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Background: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits., Methods: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method., Results: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm 3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm 3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm 3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm 3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria., Conclusion: Patients with TTV ≤ 275 cm 3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria., (© 2024. The Author(s).)

Background and Objectives: Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients., Methods: Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated., Results: Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P < .0001). In model 2, the patients were divided into five groups with 5-year DFS of 58.0%, 43.7%, 24.0%, 15.4%, and 0.0%, respectively (P < .0001)., Conclusion: Based on nomogram models, DFS for the patients who had liver resection for HCC can be predicted before liver resection and re-assessed after liver resection., (© 2020 Wiley Periodicals LLC.)

Liver resection for hepatocellular carcinoma (HCC) is associated with high recurrence rates. Adequate resection margin which is carried out by surgeons may reduce tumor recurrence. Nevertheless, the margin width remains controversial particularly in cirrhotic patients where optimal parenchymal preservation is necessary. This study aims to find a reference for proposing the resection margin when liver resection is planning.Totally, 534 patients who received liver resection for HCC were included. The clinical profiles of the patients, tumor characteristics and patients' survival were all collected. The patients were classified according to resection margin (<0.5 cm, 0.5-0.99 cm, and ≥1 cm) and preoperative α-fetoprotein (AFP) levels (<15 ng/ml, 15-200 ng/ml, and >200 ng/ml), then survival was calculated.Most of the patients had hepatitis B (52.4%) and hepatitis C (24.0%) infection. Multivariate analysis showed that narrow resection margin (<0.5 cm) (hazard ratio [HR]: 1.323, P = .024), high AFP level (≥15 ng/ml) (HR: 1.305, P = .039), major extent of resection (≥3 segments) (HR: 1.507, P = .034), and underlying cirrhosis (HR: 1.404, P = .009) were independent risk factors for disease-free survival. In further survival analysis, resection margin was not significant for disease-free survival if serum AFP levels were <15ng/ml. However, for the patients with AFP level between 15 and 200 ng/ml, resection margin ≥0.5 cm was significant to improve 5-year disease-free survival from 24.6 months to 38.7 months (P = .040). For the patients with AFP >200 ng/ml, resection margin had to be extended to ≥1 cm to improve 5-year disease-free survival from 33.9 months to 48.8 months (P = .012). When the patients meeting AFP <15 ng/ml with tumor-free margin, AFP between 15 and 200 ng/ml with margin ≥0.5 cm, and AFP level >200 ng/ml with margin ≥1 cm were compared, their survival rates were not different.Adequate resection margin can be guided by pre-operative AFP levels. Tumor-free margin is enough for patients with normal AFP level. A resection margin ≥0.5 cm is advised for the patients with AFP between 15 and 200 ng/ml, and ≥1 cm for the patients with AFP over 200 ng/ml.

Background: Clinically severe infection-related inflammation after major liver resection may cause hyperbilirubinemia. This study aims to clarify the impact of bacterial infection and endotoxins on the hepatobiliary transporter system and to explore possible mechanisms of endotoxin-related postoperative hyperbilirubinemia., Method: Mice that underwent major hepatectomy with removal of at least 70% of liver volume were exposed to lipopolysaccharide (LPS) at different dosages. Subsequently, hepatobiliary transporter compounds related to bile salt excretion were further investigated., Results: The expression of genes related to hepatobiliary transporter compounds was not significantly different in the liver tissue of mice after major hepatectomy and LPS exposure. However, bile salt export pump (BSEP) protein expression within the liver tissue of mice treated with LPS after major hepatectomy was relatively weaker and was even further reduced in the high-dose LPS group. The formation of antibodies against the BSEP in response to endotoxin exposure was also detected., Conclusion: This study illustrates a possible mechanism whereby the dysfunction of hepatobiliary transporter systems caused by endotoxin-induced autoantibodies may be involved in the development of postoperative jaundice associated with bacterial infection after major hepatectomy.

Background: Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved., Methods: A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed., Results: Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07-2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99-1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors., Conclusion: The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.

Background: Neutrophil-lymphocyte ratio (NLR) represents a pro-tumor inflammatory environment and host immunity. The aim of this study was to examine the effect of subsequent NLR for hepatocellular carcinoma (HCC) after liver resection., Methods: A total of 672 patients had liver resection for HCC were included in this study. NLR at diagnosis of HCC and HCC recurrence were collected. NLR at 2.5 was used as cut-off value to calculate its prognostic effect., Results: According to NLR cut-off value, the patients with NLR >2.5 had larger tumor size, higher histology grade, and higher rates of tumor multiplicity and vascular invasion. After a median follow-up of 76.3 months, 437 (65.0%) patients had tumor recurrence. The 1-, 3- and 5-year recurrence-free survival were 77.4%, 55.2% and 44.8% in NLR ≤2.5 group, compared to 64.1%, 45.2% and 35.5% in NLR >2.5 group (P = 0.016). When patients had tumor recurrence, 5-year post-recurrent survival was best in the patients staying with NLR ≤2.5 all the time and decreased from 45.9% to 24.6% if NLR was ≤2.5 at resection and became >2.5 at recurrence (P = 0.013)., Conclusion: High NLR was an independent unfavorable prognostic factor. Subsequent change of NLR between liver resection and HCC recurrence could predict post-recurrent survival., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Aims: Surgical treatment for early-stage hepatocellular carcinoma (HCC) is toward transplantation. However, liver resection remains the major surgical treatment for HCC in Asia. This study is to examine the results of liver resection when liver transplantation became an option of treatment for early-stage HCC., Methods: In this retrospective cohort study, 1639 patients with resectable HCC were reviewed and divided into two groups. In the 1st period (2002-2005), all 679 patients received liver resection. In the 2nd period (2006-2010), 916 patients had liver resection and 44 patients jointed liver transplantation program. The results of treatment in these two periods were analyzed., Results: The characteristics of tumors were the most important factors of tumor recurrence after liver resection. Liver function reserve, characteristics of tumors, and surgeons' endeavor were all independent factors for overall survival after liver resection. When the patients with oligo-nodular tumors or portal hypertension with low platelet count had liver transplantation rather than liver resection in the 2nd period, the survival rates in the 2nd period were improved. When the patients in the 1st period with low platelet count (≤105 × 10(3)/uL) were subtracted, the 5-year survival rate of the patients with one-segmentectomy for small-sized HCC in the 1st period was similar to those in the 2nd period and transplant patients., Conclusions: The outcomes of liver resection were improved while liver transplantation was performed for the patients with suspicious portal hypertension. Platelet count, 105 × 10(3)/uL, could be a watershed for early stage HCC patients to undergo liver resection or liver transplantation., (Copyright © 2015. Published by Elsevier Ltd.)

Surgical treatment for primary hepatocellular carcinoma (HCC) has progressed enormously over time. The aim of this study was to analyze the evolution of surgical techniques and outcomes of patients undergoing major right hepatectomy (RH) over the last few decades.A retrospective review of 557 consecutive patients who had undergone RH for HCC between January 1982 and December 2011 was performed. Patients were categorized into subgroups and analyzed according to period and surgical approach to hepatectomy. Based on a propensity score-matching model, the surgical approach in patients in the second period was also analyzed in terms of anterior approach (AA) and conventional approach (CA)-RH.Tumor factors remained the most important prognostic factors related to postoperative HCC recurrence throughout the 2 periods examined in this study. Comparison of patients selected by a propensity score-matching model showed that AA-RH led to significantly better outcomes including recurrence-free survival (RFS) (P = 0.011) and overall survival (OS) (P = 0.012) in patients with HCC as compared with CA-RH. The 5-year RFS and OS were 33.4% and 52.2% after AA-RH, and 21.0% and 36.5% after CA-RH.Major hepatectomy has evolved into a safe procedure that can be performed with confidence. RH by an AA has shown several advantages over CA-RH, and can thus be recommended as the standard procedure for liver resection in patients who require right hepatectomy.

Background: Centrally located large hepatocellular carcinoma (HCC) is a difficult issue in surgery. These HCCs can be treated by hemi-/extended or central hepatectomies. The aim of this study was to analyze the results of hemi-/extended and central hepatectomies., Methods: One hundred and four patients with centrally-located large tumors were retrospectively reviewed. Patients were divided into group 1 (n = 41) with hemi-/extended hepatectomies, and group 2 (n = 63) with central hepatectomies. Characteristics were analyzed between groups and survival rates were calculated., Results: Parenchyma resection was limited in group 2. The resection margin in 92.6% of group 2 patients was < 1 cm, compared with 78.9% of group 1 patients (p = 0.056). The 1- and 5-year disease-free survival rates were 50% and 38.9% for group 1, and 50% and 15% for group 2 (p = 0.279). The 1-, 5-year overall survival rates were 89.5% and 66.2% for group 1 and 87.5% and 53.1% for group 2 (p = 0.786). Cirrhosis, the preoperative aspartate aminotransferase (AST) level and lower resected liver weight were independent factors impairing survival., Conclusion: Hemi-/extended and central hepatectomies have comparable complication rates and long-term survival rates for patients with centrally located large HCC. Cirrhosis, the AST level and resected liver weight were independent factors determining long-term survival.

Background: Postoperative ascites (POA) is a common complication after liver resection (LR). The aim of the present study was to identify the risk factors for developing POA and to evaluate its clinical significance in the prognosis of patients with hepatocellular carcinoma (HCC)., Methods: We performed a retrospective analysis of data obtained from 651 patients who underwent LR for the treatment of HCC between January 2001 and July 2005. The patients selected for the study were categorized and analyzed on the basis of the presence or absence of POA., Results: Overall, 166 (25.5%) patients developed POA. A multivariate logistic regression analysis identified that five significant factors--cirrhotic liver, high indocyanine green retention, portal hypertension, hypoalbuminemia, and extent of LR--were associated with the development of POA. The recurrence-free survival and overall survival of patients with POA were significantly lower than those of patients without POA. The 5-year recurrence-free survival rates of patients with intractable POA over those of patients without POA were 31.7% versus 36.1%, and the corresponding 5-year overall survival rates were 17.4% versus 57.0%. The relative risk of mortality within 1 year in patients with POA was 2.4 times (95% confidence interval, 1.76-3.27; p < 0.001) higher than that in patients without POA., Conclusions: A nomogram for predicting the probability of POA after LR for HCC was constructed on the basis of the identified risk factors, which may be used for risk-stratifying patients who may or may not benefit from surgical resection. Because patients with POA after LR show a high incidence of HCC recurrence and mortality risk, those with intractable ascites should be considered for prompt liver transplantation.

Background and Purpose: The outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment., Methods: We conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined., Results: Of the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 vs. 69.5% in era 2; p = 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% vs. 2.2% for 5-year survival; p < 0.0001)., Conclusion: The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.

Objective: Lymph node metastasis (LNM) rarely occurs in hepatocellular carcinoma (HCC). Few studies have reported the potential risk factors of LNM and the influence of LNM on the progression and prognosis of HCC. The purposes of this study were to explore the clinicopathological characteristics of operable HCC with LNM and to demonstrate the effects of LNM on HCC prognosis., Methods: A retrospective review of 2,034 HCC patients undergoing surgery from 1982 to 2005 was performed. The influence of LNM was assessed by clinicopathological factors, tumour recurrence, and overall survival. A total of 66 randomly selected patients matched for clinicopathological variables were used to analyse the difference in survival., Results: A total of 25 patients (1.23%) were reported to have LNM. Higher preoperative carcinoembryonic antigen levels (> 10 ng/mL) were significantly associated with a higher incidence of LNM than were low preoperative carcinoembryonic antigen levels (≤ = 10 ng/mL) (15.38%vs. 3.79%, p = 0.042). Furthermore, HCC with LNM (N1 disease) was larger in size (mean, 9.44 vs. 5.85 cm, p = 0.016) and significantly associated with vascular invasion, worse histological grade, and nonencapsulation (p = 0.002, < 0.001, and < 0.001, respectively). Finally, patients with HCC accompanied by LNM had shorter mean disease-free survival and overall survival (p = 0.001 and < 0.001, respectively)., Conclusion: This study identified the worst prognosis of HCC in a population with LNM. HCC with LNM tends to be the infiltrating type with larger tumour size (> 5 cm), presence of microvascular invasion, and worse histological grade. Liver resection with lymphadenectomy is possibly beneficial for patients with HCC accompanied by LNM., (Copyright © 2011 Asian Surgical Association. Published by Elsevier B.V. All rights reserved.)

Background: The choice between minor versus major resection or anatomic versus nonantatomic resection for small (<5 cm) solitary hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. The aim of our study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) after minor or major hepatic resection for small solitary HCC in cirrhotic patients., Methods: Between January 1983 and December 2002, patients with solitary HCC of < or = 5 cm in size who had histologically proven liver cirrhosis and microscopically tumor-free margin were included. These selected patients underwent either minor (< or = 2 segments) or major (> or = 3 segments) hepatectomy., Results: In 373 patients, 259 underwent minor and 114 underwent major hepatectomy. Patients in the minor resection group had more severe underlying liver disease (P = .005). Therefore, only 29.3% received anatomic resection in the minor resection group in comparison with 72.8% in the major hepatectomy group (P = .0001). No difference was found in postoperative morbidity (P = .105), mortality (P =.222), intrahepatic recurrence (P = .742), and 5-year DFS and OS (31.6% vs 31.8%, P = .932 and 50.7% vs 44.0%, P = .114) in both groups. The type of operative resection was not found to be a significant factor affecting survival in univariate analysis, but the preoperative liver function (alanine aminotransferase [AST] or alanine aminotransferase [ALT], serum albumin, or Child-Pugh status), tumor characteristics (alpha-feto protein, size, and presence of daughter nodules), and blood transfusion were found to be independent factors that affect the DFS and OS in a multivariate analysis., Conclusion: The severity of cirrhosis and tumor characteristics depicts long-term survival rather than the type of resection in HCC., (Crown Copyright 2010. Published by Mosby, Inc. All rights reserved.)

Split-liver transplantation is a well-known procedure for increasing the donor pool. The procedure is commonly used in 1 adult and 1 child, but is less commonly performed in 2 adults because of technical difficulty and poor outcome in left-lobe recipients. Preservation of caudate lobe function is important in recipients with borderline graft-recipient weight ratio to achieve better results. Herein, we report a case in which caudate lobe outflow was reconstructed in a left lobe with a caudate lobe graft in split-liver transplantation in 2 adults.

Background: Post-operative hepatic failure is the most important concern for hepatocellular carcinoma (HCC) patients undergoing hepatectomy. The aim of this study was to determine the safe line of hepatectomy to prevent liver failure., Method: Clinical profiles of 117 patients with HCC who underwent hepatectomies in Chang Gung Memorial Hospital from Jan. 2002 through Jun. 2003 were reviewed. Patients with heart disease, azotemia, intra-operative blood loss > or = 1500 ml or international ratio of prothrombin time > or = 1.2 were excluded. All 117 patients studied had preoperative 15-minute retention rates of ICG (ICG15). Whole liver volumes (LV) were calculated from the equation: LV (ml) = 706.2 x body surface area (BSA, m2) + 2.4. The resected liver volumes were measured by pathologists. Postoperative liver dysfunction was defined as an international prothrombin ratio of > or = 1.5., Results: Thirteen of the 117 HCC patients experienced postoperative liver dysfunction. The relationship between ICG15 retention rates and the ratio of remnant liver volume (RR) in the patients with postoperative liver dysfunction was established by regression, producing an equation: RR = 1.98 x ICG + 0.3672 (r = 0.92, p < 0.001)., Conclusion: Hepatectomies will be safer if the estimated ratio of remnant liver volume prior to surgery is higher than the calculated value of RR = 1.98 x ICG + 0.3672.

Kun-Ming Chan, Tsung-Han Wu, Chih-Hsien Cheng, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou, Wei-Chen Lee Department of General Surgery and Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan Background: Sorafenib is the first regimen listed in the treatment algorithm for hepatocellular carcinoma (HCC) worldwide. This study aimed to assess the efficacy of sorafenib treatment for advanced HCC in a clinical practice using a nationwide population study. Methods: All patients registered with a diagnosis of primary HCC and identified as having been prescribed sorafenib between August 2012 and December 2015 were selected from a national database and retrospectively reviewed. Outcomes related to prescription of sorafenib for these patients were further assessed. Results: A total of 9,738 patients were enrolled and analyzed. As a result, 32.33% of patients had an initial treatment response and were eligible for the prescribed second term (240 tablets/term) of sorafenib and 8.91% of patients received more than three terms of sorafenib. Meanwhile, the duration of sorafenib usage beyond 6 months was noted in 15.49% of patients, including 10.59% of patients with a period of usage between 6 and 12 months and 4.9% of patients with more than 12 months usage. Survival analysis showed that patients who received locoregional therapy plus sorafenib had significantly better survival rates than those who underwent only sorafenib treatment. Certain patients who underwent hepatectomy (n=12) or liver transplantation (n=13) were subsequently free of HCC. Conclusion: The disease control rate of sorafenib in advanced HCC patients in this study seemed similarly poorer as what has been previously reported by clinical trials. The combination of sorafenib and additional treatments could perhaps provide survival benefits and possibly cure disease in combination with surgical management. Keywords: sorafenib, hepatocellular carcinoma, hepatectomy, liver transplantation, locoregional therapy, outcome