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The efficacy of contrast-enhanced computed tomography on the management of gastroesophageal varices in patients with hepatocellular carcinoma


Patient characteristics and CT findings compared to endoscopic findings

This study included 312 subjects (Table 1). The study flow chart is shown in Fig. 1. The median observation period was 39.7 months. Initially, 179 (57.4%) patients received potentially curative treatment for HCC. The cumulative overall survival rate was significantly higher in the curative treatment group (n = 179, 96.0%, 91.8%, and 85.0% at 1, 2, and 3 years, respectively) than in the noncurative treatment group (n = 133, 62.0%, 41.8%, and 33.8% at 1, 2, and 3 years, respectively; p < 0.001).

Table 1 Patient characteristics.
Figure 1
figure 1

Among the 312 consecutive patients, 231 patients underwent EGD within 3 months before and after CECT. The EIV diameter, subdivided based endoscopic variceal classification, was as follow: no varices. 1.1 ± 1.3 mm (n = 165); small varices (F1), 4.1 ± 0.8 mm (n = 41); medium varices (F2), 7.3 ± 1.2 mm (n = 23); and large varices (F3), 9.2 ± 3.0 mm (n = 2). The best cutoff values were F1: 3.1 mm (AUC = 0.986) and F2: 5.5 mm (AUC = 0.995). There was no red-color (RC) sign on EGD in the no varices group, and 7 (17.1%) patients in the F1 EV group and 10 (40.0%) patients in the F2-3 EV group exhibited the RC sign. The best cutoff value for the RC sign was 4 mm of the EIV diameter (AUC = 0.936).

The FIV diameter, subdivided based on endoscopic variceal classification, was as follows: no varices, 0.1 ± 0.5 mm (n = 210); small varices (F1), 3.7 ± 1.5 mm (n = 10); medium varices (F2), 8.7 ± 2.1 mm (n = 5); and large varices (F3), 12.0 ± 2.4 mm (n = 6). The best cutoff values were F1:3.4 mm (AUC = 0.972) and F2: 5.7 mm (AUC = 0.999).

The cumulative overall survival rate was significantly lower in patients with EV of F1 or greater on CECT (n = 84, 78.2%, 59.9%, and 54.4% at 1, 2, and 3 years, respectively) than those without (n = 228, 83.4%, 76.0%, and 68.2% at 1, 2, and 3 years, respectively; p < 0.001).

GEV bleeding

During the study periods, 26 patients had GEV bleeding and 7 received prophylactic EV treatment. Cumulative GEV bleeding rates were 3.4%, 5.9%, and 10.8% at 1, 3, and 5 years, respectively. Table 2 shows the predictive factors for GEV bleeding according to the univariate analysis. The multivariate analysis revealed the EIV diameter (p < 0.001), FIV diameter (p = 0.011), and the presence of portal vein tumor thrombus (PVTT) (p = 0.043) as the significant predictive factors for GEV bleeding (Table 2). Cumulative GEV bleeding rates were significantly worsened with the severity of EV classification using CECT (no varices, F1, and F2–F3 of 1.0%, 4.6%, and 19.6% at 1 year; 1.0%, 7.6%, and 24.3% at 2 years; 1.6%, 14.7%, and 24.3% at 3 years, respectively, p < 0.001, Fig. 2). No significant difference was found in GEV bleeding between HCC stages. However, the 1-year cumulative GEV bleeding rate was significantly higher in patients with advanced HCC stages (10.7%) than in those with early-intermediate HCC stages (2.5%, p = 0.034). The cumulative overall survival rate was significantly lower in patients with variceal bleeding within 1 year after HCC diagnosis (55.6%, 33.3%, and 33.3% at 1, 2, and 3 years, respectively) than in those without (82.8%, 72.8%, and 65.5% at 1, 2, and 3 years, respectively; p = 0.013).

Table 2 Cox regression analyses of predictive factors for variceal bleeding.
Figure 2
figure 2

Comparison of cumulative GEV bleeding rates between no varices, F1, and F2/3 on CECT. CECT: contrast-enhanced computed tomography; F1: small varices; F2/3: medium to large varices; GEV: gastroesophageal varices.

Of the 196 patients with viral hepatitis, 91 (46.4%) received antiviral therapy. The cumulative GEV bleeding rates tended to be lower in patients who received antiviral therapy (n = 91, 1.1%, 1.1%, and 1.1% at 1, 2, and 3 years, respectively) than those who did not (n = 105, 2.6%, 4.0%, and 4.0% at 1, 2, and 3 years, respectively, p = 0.051).

Among the 231 patients who underwent EGD, the RC sign (relative risk = 5.035, 95% confidence interval 2.245–11.293) and F1 or more in the EV classification using CECT (relative risk = 9.775, 95% confidence interval 3.412–28.001) were associated with GEV bleeding.

Changes in gastroesophageal intramural vessels and portosystemic shunt over time

CECT was conducted in 157, 141, and 131 patients after 1, 2, and 3 years, respectively. The EIV diameter did not significantly change after 1 year, but the FIV diameter and portosystemic shunt significantly worsened after 1 year (Table 3). The EIV and FIV diameter and portosystemic shunt significantly deteriorated after 2 and 3 years (Table 4). When divided according to the presence or absence of EV based on the classification using CECT, no significant change was found in the EIV diameters in patients with 3 mm or lesser EIV diameters, but an FIV diameter and portosystemic shunt worsening were observed. In the case of patients without cirrhosis, there is only 1 patient with EIV diameter > 3 mm and no patient with FIV diameter > 3.3 mm, and no significant change was found in EIV and FIV diameter and portosystemic shunt over time. The presence of fundal varices based on the classification using CECT and large portosystemic shunt has a positive impact on esophageal variceal exacerbations over time (Tables 3 and 4). When stratified according to HCC stage or treatment, a trend toward worsening the EIV and FIV diameter in the early stage and the curative treatment group was observed after 2 and 3 years (Tables 3 and 4).

Table 3 Change in diameter of variceal veins and portosystemic shunt after 1 year.
Table 4 Change in diameter of variceal veins and portosystemic shunt after 2 and 3 years.

Focusing specifically on patients with viral hepatitis, antiviral therapy potentially slowed the exacerbation of the EIV (pre vs. 1 year later: with antiviral therapy, n = 54, 1.3 ± 1.5 vs. 1.3 ± 1.6 mm, p = 0.876; without antiviral therapy, n = 48, 3.0 ± 2.6 vs. 3.3 ± 3.0 mm, p = 0.022) and FIV diameter (pre vs. 1 year later: with antiviral therapy, 0.2 ± 1.1 vs. 0.3 ± 1.4 mm, p = 0.294; without antiviral therapy, 0.6 ± 2.0 vs. 0.7 ± 2.2 mm, p = 0.045) and portosystemic shunt (pre vs. 1 year later: with antiviral therapy, 2.5 ± 4.0 vs. 2.7 ± 3.9 mm, p = 0.156; without antiviral therapy, 3.1 ± 4.2 vs. 3.7 ± 4.6 mm, p = 0.002) after 1 year.

The EIV deterioration after 1, 2, and 3 years was significantly higher in patients with variceal bleeding (1.7 ± 1.2 mm, 2.9 ± 2.7 mm, and 3.8 ± 1.6 mm after 1, 2, and 3 years, respectively) than those without (0.1 ± 1.1 mm [p < 0.001], 0.2 ± 1.7 mm [p < 0.001], 0.1 ± 1.4 mm [p < 0.001] after 1, 2, and 3 years, respectively).

The best cutoff values were 0.3, 0.7, and 2.3 mm at 1, 2, and 3 years, respectively, (AUC = 0.883, 0.842, 0.961, respectively) correlated with variceal bleeding.



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