The impact of preoperative nutritional status on postoperative outcomes: an insight from Geriatric Nutritional Risk Index in elderly pancreaticoduodenectomy patients.

BACKGROUND: Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD. MATERIALS AND METHODS: This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N = 54), low nutrition risk (92 < GNRI ≤ 98, N = 35), and no nutrition risk (GNRI > 98, N = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS). RESULTS: Patients in the high/moderate risk group were significantly older, with lower BMI (P = 0.012), higher mortality rate (11.1%, P = 0.024), longer PLOS (P < 0.001), and higher incidence of over grade IIIB complications (37.0%, P = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P = 0.032), increased age (OR 1.11, P = 0.014) and operative time over 8 h (OR 3.04, P = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P = 0.002). CONCLUSIONS: Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD.

Circadian Rhythm Disruption in Hepatocellular Carcinoma Investigated by Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data.

Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan-Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC.

Tumor Necrosis Is an Indicator of Poor Prognosis Among Hepatoma Patients Undergoing Resection.

INTRODUCTION: Tumor necrosis has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients undergoing liver resection (LR). However, more evidence is needed to clarify this issue. METHODS: Patients who underwent upfront LR between 2010 and 2018 for newly diagnosed HCC without undergoing neoadjuvant therapy were enrolled in this retrospective study. Tumor necrosis was classified as present or absent according to retrospective examinations. The association between tumor necrosis, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed. RESULTS: Among 756 patients who underwent LR for HCC, tumor necrosis was present in 279 (36.9%) patients. Compared with patients without tumor necrosis, patients with tumor necrosis had higher proportions of tumors sized >5.0 cm (P < 0.001), multiple tumors (P < 0.001), microvascular or macrovascular invasion (P < 0.001), poorly differentiated or undifferentiated tumors (P < 0.001), and T stage 3 or 4 (P < 0.001) on pathological examination. The presence of tumor necrosis was associated with worse OS and RFS compared with the absence of tumor necrosis: 5-y OS was 56% versus 78% (P < 0.001); 5-y RFS was 42% versus 55% (P < 0.001). In multivariate analysis, the presence of tumor necrosis was an independent factor associated with worse OS (hazard ratio: 1.956; 95% confidence interval: 1.409-2.716; P < 0.001) and RFS (hazard ratio: 1.422; 95% confidence interval: 1.085-1.865; P = 0.011). CONCLUSIONS: Tumor necrosis was associated with worse OS and RFS among patients who underwent LR for HCC.

Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. METHODS: We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. RESULTS: This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20 ng/ml (p = 0.562), patients with AFP ≤ 20 ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). CONCLUSION: No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

Radiographic tumor burden score is useful for stratifying the overall survival of hepatocellular carcinoma patients undergoing resection at different Barcelona Clinic Liver Cancer stages.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages. METHODS: Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007-2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile. RESULTS: Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3%) BCLC-A, and 69 (9.2%) BCLC-B HCC; 76 (10.1%) had a high TBS (> 7.9), 477 (63.7%) a medium TBS (2.6-7.9), and 196 (26.2%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p < 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024-5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI = 1.443-10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077-6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p < 0.001). CONCLUSION: The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

Seven centimeters as an optimal cutoff value for prognosis stratification in large monofocal hepatocellular carcinoma.

PURPOSE: Barcelona Clinic Liver Cancer (BCLC) guidelines designate monofocal hepatocellular carcinoma (HCC) > 2 cm as BCLC A, and large monofocal HCC is defined at > 5 cm. We aimed to evaluate the optimal cutoff value for large monofocal HCC based on prognosis stratification. METHODS: From 2011 to 2018, 3055 patients with newly diagnosed HCC, who were managed in our institution, including 868 patients with monofocal HCC > 2 cm and 330 patients with BCLC B, were enrolled in this retrospective study. RESULTS: Monofocal HCC > 5 cm patients had worse overall survival (OS) than monofocal HCC 2-5 cm patients (5-year OS: 54% vs. 57%; p = 0.047), confirmed by multivariate analysis (hazard ratio (HR): 1.492, 95% confidence interval (CI): 1.055-2.110; p = 0.024). Monofocal HCC > 5 cm patients had better OS than BCLC B HCC patients (5-year OS: 54% vs. 25%; p < 0.001), confirmed by multivariate analysis (HR: 0.670, 95% CI: 0.481-0.934; p = 0.018). Using 7 cm as the monofocal HCC cutoff value resulted in worse OS than monofocal HCC 2-7 cm (5-year OS: 50% vs. 57%; p = 0.02), confirmed by multivariate analysis (HR: 1.625, 95% CI: 1.039-2.540; p = 0.033). Monofocal HCC > 7 cm patients had better OS than BCLC B patients (p = 0.006). However, no significant difference was identified in the multivariate analysis (HR: 0.726; 95% CI: 0.473-1.115; p = 0.144). CONCLUSIONS: The prognosis of monofocal HCC > 7 cm was similar to that of BCLC B, indicating that 7 cm represents an optimal cutoff value for prognosis stratification in large monofocal HCC.

Near-infrared cholangiography can increase the chance of success in laparoscopic approaches to common bile duct stones, even with previous abdominal surgery.

BACKGROUND: The treatment of common bile duct (CBD) stones with minimally invasive surgery (MIS) is more technical demanding than laparoscopic cholecystectomy (LC), especially in patients with history of previous abdominal surgery, cholangitis or cholecystitis. Near-infrared (NIR) cholangiography via systemic or biliary tree administration of indocyanine green (ICG), which enhances the visualization of the biliary tree anatomy, may increase the reassurance of CBD localization. The aim of this study was to identify the benefit of near-infrared cholangiography for laparoscopic common bile duct exploration (LCBDE). METHODS: Three groups of CBD stone patients were included in this retrospective study depending on the surgical methods: 1) open choledocholithotomy (OCC), 2) laparoscopic choledocholithotomy (LCC), and 3) near-infrared cholangiography-assisted laparoscopic choledocholithotomy (NIR-CC). For the NIR-CC group, either 3 ml (concentration: 2.5 mg/mL) of ICG were intravenously administered or 10 ml (concentration: 0.125 mg/mL) of ICG were injected directly into the biliary tree. The enhancement rate of the cystic duct (CD), CBD, the upper and lower margin of the CBD were compared using white light image. RESULTS: A total of 187 patients with a mean age of 68.3 years were included (OCC, n = 56; LCC, n = 110; NIR-CC, n = 21). The rate of previous abdominal surgery was significantly lower in the LCC group. The conversion rate was similar between the LCC and the NIR CC groups (p = 0.746). The postoperative hospital stay was significantly longer in the OCC group. No differences in morbidity and mortality were found between the three groups. In the NIR-CC group, the localization of CBD was as high as 85% compared to 24% with white light imaging. CONCLUSIONS: Near-infrared cholangiography helps increase the chance of success in minimally invasive approaches to CBD stones even in patients with previous abdominal surgeries, without increasing the rate of conversion.

Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.

A simple preoperative model to predict overall survival of patients undergoing liver resection for hepatocellular carcinoma ≥10 cm.

BACKGROUND: Studies have rarely reported on preoperative predictors of prognosis of patients undergoing liver resection (LR) for HCC ≥10 cm. We developed a simple model to predict overall survival (OS) of these patients. METHODS: We enrolled 305 patients with HCC ≥10 cm undergoing LR. Cirrhosis and imaging-defined AJCC stage were used to develop a preoperative model. Patients were divided into three groups based on the Kaplan-Meier estimator. RESULTS: Group 1 included patients with AJCC stage 1 and no cirrhosis (n = 86), group 2 those with AJCC stage 1 and cirrhosis plus those with AJCC stage 2 or 3 and no cirrhosis (n = 166), and group 3 those with AJCC stage 2 or 3 and cirrhosis (n = 51). The five-year OS of group 1, 2, and 3 was 55%, 32%, and 25%, respectively (p < 0.001). With group 1 as the reference, multivariate analysis of OS showed that group 2 (HR = 2.043; 95% CI = 1.332-3.134; p = 0.001) and group 3 (HR = 2.740; 95% CI = 1.645-4.564; p < 0.001) were independent predictors of OS. CONCLUSION: We developed a simple model to predict OS of patients undergoing LR for HCC ≥10 cm.

The Impact of Direct-Acting Antiviral Therapy on the Risk of Recurrence after Curative Resection in Patients with Hepatitis-C-Virus-Related Early Stage Hepatocellular Carcinoma.

Background and Objectives: The impact of direct-acting antiviral (DAA)-based regimens on the recurrence of hepatocellular carcinoma (HCC) after successful curative hepatectomy is controversial. Aims: This study aimed to assess the association between DAAs treatment and recurrence risk in HCC after resection. Materials and Methods: We retrospectively assessed 152 cases of early stage (BCLC stage 0/A) hepatitis C virus (HCV)-related HCC (HCV-HCC) that underwent resection with curative intent between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital; 48 cases achieved a sustained virological response (SVR) by DAA, and 104 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative resection was analyzed by using the log-rank test and Kaplan-Meier method. A Cox proportional hazards model was used to analyze the factors that impacted RFS and OS. Results: Five patients (10.4%) experienced HCC recurrence after DAA therapy. The cumulative HCC recurrence rate was significantly lower in the DAA group than the non-treatment group (p < 0.001). Multivariate analysis revealed a significant difference in RFS between the non-treatment group and DAA group (p = 0.001; hazard ratio (HR), 4.978; 95% CI, 1.976-12.542); liver cirrhosis (p = 0.005; HR, 2.062; 95% CI, 1.247-3.410), microvascular invasion (p = 0.001; HR, 2.331; 95% CI, 1.408-3.860) and AFP > 15 ng/mL (p = 0.022; HR, 1.799; 95% CI, 1.089-2.970) were also independent factors for HCC recurrence. ALBI stage II/III (p = 0.005; HR, 3.249; 95% CI, 1.418-7.443) and microvascular invasion (p < 0.001; HR, 4.037 95% CI, 2.071-7.869) were independent factors for OS; no significant difference in OS was observed between the DAA and no DAA treatment groups. Conclusions: DAA treatment could reduce the risk of recurrence after curative treatment for early stage HCC.

Statin use is associated with a lower risk of recurrence after curative resection in BCLC stage 0-A hepatocellular carcinoma.

BACKGROUND: Use of statins is associated with a reduced risk of hepatocellular carcinoma (HCC). However, the effect of statin use on HCC recurrence is unclear. This study aimed to evaluate the effect of statin use on recurrence after curative resection among patients with HCC. METHODS: We retrospectively assessed 820 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statins was defined as use of a statin for at least 3 months before HCC recurrence. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. RESULTS: Of the 820 patients, 46 (5.6%) used statins (statin group) and 774 (94.4%) did not (non-statin group). During the mean follow-up of 76.5 months, 440 (53.7%) patients experienced recurrence and 146 (17.8%) patients died. The cumulative incidence of HCC recurrence was significantly lower in the statin group than the non-statin group (p = 0.001); OS was not significantly different between groups. In multivariate analysis, age (hazard ratio [HR]: 1.291; p = 0.010), liver cirrhosis (HR: 1.743; p < 0.001), diabetes (HR:1.418; p = 0.001), number of tumors (HR: 1.750; p < 0.001), tumor size (HR: 1.406; p = 0.004) and vascular invasion (HR: 1.659; p < 0.001) were independent risk factors for HCC recurrence, whereas statin use (HR: 0.354; p < 0.001) and antiviral therapy (HR: 0.613; p < 0.001) significantly reduced the risk of HCC recurrence. The statin group still had lower RFS than the non-statin group after one-to-four propensity score matching. CONCLUSION: Statins may exert a chemo-preventive effect on HCC recurrence after curative resection.

Microscopic portal vein invasion is a powerful predictor of prognosis in patients with hepatocellular carcinoma who have undergone liver resection.

BACKGROUND AND OBJECTIVES: A recent study proposed simple classifications of microscopic vascular invasion (MVI): microscopic portal vein invasion (MPVI) and microvessel invasion (MI). We aim to validate these classifications of MVI. METHODS: This retrospective study consecutively enrolled 514 Barcelona Clinic Liver Cancer stage 0, A, and B naïve hepatocellular carcinoma patients who underwent liver resection in our institution from 2011 to 2017. RESULTS: Among these 514 patients, 240 patients were classified as having no MVI at all (designated as no vascular invasion, NVI), 157 patients were classified as having MI only, and 117 patients were classified as having MPVI. The 5-year overall survival (OS) rate in the MI-only group was 83.3%, which was not significantly different from that of the NVI group (87.2%), p = .20. Using NVI as a reference, multivariate analysis showed that MI-only is not an independent variable associated with OS. The 5-year OS in the MPVI group was 59.2%, which was significantly lower than those for MI-only (p < .001) and NVI groups (p < .001). Using NVI as a reference, multivariate analysis showed that MPVI is an independent variable associated with OS (HR, 3.12; 95% CI, 1.80-5.40; p < .001). CONCLUSIONS: The results of this study validate the simple MVI classifications to be clinically useful.

Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection.

BACKGROUND: The albumin-bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. AIM: This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. METHOD: From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. RESULTS: There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child-Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS. CONCLUSION: The preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.

Short-term outcomes after minimally invasive versus open pancreaticoduodenectomy in elderly patients: a propensity score-matched analysis.

BACKGROUND: To date, the evidence on the safety and benefits of minimally invasive pancreatoduodenectomy (MIPD) in elderly patients is still controversy. This study aim to compare the risk and benefit between MIPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: From 2016 to 2020, we retrospective enrolled 26 patients underwent MIPD and other 119 patients underwent OPD. We firstly compared the baseline characteristics, 90-day mortality and short-term surgical outcomes of MIPD and OPD. Propensity score matching was applied for old age patient (≥ 65-year-old vs. < 65-year-old) for detail safety and feasibility analysis. RESULTS: Patients received MIPD is significantly older, had poor performance status, less lymph node harvest, longer operation time, less postoperative hospital stay (POHS) and earlier drain removal. After 1:2 propensity score matching analysis, elderly patients in MIPD group had significantly poor performance status (P = 0.042) compared to OPD group. Patients receiving MIPD had significantly shorter POHS (18 vs. 25 days, P = 0.028), earlier drain removal (16 vs. 21 days, P = 0.012) and smaller delay gastric empty rate (5.9 vs. 32.4% P = 0.036). There was no 90-day mortality (0% vs. 11.8%, P = 0.186) and pulmonary complications (0% vs. 17.6%, P = 0.075) in MIPD group, and the major complication rate is comparable to OPD group (17.6% vs. 29.4%, P = 0.290). CONCLUSION: For elderly patients, MIPD is a feasible and safe option even in patients with inferior preoperative performance status. MIPD might also provide potential advantage for elderly patients in minimizing pulmonary complication and overall mortality over OPD.

Super-Selective Intra-Arterial Indocyanine Green Administration for Near-Infrared Fluorescence-Based Positive Staining of Hepatic Segmentation: A Feasibility Study.

BACKGROUND: Despite the increasing number of laparoscopic hepatic procedures for the resection of hepatocellular carcinoma (HCC), intraoperative tumor localization and demarcation remains challenging in comparison to open surgery. In this study, we evaluated the feasibility of positive liver segment staining through the super-selective intra-arterial indocyanine green (ICG) administration. METHODS: Eight patients presenting with a single HCC underwent an interventional vascular procedure followed by laparoscopic surgery. A microcatheter was advanced into the hepatic artery branches perfusing the HCC followed by digital subtraction angiography and angiography computed tomography (angio-CT). Patients were then transferred to the operating room, and a laparoscopic hepatectomy was performed under ultrasound guidance. A 5 mL bolus of ICG with a concentration of .125 mg/mL was injected through the microcatheter, and a near-infrared laparoscope was used to detect the fluorescence signal to assess the correspondence between the fluorescence-based demarcation and the intraoperative ultrasound-based demarcation. RESULTS: The duration for the angiography procedure was 32.7 +/- 5.3 min, and it took 242 +/- 118 min from the end of angiography procedure until the start of the surgical procedure. In all cases, the fluorescent liver segment was corresponding to the angio-CT findings. In 6/8 cases, fluorescence imaging was considered helpful in the identification of the resection line. In 3 patients, the resection line was changed according to the positively stained liver segment. CONCLUSION: We successfully demonstrated the feasibility of the super-selective intra-arterial ICG administration for fluorescence-based positive staining of hepatic segmentation during laparoscopic surgery for HCC (NCT04266548).

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy.

Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

Liver resection of hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guideline recommendations: Results from a high-volume liver surgery center in East Asia.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) guidelines were updated in 2012, and a single large hepatocellular carcinoma (HCC) more than 5 cm was regarded as BCLC stage A rather than B in the updated version. In this study, we sought to re-evaluate the outcomes of patients with HCC who underwent liver resection (LR) within (stage 0 and A) and beyond (stage B and C) the BCLC guideline recommendations of the updated BCLC staging system. METHODS: This retrospective study enrolled 774 consecutive patients with naïve HCC who underwent LR from 2011 to 2018 at our institution. The overall survival (OS) and recurrence-free survival (RFS) of these patients were examined. RESULTS: Of the patients, 606 had BCLC stage 0 or A HCC, and 168 had BCLC stage B or C HCC. The 5-year OS and RFS among the patients within the BCLC criteria for LR were 75.2% and 56.1%, respectively, vs 54.9% and 34.0%, respectively, among the patients beyond the BCLC criteria (P < .001). Alpha-fetoprotein more than 400 ng/mL (hazard ratio = 2.06, 95% confidence interval, 1.31-3.26, P = .002) was the only independent variable associated with recurrence among the patients beyond the BCLC criteria. CONCLUSIONS: LR provided acceptable outcomes among selected patients with BCLC stage B and C HCC.

Combined resection and radiofrequency ablation versus transarterial embolization for intermediate-stage hepatocellular carcinoma: A propensity score matching study.

BACKGROUND/PURPOSE: This study aimed to compare the outcomes of combined hepatic resection (HR) plus intraoperative radiofrequency ablation (RFA) and transarterial embolization (TAE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) in case-controlled patient groups using the propensity score. METHODS: A total of 179 patients with multifocal HCC treated with HR plus RFA (n = 26) or TAE (n = 153) were retrospectively studied. All patients were classified as BCLC stage B and Child-Pugh class A. Analyses were performed over all participants as well as for propensity score-matched (1:3) patients to adjust for baseline differences. Cumulative overall survival (OS) and time to progression (TTP) were compared between the two groups using the Kaplan-Meier method, and independent predictors were identified by multivariate Cox regression analysis. RESULTS: Patients treated with HR plus RFA had better OS and longer TTP than those with TAE (p = 0.011 and p < 0.001, respectively). Multivariate Cox regression analysis showed that combined therapy (hazard ratio 0.31; 95% confidence interval (CI), 0.12-0.78; p = 0.013), BCLC substage B2 (hazard ratio 1.82; 95% CI, 1.13-2.92; p = 0.013) and alpha-fetoprotein ≥ 400 ng/ml (hazard ratio 1.85; 95% CI, 1.12-3.05; p = 0.016) were independent factors associated with OS. After propensity score matching, combined therapy was the significant factor associated with OS and TTP by univariate and multivariate analyses. CONCLUSION: Combined HR plus RFA may provide survival advantage compared to TAE in patients with BCLC stage B HCC.

Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Hepatoma Management: A Prospective Study.

BACKGROUND: For patients with hepatocellular carcinoma (HCC), gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) improved the diagnosis, migrated Barcelona Clinic Liver Cancer (BCLC) stage, and changed therapeutic decision in retrospective analysis. AIM: This prospective study was to evaluate the clinical impact of EOB-MRI on HCC management. METHODS: From September 2012 to February 2014, consecutive patients with suspicion of HCC in BCLC early stage by multidetector computed tomography or dynamic MRI with non-specific gadolinium, well liver function reserve, and admitted for resection evaluation were enrolled prospectively. Additional EOB-MRI was performed. The HCC diagnosis, BCLC staging, and treatment decision were obtained in a liver cancer conference. EOB-MRI impact on HCC management was analyzed. RESULTS: One hundred and three patients including 68 with typical and 35 with atypical HCC nodules in dynamic imaging studies were enrolled. EOB-MRI characterized 3 (4.4 %) benign and 33 (94.3 %) HCC for patients with typical and atypical HCC nodules, respectively. For 90 HCC patients, additional EOB-MRI changed BCLC stage in 25 (27.8 %) and treatment decision in 17 (18.9 %) patients. There were 66 patients with 78 resected nodules including 65 HCCs, 4 intrahepatic cholangiocarcinomas, and 9 benign nodules. Dynamic study and EOB-MRI detected and characterized 69 and 77 nodules, respectively. The sensitivity and accuracy in HCC diagnosis were 98.5 and 85.7 % for EOB-MRI, which were better than those of dynamic study (p < 0.001). CONCLUSIONS: Additional EOB-MRI improved HCC diagnosis in sensitivity, accuracy but not specificity. It changed BCLC staging and treatment decision in 27.8 and 18.9 % of early-stage HCC patients.

Extensive Adhesions in Living Donor Liver Transplantation: A Retrospective Analysis.

BACKGROUND: Adhesions are abnormal fibrous bands of scar tissue between internal organs and tissues. With respect to recipient hepatectomy in living donor liver transplantation (LDLT), we defined extensive adhesions as adhesions in at least two separate locations that required more than 5 % of the total surgical time to lyse. We aimed to identify the etiology and consequences of this preventable burden. METHODS: A simple retrospective case-control study of all cases with extensive adhesions from August 2011 to September 2014 matched by age, sex, and diagnosis at surgery. RESULTS: A total of 380 cases were studied. Thirty-eight and five patients had extensive adhesions from surgical and non-surgical causes, respectively. The incidence and complications in pediatric patients were far less than in adults. In the adult group, the mean operative time was increased by 75 min (12.3 %) and blood loss by 2.5 L.The incidence of bowel perforation and biliary infections were increased in adults, while there was no significant difference in the rate of ascitic or wound infections. The 1-year survival was slightly less (92 %) than the control group (100 %). CONCLUSIONS: The most common cause of extensive adhesions at LDLT was prior liver resection. Extensive adhesions caused increased morbidity by increased blood loss, transfusion requirements, and increased cold ischemia time. There is also a higher risk of bowel perforation during enterolysis. The use of commercially available barrier techniques is advisable in adults at high risk of developing adhesions with a possibility of liver transplantation, such as liver resection for HCC.