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// Naoko Komura 1 , Seiji Mabuchi 1 , Eriko Yokoi 1 , Kotaro Shimura 1 , Mahiru Kawano 1 , Yuri Matsumoto 1 and Tadashi Kimura 1 1 Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan Correspondence to: Seiji Mabuchi, email: smabuchi@gyne.med.osaka-u.ac.jp Keywords: ovarian cancer; prognostic nutritional index; clinical stage; survival; prognostic factor Received: July 23, 2018 Accepted: April 14, 2019 Published: June 04, 2019 ABSTRACT Objective We retrospectively investigated the prognostic significance of the pretreatment prognostic nutritional index (PNI) in patients with epithelial ovarian cancer (EOC) according to the clinical stage. Methods The baseline characteristics and clinical outcomes of 308 EOC patients were collected and retrospectively reviewed. PNI was defined as 10 × serum albumin (g/L) + 0.005 × lymphocyte count (per mm 3 ) in the peripheral blood. The cut-off value of PNI was defined by time-dependent receiver operating characteristics (ROC) analysis. Univariate or multivariate analysis was conducted to evaluate the association between pretreatment PNI, progression-free survival (PFS), and disease-specific survival (DSS) according to the clinical stage. Results The cut-off value of PNI was defined as 44.7 in early-stage patients and 42.9 in advanced-stage patient by ROC analysis, respectively. Although decreased PNI was not associated with short PFS or DSS in early-stage patients, it was significantly correlated with short PFS (p

// Wei Xu 1, * , Rui Guo 2, * , Gang Xu 1 , Lejia Sun 1 , Dandan Hu 1 , Haifeng Xu 1 , Huayu Yang 1 , Xinting Sang 1 , Xin Lu 1 and Yilei Mao 1 1 Professor of Surgery, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2 Professor of Surgery, Department of Surgery, Peking Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China * These authors have contributed equally to this work (co-first author) Correspondence to: Yilei Mao, email: pumch-liver@hotmail.com ; xuwei.com.cn@163.com Keywords: hepatocellular carcinoma; hepatectomy; clinical stage; early recurrence; prognosis Received: May 19, 2017 Accepted: November 13, 2017 Published: November 30, 2017 ABSTRACT Background: Although patients with Barcelona clinic liver cancer stage B or C hepatocellular carcinoma derive survival benefit from hepatectomy, prognostic factors and management after curative resection are unclear. This study aims to evaluate predictive factors, therapy and prognosis of intra-hepatic recurrences after curative resection of Barcelona clinic liver cancer stage B or C hepatocellular carcinoma. Methods: We retrospectively analyzed 397 patients with Barcelona clinic liver cancer stage B or C hepatocellular carcinoma who underwent curative resections from January 1989 to October 2011. Intra-hepatic recurrences were classified into early (

Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to FGFR inhibitors. The aim of this study was to investigate the frequency and the prognostic impact of FGFR1 amplification in patients with resected esophageal squamous cell carcinoma (ESCC) by using fluorescent in situ hybridization. Microarrayed paraffin embedded blocks were constructed, and the cohort of tissues came from 506 patients with ESCC. FGFR1 high amplification (FGFR1high ) was defined by an FGFR1/centromere 8 ratio of ≥ 2.0, or average number of FGFR1 signals/tumor cell nucleus ≥ 6.0, or percentage of tumor cells containing ≥ 15 FGFR1 signals, or large cluster in ≥ 10% of cancer cells. FGFR1 low amplification was defined by ≥ 5 FGFR1 signals in ≥ 50% of cancer cells. Kaplan-Meier curves with log-rank tests and Cox proportional hazards model were used to analyze patients' survival. Among 506 patients, high amplification, low amplification, and disomy were detected in 8.7%, 3.6% and 87.7%, respectively. In general, the FGFR1high group trended towards worse disease-free survival (DFS) and overall survival (OS) compared to the FGFR1 low amplification/disomy (FGFR1low/disomy ) group (DFS, P=0.108; OS, P=0.112), but this trend was amplified for patients with DFS ≥ 30 months (DFS, P=0.009; OS, P=0.007). Furthermore, when patients were stratified into stage I-II and stage III-IV, the FGFR1high group directly presented with adverse DFS and OS than the FGFR1low/disomy group in stage I-II patients (DFS, P=0.019; OS, P=0.034), especially with DFS ≥ 30 months (DFS, P=0.002; OS, P=0.001). However, for patients in stage III-IV, FGFR1high had no effect on prognosis regardless of DFS time. FGFR1high occurs in a minority of ESCC, and it predicts delayed poor prognosis in stage I and II ESCC patients.

// Xiao-Quan Xu 1, * , Gao Ma 1, * , Yan-Jun Wang 1 , Hao Hu 1 , Guo-Yi Su 1 , Hai-Bin Shi 1 and Fei-Yun Wu 1 1 Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Fei-Yun Wu, email: wfy_njmu@163.com Keywords: nasopharyngeal carcinoma, clinical stage, magnetic resonance imaging, diffusion kurtosis imaging, histogram Received: January 17, 2017 Accepted: April 16, 2017 Published: May 03, 2017 ABSTRACT Purpose: To evaluate the correlation between histogram parameters derived from diffusion-kurtosis (DK) imaging and the clinical stage of nasopharyngeal carcinoma (NPC). Results: High T-stage (T3/4) NPC showed significantly higher K app-mean ( P = 0.018), K app-median ( P = 0.029) and K app-90th ( P = 0.003) than low T-stage (T1/2) NPC. High N-stage NPC (N2/3) showed significantly lower Dapp-mean ( P = 0.002), Dapp-median ( P = 0.002) and Dapp-10th ( P < 0.001) than low N-stage NPC (N0/1). High AJCC-stage NPC (III/IV) showed significantly lower D app-10th ( P = 0.038) than low AJCC-stage NPC (I/II). ROC analyses indicated that Kapp-90th was optimal for predicting high T-stage (AUC, 0.759; sensitivity, 0.842; specificity, 0.607), while Dapp-10th was best for predicting high N- and AJCC-stage (N-stage, AUC, 0.841; sensitivity, 0.875; specificity, 0.807; AJCC-stage, AUC, 0.671; sensitivity, 0.800; specificity, 0.588). Materials and Methods: DK imaging data of forty-seven consecutive NPC patients were retrospectively analyzed. Apparent diffusion for Gaussian distribution (D app ) and apparent kurtosis coefficient (K app ) were generated using diffusion-kurtosis model. Histogram parameters, including mean, median, 10th, 90th percentiles, skewness and kurtosis of D app and K app were calculated. Patients were divided into low and high T, N and clinical stage based on American Joint Committee on Cancer (AJCC) staging system. Differences of histogram parameters between low and high T, N and AJCC stages were compared using t test. Multiple receiver operating characteristic (ROC) curves were used to determine and compare the value of significant parameters in predicting high T, N and AJCC stage, respectively. Conclusions: DK imaging-derived parameters correlated well with clinical stage of NPC, therefore could serve as an adjunctive imaging technique for evaluating NPC.

// Ren Zhao 1, * , Zhen Cai 2, * , Sheng Li 3, * , Yong Cheng 4 , Hua Gao 5 , Fang Liu 6 , Shiyang Wu 6 , Suyan Liu 6 , Yan Dong 6 , Lei Zheng 2 , Wenbin Zhang 7 , Xiaojun Wu 8 , Xueqing Yao 3 1 Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 Department of Laboratory Medicine, Sino-UK Circulating Biomarkers’ Exploration and Detection Center, Nanfang Hospital, Southern Medical University, Guangzhou, China 3 3Department of General surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China 4 Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China 5 Department of General Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China 6 SurExam Bio-Tech Co., Guangzhou, China 7 Department of Gastrointestinal Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China 8 Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China * These authors are contributed equally to this work Correspondence to: Xiaojun Wu, email: wuxj_1@sina.com Xueqing Yao, email: Yjb9211@21cn.com Keywords: colorectal cancer, circulating tumor cells, epithelial-mesenchymal transition, clinical stage, metastasis Received: September 27, 2016 Accepted: December 13, 2016 Published: December 21, 2016 ABSTRACT Circulating tumor cells (CTCs) with phenotypic hallmarks of epithelial-mesenchymal transition (EMT) reportedly contribute to tumor metastasis in different cancer types. We therefore evaluated the expression of EMT markers in CTCs obtained from a large cohort of Chinese patients with colorectal cancer (CRC) and investigated their clinical relevance. The CanPatrol TM CTC enrichment technique was used to isolate and classify CTCs. CTCs were detected in 1046 of 1203 patients (86.9%), and three phenotypes were identified based on the expression of epithelial and mesenchymal markers: epithelial CTCs, biophenotypic (epithelial/mesenchymal) CTCs, and mesenchymal CTCs. Total CTC numbers positively correlated with both clinical stage and lymph node metastasis and distant metastasis. Furthermore, both biophenotypic and mesenchymal, but not epithelial, CTCs, correlated with the above parameters, suggesting CTCs displaying a mesenchymal phenotype denote more aggressive disease and metastatic potential. This is the first study to demonstrate a significant correlation between CTCs displaying a mesenchymal phenotype and both clinical stage and metastasis in a large cohort of patients with CRC. Our findings suggest that assessment of not only epithelial, but also mesenchymal markers in CTC analyses may offer valuable assistance for tumor staging and metastasis evaluation in patients with CRC.

// Peng-Zhou Kong 1, 2, * , Guang-Ming Li 3, * , Yin Tian 4, 5 , Bin Song 1, 6 , RuYi Shi 1, 7 1 Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, China 2 Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China 3 School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China 4 Department of General Surgery, The Second Hospital of JingZhou, JingZhou 434000, China 5 Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 6 Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan 030001, China 7 Department of Cell Biology and Genetics, Shanxi Medical University, Taiyuan 030001, China * Both authors have shared co-first authorship Correspondence to: Peng-Zhou Kong, email: kongpzh@163.com Keywords: FOXF2, non-small-cell lung carcinoma, survival, clinical stage Received: April 13, 2016 Accepted: July 10, 2016 Published: July 28, 2016 ABSTRACT Background: Forkhead box F2 ( FOXF2 ) is relatively limited to the adult lung, but its contribution to non-small cell lung cancer (NSCLC) prognosis is unclear. Results: FOXF2 mRNA levels in NSCLC were lower than that in paired normal lung tissues ( P = 0.012). The FOXF2 low patients had shorter survival time than the FOXF2 high patients ( P = 0.024) especially in stage I ( P = 0.002), chemotherapy ( P = 0.018) and < 60 age groups ( P = 0.002). Lower FOXF2 mRNA levels could independently predict poorer survival for patients with NSCLC (HR = 2.384, 95% CI = 1.241–4.577; P = 0.009), especially in stage I (HR =4.367, 95% CI =1.599–11.925; P = 0.004). The two independent datasets confirmed our findings. Methods: We examined FOXF2 mRNA levels in 84 primary NSCLC and 8 normal lung tissues using qRT-PCR. Rank-sum tests and chi-square tests were used to assess the differences among groups with various clinicopathological factors. Kaplan-Meier tests were used to compare survival status in patients with different FOXF2 mRNA levels. Cox proportional hazards regression model was used to evaluate the predictive value of FOXF2 mRNA level in NSCLC patients. Independent validation was performed using an independent dataset (98 samples) and an online survival analysis software Kaplan-Meier plotter (1928 samples). Conclusions: Our results demonstrated that decreased FOXF2 expression is an independent predictive factor for poor prognosis of patients with NSCLC, especially in stage I NSCLC.

Objective This study aims to investigate the expression and significance of p57kip2 and cyclinD1 in gastric cardia adenocarcinoma (GCA). p57kip2 is a negative regulator in the cell cycle. On the contrary, cyclinD1 is a positive regulator of cell cycle progression. Methods Thirty-two cases of GCA tissues and adjacent non-cancerous tissues were collected for this study. Immunohistochemistry and fluorescence qualitative PCR was used to determine the level of p57kip2 and cyclinD1 in GCA and its adjacent non-cancerous tissues. Furthermore, the correlation between the mRNA/protein and GCA clinical pathologic parameters were analyzed, and the relationship of p57kip2 and cyclinD1 in GCA were also evaluated. Results The expression of p57kip2 significantly lower in GCA (P = 0.036), and there was a significant correlation in the different degrees of differentiation (P < 0.05). Furthermore, median survival time was 41 months for patients with high mRNA expression of p57kip2. This was longer compared to patients with low mRNA expression of P57kip2 (37 months, X2 = 4.788, P = 0.029).The expression of cyclinD1 was significantly higher in GCA(P = 0.002), and was significant correlated to clinical stage(P

Background MCL1 copy number variations have been reported to be associated with cancer prognosis in several cancers. However, the role of MCL1 gain has not yet been determined in esophageal squamous cell carcinomas (ESCC). Methods Fluorescence in situ hybridization (FISH) for MCL1 was performed on 262 ESCC samples using tissue microarray (TMA). Results The median age of ESCC patients was 62 years (range 37–83), with frequencies between women (16.4%) and men (83.6%). Of the 262 tumors, 77 tumors (29.4%) had high MCL1 gain. In the multivariate analysis, lymph node metastasis (HR: 3.236, P

// Dongxian Jiang 1, * , Qi Song 1, * , Haixing Wang 1 , Jie Huang 1 , Hao Wang 2 , Jun Hou 1 , Xiaojing Li 1 , Yifan Xu 1 , Akesu Sujie 1 , Haiying Zeng 1 , Lijie Tan 2 , Yingyong Hou 1, 3 1 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China 2 Department of thoracic surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China 3 Department of Pathology, School of Basic Medical Sciences & Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China * These authors have contributed equally to this work Correspondence to: Yingyong Hou, email: houyingyong@aliyun.com Keywords: PD-L1 expression, clinical stage, lymph node metastasis, prognostic marker, ESCC Received: August 15, 2016 Accepted: November 22, 2016 Published: December 26, 2016 ABSTRACT Accumulating evidence has shown that PD-L1 expression is associated with clinicopathological features in various human malignancies. We searched for correlations between PD-L1 expression and clinicopathological data in esophageal squamous cell carcinoma (ESCC) patients. PD-L1 expression in primary tumors from 278 patients was evaluated using immunohistochemistry (IHC) in ESCC tissue microarray. Survival curves were constructed by using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. Overall, tumoral PD-L1 expression (≥10%, 20% or 30% as cut-off value) was associated with favorable DFS and OS upon multivariate analysis. When the patients stratified into stage I-II (168, 60.4%) and stage III-IV (110, 39.6%), or with lymph node metastasis (133, 47.8%), the prognostic role was not consistent. In patients with stage I-II disease, tumoral PD-L1 expression (≥5%, 10%, 20% or 30%) was associated with better DFS and OS upon multivariate analysis. In patients without lymph node metastasis, tumoral PD-L1 expression (≥1%, 5%, 10%, 20%, or 30%) was associated with improved DFS and OS in univariate or multivariate analysis. However, PD-L1 expression was not correlated with prognosis in patients with stage III-IV disease or with lymph node metastasis. Our results for the first time showed the prognostic role of tumoral PD-L1 expression was variable in different stages and lymph node status of ESCC. Tumoral PD-L1 expression was independent favorable predictor in ESCC patients with Stage I-II disease or without lymph node metastasis, not in stage III-IV or lymph node metastasis.