RÉSUMÉ
Purpose@#Clinical prognostic criteria using preoperative factors were not developed for post–neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria. @*Materials and Methods@#Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system. @*Results@#One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, –0.012 to 0.142). @*Conclusion@#“Any degree of decrease in tumor size on CT” and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.
RÉSUMÉ
Purpose@#Acquisition time reduction in diffusion-weighted imaging (DWI) can be achieved by the combining multiband and variable-rate selective excitation (MB-VERSE). This study attempted to evaluate and compare the image quality (IQ) and focal lesion detectability of the respiratory-triggered MB-VERSE DWI with conventional DWI for liver magnetic resonance imaging. @*Materials and Methods@#The acquisition time, IQ, and focal lesion detectability of MBVERSE DWI and conventional DWI were compared in 144 patients. Qualitative (overall IQ, IQ at the liver dome, sharpness of the liver margin, and degree of artifacts) and quantitative (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and apparent diffusion co efficient) IQ parameters were compared with the Wilcoxon signed-rank test. The diagnostic accuracy for focal lesion detectability was estimated with the mean figure of merit (FOM) from the area under the jackknife alternative free-response receiver operating characteristic curve. @*Results@#The MB-VERSE DWI exhibited significantly shorter scan time (153.1 ± 34.5 s vs.225.1 ± 33.0 s, p 0.050) and similar diagnostic accuracy (FOM, 0.958 vs.0.957, p = 0.583) compared to those of the conventional DWI. @*Conclusion@#MB-VERSE DWI exhibited a significantly shorter acquisition time than conventional DWI, with compromised overall IQ and lower SNR but preserved CNR and focal liver lesion detectability. MB-VERSE DWI may be a useful alternative for patients requiring a short acquisition time.
RÉSUMÉ
Background/Aims@#To compare the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2018 and Korean Liver Cancer Association-National Cancer Center (KLCANCC) 2018 criteria for diagnosing hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI) with hepatobiliary agent (HBA). @*Methods@#We searched the MEDLINE and EMBASE for studies from January 1, 2018, to October 20, 2021, that compared the diagnostic performance of two imaging criteria on HBA-MRI. A bivariate random-effects model was fitted to calculate the per-observation sensitivity and specificity, and the estimates of paired data were compared. Subgroup analysis was performed based on the observation size. Meta-regression analysis was also performed for study heterogeneity. @*Results@#Of the six studies included, the pooled sensitivity of the definite HCC category of the KLCA-NCC criteria (82%; 95% confidence interval [CI], 74% to 90%; I 2 =84%) was higher than that of LR-5 of LI-RADS v2018 (65%; 95% CI, 52% to 77%; I 2 =96%) for diagnosing HCC (p<0.001), while the specificity was lower for KLCA-NCC criteria (87%; 95% CI, 84% to 91%; I 2 =0%) than LI-RADS v2018 (93%; 95% CI, 91% to 96%; I 2 =0%) (p=0.017). For observations sized ≥20 mm, the sensitivity was higher for KLCA-NCC 2018 than for LI-RADS v2018 (84% vs 74%, p=0.012), with no significant difference in specificity (81% vs 85%, p=0.451). The reference standard was a significant factor contributing to the heterogeneity of sensitivities. @*Conclusions@#The definite HCC category of KLCA-NCC 2018 provided a higher sensitivity and lower specificity than the LR-5 of LI-RADS v2018 for diagnosing HCC using MRI with HBA.
RÉSUMÉ
Background/Aims@#Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. @*Methods@#We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. @*Results@#Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. @*Conclusions@#We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.
RÉSUMÉ
Purpose@#A meta-analysis was conducted to determine the proportion of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System category M (LR-M) in hepatocellular carcinomas (HCCs) and non-HCC malignancies and to investigate the frequency of individual CEUS LR-M imaging features. @*Methods@#The MEDLINE and Embase databases were searched from January 1, 2016 to July 23, 2020 for studies reporting the proportion of CEUS LR-M in HCC and non-HCC malignancies. The meta-analytic pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were calculated. The meta-analytic frequencies of CEUS LR-M imaging features in nonHCC malignancies were also determined. Risk of bias and applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. @*Results@#Twelve studies reporting the diagnostic performance of the CEUS LR-M category were identified, as well as seven studies reporting the frequencies of individual CEUS LR-M imaging features. The pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were 54% (95% confidence interval [CI], 44% to 65%) and 40% (95% CI, 28% to 53%), respectively. The pooled frequencies of individual CEUS LR-M imaging features in non-HCC malignancies were 30% (95% CI, 17% to 45%) for rim arterial phase hyperenhancement, 79% (95% CI, 66% to 90%) for early (<60 s) washout, and 42% (95% CI, 21% to 64%) for marked washout. @*Conclusion@#In total, 94% of CEUS LR-M lesions were malignancies, with HCCs representing 54% and non-HCC malignancies representing 40%. The frequencies of individual CEUS LR-M imaging features varied; early washout showed the highest frequency for non-HCC malignancies.
RÉSUMÉ
Purpose@#To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. @*Materials and Methods@#Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7–12 months (1Y), 13–24 months (2Y), and 25–36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. @*Results@#The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77;never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). @*Conclusion@#HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.
RÉSUMÉ
Imaging studies play an important role in the detection, diagnosis, assessment of resectability, staging, and determination of patient-tailored treatment options for pancreatic adenocarcinoma. Recently, for patients diagnosed with borderline resectable or locally advanced pancreatic cancers, it is recommended to consider curative-intent surgery following neoadjuvant or palliative therapy, if possible. This review covers how to interpret imaging tests and what to consider when assessing resectability, diagnosing distant metastasis, and re-assessing the resectability of pancreatic cancer after neoadjuvant or palliative therapy.
RÉSUMÉ
Biliary adenofibromas are rare biliary epithelial tumors that are classified as benign. Nevertheless, some cases have been reported to show malignant transformations. The radiologic findings of biliary adenofibromas and their malignant transformation are not well-established because of their rarity. We present a case of a cholangiocarcinoma arising from a biliary adenofibroma assessed using ultrasonography, CT, and MRI. The differential diagnoses include other hepatic tumors.
RÉSUMÉ
Objective@#Based on the Liver Imaging Reporting and Data System version 2018 (LI-RADS, v2018), this study aimed to analyze LR-5 diagnostic performance for hepatocellular carcinoma (HCC) when threshold growth as a major feature is replaced by a more HCC-specific ancillary feature, as well as the frequency of threshold growth in HCC and non-HCC malignancies and its association with tumor size. @*Materials and Methods@#This retrospective study included treatment-naive patients who underwent gadoxetate disodiumenhanced MRIs for focal hepatic lesions and surgery between January 2009 and December 2016. The frequency of major and ancillary features was evaluated for HCC and non-HCC malignancies, and the LR-category was assessed. Ancillary features that were significantly more prevalent in HCC were then used to either replace threshold growth or were added as additional major features, and the diagnostic performance of the readjusted LR category was compared to the LI-RADS v2018. @*Results@#A total of 1013 observations were analyzed. Unlike arterial phase hyperenhancement, washout, or enhancing capsule which were more prevalent in HCCs than in non-HCC malignancies (521/616 vs. 18/58, 489/616 vs. 19/58, and 181/616 vs. 5/58, respectively; p 0.999) were comparable to the LI-RADS v2018. @*Conclusion@#Threshold growth is not a significant diagnostic indicator of HCC and is more common in non-HCC malignancies. The diagnostic performance of LR-5 was comparable when threshold growth was recategorized as an ancillary feature and replaced by a more HCC-specific ancillary feature.
RÉSUMÉ
Purpose@#To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. @*Materials and Methods@#Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7–12 months (1Y), 13–24 months (2Y), and 25–36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. @*Results@#The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77;never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). @*Conclusion@#HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.
RÉSUMÉ
Imaging studies play an important role in the detection, diagnosis, assessment of resectability, staging, and determination of patient-tailored treatment options for pancreatic adenocarcinoma. Recently, for patients diagnosed with borderline resectable or locally advanced pancreatic cancers, it is recommended to consider curative-intent surgery following neoadjuvant or palliative therapy, if possible. This review covers how to interpret imaging tests and what to consider when assessing resectability, diagnosing distant metastasis, and re-assessing the resectability of pancreatic cancer after neoadjuvant or palliative therapy.
RÉSUMÉ
Biliary adenofibromas are rare biliary epithelial tumors that are classified as benign. Nevertheless, some cases have been reported to show malignant transformations. The radiologic findings of biliary adenofibromas and their malignant transformation are not well-established because of their rarity. We present a case of a cholangiocarcinoma arising from a biliary adenofibroma assessed using ultrasonography, CT, and MRI. The differential diagnoses include other hepatic tumors.
RÉSUMÉ
Phospholipase C beta 2 (PLC-β2) regulates various essential functions in cell signaling, differentiation, growth, and mobility. We investigated the clinical implications of PLC-β2 protein expression in newly diagnosed normal karyotype acute myeloid leukemia (NKAML). The PLC-β2 expression status in bone marrow tissues obtained from 101 patients with NK-AML was determined using semiquantitative immunohistochemistry (IHC). IHC results were compared with those for known prognostic markers. Using a cutoff score for positivity of 7.0, the PLC-β2 overexpression group showed superior overall survival (OS) (72.6% vs. 26.5%; P = 0.016) and low hazard ratio (HR) (0.453; P = 0.019) compared with the PLC-β2 low-expression group. The PLC-β2 overexpression group showed no significant gain in event-free survival (50.6% vs. 43.0%, P =0.465) and HR (0.735; P =0.464).Among the known prognostic markers, only FLT3-ITD positivity was associated with a significantly low OS and high HR. In conclusion, PLC-β2 overexpression was associated with favorable OS in NK-AML patients. Our results suggest that PLC-β2 expression assessment using IHC allows prognosis prediction in NK-AML.
RÉSUMÉ
In pancreatic cancer, imaging plays an essential role in surveillance, diagnosis, resectability evaluation, and treatment response evaluation. Pancreatic cancer surveillance in high-risk individuals has been attempted using endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI). Imaging diagnosis and resectability evaluation are the most important factors influencing treatment decisions, where computed tomography (CT) is the preferred modality. EUS, MRI, and positron emission tomography play a complementary role to CT. Treatment response evaluation is of increasing clinical importance, especially in patients undergoing neoadjuvant therapy. This review aimed to comprehensively review the role of imaging in relation to the current treatment strategy for pancreatic cancer, including surveillance, diagnosis, evaluation of resectability and treatment response, and prediction of prognosis.
RÉSUMÉ
Objective@#Based on the Liver Imaging Reporting and Data System version 2018 (LI-RADS, v2018), this study aimed to analyze LR-5 diagnostic performance for hepatocellular carcinoma (HCC) when threshold growth as a major feature is replaced by a more HCC-specific ancillary feature, as well as the frequency of threshold growth in HCC and non-HCC malignancies and its association with tumor size. @*Materials and Methods@#This retrospective study included treatment-naive patients who underwent gadoxetate disodiumenhanced MRIs for focal hepatic lesions and surgery between January 2009 and December 2016. The frequency of major and ancillary features was evaluated for HCC and non-HCC malignancies, and the LR-category was assessed. Ancillary features that were significantly more prevalent in HCC were then used to either replace threshold growth or were added as additional major features, and the diagnostic performance of the readjusted LR category was compared to the LI-RADS v2018. @*Results@#A total of 1013 observations were analyzed. Unlike arterial phase hyperenhancement, washout, or enhancing capsule which were more prevalent in HCCs than in non-HCC malignancies (521/616 vs. 18/58, 489/616 vs. 19/58, and 181/616 vs. 5/58, respectively; p 0.999) were comparable to the LI-RADS v2018. @*Conclusion@#Threshold growth is not a significant diagnostic indicator of HCC and is more common in non-HCC malignancies. The diagnostic performance of LR-5 was comparable when threshold growth was recategorized as an ancillary feature and replaced by a more HCC-specific ancillary feature.
RÉSUMÉ
Tumor thrombus in the portal vein without any liver parenchymal abnormality is extremely rare. In the liver, the primary tumor most frequently presenting with intravascular tumor thrombi is hepatocellular carcinoma and lymphoma is rarely considered. Even though thrombosis occurs quite often in lymphoma, cases of tumor thrombus are rare and cases of tumor thrombus in the portal vein are even rarer. Only four cases of lymphoma with portal vein tumor thrombosis have been reported to date and all cases were the result of direct extensions of a dominant nodal or extra-nodal mass. To our knowledge, there has been no report on diffuse large B-cell lymphoma (DLBCL) presenting only within the lumen of the portal vein and not intravascular B-cell lymphoma. We present the first case of DLBCL presenting only within the lumen of the portal vein in an immunocompetent patient.
RÉSUMÉ
BACKGROUND/OBJECTIVES@#The Seoul Metabolic Syndrome Management (SMESY) program is a 1-yr lifestyle modification program targeting metabolic syndrome (MetS) in Seoul residents. This study investigated the associations between adherence to dietary guidelines and MetS among the SMESY program participants. @*SUBJECTS/METHODS@#Data of 54,385 participants aged 20–64 yrs who completed the SMESY program in 2015, had information on adherence to dietary guidelines, and were not medicated for diabetes, hypertension, or dyslipidemia were analyzed. Participants underwent MetS screening and completed a lifestyle questionnaire including adherence to 10 dietary guidelines before and after participation. Participants were classified according to the number of MetS risk factors at baseline (MetS group, ≥ 3; risk group, 1–2; healthy group, none). Adherence to dietary guidelines was determined from the number of “yes” responses regarding the fulfillment of each guideline on ≥ 5 days/week. Multiple logistic regression was used to evaluate associations between newly diagnosed MetS and changes in adherence to dietary guidelines. @*RESULTS@#In the MetS group, MetS prevalence decreased after the SMESY program (men, −41.9%p; women, −48.7%p), and all risk factors were significantly improved (P < 0.0001). All groups exhibited improved adherence to all dietary guidelines after participation (P < 0.0001). In the MetS group with positively changed adherence scores, the MetS prevalence decreased by −44.1%p for men and −49.5%p for women, whereas the prevalence in those with negative changes decreased by −38.1%p for men and −48.6%p for women. In the risk group, those with positively changed adherence scores had significantly decreased odds ratios (ORs) for newly diagnosed MetS compared with those with negative changes (OR, 0.70; 95% confidence interval [CI], 0.61–0.80 for men; OR, 0.88; 95% CI, 0.79–0.99 for women). @*CONCLUSIONS@#The SMESY program may effectively reduce the risk of MetS among adults with risk factors by improving adherence to dietary guidelines.
RÉSUMÉ
The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
RÉSUMÉ
Background/Aims@#The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria have been used to assess treatment responses for hepatocellular carcinoma (HCC) patients. We investigated which criteria provides better survival predictions in HCC patients treated with transarterial radioembolization (TARE). @*Methods@#In total, 102 patients with unresectable intrahe-patic HCC, who were treated with TARE between 2012 and 2017, were reviewed retrospectively. The treatment response after TARE was evaluated at 1, 3, and 6 months by the mRE-CIST and RECIST 1.1. Responders were defined as patients with complete or partial responses by each criterion. @*Results@#The median age of 83 men and 19 women was 64.3 years.The median alpha-fetoprotein and des-gamma-carboxy pro-thrombin levels were 37.1 ng/mL and 1,780.0 mAU/mL, re-spectively. The median maximal tumor size was 8.3 cm, and multiple tumors were observed in 36 patients (35.3%). Dur-ing the follow-up period (median, 20.7 months), 21 patients (20.6%) died, with a mean survival time of 55.5 months. The cumulative survival rate was 96.1% at 6 months and 89.3% at 12 months. Responders, defined by the mRECIST at 1, 3, and 6 months after TARE, showed better survival outcomes than nonresponders (hazard ratio [HR]=5.736, p=0.008 at 1 month; HR=3.145, p=0.022 at 3 months, and HR=2.887, p=0.061 at 6 months). The survival rates of responders and nonresponders defined by the RECIST 1.1 were similar (all p>0.05). @*Conclusions@#Response evaluations that use the mRECIST provide more accurate prognoses than those that use the RECIST 1.1 in HCC patients treated with TARE.
RÉSUMÉ
PURPOSE: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx).MATERIALS AND METHODS: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method.RESULTS: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014).CONCLUSION: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.