High standard uptake value of the primary lesion of hepatocellular carcinoma correlates with early recurrence after curative resection

High standard uptake value of the primary lesion of hepatocellular carcinoma correlates with early recurrence after curative resection | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article High standard uptake value of the primary lesion of hepatocellular carcinoma correlates with early recurrence after curative resection Kazuya Kato, Takehiro Noda, Shogo Kobayashi, Chihiro Yamanaka, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4239792/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful for detecting the presence of distant metastases in many types of cancer, including hepatocellular carcinoma (HCC). However, the clinical significance of the standard uptake value (SUV) in primary HCC lesions is unclear. Aim We investigated the relationship between the SUV, clinicopathological factors, and prognosis in HCC. Methods The retrospective analysis included 86 patients with HCC who underwent FDG-PET/CT prior to liver resection. The distribution of SUV was compared in three groups: no recurrence after surgery, recurrence within 2 years, and recurrence after 2 years. The optimal cut-off SUV were determined based on receiver operating characteristic curve analysis to detect the recurrence within 2 years. All patients were divided into two groups based on the cut-off: low and high SUV. Cox univariate and multivariate analyses were performed for disease-free survival. Results The SUV was significantly higher in patients with recurrence within 2 years. The optimal cut-off SUV was 5.0. The patients in the high SUV group had significantly higher des-γ-carboxy prothrombin, poorer differentiation, and larger tumor diameter than the low SUV group, and presented with pathologically positive intrahepatic metastases. Moreover, high SUV was a significant and independent prognostic factor. In a subgroup analysis, high SUV had a significantly lower 2-year disease-free survival rate than the low SUV group in tumors ≤ 3.5 cm. Conclusions High SUV (≥ 5) on FDG-PET/CT of the primary HCC lesion, especially tumors ≤ 3.5 cm, correlates with early recurrence after curative resection and is an independent prognostic factor. HCC SUV early recurrence postoperative recurrence prognosis disease-free survival Figures Figure 1 Figure 2 Figure 3 Introduction Primary liver cancer is the sixth most frequently occurring cancer and the third leading cause of cancer mortality worldwide, with approximately 906,000 new cases and 830,000 deaths per year. Incidence rates have increased in many countries in recent decades. Hepatocellular carcinoma (HCC) is the dominant type of primary liver cancer, accounting for approximately 80% of the total number of cases worldwide. 1 , 2 Although various testing and treatment methods have been developed for HCC patients, the survival rate remains low, with a global 5-year survival rate of 5–30%. 3 HCC has a high recurrence rate after treatment; approximately 70% of patients with HCC experience recurrence within 5 years after surgery, even after radical resection. 4 , 5 , 6 This high recurrence rate may be the reason why the survival rate remains unsatisfactory for HCC. Therefore, we must develop a better understanding of the mechanisms of HCC recurrence and the optimal treatment strategy. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an effective and noninvasive modality for scanning the whole body. FDG-PET/CT has high sensitivity for detecting distant metastases in various types of malignant tumors, including HCC. In addition, FDG accumulation in primary tumors may reflect tumor characteristics based on the metabolic activity. 7 , 8 The standard uptake value (SUV) can be applied to the diagnosis of the metabolic and proliferative potential of primary tumors. In recent years, the relationships between the SUV on FDG-PET/CT and tumor differentiation, vascular invasion, tumor markers, and prognosis have been pointed out in various cancers. 9 , 10 , 11 The usefulness of FDG-PET/CT in the evaluation of primary lesions has attracted much attention. 12 According to the 2021 Japan Society of Hepatology guidelines for HCC, FDG-PET/CT imaging is recommended only for patients with risk factors for extrahepatic metastasis. However, the clinical significance of SUV in primary HCC lesions is still unclear. In this study, we evaluated the relationship between the SUV in the primary lesion, clinicopathological factors, and prognosis in HCC patients. Materials and Methods Patients A total of 86 patients underwent preoperative FDG-PET/CT and curative surgery for primary HCC between January 2010 and December 2020 at the Department of Gastroenterological Surgery of Osaka University Hospital. The patients’ medical records were reviewed retrospectively, and the following clinical, surgical, and pathological factors were collected; sex, age, alcohol, hepatitis B surface antigen (HBs-Ag), hepatitis C virus antibody (HCV-Ab), Child–Pugh classification, liver damage classification established by the Liver Cancer Study Group of Japan, α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels, tumor number, tumor diameter, histological differentiation, and stage based on General Rules for the Clinical and Pathological Study of Primary Liver Cancer (6th edition). A history of heavy alcohol use was defined as consumption of 30 g or more of pure alcohol equivalent per day. Hepatic resection was carried out as reported previously. 13 All aspects of our study protocol were approved by the Human Ethics Committee of the Graduate School of Medicine, Osaka University, Japan. Written informed consent was obtained from all patients for research use of their clinicopathological data. This study was performed in accordance with the ethical guidelines of the Declaration of Helsinki. FDG-PET/CT The SUV of primary tumors was measured preoperatively, and the procedure for FDG-PET/CT was described previously. 14 Briefly, whole-body FDG-PET/CT was carried out using the Gemini GXL (Phillips, Eindhoven, the Netherlands). Prior to imaging, all patients fasted for 5 hours before intravenous administration of FDG at a dose of 3.7 MBq/kg. The PET/CT images were acquired 120 minutes after FDG administration. The SUV was calculated by measuring FDG uptake in the non-tumorous liver and primary HCC tumors as follows: SUV = [maximal radioactivity concentration]/[injected dose/patient weight (kg)]. Relationship between SUV and survival The distributions of the SUV in normal liver and primary HCC tumor were compared. The patients were divided into three groups based on postoperative recurrence: no recurrence, recurrence within 2 years, and recurrence after 2 years. The distribution of SUV in the three groups was compared by one-way analysis of variance. The optimal cut-off values for the SUV were set based on the receiver operating characteristic curve (ROC) analysis in the primary HCC tumor. The cut-off value, which is located at the highest point on the vertical axis and the left end of the horizontal axis on the ROC curve, was calculated to maximize the sensitivity and specificity to detect the tumor recurrence within 2 years after hepatic resection. All patients were divided into two groups using the determined cut-off value: low SUV or high SUV. The patients’ clinicopathological indicators were compared between the two groups using chi-squared and Student's t-tests. Disease-free survival (DFS) and overall survival (OS) curves were analyzed using the Kaplan–Meier method, and differences between survival curves were compared by the log-rank test. To evaluate the risks associated with the prognostic variables, univariate and multivariate analyses using a Cox model were performed, with determination of hazard ratios and 95% confidence intervals. As a subgroup analysis, we examined differences in the SUV relationships between small and large tumors. First, patients were divided based on median tumor diameter into two groups (small or large) and the distribution of tumor SUV examined. Next, DFS and OS rates were analyzed between the low and high SUV groups in each subgroup. Statistical analysis All statistical analyses were performed using R version 4.2.2 (Vienna, Austria; http://www.R-project.org/ ). P < 0.05 was considered significant. Results Patient characteristics The patients’ baseline characteristics are summarized in Table 1 . The median patient age was 74 years (range 14–88 years); 68 patients were male and 18 were female. Twenty-four patients had a history of heavy alcohol use. Twelve patients were HBs-Ag-positive and 22 HCV-Ab-positive. Among all patients, 81 were categorized into Child-Pugh A and 5 into Child-Pugh B, whereas 72 and 14 patients were categorized as having liver damage grades A and B, respectively. Regarding tumor markers, the median AFP and DCP levels were 10.5 ng/mL and 176.5 mAU/mL, respectively. Seventy-six cases had a solitary tumor and 10 cases multiple tumors. Regarding histological differentiation, well-differentiated HCC was found in 8 cases, moderately differentiated in 60, and poorly differentiated in 18. The stage was I in 14 patients, II in 57, III in 11, and IV in 4. Table 1 Baseline characteristics Characteristics Values Sex (male / female) 68 / 18 Age (years) 74 (14–88) Alcohol (- / +) 62 / 24 HBs-Ag (- / +) 74 / 12 HCV-Ab (- / +) 64 / 22 Child Pugh (A / B / C) 81 / 5 / 0 Liver damage (A / B / C) 72 / 14 / 0 AFP (ng/mL) 10.5 (1–147064) DCP (mAU/mL) 176.5 (12–88400) Number of tumors (solitary / multiple) 76 / 10 Tumor diameter (cm) 3.5 (0.9–18.0) Histological differentiation (wel. / mod. / por.) 8 / 60 / 18 Stage (I / II / III / IV) 14 / 57 / 11 / 4 SUV 3.8 (2.4–14.4) Distribution of SUV in normal liver and tumor and the cut-off value for tumor SUV The distributions of SUV in the normal liver and primary lesion are shown in Fig. 1 A; the median SUV in all patients was 2.5 and 3.8, respectively. The ranges in normal liver and the primary lesion were 1.7–3.6 and 2.4–14.4, respectively. The tumor SUV was significantly higher in the patients with recurrence within 2 years after surgery (6.14 ± 3.46) than those without recurrence (3.97 ± 1.63) or recurrence after 2 years (4.38 ± 2.17, P < 0.001; Fig. 1 B). The ROC analysis for recurrence within 2 years after surgery (Fig. 1 C) showed that the optimal tumor SUV cut-off was 5.0, with an area under the curve (AUC) of 0.741. With this cut-off value, the sensitivity and specificity were 0.520 and 0.869, respectively. In our cohort, the positive predictive value was 61.9% and false negative rate 48.0%. Based on the above, we set the cut-off for the tumor SUV to 5.0, which was about twice that of normal liver. Using our cut-off value, we divided all patients into two groups: low SUV (SUV < 5; n = 65) and high SUV (SUV ≥ 5; n = 21). Comparison of clinicopathological factors in the low SUV and high SUV groups In the comparison of clinicopathological factors between the low SUV and high SUV groups, there were significant differences in the levels of DCP (3819 mAU/mL vs. 15543 mAU/mL, P = 0.008), histological differentiation (wel./mod./por. : 8/52/5 vs. 0/8/13, P < 0.001), tumor diameter (4.03 cm vs. 6.32 cm, P = 0.006), and microscopic intrahepatic metastasis (16.9% vs. 47.6%, P = 0.011; Table 2 ). Table 2 Comparison of clinicopathological factors between the low SUV and high SUV groups Variables Low SUV (< 5) High SUV (≥ 5) P-value n = 65 N = 21 Sex (male/female) 52 / 13 16 / 5 0.949 Age (years) 69.9 ± 13.6 73.4 ± 13.4 0.315 Alcohol (- / +) 45 / 20 17 / 4 0.446 HBs-Ag (- / +) 58 / 7 16 / 5 0.255 HCV-Ab (- / +) 46 / 19 18 / 3 0.281 Child Pugh (A / B) 62 / 3 19 / 2 0.765 Liver damage (A / B) 55 / 10 17 / 4 0.956 WBC (/µL) 5093 ± 1548 5256 ± 1426 0.672 Hb (g/dL) 13.4 ± 1.7 12.7 ± 1.7 0.101 PLT (×10 3 /µL) 174.3 ± 61.5 164.1 ± 46.3 0.487 Alb (g/dL) 3.9 ± 0.4 3.7 ± 0.4 0.201 AST (U/L) 36 ± 17 33 ± 13 0.439 ALT (U/L) 29 ± 15 24 ± 10 0.179 T-Bil (mg/dL) 0.8 ± 0.4 0.7 ± 0.3 0.174 AFP (ng/mL) 2261 ± 13868 9446 ± 32053 0.152 DCP (mAU/mL) 3819 ± 13329 15543 ± 26150 0.008 Operative time (min) 316 ± 140 323 ± 137 0.821 Blood loss (mL) 741 ± 1711 804 ± 1381 0.879 Histological differentiation (wel. / mod. / por.) 8 / 52 / 5 0 / 8 / 13 < 0.001 Tumor diameter (cm) 4.03 ± 3.15 6.32 ± 3.47 0.006 Number of tumors (solitary / multiple) 56 / 9 20 / 1 0.461 Growth (Eg / Ig) 61 / 4 19 / 2 0.973 Microscopic portal vein invasion (- / +) 59 / 6 15 / 6 0.063 Microscopic intrahepatic metastasis (- / +) 54 / 11 11 / 10 0.011 DFS and OS rates according to SUV The median follow-up time in 86 patients was 3.56 years, and postoperative recurrence developed in 37 patients (43.0%), including 32 patients with intrahepatic recurrence, 3 patients with lung metastases, 1 patient with bone metastasis, and 1 patient with lymph node metastases. The median DFS was 3.63 years. The DFS and OS curves in the low SUV and high SUV groups are shown in Fig. 2 A and 2 B. The cumulative DFS rate in the high SUV group was significantly lower than the rate in the low SUV group (P = 0.001). However, there was no significant difference in the OS analysis (P = 0.700). The 2-year DFS rates were 71.1% and 34.5% and the 5-year OS rates 71.3% and 59.0% in the low and high SUV groups, respectively. Univariate and multivariate analyses of DFS rates The high SUV group had a significantly lower DFS rate in the survival curve analysis; therefore, Cox regression analysis was performed for DFS rates. Univariate analysis of 16 perioperative factors for DFS identified the following 4 factors as significant prognostic factors: DCP ≥ 100 mAU/mL, multiple tumors, positive microscopic intrahepatic metastasis, and high SUV (≥ 5). In multivariate analysis, high SUV was identified as a significant and independent factor (hazard ratio: 2.50, P = 0.014; Table 3 ). Table 3 Univariate and multivariate analyses of disease-free survival Univariate Multivariate Variables Hazard ratio (95% CI) P-value Hazard ratio (95% CI) P-value Sex, female 0.97 (0.48–1.97) 0.931 Age ≥ 74 years 1.73 (0.97–3.09) 0.066 Alcohol (+) 0.86 (0.45–1.63) 0.642 HBs-Ag (+) 0.61 (0.24–1.55) 0.298 HCV-Ab (+) 0.85 (0.43–1.68) 0.649 Child Pugh B 0.98 (0.30–3.18) 0.972 Liver damage grade B 0.83 (0.37–1.88) 0.655 AFP > 100 ng/mL 0.82 (0.43–1.56) 0.543 DCP ≥ 100 mAU/mL 2.02 (1.08–3.78) 0.028 1.30 (0.64–2.66) 0.473 Multiple tumors 2.30 (1.02–5.18) 0.044 1.97 (0.69–5.61) 0.203 Invasive growth 1.10 (0.39–3.10) 0.853 Tumor diameter > 5 cm 1.36 (0.73–2.54) 0.340 Poor histological differentiation 1.65 (0.87–3.15) 0.126 Microscopic portal vein invasion (+) 1.02 (0.45–2.28) 0.971 Microscopic intrahepatic metastasis (+) 2.25 (1.21–4.18) 0.010 1.41 (0.65–3.07) 0.386 SUV ≥ 5 2.77 (1.50–5.12) 0.001 2.50 (1.20–5.19) 0.014 HBs-Ag, hepatitis B surface antigen; HCV-Ab, hepatitis C virus antibody; AFP, α-fetoprotein; DCP, des-γ-carboxy prothrombin; SUV, standard uptake value. Subgroup analysis of DFS and OS rates according to SUV In the subgroup analysis, the median tumor diameter was 3.5 cm and all patients were divided into two groups by this cut-off value. The clinicopathological factors of the small tumor (n = 45) and large tumor groups (n = 41) is shown in Supplementary Table 1. In the large tumor group, the DCP level was higher (12140 mAU/mL vs. 1708 mAU/mL, P = 0.006) and microscopic intrahepatic metastasis was more frequently observed (37% vs. 13%, P = 0.024). The distribution of SUV in both subgroups is shown in Fig. 3 A. In the small tumor group, the patients were divided into low SUV (n = 39) and high SUV group (n = 6). In the large tumor group, the patients were divided into low SUV (n = 26) and high SUV group (n = 15). In a survival analysis of the small tumor group, patients with high SUV had a significantly lower DFS rate than those with low SUV (P < 0.001) but OS rates were not significantly different (Fig. 3 B). The 2-year DFS rates were 78.6% and 16.7% and 5-year OS rates 76.0% and 66.7% in the low and high SUV groups, respectively. Conversely, in the large tumor group, there was no significant difference in the DFS or OS rates between the high and low SUV groups (Fig. 3 C). The 2-year DFS rates were 59.8% and 43.1% and the 5-year OS rates 62.7% and 57.0% in the low and high SUV groups, respectively. Discussion Hepatic resection is one of the major treatment modalities for HCC in patients with preserved liver function. 15 In recent years, advances in preoperative imaging modalities have led to precise preoperative diagnosis and evaluation of tumor characteristics. Despite these advances, the postoperative recurrence rate still remains high, with a 5-year recurrence rate of approximately 70% after curative resection of HCC. 4 , 6 It is important to identify the patients with several risk factors for tumor recurrence before surgery so that the operative approach can be adjusted for the probability of portal invasion or intrahepatic metastasis and the postoperative follow-up can be more personalized to the patient with high risk of tumor relapse. FDG-PET/CT may provide some information to the surgeon on this issue. Although qualitative diagnosis of tumors has been impossible with existing imaging modalities, FDG-PET/CT enables noninvasive and effective prediction of intra-tumor metabolic dynamics. The association of SUV with clinicopathological factors and prognosis has been investigated in various types of cancer. 9 , 11 , 16 , 17 Our study showed that a high SUV in the primary HCC tumor may be associated with high levels of DCP, histological classification of poorly differentiated HCC, large tumor diameter, and the presence of microscopic intrahepatic metastasis. These results may have an impact on decision-making in regard to the extent of liver resection. In other words, if the primary tumor with high SUV can predict intrahepatic metastasis and poor differentiation of HCC that cannot be diagnosed by conventional imaging, we could consider the choice of surgical procedure for anatomical liver resection that ensures negative surgical margins instead of non-anatomical hepatectomy. In the prognostic analysis, high SUV was an independent poor prognostic factor in terms of DFS. Moreover, we demonstrated that the patients with tumor recurrence within 2 years after hepatectomy had significantly higher SUVs in the primary tumor than those who were recurrence-free or experienced recurrence after 2 years. The optimal cut-off value for the SUV in the primary HCC tumor was identified as 5.0 in the ROC analysis. In a previous study of the patterns of HCC recurrence, recurrence due to residual intrahepatic metastasis was more common within 2 years after surgery, and recurrence due to metachronous, multicentric liver carcinogenesis increased after 2 years. 18 Thus, the patients with a high SUV in the primary HCC tumor had more residual microscopic intrahepatic metastatic lesions after surgery, resulting in more recurrences within 2 years after surgery. This is consistent with our finding that intrahepatic metastasis was more common in cases with high SUV. Thus, it may be necessary to consider a close follow-up schedule after surgery for HCC patients with high SUV. Although we found that more patients in the high SUV group had large tumor diameters, we also found that a certain number of patients with small tumors also had high SUVs (Fig. 3 A). Thus, we performed a subgroup analysis of patients with small tumors. Among patients with tumor diameters ≤ 3.5 cm, six patients had an SUV ≥ 5, and their DFS rates were drastically lower than those of patients with SUV 3.5 cm), there was no significant difference in DFS rates between the high and low SUV groups. A further detailed study of six patients with small tumor (≤ 3.5 cm) and high SUV (≥ 5) revealed that all patients had postoperative recurrence within the observation period; 5 (83.3%) of these patients had postoperative recurrence within 2 years, 5 (83.3%) had poorly differentiated HCC, 3 (50%) had microscopic portal vein invasion, and 3 (50%) had microscopic intrahepatic metastasis. The results of the subgroup analyses suggest that small HCC with high SUV may have higher tendency for oncological malignancy and higher risk of early recurrence after curative surgery. This may provide further support for pretreatment FDG-PET/CT in HCC patients. Several reports have shown that a high SUV in the malignant tumor correlates with the expression of specific molecules, such as glucose transporter 1, Ki-67, hypoxia-induced factor-1α, and markers of the epithelial-mesenchymal transition. 19 , 20 , 21 Moreover, recent studies have demonstrated a correlation between SUV and forkhead box protein M1 expression, a downstream gene of the Wnt/β-catenin pathway, in breast cancer. 22 Activation of the Wnt/β-catenin signaling pathway has been reported to correlate with metastasis, 23 proliferation, 24 drug resistance, 25 , 26 and resistance to immune checkpoint inhibitor in many tumors, including HCC. 27 , 28 These molecular changes would contribute to the malignant behavior of HCC with high SUV and influence the worse prognosis with high recurrence rate after curative resection. There are several limitations to this study, including the small number of patients from a single institution and the retrospective research design. To address these limitations, it will be necessary to increase the number of cases by extending the facilities and using a prospective observational design. Furthermore, an investigation of the effect of anatomical liver resection in HCC patients with high SUV would be important and necessary for improving surgical outcomes for HCC patients. In conclusion, a high SUV in the primary lesion is related to high DCP, poor histological differentiation, large tumor diameter, and microscopic intrahepatic metastasis in HCC. Moreover, high SUV (≥ 5) on FDG-PET/CT of the primary lesion, especially if ≤ 3.5 cm in size, correlates with early recurrence after curative resection (within 2 years) and is an independent poor prognostic factor in terms of DFS. In patients with HCC, FDG-PET/CT before treatment could provide useful information in selecting treatment options. Abbreviations AFP, α-fetoprotein AUC, area under the curve Cl, confidence interval DCP, des-γ-carboxy prothrombin DFS, disease-free survival FDG-PET/CT, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography HBs-Ab, hepatitis B surface antigen HCC, hepatocellular carcinoma HCV-Ab, hepatitis C virus antibody OS, overall survival SUV, standard uptake value Declarations Acknowledgments None. Funding Information None. Conflicts of Interest All authors declare no Conflict of Interests for this article. Ethics Statement All studies were performed in accordance with the ethical guidelines of the Declaration of Helsinki and Japanese Ethical Guidelines for Human Genome/Gene Analysis Research. The use of clinicopathological data was approved by the Human Ethics Review Committee of the Graduate School of Medicine, Osaka University (23447). All patients gave written informed consent for research use of their clinicopathological data, and patient anonymity was preserved. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–49. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021; 73 Suppl 1(Suppl 1): 4–13. Wang J, Li J, Tang G, Tian Y, Su S, Li Y. Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma. Oncol Lett. 2021; 21(4): 279. Tabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg. 2015; 261(5): 947–55. Taura K, Ikai I, Hatano E, Fujii H, Uyama N, Shimahara Y. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old. Ann Surg. 2006; 244(2): 265–73. Roayaie S, Obeidat K, Sposito C, Mariani L, Bhoori S, Pellegrinelli A, et al. Resection of hepatocellular cancer </=2 cm: results from two Western centers. Hepatology. 2013; 57(4): 1426–35. Lu RC, She B, Gao WT, Ji YH, Xu DD, Wang QS, et al. Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects. World J Gastroenterol. 2019; 25(32): 4682–95. Hirata K, Tamaki N. Quantitative FDG PET Assessment for Oncology Therapy. Cancers (Basel). 2021; 13(4). Maman A, Sahin A, Ayan AK. The Relationship of SUV Value in PET-CT with Tumor Differentiation and Tumor Markers in Gastric Cancer. Eurasian J Med. 2020; 52(1): 67–72. Li Y, Zhang Y, Fang Q, Zhang X, Hou P, Wu H, et al. Radiomics analysis of [(18)F]FDG PET/CT for microvascular invasion and prognosis prediction in very-early- and early-stage hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2021; 48(8): 2599–614. Reinert CP, Gatidis S, Sekler J, Dittmann H, Pfannenberg C, la Fougere C, et al. Clinical and prognostic value of tumor volumetric parameters in melanoma patients undergoing (18)F-FDG-PET/CT: a comparison with serologic markers of tumor burden and inflammation. Cancer Imaging. 2020; 20(1): 44. An J, Oh M, Kim SY, Oh YJ, Oh B, Oh JH, et al. PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma. Clin Cancer Res. 2022; 28(9): 1821–31. Noda T, Eguchi H, Iwagami Y, Yamada D, Asaoka T, Gotoh K, et al. Minimally invasive liver resection for hepatocellular carcinoma of patients with liver damage B: A propensity score-based analysis. Hepatol Res. 2018; 48(7): 539–48. Kubo M, Kobayashi S, Gotoh K, Takayama H, Iwagami Y, Yamada D, et al. Preoperative FDG-Positive Lymph Nodes Predict the Postoperative Prognosis in Resectable Biliary Tract Cancers. Ann Surg Oncol. 2022; 29(2): 935–44. Kokudo N, Takemura N, Hasegawa K, Takayama T, Kubo S, Shimada M, et al. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update. Hepatol Res. 2019; 49(10): 1109–13. Watanabe A, Harimoto N, Araki K, Yoshizumi T, Arima K, Yamashita Y, et al. A new strategy based on fluorodeoxyglucose-positron emission tomography for managing liver metastasis from colorectal cancer. J Surg Oncol. 2018; 118(7): 1088–95. Mantziari S, Pomoni A, Prior JO, Winiker M, Allemann P, Demartines N, et al. (18)F- FDG PET/CT-derived parameters predict clinical stage and prognosis of esophageal cancer. BMC Med Imaging. 2020; 20(1): 7. Sakon M, Umeshita K, Nagano H, Eguchi H, Kishimoto S, Miyamoto A, et al. Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves. Arch Surg. 2000; 135(12): 1456–9. Li YC, Yang CS, Zhou WL, Li HS, Han YJ, Wang QS, et al. Low glucose metabolism in hepatocellular carcinoma with GPC3 expression. World J Gastroenterol. 2018; 24(4): 494–503. Watanabe A, Harimoto N, Yokobori T, Araki K, Kubo N, Igarashi T, et al. FDG-PET reflects tumor viability on SUV in colorectal cancer liver metastasis. Int J Clin Oncol. 2020; 25(2): 322–9. Sugita S, Yamato M, Hatabu T, Kataoka Y. Involvement of cancer-derived EMT cells in the accumulation of (18)F-fluorodeoxyglucose in the hypoxic cancer microenvironment. Sci Rep. 2021; 11(1): 9668. Kim SK, Ahn SG, Mun JY, Jeong MS, Bae SJ, Lee JS, et al. Genomic Signature of the Standardized Uptake Value in (18)F-Fluorodeoxyglucose Positron Emission Tomography in Breast Cancer. Cancers (Basel). 2020; 12(2). Liu L, Zhu XD, Wang WQ, Shen Y, Qin Y, Ren ZG, et al. Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Clin Cancer Res. 2010; 16(10): 2740–50. An FQ, Matsuda M, Fujii H, Tang RF, Amemiya H, Dai YM, et al. Tumor heterogeneity in small hepatocellular carcinoma: analysis of tumor cell proliferation, expression and mutation of p53 AND beta-catenin. Int J Cancer. 2001; 93(4): 468–74. Noda T, Nagano H, Takemasa I, Yoshioka S, Murakami M, Wada H, et al. Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma. Br J Cancer. 2009; 100(10): 1647–58. Liu Y, Ye X, Zhang JB, Ouyang H, Shen Z, Wu Y, et al. PROX1 promotes hepatocellular carcinoma proliferation and sorafenib resistance by enhancing beta-catenin expression and nuclear translocation. Oncogene. 2015; 34(44): 5524–35. Harding JJ, Nandakumar S, Armenia J, Khalil DN, Albano M, Ly M, et al. Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next-Generation Sequencing for Matching Patients to Targeted and Immune Therapies. Clin Cancer Res. 2019; 25(7): 2116–26. Ruiz de Galarreta M, Bresnahan E, Molina-Sanchez P, Lindblad KE, Maier B, Sia D, et al. beta-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma. Cancer Discov. 2019; 9(8): 1124–41. Additional Declarations No competing interests reported. Supplementary Files SupplementalTable.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4239792","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":289841962,"identity":"42736bff-acae-4332-8185-3c100cb03e24","order_by":0,"name":"Kazuya Kato","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Kazuya","middleName":"","lastName":"Kato","suffix":""},{"id":289841963,"identity":"a58ce2f7-1593-4a68-8b80-5ce43fa480f2","order_by":1,"name":"Takehiro Noda","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Takehiro","middleName":"","lastName":"Noda","suffix":""},{"id":289841964,"identity":"9f2f2098-be69-4b02-ada0-3c768dfc2a03","order_by":2,"name":"Shogo Kobayashi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYFACNgZmMC3B2PgASEIEJYjU0mxAqhYGNvwKYUC+gS3xcUHNYXn52c1t1bw5FnkM7IcfMFjuwK3F4ADbYeMZxw4bbrhzsO027zaJYgaeNAMGyTN4tMg/b5PmYTvMuEEiEawlsYEhh4FBsg2fw9iBWv4dtp8/I7GtGKyF/w1+LQwH2I5J87YdTmy4kdjGDNYiQcAWoF+SjWf2pSdvuJHYLDkXqKVN4pnBAXx+AYaY4eOCb9a282ekP/zwdltdYj9/8sPHknhCDAqaEUw2ID4s2UBQSx0ql/EjYS2jYBSMglEwcgAAQsFNOeqj/hUAAAAASUVORK5CYII=","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":true,"prefix":"","firstName":"Shogo","middleName":"","lastName":"Kobayashi","suffix":""},{"id":289841965,"identity":"a1e805f2-e538-4c07-83b8-85f1e5b7e89b","order_by":3,"name":"Chihiro Yamanaka","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Chihiro","middleName":"","lastName":"Yamanaka","suffix":""},{"id":289841966,"identity":"8b245214-05d2-48c5-a7d1-86398149d2db","order_by":4,"name":"Kazuki Sasaki","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Kazuki","middleName":"","lastName":"Sasaki","suffix":""},{"id":289841967,"identity":"105e2b39-bf3e-4248-8125-d19aa135dfff","order_by":5,"name":"Yoshifumi Iwagami","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Yoshifumi","middleName":"","lastName":"Iwagami","suffix":""},{"id":289841968,"identity":"ee2eee2a-5078-4ac7-9480-2ad4b9b721fe","order_by":6,"name":"Daisaku Yamada","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Daisaku","middleName":"","lastName":"Yamada","suffix":""},{"id":289841969,"identity":"130a13d3-4fb0-418e-baf9-82ed65198b49","order_by":7,"name":"Yoshito Tomimaru","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Yoshito","middleName":"","lastName":"Tomimaru","suffix":""},{"id":289841970,"identity":"efc9036a-1421-40a0-b80f-2a0bb1118935","order_by":8,"name":"Hidenori Takahashi","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Hidenori","middleName":"","lastName":"Takahashi","suffix":""},{"id":289841971,"identity":"4df3946e-873b-4b3f-b809-0be2574186c9","order_by":9,"name":"Tadafumi Asaoka","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Tadafumi","middleName":"","lastName":"Asaoka","suffix":""},{"id":289841972,"identity":"dd7c5aa5-602e-40f1-ac74-8e7d05ee3f28","order_by":10,"name":"Junzo Shimizu","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Junzo","middleName":"","lastName":"Shimizu","suffix":""},{"id":289841973,"identity":"237407c2-e118-4cd5-9aba-98ee9f102e7b","order_by":11,"name":"Yuichiro Doki","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Yuichiro","middleName":"","lastName":"Doki","suffix":""},{"id":289841974,"identity":"b599191f-1c99-45f5-a89b-54c0470e6105","order_by":12,"name":"Hidetoshi Eguchi","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka","correspondingAuthor":false,"prefix":"","firstName":"Hidetoshi","middleName":"","lastName":"Eguchi","suffix":""}],"badges":[],"createdAt":"2024-04-09 05:29:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4239792/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4239792/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54578134,"identity":"87696cce-93cb-499b-b178-a04c2d022bdb","added_by":"auto","created_at":"2024-04-12 14:03:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":59394,"visible":true,"origin":"","legend":"\u003cp\u003eThe distribution of SUV and relationship with early recurrence after surgery. (A) Distribution of SUV in normal liver and tumor. (B) Distribution of SUV in the no recurrence group, recurrence within 2 years after surgery group, and recurrence after 2 years group. (C) Receiver operating characteristic curve analysis. AUC = 0.741.\u003c/p\u003e","description":"","filename":"OnlineFig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4239792/v1/f5b5df4ead273988c1dccc53.png"},{"id":54577351,"identity":"854d4ffa-a0ce-47b7-ba95-686335730242","added_by":"auto","created_at":"2024-04-12 13:55:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":86314,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative disease-free and overall survival curves of HCC patients in the low SUV and high SUV groups. (A) Cumulative disease-free survival curves of HCC patients with low SUV (\u0026lt;5; n = 65) and high SUV (≥5; n = 21). (B) Cumulative overall survival curves for the two groups.\u003c/p\u003e","description":"","filename":"OnlineFig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4239792/v1/0272ecb6116db0176c087c16.png"},{"id":54577355,"identity":"9ffe2c32-82af-4c4f-95f3-9b9b98bf76e2","added_by":"auto","created_at":"2024-04-12 13:55:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":87592,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis by tumor diameter. (A) Distribution of SUV in small tumors (≤3.5 cm) and large tumors (\u0026gt;3.5 cm). (B) Cumulative disease-free and overall survival curves for the low and high SUV patients with small tumors (≤3.5 cm). (C) Cumulative disease-free and overall survival curves for the low and high SUV patients with large tumors (\u0026gt;3.5 cm).\u003c/p\u003e","description":"","filename":"OnlineFig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4239792/v1/f27fce5c78de2a3885d41fb6.png"},{"id":55438265,"identity":"a7b8a10c-2d0d-43d3-b3e1-b5b462062eea","added_by":"auto","created_at":"2024-04-27 17:01:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1049797,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4239792/v1/8e29468e-c074-4098-afc0-33e76acd7b12.pdf"},{"id":54578792,"identity":"5cc1de22-0739-472f-abde-dd4cda816993","added_by":"auto","created_at":"2024-04-12 14:11:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":39674,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-4239792/v1/f973b4c1f51175de9262850a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"High standard uptake value of the primary lesion of hepatocellular carcinoma correlates with early recurrence after curative resection","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary liver cancer is the sixth most frequently occurring cancer and the third leading cause of cancer mortality worldwide, with approximately 906,000 new cases and 830,000 deaths per year. Incidence rates have increased in many countries in recent decades. Hepatocellular carcinoma (HCC) is the dominant type of primary liver cancer, accounting for approximately 80% of the total number of cases worldwide.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Although various testing and treatment methods have been developed for HCC patients, the survival rate remains low, with a global 5-year survival rate of 5\u0026ndash;30%.\u003csup\u003e3\u003c/sup\u003e HCC has a high recurrence rate after treatment; approximately 70% of patients with HCC experience recurrence within 5 years after surgery, even after radical resection.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e This high recurrence rate may be the reason why the survival rate remains unsatisfactory for HCC. Therefore, we must develop a better understanding of the mechanisms of HCC recurrence and the optimal treatment strategy.\u003c/p\u003e \u003cp\u003eFluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an effective and noninvasive modality for scanning the whole body. FDG-PET/CT has high sensitivity for detecting distant metastases in various types of malignant tumors, including HCC. In addition, FDG accumulation in primary tumors may reflect tumor characteristics based on the metabolic activity.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The standard uptake value (SUV) can be applied to the diagnosis of the metabolic and proliferative potential of primary tumors. In recent years, the relationships between the SUV on FDG-PET/CT and tumor differentiation, vascular invasion, tumor markers, and prognosis have been pointed out in various cancers.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e The usefulness of FDG-PET/CT in the evaluation of primary lesions has attracted much attention.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e According to the 2021 Japan Society of Hepatology guidelines for HCC, FDG-PET/CT imaging is recommended only for patients with risk factors for extrahepatic metastasis. However, the clinical significance of SUV in primary HCC lesions is still unclear. In this study, we evaluated the relationship between the SUV in the primary lesion, clinicopathological factors, and prognosis in HCC patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eA total of 86 patients underwent preoperative FDG-PET/CT and curative surgery for primary HCC between January 2010 and December 2020 at the Department of Gastroenterological Surgery of Osaka University Hospital. The patients\u0026rsquo; medical records were reviewed retrospectively, and the following clinical, surgical, and pathological factors were collected; sex, age, alcohol, hepatitis B surface antigen (HBs-Ag), hepatitis C virus antibody (HCV-Ab), Child\u0026ndash;Pugh classification, liver damage classification established by the Liver Cancer Study Group of Japan, α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels, tumor number, tumor diameter, histological differentiation, and stage based on General Rules for the Clinical and Pathological Study of Primary Liver Cancer (6th edition). A history of heavy alcohol use was defined as consumption of 30 g or more of pure alcohol equivalent per day. Hepatic resection was carried out as reported previously.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e All aspects of our study protocol were approved by the Human Ethics Committee of the Graduate School of Medicine, Osaka University, Japan. Written informed consent was obtained from all patients for research use of their clinicopathological data. This study was performed in accordance with the ethical guidelines of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eFDG-PET/CT\u003c/h2\u003e \u003cp\u003eThe SUV of primary tumors was measured preoperatively, and the procedure for FDG-PET/CT was described previously.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Briefly, whole-body FDG-PET/CT was carried out using the Gemini GXL (Phillips, Eindhoven, the Netherlands). Prior to imaging, all patients fasted for 5 hours before intravenous administration of FDG at a dose of 3.7 MBq/kg. The PET/CT images were acquired 120 minutes after FDG administration. The SUV was calculated by measuring FDG uptake in the non-tumorous liver and primary HCC tumors as follows: SUV = [maximal radioactivity concentration]/[injected dose/patient weight (kg)].\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eRelationship between SUV and survival\u003c/h2\u003e \u003cp\u003eThe distributions of the SUV in normal liver and primary HCC tumor were compared. The patients were divided into three groups based on postoperative recurrence: no recurrence, recurrence within 2 years, and recurrence after 2 years. The distribution of SUV in the three groups was compared by one-way analysis of variance. The optimal cut-off values for the SUV were set based on the receiver operating characteristic curve (ROC) analysis in the primary HCC tumor. The cut-off value, which is located at the highest point on the vertical axis and the left end of the horizontal axis on the ROC curve, was calculated to maximize the sensitivity and specificity to detect the tumor recurrence within 2 years after hepatic resection. All patients were divided into two groups using the determined cut-off value: low SUV or high SUV. The patients\u0026rsquo; clinicopathological indicators were compared between the two groups using chi-squared and Student's t-tests. Disease-free survival (DFS) and overall survival (OS) curves were analyzed using the Kaplan\u0026ndash;Meier method, and differences between survival curves were compared by the log-rank test. To evaluate the risks associated with the prognostic variables, univariate and multivariate analyses using a Cox model were performed, with determination of hazard ratios and 95% confidence intervals.\u003c/p\u003e \u003cp\u003eAs a subgroup analysis, we examined differences in the SUV relationships between small and large tumors. First, patients were divided based on median tumor diameter into two groups (small or large) and the distribution of tumor SUV examined. Next, DFS and OS rates were analyzed between the low and high SUV groups in each subgroup.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using R version 4.2.2 (Vienna, Austria; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org/\u003c/span\u003e\u003cspan address=\"http://www.R-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThe patients\u0026rsquo; baseline characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median patient age was 74 years (range 14\u0026ndash;88 years); 68 patients were male and 18 were female. Twenty-four patients had a history of heavy alcohol use. Twelve patients were HBs-Ag-positive and 22 HCV-Ab-positive. Among all patients, 81 were categorized into Child-Pugh A and 5 into Child-Pugh B, whereas 72 and 14 patients were categorized as having liver damage grades A and B, respectively. Regarding tumor markers, the median AFP and DCP levels were 10.5 ng/mL and 176.5 mAU/mL, respectively. Seventy-six cases had a solitary tumor and 10 cases multiple tumors. Regarding histological differentiation, well-differentiated HCC was found in 8 cases, moderately differentiated in 60, and poorly differentiated in 18. The stage was I in 14 patients, II in 57, III in 11, and IV in 4.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValues\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male / female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 / 18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (14\u0026ndash;88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 / 24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBs-Ag (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 / 12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV-Ab (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 / 22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild Pugh (A / B / C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 / 5 / 0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver damage (A / B / C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 / 14 / 0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.5 (1\u0026ndash;147064)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCP (mAU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e176.5 (12\u0026ndash;88400)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of tumors (solitary / multiple)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 / 10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor diameter (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5 (0.9\u0026ndash;18.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistological differentiation (wel. / mod. / por.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 / 60 / 18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage (I / II / III / IV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 / 57 / 11 / 4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.8 (2.4\u0026ndash;14.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eDistribution of SUV in normal liver and tumor and the cut-off value for tumor SUV\u003c/h2\u003e \u003cp\u003eThe distributions of SUV in the normal liver and primary lesion are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA; the median SUV in all patients was 2.5 and 3.8, respectively. The ranges in normal liver and the primary lesion were 1.7\u0026ndash;3.6 and 2.4\u0026ndash;14.4, respectively. The tumor SUV was significantly higher in the patients with recurrence within 2 years after surgery (6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46) than those without recurrence (3.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63) or recurrence after 2 years (4.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.17, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The ROC analysis for recurrence within 2 years after surgery (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC) showed that the optimal tumor SUV cut-off was 5.0, with an area under the curve (AUC) of 0.741. With this cut-off value, the sensitivity and specificity were 0.520 and 0.869, respectively. In our cohort, the positive predictive value was 61.9% and false negative rate 48.0%. Based on the above, we set the cut-off for the tumor SUV to 5.0, which was about twice that of normal liver. Using our cut-off value, we divided all patients into two groups: low SUV (SUV\u0026thinsp;\u0026lt;\u0026thinsp;5; n\u0026thinsp;=\u0026thinsp;65) and high SUV (SUV\u0026thinsp;\u0026ge;\u0026thinsp;5; n\u0026thinsp;=\u0026thinsp;21).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eComparison of clinicopathological factors in the low SUV and high SUV groups\u003c/h2\u003e \u003cp\u003eIn the comparison of clinicopathological factors between the low SUV and high SUV groups, there were significant differences in the levels of DCP (3819 mAU/mL vs. 15543 mAU/mL, P\u0026thinsp;=\u0026thinsp;0.008), histological differentiation (wel./mod./por. : 8/52/5 vs. 0/8/13, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), tumor diameter (4.03 cm vs. 6.32 cm, P\u0026thinsp;=\u0026thinsp;0.006), and microscopic intrahepatic metastasis (16.9% vs. 47.6%, P\u0026thinsp;=\u0026thinsp;0.011; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinicopathological factors between the low SUV and high SUV groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow SUV (\u0026lt;\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh SUV (\u0026ge;\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male/female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 / 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 / 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.949\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.9\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.4\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;13.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 / 20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 / 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.446\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBs-Ag (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 / 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 / 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV-Ab (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 / 19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 / 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild Pugh (A / B)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 / 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 / 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver damage (A / B)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 / 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 / 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5093\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1548\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5256\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1426\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.672\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.4\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.7\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174.3\u0026thinsp;\u0026plusmn;\u0026thinsp;61.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e164.1\u0026thinsp;\u0026plusmn;\u0026thinsp;46.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.487\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlb (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.439\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-Bil (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2261\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;13868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9446\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;32053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCP (mAU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3819\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;13329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15543\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;26150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e316\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e323\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.821\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e741\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1711\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e804\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistological differentiation (wel. / mod. / por.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 / 52 / 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 / 8 / 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor diameter (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.03\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.32\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;3.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of tumors (solitary / multiple)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 / 9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 / 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.461\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrowth (Eg / Ig)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 / 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 / 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicroscopic portal vein invasion (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 / 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 / 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicroscopic intrahepatic metastasis (- / +)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 / 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 / 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eDFS and OS rates according to SUV\u003c/h2\u003e \u003cp\u003eThe median follow-up time in 86 patients was 3.56 years, and postoperative recurrence developed in 37 patients (43.0%), including 32 patients with intrahepatic recurrence, 3 patients with lung metastases, 1 patient with bone metastasis, and 1 patient with lymph node metastases. The median DFS was 3.63 years. The DFS and OS curves in the low SUV and high SUV groups are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB. The cumulative DFS rate in the high SUV group was significantly lower than the rate in the low SUV group (P\u0026thinsp;=\u0026thinsp;0.001). However, there was no significant difference in the OS analysis (P\u0026thinsp;=\u0026thinsp;0.700). The 2-year DFS rates were 71.1% and 34.5% and the 5-year OS rates 71.3% and 59.0% in the low and high SUV groups, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate and multivariate analyses of DFS rates\u003c/h2\u003e \u003cp\u003eThe high SUV group had a significantly lower DFS rate in the survival curve analysis; therefore, Cox regression analysis was performed for DFS rates. Univariate analysis of 16 perioperative factors for DFS identified the following 4 factors as significant prognostic factors: DCP\u0026thinsp;\u0026ge;\u0026thinsp;100 mAU/mL, multiple tumors, positive microscopic intrahepatic metastasis, and high SUV (\u0026ge;\u0026thinsp;5). In multivariate analysis, high SUV was identified as a significant and independent factor (hazard ratio: 2.50, P\u0026thinsp;=\u0026thinsp;0.014; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analyses of disease-free survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard ratio (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHazard ratio (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.97 (0.48\u0026ndash;1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;74 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.73 (0.97\u0026ndash;3.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.86 (0.45\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBs-Ag (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.61 (0.24\u0026ndash;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV-Ab (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85 (0.43\u0026ndash;1.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.649\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild Pugh B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.30\u0026ndash;3.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver damage grade B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.83 (0.37\u0026ndash;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP\u0026thinsp;\u0026gt;\u0026thinsp;100 ng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.82 (0.43\u0026ndash;1.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCP\u0026thinsp;\u0026ge;\u0026thinsp;100 mAU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.02 (1.08\u0026ndash;3.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.30 (0.64\u0026ndash;2.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple tumors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.30 (1.02\u0026ndash;5.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.97 (0.69\u0026ndash;5.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive growth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.10 (0.39\u0026ndash;3.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.853\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor diameter\u0026thinsp;\u0026gt;\u0026thinsp;5 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.36 (0.73\u0026ndash;2.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.340\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoor histological differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.65 (0.87\u0026ndash;3.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicroscopic portal vein invasion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.02 (0.45\u0026ndash;2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.971\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicroscopic intrahepatic metastasis (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.25 (1.21\u0026ndash;4.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.41 (0.65\u0026ndash;3.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.386\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u0026thinsp;\u0026ge;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.77 (1.50\u0026ndash;5.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.50 (1.20\u0026ndash;5.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eHBs-Ag, hepatitis B surface antigen; HCV-Ab, hepatitis C virus antibody; AFP, α-fetoprotein; DCP, des-γ-carboxy prothrombin; SUV, standard uptake value.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis of DFS and OS rates according to SUV\u003c/h2\u003e \u003cp\u003eIn the subgroup analysis, the median tumor diameter was 3.5 cm and all patients were divided into two groups by this cut-off value. The clinicopathological factors of the small tumor (n\u0026thinsp;=\u0026thinsp;45) and large tumor groups (n\u0026thinsp;=\u0026thinsp;41) is shown in Supplementary Table\u0026nbsp;1. In the large tumor group, the DCP level was higher (12140 mAU/mL vs. 1708 mAU/mL, P\u0026thinsp;=\u0026thinsp;0.006) and microscopic intrahepatic metastasis was more frequently observed (37% vs. 13%, P\u0026thinsp;=\u0026thinsp;0.024). The distribution of SUV in both subgroups is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA. In the small tumor group, the patients were divided into low SUV (n\u0026thinsp;=\u0026thinsp;39) and high SUV group (n\u0026thinsp;=\u0026thinsp;6). In the large tumor group, the patients were divided into low SUV (n\u0026thinsp;=\u0026thinsp;26) and high SUV group (n\u0026thinsp;=\u0026thinsp;15). In a survival analysis of the small tumor group, patients with high SUV had a significantly lower DFS rate than those with low SUV (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) but OS rates were not significantly different (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). The 2-year DFS rates were 78.6% and 16.7% and 5-year OS rates 76.0% and 66.7% in the low and high SUV groups, respectively. Conversely, in the large tumor group, there was no significant difference in the DFS or OS rates between the high and low SUV groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). The 2-year DFS rates were 59.8% and 43.1% and the 5-year OS rates 62.7% and 57.0% in the low and high SUV groups, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eHepatic resection is one of the major treatment modalities for HCC in patients with preserved liver function.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In recent years, advances in preoperative imaging modalities have led to precise preoperative diagnosis and evaluation of tumor characteristics. Despite these advances, the postoperative recurrence rate still remains high, with a 5-year recurrence rate of approximately 70% after curative resection of HCC.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e It is important to identify the patients with several risk factors for tumor recurrence before surgery so that the operative approach can be adjusted for the probability of portal invasion or intrahepatic metastasis and the postoperative follow-up can be more personalized to the patient with high risk of tumor relapse. FDG-PET/CT may provide some information to the surgeon on this issue. Although qualitative diagnosis of tumors has been impossible with existing imaging modalities, FDG-PET/CT enables noninvasive and effective prediction of intra-tumor metabolic dynamics. The association of SUV with clinicopathological factors and prognosis has been investigated in various types of cancer.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Our study showed that a high SUV in the primary HCC tumor may be associated with high levels of DCP, histological classification of poorly differentiated HCC, large tumor diameter, and the presence of microscopic intrahepatic metastasis. These results may have an impact on decision-making in regard to the extent of liver resection. In other words, if the primary tumor with high SUV can predict intrahepatic metastasis and poor differentiation of HCC that cannot be diagnosed by conventional imaging, we could consider the choice of surgical procedure for anatomical liver resection that ensures negative surgical margins instead of non-anatomical hepatectomy.\u003c/p\u003e \u003cp\u003eIn the prognostic analysis, high SUV was an independent poor prognostic factor in terms of DFS. Moreover, we demonstrated that the patients with tumor recurrence within 2 years after hepatectomy had significantly higher SUVs in the primary tumor than those who were recurrence-free or experienced recurrence after 2 years. The optimal cut-off value for the SUV in the primary HCC tumor was identified as 5.0 in the ROC analysis. In a previous study of the patterns of HCC recurrence, recurrence due to residual intrahepatic metastasis was more common within 2 years after surgery, and recurrence due to metachronous, multicentric liver carcinogenesis increased after 2 years.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Thus, the patients with a high SUV in the primary HCC tumor had more residual microscopic intrahepatic metastatic lesions after surgery, resulting in more recurrences within 2 years after surgery. This is consistent with our finding that intrahepatic metastasis was more common in cases with high SUV. Thus, it may be necessary to consider a close follow-up schedule after surgery for HCC patients with high SUV.\u003c/p\u003e \u003cp\u003eAlthough we found that more patients in the high SUV group had large tumor diameters, we also found that a certain number of patients with small tumors also had high SUVs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Thus, we performed a subgroup analysis of patients with small tumors. Among patients with tumor diameters\u0026thinsp;\u0026le;\u0026thinsp;3.5 cm, six patients had an SUV\u0026thinsp;\u0026ge;\u0026thinsp;5, and their DFS rates were drastically lower than those of patients with SUV\u0026thinsp;\u0026lt;\u0026thinsp;5. Conversely, when limited to patients with a large tumor (\u0026gt;\u0026thinsp;3.5 cm), there was no significant difference in DFS rates between the high and low SUV groups. A further detailed study of six patients with small tumor (\u0026le;\u0026thinsp;3.5 cm) and high SUV (\u0026ge;\u0026thinsp;5) revealed that all patients had postoperative recurrence within the observation period; 5 (83.3%) of these patients had postoperative recurrence within 2 years, 5 (83.3%) had poorly differentiated HCC, 3 (50%) had microscopic portal vein invasion, and 3 (50%) had microscopic intrahepatic metastasis. The results of the subgroup analyses suggest that small HCC with high SUV may have higher tendency for oncological malignancy and higher risk of early recurrence after curative surgery. This may provide further support for pretreatment FDG-PET/CT in HCC patients.\u003c/p\u003e \u003cp\u003eSeveral reports have shown that a high SUV in the malignant tumor correlates with the expression of specific molecules, such as glucose transporter 1, Ki-67, hypoxia-induced factor-1α, and markers of the epithelial-mesenchymal transition.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Moreover, recent studies have demonstrated a correlation between SUV and forkhead box protein M1 expression, a downstream gene of the Wnt/β-catenin pathway, in breast cancer.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Activation of the Wnt/β-catenin signaling pathway has been reported to correlate with metastasis,\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e proliferation,\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e drug resistance,\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and resistance to immune checkpoint inhibitor in many tumors, including HCC.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e These molecular changes would contribute to the malignant behavior of HCC with high SUV and influence the worse prognosis with high recurrence rate after curative resection.\u003c/p\u003e \u003cp\u003eThere are several limitations to this study, including the small number of patients from a single institution and the retrospective research design. To address these limitations, it will be necessary to increase the number of cases by extending the facilities and using a prospective observational design. Furthermore, an investigation of the effect of anatomical liver resection in HCC patients with high SUV would be important and necessary for improving surgical outcomes for HCC patients.\u003c/p\u003e \u003cp\u003eIn conclusion, a high SUV in the primary lesion is related to high DCP, poor histological differentiation, large tumor diameter, and microscopic intrahepatic metastasis in HCC. Moreover, high SUV (\u0026ge;\u0026thinsp;5) on FDG-PET/CT of the primary lesion, especially if\u0026thinsp;\u0026le;\u0026thinsp;3.5 cm in size, correlates with early recurrence after curative resection (within 2 years) and is an independent poor prognostic factor in terms of DFS. In patients with HCC, FDG-PET/CT before treatment could provide useful information in selecting treatment options.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAFP, \u0026alpha;-fetoprotein\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAUC, area under the curve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCl, confidence interval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDCP, des-\u0026gamma;-carboxy prothrombin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDFS, disease-free survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFDG-PET/CT, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBs-Ab, hepatitis B surface antigen\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCC, hepatocellular carcinoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCV-Ab, hepatitis C virus antibody\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOS, overall survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSUV, standard uptake value\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no Conflict of Interests for this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll studies were performed in accordance with the ethical guidelines of the Declaration of Helsinki and Japanese Ethical Guidelines for Human Genome/Gene Analysis Research. The use of clinicopathological data was approved by the Human Ethics Review Committee of the Graduate School of Medicine, Osaka University (23447). All patients gave written informed consent for research use of their clinicopathological data, and patient anonymity was preserved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021; 73 Suppl 1(Suppl 1): 4\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Li J, Tang G, Tian Y, Su S, Li Y. Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma. Oncol Lett. 2021; 21(4): 279.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg. 2015; 261(5): 947\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaura K, Ikai I, Hatano E, Fujii H, Uyama N, Shimahara Y. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old. Ann Surg. 2006; 244(2): 265\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoayaie S, Obeidat K, Sposito C, Mariani L, Bhoori S, Pellegrinelli A, et al. Resection of hepatocellular cancer \u0026lt;/=2 cm: results from two Western centers. Hepatology. 2013; 57(4): 1426\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu RC, She B, Gao WT, Ji YH, Xu DD, Wang QS, et al. Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects. World J Gastroenterol. 2019; 25(32): 4682\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirata K, Tamaki N. Quantitative FDG PET Assessment for Oncology Therapy. Cancers (Basel). 2021; 13(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaman A, Sahin A, Ayan AK. The Relationship of SUV Value in PET-CT with Tumor Differentiation and Tumor Markers in Gastric Cancer. Eurasian J Med. 2020; 52(1): 67\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Zhang Y, Fang Q, Zhang X, Hou P, Wu H, et al. Radiomics analysis of [(18)F]FDG PET/CT for microvascular invasion and prognosis prediction in very-early- and early-stage hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2021; 48(8): 2599\u0026ndash;614.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReinert CP, Gatidis S, Sekler J, Dittmann H, Pfannenberg C, la Fougere C, et al. Clinical and prognostic value of tumor volumetric parameters in melanoma patients undergoing (18)F-FDG-PET/CT: a comparison with serologic markers of tumor burden and inflammation. Cancer Imaging. 2020; 20(1): 44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAn J, Oh M, Kim SY, Oh YJ, Oh B, Oh JH, et al. PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma. Clin Cancer Res. 2022; 28(9): 1821\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoda T, Eguchi H, Iwagami Y, Yamada D, Asaoka T, Gotoh K, et al. Minimally invasive liver resection for hepatocellular carcinoma of patients with liver damage B: A propensity score-based analysis. Hepatol Res. 2018; 48(7): 539\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKubo M, Kobayashi S, Gotoh K, Takayama H, Iwagami Y, Yamada D, et al. Preoperative FDG-Positive Lymph Nodes Predict the Postoperative Prognosis in Resectable Biliary Tract Cancers. Ann Surg Oncol. 2022; 29(2): 935\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKokudo N, Takemura N, Hasegawa K, Takayama T, Kubo S, Shimada M, et al. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update. Hepatol Res. 2019; 49(10): 1109\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatanabe A, Harimoto N, Araki K, Yoshizumi T, Arima K, Yamashita Y, et al. A new strategy based on fluorodeoxyglucose-positron emission tomography for managing liver metastasis from colorectal cancer. J Surg Oncol. 2018; 118(7): 1088\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMantziari S, Pomoni A, Prior JO, Winiker M, Allemann P, Demartines N, et al. (18)F- FDG PET/CT-derived parameters predict clinical stage and prognosis of esophageal cancer. BMC Med Imaging. 2020; 20(1): 7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSakon M, Umeshita K, Nagano H, Eguchi H, Kishimoto S, Miyamoto A, et al. Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves. Arch Surg. 2000; 135(12): 1456\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi YC, Yang CS, Zhou WL, Li HS, Han YJ, Wang QS, et al. Low glucose metabolism in hepatocellular carcinoma with GPC3 expression. World J Gastroenterol. 2018; 24(4): 494\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatanabe A, Harimoto N, Yokobori T, Araki K, Kubo N, Igarashi T, et al. FDG-PET reflects tumor viability on SUV in colorectal cancer liver metastasis. Int J Clin Oncol. 2020; 25(2): 322\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSugita S, Yamato M, Hatabu T, Kataoka Y. Involvement of cancer-derived EMT cells in the accumulation of (18)F-fluorodeoxyglucose in the hypoxic cancer microenvironment. Sci Rep. 2021; 11(1): 9668.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim SK, Ahn SG, Mun JY, Jeong MS, Bae SJ, Lee JS, et al. Genomic Signature of the Standardized Uptake Value in (18)F-Fluorodeoxyglucose Positron Emission Tomography in Breast Cancer. Cancers (Basel). 2020; 12(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu L, Zhu XD, Wang WQ, Shen Y, Qin Y, Ren ZG, et al. Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Clin Cancer Res. 2010; 16(10): 2740\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAn FQ, Matsuda M, Fujii H, Tang RF, Amemiya H, Dai YM, et al. Tumor heterogeneity in small hepatocellular carcinoma: analysis of tumor cell proliferation, expression and mutation of p53 AND beta-catenin. Int J Cancer. 2001; 93(4): 468\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoda T, Nagano H, Takemasa I, Yoshioka S, Murakami M, Wada H, et al. Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma. Br J Cancer. 2009; 100(10): 1647\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Ye X, Zhang JB, Ouyang H, Shen Z, Wu Y, et al. PROX1 promotes hepatocellular carcinoma proliferation and sorafenib resistance by enhancing beta-catenin expression and nuclear translocation. Oncogene. 2015; 34(44): 5524\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarding JJ, Nandakumar S, Armenia J, Khalil DN, Albano M, Ly M, et al. Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next-Generation Sequencing for Matching Patients to Targeted and Immune Therapies. Clin Cancer Res. 2019; 25(7): 2116\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuiz de Galarreta M, Bresnahan E, Molina-Sanchez P, Lindblad KE, Maier B, Sia D, et al. beta-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma. Cancer Discov. 2019; 9(8): 1124\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"HCC, SUV, early recurrence, postoperative recurrence, prognosis, disease-free survival","lastPublishedDoi":"10.21203/rs.3.rs-4239792/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4239792/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful for detecting the presence of distant metastases in many types of cancer, including hepatocellular carcinoma (HCC). However, the clinical significance of the standard uptake value (SUV) in primary HCC lesions is unclear.\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eWe investigated the relationship between the SUV, clinicopathological factors, and prognosis in HCC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe retrospective analysis included 86 patients with HCC who underwent FDG-PET/CT prior to liver resection. The distribution of SUV was compared in three groups: no recurrence after surgery, recurrence within 2 years, and recurrence after 2 years. The optimal cut-off SUV were determined based on receiver operating characteristic curve analysis to detect the recurrence within 2 years. All patients were divided into two groups based on the cut-off: low and high SUV. Cox univariate and multivariate analyses were performed for disease-free survival.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe SUV was significantly higher in patients with recurrence within 2 years. The optimal cut-off SUV was 5.0. The patients in the high SUV group had significantly higher des-γ-carboxy prothrombin, poorer differentiation, and larger tumor diameter than the low SUV group, and presented with pathologically positive intrahepatic metastases. Moreover, high SUV was a significant and independent prognostic factor. In a subgroup analysis, high SUV had a significantly lower 2-year disease-free survival rate than the low SUV group in tumors\u0026thinsp;\u0026le;\u0026thinsp;3.5 cm.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHigh SUV (\u0026ge;\u0026thinsp;5) on FDG-PET/CT of the primary HCC lesion, especially tumors\u0026thinsp;\u0026le;\u0026thinsp;3.5 cm, correlates with early recurrence after curative resection and is an independent prognostic factor.\u003c/p\u003e","manuscriptTitle":"High standard uptake value of the primary lesion of hepatocellular carcinoma correlates with early recurrence after curative resection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-12 13:55:32","doi":"10.21203/rs.3.rs-4239792/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d33c7ed8-49d3-46d2-9a97-e16ba8862e72","owner":[],"postedDate":"April 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-27T17:00:39+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-12 13:55:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4239792","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4239792","identity":"rs-4239792","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}