Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Risk factors and crucial prognostic indicators of mortality in liver transplant recipients with bloodstream infections: A comprehensives study of 1049 consecutive liver transplants over an 11-year period.

BACKGROUND: Liver transplantation (LT) is a pivotal treatment for end-stage liver disease. However, bloodstream infections (BSI) in the post-operative period present a significant threat to patient survival. This study aims to identify risk factors for post-LT BSI and crucial prognostic indicators for mortality among affected patients. METHODS: We conducted a retrospective study of adults diagnosed with end-stage liver disease who underwent their initial LT between 2010 and 2021. Those who developed BSI post-LT during the same hospital admission were classified into the BSI group. RESULTS: In this cohort of 1049 patients, 89 (8.4%) developed BSI post-LT, while 960 (91.5%) did not contract any infection. Among the BSI cases, 17 (19.1%) patients died. The average time to BSI onset was 48 days, with 46% occurring within the first month post-LT. Of the 123 isolated microorganisms, 97 (78.8%) were gram-negative bacteria. BSI patients had significantly longer stays in the intensive care unit and hospital compared to non-infected patients. The 90-day and in-hospital mortality rates for recipients with BSI were significantly higher than those without infections. Multivariate analysis indicated heightened BSI risk in patients with blood loss >3000 mL during LT (odds ratio [OR] 2.128), re-operation within 30 days (OR 2.341), post-LT bile leakage (OR 3.536), and graft rejection (OR 2.194). Additionally, chronic kidney disease (OR 6.288), each 1000 mL increase in intraoperative blood loss (OR 1.147) significantly raised mortality risk in BSI patients, whereas each 0.1 mg/dL increase in albumin levels correlated with a lower risk of death from BSI (OR 0.810). CONCLUSIONS: This study underscores the need for careful monitoring and management in the post-LT period, especially for patients at higher risk of BSI. It also suggests that serum albumin levels could serve as a valuable prognostic indicator for outcomes in LT recipients experiencing BSI.

Gram-negative bacterial infections in surgical intensive care unit patients following abdominal surgery: high mortality associated with Stenotrophomonas maltophilia infection.

BACKGROUND: Stenotrophomonas maltophilia, a multidrug-resistant gram-negative bacteria (GNB), is an emerging nosocomial pathogen. This study assessed the clinical outcomes of GNB infections in surgical intensive care unit (SICU) patients post-abdominal surgery, focusing on the differences between S. maltophilia and other GNBs, including Pseudomonas aeruginosa. METHODS: A retrospective study was conducted on SICU patients at Kaohsiung Chang Gung Memorial Hospital from 2010 to 2020, who developed GNB infections following abdominal surgery. RESULTS: Of 442 patients, 237 had S. maltophilia and 205 had non-S. maltophilia GNB infections (including 81 with P. aeruginosa). The overall mortality rate was 44.5%, and S. maltophilia infection emerged as a significant contributor to the mortality rate in patients with GNB infections. S. maltophilia patients had longer mechanical ventilation and SICU stays, with a 30-day mortality rate of 35.4%, higher than the non-S. maltophilia GNB (22.9%) and P. aeruginosa (21%) groups. In-hospital mortality was also higher in the S. maltophilia group (53.2%) compared to the non-S. maltophilia GNB (34.6%) and P. aeruginosa groups (29.6%). Risk factors for acquiring S. maltophilia included a higher Sequential Organ Failure Assessment score and prior broad-spectrum antibiotics use. Older age, polymicrobial infections, and elevated bilirubin were associated with increased 30-day mortality in S. maltophilia patients. CONCLUSION: S. maltophilia infections in post-abdominal surgery patients are linked to higher mortality than non-S. maltophilia GNB and P. aeruginosa infections, emphasizing the need for early diagnosis and treatment to improve outcomes.

The incidence and risk factors of proximal lower extremity deep vein thrombosis without pharmacologic prophylaxis in critically ill surgical Taiwanese patients: A prospective study.

Background: Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis. Methods: We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT. Results: Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067-34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547-13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270-12.707), and swollen leg (OR = 3.427, 95% CI: 1.075-10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p = 0.045) and ICU stays (p = 0.044). Conclusion: Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

A preoperative model to predict overall survival in patients with hepatoma undergoing resection.

BACKGROUND: We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR). METHODS: Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 â€‹+ â€‹(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9. RESULTS: Multivariate analysis showed that radiographic TBS (low: referent; medium: HR â€‹= â€‹2.89; 95 â€‹% CI: 1.60-5.21; p â€‹< â€‹0.001; high, HR â€‹= â€‹7.60; 95 â€‹% CI: 3.80-15.2; p â€‹< â€‹0.001), AFP (<400 â€‹ng/mL: referent; ≧400 â€‹ng/mL: HR â€‹= â€‹1.67, 95 â€‹% CI: 1.11-2.52, p â€‹= â€‹0.014), and cirrhosis (absence: referent; presence: HR â€‹= â€‹1.88, 95 â€‹% CI: 1.30-2.72, p â€‹< â€‹0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623). CONCLUSIONS: We have developed a preoperative model that performs better in predicting OS than the BCLC system.

Patients undergoing liver resection for non-alcoholic fatty liver disease-related hepatocellular carcinoma and those for viral hepatitis-related hepatocellular carcinoma have similar survival outcomes.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

The outcomes and biliary complications of a staged biliary reconstruction in living donor liver transplantation: a propensity score matched analysis.

BACKGROUND: Uncontrolled massive bleeding and bowel edema are critical issues during liver transplantation. Temporal intra-abdominal packing with staged biliary reconstruction (SBR) yields acceptable outcomes in deceased donor liver transplantation; however, data on living donor liver transplantation (LDLT) are scarce. METHODS: A retrospective analysis of 1269 patients who underwent LDLT was performed. After one-to-two propensity score matching, patients who underwent LDLT with SBR were compared with those who underwent LDLT with one-stage biliary reconstruction (OSBR). The primary outcomes were graft survival (GS) and overall survival (OS), and the secondary outcomes were postoperative biliary complications. RESULTS: There were 55 and 110 patients in the SBR and OSBR groups, respectively. The median blood loss was 6500 mL in the SBR and 4875 mL in the OSBR group. Patients receiving SBR-LDLT had higher incidence of sepsis (69.0% vs. 43.6%; P < 0.01) and intra-abdominal infections (60.0% vs. 30.9%; P < 0.01). Biliary complication rates (14.5% vs. 19.1%; P = 0.47) and 1-and 5-year GS (87.27%, 74.60% vs. 83.64%, 72.71%; P = 0.98) and OS (89.09%, 78.44% vs. 84.55%, 73.70%; P = 0.752) rates were comparable between the two groups. CONCLUSIONS: SBR could serve as a life-saving procedure for patients undergoing complex critical LDLT, with GS, OS, and biliary outcomes comparable to those of OSBR.

Single center experience with ALPPS and timing with stage 2 in patients with fibrotic/cirrhotic liver.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel procedure for major resection in patients with insufficient future liver remnant (FLR). Effective FLR augmentation is pivotal in the completion of ALPPS. Liver fibrosis/cirrhosis associated with chronic viral hepatitis impairs liver regeneration. To investigate the augmentation of FLR in associating ALPPS between patients with fibrotic/cirrhotic livers (FL) and non-fibrotic livers (NFL) and compare their short-term clinical outcomes and long-term survival. Patients were divided into two groups based on the Ishak modified staging: non-fibrotic liver group (NFL, stage 0) and fibrotic/cirrhotic liver group (FL, stage 1-5/6). Weekly liver regeneration in FLR, perioperative data, and survival outcomes were investigated. Twenty-seven patients with liver tumors underwent ALPPS (NFL, n = 7; FL, n = 20). NFL and FL patients had viral hepatitis (28.6% [n = 2] and 95% [n = 19]), absolute FLR volume increments of 134.90 ml and 161.85 ml (p = 0.825), and rates of hypertrophy were 16.46 ml/day and 13.66 ml/day (p = 0.507), respectively. In the FL group, baseline FLR volume was 360.13 ml, postoperatively it increased to a plateau (542.30 ml) in week 2 and declined (378.45 ml) in week 3. One patient (3.7%) with cirrhotic liver (stage 6) failed to proceed to ALPPS-II. The overall ALPPS-related major complication rate was 7.4%. ALPPS is feasible for fibrotic liver patients classified by Ishak modified stages ≤ 5. After ALPPS-I, 14 days for FLR augmentation seems an appropriate waiting time to reach a maximum FLR volume in these patients.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

BACKGROUND: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. MATERIALS AND METHODS: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. RESULTS: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). CONCLUSION: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma.

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.

Sarcopenia Affects Liver Regeneration and Long-Term Survival Rate After Living-Donor Liver Transplantation in Patients With Hepatocellular Carcinoma.

PURPOSE: Despite technological and immunologic innovations, some living-donor liver transplant (LDLT) recipients still face poor liver regeneration. Sarcopenia is often recognized as a biomarker for poor outcomes in surgical patients. This study aimed to evaluate associations between sarcopenia and liver regeneration in LDLT recipients. MATERIALS AND METHODS: This retrospective review included consecutive patients who had received LDLT at Chang Gung Memorial Hospital between 2005 and 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. Receiver operating characteristic curve analysis was used to determine the ability of PMI to predict relatively poor survival rates. Correlations between liver regeneration and sarcopenia were evaluated using regression analysis. RESULTS: A total of 109 LDLT recipients were included. The 1-, 3-, 5, 10-, and 15-year survival rates were 93.7%, 84.8%, 79.7%, 74.7%, and 73.3% in males and 93.3%, 83.3%, 83.3%, 71.4%, and 71.4% in females. PMIs were significantly different based on 10- and 15-year overall survival rates (P = .001 and P = .000) in male patients. Receiver operating characteristic curve analysis revealed the PMI cutoff point at 6.7 cm2/m2 (sensitivity = 48.3%, specificity = 81%, AUC (area under the ROC curve) = 0.685) based on 10-year survival. Linear regression analysis revealed that PMI was significantly associated with liver regeneration in males (P = .013). CONCLUSIONS: Sarcopenia and low PMI are associated with poor liver regeneration and long-term survival after LDLT in male patients. Further studies, including sarcopenia with conventional scores, may help to more reliably predict liver regeneration and mortality among LDLT patients with hepatocellular carcinoma.

Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury.

BACKGROUND AND AIMS: The impact of antibody responses following direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. METHODS: In this observational cohort study, we aimed to explore the association between changes in anti-HCV antibody titers following pre-LT DAA therapy and allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). RESULTS: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (the DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (the DAA-naïve group). A higher incidence of post-LT BCs was observed in the DAA group (p = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (p = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (p < 0.005). CONCLUSIONS: In conclusion, we speculate that the upregulation of anti-HCV antibody titers, which might have been induced via the restoration of HCV-specific immune responses through pre-LT DAA therapy, was associated with post-LT allograft injury.

Risk factors for pre-transplantation bacteremia in adults with end-stage liver disease: Effects on outcomes of liver transplantation.

BACKGROUND AND AIM: Limited data are available regarding pre-liver transplantation (LT) bacteremia in adults with end-stage liver disease. In this study, we investigated the risk factors independently associated with pre-LT bacteremia and their effects on clinical outcomes of LT. METHODS: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre-LT bacteremia and those without pre-LT infection. Pre-LT bacteremia was defined as bacteremia detected within 90 days before LT. RESULTS: Among 1287 LT recipients, 92 (7.1%) developed pre-LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram-negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048-2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074-1.257) were independent risk factors for pre-LT bacteremia in patients with end-stage liver disease. Intensive care unit and in-hospital stay were significantly longer, and in-hospital mortality was significantly higher among LT recipients with pre-LT bacteremia than among those without pre-LT infection. CONCLUSIONS: This study highlights predictors of pre-LT bacteremia in patients with end-stage liver disease. Pre-LT bacteremia increases the post-transplantation mortality risk.

Prognostic factors for critically ill surgical patients with unplanned intensive care unit readmission: Developing a novel predictive scoring model for predicting readmission.

BACKGROUND: Unplanned readmission to the surgical intensive care unit has been demonstrated to worsen patient outcomes. Our objective was to identify risk factors and outcomes associated with unplanned surgical intensive care unit readmission and to develop a predictive scoring model to identify patients at high risk of readmission. METHODS: We retrospectively analyzed patients admitted to the surgical intensive care unit (2020-2021) and categorized them as either with or without unplanned readmission. RESULTS: Of 1,112 patients in the derivation cohort, 76 (6.8%) experienced unplanned surgical intensive care unit readmission, with sepsis being the leading cause of readmission (35.5%). Patients who were readmitted had significantly higher in-hospital mortality rates than those who were not. Multivariate analysis identified congestive heart failure, high Sequential Organ Failure Assessment-Hepatic score, use of carbapenem during surgical intensive care unit stay, as well as factors before surgical intensive care unit discharge such as inadequate glycemic control, positive fluid balance, low partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, and receipt of total parenteral nutrition as independent predictors for unplanned readmission. The scoring model developed using these predictors exhibited good discrimination between readmitted and non-readmitted patients, with an area under the curve of 0.74. The observed rates of unplanned readmission for scores of <4 points and ≥4 points were 4% and 20.2% (P < .001), respectively. The model also demonstrated good performance in the validation cohort, with an area under the curve of 0.74 and 19% observed unplanned readmission rate for scores ≥4 points. CONCLUSION: Besides congestive heart failure, clinicians should meticulously re-evaluate critical variables such as the Sequential Organ Failure Assessment-Hepatic score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, glycemic control, and fluid status before releasing the patient from the surgical intensive care unit. It is crucial to determine the reasons for using carbapenems during surgical intensive care unit stay and the causes for the inability to discontinue total parenteral nutrition before discharging the patient from the surgical intensive care unit.

Tumor necrosis as a predictor of early tumor recurrence after resection in patients with hepatoma.

BACKGROUND: Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. MATERIALS AND METHODS: Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. RESULTS: Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. CONCLUSION: We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

The Extended Surgical Concepts for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.

Surgical resection remains one of the most effective curative therapies for HCC. However, the majority of patients have advanced unresectable diseases upon presentation. It is of paramount importance to raise the resectability of patients with HCC. The remarkable objective response rate reported by Phase III IMbrave150 trial has led to the concept of "Atezo/Bev followed by curative conversion (ABC conversion)" for initially unresectable HCC. With this revolutionary treatment strategy, the concept of surgical resection for HCC should be amended. The current opinion illustrated three extended surgical concepts, which could be integrated into clinical practice in the era of immune checkpoint inhibitors (ICI).

Using the hazard function to evaluate hepatocellular carcinoma recurrence risk after curative resection.

Predicting recurrence patterns of hepatocellular carcinoma (HCC) can be helpful in developing surveillance strategies. This study aimed to use the hazard function to investigate recurrence hazard and peak recurrence time transitions in patients with HCC undergoing liver resection (LR). We enrolled 1204 patients with HCC undergoing LR between 2007 and 2018 at our institution. Recurrence hazard, patterns, and peak rates were analyzed. The overall recurrence hazard peaked at 7.2 months (peak hazard rate [pHR]: 0.0197), but varied markedly. In subgroups analysis based on recurrence risk factors, patients with a high radiographic tumor burden score (pHR: 0.0521), alpha-fetoprotein level ≥ 400 ng/ml (pHR: 0.0427), and pT3-4 (pHR: 0.0656) showed a pronounced peak within the first year after LR. Patients with cirrhosis showed a pronounced peak within three years after LR (pHR: 0.0248), whereas those with Barcelona Clinic Liver Cancer stage B (pHR: 0.0609) and poor tumor differentiation (pHR: 0.0451) showed multiple peaks during the 5-year follow-up period. In contrast, patients without these recurrence risk factors had a relatively flat hazard function curve. HCC recurrence hazard, patterns, and peak rates varied substantially depending on different risk factors of HCC recurrence.

Perception and Mental Health Status Regarding COVID-19 Vaccination Among Taiwanese Adolescents and Their Caregivers.

Background: Vaccinating adolescents is a vital strategy to enhance population protection without imposing overly restrictive measures on our daily lives during the COVID-19 pandemic. As teenagers gain more independence, their willingness to get vaccinated may depend on their own understanding of the pandemic, vaccines, and mental well-being, as well as that of their caregivers. Our study aimed to examine how Taiwanese adolescents and their caregivers perceive COVID-19 vaccination and assess their mental health status. Methods: We invited a total of 138 vaccinated adolescents and their caregivers to complete several questionnaires, including the Drivers of COVID-19 Vaccination Acceptance Scale (DrVac-COVID19S), Impact of Event Scale (IES), and Chinese Health Questionnaire (CHQ). Results: Among the adolescents, 76.8% considered the BNT162b2 vaccine (Pfizer-BioNTech) as the ideal option for COVID-19 vaccination, while 27.5% of caregivers expressed acceptance of any available vaccine. Adolescents scored higher than caregivers in terms of vaccine value (p<0.001) and autonomy (p<0.001), but lower in knowledge (p<0.001), as assessed by the DrVac-COVID19S subscales. The adolescents' intention to get vaccinated against COVID-19 (DrVac-COVID19S total score) showed a positive correlation with their perception of the pandemic's impact (IES scores, r=0.214, p=0.012) and their caregivers' vaccination intention (r=0.371, p<0.001). Furthermore, adolescents' mental health demonstrated a positive association with the mental health of their caregiver (CHQ total scores, r=0.481, p<0.001). Conclusion: During the COVID-19 outbreak, caregivers have encountered heightened levels of mental stress, and this stress has been found to be positively correlated with the mental stress experienced by adolescents and their intentions regarding vaccination. These findings can serve as crucial references for healthcare providers and governments when formulating vaccination policies for adolescents in the future.

Survival Evidence of Local Control for Colorectal Cancer Liver Metastases by Hepatectomy and/or Radiofrequency Ablation.

Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.

Impact of Genomic Alterations on the Clinical Outcome of Patients With Hepatitis B-related Hepatocellular Carcinoma Receiving Curative Surgery: A Retrospective Cohort Study.

BACKGROUND/AIM: The aim of the current study was to obtain comprehensive genomic information on viral hepatitis B (HBV)-related hepatocellular carcinoma (HCC) and identify potential biomarkers of early recurrence in patients receiving curative surgery. PATIENTS AND METHODS: A total of 104 patients with HBV-related HCC receiving curative surgery at Kaohsiung Chang Gung Memorial Hospital between January 2017 and December 2020 were identified, including 52 patients each with and without recurrence. Next-generation sequencing was performed to investigate genomic alterations caused by surgical resection of specimens. The Kaplan-Meier method was used to estimate disease-free survival and overall survival. RESULTS: The landscape of gene mutations in HCC patients of our cohort showed a median number of single nucleotide variants of 250, a median number of insertions and deletions of 22, and a median number of protein-coding mutations of 185. The 10 most frequently mutated genes were TP53 (43%), TTN (39%), MUC16 (28%), PCLO (25%), OBSCN (22%), ADGRV1 (19%), ALB (18%), SYNE1 (18%), DNAH17 (17%), and RYR1 (17%). The tumour mutation burden was 4.8 mutations per megabase, and high microsatellite instability was reported in only three patients. In addition, the mutational signatures showed that aristolochic acid exposure was highly implicated in our HCC cohort. Five mutant genes, TBC1D4, ITGA4, RPS6KA3, VWA8, and FMN2, were more frequent in the recurrence group than that in the non-recurrence group. CONCLUSION: Our results present an in-depth genomic analysis of HBV-related HCC. The study findings provide an improved understanding of the related molecular mechanisms and identify potential biomarkers associated with early tumour recurrence after curative resection.