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• W2088644829 abstract "See “Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival,” by Kim H-D, Lim Y-S, Han S, et al, on page 1371.One of the major goals of radiologic imaging is the precise detection of cancer, in the hope that sensitive early diagnosis and accurate staging will facilitate the optimal management of cancer patients and favorably impact morbidity and mortality. In this issue of Gastroenterology, which highlights an increasingly prevalent and often lethal tumor, hepatocellular carcinoma (HCC), Kim et al1Kim H.D. Lim Y.S. Han S. et al.Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival.Gastroenterology. 2015; 148: 1371-1382Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar have studied 700 patients and present evidence that an imaging strategy including gadoxetic acid-enhanced MRI in conjunction with multiphasic CT-based imaging can improve cancer staging in patients with cirrhosis by detecting additional sites of neoplasm, enhance treatment and, most important, improve survival.1Kim H.D. Lim Y.S. Han S. et al.Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival.Gastroenterology. 2015; 148: 1371-1382Abstract Full Text Full Text PDF PubMed Scopus (75) Google ScholarContrast-enhanced CT and MRI are the radiologic mainstays for the diagnosis of HCC. The use of intravenous contrast is essential, because the sensitivity of unenhanced imaging is limited, especially for CT scanning. CT contrast agents are based on the radiodense element iodine, whereas those for MRI are based on the paramagnetic element gadolinium. With similar pharmacokinetic behavior, the agents are injected intravenously and pass into the capillary beds of viscera where, except in the central nervous system, the capillary endothelium is permeable to the contrast. After administration, the radiodensity of organ parenchyma on CT, or signal intensity on T1-weighted MRI, increases owing to the presence of contrast in the vessels and its accumulation in extracellular fluid.2Bae K.T. Optimization of contrast enhancement in thoracic MDCT.Radiol Clin North Am. 2010; 48: 9-29Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar The timing and magnitude of the increase is determined by the physiology relating to local tissue characteristics and capillary perfusion. Radiologic diagnosis of HCC is facilitated by the dual blood supply to the liver and its biphasic perfusion, because blood containing intravenous contrast is received first via the hepatic artery and second via the portal vein. The nontumor liver parenchyma receives most of its blood supply from the portal vein, whereas neoplasms, including HCC, typically receive a greater proportion of flow from the hepatic artery as a result of tumor induced arterial neovascularity3Baron R.L. Understanding and optimizing use of contrast material for CT of the liver.AJR Am J Roentgenol. 1994; 163: 323-331Crossref PubMed Scopus (280) Google Scholar (although the difference may be reduced in cirrhosis). The lesions tend to enhance relative to normal liver during the so-called arterial phase after contrast administration, visualized as enhanced, hyperdense lesions on images typically acquired 20–40 seconds after the initiation of a contrast bolus. Over the next 30–60 seconds, this density (for CT) or signal pattern (for MRI) reverses, as the portal vein supplies increased contrast to the non-neoplastic liver; the HCC lesions typically become less dense than the surrounding tissues, a phenomenon termed “washout.” This characteristic enhancement pattern of most HCCs is well-recognized and in fact is one of the main criteria used to diagnose HCC on enhanced CT and MRI.4Wald C. Russo M.W. Heimbach J.K. et al.New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma.Radiology. 2013; 266: 376-382Crossref PubMed Scopus (275) Google ScholarDespite these classic features, the diagnosis of small liver lesions can be difficult. The cirrhotic liver is often heterogeneous, particularly after the administration of intravenous contrast, and it is possible to miss small neoplastic lesions owing to a lack of sensitivity. Compounding this, both normal and cirrhotic livers often have small, non-neoplastic areas of arterial phase hypervascularity that can mimic neoplasms. Such pseudolesions are often attributed to vascular shunting and may present false positive findings on either CT or MRI.5Hwang S.H. Yu J.S. Kim K.W. et al.Small hypervascular enhancing lesions on arterial phase images of multiphase dynamic computed tomography in cirrhotic liver: fate and implications.J Comput Assist Tomogr. 2008; 32: 39-45Crossref PubMed Scopus (32) Google Scholar, 6Holland A.E. Hecht E.M. Hahn W.Y. et al.Importance of small (< or = 20-mm) enhancing lesions seen only during the hepatic arterial phase at MR imaging of the cirrhotic liver: evaluation and comparison with whole explanted liver.Radiology. 2005; 237: 938-944Crossref PubMed Scopus (139) Google Scholar Kim et al have explored a relatively new, nontypical MRI contrast agent, gadoxetic acid, or gadolinium ethoxybenzyl diethylenetriaminepentaacetic (Eovist, Bayer, Whippany, NJ; Primovist, Bayer, Osaka, Japan). Gadoxetic acid has the usual properties of an extracellular gadolinium chelate, which allows assessment of tumor vascularity in an arterial phase. In addition, however, it is hepatocyte targeting, enabling a hepatic “functional phase” assessment approximately 20 minutes after administration. Approximately 50% of an administered dose of gadoxetic acid will be taken up by hepatocytes, possibly less in cirrhotic liver, before excretion in the bile. Crucially, most HCCs will not take up gadoxetic acid, reportedly because they do not express the hepatocyte sinusoidal transporter required for uptake,7Tsuboyama T. Onishi H. Kim T. et al.Hepatocellular carcinoma: hepatocyte-selective enhancement at gadoxetic acid-enhanced MR imaging–correlation with expression of sinusoidal and canalicular transporters and bile accumulation.Radiology. 2010; 255: 824-833Crossref PubMed Scopus (215) Google Scholar and therefore appear as lesions with reduced signal compared with the surrounding liver. This property of gadoxetic acid may increase both the sensitivity and the specificity of the agent, especially for small lesions.8Sano K. Ichikawa T. Motosugi U. et al.Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR imaging.Radiology. 2011; 261: 834-844Crossref PubMed Scopus (269) Google Scholar A weakness, and reason it should not be used as an isolated staging tool, is poorer enhancement and less apparent washout in the arterial and venous phases as a consequence of the typical gadoxetic acid bolus containing only 25%-50% of the molar quantity of gadolinium relative to traditional agents. This can also detrimentally affect the ability to assess the hepatic vessels and detection of thrombus, for example.Over the last 10–15 years, cumulative studies have demonstrated improvements in the sensitivity and specificity of standard cross-sectional imaging. Earlier comparisons, from 2000 to 2002, of staging at preoperative imaging to pathologic stage assessed at liver explants reported sensitivities of 50%-60% (slightly better for MRI),9Krinsky G.A. Lee V.S. Theise N.D. et al.Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis: prospective diagnosis with MR imaging and explantation correlation.Radiology. 2001; 219: 445-454Crossref PubMed Scopus (284) Google Scholar, 10Peterson M.S. Baron R.L. Marsh Jr., J.W. et al.Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation.Radiology. 2000; 217: 743-749Crossref PubMed Scopus (153) Google Scholar, 11de Ledinghen V. Laharie D. Lecesne R. et al.Detection of nodules in liver cirrhosis: spiral computed tomography or magnetic resonance imaging? A prospective study of 88 nodules in 34 patients.Eur J Gastroenterol Hepatol. 2002; 14: 159-165Crossref PubMed Scopus (114) Google Scholar with a specificity of >80%.9Krinsky G.A. Lee V.S. Theise N.D. et al.Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis: prospective diagnosis with MR imaging and explantation correlation.Radiology. 2001; 219: 445-454Crossref PubMed Scopus (284) Google Scholar In a metaanalysis published in 2006, the pooled sensitivities and specificities were 68% and 93%, respectively, for CT and 81% and 85% for MRI.12Colli A. Fraquelli M. Casazza G. et al.Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review.Am J Gastroenterol. 2006; 101: 513-523Crossref PubMed Scopus (411) Google Scholar In a very recent review, further advances have been reported, with per-lesion sensitivity for MRI of 79% (72% for CT) and per-patient sensitivity of MRI of 88%; the per-patient specificity of MRI was 94%. MRI generally outperformed CT.13Lee Y.J. Lee J.M. Lee J.S. et al.Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis.Radiology. 2015; : 140690Google Scholar Not surprisingly, accuracy with both modalities for diagnosis of small HCC <2 cm in size was substantially inferior to that for larger lesions, hence the potential benefit of gadoxetic acid MRI.13Lee Y.J. Lee J.M. Lee J.S. et al.Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis.Radiology. 2015; : 140690Google Scholar, 14Wu L.M. Xu J.R. Gu H.Y. et al.Is liver-specific gadoxetic acid-enhanced magnetic resonance imaging a reliable tool for detection of hepatocellular carcinoma in patients with chronic liver disease?.Dig Dis Sci. 2013; 58: 3313-3325Crossref PubMed Scopus (25) Google Scholar A recent meta-analysis reported an overall sensitivity of gadoxetic acid of 91%, which is better than CT or standard MRI, with a specificity 93%.14Wu L.M. Xu J.R. Gu H.Y. et al.Is liver-specific gadoxetic acid-enhanced magnetic resonance imaging a reliable tool for detection of hepatocellular carcinoma in patients with chronic liver disease?.Dig Dis Sci. 2013; 58: 3313-3325Crossref PubMed Scopus (25) Google Scholar As yet, however, broad experience with gadoxetic acid MRI is lacking and these data need further corroboration. The study by Kim et al1Kim H.D. Lim Y.S. Han S. et al.Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival.Gastroenterology. 2015; 148: 1371-1382Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar supports the use of gadoxetic acid MRI in conjunction with multiphase CT as a means to obtain optimal sensitivity and diagnostic efficacy for the management of patients with HCC. This would have significant cost implications and would need careful consideration.So, how reliable are the data from Kim et al? The study is fairly large but retrospective. The retrospective nature introduces the possibility of selection bias: of the 1,136 patients presenting to their hospital between January 2009 and December 2010 with a single nodule presumed HCC at initial CT, 436 were excluded. The exclusions included 51 cases with an Eastern Cooperative Oncology Group (ECOG) performance of >2 and 169 with Child Pugh class C cirrhosis who were presumably deemed unsuitable for curative or palliative treatment. Other exclusions were based on age, atypical diagnostic imaging, or a nonstandard CT imaging protocol. These are reasonable exclusions, but included in combination >400 patients. Of the 700 patients included in the study, all had a quadruple phase CT scan. In 377, this was the only scan (group 1) whereas 323 had imaging with gadoxetic acid in addition to CT (group 2). The allocation to receive gadoxetic MRI was not a random event, but attributed to the preference of the practicing clinician. This too may have introduced selection bias. The other factor quite difficult to compare in a retrospective study is the impact of differences in the treatments between the 2 groups. Although treatment was delivered according to best practice in a busy center treating large numbers of patients with HCC, it was not protocol driven and many patients received >1 treatment. Having said all that, there is little doubt that additional nodules presumed to be HCC—74 in 53 patients from group 2, to be exact—were detected, and although the proportions of patients in groups 1 and 2 receiving potentially curative treatments (transplantation, resection, ablation) were not different, detection of additional nodules impacted Barcelona Clinic Liver Cancer (BCLC) stage in 42 cases and altered management decisions. Specific targeting of additional nodules included 27 additional transarterial chemoembolization and 9 radiofrequency ablation procedures, as well as 14 additional resections and 3 patients who underwent liver transplantation. The authors also point out that, in some instances, accurate staging led to avoidance of futile resection. Kim et al have gone to some lengths to ensure their data are as robust as possible, acknowledging the limitations of a retrospective study, including inverse probability treatment weighting and propensity score matching in their statistical analyses. A final point to acknowledge is that, although there is literature evidence supporting the possible benefit of gadoxetic acid in detecting small HCCs over traditional MRI with conventional gadolinium contrast agents, different MRI techniques and other contrast agents have not been rigorously compared by Kim et al during the same study period. Thus, for example, it is possible that CT in combination with MRI with a traditional contrast agent for staging would have similar benefit.In conclusion, despite the limitations of a retrospective study, it seems that knowing about additional nodules at the outset, in a subgroup of patients with preserved liver function and preserved functional status, led to additional treatments for some patients while avoiding futile resections in others, thereby positively impacting the overall survival of patients with HCC. This study substantiates the importance of accurate staging at diagnosis. It may be pertinent also to raise the parallel matter of tumor grade. Routine biopsy of HCC for a formal assessment of histological grade from biopsy at diagnosis is a contentious issue.15Sherman M. Bruix J. Biopsy for liver cancer: How to balance research needs with evidence-based clinical practice.Hepatology. 2015; 61: 433-437Crossref PubMed Scopus (30) Google Scholar, 16Torbenson M. Schirmacher P. Liver cancer biopsy - back to the future?!.Hepatology. 2015; 61: 431-433Crossref PubMed Scopus (46) Google Scholar Perhaps, however, knowledge of this too would steer toward aggressive alternative treatment before surgery, or ultimately inform the avoidance of surgery, with improved overall survival despite the small risks of liver biopsy. In the absence of prospective, randomized, controlled studies providing guidance for selecting the best combination of imaging tools for assessing stage, or the role of tumor grade in clinical decision making for HCC, it is likely that debate on these key matters will continue, stimulated in this instance by Kim et al. See “Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival,” by Kim H-D, Lim Y-S, Han S, et al, on page 1371. See “Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival,” by Kim H-D, Lim Y-S, Han S, et al, on page 1371. See “Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival,” by Kim H-D, Lim Y-S, Han S, et al, on page 1371. One of the major goals of radiologic imaging is the precise detection of cancer, in the hope that sensitive early diagnosis and accurate staging will facilitate the optimal management of cancer patients and favorably impact morbidity and mortality. In this issue of Gastroenterology, which highlights an increasingly prevalent and often lethal tumor, hepatocellular carcinoma (HCC), Kim et al1Kim H.D. Lim Y.S. Han S. et al.Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival.Gastroenterology. 2015; 148: 1371-1382Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar have studied 700 patients and present evidence that an imaging strategy including gadoxetic acid-enhanced MRI in conjunction with multiphasic CT-based imaging can improve cancer staging in patients with cirrhosis by detecting additional sites of neoplasm, enhance treatment and, most important, improve survival.1Kim H.D. Lim Y.S. Han S. et al.Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival.Gastroenterology. 2015; 148: 1371-1382Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Contrast-enhanced CT and MRI are the radiologic mainstays for the diagnosis of HCC. The use of intravenous contrast is essential, because the sensitivity of unenhanced imaging is limited, especially for CT scanning. CT contrast agents are based on the radiodense element iodine, whereas those for MRI are based on the paramagnetic element gadolinium. With similar pharmacokinetic behavior, the agents are injected intravenously and pass into the capillary beds of viscera where, except in the central nervous system, the capillary endothelium is permeable to the contrast. After administration, the radiodensity of organ parenchyma on CT, or signal intensity on T1-weighted MRI, increases owing to the presence of contrast in the vessels and its accumulation in extracellular fluid.2Bae K.T. Optimization of contrast enhancement in thoracic MDCT.Radiol Clin North Am. 2010; 48: 9-29Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar The timing and magnitude of the increase is determined by the physiology relating to local tissue characteristics and capillary perfusion. Radiologic diagnosis of HCC is facilitated by the dual blood supply to the liver and its biphasic perfusion, because blood containing intravenous contrast is received first via the hepatic artery and second via the portal vein. The nontumor liver parenchyma receives most of its blood supply from the portal vein, whereas neoplasms, including HCC, typically receive a greater proportion of flow from the hepatic artery as a result of tumor induced arterial neovascularity3Baron R.L. Understanding and optimizing use of contrast material for CT of the liver.AJR Am J Roentgenol. 1994; 163: 323-331Crossref PubMed Scopus (280) Google Scholar (although the difference may be reduced in cirrhosis). The lesions tend to enhance relative to normal liver during the so-called arterial phase after contrast administration, visualized as enhanced, hyperdense lesions on images typically acquired 20–40 seconds after the initiation of a contrast bolus. Over the next 30–60 seconds, this density (for CT) or signal pattern (for MRI) reverses, as the portal vein supplies increased contrast to the non-neoplastic liver; the HCC lesions typically become less dense than the surrounding tissues, a phenomenon termed “washout.” This characteristic enhancement pattern of most HCCs is well-recognized and in fact is one of the main criteria used to diagnose HCC on enhanced CT and MRI.4Wald C. Russo M.W. Heimbach J.K. et al.New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma.Radiology. 2013; 266: 376-382Crossref PubMed Scopus (275) Google Scholar Despite these classic features, the diagnosis of small liver lesions can be difficult. The cirrhotic liver is often heterogeneous, particularly after the administration of intravenous contrast, and it is possible to miss small neoplastic lesions owing to a lack of sensitivity. Compounding this, both normal and cirrhotic livers often have small, non-neoplastic areas of arterial phase hypervascularity that can mimic neoplasms. Such pseudolesions are often attributed to vascular shunting and may present false positive findings on either CT or MRI.5Hwang S.H. Yu J.S. Kim K.W. et al.Small hypervascular enhancing lesions on arterial phase images of multiphase dynamic computed tomography in cirrhotic liver: fate and implications.J Comput Assist Tomogr. 2008; 32: 39-45Crossref PubMed Scopus (32) Google Scholar, 6Holland A.E. Hecht E.M. Hahn W.Y. et al.Importance of small (< or = 20-mm) enhancing lesions seen only during the hepatic arterial phase at MR imaging of the cirrhotic liver: evaluation and comparison with whole explanted liver.Radiology. 2005; 237: 938-944Crossref PubMed Scopus (139) Google Scholar Kim et al have explored a relatively new, nontypical MRI contrast agent, gadoxetic acid, or gadolinium ethoxybenzyl diethylenetriaminepentaacetic (Eovist, Bayer, Whippany, NJ; Primovist, Bayer, Osaka, Japan). Gadoxetic acid has the usual properties of an extracellular gadolinium chelate, which allows assessment of tumor vascularity in an arterial phase. In addition, however, it is hepatocyte targeting, enabling a hepatic “functional phase” assessment approximately 20 minutes after administration. Approximately 50% of an administered dose of gadoxetic acid will be taken up by hepatocytes, possibly less in cirrhotic liver, before excretion in the bile. Crucially, most HCCs will not take up gadoxetic acid, reportedly because they do not express the hepatocyte sinusoidal transporter required for uptake,7Tsuboyama T. Onishi H. Kim T. et al.Hepatocellular carcinoma: hepatocyte-selective enhancement at gadoxetic acid-enhanced MR imaging–correlation with expression of sinusoidal and canalicular transporters and bile accumulation.Radiology. 2010; 255: 824-833Crossref PubMed Scopus (215) Google Scholar and therefore appear as lesions with reduced signal compared with the surrounding liver. This property of gadoxetic acid may increase both the sensitivity and the specificity of the agent, especially for small lesions.8Sano K. Ichikawa T. Motosugi U. et al.Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR imaging.Radiology. 2011; 261: 834-844Crossref PubMed Scopus (269) Google Scholar A weakness, and reason it should not be used as an isolated staging tool, is poorer enhancement and less apparent washout in the arterial and venous phases as a consequence of the typical gadoxetic acid bolus containing only 25%-50% of the molar quantity of gadolinium relative to traditional agents. This can also detrimentally affect the ability to assess the hepatic vessels and detection of thrombus, for example. Over the last 10–15 years, cumulative studies have demonstrated improvements in the sensitivity and specificity of standard cross-sectional imaging. Earlier comparisons, from 2000 to 2002, of staging at preoperative imaging to pathologic stage assessed at liver explants reported sensitivities of 50%-60% (slightly better for MRI),9Krinsky G.A. Lee V.S. Theise N.D. et al.Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis: prospective diagnosis with MR imaging and explantation correlation.Radiology. 2001; 219: 445-454Crossref PubMed Scopus (284) Google Scholar, 10Peterson M.S. Baron R.L. Marsh Jr., J.W. et al.Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation.Radiology. 2000; 217: 743-749Crossref PubMed Scopus (153) Google Scholar, 11de Ledinghen V. Laharie D. Lecesne R. et al.Detection of nodules in liver cirrhosis: spiral computed tomography or magnetic resonance imaging? A prospective study of 88 nodules in 34 patients.Eur J Gastroenterol Hepatol. 2002; 14: 159-165Crossref PubMed Scopus (114) Google Scholar with a specificity of >80%.9Krinsky G.A. Lee V.S. Theise N.D. et al.Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis: prospective diagnosis with MR imaging and explantation correlation.Radiology. 2001; 219: 445-454Crossref PubMed Scopus (284) Google Scholar In a metaanalysis published in 2006, the pooled sensitivities and specificities were 68% and 93%, respectively, for CT and 81% and 85% for MRI.12Colli A. Fraquelli M. Casazza G. et al.Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review.Am J Gastroenterol. 2006; 101: 513-523Crossref PubMed Scopus (411) Google Scholar In a very recent review, further advances have been reported, with per-lesion sensitivity for MRI of 79% (72% for CT) and per-patient sensitivity of MRI of 88%; the per-patient specificity of MRI was 94%. MRI generally outperformed CT.13Lee Y.J. Lee J.M. Lee J.S. et al.Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis.Radiology. 2015; : 140690Google Scholar Not surprisingly, accuracy with both modalities for diagnosis of small HCC <2 cm in size was substantially inferior to that for larger lesions, hence the potential benefit of gadoxetic acid MRI.13Lee Y.J. Lee J.M. Lee J.S. et al.Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis.Radiology. 2015; : 140690Google Scholar, 14Wu L.M. Xu J.R. Gu H.Y. et al.Is liver-specific gadoxetic acid-enhanced magnetic resonance imaging a reliable tool for detection of hepatocellular carcinoma in patients with chronic liver disease?.Dig Dis Sci. 2013; 58: 3313-3325Crossref PubMed Scopus (25) Google Scholar A recent meta-analysis reported an overall sensitivity of gadoxetic acid of 91%, which is better than CT or standard MRI, with a specificity 93%.14Wu L.M. Xu J.R. Gu H.Y. et al.Is liver-specific gadoxetic acid-enhanced magnetic resonance imaging a reliable tool for detection of hepatocellular carcinoma in patients with chronic liver disease?.Dig Dis Sci. 2013; 58: 3313-3325Crossref PubMed Scopus (25) Google Scholar As yet, however, broad experience with gadoxetic acid MRI is lacking and these data need further corroboration. The study by Kim et al1Kim H.D. Lim Y.S. Han S. et al.Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival.Gastroenterology. 2015; 148: 1371-1382Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar supports the use of gadoxetic acid MRI in conjunction with multiphase CT as a means to obtain optimal sensitivity and diagnostic efficacy for the management of patients with HCC. This would have significant cost implications and would need careful consideration. So, how reliable are the data from Kim et al? The study is fairly large but retrospective. The retrospective nature introduces the possibility of selection bias: of the 1,136 patients presenting to their hospital between January 2009 and December 2010 with a single nodule presumed HCC at initial CT, 436 were excluded. The exclusions included 51 cases with an Eastern Cooperative Oncology Group (ECOG) performance of >2 and 169 with Child Pugh class C cirrhosis who were presumably deemed unsuitable for curative or palliative treatment. Other exclusions were based on age, atypical diagnostic imaging, or a nonstandard CT imaging protocol. These are reasonable exclusions, but included in combination >400 patients. Of the 700 patients included in the study, all had a quadruple phase CT scan. In 377, this was the only scan (group 1) whereas 323 had imaging with gadoxetic acid in addition to CT (group 2). The allocation to receive gadoxetic MRI was not a random event, but attributed to the preference of the practicing clinician. This too may have introduced selection bias. The other factor quite difficult to compare in a retrospective study is the impact of differences in the treatments between the 2 groups. Although treatment was delivered according to best practice in a busy center treating large numbers of patients with HCC, it was not protocol driven and many patients received >1 treatment. Having said all that, there is little doubt that additional nodules presumed to be HCC—74 in 53 patients from group 2, to be exact—were detected, and although the proportions of patients in groups 1 and 2 receiving potentially curative treatments (transplantation, resection, ablation) were not different, detection of additional nodules impacted Barcelona Clinic Liver Cancer (BCLC) stage in 42 cases and altered management decisions. Specific targeting of additional nodules included 27 additional transarterial chemoembolization and 9 radiofrequency ablation procedures, as well as 14 additional resections and 3 patients who underwent liver transplantation. The authors also point out that, in some instances, accurate staging led to avoidance of futile resection. Kim et al have gone to some lengths to ensure their data are as robust as possible, acknowledging the limitations of a retrospective study, including inverse probability treatment weighting and propensity score matching in their statistical analyses. A final point to acknowledge is that, although there is literature evidence supporting the possible benefit of gadoxetic acid in detecting small HCCs over traditional MRI with conventional gadolinium contrast agents, different MRI techniques and other contrast agents have not been rigorously compared by Kim et al during the same study period. Thus, for example, it is possible that CT in combination with MRI with a traditional contrast agent for staging would have similar benefit. In conclusion, despite the limitations of a retrospective study, it seems that knowing about additional nodules at the outset, in a subgroup of patients with preserved liver function and preserved functional status, led to additional treatments for some patients while avoiding futile resections in others, thereby positively impacting the overall survival of patients with HCC. This study substantiates the importance of accurate staging at diagnosis. It may be pertinent also to raise the parallel matter of tumor grade. Routine biopsy of HCC for a formal assessment of histological grade from biopsy at diagnosis is a contentious issue.15Sherman M. Bruix J. Biopsy for liver cancer: How to balance research needs with evidence-based clinical practice.Hepatology. 2015; 61: 433-437Crossref PubMed Scopus (30) Google Scholar, 16Torbenson M. Schirmacher P. Liver cancer biopsy - back to the future?!.Hepatology. 2015; 61: 431-433Crossref PubMed Scopus (46) Google Scholar Perhaps, however, knowledge of this too would steer toward aggressive alternative treatment before surgery, or ultimately inform the avoidance of surgery, with improved overall survival despite the small risks of liver biopsy. In the absence of prospective, randomized, controlled studies providing guidance for selecting the best combination of imaging tools for assessing stage, or the role of tumor grade in clinical decision making for HCC, it is likely that debate on these key matters will continue, stimulated in this instance by Kim et al. Evaluation of Early-Stage Hepatocellular Carcinoma by Magnetic Resonance Imaging With Gadoxetic Acid Detects Additional Lesions and Increases Overall SurvivalGastroenterologyVol. 148Issue 7PreviewHepatocellular carcinoma (HCC) has a high rate of intrahepatic recurrence after curative treatment, possibly because metastases are not always identified before treatment. Magnetic resonance (MR) imaging with a liver-specific contrast agent, gadoxetic acid, can detect small HCCs with high levels of sensitivity. We investigated whether MR imaging with gadoxetic acid increases overall and recurrence-free survival of patients initially assessed by computed tomography (CT). Full-Text PDF" @default.
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