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Jorge A Marrero

Publications and source records attributed to Jorge A Marrero.

At least 19 recordsLinked to original sources
PubMed2024

Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified Delphi panel.

HCC surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on 21 statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities. The experts agreed that current data have methodologic limitations as well as unclear generalizability to Western populations. Although a randomized clinical trial of surveillance versus no surveillance is unlikely feasible, they concurred that alternative designs, such as a comparison of 2 surveillance modalities, could provide indirect evidence of surveillance efficacy. The panel acknowledged the presence of surveillance harms, but concurred the overall value of surveillance appears high, particularly given a greater emphasis on benefits over harms by both patients and clinicians. The experts underscored the importance of a framework for measuring both benefits and harms when evaluating emerging surveillance strategies. The panel acknowledged performance metrics of emerging methods may differ from other cancer screening programs given differences in populations, including higher risk of cancer development and competing risk of morality, and differences in diagnostic workflow in patients at risk of HCC. These data provide insights into the perceived value of HCC surveillance in an era of emerging blood- and imaging-based surveillance strategies.

Humans↗
PubMed2006

Who decides? Living donor liver transplantation for advanced hepatocellular carcinoma.

Few effective treatment options are available for patients with advanced hepatocellular carcinoma (HCC). Some transplant centers have begun offering living donor liver transplantation (LDLT) for selected patients whose HCC exceeds Milan criteria by a small margin. However, this remains a controversial subject. In this article, we weigh the arguments for and against LDLT for advanced HCC. Because donor autonomy forms the crux of this dilemma, the real question becomes: to whom does the decision belong, the individual donors or the medical community? We argue that donor autonomy should not be paramount in settings where the recipient benefit is uncertain.

Carcinoma, Hepatocellular↗
PubMed2006

Immune thrombocytopenic purpura following liver transplantation: a case series and review of the literature.

Thrombocytopenia is common among liver transplant candidates and recipients. The aim of our study was to determine the incidence and outcome of new-onset immune-mediated thrombocytopenic purpura (ITP) following liver transplantation at a single center. Among the 256 liver transplant recipients with an International Classification of Diseases, Ninth Edition code for thrombocytopenia, 8 cases of new-onset ITP were identified, leading to an overall incidence of 0.7% in 1,105 consecutive liver transplant recipients over a 15-year period. All 8 patients were Caucasian, 5 (63%) were male, and the median age at ITP onset was 54 years (range, 15-63). The median platelet count at presentation was 3,500 cells/mL (range, 1,000-12,000) and liver disease was due to hepatitis C (38%), primary sclerosing cholangitis (38%), and cryptogenic cirrhosis (25%). The median time from transplant to ITP onset was 53.5 months (range, 1.9-173). Three of the 6 patients tested (50%) had cell-bound antiplatelet antibodies, 1 patient had an underlying hematological malignancy, and none of the organ donors had a history of ITP. Corticosteroids and/or immunoglobulin infusions were effective in 4 patients. However, serial rituximab infusions were required in 4 patients with persistent thrombocytopenia, and 3 of them eventually required splenectomy to induce disease remission. At a median follow-up of 19.7 months, 7 long-term survivors remain in remission with a median platelet count of 267,000 cells/mL. In conclusion, new-onset ITP is an infrequent but important cause of severe thrombocytopenia in liver transplant recipients. Corticosteroids and immunoglobulin infusions were effective in 50% while the remainder of patients required rituximab infusions or eventual splenectomy for long-term disease remission.

Adolescent↗
PubMed2006

Hepatocellular carcinoma.

The number of patients who have hepatocellular carcinoma (HCC) is expected to more than double over the next 1 to 2 decades. Patients who have cirrhosis, regardless of cause, are at the highest risk for developing HCC. This article discusses surveillance of these patients for HCC by alpha-fetoprotein and ultrasound, evaluation using imaging, classification of HCC using the Barcelona staging classification, and treatment. Resection, transplantation, and percutaneous ablation are considered curative interventions and are applied to about 30% of all patients who have HCC. Currently, there is no standard therapy for advanced HCC.

Antineoplastic Agents↗
PubMed2006

Hepatocellular carcinoma.

PURPOSE OF REVIEW: Our aim is to review the latest information regarding the risk factors, markers for early detection, diagnosis, and therapy for this tumor type. RECENT FINDINGS: Alcohol, tobacco, and obesity interact together to increase the risk of hepatocellular carcinoma, which may allow us to identify a high-risk group for hepatocellular carcinoma among patients with cirrhosis. For the first time, a randomized controlled trial of surveillance for hepatocellular carcinoma showed improved survival for those patients who underwent surveillance compared with no surveillance. Another study showed that washout of contrast of an arterially enhancing lesion is sensitive and specific for hepatocellular carcinoma. The Barcelona Clinic Liver Cancer staging classification is the best at stratifying prognosis and treatment strategy for patients with hepatocellular carcinoma. Three randomized trials showed that radiofrequency ablation improves survival when compared to percutaneous ethanol injection for early hepatocellular carcinoma. SUMMARY: Not all patients with cirrhosis have an equal risk for developing hepatocellular carcinoma. Further studies should stratify the risk of hepatocellular carcinoma so surveillance is tailored to those at the highest risk. Washout of contrast of arterially enhancing mass is regarded as the typical appearance of hepatocellular carcinoma in triple-phase imaging. Radiofrequency ablation is the best ablative technique for the treatment of small hepatocellular carcinoma.

Algorithms↗
PubMed2006

Lack of tumor seeding of hepatocellular carcinoma after percutaneous needle biopsy using coaxial cutting needle technique.

OBJECTIVE: The objective of our study was to determine the incidence of tumor seeding after biopsy of hepatocellular carcinoma (HCC) using a coaxial cutting needle technique. Seeding along the needle track is a dreaded complication of percutaneous biopsy in patients with HCC, particularly in potential liver transplant recipients. Reported seeding rates range from 0.6% to 5.1% using various biopsy techniques. To our knowledge, the rate of seeding using a coaxial cutting needle technique has not been reported. MATERIALS AND METHODS: Retrospective review identified 128 patients with imaging-guided percutaneous liver biopsies positive for HCC. A coaxial cutting needle technique was uniformly used with a 17-gauge introducer and 18-gauge biopsy needle. Radiology and clinical reports were reviewed, and findings at clinical and imaging follow-up were assessed. RESULTS: During the 6-year study period, 1,012 liver mass biopsies were performed, with 128 positive for HCC (100 men and 28 women; average age, 58.4 years). One hundred one patients had more than 30 days of clinical or imaging follow-up (or both) after biopsy (mean, 410 days; range, 33-1,989 days) and constituted the study population. The remaining 27 were excluded because of inadequate follow-up. No suspected or confirmed tumor seeding on imaging, physical examination, or laparotomy was identified. CONCLUSION: We found no tumor seeding after percutaneous biopsy of HCC using a coaxial cutting needle technique. This rate, 0%, is lower than those reported with other techniques. The use of a needle introducer that remains in position during multiple cutting needle passes protects normal tissue along the track and may reduce seeding. This has particular importance for patients with stage I-II HCC, for whom liver transplantation may be curative.

Biopsy, Needle↗
PubMed2005

Antibody microarray profiling reveals individual and combined serum proteins associated with pancreatic cancer.

We used antibody microarrays to probe the associations of multiple serum proteins with pancreatic cancer and to explore the use of combined measurements for sample classification. Serum samples from pancreatic cancer patients (n = 61), patients with benign pancreatic disease (n = 31), and healthy control subjects (n = 50) were probed in replicate experiment sets by two-color, rolling circle amplification on microarrays containing 92 antibodies and control proteins. The antibodies that had reproducibly different binding levels between the patient classes revealed different types of alterations, reflecting inflammation (high C-reactive protein, alpha-1-antitrypsin, and serum amyloid A), immune response (high IgA), leakage of cell breakdown products (low plasma gelsolin), and possibly altered vitamin K usage or glucose regulation (high protein-induced vitamin K antagonist-II). The accuracy of the most significant antibody microarray measurements was confirmed through immunoblot and antigen dilution experiments. A logistic-regression algorithm distinguished the cancer samples from the healthy control samples with a 90% and 93% sensitivity and a 90% and 94% specificity in duplicate experiment sets. The cancer samples were distinguished from the benign disease samples with a 95% and 92% sensitivity and an 88% and 74% specificity in duplicate experiment sets. The classification accuracies were significantly improved over those achieved using individual antibodies. This study furthered the development of antibody microarrays for molecular profiling, provided insights into the nature of serum-protein alterations in pancreatic cancer patients, and showed the potential of combined measurements to improve sample classification accuracy.

Adenocarcinoma↗
PubMed2005

Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.

BACKGROUND/AIMS: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. METHODS: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. RESULTS: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients. CONCLUSIONS: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.

Adenine↗
PubMed2005

GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma.

BACKGROUND/AIMS: Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC). The aims of this study were to determine if GP73 is detected in the serum, and to establish the sensitivity and specificity of serum GP73 for diagnosing HCC. METHODS: Serum GP73 was detected by immunoblots and quantified by densitometric analysis. RESULTS: A total of 352 patients were studied. Serum GP73 levels were significantly higher in patients with HCC compared to those with cirrhosis (P < 0.001). GP73 had a sensitivity of 69% and a specificity of 75% at the optimal cutoff point of 10 relative units, with an area under the receiver operating curve of 0.79 vs. 0.61 for AFP (P = 0.001). GP73 levels had significantly higher sensitivity (62%) than AFP (25%) for diagnosing early HCC (P < 0.0001). Moreover, GP73 levels were elevated in the serum of 57% (32/56) of individuals with HCC who had serum AFP levels less than 20ng/ml. CONCLUSIONS: Higher levels of GP73 can be found in the serum of patients with HCC than of those without. GP73 was better than AFP for the diagnosis of early HCC. Further validation studies are needed to confirm the role of GP73 in the early detection of HCC.

Aged↗
PubMed2005

SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma.

Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC). A cohort of 170 serum samples obtained from subjects in the United States with no liver disease (n = 39), liver diseases not associated with cirrhosis (n = 36), cirrhosis (n = 38), or HCC (n = 57) were applied to metal affinity protein chips for protein profiling by SELDI-TOF MS. Across the four test groups, 38 differentially expressed proteins were used to generate multiple decision classification trees to distinguish the known disease states. Analysis of a subset of samples with only hepatitis C virus (HCV)-related disease was emphasized. The serum protein profiles of control patients were readily distinguished from each HCV-associated disease state. Two-way comparisons of chronic hepatitis C, HCV cirrhosis, or HCV-HCC versus healthy had a sensitivity/specificity range of 74% to 95%. For distinguishing chronic HCV from HCV-HCC, a sensitivity of 61% and a specificity of 76% were obtained. However, when the values of known serum markers alpha fetoprotein, des-gamma carboxyprothrombin, and GP73 were combined with the SELDI peak values, the sensitivity and specifity improved to 75% and 92%, respectively. In conclusion, SELDI-TOF MS serum profiling is able to distinguish HCC from liver disease before cirrhosis as well as cirrhosis, especially in patients with HCV infection compared with other etiologies.

Adult↗
PubMed2005

Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort.

Currently there is no consensus as to which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1- and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P = .001), portal vein thrombosis (P = .0001), and tumor diameter greater than 4 cm (P = .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC.

Carcinoma, Hepatocellular↗
PubMed2005

Improving the prediction of hepatocellular carcinoma in cirrhotic patients with an arterially-enhancing liver mass.

In the United States, cirrhotic patients with known or suspected hepatocellular carcinoma (HCC) are prioritized for liver transplantation. Noninvasive criteria for the diagnosis of HCC rely on arterial enhancement of a mass. The aim of this study was to determine whether clinical, laboratory, and / or radiologic data can improve the prediction of HCC in cirrhotic patients with an arterially-enhancing mass. Between May 2002 and June 2003, dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of consecutive patients with liver cirrhosis and a solid mass were reviewed by 2 radiologists blinded to the clinical diagnosis. Clinical, laboratory, and radiologic data were recorded for all patients. A total of 94 patients with cirrhosis and an arterially-enhancing liver mass were studied, 66 (70%) of whom had HCC. Alpha-fetoprotein (AFP) >20 ng/mL (P = .029), tumor size >2 cm (P = .0018), and delayed hypointensity (P = .0001) were independent predictors of HCC. Delayed hypointensity of an arterially-enhancing mass had a sensitivity of 89% and a specificity of 96% for HCC. The presence of delayed hypointensity was the only independent predictor of HCC among patients with arterially-enhancing lesions <2 cm (odds ratio, 6.3; 95% confidence interval [CI], 1.8-13), with a sensitivity of 80% and a specificity of 95%. In conclusion, delayed hypointensity of an arterially-enhancing mass was the strongest independent predictor of HCC, regardless of the size of the lesion. If additional studies confirm our results, the noninvasive criteria utilized to make a diagnosis of HCC should be revised.

Carcinoma, Hepatocellular↗
PubMed2005

Screening tests for hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) is rising throughout the world. HCC meets the criteria for which a disease benefits from screening or surveillance: it is an important health problem; those with cirrhosis are the targets for surveillance; there is acceptable treatment if diagnosed early; surveillance using alpha-fetoprotein and ultrasound has been shown to be cost effective; surveillance is widely implemented by health care professionals and accepted by patients; standardized recall procedures exists; and the screening tests must achieve an acceptable level of accuracy in the population undergoing screening. The latter point is the main limitation of surveillance for HCC. In this review we will discuss the currently available tests for the surveillance of HCC.

Biomarkers, Tumor↗
PubMed2005

Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma.

BACKGROUND/AIMS: Alcohol has been shown to be an important risk factor for hepatocellular carcinoma (HCC). The role of tobacco as a risk factor for HCC is controversial. Recently, obesity has been reported to be a risk factor for HCC. We investigated whether these factors increase the risk of HCC in American patients. METHODS: Consecutive patients with HCC, cirrhosis without HCC and, control patients without liver disease were enrolled and exposure to risk factors was assessed. RESULTS: When HCC cases were compared to cirrhotic controls, the risk of HCC increased 6-fold for alcohol (OR 5.7; 95% CI: 2.4-13.7), 5-fold for tobacco (OR 4.9; 95% CI: 2.2-10.6), and 4-fold with obesity (OR 4.3; 95% CI: 2.1-8.4). Using spline regression, a dose-dependent relationship between alcohol and tobacco exposure with risk of HCC was noted. There was significant interaction between alcohol, tobacco and obesity, with synergistic indices greater than 1. CONCLUSIONS: Alcohol, tobacco and obesity are independent risk factors for HCC in our patient population, and they interact synergistically to increase the risk of HCC. Data from this study may allow us to stratify cirrhotics into low- and high-risk groups for the development of HCC surveillance strategies.

Alcohol Drinking↗
PubMed2005

Hepatocellular carcinoma.

PURPOSE OF REVIEW: The incidence of hepatocellular carcinoma (HCC) is expected to continue to increase over the next two decades. The risk factors for the development of HCC are unknown and there is a lack of standardization of the diagnostic criteria for HCC. Our aim is to review the latest information regarding the risk factors, surveillance and diagnosis of this tumor. RECENT FINDINGS: Alcohol, tobacco, obesity, diabetes and viral etiology interact together to increase the risk of hepatocellular carcinoma in patients with cirrhosis, which may allow us to identify a high-risk group for HCC among patients with cirrhosis. Several studies showed that surveillance of cirrhotic patients is cost-effective and leads to an overall improvement in survival. This year a study from the United Network of Organ Sharing in the United States indicated that 30% of patients were understaged by imaging pre-transplant and 31% of patients with a diagnosis of stage 1 HCC (single lesion < 2 cm in diameter) did not have a tumor on the explant examination. Another study showed that washout of arterially enhancing lesions is very sensitive and specific for a diagnosis of HCC. SUMMARY: Not all patients with cirrhosis have an equal risk for developing hepatocellular carcinoma. Therefore, further studies should stratify the risk of HCC so surveillance is tailored to those at the highest risk. Standardization of the diagnostic criteria of HCC is critically important for better patient care and future research. Washout of arterially enhancing lesions should be important criteria of HCC.

Carcinoma, Hepatocellular↗
PubMed2004

Two-color, rolling-circle amplification on antibody microarrays for sensitive, multiplexed serum-protein measurements.

The ability to conveniently and rapidly profile a diverse set of proteins has valuable applications. In a step toward further enabling such a capability, we developed the use of rolling-circle amplification (RCA) to measure the relative levels of proteins from two serum samples, labeled with biotin and digoxigenin, respectively, that have been captured on antibody microarrays. Two-color RCA produced fluorescence up to 30-fold higher than direct-labeling and indirect-detection methods using antibody microarrays prepared on both polyacrylamide-based hydrogels and nitrocellulose. Replicate RCA measurements of multiple proteins from sets of 24 serum samples were highly reproducible and accurate. In addition, RCA enabled reproducible measurements of distinct expression profiles from lower-abundance proteins that were not measurable using the other detection methods. Two-color RCA on antibody microarrays should allow the convenient acquisition of expression profiles from a great diversity of proteins for a variety of applications.

Antibodies↗
PubMed2004

Effectiveness of interferon alpha-2b and ribavirin combination therapy in the treatment of naive chronic hepatitis C patients in clinical practice.

BACKGROUND & AIMS: Studies in many diseases have shown that efficacy in clinical trials often does not translate into effectiveness in clinical practice. The aims of this study were to determine the rate of sustained virological response (SVR) and the factors associated with SVR in therapy naive chronic hepatitis C patients treated with interferon alpha-2b and ribavirin combination therapy at a university outpatient clinic. METHODS: The medical records of 153 consecutive chronic hepatitis C patients treated between June 1998 and May 2001 were reviewed. RESULTS: The mean subject age was 44 years, 64% were men, 85% were white, 56% had HCV genotype 1, and 21% had cirrhosis on biopsy. The overall SVR rate was 42% (29% in genotype 1/4; 65% in genotype 2/3). Side effects resulted in interferon or ribavirin dose reductions in 22% of patients and premature termination of treatment in 10%. The SVR rate was significantly higher in the 102 patients who received >80% of the recommended dose and duration of therapy compared with the 51 patients who did not (53% vs. 20%, P = 0.00008). HCV genotype, subject race, and adherence were independently associated with SVR (P < 0.01). Although the incidence of side effects and medication adherence was similar in blacks and whites, adherent blacks had a significantly lower SVR rate (14% vs. 58%, P < 0.01). CONCLUSIONS: Despite the inclusion of a broader spectrum of patients and less frequent monitoring, combination antiviral therapy in our treatment-naive chronic hepatitis C patients was of similar efficacy to that reported in large multicenter trials. In addition, our data show that medication adherence is an important predictor of SVR in an academic clinical practice.

Adolescent↗