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Background: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. Methods: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery and Korean Association of Hepato‐Biliary‐Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. Results: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien‐Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3‐year survival rate was 53.9%, and the 5‐year survival rate was 39.1%. Conclusions: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required. [ABSTRACT FROM AUTHOR]

Background: Robotic liver resections (RLR) may have the ability to address some of the drawbacks of laparoscopic liver resections (LLR) but few studies have done a head‐to‐head comparison of the outcomes after anterolateral segment resections by the two techniques. Methods: A retrospective study was conducted of 3202 patients who underwent minimally invasive LR of the anterolateral liver segments at 26 international centres from 2005 to 2020. Two thousand six hundred and six cases met study criteria of which there were 358 RLR and 1868 LLR cases. Perioperative outcomes were compared between the two groups using a 1:3 Propensity Score Matched (PSM) and 1:1 Coarsened Exact Matched (CEM) analysis. Results: Patients matched after 1:3 PSM (261 RLR vs 783 LLR) and 1:1 CEM (296 RLR vs 296 LLR) revealed no significant differences in length of stay, readmission rates, morbidity, mortality, and involvement of or close oncological margins. RLR surgeries were associated with significantly less blood loss (50 mL vs 100 ml, P <.001) and lower rates of open conversion on both PSM (1.5% vs 6.8%, P =.003) and CEM (1.4% vs 6.4%, P =.004) compared to LLR. Though PSM analysis showed RLR to have a longer operating time than LLR (170 minutes vs 160 minutes, P =.036), this difference proved to be insignificant on CEM (167 minutes vs 163 minutes, P =.575). Conclusion: This multicentre international combined PSM and CEM study showed that both RLR and LLR have equivalent perioperative outcomes when performed in selected patients at high‐volume centres. The robotic approach was associated with significantly lower blood loss and allowed more surgeries to be completed in a minimally invasive fashion. [ABSTRACT FROM AUTHOR]

Background: Although laparoscopic minor liver resections (LLR) of posterosuperior (PS) segments are technically challenging, several expert centers are increasingly performing this procedure. In the present study, we introduced novel techniques, including the rubber band traction method and positional changes, and compared surgical outcomes of LLR for hepatocellular carcinoma (HCC) located in PS segments with open minor liver resection (OLR). Methods: From January 2008 to August 2019, 113 patients underwent laparoscopic (n = 55) or open (n = 58) minor liver resections for single small HCCs (<5 cm) located in PS segments. Propensity score matching in a 1:1 ratio was conducted to minimize preoperative selection bias, and surgical outcomes were compared between the two groups. Results: There was no intraoperative mortality or reoperation in either group. One conversion to open surgery was necessary due to severe post-operative adhesions. The matched LLR group compared to OLR had significantly shorter operative time (215.16 vs. 251.41 min, P = 0.025), lesser blood loss (218.11 vs. 358.92 mL, P = 0.046), lower complication rate (8.1% vs. 29.7%, P = 0.018), and shorter hospital stay (7.03 vs. 11.78 days, P = 0.001). Intraoperative transfusion, R0 resection, resection margin, 5-year disease-free survival and 5-year overall survival were comparable. Conclusion: Our standardized LLR provided improved short-term outcomes and similar long-term outcomes, when compared with OLR. With advanced techniques and accumulated surgical experience, LLR can be the first option for HCC in PS segments at expert centers. [ABSTRACT FROM AUTHOR]

Background: The dissemination of robotic liver surgery is slow‐paced and must face the obstacle of demonstrating advantages over open and laparoscopic (LLS) approaches. Our objective was to show the current position of robotic liver surgery (RLS) worldwide and to identify if improved short‐term outcomes are observed, including secondary meta‐analyses for type of resection, etiology, and cost analysis. Methods: A PRISMA‐based systematic review was performed to identify manuscripts comparing RLS vs open or LLS approaches. Quality analysis was performed using the Newcatle‐Ottawa score. Statistical analysis was performed after heterogeneity test and fixed‐ or random‐effect models were chosen accordingly. Results: After removing duplications, 2728 RLS cases were identified from the final set of 150 manuscripts. More than 75% of the cases have been performed on malignancies. Meta‐analysis from the 38 comparative reports showed that RLS may offer improved short‐term outcomes compared to open procedures in most of the variables screened. Compared to LLS, some advantages may be observed in favour of RLS for major resections in terms of operative time, hospital stay and rate of complications. Cost analyses showed an increased cost per procedure of around US$5000. Conclusions: The advantages of RLS still need to be demonstrated although early results are promising. Advantages vs open approach are demonstrated. Compared to laparoscopic surgery, minor perioperative advantages may be observed for major resections although cost analyses are still unfavorable to the robotic approach. [ABSTRACT FROM AUTHOR]

Background & Aims: Extrahepatic metastasis from hepatocellular carcinoma (HCC) is a catastrophic event, yet organ‐specific pathological characteristics of metastatic HCC remain unclear. We aimed to characterize the pathological aspects of HCC metastases to various organs. Methods: We collected intrahepatic HCC (cohort 1, n = 322) and extrahepatic metastatic HCC (cohort 2, n = 130) samples. Clinicopathological evaluation and immunostaining for K19, CD34, αSMA, fibroblast‐associated protein (FAP), CAIX, VEGF, PD‐L1, CD3, CD8, Foxp3, CD163 and epithelial–mesenchymal transition (EMT)‐related markers were performed. Results: Independent factors for extrahepatic metastasis included BCLC stage B–C, microvascular invasion (MVI), vessels encapsulating tumour clusters (VETC)‐HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, P <.05 for all). Lung metastases (n = 63) had the highest proportion of VETC‐HCC and macrotrabecular‐massive (MTM)‐HCC. Lymph node metastases (n = 19) showed significantly high rates of EMT‐high features, K19 expression, fibrous tumour stroma with αSMA and FAP expression, high immune cell infiltration, PD‐L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell and CD163+ macrophage infiltration (adjusted P <.05 for all). In both cohorts, EMT‐high HCCs showed higher rates of K19 expression, fibrous tumour stroma, high immune cell infiltration, PD‐L1 expression and CD3+ T cell infiltration, whereas EMT‐low HCCs were more frequent among VETC‐HCCs (P <.05 for all). Overall phenotypic features were not significantly different between paired primary‐metastatic HCCs (n = 32). Conclusions: Metastatic HCCs to various organs showed different pathological features. VETC and MTM subtypes were related to lung metastasis, whereas K19 expression, EMT‐high features with fibrous tumour stroma and high immune cell infiltration were related to lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: To date, there are few studies comparing the outcomes of robotic hepatectomy (RH) versus open hepatectomy (OH). We report the first systematic review and meta‐analysis comparing the outcomes of RH versus OH. Methods: A systemic review was performed of all comparative studies of RH versus OH that reported the perioperative outcome(s) of interest. Results: Seven retrospective cohort studies were included. There was no significant difference in patients' baseline characteristics. RH was associated with a longer operation time (mean difference (MD) 61.47 min; 95% confidence interval (CI) (7.03, 115.91); P = 0.03), shorter hospital stay (MD −2.57 days; 95% CI (−3.31, −1.82); P < 0.001), lower costs, less overall (risk ratio (RR) 0.63; 95% CI (0.46, 0.86); P = 0.004), minor (RR 0.64; 95% CI (0.43, 0.95); P = 0.03) and major (RR 0.45; 95% CI (0.22, 0.94); P = 0.03) post‐operative complications compared to OH. Conclusion: RH had superior perioperative outcomes and was not cost prohibitive compared to OH, but had longer operation times. [ABSTRACT FROM AUTHOR]

Somatic mutations in the telomerase reverse transcriptase (TERT) promoter are related to telomerase activation and frequently occur at two hot spots located at −124 and −146 bp relative to the start codon in various cancers. Here, we investigated the occurrence and implications of genetic alterations in the TERT promoter in hepatitis B viral hepatocellular carcinoma (B viral HCC). TERT promoter mutations, especially −124C>T, clearly enhanced transcriptional activity in HCC cell lines. In contrast, TERT mRNA expression was lower in B viral HCC patients with TERT promoter mutations than in those without. We identified prospero homeobox protein 1 (PROX1) as a novel transcriptional activator of TERT; this protein was shown to have particularly strong binding affinity for the mutant TERT promoter. However, stable expression of the hepatitis B virus X (HBx) protein inhibited PROX1‐mediated TERT expression in vitro. Our data suggest that TERT promoter mutations can enhance the promoter activity in HCC cell lines expressing PROX1 but are not the predominant mechanism of TERT upregulation in B viral HCC patients, based on the inhibition of PROX1‐dependent transcriptional activation by HBx. What's new? Telomerase activation and cell immortalization are critical steps in cancer development and progression and are associated with mutations in the telomerase reverse transcriptase (TERT) gene. Here, in hepatocellular carcinoma (HCC) cells, the transcription factor prospero homeobox protein 1 (PROX1) was found to regulate the TERT gene by binding to the mutated TERT promoter with a consensus ETS/TCF‐binding sequence. Hepatitis B virus X protein (HBx) inhibited PROX1 binding to the TERT promoter, resulting in TERT mRNA downregulation. The findings suggest that in B viral HCC, mutations enhancing TERT promoter activity in PROX1‐expressing cells are not the primary mechanism behind TERT upregulation. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated lactate clearance ( LC), measured at 6, 12, 18, and 24 hours after reperfusion, as a predictor of early allograft dysfunction ( EAD) and short-term outcomes in patients receiving deceased donor liver transplantation. Of 181 transplant recipients, 44 (24.3%) developed EAD and had lower LCs than those who did not develop EAD. A receiver operating characteristic analysis showed that LC determined at 6 hours showed the highest area under curve value of 0.828 (95% confidence interval [ CI]: 0.755-0.990) for predicting the development of EAD at a cutoff value of 25.8% with 76.7% sensitivity and 77.9% specificity. LC values that fell below the cutoff values were significantly associated with EAD in a multivariate analysis, with values at 6 hours having the highest adjusted odds ratio (11.891, 95% CI: 4.469-31.639). In-hospital and 6 month mortalities were higher in patients with LC values below the cutoffs compared with those above the cutoff values at each time point. Thus, LC calculated shortly after reperfusion of an allograft is significantly discriminative for the development of EAD and is associated with short-term prognosis after deceased donor liver transplantation. [ABSTRACT FROM AUTHOR]

Background Recurrence of hepatocellular carcinoma ( HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus ( HBV)-related HCC after curative resection. Methods Patients with HBV-related HCC who underwent curative resection and showed Laennec stage 3 to 4 were enrolled and the cases with stage 4 were subclassified histologically into three groups (stages 4A, 4B and 4C) according to the Laennec system. Between February 2006 and August 2009, 92 patients were recruited. Results Stage 3, 4A, 4B and 4C were identified in 24 (26.1%), 15 (16.3%), 43 (46.7%) and 10 (10.9%) patients respectively. The cumulative incidence rates of recurrence at 1, 2 and 3 years were 24.2%, 40.5% and 55.1% respectively. On multivariate analysis, serum albumin [hazard ratio ( HR), 0.528; 95% confidence interval ( CI), 0.312-0.891; P = 0.017] and Edmondson-Steiner grade III- IV ( HR, 3.456; 95% CI, 1.123-10.517; P = 0.031) were significantly correlated with early recurrence (<1 year), whereas stage 4C ( HR, 5.426; 95% CI, 1.030-28.598; P = 0.046) was the only independent risk factor for late recurrence (≥1 year). Conclusions Histological subclassification of cirrhosis using the Laennec system is a significant predictor of late recurrence in patients with HBV-related HCC after curative resection. [ABSTRACT FROM AUTHOR]

Introduction Hypersplenism with thrombocytopenia is a common complication of cirrhosis with portal hypertension. We evaluated the role of splenectomy in patients with hepatocellular carcinoma ( HCC) in terms of the improvement of biochemical indices and liver volume. Methods Nineteen patients with HCC underwent liver resection and splenectomy from January 2000 to December 2009. Thirty-nine patients who underwent liver resection during the same period were enrolled as case-matched controls. We performed a retrospective review of prospectively collected data. We analysed the results of biochemical tests, disease-free survival and overall survival and measured the liver volume before and at 90 days after operation. Results Preoperative white blood cell counts ( P = 0.001), platelet counts ( P = 0.021), total bilirubin ( P ≤ 0.001) and prothrombin time by international normalized ratio ( P = 0.043) were significantly different. However, these results had converged to similar levels 90 days after the operation. The degree of increment in liver volume were similar ( P = 0.763). In splenectomy group, portal vein thrombosis developed in eight patients and all patients except one recovered using only conservative treatments. There was an operative mortality because of liver failure by thrombosis. Conclusions Although splenectomy may induce thrombosis, liver failure and subsequent mortality, splenectomy may improve liver function and expand the indication of liver resection if postoperative management is conducted conservatively. [ABSTRACT FROM AUTHOR]

Background and Aim Although tumor differentiation is a known prognostic factor after the treatment of hepatocellular carcinoma ( HCC), there have not been any studies on the prognostic significance of tumor differentiation in HCC with heterogeneous histologic grades. In this study, we attempted to ascertain whether the major or the worst grade in mixed histologic type HCC determines the prognosis after liver resection. Methods From January 1996 to March 2010, a total of 724 patients underwent curative resection of HCC at Yonsei University Health System, Korea. Of those, we excluded 99 patients who had total necrosis because of previous treatment. Among the remaining 625 patients, we compared the homogeneous moderately differentiated group ( HG2, n = 241), mixed histologic grades with the worst component as poorly differentiated group ( M2, n = 142), and homogeneous poorly differentiated group ( HG3, n = 156). The clinicopathologic features, disease-free survival ( DFS) and overall survival ( OS) in each group were analyzed. Results The DFS and OS were significantly lower in M2 than in HG2 ( P = 0.004 and 0.025, respectively) whereas those of M2 were not significantly different from HG3. There were no significant differences in the clinicopathologic features of each group except that microvascular invasion was more frequently observed in M2 than in HG2. On multivariate analysis, being in the worst histologic group ( M2 and HG3) was an independent poor prognostic factor for DFS and OS ( P = 0.028 and < 0.001, respectively). Conclusions In patients with advanced histologic grade, the worst histologic grade may determine the prognosis after curative resection of HCC. [ABSTRACT FROM AUTHOR]

Introduction: We report our experience with laparoscopic major liver resection in Korea based on a multicenter retrospective study. Materials and methods: Data from 1,009 laparoscopic liver resections conducted from 2001 to 2011 were retrospectively collected. Twelve tertiary medical centers with specialized hepatic surgeons participated in this study. Results: Among 1,009 laparoscopic liver resections, major liver resections were performed in 265 patients as treatment for hepatocellular carcinoma, metastatic tumor, intrahepatic duct stone, and other conditions. The most frequently performed procedure was left hemihepatectomy (165 patients), followed by right hemihepatectomy (53 patients). Pure laparoscopic procedure was performed in 190 patients including 19 robotic liver resections. Hand-assisted laparoscopic liver resection was performed in three patients and laparoscopy-assisted liver resection in 55 patients. Open conversion was performed in 17 patients (6.4 %). Mean operative time and estimated blood loss in laparoscopic major liver resection was 399.3 ± 169.8 min and 836.0 ± 1223.7 ml, respectively. Intraoperative transfusion was required in 65 patients (24.5 %). Mean postoperative length of stay was 12.3 ± 7.9 days. Postoperative complications were detected in 53 patients (20.0 %), and in-hospital mortality occurred in two patients (0.75 %). Mean number and mean maximal size of resected tumors was 1.22 ± 1.54 and 40.0 ± 27.8 mm, respectively. R0 resection was achieved in 120 patients with hepatic tumor, but R1 resection was performed in eight patients. Mean distance of safe resection margin was 14.6 ± 15.8 mm. Conclusions: Laparoscopic major liver resection has become a reliable option for treatment of liver disease in Korea. [ABSTRACT FROM AUTHOR]

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are widely used complementary tumor markers for hepatocellular carcinoma (HCC). In this study, we investigated whether preoperative AFP and DCP levels predict recurrence after curative resection in patients with hepatitis B virus (HBV)-related HCC. Records for 267 patients who were diagnosed with HBV-related HCC and who underwent curative resection for HCC were retrospectively reviewed. Patients were divided into two preoperative groups: pre-op I (AFP ≥20 ng/dL and DCP ≥40 mAU/mL) and pre-op II (AFP ≥20 ng/dL and DCP <40 mAU/mL; AFP <20 ng/dL and DCP ≥40 mAU/mL; or AFP <20 ng/dL and DCP <40 mAU/mL). Among 267 patients, 102 (38.2%) patients were classified as pre-op I, whereas the other 165 (61.8%) belonged to pre-op II. During the post-resection follow-up [69.0 (3.0-136.0) months] period, 154 (57.7%) patients developed recurrences [68 (66.7%) patients in pre-op I vs. 86 (52.1%) in pre-op II, p = 0.029]. A multivariate analysis revealed that multiple tumors [hazard ratio (HR), 2.210; 95% confidence interval (CI), 1.185-4.121] and pre-op I (HR: 1.890; 95% CI; 1.080-3.289) were significant predictors for recurrence. Disease-free survival (DFS) was significantly shorter in pre-op I compared to that in pre-op II (20.0 vs. 46.8 months, p = 0.006). Elevated preoperative AFP and DCP levels were associated with a higher recurrence rate and shorter DFS in patients with HBV-related HCC after curative resection. The combined measurement of preoperative AFP and DCP may be a prognostic factor for future recurrence. [ABSTRACT FROM AUTHOR]

Background and Aim: Liver stiffness (LS) measurement can distinguish individuals with potential liver disease (LD) from the general population. However, if LS is sex-sensitive, prevalence of LD may be incorrectly estimated when the same reference LS value is applied irrespective of sex. Here, we evaluated whether normal ranges of LS differ between healthy men and women. Methods: LS was measured in a cohort of healthy living liver and kidney donors, none of whom suffered from diabetes mellitus, hypertension, hepatitis B or C virus infection, heart or liver dysfunction, or metabolic syndrome. Patients with abnormal laboratory findings related to potential LD (platelet count < 150 × 103/µL; aspartate aminotransferase > 40 IU/L; alanine aminotransferase [ALT] > 40 IU/L; albumin < 3.3 g/dL; total bilirubin > 1.2 mg/dL; gamma-glutamyl transpeptidase > 54 IU/L; alkaline phosphatase > 115 IU/L) were excluded. Results: Among 242 patients analyzed, the mean age was 34.1 for men ( n = 121) and 40.5 years for women ( n = 121) ( P < 0.001). Men had a higher mean LS value than women (5.2 ± 1.2 vs 4.8 ± 1.1 kPa/ P < 0.001). Multivariate-linear regression analysis identified sex as the only independent factor for LS values ( β = 0.361/ P = 0.021). Using the 5th-95th percentiles, we determined normal LS ranges of 3.7-7.0 kPa in men and 3.3-6.8 kPa in women. In subgroups with ALT < 30 IU/L (subgroup-1, n = 216) and ALT < 20 IU/L (subgroup-2, n = 163), men had significantly higher LS values than women (5.2 ± 1.3 vs 4.7 ± 1.1 kPa/ P = 0.003 and 5.1 ± 1.2 vs 4.7 ± 1.1 kPa/ P = 0.030, respectively), demonstrating an independent sex effect ( β = 0.483/ P = 0.003 and β = 0.389/ P = 0.030, respectively). Conclusions: An independent sex effect on LS values was confirmed. Thus, sex-specific references should be used for effective screening based on LS measurements. [ABSTRACT FROM AUTHOR]

Background & Aims To determine whether magnetic resonance ( MR) imaging features differ between hepatocellular carcinomas ( HCCs) with and without expression of progenitor cell markers, such as cytokeratin ( CK) 19 and epithelial cell adhesion molecule ( EpCAM). Methods Sixty-three patients with 71 HCCs who underwent surgery after preoperative gadoxetic acid-enhanced MR imaging were evaluated. HCCs expressing progenitor cell markers were defined as showing CK19 or EpCAM expression. MR imaging features, including the fat component, arterial enhancement (global vs. peripheral), dynamic enhancement (washout vs. progressive or persistent), nodule-in-nodule appearance and MR gross morphology (expanding vs. non-expanding), were compared between HCCs with and without progenitor cell markers expression. Lesion-to-liver signal intensity ratio ( SIR) and apparent diffusion coefficient values were compared using an independent samples t-test. Early recurrence rates were also compared. Results HCCs expressing progenitor cell markers were more commonly of the non-expanding type ( P = 0.016), more frequently had a progressive or persistent dynamic enhancement pattern ( P = 0.008) and less frequently demonstrated a nodule-in-nodule appearance ( P = 0.009). HCCs expressing progenitor cell markers had significantly higher SIRs on diffusion-weighted images ( DWIs) ( b = 50 and 800, P < 0.001; b = 400, P = 0.001) and a significantly lower SIR on hepatobiliary phase images ( P = 0.024). The early recurrence rate was significantly higher in patients with prior HCCs that expressed progenitor cell markers ( P = 0.045). Conclusions HCCs expressing progenitor cell markers can be characterized according to their non-expanding MR gross morphology, persistent or progressive dynamic enhancement patterns, higher SIRs on DWIs, lower SIRs on hepatobiliary phase images and less frequent nodule-in-nodule appearance. [ABSTRACT FROM AUTHOR]

Purpose: To assess the incremental value of hepatobiliary phase images in gadoxetate disodium-enhanced magnetic resonance imaging (MRI), and to compare diagnostic accuracy and lesion conspicuity on 10- and 20-minute delayed images for preoperative detection of hepatic metastases with subgroup analysis according to size and history of chemotherapy. Materials and Methods: Forty-six patients with 107 metastases who underwent surgery after gadoxetate disodium-enhanced MRI were evaluated. Four observers independently interpreted three sets: dynamic set comprising precontrast T1-, T2-weighted, and dynamic images; 10-minute set comprising dynamic set and 10-minute delayed; 20-minute set comprising 10-minute set and 20-minute delayed. Diagnostic accuracy was compared with subgroup analysis. Liver-to-lesion signal ratio (SR) was calculated using the region of interest method and compared. Results: Mean Az and sensitivities were significantly higher for 10- ( Az = 0.894, sensitivity = 95.6%) and 20-minute (0.910, 97.2%) than dynamic set (0.813, 79.9%) ( P < 0.001), with no significant difference between 10- and 20-minute sets ( P = 0.140). In patients with small (≤1 cm) metastases and a history of chemotherapy, sensitivities were significantly higher with 10- (88.2%) and 20-minute (91.6%) sets than dynamic set (48.6%) ( P < 0.001). SR was significantly higher for 10- and 20-minute delayed than precontrast and dynamic, with significantly higher SR on 20- than 10-minute delayed. Conclusion: Regardless of size or prior chemotherapy, detection of hepatic metastases was significantly improved by adding hepatobiliary phase images without significant differences between 10- and 20-minute delayed. J. Magn. Reson. Imaging 2012;35:635-643. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and Aim: Although several studies have investigated the normal range of liver elasticity using acoustic radiation force impulse (ARFI) elastography in healthy volunteers, they could not strictly exclude the morphological and functional liver abnormalities. The aim of this study was to identify the normal range of ARFI velocity by recruiting healthy living liver and kidney donors who passed the full laboratory tests and imaging studies. Methods: The study prospectively enrolled 108 healthy living liver ( n = 42) and kidney donors ( n = 66) who were admitted for transplantation between July 2010 to April 2011. None of the subjects had abnormal liver function test and imaging findings including conventional ultrasonography, computed tomography or magnetic resonance imaging. Results: The mean age of the study population (58 men and 50 women) was 35.5 years, and the mean ARFI velocity was 1.07 ± 0.11 m/s (range: 0.79-1.27). ARFI velocity was not significantly different between subjects with body mass index (BMI) < 23.5 kg/m2 and those with BMI ≥ 23.5 kg/m2 (1.05 ± 0.12 m/s vs 1.07 ± 0.10 m/s, P = 0.518), nor was it significantly different according to age ( P = 0.067) and gender (1.08 ± 0.12 m/s for men vs 1.05 ± 0.11 m/s for women, P = 0.085). Using the 5th and 95th percentiles, we determined the normal range and mean of ARFI velocity to be 0.85-1.25 m/s and 1.07 ± 0.11 m/s. Conclusions: We identified the normal range of ARFI velocity as 0.85-1.25 m/s and found that it was not significantly influenced by BMI, gender, and age. [ABSTRACT FROM AUTHOR]

Background and Aim: Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection. Methods: A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease-free survival for more than 5 years (DFS group). Variables were compared between the two groups. Results: Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor-rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio = 3.2, P = 0.03, standard error = 0.5, Logistic regression analysis). Conclusions: Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors. [ABSTRACT FROM AUTHOR]

Subtelomeric chromatin modifications are important regulators of telomere length. We examined the subtelomeric DNA methylation status of 7q, 8q, 17q, 18p, 21q and XpYp in 32 pairs of hepatocellular carcinomas (HCCs) and their adjacent non-HCCs via methylation-specific PCR (quantified as methylation ratio). In addition, 10q was subjected to bisulfite-genomic-sequencing. Telomere length was determined by Southern hybridization. In all cases, the relationship between methylation ratio and telomere length was determined. High levels of methylation ratio were found on chromosomes 7q, 18p and XpYp, whereas 8q 17q and 21q were less methylated in both HCCs and non-HCCs. Compared to non-HCCs, HCCs exhibited a higher methylation ratio on 18p and 21q, and a wider distribution of methylation ratio on 7q, 21q and 10q ( p < 0.05). The methylation ratio of 18p and of 21q was negatively and positively correlated with telomere length of HCCs, respectively ( p < 0.05). We evaluated changes in methylation pattern between non-HCCs and HCCs. Out of 185 sites, hypermethylation changes from non-HCC to HCC were found at 47 sites and hypomethylation changes at 31 sites. Changes in methylation pattern were observed at three to four sites among six chromosomal sites in 15 patients (47%). There was a tendency toward hypomethylation changes at 7q ( p = 0.013) and hypermethylation changes at 21q ( p = 0.057) when telomere lengthened from non-HCCs to HCCs. In summary, subtelomeric methylation patterns dynamically changed during hepatocarcinogenesis. Subtelomeric methylation at certain regions was related to telomere lengthening or shortening, suggesting an association between subtelomeric chromatin structure and telomere length regulation in human hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Background & Aims Methods Results Conclusion Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA‐MRI) and hepatobiliary agent (HBA‐MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs.The present study included 102 prospectively enrolled at‐risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA‐MRI and HBA‐MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs.The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non‐smooth tumour margin (ECA‐MRI, odds ratio [OR] = 5.30; HBA‐MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA‐MRI, OR = 4.26; HBA‐MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two‐trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA‐MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA‐MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA‐MRI vs 51.3% on HBA‐MRI, p = .75) were not significantly different between the two MRIs.Prognostic imaging features of HCC may be comparable between ECA‐MRI and HBA‐MRI. [ABSTRACT FROM AUTHOR]

Aims: To identify the normal range of liver stiffness (LS) values by recruiting healthy living liver and kidney donors in South Korea., Methods: Liver stiffness measurement (LSM) was performed in 69 healthy living liver and kidney donors who were admitted for transplantation. None of the subjects suffered from diabetes mellitus, hypertension, hepatitis B virus infection, hepatitis C virus infection, heart dysfunction, liver dysfunction or metabolic syndrome., Results: LSM failure rate was 2.7%. Among 12 liver donors (17.4%) with available liver histology, eight showed normal liver histology and four showed liver steatosis of <5% of the hepatocytes. The mean age of our study population was 38.9+/-11.9 years (35 men and 34 women), with a mean LS value of 4.6+/-0.5 kPa (range 3.3-5.6 kPa). LS values were not significantly different between men (4.6+/-0.6 kPa) and women (4.5+/-0.5 kPa, P=0.636), nor were they significantly different according to age (P=0.851). Using the fifth and 95th percentiles, we determined the normal range of LS values to be 3.9-5.3 kPa., Conclusions: We identified the normal range of LS values and found that LS values were not significantly influenced by age and gender.