scholarly journals Hepatocarcinoma: from pathogenic mechanisms to target therapy

2011 ◽  
Vol 2 (4) ◽  
pp. 214
Author(s):  
Luigi Manzione ◽  
Antonio Maria Grimaldi ◽  
Rosangela Romano ◽  
Domenica Ferrara ◽  
Angelo Dinota
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Target Therapy ◽  
The United States ◽  
Percutaneous Ablation ◽  
High Risk Patients ◽  
Risk Patients

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. It is currently estimated that there are 14,000–18,000 new cases of hepatocellular carcinoma in the United States each year. It is often difficult to identify individuals at risk for HCC. The main associated diseases are chronic hepatitis B and chronic hepatitis C viral infections. While a significant number of potential mutations have been generated including p53 and Insulin-like Growth Factor, our understanding of the molecular mechanisms driving the genesis and progression of HCC remain limited. HCC screening is recommended in high-risk patients. High-risk patients include virtually all patients with cirrhosis and some HBV-infected patients irrespective of cirrhosis (>40 years in men and >50 years in women). A diagnostic approach to HCC has been developed incorporating serology, cytohistology, and radiological characteristics. A precise staging of the disease may help decide on prognosis as well as choice of therapy with the greatest survival potential. Liver transplantation, in theory, is the optimal therapeutic option for HCC; it simultaneously removes the tumor and underlying cirrhosis thus minimizing the risk of HCC recurrence. When it is impossible for this to be performed, percutaneous ablation, chemoembolization, chemotherapy and the newer molecular therapies can be used. Sorafenib is the only drug registered today for the treatment of advanced HCC.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review

2008 ◽  
Vol 26 (16) ◽  
pp. 2767-2778 ◽  
Author(s):  
Bertrand Coiffier ◽  
Arnold Altman ◽  
Ching-Hon Pui ◽  
Anas Younes ◽  
Mitchell S. Cairo
Keyword(s):  
At Risk ◽  
High Risk ◽  
Tumor Lysis Syndrome ◽  
The United States ◽  
Standards Of Care ◽  
Close Monitoring ◽  
Tumor Lysis ◽  
High Risk Patients ◽  
Patients At Risk ◽  
Risk Patients

PurposeTumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS.MethodsA panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used.ResultsNew guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States.ConclusionThe potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Hepatocellular Carcinoma: Diagnostic Performance and Interobserver Agreement

2020 ◽  
Author(s):  
Hang Zhou ◽  
Chao Zhang ◽  
Linyao Du ◽  
Jiapeng Jiang ◽  
Qing Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Diagnostic Performance ◽  
Data System ◽  
Liver Imaging ◽  
Contrast Enhanced Ultrasound ◽  
High Risk Patients ◽  
Contrast Enhanced ◽  
Sensitivity Range ◽  
Risk Patients

Abstract Objectives To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. Methods In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96 histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). Results In cirrhotic patients, the specificity of LR-5 (range: 92.7–100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6–64.3 %). However, the sensitivity (range: 38.6–63.6 %) and accuracy (range: 53.4–70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6–100.0 %; accuracy range: 77.6–86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). Conclusion CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.

scholarly journals Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8900 high-risk patients

2020 ◽  
Vol 46 (2) ◽  
pp. e26
Author(s):  
Francesco Izzo ◽  
Mauro Piccirillo ◽  
Vittorio Albino ◽  
Raffaele Palaia ◽  
Andrea Belli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals Screening for hepatocellular carcinoma in high-risk patients: Western versus Eastern virus

Hepatology ◽  
2003 ◽  
Vol 38 (1) ◽  
pp. 269-269 ◽  
Author(s):  
Teh-Ia Huo ◽  
Shou-Dong Lee ◽  
Jaw-Ching Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
High Risk Patients ◽  
Risk Patients
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