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Abstract 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.

Abstract 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 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

Ventilator-associated pneumonia (VAP) is a critical hospital-acquired infection following non-cardiac surgeries, leading to poor outcomes. This study identifies VAP risk factors in non-cardiac surgical patients and determines the causative pathogens. A retrospective analysis with 1:4 propensity-score matching was conducted on patients in a surgical intensive care unit (ICU) from 2010 to 2020 at a private tertiary medical center. Among 99 VAP patients, the mortality rate was 64.7%. VAP risk factors included prolonged mechanical ventilation (odds ratio [OR] 6.435; p < 0.001), repeat intubation (OR 6.438; p < 0.001), lower oxygenation levels upon ICU admission (OR 0.950; p < 0.001), and undergoing gastrointestinal surgery (OR 2.257; p = 0.021). The 30-day mortality risk factors in the VAP group were late-onset VAP (OR 3.450; p = 0.022), inappropriate antibiotic treatment (OR 4.083; p = 0.041), and undergoing gastrointestinal surgeries (OR 4.776; p = 0.019). Nearly half of the Gram-negative infections were resistant strains, and a third were polymicrobial infections. Non-cardiac surgical patients with VAP face adverse hospital outcomes. Identifying high-risk patients and understanding VAP’s resistant and microbial nature are crucial for appropriate treatment and improved health outcomes.

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.

Abstract 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.

BackgroundWhether 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 methodsBetween 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.ResultsAmong 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 65 years (pConclusionPatients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Aldo–keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive scoring system based on immunohistochemistry. Adjuvant chemotherapy with S-1 or oxaliplatin plus capecitabine was administered to pathological stage II or III disease patients. There were 117 (32.6%) and 242 (67.4%) patients with AKR1B10 overexpression and low expression, respectively. Patients overexpressing AKR1B10 had worse 5-year disease-free survival (DFS) and overall survival (OS) rates than those with low expression of AKR1B10. Pathological T3–T4 stage, pathological stage III, lymph node ratio ≥25%, and AKR1B10 overexpression were independent prognostic factors for worse DFS and OS in univariate and multivariate analyses. For 162 stage II or III patients who received adjuvant chemotherapy after surgical resection and 59 patients with signet ring cell carcinoma histology, AKR1B10 overexpression was also associated with inferior DFS and OS. AKR1B10 was not associated with clinical survival in stage I GC patients. In conclusion, AKR1B10 overexpression may be an independent prognostic factor for worse survival in GC patients who underwent gastrectomy with D2 lymph node dissection.

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.

BackgroundTumor 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 methodsPatients 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.ResultsEarly 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.ConclusionWe developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Background/objectiveTo determine the impact of microvascular invasion (MVI) on outcome in patients with solitary hepatocellular carcinoma (HCC) of ≤ 2 cm undergoing liver resection (LR).MethodsThis retrospective study enrolled consecutive patients between 2007-2019 with newly diagnosed solitary HCC ≤ 2 cm who were undergoing LR at our institution. Overall survival (OS) and recurrent-free survival (RFS) were compared between patients with or without MVI.ResultsOf the 229 patients included in this study, 71 had MVI. The median follow-up period was 28.8 months (interquartile range: 13.5-70.1). Although the 90-day mortality rate was 0, 18 deaths occurred during the study, and the 5-year survival rate was 87.1%. Tumor recurrence occurred in 45 cases, and 5-year RFS was 71.9%. The presence or absence of MVI did not significantly affect the OS and RFS rates (log rank test, p = 0.10 and 0.38, respectively). In univariate and multivariate analysis, the presence of MVI was not associated with OS and RFS.ConclusionThe presence of MVI was not associated with OS and RFS in patients with solitary HCC ≤ 2 cm who underwent LR in this cohort.

Abstract 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 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

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified to play a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of the lncRNA-miRNA/mRNA network may yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for the next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there were different expressions of 34 transcripts (2 lncRNAs, XISTs, and MIR222HGs; 29 mRNAs; and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of lncRNA-XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA–miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells, particularly resting memory CD4+ T cells, and negative correlations in the infiltration of Th1 CD4+ T cells.

Abstract Curative resection is recommended for patient with early stage hepatocellular carcinoma (HCC), however, the prognosis is limited by high recurrence rate. This study was to investigate liver stiffness (LS) and metabolic factor in prediction of HCC recurrence for patients with early stage HCC who had undergone curative resection. Consecutive patients with suspicion of HCC who had undergone curative resection were prospectively enrolled. Transient elastography was performed to determine LS pre-operatively. The demographics, clinical characteristics and histological findings were recorded. All patients were followed up regularly until recurrence, death or last visit. Ninety-four patients with early stage HCC were enrolled. LS positively correlated with fibrosis stage (r = 0.666). In a median follow-up of 3.2 years, forty patients developed recurrences including 22 recurrences after 1-year post resection. The 5-year cumulative recurrence rate was 44.2%. LS was the independent factor associated with recurrence. Patients with LS > 8.5 kPa had higher 5-year cumulative recurrence rate (59.8% vs 25.1%, p = 0.007). For the prediction of recurrence after 1-year post resection, LS > 8.5 kPa (hazard ratio 2.72) and homeostatic model assessment for insulin resistance index (HOMA-IR) (hazard ratio 1.24) were independent factors in multivariate analysis. Those patients with both LS > 8.5 kPa and HOMA-IR > 2.3 had the highest recurrence rate after 1-year post resection.

Abstract 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

Abstract 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.

Background: The geriatric nutritional risk index (GNRI) calculated as 1.489 × albumin (g/dL) +41.7× (current body weight/ideal body weight) is useful in identifying high-risk for malnutrition in elderly patients with subacute or chronic diseases. Given that trauma patients have sustained injuries in an acute condition, this study is designed to explore the association between GNRI on admission and outcomes in elderly and young adult patients with trauma. Materials and Methods: From January 01, 2009, to December 31, 2019, a total of 1772 elderly and 2194 young adult trauma patients were categorized into four nutritional risk groups according to GNRI: high-risk group (GNRI 98). Propensity score-matched patient cohorts were created in different nutritional risk groups against the no-risk group to minimize the confounding effects of sex, age, pre-existing comorbidities, Glasgow Coma Scale score, and Injury Severity Score on outcome measurements. Primary outcome was in-hospital mortality, and secondary outcome was the length of hospital stay. Results: Young adult patients with trauma were comparable in pattern of mortality outcomes and hospital stays to that in elderly patients. Analysis of the selected propensity score-matched patient cohorts revealed that both elderly and young adult patients in the high-risk group had significantly higher odds of mortality (elderly, odds ratio [OR], 6.5; 95% confidence interval [CI], 3.00-14.03; P < 0.009; young adult, OR, 2.7; 95% CI, 1.45-5.11; P = 0.001) and longer hospital stay (elderly, 21.5 days vs. 12.4 days, respectively, P < 0.001; young adults, 22.5 days vs. 14.1 days, respectively, P < 0.001) than those of the no-risk group. Conclusion: This study demonstrated that the GNRI could serve as a useful screening method to identify high-risk malnutrition in acutely injured trauma patients, including not only the elderly trauma patients but also the young adult trauma patients.

BackgroundNon-B, non-C hepatocellular carcinoma (NBNC-HCC) may be related to metabolic syndrome, and the incidence of this tumor type is increasing annually. The definition of metabolic-associated fatty liver disease (MAFLD) proposed in 2020 may help to more accuratelyassess the association between metabolic syndrome and NBNC-HCC. However, this new concept has not yet been applied in NBNC-HCC research. Therefore, this study aimed to compare the clinicopathological characteristics of patients with NBNC-HCC and CHB-HCC diagnosed between 2009-13 and 2014-18, focusing on metabolic risk factors and the new concept of MAFLD.MethodPatients with BCLC-0/A-HCC who received curative hepatectomy between January 2009 and December 2018 were retrospectively assessed; the associations between clinicopathological characteristics and clinical outcomes of NBNC-HCC and CHB-HCC were analyzed by multivariate analysis.ResultCompared to patients diagnosed in 2009-13, the frequency of metabolic disorders in NBNC-HCC was significantly higher in 2014-18 [DM (p=0.049), HTN (p=0.004), BMI (p=0.017) and MAFLD (p=0.003)]; there was no significant change in patients with CHB-HCC. Moreover, CHB-HCC was an independent risk factor for HCC recurrence (HR, 1.339; 95% CI, 1.010-1.775, p=0.043) and death (HR, 1.700; 95% CI, 1.017-2.842, p=0.043) compared to NBNC-HCC.ConclusionsTherisk of MAFLD, obesity, DM, and hypertension in patients with early-stage NBNC have significantly increased in recent years, thus metabolic syndrome should be monitored in this special population. Moreover, NBNC-HCC tend to had a better prognosis than CHB-HCC, probably due to their distinct clinicopathological features.

Summary: Background: Breast cancer is a collection of molecularly and clinically distinct neoplastic disease. Recent research has shown the information regarding gene expression in breast cancer could be beneficial in the designing of an optimal treatment plan and may also provide with prognostic information. The creation of tissue microarrays (TMA) allows for the rapid immunohistochemical analysis of thousands of tissue samples in parallel with minimal damage to the original blocks. This study was designed with the application of tissue microarray (TMA) to analyze the afamin status in breast cancer with the hope of elucidating the possible relationship between afamin expressions and breast cancer. Methods: Archival tissue specimens from 106 patients with primary invasive breast cancer were analyzed for afamin expression by immunhistochemical staining with TMA. Results were compared to clinicopathologic data by multivariate analysis. Results: TNM stage has shown significant relationship to the overall 5-year survival rate. However, afamin expression was not significantly related to overall five-year survival. Conclusion: Immunohistochemical staining with TMA was convenient and feasible for analyzing afamin expression status in breast cancer. Our preliminary results show that afamin expression showed no significant prognostic value in breast cancer.

Epidemiologic data have suggested that etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas, and might be associated with different outcomes. We compared the viral etiology, clinicopathological characteristics and surgical outcomes between 706 Taiwanese and 1704 Vietnamese patients with HCC undergoing liver resection. Vietnamese patients had a significantly higher ratio of hepatitis B virus (HBV) (p < 0.001) and a lower ratio of hepatitis C virus (HCV) (p < 0.001) and non-B non-C than Taiwanese patients. Among patients with HBV or non-B non-C, the mean age was younger in Vietnam than in Taiwan (p < 0.001, p = 0.001, respectively). The HCC patients in Vietnam had significantly higher serum alpha-fetoprotein (AFP) levels (p < 0.001), larger tumors (p < 0.001), and a higher ratio of macrovascular invasion (p < 0.001) and extrahepatic metastasis (p < 0.001), compared to those in Taiwan. Patients treated in Vietnam had a higher tumor recurrent rate (p < 0.001), but no difference in overall survival was found between both groups. In subgroup analysis, the recurrent rate of HCC was the highest in patients with dual HBV/HCV, followed by HCV or HBV, and non-B non-C (p < 0.001). In conclusion, although the viral etiology and clinicopathological characteristics of HCC differed, postoperative overall survival was comparable between patients in Taiwan and Vietnam.

BackgroundMetformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC.MethodsWe retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis.ResultsDuring the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p 9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

Background Lenvatinib has been approved for use in the systemic treatment for unresectable hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy and safety of lenvatinib in patients with unresectable HCC who received sorafenib. Methods A total of 40 patients who received lenvatinib after sorafenib were retrospectively identified: as second line in 20 patients, third line in 10 patients, and fourth line and later lines in 10 patients. The treatment response to lenvatinib was determined in accordance with the guidelines of the modified Response Evaluation Criteria in Solid Tumors (mRECIST) every 2–3 months after commencement of lenvatinib. Results Median progression-free survival (PFS) and median overall survival (OS) of the whole population were 3.3 and 9.8 months, respectively. The objective response rate was 27.5%. Univariate and multivariate analyses showed that alpha-fetoprotein level >400 ng/mL was an independent prognostic factor of worse PFS and OS. The clinical outcomes of lenvatinib therapy as second-line, third-line, or fourth line and later line treatment were similar, and previous response to sorafenib could predict the response to subsequent lenvatinib. Most adverse events were grades 1–2, and the majority of patients tolerated the side effects. Our study confirms the efficacy and safety of lenvatinib as second-line and later line treatment for patients with unresectable HCC who received sorafenib in clinical practice.

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.

BACKGROUND AND AIMS:The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafeninb is one of the recommended therapies. We aim to evaluate the real world clinical treatment and survival of BCLC stage C patients in an Asian cohort. METHODS:This is a retrospective cohort study that enrolled 427 consecutive BCLC stage C patients diagnosed between 2011 and 2017 by using the HCC registry data for our hospital. All patients were managed via a multidisciplinary team (MDT) approach. RESULTS:Hepatitis B surface antigen positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n = 83; 19.4%), PS2 alone (n = 23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n = 321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type. CONCLUSIONS:We reported the real world management in BCLC stage C patients in an Asian cohort through the use of personalized management via a MDT approach.

Background & aimsIn 2012, the Barcelona Clinic Liver Cancer (BCLC) system designated a single large hepatocellular carcinoma (SLHCC) (>5 cm) as BCLC stage A rather than stage B. However, a recent study from western countries reported that prognosis following liver resection (LR) among patients with SLHCC was similar to that among patients with BCLC stage B. We aim to evaluate the prognosis following LR among patients with SLHCC from an Asian high-volume liver surgery center.MethodsPatients who underwent curative-intent LR for histologically proven HCC between 2011 and 2017 were enrolled using an HCC registry database. Overall survival (OS) among patients with BCLC stages 0, A, and B was examined. Patients with a SLHCC were classified as BCLC stage A1.ResultsAmong 543 patients, 89 (16.4%) were BCLC stage 0, 289 (53.2%) were BCLC stage A, 92 (16.9%) were BCLC stage A1, and 73 (13.4%) were BCLC stage B. The median follow-up was 38 months. The five-year OS rates among patients with BCLC stages 0, A, A1, and B were 83.5%, 83.7%, 77.4%, and 55.4%, respectively (pConclusionPrognosis following LR among patients with SLHCC was similar to that among patients with BCLC stage A. The prognosis for SLHCC should thus be considered comparable to that for BCLC stage A.

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

Spinal anesthesia is generally accepted as an effective and safe practice. Three rare incidents of postoperative cerebral infarction after surgery under spinal anesthesia prompted us to assess whether spinal bupivacaine may compromise carotid or cerebral blood flow. Postoperative examination after the stroke incident revealed that all three patients shared a common pathology of stenosis or atheromatosis in the carotid or middle cerebral artery. In a companion study using 69 Sprague-Dawley rats, subarachnoid application of bupivacaine elicited an initial (Phase I) reduction in the mean arterial pressure, carotid blood flow (CBF) and baroreflex-mediated sympathetic vasomotor tone, all of which subsequently returned to baseline (Phase II). Whereas heart rate (HR) exhibited sustained reduction, cardiac vagal baroreflex, baroreflex efficiency index (BEI) and tissue perfusion and oxygen in the cerebral cortex remained unaltered. However, in one-third of the rats studied, Phase II gave way to Phase III characterized by secondary hypotension and depressed baroreflex-mediated sympathetic vasomotor tone, along with declined HR, sustained cardiac vagal baroreflex, decreased BEI, reduced CBF and waning tissue perfusion or oxygen in the cerebral cortex. We concluded that carotid and cerebral blood flow can indeed be compromised after spinal anesthesia, and an impaired baroreflex-mediated sympathetic vasomotor tone, which leads to hypotension, plays a contributory role.

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.

BACKGROUND: Liver transplantation is the only therapeutic modality for patients with acute-on chronic liver failure (ACLF). These patients are at high risk for bacterial infections while awaiting transplantation. The aim of this study was to elucidate whether an adequately treated bacterial infection influences the outcomes after transplantation in this patient population. METHODOLOGY/PRINCIPAL FINDINGS: 54 recipients (median age, 49.5 years [range, 22-60]) of adult-to-adult living donor liver transplant (LDLT) for ACLF were categorized as those with pretransplant infection (Group 1, n=34) or without pretransplant infection (Group 2, n=20) for retrospective analyses. With the exception of a higher male-female ratio (P=0.046) and longer length of pretransplant hospital stay (P=0.026) in Group 1, similar demographic, laboratory and clinical features were found in both groups. Patients in Group 1 (totally 42 pretransplant infection episodes) were adequately treated with effective antibiotic(s) before receiving LDLT. All included patients were followed up until one year after transplantation or death. Sixty-one posttransplant infection episodes were found in an overall of 44 ACLF patients (27 in Group 1 vs. 15 in Group 2; P=0.352). Frequently encountered posttransplant infections were intraabdominal infection, pneumonia, bloodstream infection and urinary tract infection. Two patients died in each group (P=0.622). No significant difference was found in the length of posttransplant ICU stay, and in one-year survival, graft rejection, and posttransplant infection rate between both groups. The longer overall hospital stay (mean day, 89.0 vs. 65.5, P=0.024) found in Group 1 resulted from a longer pretransplant hospital stay receiving treatment for pretransplant infection(s) and/or awaiting transplantation. CONCLUSIONS: These data suggested that an adequately treated pretransplant infection do not pose a significant risk for clinical outcomes including posttransplant fatality in recipients in adult-to-adult LDLT for ACLF.