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Find video protocols related to scientific articles indexed in Pubmed.
Pharmacogenomic modeling of circulating tumor and invasive cells for prediction of chemotherapy response and resistance in pancreatic cancer.
Clin. Cancer Res.
PUBLISHED: 08-08-2014
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Despite a challenging prognosis, modern cytotoxic therapy can induce tumor responses and extend life in pancreatic adenocarcinoma (PDAC). Pharmacogenomic (PGx) modeling of tumor tissue can predict the efficacy of chemotherapeutic agents in preclinical cancer models. We hypothesized that PGx profiling of circulating tumor and invasive cells (CTIC) isolated from peripheral blood could predict tumor response, progression, and resistance.
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The role of tyrosine kinase inhibitors in hepatocellular carcinoma.
Clin Adv Hematol Oncol
PUBLISHED: 07-08-2014
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Since the approval of the multityrosine kinase inhibitor (TKI) sorafenib (Nexavar, Bayer and Onyx) as the standard of care for intermediate to advanced stages of hepatocellular carcinoma (HCC), there has been considerable interest in developing more potent TKIs to improve morbidity and mortality for patients with HCC. Much of the research on TKIs targets pathways implicated in angiogenesis, given that HCC is a highly vascularized cancer type. It was theorized that the efficacy of sorafenib is primarily attributable to its angiogenesis targets-namely, vascular endothelial growth factor receptors, platelet-derived growth factor receptors, FLT-3, and RAF kinases. Over the past 2 years, several pivotal phase 3 trials of newer TKIs targeting similar pathways have failed to meet criteria for superiority or noninferiority to sorafenib. Reasons for this may stem from the genetic and biologic heterogeneity of HCC. Genomic studies of tumor samples have shown scarce uniformity in kinase mutations, underscoring the variability that exists in HCC. This beckons the question of whether efforts should shift to other potential targets, either within the realm of TKIs or other targets entirely. Receptor tyrosine kinases, such as those encoded by the MET proto-oncogene, are expressed in certain individuals and have shown to be susceptible to targeted TKIs. As researchers continue to investigate therapies, the goal is to further research efforts into culprit oncogenes that mediate tumor progression, which will likely lead to more personalized and targeted regimens.
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Predicting responsiveness to sorafenib: can the determination of FGF3/FGF4 amplifications enrich for clinical benefit?
Hepatobiliary Surg Nutr
PUBLISHED: 07-02-2014
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A small proportion of patients with advanced hepatocellular carcinoma harbor FGF3/4 gene amplifications in an 11q13 amplicon. A recent report suggests that the presence of this alteration might enrich for sensitivity to sorafenib. Further, there is growing evidence that interference with the FGF/FGFR axis has therapeutic potential in patients with advanced hepatocellular carcinoma.
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Treating advanced hepatocellular carcinoma: How to get out of first gear.
Cancer
PUBLISHED: 03-12-2014
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Hepatocellular carcinoma is a common malignancy with a poor prognosis. Sorafenib is the only systemic therapy known to improve the overall survival of patients with advanced disease. The clinical benefit of sorafenib is modest and the mechanistic basis for its activity is unknown. Four phase 3 clinical trials have failed to improve on sorafenib in the frontline setting and no agent has been shown to impact outcomes after sorafenib failure. Several factors have contributed to this recent stall in drug development but new approaches hold promise and currently are being investigated. This review will focus on the current pipeline of experimental therapeutics for patients with advanced hepatocellular carcinoma and shed a light on scientific limitations that hamper the advancement of new therapies for this disease, and ways around it.
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Challenges in combining antiangiogenic therapy with transarterial chemoembolization for hepatocellular carcinoma.
Gastrointest Cancer Res
PUBLISHED: 01-07-2014
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The combination of systemic antiangiogenic therapy and transarterial chemoembolization (TACE) for the treatment of unresectable hepatocellular carcinoma (HCC) is the subject of several ongoing clinical trials. We present a series of patients treated with sorafenib and TACE at our institution, highlighting the technical challenges of combining these two modalities of treatment.
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c-MET and HGF mRNA expression in hepatocellular carcinoma: correlation with clinicopathological features and survival.
Anticancer Res.
PUBLISHED: 07-31-2013
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Data on the clinicopathological features and prognostic impact of c-N-Methyl-N-nitro-N-nitroso-guanidine HOS Transforming gene (c-MET) and hepatocyte growth factor (HGF) in hepatocellular carcinoma (HCC) are inconsistent. We assessed c-MET and HGF expression in 49 patients with early-stage HCC and correlated the results with disease characteristics and survival.
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A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma.
J. Hepatol.
PUBLISHED: 06-19-2013
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IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity of anti-IGF-1R monoclonal antibody cixutumumab in phase I trials prompted this phase II study.
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An update on clinical trials in the treatment of advanced hepatocellular carcinoma.
J. Clin. Gastroenterol.
PUBLISHED: 06-12-2013
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Despite the successful FDA approval of sorafenib as the standard of care therapy in patients with advanced hepatocellular carcinoma (HCC), its clinical benefits have been modest. The mortality rate remains high and prognosis poor for patients with advanced-stage HCC. The exact mechanism of sorafenib in the treatment of HCC and its resistance at the molecular levels are largely unknown. There are no other treatment options in first-line therapy and there is currently no standard of care second-line therapies available. Thus, there is a critical need for novel therapeutic approaches for the treatment of advanced HCC, and thus a clear justification for the already reported, currently ongoing, and planned clinical trials.
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The antiangiogenic ceiling in hepatocellular carcinoma: does it exist and has it been reached?
Lancet Oncol.
PUBLISHED: 06-04-2013
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The recommendation of sorafenib as standard of care in advanced hepatocellular carcinoma has lent support to the increased use of antiangiogenic therapies. However, in three phase 3 randomised trials that compared other antiangiogenics with sorafenib, results did not show superiority or non-inferiority of the new therapies. The 10-month median overall survival shown in these studies for patients given sorafenib might be a ceiling for single-agent antiangiogenic therapy. Strategies to increase survival time include combination therapies that pair antiangiogenic treatment with biological therapy or chemotherapy. The combination of sorafenib and erlotinib was not superior to sorafenib alone, which suggests no positive interaction between antiangiogenics and tyrosine kinase inhibitors in the treatment of advanced hepatocellular carcinoma. A combination of sorafenib and doxorubicin is being assessed in a randomised phase 3 trial. Differences in patient outcome with sorafenib because of disease cause and the ethnic origin of patients suggest that sorafenibs multitarget capacity, including RAF kinase inhibition, might be important. MET inhibitors cabozantinib and tivantinib are drugs that might also bypass the so-called antiangiogenic ceiling and have led to selective treatment of patients that overexpress MET with these drugs. Although this intense period of research activity has not yet resulted in significant improvements in survival for patients with advanced hepatocellular carcinoma, we are certainly closer to a customised treatment, which should increase the antiangiogenic survival ceiling.
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Shaping the future management of hepatocellular carcinoma.
Semin. Liver Dis.
PUBLISHED: 03-01-2013
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Several advances in recent years have led to improved surveillance, diagnostic, and treatment options for hepatocellular carcinoma (HCC). Despite these advances, care for this malignancy remains suboptimal, in part because of poor adherence to established guidelines. When diagnosed at an early stage, outcomes for HCC are positive; however, use of appropriate screening techniques and surveillance of at risk patients is still not widely employed. Although a multidisciplinary care team is considered an essential part of successful HCC treatment, fewer than half of the patients with HCC in the United States receive multidisciplinary care. The current suboptimal utilization of potentially curative treatments, including those recommended by treatment guidelines, can be linked to the absence of multidisciplinary care. Additionally, the lack of prognostic and predictive biomarkers for HCC remains challenging, particularly as therapeutic approaches in advanced disease evolve to the use of molecularly targeted agents. Much research is currently focused on the identification of biomarkers for HCC, but improvements in adherence to guidelines for surveillance and appropriate use of available therapies is necessary before care for patients with HCC will improve.
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Postoperative outcomes following pancreaticoduodenectomy: how should age affect clinical practice?
World J Surg Oncol
PUBLISHED: 02-15-2013
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Pancreaticoduodenectomy is an increasingly common procedure performed for both benign and malignant disease. There are conflicting data regarding the safety of pancreatic resection in older patients. Potentially modifiable perioperative risk factors to improve outcomes in older patients have yet to be determined.
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Targeted agents and systemic therapy in hepatocellular carcinoma.
Recent Results Cancer Res.
PUBLISHED: 01-31-2013
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Cytotoxic chemotherapy, hormonal agents, and immunotherapy have been tested in hepatocellular cancer (HCC) with marginal efficacy to date. Recent insights into the molecular pathogenesis of HCC have identified several aberrant signaling pathways that have served as targets for novel therapeutic agents. These discoveries have been translated into the clinical realm with the use of the antiangiogenic and the Raf kinase inhibitor, sorafenib, and have revealed the potential of targeted agents to produce clinically meaningful survival benefits in patients with advanced HCC. Efforts continue in the quest to improve the outcome of HCC patients through the development and evaluation of other targeted agents, and to better understand the interactions between the underlying disease biology and response to therapy. Several pathways are now implicated in hepatocarcinogenesis and agents that target these pathways continue to be developed.
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Clinicopathologic characteristics and survival outcomes of patients with fibrolamellar carcinoma: data from the fibrolamellar carcinoma consortium.
Gastrointest Cancer Res
PUBLISHED: 01-10-2013
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Fibrolamellar carcinoma is a rare and poorly understood malignancy that affects the young in the absence of underlying liver disease. Despite reported small review series, the literature lacks large retrospective studies that may help in understanding this disease.
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Gastrointestinal cancer educational case series: management of metastatic adenocarcinoma of unknown primary origin in a Ph+ ALL survivor.
J Gastrointest Cancer
PUBLISHED: 12-13-2011
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Secondary malignancies and chronic end-organ sequelae are significant and steadily rising consequences of cancer therapy. The workup and management of a carcinoma of unknown primary must consider the patients clinical presentation, radiologic and pathologic findings, and comorbidities.
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Shape factors of cylindrical piezometers in uniform soil.
Ground Water
PUBLISHED: 08-17-2011
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This article presents the analytical solution of Laplace equation for the steady flow around open-ended cylindrical piezometers located in an infinite, isotropic, and incompressible saturated soil. Shape factors are obtained for piezometers with varying length-to-diameter ratios. Comparisons are made with published factors obtained by means of approximate analytical solutions, numerical approaches, and measurements in electric analog models. It is shown that some expressions that are currently used in practice are inadequate and should be abandoned.
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Safety and Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma (HCC) and Child-Pugh A versus B Cirrhosis.
Gastrointest Cancer Res
PUBLISHED: 06-16-2011
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We performed a retrospective analysis of data from a phase II study evaluating sorafenib in patients with advanced hepatocellular carcinoma (HCC) to assess differences in safety and efficacy based on Child-Pugh (CP) status (A/B).
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PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma.
Cancer Chemother. Pharmacol.
PUBLISHED: 03-31-2011
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PR-104 is activated by reductases under hypoxia or by aldo-keto reductase 1C3 (AKR1C3) to form cytotoxic nitrogen mustards. Hepatocellular carcinoma (HCC) displays extensive hypoxia and expresses AKR1C3. This study evaluated the safety and efficacy of PR-104 plus sorafenib in HCC.
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A Cancer and Leukemia Group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603).
Oncologist
PUBLISHED: 12-10-2010
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The Cancer and Leukemia Group B (CALGB) conducted a phase II study evaluating sunitinib in patients with progressive metastatic pancreas adenocarcinoma following prior gemcitabine-based therapy (trial CALGB 80603; ClinicalTrials.gov identifier, NCT00397787). The primary endpoint was to determine the disease control rate (DCR) as measured by the Response Evaluation Criteria in Solid Tumors (complete response, partial response [PR], and stable disease) at 6 weeks.
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Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial.
JAMA
PUBLISHED: 11-18-2010
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In a randomized phase 3 trial, 400 mg of sorafenib twice daily prolonged overall survival of patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh A disease. In a phase 1 study, sorafenib combined with doxorubicin, 60 mg/m(2), was well tolerated by patients with refractory solid tumors. The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial.
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Integrating recent data in managing adverse events in the treatment of hepatocellular carcinoma.
Gastroenterol Hepatol (N Y)
PUBLISHED: 09-01-2010
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Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality worldwide. In the United States, HCC is the main cause of death in patients with cirrhosis, and the incidence of this malignancy is on the rise. Because HCC is associated with a particularly poor prognosis, emphasis is placed on surveillance of high-risk patients. Early detection allows a greater chance of diagnosing HCC before it has spread, thus increasing the chances that the patient can be potentially cured with surgical techniques such as resection and transplantation. However, most cases of HCC are not diagnosed until at least some of the cancer has spread or multiple nodules exist. For these patients, treatment options include percutaneous and transarterial ablation, as well as systemic chemotherapy. Systemic therapy is now considered the standard of care for patients with advanced tumors. Traditional treatment was based on cytotoxic chemotherapeutic agents, such as doxorubicin. This approach was associated with minimal benefit and a high rate of toxicity. Recently, targeted agents have proven more effective and safer in this setting. The oral multikinase inhibitor sorafenib is now approved for the treatment of unresectable HCC and is currently the only approved agent for advanced HCC. In order to maximize the benefit of sorafenib and other investigational agents for patients with advanced disease, effective interventions have been designed to mitigate their associated adverse events, such as hand-foot skin reactions and hypertension.
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Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement.
HPB (Oxford)
PUBLISHED: 07-02-2010
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Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options.
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Advanced hepatocellular carcinoma: which staging systems best predict prognosis?
J. Clin. Oncol.
PUBLISHED: 05-10-2010
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The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival.
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Clinical roundtable monograph. Integrating recent data in managing adverse events in the treatment of hepatocellular carcinoma.
Clin Adv Hematol Oncol
PUBLISHED: 04-14-2010
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Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality worldwide. In the United States, HCC is the main cause of death in patients with cirrhosis, and the incidence of this malignancy is on the rise. Because HCC is associated with a particularly poor prognosis, emphasis is placed on surveillance of high-risk patients. Early detection allows a greater chance of diagnosing HCC before it has spread, thus increasing the chances that the patient can be potentially cured with surgical techniques such as resection and transplantation. However, most cases of HCC are not diagnosed until at least some of the cancer has spread or multiple nodules exist. For these patients, treatment options include percutaneous and transarterial ablation, as well as systemic chemotherapy. Systemic therapy is now considered the standard of care for patients with advanced tumors. Traditional treatment was based on cytotoxic chemotherapeutic agents, such as doxorubicin. This approach was associated with minimal benefit and a high rate of toxicity. Recently, targeted agents have proven more effective and safer in this setting. The oral multikinase inhibitor sorafenib is now approved for the treatment of unresectable HCC and is currently the only approved agent for advanced HCC. In order to maximize the benefit of sorafenib and other investigational agents for patients with advanced disease, effective interventions have been designed to mitigate their associated adverse events, such as hand-foot skin reactions and hypertension.
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Indications for neoadjuvant, adjuvant, and palliative chemotherapy in the treatment of biliary tract cancers.
Surg. Oncol. Clin. N. Am.
PUBLISHED: 03-25-2009
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Advanced biliary tract carcinomas represent a group of aggressive diseases that still carries a poor prognosis. Chemotherapy has been shown to provide disease control and may also prolong survival. An established role for systemic therapy in the adjuvant setting is still lacking. This article reviews the available evidence to support indications of systemic chemotherapy in the palliative setting and discuss the attempts to study it in the perioperative settings.
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Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301.
J. Clin. Oncol.
PUBLISHED: 03-02-2009
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We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction.
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Selection of patients with hepatocellular carcinoma for sorafenib.
J Natl Compr Canc Netw
PUBLISHED: 02-02-2009
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Sorafenib, a multitargeted anti-VEGF receptor and raf kinase inhibitor, was recently approved by the FDA for treating unresectable hepatocellular carcinoma (HCC) based on 2 randomized phase III studies. In addition, a phase II study evaluating sorafenib in patients with HCC and Child-Pugh A and B and a phase I study evaluating sorafenib in patients with organ dysfunction have provided insight about the safety and efficacy of sorafenib in patients with HCC and more advanced cirrhosis, and any difference in outcome based on etiology of HCC. The lack of objective responses observed in the sorafenib arm in the SHARP study also raises practical issues about how to assess response or efficacy of the therapy and thus how long a patient should receive sorafenib. This article addresses these questions on the use of sorafenib in HCC, both in the locally advanced and metastatic settings, in addition to the potential future applications and uses of sorafenib.
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A Nonrandomized, Phase II Study of Sequential Irinotecan and Flavopiridol in Patients With Advanced Hepatocellular Carcinoma.
Gastrointest Cancer Res
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Flavopiridol, a Cdk inhibitor, potentiates irinotecan-induced apoptosis. In a phase I trial of sequential irinotecan and flavopiridol, 2 patients with advanced hepatocellular carcinoma (HCC) had stable disease (SD) for ?14 months. We thus studied the sequential combination of irinotecan and flavopiridol in patients with HCC.
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ACR Appropriateness Criteria radiologic management of hepatic malignancy.
J Am Coll Radiol
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Management of hepatic malignancy is a challenging clinical problem involving several different medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and locoregional therapies, such as thermal ablation and transarterial embolization. The authors discuss treatment strategies for the 3 most common subtypes of hepatic malignancy treated with locoregional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Lymph-node ratio is an independent prognostic factor in patients with stage III colorectal cancer: a retrospective study from the Middle East.
World J Surg Oncol
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In this retrospective study, we evaluated the prognostic effect of positive lymph-node ratio (pLNR) on patients with stage III colorectal cancer (CRC). Our paper is the first analysis, to our knowledge, to deal with such data from the Middle East.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.