Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Clinical and Dosimetric Results of Proton or Photon Radiation Therapy for Large (>5 cm) Hepatocellular Carcinoma: A Retrospective Analysis.

PURPOSE: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy. METHODS AND MATERIALS: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison. RESULTS: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 Gy exhibited significantly better local control (LC; 2-year: 85.6% vs 20.5%; P < .001), progression-free survival (PFS; median, 7.4 vs 3.2 months; P < .001), and overall survival (OS; median, 18.1 vs 7.3 months; P < .001) compared with those with BED10 < 75 Gy. Notably, proton-treated patients had a significantly higher BED10 (96 vs 67 Gy; P < .001) and improved LC (2-year: 88.5% vs 33.8%; P < .001), PFS (median, 7.4 vs 3.3 months; P = .001), and OS (median, 18.9 vs 8.3 months; P < .001) than those undergoing photon radiation therapy. Furthermore, patients treated with protons had significantly lower V1 of the liver (P < .001), mean upper gastrointestinal tract dose (P < .001), and mean splenic dose (P < .001), with significantly decreased incidences of radiation-induced liver disease (P = .007), grade ≥3 upper gastrointestinal bleeding (P = .001), and grade ≥3 lymphopenia (P = .003). On multivariate analysis, proton radiation therapy consistently correlated with superior LC (P < .001), PFS (P < .001), and OS (P < .001). In intragroup dosimetric comparison, photon plans demonstrated significantly higher mean liver dose (P < .001) compared with actually delivered proton treatments, and 72 (69%) of them had mean liver dose exceeding 28 Gy, which necessitated target dose de-escalation. CONCLUSIONS: In the context of large HCC radiation therapy, a higher target BED10 was associated with improved outcomes. Notably, proton therapy has demonstrated the capability to deliver ablative doses while also being accompanied by fewer instances of severe toxicity.

Adding nutritional status to the original BCLC stage improves mortality prediction for hepatocellular carcinoma patients in HBV-endemic regions.

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.

Significance of Physical Status and Liver Function Reserve for Outcome of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib Treatment.

Background: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment. Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed. Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients. Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.

Laparoscopic liver resection is associated with less significant muscle loss than the conventional open approach.

BACKGROUND: Laparoscopic liver resections (LLR) have been shown a treatment approach comparable to open liver resections (OLR) in hepatocellular carcinoma (HCC). However, the influence of procedural type on body composition has not been investigated. The aim of the current study was to compare the degree of skeletal muscle loss between LLR and OLR for HCC. METHODS: By using propensity score matching (PSM) analysis, 64 pairs of patients were enrolled. The change of psoas muscle index (PMI) after the operation was compared between the matched patients in the LLR and OLR. Risk factors for significant muscle loss (defined as change in PMI > mean change minus one standard deviation) were further investigated by multivariate analysis. RESULTS: Among patients enrolled, there was no significant difference in baseline characteristics between the two groups. The PMI was significantly decreased in the OLR group (P = 0.003). There were also more patients in the OLR group who developed significant muscle loss after the operations (P = 0.008). Multivariate analysis revealed OLR (P = 0.023), type 2 diabetes mellitus, indocyanine green retention rate at 15 min (ICG-15) > 10%, and cancer stage ≧ 3 were independent risk factors for significant muscle loss. In addition, significant muscle loss was associated with early HCC recurrence (P = 0.006). Metabolomic analysis demonstrated that the urea cycle may be decreased in patients with significant muscle loss. CONCLUSION: LLR for HCC was associated with less significant muscle loss than OLR. Since significant muscle loss was a predictive factor for early tumor recurrence and associated with impaired liver metabolism, LLR may subsequently result in a more favorable outcome.

Modified preoperative score to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND: No prognostic models specific to hepatocellular carcinoma patients receiving surgical resection have been considered strong and convincing enough for survival prediction thus far, and there are no models including only preoperative predictors. We derived a nomogram to predict disease-free survival in a previous study. AIM: To simplify our score and compare research outcomes among other scoring systems. METHODS: We retrospectively reviewed data from 1106 patients with hepatocellular carcinoma who underwent liver resection at the Linkou Chang Gung Memorial Hospital between April 2003 and December 2012. Multivariate analyses were conducted to identify the significant survival predictors. Homogeneity, Harrell's C-index, and Akaike information criterion were compared between our score, AJCC 8th edition, Tokyo score, and Taipei Integrated Scoring System (TTV-CTP-AFP model). RESULTS: Among the 1106 patients, 731 (66.1%) had tumor recurrence at a median follow-up of 83.9 mo. Five risk factors were identified: platelet count, albumin level, indocyanine green retention rate, multiplicity, and radiologic total tumor volume. Patients were divided into three risk groups, and the 5-year survival rates were 61.7%, 39%, and 25.7%, respectively. The C-index was 0.617, which was higher than the Tokyo score (0.613) and the Taipei Integrated Scoring System (0.562) and equal to the value of the AJCC 8th edition (0.617). CONCLUSION: The modified score provides an easier method to predict survival. Appropriate treatment can be planned preoperatively by dividing patients into risk groups.

Enhancement of dendritic cell immunotherapy by recalling antigens for hepatocellular carcinoma in mice.

Background: The therapeutic efficacy of dendritic cell (DC)-immunotherapy for large hepatoma in mice is unsatisfactory. Materials & methods: DC-based immunotherapy was used to treat Hepa1-6 tumors measuring 6 ± 1 mm in diameter, enhanced by boosting tumor antigens. Results: CD4+ and CD8+ T-cells were contracted and transformed into memory phenotypic cells after DC-based vaccination. When T-cells were re-stimulated, T-cells obtained from mice boosted by tumor antigen injection showed highest proliferation capacity. When mice with large tumors were treated, DC-based vaccination boosted by tumor antigen and an additional DC-infusion yielded curative rates of 50% and 23.1%, respectively. Conclusion: DC vaccination induced effector memory cells. Antigen presentation recalled by DC or tumor antigens increased the curative rate in mice with large tumors.

Hepatocellular carcinoma is the most common liver malignancy and is often found at advanced stage. Immune checkpoint inhibitor combined with a molecular targeting agent is a new strategy for the treatment of advanced hepatocellular carcinoma and yields 30% of objective response rate. However, we still need another treatment for the patients who are not responsive to immune checkpoint inhibitor combined with a molecular targeting agent. Dendritic cell-based immunotherapy is one of the treatments for advanced hepatocellular carcinoma. In this animal study, dendritic cells can activate T-lymphocytes to kill cancer cells. Dendritic cells can also induce memory T-lymphocytes, which can be reactive by boost tumor antigens and increase therapeutic efficacy. This treatment strategy, dendritic cell infusion followed by tumor-antigen injection, can be translated into clinical practice in the future.

Recurrence Patterns After Hepatectomy With Very Narrow Resection Margins for Hepatocellular Carcinoma.

Background: The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. Methods: Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1 mm) or wider (>1 mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. Results: 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5 cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. Conclusions: Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.

Individualized Selection Criteria Based on Tumor Burden in Future Remnant Liver for Staged Hepatectomy of Advanced CRLM: Conventional TSH or ALPPS.

Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM.

Living-Donor Liver Transplantation for Hepatocellular Carcinoma: Impact of the MELD Score and Predictive Value of NLR on Survival.

Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR). Patients and Method: This retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004−2019 in our institute. We defined a high MELD score as ≥20. Results: The MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02−1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532−0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005). Conclusions: Pre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores.

Hepatectomy or/with Metastatectomy for Recurrent Intrahepatic Cholangiocarcinoma: Of Promise for Selected Patients.

Introduction: Intrahepatic cholangiocarcinoma (ICC) has devastating outcomes owing to its advanced stage at diagnosis and high recurrence after hepatectomy. There is no preferred treatment for recurrent ICC. We retrospectively reviewed our patients who underwent repeated operations for recurrent ICCs based on their different indications to appraise the outcomes. Methods: In all, 160 out of 216 patients with ICC (71.4%) experienced recurrence after curative resection from 1977 to 2014. The patterns of recurrence were categorized according to the locations and numbers of recurrent tumors. Results: Patients with merely intrahepatic recurrence (n = 38) had superior overall survival (OS) compared with those with beyond intrahepatic recurrence (p < 0.0001). Twenty-seven out of 160 patients (16.8%) underwent repeat hepatectomy or/with metastatectomy for recurrence and had superior OS when compared to the remaining 133 patients who received nonoperative treatment/palliation (85.6 months versus 20.9 months, p < 0.001). Furthermore, patients suitable for repeat hepatectomy in the intrahepatic recurrent group (n = 12) had superior post-recurrence overall survival (PROS) than the remaining 26 patients receiving nonoperative treatment (61.6 months versus 14.7 months, p < 0.05). Conclusion: Liver is the most commonly involved site of recurrent ICC. However, merely intrahepatic recurrence may have a favorable prognosis compared to recurrence involving other sites. Aggressive hepatectomy may provide a survival benefit in selected patients.

Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.

Reconstruction of Separated Intrahepatic Ducts Using the Cystic and Common Hepatic Ducts in Right-Lobe Living-Donor Liver Transplantation: Experiences of Surgical Techniques, Biliary Complications, and Outcomes in a Single Institution.

BACKGROUND Duct-to-duct biliary reconstruction has been increasingly used in living-donor liver transplantation. Information regarding dual duct-to-duct biliary anastomoses is limited. We present the largest case series to date on the use of the cystic and common hepatic ducts as dual-ductal anastomosis, along with long-term follow-up results. MATERIAL AND METHODS In this study, 740 patients underwent right-lobe living-donor liver transplantation; 56 of them were documented as dual-ductal anastomoses. We analyzed recipient and donor characteristics, surgical procedures, appearance of biliary complications, corresponding interventions, and long-term biliary outcomes. RESULTS Cystic and common hepatic ducts were utilized in 56 cases of dual-ductal biliary reconstruction, which we categorized into 2 types: A (78.6%), in which the right anterior intrahepatic duct was anastomosed to the common hepatic duct and the right posterior intrahepatic duct to the cystic duct; and B (21.4%), which was the reverse of A. After a median follow-up period of 46.4 months, 23 patients (41.1%) experienced complications, including biliary leakage and biliary stricture. However, after aggressive intervention (patent biliary anastomosis in most of them), 50 of 56 patients (89.3%) had patent biliary anastomosis and restored normal liver function at the end of follow-up. A small graft (graft-to-recipient weight ratio <0.9%) was the only predictor of biliary complications after multivariate analysis. CONCLUSIONS Dual-ductal biliary reconstruction in adult right-lobe living-donor liver transplantation is challenging but feasible. Our findings support the use of the cystic duct for reconstruction in selected patients. Good long-term results can be achieved with adequate management of patients with biliary complications.

Preferred Treatment with Curative Intent for Left Lateral Segment Early Hepatocellular Carcinoma under the Era of Minimal Invasive Surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. METHODS: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. RESULTS: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1-60.9 months) and 17.6 (range: 2.4-94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

Human Cytomegalovirus Is Associated with Lower HCC Recurrence in Liver Transplant Patients.

Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia (p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20-0.97), microscopic vascular invasion (p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78-8.36), and tumor status beyond the Milan criteria (p = 0.001; OR = 3.69; 95% CI = 1.77-7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.

Improving outcomes of liver resection for hepatocellular carcinoma associated with portal vein tumor thrombosis over the evolving eras of treatment.

BACKGROUND: The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment. MATERIALS AND METHODS: A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined. RESULTS: Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months. CONCLUSION: The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.

Risk Score Model for Microvascular Invasion in Hepatocellular Carcinoma: The Role of Tumor Burden and Alpha-Fetoprotein.

Microvascular invasion (MVI) is a significant risk factor for the recurrence of hepatocellular carcinoma, but it is a histological feature that needs to be confirmed after hepatectomy or liver transplantation. The preoperative prediction of MVI can optimize the treatment plan of HCC, but an easy and widely applicable model is still lacking. The aim of our study was to predict the risk of MVI using objective preoperative factors. We retrospectively collected 1153 patients who underwent liver resection for HCC, and MVI was found to be associated with significantly poor disease-free survival. The patients were randomly split in a 3:1 ratio into training (n = 864) and validation (n = 289) datasets. The multivariate analysis of the training dataset found preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We built a risk score model with cutoff points of TTV at 30, 60, and 300 cm3 and AFP at 160 and 2000 ng/mL, and the model stratified the risk of MVI into low risk (14.1%), intermediate risk (36.4%), and high risk (60.5%). The validation of the risk score model with the validation dataset showed moderate performance (the concordance statistic: 0.731). The model comprised simple and objective preoperative factors with good applicability, which can help to guide treatment plans for HCC and future study design.

Sedative and Immunosuppressive Effects of Dexmedetomidine in Transplantation.

Dexmedetomidine, an α2-adrenergic receptor agonist, is used as an anti-anxiety medication. It exerts a cholinergic effect, thereby reducing the release of tumor necrosis factor alpha (TNF-α). We hypothesized that the use of dexmedetomidine as a sedative agent in transplantation would also protect allografts. We examined our patients who underwent living donor liver transplantation. Subsequently, we generated a series of mouse models to investigate the effect of dexmedetomidine on sedation-based tolerance post transplantation. A total of 49 liver recipients were enrolled in this study, of which 23 (47%) were administered dexmedetomidine through 24 h infusion on postoperative day 1. A trend toward the improvement of hepatocyte injury along with better liver function was observed in the dexmedetomidine-treated group during the first postoperative week. In animal models, dexmedetomidine inhibited the proliferation of CD4+ and CD8+ T cells and TNF-α production in a dose-dependent manner. We used dexmedetomidine to treat skin-transplanted mice and observed a significantly prolonged graft survival in mice that were administered a higher dose of dexmedetomidine. Our results revealed that dexmedetomidine exerts a dual effect of sedation and immunosuppression. This light-sedation approach will not only make patients calmer in the intensive care unit but also protect allografts from injury.

Application of mentorship program for another aspect of surgical residency training: The importance of academia in surgical training.

ABSTRACT: Traditionally, surgical residency training is more focused on obtaining surgical skills through a well-established coaching system worldwide. However, constant advances in medical science require surgeons to learn not only surgical skills but also the ability of scientific research to improve clinical practice and future professional development. The study aims to emphasize that professional education in terms of scientific research is also significant for surgical residency training.All residents who had been recruited in a medical center for the surgery residency program between years 2006 and 2015 were evaluated in the study. Generally, every resident is assigned to a mentor since the first year of residency. Then, the mentor would help the resident qualify a 2-step evaluation in terms of scientific research during the residency training program.A total of 193 residents were evaluated in the study. All of them had completed the first step regarding oral presentation of their designated research, and the majority of residents obtained 80 to 90 points that were rated by referees. Overall, 102 residents (52.8%) had completed the second step with the publication of a research manuscript. The percentage of residents who had fulfilled the criteria of this 2-step assessment ranged from 35.3% to 81.8% by year.The continuing education for surgical residents should not be limited in coaching clinical practice. Scientific research is also essential for current surgical residency training, and a formal mentorship program may be beneficial for the future professional development of surgical residents. However, the success of the 2-step evaluation could possibly depend on the career choices of the residents instead of the mentorship program.

Immunological discrepancy in aged mice facilitates skin allograft survival.

More and more aged people are undergoing organ transplantation. Understanding aging effects on immunity will be helpful for post-transplantation care and adjustment of immunosuppressants for aged recipients. A mouse model, using C3H mice as donors and aged/young C57BL/10J mice as recipients, was employed to study aging effects on immunity. The results showed that frequency of myeloid-derived suppressor cells (MDSC) and level of TGF-ß was higher in aged mice than in young mice (4.4 ± 1.4% versus 1.6 ± 1.1%, p = 0.026 for MDSC; 21.04 ± 3.91 ng/ml versus 15.26 ± 5.01 ng/ml, p = 0.026 for TGF-ß). In vivo, skin allograft survived longer on the aged than on young mice (19.7 ± 5.2 days versus 11.9 ± 4.1 days, p = 0.005). When entinostat was applied to block MDSC, the survival of skin allografts on aged mice was shorten to 13.5 ± 4.7 days which was not different from the survival on young mice (p = 0.359). In conclusion, allogeneic immunity was different in aged from young mice in high frequency of MDSC and high serum level of TGF-ß. Blocking the function of MDSC reversed the low immunity in aged mice and caused skin allograft rejection similar to young recipients.