Sex Differences in Early and Late Recurrence after Liver Resection of Hepatocellular Carcinoma (A Multicenter Study from China)

( Jiong-jie Yu ),( Ju-dong Li ),( Xin-fei Xu ),( Zhen-li Li ),( Jun Han ),( Hao Xing ),( Han Wu ),( Jian-hong Zhong ),( Yi-sheng Huang ),( Ya- Hao Zhou ),( Ting-hao Chen ),( Hong Wang ),( Wei-min Gu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: There is a striking sex difference in the incidence of hepatocellular carcinoma (HCC), with a strong predominance for males. However, the impact of sex on the incidence of recurrence after curative resection of HCC remains controversial. Herein, we assess sex differences in the risks of recurrence and mortality for patients undergone curative resection of HCC. Methods: Data from 1,435 HCC patients undergone curative resection (1,228 males and 207 females) between 2004 and 2014 at five institutions in China were retrospectively analyzed. Patients’ baseline characteristics, operative variables, and rates of early recurrence (≤ 2 years after resection), late recurrence (> 2 years) and cancer-specific mortality (CSM) were evaluated and compared. Multivariable competing-risks regression analyses were performed to identify predictors associated with CSM, early and late recurrence. Results: The early recurrence rates between males and females were similar (43.3% vs. 42.0%, P=0.728), but the late recurrence and CSM rates in males were higher when compared to females (17.2% vs. 11.2%, P=0.044; 42.8% vs. 34.3%, P=0.022). Multivariable competing-risks regression analyses revealed no sex difference in early recurrence; however, males had significantly higher late recurrence rate [hazard ratio (HR), 1.752; 95% CI, 1.145-2.682; P=0.010] and CSM rate (HR, 1.307; 95% CI, 1.015-1.683; P=0.038) than females. Conclusions: Males had significantly higher late recurrence and CSM rates after curative resection of HCC than females. This suggests postoperative surveillance for HCC recurrence be varied by sex, especially for patients without recurrence at 2 years after resection.

Serum Tumor Marker Levels might have Little Significance in Evaluating Neoadjuvant Treatment Response in Locally Advanced Breast Cancer

Wang, Yu-Jie,Huang, Xiao-Yan,Mo, Miao,Li, Jian-Wei,Jia, Xiao-Qing,Shao, Zhi-Min,Shen, Zhen-Zhou,Wu, Jiong,Liu, Guang-Yu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

Study on modulation of near infrared radiation based on plasma photonic crystal

Hao Jiong-Ju,Xie Xun,Gu Ke-Da,Liu Yu-Jie,Xia Lei,Yang Hong-Wei 한국물리학회 2020 Current Applied Physics Vol.20 No.8

In this paper, a plasma photonic crystal (PPC) for infrared radiation modulation which is composed of indium tin oxide (ITO) and plasma is proposed. The performance of plasma photonic crystal in near infrared radiation modulation is researched by transfer matrix method (TMM). The simulation results show that the near infrared radiation pass band can be adjusted by the changing of plasma frequency of plasma. The reflection to near infrared radiation by plasma photonic crystal increases with plasma frequency and that of absorption decreases. In addition, the modulation performance of the plasma photonic crystal at different incidence wave angles is also studied. The results show that the incident wave angles have little effect on the transmission of plasma photonic crystal in near infrared band. The reflection of the plasma photonic crystal to near infrared radiation decreases with increasing of the incident wave angle, but that of the absorption increases with the incident wave angle. Therefore, the proposed plasma photonic crystal has a potential application in tunable near infrared filter devices.

Risk Factors, Patterns, and Outcomes of Late Recurrence after Liver Resection for Patients with Hepatocellular Carcinoma (Analysis of a Multicenter Cohort over 15 Years)

( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Hao Xing ),( Jun Han ),( Zhen-li Li ),( Han Wu ),( Han Zhang ),( Jian-hong Zhong ),( Yi- Sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Late recurrence (> 2 years) after liver resection of hepatocellular carcinoma (HCC) is usually considered as multi-centric tumors or de novo cancer formation. We aimed to investigate risk factors, patterns and outcomes of late recurrence after HCC resection. Methods: From a multicenter database from 2001 to 2015, 734 patients who were alive and recurrence-free at 2 years after curative resection of initial HCC were enrolled into this retrospective study. Univariate and multivariate Cox-regression analysis were used to identify independent risk factors of late recurrence. Patterns, treatments and outcomes of late recurrence were investigated and analyzed. Results: During a median follow-up of 78.0 months after surgery, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that cirrhosis, macroscopic vascular invasion, satellites, and tumor size > 5cm were independent risk factors of late recurrence. Among them, 273 (90.1%) were sole intrahepatic recurrence, 30 (9.9%) were concurrent intrahepatic and extrahepatic recurrence, and none of them was sole extrahepatic recurrence; 165 (54.4%) patients received curative treatments for recurrent HCC, including re-resection, transplantation and local ablation. Multivariate analysis showed regular postoperative surveillance and receiving curative treatments were two independent protective factors of prolonging survival for those patients with late recurrence. Conclusions: Late recurrence is correlated with cirrhosis and certain tumor-related characteristics of initial HCC. The patterns of late recurrence suggest that postoperative surveillance after 2 years of surgery could be adjusted and more targeted. Regular postoperative surveillance improves the probability to receive curative treatments again, yielding to better outcomes for patients with late recurrence.

Risk Factors for Surgical Site Infections after Liver Resec-tion (A Multivariate Analysis of 6,132 Patients)

( Li-yang Sun ),( Jiong-jie Yu ),( Ju-dong Li ),( Xin-fei Xu ),( Jia-he Wang ),( Bing Quan ),( Wen-tao Yan ),( Feng Shen ),( Chao Li ),( Lei Liang ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Surgical site infection (SSI) is a common postoperative complication and associated with an increased morbidity, hospital stay, and overall cost. The aim of the present study was to identify risk factors for SSIs after hepatic resection based on a large single-center cohort. Methods: A retrospective study was conducted of 6,132 patients who underwent liver resection without concomitant biliary reconstruction or gastrointestinal procedures between 2014 and 2016 at the largest hepatic center in China. The occurrences of SSI, classified as incisional SSI and organ/space SSI within 30 days after operation were investigated. Patient- and surgical-related risk variables were collected using standardized data collection form. A likelihood ratio forward regression model was used to assess the independent association of risk factors with SSI. Results: SSI developed in 587 patients (9.6%), including superficial/deep incisional SSI in 357 patients (5.8 %), and organ/ space SSI in 304 patients (5.0 %). Multivariate logistic regression analysis showed that obesity, diabetes mellitus, ASA score ≥ 2, liver cirrhosis, re-hepatectomy, hepatoliathiasis, and intraoperative blood transfusion were independent risk factors of overall SSI. However, incisional and organ/space SSI differed from each other with respect to risk factors. Among a variety of risk factors, hepatolithiasis, liver cirrhosis, and intraoperative blood transfusion were consistently associated with both incisional and organ/space SSI. Conclusions: SSI is a common complication after liver resection, and more caution should be taken in patients with hepatolithiasis or liver cirrhosis. Prevention strategies focusing on factors associated with SSI is necessary in order to reduce SSI after liver resection.

Association of Family History with Cancer Recurrence and Survival in Patients with Hepatitis B-Related Hepatocellular Carcinoma (A Propensity Score Matching Analysis)

( Ju-dong Li ),( Xin-fei Xu ),( Jiong-jie Yu ),( Zhen-li Li ),( Hao Xing ),( Han Wu ),( Han Zhang ),( Chao Li ),( Ming-da Wang ),( Meng-chao Wu ),( Wan-yee Lau ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: A family history of liver cancer is regarded as a risk factor for hepatocellular carcinoma (HCC) development. We investigated the association between family history and cancer recurrence and survival in patients with hepatitis B virus (HBV)- related HCC. Methods: Patients who underwent curative resection of HBV-related HCC between 2003 and 2013 from a tertiary hepatobiliary center in China were enrolled in this study. A family history was defined as a self-reported history of primary liver cancer in the first-degree relatives. Propensity score matching (PSM) and multivariable Cox-regression analyses were performed to compare the overall survival (OS) and recurrence-free survival (RFS) between patients with and without a family history of liver cancer. Results: Of 1,112 patients, 183 patients (16.5%) had a family history of liver cancer. A family history was not associated with OS and RFS (P=0.994 and 0.428) in the entire cohort. Using PSM, 179 pairs of patients with and without a family history but with comparable baseline characteristics and operative variables were created. A family history was associated with decreased OS and RFS (P=0.042 and 0.006) in the PSM cohort. On multivariable Cox-regression analyses, a family history was significantly associated with decreased OS (HR: 1.574, 95% CI: 1.171-2.116, P=0.003) and RFS (HR: 1.534, 95% CI: 1.176-2.002, P=0.002) after adjusting for other prognostic factors. Conclusions: A family history of liver cancer was associated with decreased OS and RFS rates after curative resection in patients with HBV-related HCC.

Is Surgical Resection Justified for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus? (A Systematic Review and Meta-Analysis)

( Liang Lei ),( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Zhen-li Li ),( Jun Han ),( Han Zhang ),( Hao Xing ),( Han Wu ),( Ming-da Wang ),( Chao Li ),( Zheng Wang ),( Feng Shen ),( Meng-chao Wu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very poor. According to the BCLC treatment recommendations, sorafenib or other palliative treatment (PT) is recommended as the first-line therapy when it happens. In real world, however, a significant number of selected patients with HCC and PVTT suffered from surgical resection (SR). Methods: PubMed, Embase, Medline and Cochrane library were searched for studies comparing SR with PT (including TACE, sorafenib, etc.) for HCC with PVTT, which were published before September 2017. Results: 4,810 patients from 7 studies were enrolled in this meta-analysis, which divided into the SR group (n = 2,344) and the PT group (n = 2476). When compared with the PT group, the pooled hazard ratio (HR) for the 1, 3 and 5-year OS rates of the SR group were 0.56 (95% CI 0.52-0.60, P=0.03), 0.56 (95% CI 0.53-0.59, P<0.001) and 0.55 (95% CI 0.54-0.57, P<0.001). For subgroup analysis, when compared with the mere TACE group, the pooled HR for the 1, 3 and 5-year OS rates of the SR group were 0.54 (95% CI 0.43-0.67, P=0.81), 0.75 (95% CI 0.65-0.87, P=0.25) and 0.76 (95% CI 0.67-0.88, P=0.25). Conclusions: This meta-analysis demonstrated SR had better OS than TACE or other palliative therapy for HCC with PVTT. SR may be suitable as the first-line treatment for selected patients with resectable HCC and removable PVTT.

Preoperative Prealbumin Level as an Independent Predictor of Long-Term Prognosis after Curative Liver Resection of Hepatocellular Carcinoma (a Multicenter Study of 1,483 Patients)

( Ju-dong Li ),( Xin-fei Xu ),( Jiong-jie Yu ),( Jia-he Wang ),( Li- Yang Sun ),( Wen-tao Yan ),( Bing Quan ),( Jian-hong Zhong ),( Yi-sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ),( W 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Serum prealbumin is more sensitive to profile nutritional status and liver function than albumin, which could hardly be affected by infusion supplement. This study aims: to identify the relationship between preoperative prealbumin level and the long-term prognosis after curative resection of hepatocellular carcinoma (HCC). Methods: Patients undergone HCC curative resection between 2001 and 2014 at six institutions in China were enrolled. By using 170 mg/dl as cut-off value of serum prealbumin level, these patients were divided into the low and normal preoperative prealbumin groups. The overall survival (OS) and recurrence-free survival (RFS) were analyzed and compared. Univariable and multivariable Cox-regression analyses were performed to identify predictive factors of OS and RFS. Results: Among 1,483 patients, 437 (29.5%) had a low prealbumin level within a week before surgery. The 1-, 3-, and 5-year OS and RFS rates of patients in the low prealbumin group were 83.8, 57.0, and 31.1%, and 67.0, 39.8, and19.9%, respectively, which was significantly poorer than those in the normal group (93.0, 75.5, and 42.6%, and 77.0, 56.4, and 28.4%, both P<0.001). Multivariable analyses revealed that preoperative prealbumin level, but not albumin level, was an independent predictor of OS (HR, 1.789; 95% CI: 1.544 -2.072, P<0.001) and RFS (HR, 1.420; 95% CI: 232-1.636, P<0.001). Conclusions: Preoperative prealbumin level is useful for predicting long-term prognosis in patients undergoing liver resection for HCC. Prealbumin may be suitable to displace albumin, yielding to an updated Child-Pugh grade for accessing liver function.

Phosphorylation of DYNLT1 at Serine 82 Regulates Microtubule Stability and Mitochondrial Permeabilization in Hypoxia

Xue Xu,Yue-sheng Huang,Qiong Zhang,Jiong-yu Hu,Dong-xia Zhang2,Xu-pin Jiang,jie-zhi Jia,Jing-ci Zhu 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.4

Hypoxia-induced microtubule disruption and mitochondrial permeability transition (mPT) are crucial events leading to fatal cell damage and recent studies showed that microtubules (MTs) are involved in the modulation of mitochondrial function. Dynein light chain Tctex-type 1 (DYNLT1) is thought to be associated with MTs and mitochondria. Previously we demonstrated that DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, which indicates a role of DYNLT1 in hypoxic cytoprotection. But the underlying regulatory mechanism of DYNLT1 remains illusive. Here we aimed to investigate the phosphorylation alteration of DYNLT1 at serine 82 (S82) in hypoxia (1% O2). We therefore constructed recombinant adenoviruses to generate S82E and S82A mutants, used to transfect H9c2 and HeLa cell lines. Development of hypoxia-induced mPT (MMP examining, Cyt c release and mPT pore opening assay), hypoxic energy metabolism (cellular viability and ATP quantification), and stability of MTs were examined. Our results showed that phosph-S82 (S82-P) expression was increased in early hypoxia; S82E mutation (phosphomimic) aggravated mitochondrial damage, ele-vated the free tubulin in cytoplasm and decreased the cellular viability; S82A mutation (dephosphomimic) seemed to diminish the hypoxia-induced injury. These data suggest that DYNLT1 phosphorylation at S82 is involved in MTs and mitochondria regulation, and their interaction and cooperation contribute to the cellular hypoxic tolerance. Thus, we provide new insights into a DYNLT1 mechanism in stabilizing MTs and mitochondria, and propose a potential therapeutic target for hypoxia cytoprotective studies.