, and prompt removal of the catheter was found to be associated with a better prognosis.

Vancomycin-resistant Enterococcus faecium: catheter colonization, esp gene, and decreased susceptibility to antibiotics in biofilm.

To evaluate the molecular characteristics and antibiotic susceptibility in biofilm of vancomycin-resistant Enterococcus faecium (VREF) organisms that had caused catheter-related VREF bacteremia (VREF-CRB), we compared 22 isolates causing bacteremia obtained from patients with VREF-CRB with 30 isolates from control patients with gastrointestinal colonization by VREF. Using pulsed-field gel electrophoresis, we identified 17 unique strains among the 22 VREF-CRB isolates and 23 strains among the gastrointestinal isolates. The esp gene was detected in 53% (9 of 17) of the VREF-CRB and 61% (14 of 23) of the control strains (P = 0.6). VREF-CRB produced heavier biofilm colonization of silicone disks than did control organisms (P < 0.001). Daptomycin, minocycline, and quinupristin-dalfopristin were each independently more active than linezolid in reducing biofilm colonization by VREF-CRB (P < 0.01), with daptomycin being the most active, followed by minocycline. In conclusion, the esp gene in VREF is not associated with heavy biofilm colonization or catheter-related bacteremia. In biofilm, daptomycin and minocycline were the most active antibiotics against VREF, and linezolid was the least active.

Catheter-related vancomycin-resistant Enterococcus faecium bacteremia: clinical and molecular epidemiology.

OBJECTIVE: To study the clinical and molecular epidemiology of vancomycin-resistant Enterococcus faecium organisms causing catheter-related bacteremia in patients with cancer. DESIGN: Retrospective case-control study. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Case-patients were patients with cancer who had catheter-related vancomycin-resistant E. faecium bacteremia and control-patients were patients with cancer and vancomycin-resistant E. faecium gastrointestinal colonization without infection. RESULTS: Ten case-patients with catheter-related vancomycin-resistant E. faecium bacteremia were compared with 30 control-patients with gastrointestinal colonization by vancomycin-resistant E. faecium. Patients with catheter-related vancomycin-resistant E. faecium bacteremia were more likely to have required mechanical ventilation (P < .01), received total parenteral nutrition (P < .01), and had polyurethane catheters (P < .01) inserted in the femoral vein (P = .01). With the use of pulsed-field gel electrophoresis, 4 of the 10 catheter-related vancomycin-resistant E. faecium bacteremia isolates were genetically indistinguishable, whereas only 2 of the 30 control vancomycin-resistant E. faecium isolates displayed this same DNA pattern (P = .03). CONCLUSION: This study suggests that catheter-related vancomycin-resistant E. faecium bacteremia occurs more frequently in patients who receive total parenteral nutrition, mechanical ventilation, and femoral catheters.

Itraconazole added to a lipid formulation of amphotericin B does not improve outcome of primary treatment of invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is associated with poor outcome in patients with hematologic malignancy treated with amphotericin B (AMB)-based therapy. Itraconazole (ITC), a triazole with activity against Aspergillus, has been used in combination with AMB or lipid formulations of AMB (LipoAMB) in the treatment of IA, although the efficacy of this strategy is uncertain. METHODS: To determine whether the addition of ITC to LipoAMB improves outcome of IA, the authors retrospectively studied 179 consecutive patients with hematologic malignancies and definite or probable IA who received primary antifungal therapy with either LipoAMB (n = 146), or lipoAMB plus ITC (n = 33) between June 1993 and June 2003. In view of the erratic absorption of ITC tablets, only patients who received either intravenous or liquid ITC were analyzed. Patients who received < 1 week of treatment were excluded. RESULTS: Evaluable patients in both groups (LipoAMB: n =101; ITC and LipoAMB: n = 11) had comparable distribution of risk factors of poor outcome such as neutropenia at onset of IA, persistent neutropenia, systemic steroids, previous antifungal prophylaxis, admission to the intensive care unit, disseminated IA, previous bone marrow transplant, and IA due to infection by a non-fumigatus Aspergillus species. Response to primary antifungal therapy was equally poor in both groups (LipoAMB group: 10%; ITC and LipoAMB group: 0%; P = not significant). CONCLUSIONS: In the authors' 10-year study of patients with hematologic malignancy and IA, the response rate to LipoAMB given as primary therapy was very poor. In a comparable group of patients, the addition of ITC did not result in a therapeutic benefit.

Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections.

BACKGROUND: The efficacy and feasibility of donor granulocyte transfusion therapy (GTX) have changed considerably over the past four decades. The authors sought to determine the impact of high-dose (approximately 5.5 x 10(10) cells) GTX in patients with candidemia. METHODS: The authors' case-control retrospective analysis comprised 491 consecutive patients treated at The University of Texas M. D. Anderson Cancer Center (Houston,TX) from 1993 to 2000. The cohort included 29 patients with Candida species bloodstream infection who had received GTX and 462 who had not. RESULTS: Both groups were comparable in age, gender, APACHE II score, recent chemotherapy received, broad-spectrum antibiotics, systemic corticosteroids, radiotherapy, intravascular catheter, and concordant antifungal therapy (P > or = 0.1). The patients who received GTX compared with those who did not had a higher incidence of underlying leukemia (86% vs. 29%, P <0.001), persistent neutropenia (59% vs. 18%, P <0.001), non-Candida albicans candidemia (Candida glabrata, 35%; Candida krusei, 31%: 90% vs. 67%, P=0.01), and breakthrough invasive mycosis (62% vs. 23%, P <0.001). Neutropenia was more prolonged in patients who received GTX (28 vs. 10 days, P <0.001). Also, more of the patients who received GTX had received hematopoietic stem cell transplantations (28% vs. 13%, P = 0.03), exposure (within 4 weeks) to antifungals (79% vs. 38%, P <0.001), and stays in critical care units (62% vs. 40%, P=0.02). The overall attributable mortality rate for 25 evaluable recipients of GTX was 48% (n=12), compared with 45% (n=115) of 254 evaluable patients in the control group (P=0.5). Of the 158 patients with leukemia, 25 (16%) had received GTX. In patients with leukemia, more of those who had received GTX experienced disseminated candidiasis (44% vs. 26%; P <0.07) and persistent neutropenia (68% vs. 43%, P <0.02), had candidemia that was more prolonged (> 72 hours, P <0.02), and had more stays in critical care units (68% vs. 44%, P <0.03). On the bases of a reduced multivariate model, a significantly increased risk of death was found for patients with hematopoietic stem cell transplantation (odds ratio [OR]=2.51; 95% confidence interval [95% CI], 0.99-6.31; P <0.05), for patients with persistent neutropenia (OR=4.57; 95% CI, 1.99-10.47; P <0.0003), and for patients with leukemia who also had prolonged candidemia (OR=3.59; 95% CI, 1.61-7.98; P <0.002), disseminated candidiasis (OR=5.19; 95% CI, 2.17-12.42; P <0.0002), or non-C. albicans candidemia (OR=5.02; 95% CI, 1.07-23.64; P <0.04). In patients with leukemia, death was attributable to candidemia in 50% of the GTX recipients, compared with 59% of the non-GTX patients who had received antifungal therapy alone (P=0.4). CONCLUSIONS: Despite the presence of multiple predictors of increased mortality, high-dose GTX therapy in these high-risk patients with cancer was associated with better than expected survival rates.

Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies.

BACKGROUND: Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. At The University of Texas M. D. Anderson Cancer Center (Houston, TX), Aspergillus terreus is second to A. fumigatus as the most common cause of IA. In the current study, the authors compared the risk factors and outcomes associated with IA caused by A. terreus and IA caused by A. fumigatus. METHODS: The authors retrospectively reviewed the medical records of 300 patients who received care at our institution between 1995 and 2001 and who had cultures that were positive for Aspergillus infection, including 90 patients whose cultures were positive for A. fumigatus and 70 patients whose cultures were positive for A. terreus. RESULTS: Thirty-two patients with IA caused by A. terreus and 33 patients with IA caused by A. fumigatus were evaluated. The two groups were comparable in terms of age, gender, and underlying disease. Leukemia was the most common underlying malignancy (84%). More than 40% of patients in each group had undergone bone marrow transplantation. There was a trend toward a higher frequency of neutropenia among patients with IA caused by A. terreus (P = 0.12). IA caused by A. terreus was considered to be nosocomial in origin significantly more frequently compared with IA caused by A. fumigatus (P = 0.03). In vitro, A. terreus was found to be more resistant to amphotericin B (minimal inhibitory concentration [MIC90], 4.0 microg/mL) than to antifungal therapy (MIC90, 1.0 Hg/mL) in the isolates that were tested (< 50% of all isolates). The overall rate of response to antifungal therapy was 39% for patients with A. fumigatus infection, compared with 28% for patients with A. terreus infection (P = 0.43). CONCLUSIONS: Despite the decreased in vitro susceptibility of A. terreus (relative to A. fumigatus) to amphotericin B, the two groups within the current patient population had comparably poor responses to amphotericin B preparation and somewhat improved responses to posaconazole.

Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse.

OBJECTIVE: To study the characteristics of catheter-related, gram-negative bacteremia (GNB) and the role of central venous catheter (CVC) removal. DESIGN: This retrospective study involved a search of the microbiological department records of CVC and blood cultures and patients' medical records. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Patients with cancer who had catheter-related GNB, defined as (1) a positive catheter tip culture with at least 15 colony-forming units semiquantitatively, (2) isolation of the same organism from the tip and peripheral blood cultures, (3) no other source for bacteremia except the CVC, and (4) clinical manifestations of infection (fever or chills). RESULTS: Between January 1990 and December 1996, 72 cases of catheter-related GNB were available for review. Most of the patients (67; 93%) had their CVCs removed in response to the bacteremia. Few patients (5; 7%) retained their CVCs and were treated with appropriate antibiotics. When CVCs were removed, only 1 patient (1%) relapsed with the same organism, whereas all 5 patients with retained CVCs relapsed after having responded (P < .001). The most commonly isolated organisms were Enterobacter, Klebsiella, Stenotrophomonas, Pseudomonas, and Acinetobacter species. Catheter removal within 72 hours of the onset of the catheter-related GNB was the only independent protective factor against relapse of the infection (odds ratio, 0.13; 95% confidence interval, 0.02-0.75; P = .02). CONCLUSION: In patients with documented catheter-related GNB, CVCs should be removed within 48 to 72 hours to prevent relapse.

Multiple-species candidemia in patients with cancer.

BACKGROUND: Candidemia is a common cause of bloodstream infections in patients with cancer, with the majority of these infections being caused by a single Candida species. Studies of multiple-species candidemia (MSC) have rarely been reported. METHODS: The authors identified 33 patients with cancer who had candidemia (diagnosed between 1993 and 2000) caused by more than 1 Candida species. This group of 33 patients was compared with a control group of 66 patients with cancer who had C. albicans candidemia that arose soon before or soon after each case of MSC that was investigated in the current study. RESULTS: Patients with MSC, compared with control patients, were more likely to have leukemia (33% vs. 8%; P = 0.001), to have had prolonged neutropenia before the onset of their infection (mean +/- standard deviation, 10 +/- 17 days vs. 3 +/- 6 days; P = 0.02), and to have received chemotherapy within 1 month before their infection (42% vs. 18%; P = 0.01). Patients with MSC also had higher Acute Physiology and Chronic Health Evaluation II scores at the onset of infection (score > or = 16, 45% vs. 26%; P = 0.05) and were more likely to have received previous antifungal prophylaxis compared with patients who had candidemia caused by C. albicans (33% vs. 11%; P = 0.006). The response of C. albicans candidemia to single-agent antifungal therapy was significantly better than that of MSC (69% vs. 35% P = 0.004). CONCLUSIONS: In patients with cancer, MSC was more likely to occur as breakthrough candidemia, predominantly in those with leukemia and prolonged neutropenia, and was associated with suboptimal responses to single-agent antifungal therapy.