Long-term outcomes of single-port laparoscopic hepatectomy for hepatocellular carcinoma: a retrospective comparative analysis.

Purpose: Numerous efforts have been made to achieve minimally invasive surgery, such as single-port laparoscopic surgery. However, few studies have provided long-term follow-up information, and the number of patients with hepatocellular carcinoma (HCC) in previous studies has been small. The purpose in this study is to compare the long-term oncological outcomes of HCC patients who underwent single-port laparoscopic hepatectomy (SPLH) with those of patients who underwent multiport laparoscopic hepatectomy (MPLH). Methods: We retrospectively reviewed the medical records of 135 patients with HCC who underwent laparoscopic liver between January 2008 and December 2018. Of the 135 patients, 53 underwent MPLH, and 82 underwent SPLH. Results: From January 2008 to December 2018, 135 patients underwent laparoscopic hepatectomy for HCC. Among them, 82 patients underwent SPLH, and 53 patients underwent MPLH. Neither long-term overall survival (P = 0.849) nor recurrence-free survival (P = 0.057) differed significantly between the 2 groups, even though the recurrence rate was higher in the SPLH group. In the univariable analysis of risk factors for recurrence, multiple tumors, SPLH method, and portal vein invasion were statistically significant (P < 0.05). Multivariable analysis showed that the SPLH method and portal vein invasion were independent adverse prognostic factors for recurrence-free survival. Conclusion: In terms of both short-term and long-term outcomes, the SPLH method seems to be a feasible approach for HCC in select patients. Because the potential risk of margin recurrence might produce poor oncological outcomes, strict patient selection is essential to ensure that an adequate safety margin can be secured.

Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC.

BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. APPROACH AND RESULTS: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05). CONCLUSIONS: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.

Cutting-Edge HEK293T Protein-Integrated Lipid Nanostructures: Boosting Biocompatibility and Efficacy.

Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.

Liver Transplantation at a Small Volume Center-The Role of Network System.

BACKGROUND: Liver transplantation (LT) is typically performed at specialized, high-volume centers. However, some smaller centers also offer liver transplantation services, but their outcomes and safety have been a subject of debate. To overcome these difficulties, we tried to build a Catholic Medical Center (CMC) network to share our experiences and overcome the lack of volume. In this study, we reviewed the overall outcome of patients undergoing LT at a small-volume procedure center, with a focus on patient and graft survival rates. METHODS: Between July 2014 and September 2021, 60 adults underwent LT at Bucheon Saint Mary's Hospital. The overall outcomes were analyzed in terms of perioperative outcomes, complications, and overall survival rate. In addition, the patients were divided into a benign end-stage liver disease (ESLD) group (n = 44) and a hepatocellular carcinoma (HCC) group (n = 16). The baseline characteristics, perioperative outcomes, complications, and overall survival rate were analyzed between the 2 groups. RESULTS: Of a total of 60 LT, living donor liver transplantation (LDLT) was 26, and deceased donor liver transplantation was 34. LDLT was 14 (31.8%) in the ESLD group and 12 (75.0%) in the HCC group. The overall 1-year, 3-year, and 5-year survival rates were 86.7%, 79.7%, and 77.7%, respectively. The survival difference was not statistically significant (P = .214) between the 2 groups. CONCLUSION: We suggest that with appropriate patient selection and adequate resources, LT can be safely performed at smaller centers with the assistance of the CMC network, thus expanding access to this life-saving procedure.

Effects of Livact Granule on Liver Function Recovery After Donor Right Hemi-Hepatectomy.

BACKGROUND: Living donor liver transplantation (LDLT) is currently widespread due to organ shortage. Because LDLT is a high-risk surgery for the donor, donor safety becomes an important issue. In adult LDLT, right lobe grafts are usually used, posing a greater risk to the donor than a left lobe. Reports have demonstrated that branched-chain amino acids help patients recover after hepatectomy. This study aimed to evaluate the effect of Livact granule on donor safety and recovery. METHODS: From January 2016 to December 2021, LDLT was performed on 258 patients at our center. Among them, 148 were in the non-Livact group, and 110 were in the Livact group. Six of 110 patients in the Livact group stopped taking the granules due to nausea and vomiting, leaving 104 patients in the Livact group to be analyzed. Various preoperative and postoperative factors were evaluated to assess donor safety and recovery. RESULTS: In the non-Livact group, the mean donor age was 35.8; in the Livact group, it was 40. There were no differences between the 2 groups in preoperative liver function tests and no difference in future liver remnant or steatosis. There was no difference in total bilirubin level between the 2 groups at 5 days postoperatively; however, in the Livact group, the prothrombin time international normalized ratio was lower, and albumin was higher. The days taken for total bilirubin to normalize were the same in both groups, but fewer days were needed for Livact to realize an international normalized ratio. More patients in the non-Livact group were discharged with the Jackson-Pratt drain because the drainage did not decrease. CONCLUSIONS: In donor right hepatectomy patients, taking Livact granules and branched-chain amino acids helps donor recovery. For donor safety, administration of Livact granules during the perioperative period should be considered.

Targetoid Primary Liver Malignancy in Chronic Liver Disease: Prediction of Postoperative Survival Using Preoperative MRI Findings and Clinical Factors.

OBJECTIVE: We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification. MATERIALS AND METHODS: This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan-Meier curves were used to estimate RFS and OS for the different risk-score groups. RESULTS: In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2-5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62-0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05). CONCLUSION: Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.

Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation.

BACKGROUND: Clinical factors predicting graft survival (GS) after ABO-incompatible (ABOi) liver transplantation (LT), and differences between recipients with and without hepatocellular carcinoma (HCC) are unclear. AIM: To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without HCC) in ABOi living-donor liver transplantation (LDLT). METHODS: We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT, including 47 patients with HCC. RESULTS: The 1-, 3-, 5-, and 10-year GS rates were 85.9%, 73.3%, 71.4%, and 71.4%, respectively, and there were no significant differences between HCC and non-HCC recipients. In multivariate Cox-regression analyses, tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT, in addition to the antibody-mediated rejection (AMR) were associated with poor-graft outcomes. In HCC patients, AMR [hazard ratio (HR) = 63.20, P < 0.01] and HCC recurrence (HR = 20.72, P = 0.01) were significantly associated with poor graft outcomes. HCCs outside Milan criteria, and tacrolimus concentrations at 4 wk post-LT > 7.3 ng/mL were significant predictive factors for HCC recurrence. After propensity score matching, patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival. CONCLUSION: Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence. Therefore, careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

Gallbladder polyps growth rate is an independent risk factor for neoplastic polyps.

BACKGROUND: The size of gallbladder (GB) polyps is a representative risk factor for neoplastic polyps. However, whether growth rate during follow-up is associated with neoplastic polyps remains unclear. METHODS: From 2009 to 2019, a cohort of patients with GB polyps who underwent cholecystectomy was enrolled. We included only patients who underwent at least two abdominal ultrasonography procedures at least 6 months apart prior to cholecystectomy. Performance and optimal cutoff value of polyp growth rate for predicting neoplastic polyps were estimated using receiver operating characteristic (ROC) analysis. In addition to growth rate, several other variables considered suitable for predicting neoplastic polyps were also investigated. A nomogram was created to predict neoplastic polyps. RESULTS: A total of 239 patients with neoplastic polyps (n = 27, 11.3%) and non-neoplastic polyps (n = 212, 88.7%) were included. The median follow-up period was 28.5 months. The area under the ROC curve (AUROC) of polyp growth rate for neoplastic polyps was 0.66 (95% confidence interval, 0.59-0.72). The growth rate cutoff value for prediction of neoplastic polyps was 3 mm/year (sensitivity, 37.0%; specificity, 86.3%). Multivariate analysis identified several factors predicting neoplastic polyps: polyp size ≥10 mm (odds ratio [OR], 3.74, p = 0.041), solitary polyp (OR, 3.92, p = 0.004), and polyp growth rate ≥ 3 mm/year (OR, 2.75, p = 0.031). The AUROC of the nomogram using these three significant factors in multivariate analysis was 0.71. CONCLUSION: GB polyps with a growth rate of over 3 mm per year on ultrasonography during follow-up should be considered a risk factor for neoplastic polyps.

The secretome obtained under hypoxic preconditioning from human adipose-derived stem cells exerts promoted anti-apoptotic potentials through upregulated autophagic process.

BACKGROUND: Hypoxic preconditioning (HP) is a stem cell preconditioning modality designed to augment the therapeutic effects of mesenchymal stem cells (MSCs). Although autophagy is expected to play a role in HP, very little is known regarding the relationship between HP and autophagy. METHODS AND RESULTS: The adipose-derived stem cell (ASC)-secretome obtained under normoxia (NCM) and ASC-secretome obtained under HP (HCM) were obtained by culturing ASCs for 24 h under normoxic (21% partial pressure of O2) and hypoxic (1% partial pressure of O2) conditions, respectively. Subsequently, to determine the in vivo effects of HCM, each secretome was injected into 70% partially hepatectomized mice, and liver specimens were obtained. HCM significantly reduced the apoptosis of thioacetamide-treated AML12 hepatocytes and promoted the autophagic processes of the cells (P < 0.05). Autophagy blockage by either bafilomycin A1 or ATG5 siRNA significantly abrogated the anti-apoptotic effect of HCM (P < 0.05), demonstrating that HCM exerts its anti-apoptotic effect by promoting autophagy. The effect of HCM - reduction of cell apoptosis and promotion of autophagic process - was also demonstrated in a mouse model. CONCLUSIONS: HP appears to induce ASCs to release a secretome with enhanced anti-apoptotic effects by promoting the autophagic process of ASCs.

A decrease in functional microbiomes represented as Faecalibacterium affects immune homeostasis in long-term stable liver transplant patients.

ABBREVIATIONS: LT, liver transplantation; HCC, hepatocellular carcinoma; IS, immunosuppressants; DC, dendritic cells; Treg, regulatory T; Th17, T helper 17; AST, aspartate transaminase; ALT, alanine transaminase; OUT, operational taxonomic unit; LEfSe, linear discriminant analysis effect size; LDA, linear discriminant analysis; IL, interleukin; TGF, transforming growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; TNF-α, tumor necrosis factor-α; MIP-1α, macrophage inflammatory protein-1α; IP-10, interferon γ-induced protein; MCP-1, monocyte chemoattractant protein-1; ACR, acute cellular rejection; NF-κB, nuclear factor κB; PT INR, prothrombin time; QC, quality check; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay.

Clinical Implications of a Persistent Left Superior Vena Cava in a Patient With Right Superior Vena Cava Thrombosis Undergoing Emergency Deceased Donor Liver Transplantation: A Case Report.

BACKGROUND: Persistent left superior vena cava (PLSVC) is the most common congenital thoracic venous anomaly. It is usually found incidentally on examination or during invasive procedures. In most cases, the blood flows back to the right atrium through the coronary sinus without hemodynamic abnormalities and it is usually asymptomatic. There is some controversy regarding the clinical use of PLSVC. In a few cases, a PLSVC has been used for hemodialysis or large-bore intravenous access. CASE REPORT: A 62-year-old woman with a previous hepatectomy for hepatocellular carcinoma and liver cirrhosis developed hepatic failure. Owing to her worsening condition, she needed liver transplantation (LT). However, a superior vena cava thrombus was found between the right atrium and proximal superior vena cava on preoperative transesophageal echocardiography. Usually, right-sided central venous catheterization is performed for LT preparation, but the embolic risk was very high in our patient. Fortunately, she had already been diagnosed with PLSVC. Therefore, we decided to perform fluoroscopy-guided catheterization through the PLSVC. For the safe use of a PLSVC catheter during surgery, the rapid infusion system pressure, coronary sinus inflow pressure, and intraoperative transesophageal echocardiography were monitored. The patient successfully underwent LT. CONCLUSIONS: Based on a literature review and this case, PLSVC can be used clinically when accompanied by a detailed history, preoperative imaging examination, and close intraoperative monitoring. We suggest that a PLSVC is a feasible alternative to central venous access for LT.

Prognostic Implications of Portal Venous Circulating Tumor Cells in Resectable Pancreatic Cancer.

Circulating tumor cells (CTCs) are a promising prognostic biomarker for cancers. However, the paucity of CTCs in peripheral blood in early-stage cancer is a major challenge. Our study aimed to investigate whether portal venous CTCs can be a biomarker for early recurrence and poor prognosis in pancreatic cancer. Patients who underwent upfront curative surgery for resectable pancreatic cancer were consecutively enrolled in this prospective study. Intraoperatively, 7.5 mL of portal and peripheral blood was collected, and CTC detection and identification were performed using immunofluorescence staining. Peripheral blood CTC sampling was performed in 33 patients, of which portal vein CTC sampling was performed in 28. The median portal venous CTCs (2.5, interquartile ranges (IQR) 1−7.75) were significantly higher than the median peripheral venous CTCs (1, IQR 0−2, p < 0.001). Higher stage and regional lymph node metastasis were related with a larger number of CTCs (≥3) in portal venous blood. Patients with low portal venous CTCs (≤2) showed better overall (p = 0.002) and recurrence-free (p = 0.007) survival than those with high portal venous CTCs (≥3). If validated, portal CTCs can be used as a prognostic biomarker in patients with resectable pancreatic cancer.

Long-term Clinical Outcomes and Predictive Factors for Living-donor Liver Transplant Recipients With Biliary Strictures.

BACKGROUND: Biliary strictures frequently occur in living-donor liver transplant (LDLT) recipients. However, long-term clinical outcomes and their associated factors are unclear. METHODS: We analyzed an historical cohort of 228 recipients who underwent LDLT with post-liver transplantation biliary strictures. Endoscopic retrograde cholangiography or percutaneous transhepatic biliary drainage were performed to treat biliary strictures. Patients that experienced persistent jaundice over 3 mo after the initial treatment were defined as a remission-failure group. RESULTS: Median observation period was 8.5 y after the diagnosis of biliary stricture. The 15-y graft survival (GS) rate was 70.6%, and 15-y rate of developing portal hypertension (PH) was 26.1%. Remission failure occurred in 25.0% of study participants. In the multivariate analysis, biopsy-proven acute rejection, and portal vein/hepatic artery abnormalities were risk factors for remission failure. Development of PH, retransplantation, and death were significantly more frequent in the remission-failure group. Remission failure and PH were associated with poor GS. In multivariate analyses, hepatic artery abnormality and biloma were common significant factors that were associated with a poor GS and development of PH. CONCLUSIONS: The insufficient blood supply reflected by hepatic artery abnormality and biloma might be the most important factor that can predict poor long-term survival in LDLT patients with biliary strictures. Future large-scale prospective studies are needed to validate our observations.

Patient-Derived Avatar Mouse Model to Predict the Liver Immune Homeostasis of Long-Term Stable Liver Transplant Patients.

Although rejection or tolerance can occur in liver transplantation (LT) patients, there are no reliable non-invasive methods for predicting immune homeostasis. In this study, we developed a humanized mouse model to predict liver immune homeostasis in patients who underwent LT. The patient-derived avatar model was developed by injecting peripheral blood mononuclear cells from healthy controls (HCs) or LT patients with stable, rejection, or tolerance into NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJ (NSG) mice, followed by injection of human hepatic stellate cells and Carbone tetrachloride (CCl4). After 7 weeks, the patient's T-cell engraftment and liver inflammation in the avatar model were evaluated and compared with the liver histology of LT patients. Changes in liver inflammation following treatment with tacrolimus and/or biguanide derivatives were also examined. The C-X-C Motif Chemokine Receptor 3 (CXCR3)-dependently engrafted patient T cells led to differences in liver inflammation in our model according to the status of LT patients. The livers of avatar models from rejection patients had severe inflammation with more T helper 17 cells and fewer regulatory T cells compared to those of models from tolerance and HCs showing only mild inflammation. Moreover, our model classified stable post-LT patients into severe and mild inflammation groups, which correlated well with liver immunity in these patients. Our models revealed alleviation of inflammation after combination treatment with tacrolimus and biguanide derivatives or monotherapy. Consequently, using our new patient-derived avatar model, we predicted liver immune homeostasis in patients with stable LT without biopsy. Moreover, our avatar model may be useful for preclinical analysis to evaluate treatment responses while reducing risks to patients.

Liver Imaging-Reporting and Data System treatment response algorithm predicts postsurgical recurrence in locoregional therapy-treated hepatocellular carcinoma.

OBJECTIVES: In HCC, locoregional therapy (LRT) is performed as a bridging or downstaging treatment before curative surgery. The impact of the LI-RADS Treatment Response (LR-TR) algorithm on surgical outcomes remains unknown. We aimed to evaluate radiologic and clinical factors predicting recurrence-free survival (RFS) and overall survival (OS) after curative surgery for LRT-treated HCC. MATERIALS AND METHODS: Consecutive HCC patients who underwent liver transplantation or curative resection after LRT from 2010 to 2016 and had baseline and follow-up post-LRT CT/MRI up to the point of surgery were included. The LR-TR category at the time of surgery and other features were assessed using Cox proportional hazard models. RFS was estimated and compared using the Kaplan-Meier method with log-rank tests. RESULTS: We evaluated 73 patients with 115 lesions. The LR-TR viable category at the time of surgery (hazard ratio [HR], 3.84; 95% confidence interval [CI]: 1.04, 14.16), preoperative AFP > 200 ng/mL (HR, 3.63; 95% CI: 1.63, 8.10), LRT sessions > 3 (HR, 4.99; 95% CI: 1.73, 14.38), and resection (HR, 3.35; 95% CI: 1.39, 8.09) independently predicted recurrence. The risk score categorized the patients into poor, intermediate, and favorable-risk groups with 1-year RFS rates of 35.0%, 78.3%, and 97.0%, respectively (p < 0.001). Outside Milan at the time of surgery (HR, 5.79; 95% CI: 1.94, 17.07) and recurrence within the first postoperative year (HR, 17.66; 95% CI: 6.42, 48.56) predicted death. CONCLUSION: In LRT-treated HCC, non-LR-TR viable disease achieved within fewer LRT sessions and removed by liver transplantation recurred less. KEY POINTS: • The Liver Imaging Reporting and Data System treatment response (LR-TR) viable disease (hazard ratio [HR], 3.84; p = 0.043), preoperative serum AFP level > 200 ng/mL (HR, 3.63; p = 0.002), more than three locoregional treatment (LRT) sessions (HR, 4.99; p = 0.003), and resection compared to liver transplantation (HR, 3.35; p = 0.001) were the independent predictors for postsurgical recurrence in LRT-treated HCCs. • A scoring system combining LR-TR categories and key clinical factors stratifies the patients into poor, intermediate, and favorable recurrence risk groups, with 1-year RFS rates of 35.0%, 78.3%, and 97.0%, respectively (p < 0.001). • Outside Milan at the time of surgery (HR, 5.79; p = 0.001) and recurrence within the first postoperative year (HR, 17.66; p < 0.001) were associated with poor overall survival.

Efficacy of Tumor Markers After Liver Transplantation In Patients With Hepatocellular Carcinoma.

OBJECTIVE: The most reliable treatment for hepatocellular carcinoma (HCC) is liver transplantation (LT). Recurrence of HCC after LT is the most serious problem; therefore, early diagnosis of recurrent HCC is very important. This study investigated the efficacy of tumor markers in patients with LT for HCC. METHODS AND MATERIALS: From January 2008 to December 2016, 242 patients underwent LT for HCC. The operation of LT and immunosuppressive methods were the same as those of general LT patients. All patients were followed up with alpha-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA)-II. The 41 patients (16.9%) recurred during follow-up period. RESULTS: The factors associated with recurrence were tumor markers (AFP, PIVKA-II), maximum tumor diameter, number, microvascular invasion, Milan criteria, and Edmondson-Steiner grade. In 41 patients with recurrent HCC, 14 patients (34.15%) were both elevated in 2 markers and 18 patients (43.9%) were elevated in 1 tumor marker. There was no relationship between tumor marker and recurrent site. The survival rate of patients with recurrence in 1, 3, and 5 years were 78.6%, 34.7%, and 23.7%, respectively. Curability of treatment and elevation of tumor marker before treatment were correlated with patient survival after recurrence. When the receiver operating characteristic curve was used, the area under the curve value using the sum of AFP and PIVKA-II before LT was 0.827. CONCLUSIONS: In this study, tumor markers (AFP, PIVKA-II) for HCC were correlated with post-transplant recurrence factors and may be a useful tool for early diagnosis and to predict the prognosis after recurrence.

Steroid-Resistant Rejection in Liver Transplant: A Single-Center Study for Risk Factor and Second-Line Treatment.

BACKGROUND: Steroid-resistant rejection (SRR) in liver transplant occurs in about 10% of T cell-mediated rejection; prognosis of SRR is known to be worse than steroid-sensitive rejection (SSR). Only a few studies describe treatment methods or features for SRR, and there is no clear consensus yet. Therefore, the purpose of this study is to describe the difference between SSR and SRR and to compare the effect of the SRR treatment method performed our institution. METHODS: This study is a 10-year, retrospective cohort study at Seoul St Mary's Hospital; clinical data were collected from January 2008 to December 2017. Of 663 cases, 154 patients (23.3%) underwent steroid pulse therapy for rejection; we excluded 30 patients who did not undergo liver biopsy. A total of 124 patients (18.7%) with biopsy-proven rejection were analyzed for this study. RESULTS: Child-Turcotte-Pugh score, cold ischemia time, and cytomegalovirus (CMV) infection showed a statistically significant difference in 2 groups. Multivariate analysis was performed on risk factors of SRR at first rejection. CMV infection and total bilirubin at first rejection and numbers of rejection were significant results. Both overall survival and allograft survival rate of SSR are higher than SRR (P < .001). Of second-line treatment patients, 13 patients (54.2%) recovered, and 11 patients (45.8%) failed to recover. Survival was the highest in patients using antithymocyte globulin and in patients with liver retransplant. CONCLUSIONS: When the first rejection in liver transplant occurs, patients with high bilirubin level ​​and previous CMV infections are more likely to have SRR, so if they do not respond to steroid pulse therapy for the first time, either using antithymocyte globulin or liver retransplant preparation should be considered.

Clinical application of intraoperative somatic tissue oxygen saturation for detecting postoperative early kidney dysfunction patients undergoing living donor liver transplantation: A propensity score matching analysis.

BACKGROUND: Somatic tissue oxygen saturation (SstO2) is associated with systemic hypoperfusion. Kidney dysfunction may lead to increased mortality and morbidity in patients who undergo living donor liver transplantation (LDLT). We investigated the clinical utility of SstO2 during LDLT for identifying postoperative kidney dysfunction. PATIENTS AND METHODS: Data from 304 adults undergoing elective LDLT between January 2015 and February 2020 at Seoul St. Mary's Hospital were retrospectively collected. Thirty-six patients were excluded based on the exclusion criteria. In total, 268 adults were analyzed, and 200 patients were 1:1 propensity score (PS)-matched. RESULTS: Patients with early kidney dysfunction had significantly lower intraoperative SstO2 values than those with normal kidney function. Low SstO2 (< 66%) 1 h after graft reperfusion was more highly predictive of early kidney dysfunction than the values measured in other intraoperative phases. A decline in the SstO2 was also related to kidney dysfunction. CONCLUSIONS: Kidney dysfunction after LDLT is associated with patient morbidity and mortality. Our results may assist in the detection of early kidney dysfunction by providing a basis for analyzing SstO2 in patients undergoing LDLT. A low SstO2 (< 66%), particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. SstO2 monitoring may facilitate the identification of early kidney dysfunction and enable early management of patients.

Anticancer Effect of Statins in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

The anticancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC. Consecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effects of statins on HCC recurrence and mortality were compared between statin user and statin nonuser groups. We performed the analyses in a variety of ways, including inverse probability treatment weighting (IPTW) methods to balance any confounders and the landmark method to avoid immortal time bias. A total of 430 patients were enrolled, among whom 323 (75.1%) were statin nonusers and 107 (24.9%) were statin users. During a median of 64.9 months (IQR, 26.1-122.6 months) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was a predictor of HCC recurrence (adjusted hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.1-0.6; P = 0.002), all-cause mortality (adjusted HR, 0.3; 95% CI, 0.2-0.5; P < 0.001), and HCC-related mortality (adjusted HR, 0.4; 95% CI, 0.2-0.9; P = 0.03). The effects of statin use on clinical outcomes were also identified through IPTW analysis. There was a dose-dependent relationship between statin use and HCC recurrence. The anticancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. Statin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.

Single-Center Experience with Hepatic Artery Reconstruction During Living Donor Liver Transplantation: Microscope Versus Surgical Loupe.

BACKGROUND Hepatic artery reconstruction during living donor liver transplantation is a critical step. To perform this risky procedure, a microscope has been used. However, it takes a long time to complete the procedure and it has a long and steep learning curve. Recently, some transplant surgeons have performed the procedure using a surgical loupe. We conducted this study to compare the outcomes after hepatic artery reconstruction using a microscope versus using a surgical loupe. MATERIAL AND METHODS We retrospectively reviewed the outcomes of 300 patients at our institution from April 2014 to July 2020. From April 2014 to September 2017 (era 1), hepatic artery reconstruction was performed using a microscope by an experienced plastic surgeon. From September 2017 to the end date (era 2), it was performed using a loupe (×5.0) by an experienced transplantation surgeon. RESULTS There was no difference in most perioperative outcomes between the 2 groups, including the major postoperative complications of hepatic artery complications (2/150 versus 2/150, P=1.000), postoperative bleeding (10/150 versus 5/150, P=0.185), and biliary leakage (18/150 versus 13/150, P=0.343). There was a statistically significant difference between the 2 groups in anastomosis time (42.4±11.8 versus 24.2±7.8, P<0.001) and the entire operation time (436.6±83.9 versus 415.3±68.5, P=0.035). CONCLUSIONS We suggest that when the surgeon is familiar with a loupe and vascular anastomosis, hepatic artery reconstruction using a surgical loupe is a safe and feasible method with a shorter operation time.