Peptidylarginine Deiminase Type 2 Predicts Tumor Progression and Poor Prognosis in Patients with Curatively Resected Biliary Tract Cancer.

(1) Background: PADI2 is a post-translational modification (PTM) enzyme that catalyzes citrullination, which then triggers autoimmune disease and cancer. This study aimed to evaluate the prognostic value of peptidylarginine deiminase 2 (PADI2) protein expression in biliary tract cancer (BTC) patients. (2) Methods: Using immunohistochemistry, the PADI2 protein expression in BTC tissues was analyzed. The correlations between PADI2 protein expression and clinicopathologic characteristics were analyzed using Chi-square tests. The Kaplan-Meier procedure was used for comparing survival distributions. We used Cox proportional hazards regression for univariate and multivariate analyses. From 2014 to 2020, 30 resected BTC patients were enrolled in this study. (3) Results: Patients with high PADI2 protein expression were associated with shorter progress-free survival (PFS; p = 0.041), disease-specific survival (DSS; p = 0.025), and overall survival (OS; p = 0.017) than patients with low PADI2 protein expression. (4) Conclusions: The results indicated that PADI2 protein expression was an independent poor prognostic factor for BTC patients regarding PFS, DSS, and OS.

Weight self-perception and weight loss attempts in Chinese cardiovascular patients and non-cardiovascular patients: evidence from a population-based study.

BACKGROUND: Weight loss is a significant improvement for individuals with overweight or obesity, especially for cardiovascular patients. The driving effects of weight self-perception and attempts to lose weight are vital in weight management, yet weight misperception is a direct culprit for the undesirability of weight control and obesity prevention. This study aimed to investigate weight self-perception and misperception and weight loss attempts in Chinese adults, especially among cardiovascular and non-cardiovascular patients. METHODS: We collected data from China HeartRescue Global Evaluation Baseline Household Survey 2015. Questionnaires were used to assess self-reported weight and cardiovascular patients. We used kappa statistics to check the consistency between weight self-perception and BMI. Logistic regression models were fitted to identify risk factors associated with weight misperception. RESULTS: A total of 2690 participants were enrolled in the household survey, while 157 respondents were cardiovascular patients. According to questionnaire results, 43.3% of cardiovascular patients thought they were overweight and obese, while the percentage is 35.3% among non-cardiovascular patients. Kappa statistics indicated higher consistency of self-reported weight and actual weight among cardiovascular patients. Multivariate analysis showed weight misperception was significantly associated with gender, education level, and actual BMI. Lastly, 34.5% of non-cardiovascular patients and 35.0% of cardiovascular patients were trying to lose weight or keep weight. The majority of these people adopted combined strategies of controlling diet and exercise to lose or maintain weight. CONCLUSIONS: Weight misperception was highly prevalent among cardiovascular or non-cardiovascular patients. Obese respondents, women, and individuals with lower education levels were more vulnerable to make weight misperception. However, no difference in the purpose of weight loss attempts was indicated among cardiovascular and non-cardiovascular patients.

Minor hepatectomy for hepatocellular carcinoma in a patient with portal hypertension: A case report and review of the literature.

INTRODUCTION: Curative modalities for early hepatocellular carcinoma (HCC) include liver resection (LR) and transplantation. For patients with portal hypertension (PH), liver transplantation (LT) is the preferred treatment but is oftentimes limited by organ shortage and can lead candidates to drop off due to disease progression, while hepatectomy has a higher risk of complications. This would pose a dilemma as to whether wait for donor organs or prioritize hepatectomy. PATIENT CONCERNS: The patient was a 56-year-old male, a case of liver cirrhosis due to hepatitis C with sustained virological response following direct-acting antiviral agents. He was a liver transplant candidate, presented to the gastroenterology outpatient department for a recently-diagnosed liver tumor during a regular follow-up session. Pre-operative survey revealed PH manifested by thrombocytopenia, splenomegaly, huge splenorenal shunt and varices. The patient's Child-Pugh score was 7. INTERVENTIONS AND DIAGNOSIS: Considering the patient's overall condition, tumor size and location, and a shortage of grafts, he underwent segment 5 and 6 partial hepatectomy. The pathological diagnosis was moderately differentiated HCC. OUTCOMES: His postoperative course was complicated by refractory intraabdominal infection (IAI) and recovered under aggressive antibiotics treatment. He remained recurrence-free for over a year. CONCLUSION: For patients with early resectable HCC, the approach of having a minor hepatectomy followed by salvage transplantation should serve as a compromising strategy. Tumor resection retards the progression of the disease. Comprehensive healthcare can expectantly improve clinical outcomes.

The combination of living Bifidobacterium, Lactobacillus, and Streptococcus improves social ranking and relieves anxiety-like behaviors in competitive mice in a social dominance tube test.

INTRODUCTION: Social rank has a profound influence on the behavior and health of humans and animals. METHODS: To explore the effect of a combination of living Bifidobacterium, Lactobacillus and Streptococcus (CLB) on anxiety- and depression-like behaviors and social rank, mice were subjected to a social dominance tube test (SDTT). The behaviors, rank, gut microbiota, and expression of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. RESULTS: The results indicated that CLB improved the SDTT ranking score of the losers and alleviated anxiety-like behaviors of the winners. CLB decreased the level of Desulfovibrio and augmented the level of Mollicutes in the feces, increased BDNF content, and reduced the level of tumor necrosis factor-α in the hippocampus. CONCLUSION: These findings indicated that CLB may be used for the treatment of anxiety and improvement of the rank score via regulation of gut microbiota and anti-inflammatory effects.

A preoperative parathyroid scan is important for the total removal of the transplanted parathyroid tissue in recurrent secondary hyperthyroidism: A case report and literature review.

RATIONALE: Secondary hyperparathyroidism was one of mineral and bone disorders owing to chronic kidney disease. Patients who suffer from secondary hyperparathyroidism would receive medical treatment or parathyroidectomy with or without autotransplantation (AT). However, some patients receiving parathyroidectomy with AT have recurrent hyperparathyroidism, which impacts their lives. Patients with recurrent hyperparathyroidism may present persistent hypercalcemia and hyperphosphatemia, which would cause cardiovascular disease, like atherosclerosis. PATIENT CONCERNS: A 63-year-old female of Asian descent with chronic kidney disease who suffered from recurrent hyperparathyroidism for twice. The patient underwent parathyroidectomy with AT in the left thigh when secondary hyperparathyroidism happened. After 3 months, recurrent hyperparathyroidism happened. DIAGNOSIS: The patient was diagnosed with recurrent hyperparathyroidism due to chronic kidney disease with hyperparathyroidism status post parathyroidectomy with AT in the left thigh. Our patient also suffered from mineral and bone disorder. INTERVENTION: Two parathyroid adenoma in the left thigh were found. However, one of them was too small to found in the operation. Therefore, autograftectomy of the large one was performed. However, hyperparathyroidism happened again. This time, the autograftectomy was performed under dual phase Tc-99m MIBI (99m Tc-methoxy isobutyl isonitrile) parathyroid scintigraphy and it succeeded. OUTCOMES: After secondary autograftectomy, the value of intact parathyroid hormone was surveyed immediately and dropped by two-third followed by gradual reduction in the following weeks. The calcemia and phosphatemia were back to normal gradually. LESSONS: In our case, importance of scintigraphy in the parathyroidectomy was confirmed.

Subvesical Duct Detected by Magnetic Resonance Cholangiopancreatography (MRCP) in a Patient with Bile Leak after Laparoscopic Cholecystectomy.

We report a case of bile leaks post-laparoscopic cholecystectomy (LC) with initial treatment failure by common bile duct stent insertion. The injury of a subvesical duct running from gallbladder fossa toward an area of fluid accumulation that was not revealed by computed tomography and endoscopic retrograde cholangiopancreatography previously, was eventually found by magnetic resonance cholangiopancreatography (MRCP) and proved to be the cause of bile leak. Also, several tiny branches in the right liver instead of a main trunk and another subvesical duct draining into the common bile hepatic duct was noted. These anatomic variations were scarcely reported, especially by MRCP. The aim of this case report is to discuss the link between biliary tree anomaly and bile leak due to bile duct injury during LC in our experience treating one patient. Also, we review related literature to understand more on prevention or management of subvesical duct injury.

Check point to get adequate weight loss within 6-months after laparoscopic sleeve gastrectomy for morbid obesity in Asian population.

Purpose of this study is to develope a scoring system to predict the likelihood of excess body weight loss (EBWL) ≥ 50% 6-months after laparoscopic sleeve gastrectomy (LSG). From April 2016 to September 2018, data was collected from 160 patients (BMI ≥ 32) who underwent primary LSG with at least 6-months follow-up. They were separated into score generation (operated by one surgeon, n = 122) and validation groups (operated by 3 different surgeons, n = 38). EBWL at 6-months ≥ 50% was considered adequate weight loss. Independent variables including age, gender, initial body mass index (BMI), comorbidities, life-style habits, percentage of EBWL and percentage of total body weight loss at 1-week, 1-month, and 3-months were analyzed with mutivariate logistic regression to generate the scoring system. The system was applied to internal and external validation groups to determine efficacy. As results, between the score generation and internal validation groups, the only significant difference in patient characteristics was in exercise participation. EBWL at 1-month > 19.5% (1 point) and EBWL at 3-months > 37.7% (2 points) were identified as independent factors to predict EBWL at 6-months ≥ 50%. When scores were > 1, the system had 94.03% positive predictive value (PPV) and 81.82% negative predictive value (NPV) (AUC: 0.923). Internal validation scores > 1 had a 95.83% PPV and 85.71% NPV (AUC: 0.975). External validation results showed 88.59% PPV and 72.00% NPV (AUC: 0.802). We concluded that this scoring system provides a reliable, objective prediction of EBWL at 6-months ≥ 50%. Patients requiring more aggressive clinical follow-up and intervention can be detected as early as 1- to 3-months after LSG.

Mitochondrial Fission and Mitophagy Reciprocally Orchestrate Cardiac Fibroblasts Activation.

Although mitochondrial fission has been reported to increase proliferative capacity and collagen production, it can also contribute to mitochondrial impairment, which is detrimental to cell survival. The aim of the present study was to investigate the role of mitochondrial fission in cardiac fibroblasts (CF) activation and explore the mechanisms involved in the maintenance of mitochondrial health under this condition. For this, changes in the levels of mitochondrial fission/fusion-related proteins were assessed in transforming growth factor beta 1 (TGF-ß1)-activated CF, whereas the role of mitochondrial fission during this process was also elucidated, as were the underlying mechanisms. The interaction between mitochondrial fission and mitophagy, the main defense mechanism against mitochondrial impairment, was also explored. The results showed that the mitochondria in TGF-ß1-treated CF were noticeably more fragmented than those of controls. The expression of several mitochondrial fission-related proteins was markedly upregulated, and the levels of fusion-related proteins were also altered, but to a lesser extent. Inhibiting mitochondrial fission resulted in a marked attenuation of TGF-ß1-induced CF activation. The TGF-ß1-induced increase in glycolysis was greatly suppressed in the presence of a mitochondrial inhibitor, whereas a glycolysis-specific antagonist exerted little additional antifibrotic effects. TGF-ß1 treatment increased cellular levels of reactive oxygen species (ROS) and triggered mitophagy, but this effect was reversed following the application of ROS scavengers. For the signals mediating mitophagy, the expression of Pink1, but not Bnip3l/Nix or Fundc1, exhibited the most significant changes, which could be counteracted by treatment with a mitochondrial fission inhibitor. Pink1 knockdown suppressed CF activation and mitochondrial fission, which was accompanied by increased CF apoptosis. In conclusion, mitochondrial fission resulted in increased glycolysis and played a crucial role in CF activation. Moreover, mitochondrial fission promoted reactive oxygen species (ROS) production, leading to mitophagy and the consequent degradation of the impaired mitochondria, thus promoting CF survival and maintaining their activation.

Risk of breast cancer in women with non-lactational mastitis.

Little is known regarding the association of non-lactational mastitis women with breast cancer risk. This population-based cohort study examined the breast cancer risk in women with non-lactational mastitis. We identified 3,091 women with non-lactational mastitis between 2000 and 2011 using the Taiwan National Health Insurance Research Database. We performed 1:4 propensity score matching by age, socioeconomic status and comorbidities and identified 12,364 women without non-lactational mastitis. The mean age of women with non-lactational mastitis was 37.9 years; these women had a higher breast cancer risk than the comparison group (adjusted hazard ratio = 1.94, 95% confidence interval: 1.30-2.90). The incidence rates of breast cancer in women with non-lactational mastitis and the comparison group were 14.79 and 7.57 per 10,000 person-years, respectively. Furthermore, non-lactational mastitis was a risk factor for breast cancer in women aged <50 years, women with lower socioeconomic status and women with hormonal medication (p < 0.05). Women who had more episodes of non-lactational mastitis had a higher risk of developing a breast cancer. Thus, the risk of breast cancer in women with non-lactational mastitis is significantly higher than those without non-lactational mastitis.

Correction to: Bariatric Surgery Did Not Increase the Risk of Gallstone Disease in Obese Patients: a Comprehensive Cohort Study.

In the section "Method" the first sentence should read as follows: This retrospective study was fully evaluated and approved by the Institutional Review Board of Buddhist Dalin Tzu Chi Hospital (approval B10603004) and was conducted in accordance with the principles of the Helsinki Declaration.

Bariatric Surgery Did Not Increase the Risk of Gallstone Disease in Obese Patients: a Comprehensive Cohort Study.

PURPOSE: The aim of this study was to evaluate the influence of bariatric surgery on gallstone disease in obese patients. MATERIALS AND METHODS: This large cohort retrospective study was conducted based on the Taiwan National Health Insurance Research Database. All patients 18-55 years of age with a diagnosis code for obesity (ICD-9-CM codes 278.00-278.02 or 278.1) between 2003 and 2010 were included. Patients with a history of gallstone disease and hepatic malignancies were excluded. The patients were divided into non-surgical and bariatric surgery groups. Obesity surgery was defined by ICD-9-OP codes. We also enrolled healthy civilians as the general population. The primary end point was defined as re-hospitalization with a diagnosis of gallstone disease after the index hospitalization. All patients were followed until the end of 2013, a biliary complication occurred, or death. RESULTS: Two thousand three hundred seventeen patients in the bariatric surgery group, 2331 patients in the non-surgical group, and 8162 patients in the general population were included. Compared to the non-surgery group (2.79%), bariatric surgery (2.89%) did not elevate the risk of subsequent biliary events (HR = 1.075, p = 0.679). Compared to the general population (1.15%), bariatric surgery group had a significantly higher risk (HR = 4.996, p < 0.001). In the bariatric surgery group, female gender (HR = 1.774, p = 0.032) and a restrictive procedure (HR = 1.624, p = 0.048) were risk factors for gallstone disease. CONCLUSION: The risk for gallstone disease did not increase after bariatric surgery, although the risk was still higher than the general population. The benefit of concomitant cholecystectomy during bariatric surgery should be carefully evaluated.

Risk factors for contralateral inguinal hernia repair after unilateral inguinal hernia repair in male adult patients: analysis from a nationwide population based cohort study.

BACKGROUND: To identify the rate of and risk factors for contralateral inguinal hernia (CIH) after unilateral inguinal hernia repair in adult male patients. METHODS: This retrospective cohort study identified from the Taiwan National Health Insurance Research Database (NHIRD). Information on all adult patients who underwent primary unilateral inguinal hernia repair without any other operation was collected using ICD-9 diagnostic and procedure codes. The exclusion criteria were laparoscopic hernia repair, non-primary repair, complicated hernia, other combined procedures, female and undetermined gender. RESULTS: A total of 170,492 adult male patients were included, with a median follow-up of 87 months. The overall CIH rate was 10.5%, with a median time of 48 months to a subsequent hernia operation. The 1-year, 2-year, 3-year and 5-year-recurrent rate was 2.6, 3, 4.3, and 6.7% respectively. Further, 3.7% patients who underwent CIH repair had a complicated inguinal hernia. Multivariate analysis demonstrated that age > 45 y, direct hernia, cirrhosis (HR = 1.564), severe liver disease (HR = 1.663), prostate disease (HR = 1.178), congestive heart failure (HR = 1.138), and history of malignancy (HR = 1.116) had a significantly higher risk of CIH repair. CONCLUSIONS: Among adult male patients undergoing long-term follow-up, we identified several significant risk factors for CIH repair. If these risk factors are presented, the surgeon should inform the following risk of CIH repair to patients so that it can be repaired as soon as possible.

Incidence of and Risk Factors for Pediatric Metachronous Contralateral Inguinal Hernia: Analysis of a 17-Year Nationwide Database in Taiwan.

BACKGROUND: Previous prospective, retrospective, and meta-analysis studies revealed that the overall incidence of metachronous contralateral inguinal hernia (MCIH) ranges from 5.76% to 7.3%, but long-term follow-up postoperative data are scant. We identified the incidence and risk factors of MCIH in pediatric patients during the follow-up using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: Between 1996/01/01 and 2008/12/31, all pediatric patients with primary unilateral inguinal hernia repair who were born after 1996/01/01 were collected via ICD-9 diagnostic and procedure codes recorded in NHIRD. Patients with another operation during the same admission, complicated hernia, or laparoscopic procedure were excluded. Several reported risk factors, including age, sex, preterm birth, low body weight, and previous ventriculoperitoneal shunt placement, were used for analysis. The primary endpoint was the repairmen of MCIH following the initial surgery. All patients were followed until 2013/12/31 or withdrawal from national health insurance. RESULTS: A total of 31,100 pediatric patients underwent unilateral inguinal hernia repair, and 111.76 months of median follow-up data were collected. The overall rate of MCIH was 12.3%. Among the 31,100 patients who had the hernia repair, 63.6% had MCIH within 2 years and 91.5% had MCIH within 5 years. After initial surgery, the incidence of MCIH gradually and significantly decreased with age up to approximately 6 years. Multivariable analysis showed that age <4 y and girls were risk factors for subsequent MCIH. CONCLUSIONS: After 17 years of follow-up, the overall MCIH rate was 12.3%, and 91.7% of patients needed repair for MCIH within the first 5 years after initial surgery. Age <4 years and girls were risk factors for MCIH. The contralateral exploration for inguinal hernia should be considered among these patients.

Correction: Adjusted Age-Adjusted Charlson Comorbidity Index Score as a Risk Measure of Perioperative Mortality before Cancer Surgery.

[This corrects the article DOI: 10.1371/journal.pone.0148076.].

Serum adiponectin is a negative predictor of central arterial stiffness in kidney transplant patients.

BACKGROUND: The role of adiponectin in arterial stiffness and its relationship to cardiovascular disease is not fully demonstrated and needs further elaboration. In this study, the association between adiponectin level and arterial stiffness is studied among kidney transplant patients. MATERIAL AND METHODS: Anthropometric data and biochemical data including fasting glucose, lipid profile, renal function and serum adiponectin were determined in 55 kidney transplant patients. Central arterial stiffness was measured and presented by carotid-femoral pulse wave velocity. RESULTS: Univariate linear analysis showed that body weight, waist circumference, brachial pulse pressure and body mass index were correlated positively with carotid-femoral pulse wave velocity in this patient group. However, logarithmically transformed adiponectin level (log-adiponectin) correlated negatively with carotid-femoral pulse wave velocity. In multivariate regression analysis of factors significantly associated with carotid-femoral pulse wave velocity, it showed that both log-adiponectin (ß = -0.427; R(2) = 0.205, p = 0.001) and body weight (ß = 0.327; R(2 )=( )0.106, p = 0.007) were independently predictive of central arterial stiffness. CONCLUSION: Our study suggests that fasting serum adiponectin is negatively associated with carotid-femoral pulse wave velocity, hence arterial stiffness, in kidney transplant patients.

Adjusted Age-Adjusted Charlson Comorbidity Index Score as a Risk Measure of Perioperative Mortality before Cancer Surgery.

BACKGROUND: Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index (ACCI) to identify cancer patients with increased risk of perioperative mortality. METHODS: We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90-day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed. RESULTS: The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70-80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4-7, 8-11, and ≥ 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0-3. CONCLUSIONS: The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age.

Increased gene expression of TGF-ß in peripheral blood mononuclear cells from renal transplant patients with polyomavirus BK viremia.

We aimed to investigate the roles of cytokines during polyomavirus BK (BKV) reactivation in renal transplant patients. Forty-eight renal allograft recipients were enrolled, and their sera BKV viral load and mRNA expression levels of cytokines in peripheral blood mononuclear cells were measured by real-time polymerase chain reaction. Patient's age and gene expression levels of interleukin (IL)-2 (10.04 ± 2.63 vs. 8.70 ± 2.40, p = 0.049) and transforming growth factor (TGF)-ß (12.58 ± 2.59 vs. 10.89 ± 1.91, p = 0.015) were significantly higher in BKV viremia (+) renal transplant patients. Multivariate logistic regression analysis revealed that age and mRNA expression levels of TGF-ß, but not IL-2, significantly correlated with the presence of BKV viremia. Sera BKV viral loads showed a positive correlation with patient age and the levels of TGF-ß and IL-6 mRNA. After adjusting for age and sex in the regression model, both age and TGF-ß mRNA levels maintained a significant positive association with sera BKV viral loads. Serum TGF-ß concentration tended to be higher in BKV viremia (+) patients (p = 0.079). In conclusion, expression levels of TGF-ß were found to correlate with both BKV viremia positivity and sera BKV viral loads in renal transplant patients.

Delayed-Onset Chylous Ascites After a Living-Donor Liver Transplant: First Case Successfully Treated With Conservative Treatment?

Chylous ascites is a rare complication in liver transplant. Few cases have been reported to date. In most cases, chylous ascites is diagnosed within 1 month after surgery because of intraoperative injury of the hilar lymphatic system. Preoperative massive ascites and use of a LigaSure vessel sealing system for hilar dissection have been reported as risk factors. We report a case of chylous ascites after a living-donor liver transplant that was diagnosed after 6 months of uneventful follow-up. Sirolimus was added to cyclosporine early (2 wk after the operation) owing to poor renal function and it was found to be high (> 22 ng/mL) when the chylous ascites occurred. The patient was treated with total parenteral nutrition in combination with Sandostatin and rapid tapering of sirolimus after the failed initial conservative treatment. Residual abdominal fullness after meals and lymphedema of the legs disappeared 1 month after discontinuing sirolimus. This is the first case of delayed-onset chylous ascites after a liver transplant that was successfully treated conservatively.

The safety and adequacy of resection on hepatocellular carcinoma larger than 10 cm: A retrospective study over 10 years.

BACKGROUND/PURPOSE: Current treatment options for HCC≥10 cm (huge HCC) are limited. Otherwise, the margin status is known as a prognostic factor. Our aim was to determine the safety, effectiveness, and risk factors for overall survival and disease-free survival for these patients. METHODS: A total of 211 consecutive patients from 2000/08 to 2010/12 were enrolled. Characteristics of patients, tumors, and treatment were compared between the huge group (HCCs; ≥10 cm, n = 23; 11%) and those with smaller group (HCC; <10 cm n = 188; 89%). Disease-free survival (DFS), overall survival (OS), and risk factors were analyzed. RESULTS: Median follow up was 37 months. Patients with huge HCC were more likely to be symptomatic, positive for preoperative portal vein thrombosis, longer surgical time, more blood loss and transfusions, and significantly shorter median OS and DFS. Both groups had similar postoperative mortality and morbidity rates. In the huge HCC, multivariate analysis identified two significant determinants of DFS (preoperative portal vein thrombosis on imaging and tumor-free margin less than 1 mm) and two significant determinants of OS (age over 80 and preoperative portal vein thrombosis). Even with positive margins, it still had no impact on OS. For DFS, 1 mm free margins appeared to be adequate. CONCLUSION: Tumor-free margin is an independent risk factor for recurrence but has no impact on OS. Surgical margin >1 mm is adequate in patients with tumors ≥10 cm. Postoperative close follow up, especially of distant metastasis, and appropriate treatment of recurrence by a multidisciplinary approach may improve prognosis.