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Disease monitoring of hepatocellular carcinoma through metabolomics

World Journal of Hepatology 2017年第1期9卷 1-17页

作者： Asem I Fitian roniel cabrera School of Medicine Virginia Commonwealth University Department of Medicine Division of Gastroen- terology Hepatology and Nutrition Section of Hepatobiliary Diseases University of Florida

We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included “HCC”, “metabolomics”, “metabolomics”, “metabonomic” and “biomarkers”. We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables. Where reported, we also extracted and summarized the metabolites and pathways most highly associated with the development of cirrhosis in table format. Pathways of lysophospholipid, sphingolipid, bile acid, amino acid, and reactive oxygen species metabolism were most consistently associated with HCC in the cited works. Several studies also elucidate metabolic alterations strongly associated with cirrhosis, with γ-glutamyl peptides, bile acids, and dicarboxylic acids exhibiting the highest capacity for stratifying cirrhosis patients from appropriately matched controls. Collectively, global metabolomic profiles of the referenced works exhibit a promising diagnostic capacity for HCC at a capacity greater than that of conventional diagnostic biomarker alpha-fetoprotein. Metabolomics is a powerful strategy for identifying global metabolic signatures that exhibit potential to be leveraged toward the screening, diagnosis, and management of HCC. A streamlined study design and patient matching methodology may improve concordance among metabolomic datasets in future works.

关键词： Metabolomics Hepatocellular carcinoma Biomarkers Metabolic profiling Chromatography/mass spectrometry Noninvasive biomarkers Cirrhosis

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Down staging of hepatocellular carcinoma—can we push the boundaries?

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 540-542页

作者： Joydeep Chakraborty Andreas Giovanni Zori roniel cabrera Department of Medicine Division of GastroenterologyHepatology and NutritionUniversity of FloridaGainesvilleFLUSA

Liver transplantation(LT)has been the cornerstone of treatment of early hepatocellular carcinoma(HCC)within Milan criteria due to favorable long-term survival rates(1).

关键词： hepatocellular Liver staging

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Current and future treatments for hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第28期21卷 8478-8491页

作者： Alexander Schlachterman Willie W Craft Jr Eric Hilgenfeldt Avir Mitra roniel cabrera Department of Gastroenterology Hepatology and Nutrition University of Florida College of Medicine Department of Hospital Medicine Upper Valley Medical Center Department of Internal Medicine University of Florida College of Medicine Department of Internal Medicine Drexel University College of Medicine roniel cabrera Department of Gastroenterology Hepatology and Nutrition University of Florida College of Medicine

Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and *** is no definitively curative ***,many treatment and management modalities exist with differing advantages and *** current guidelines and individual patient concerns must be taken into account in order to properly manage *** addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment ***,considering all the options and their various pros and cons can quickly become complex for both clinicians and *** this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each *** options discussed include resection,transplantation and *** also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion *** biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are *** then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug *** hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.

关键词： Hepatocellular carcinoma Hepatoma Hepatocellular cancer Liver cancer Adult Liver cell carcinoma Liver neoplasm Hepatic neoplasm

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Advances in the management of cholangiocarcinoma

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World Journal of Hepatology 2021年第9期13卷 1003-1018页

作者： Andreas G Zori Dennis Yang Peter V Draganov roniel cabrera Division of Gastroenterology Hepatologyand NutritionUniversity of FloridaGainesvilleFL 32608United States

Cholangiocarcinoma(CCA)is a primary malignancy of the bile ducts with three anatomically and molecularly distinct entities:Intrahepatic CCA(iCCA),perihilar CCA(pCCA),and distal *** a result of phenotypic and anatomic differences they differ significantly with respect to *** each type of CCA there have been significant changes in management over the last several years which will be discussed in this *** resection remains the standard of care for all types of CCA,liver transplantation has been established as curative treatment for selected patients with pCCA and is being evaluated for iCCA with early *** respect to systemic therapy capecitabine is now first line adjuvant therapy for all biliary tract malignancies after curative intent *** in exploiting the pathologic mutations and molecular abnormalities has also yielded regulatory approval of targeted therapy for CCA in patients with acquired alterations in the fibroblast growth factor *** is also increased consensus in managing malignant biliary obstruction associated with CCA where pre-operative biliary stenting is not beneficial while self-expanding metal stents have been shown to be superior to plastic stents in patients who are not surgical candidates.

关键词： Cholangiocarcinoma Intrahepatic cholangiocarcinoma Perihilar cholangiocarcinoma Liver transplantation Chemotherapy

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Guitarist Pick for Melena: A Unique Case of an Upper GI Bleed

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International Journal of Clinical Medicine 2017年第8期8卷 514-518页

作者： Tiffany Lambrou Vikas Khullar Devi Rampertab roniel cabrera Division of Gastroenterology Hepatology & Nutrition Department of Internal Medicine University of Florida Gainesville Florida USA

Gastrointestinal bleeds are a commonly observed complication after left ventricular assist device placement and usually caused by formation of arteriovenous malformations or acquired von Willebrand disease in the setting of anticoagulation use. We present a unique case of an upper GI bleed in which the cause was likely due to the impaction of a guitar pick into the duodenal bulb in the setting of continuous flow-LVAD on anticoagulation with elevated INR and discuss the pathophysiology of GI bleeds post-LVAD placement and relevant concerns about finding foreign bodies in the GI tract and their complications.

关键词： Foreign Body GI Bleed Endoscopy Left Ventricular Assist Device (LVAD)

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Adherence to guideline-directed hepatocellular carcinoma screening:A single-center US experience

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World Journal of Hepatology 2023年第3期15卷 410-418页

作者： William W King Raymond Richhart Tyler Culpepper Maneola Mota Debdeep Banerjee Media Ismael Joydeep Chakraborty Michael Ladna Walid Khan Nicole Ruiz Jake Wilson Ellery Altshuler Virginia Clark roniel cabrera Department of Medicine University of FloridaGainesvilleFL 32610United States Department of Gastroenterology University of FloridaGainesvilleFL 32610United States Department of Hospital Medicine University of FloridaGainesvilleFL 32610United States

BACKGROUND The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma(HCC)using imaging with or without alpha-fetoprotein every six ***,screening rates remain *** To assess root causes of screening failure in a subspecialty hepatology *** The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening,defined as two cross-sectional images between five and seven months *** authors characterized the primary driver of screening ***,other hepatologists were surveyed to determine provider perceptions of screening failure *** 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1±*** C virus was the most common cirrhosis etiology.489(47%)underwent appropriate *** demographic or clinical differences were detected between those who underwent appropriate screening and those who did *** most common etiologies of screening failure,in descending order,were:radiology unable to schedule timely imaging,provider did not order imaging,patient canceled follow up appointment,appointments scheduled too far apart,lost to follow up,no-show to radiology appointment,and provider canceled *** surveyed believed the most common cause of screening failure was no-show to *** Rates of screening were poor even in a subspecialty hepatology *** failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.

关键词： Hepatocellular carcinoma Cirrhosis Health maintenance Quality improvement Screening Hepatology

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Incidentally Discovered HCC (iHCC) in Explant Liver-Histopathologic Features and Clinical Outcome

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Journal of Cancer Therapy 2013年第2期4卷 394-398页

作者： Renumathy Dhanasekaran Davinderbir S. Pannu Alpna Limaye Ivan Zendejas Roberto J. Firpi Consuelo Soldevila-Pico Giuseppe Morelli Virginia C. Clark Amitabh Suman David R. Nelson roniel cabrera Department of Medicine University of Florida Gainesville USA Department of Surgery University of Florida Gainesville USA Division of Gastroenterology Hepatology and Nutrition University of Florida Gainesville USA

Incidentally discovered hepatocellular carcinomas (iHCC) are tumors which are discovered on the explanted liver which were not present on imaging prior to transplant. The natural history, histopathologic characteristics and prognosis of iHCC are not clearly defined. Methods: A retrospective analysis was performed to compare the characteristics of iHCC and established HCC within Milan criteria (eHCC) in patients who underwent liver transplantation at our center between 2000 and 2010. Results: During the study period a total of 975 adult patients were transplanted in our center;124 (12.7%) patients had eHCC and 26 (2.6%) patients had iHCC. A larger number of patients with iHCC (73.1%) had ascites when compared to eHCC (41.3%) (p = 0.035). Patients with iHCC had a higher mean bilirubin (p 0.001) and mean INR (p = 0.05) than patients with eHCC. Around 70% of patients with iHCC had a Model for End Stage Liver Disease (MELD) score greater than 15 at the time of listing while only 25% of patients with eHCC had a MELD greater than 15 at listing (p 0.001).The mean alphafetoprotein (AFP) in patients with iHCC was significantly lower (11.6 ± 16.5) than the patients with eHCC (564.9 ± 2180;p = 0.024). In patients with iHCC, 30.8% had a multiple tumors and 23% had bilobar involvement. The average number of tumors was 1.6 and the cumulative tumor size was 2.1 cm (SD 1.4). The cumulative tumor size in iHCC was significantly smaller than in eHCC (mean 3.9 cm) (p = 0.035). American Joint Committee on Cancer (AJCC) T1 tumor stage was found in 58% of patients with iHCC and 48.4% of patients with eHCC (p = 0.829).The median survival was 9.47 years for iHCC (95% CI 7.0 - 11.9) and 8.7 years (95% CI 6.1 - 11.4) for eHCC (p = 0.328). While none of the patients with iHCC had recurrence of HCC, the incidence of recurrence in patients with eHCC was 6.4%. Conclusion: iHCC occurred in patients with more advanced liver disease than eHCC. AFP was usually not elevated in patients with iHCC. The c

关键词： Incidental HCC Recurrence Survival

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