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Purposes: The purposes of this study were to assess the correlation between the plasma level of Hsp90α and the clinicopathological characteristics of patients with liver cancer and compare the diagnostic efficacy of Hsp90α, AFP, CEA, and CA199 in HCC. Experimental design: A total of 200 individuals, including 140 patients with liver cancer or benign liver diseases and 60 healthy people, were enrolled for quantitative measurement of plasma Hsp90α by ELISA. Results: The plasma level of Hsp90α was significantly different between patients with liver cancer or benign liver diseases and healthy controls (P < 0.001). The sensitivity, specificity, and AUC (95% CI) of Hsp90α were 93.2%, 85.4%, and 0.931% (0.891–0.972%), respectively, when Hsp90α was applied to differentiate liver cancer patients and healthy controls. Significant positive correlations between the plasma Hsp90α level and clinicopathological characteristics such as the history of basic liver disease (P = 0.038), active stage of hepatitis (P = 0.039), Child-Pugh score (P < 0.001), size of focal liver lesions (P = 0.004), and extrahepatic metastasis (P < 0.001) were observed. AFP + Hsp90α was the best combination strategy for the auxiliary diagnosis of HCC, with a sensitivity of 95.7%, a specificity of 97.5%, and an AUC of 0.990 (0.976–1.000). The level of plasma Hsp90α decreased significantly (P < 0.001) after resection of tumor tissue. Conclusions: This study demonstrated that plasma Hsp90α levels are useful as a diagnostic biomarker in liver cancer and may predict the responses of patients with liver cancer to surgery. Some clinicopathological characteristics could affect the plasma Hsp90α levels. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is one of the worst prognoses amongst all malignant diseases. It is therefore of great significance to identify biomarkers with predictive clinical value for the prognosis and recurrence of PC. Methods: In our study, enzyme-linked immunosorbent assays (ELISA) were used to detect the expression of Exo-EphA2 in the serum of PC patients and controls. Kaplan–Meier curve and Cox regression analyses were used to evaluate the prognostic value of Exo-EphA2 expression in patients with primary and recurrent PC. Results: The level of serum Exo-EphA2 was significantly higher in the PC group when compared to that of the control group. High expression of Exo-EphA2 in PC was associated with shorter overall survival (OS) and proved to be a significant negative prognostic factor in the multivariate analysis (HR = 1.04, 95% CI: 1.00– 1.09, P < 0.001). Additionally, we found that the level of serum Exo-EphA2 in recurrent PC patients (first recurrence < 12 months) was positively correlated with the level of Exo-EphA2 at primary diagnosis. Multivariate analysis showed that a high expression of Exo-EphA2 in recurrent PC was associated with shorter recurrence-free survival (RFS) (HR = 1.41, 95% CI: 1.10– 1.70, P < 0.001). Conclusion: High expression of serum Exo-EphA2 represents a novel biomarker for a poor prognosis in PC patients. [ABSTRACT FROM AUTHOR]

Purpose: There are limited data regarding postoperative complications and autoimmune reactions caused by surgery in early-stage cervical cancer patients who underwent laparoscopic radical resection (LRR). This study aimed to investigate the therapeutic effect of LRR of cervical cancer patients and its effect on cytokines.Methods: 168 patients with cervical cancer were enrolled. The patients were divided into open group and laparoscopic group according to the random number table method, with 84 cases in each group. The surgical-related indexes and the incidence of complications of the two groups were observed, and the IFN-γ, TNF, and IL-1/2/4/6/8/10/12 levels in peripheral blood were compared before and after surgery in both groups.Results: The operation time of the patients in the laparoscopic group was significantly shorter than that in the open group (119.56 ± 45.26 vs. 206.36 ± 54.39, P < 0.01). The intraoperative blood loss in the laparoscopic group was significantly less than that in the open group (155.29 ± 57.58 vs. 529.58 ± 162.4, P < 0.01). The postoperative visual analog scale (VAS) score was also significantly lower than that in the open group (3.65 ± 0.88 vs. 6.32 ± 1.12, P < 0.01). There was no significant difference in the incidence of complications between the two groups. The degree of inflammatory cytokines changes caused by LRR was less than that of open radical surgery (P < 0.001).Conclusions: LRR surgery has less stress on patients with early cervical cancer than open surgery within 5 days after surgery, which has certain reference value for early cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The calculation of the tumor burden score (TBS) is not perfect because the bilobar spread of colorectal liver metastasis (CRLM) is neglected. The identification of an ideal prognostic scoring system for CRLM remains controversial. Materials and Methods: Patients who underwent curative intent liver resection for CRLM from one medical center were enrolled in cohort 1 (787 patients) and cohort 2 (162 patients). Tumor relapse‐free survival (RFS) was the main outcome. A Cox regression model was used to identify independent predictors of prognosis. The time‐dependent area under the curve, calibration curve, and C‐index were employed to validate the predictive ability of the survival model. Results: Modified TBS (mTBS) was established by a mathematical equation with parameters including CRLM size, CRLM number, and unilobar or bilobar metastasis. Five preoperative predictors of worse RFS were identified in cohort 1 and incorporated into the Comprehensive Evaluation of Relapse Risk (CERR) score: KRAS/NRAS/BRAF‐mutated tumor (1 point); node‐positive primary (1 point); extrahepatic disease (1 point); carcinoembryonic antigen level > 200 ng/mL or carbohydrate antigen 19‐9 (CA19‐9) >200 U/mL (1 point); and mTBS between 5 and 11 (1 point) or 12 and over (2 points). Patients in cohort 1 were stratified by their CERR score into risk groups: the high‐risk group (CERR score 4 or more), the medium‐risk group (CERR score 2–3), and the low‐risk group (CERR score 0–1). Importantly, internal validation in cohort 1 and further validation in cohort 2 both showed the superior discriminatory capacity of the CERR score. Conclusion: mTBS should be promoted. The CERR score is a powerful prognostic tool that can help determine optimal clinical management strategies. Implications for Practice: This work resulted in the successful modification of the tumor burden score and development of a comprehensive and practical prognostic scoring system—the Comprehensive Evaluation of Relapse Risk (CERR) score. The CERR score, with a better prognostic discriminatory ability, outperformed the Fong score. Perhaps more importantly, the CERR score is a powerful prognostic tool because it unified the most consistently reported prognostic factors. Therefore, the CERR score can assist doctors in determining optimal clinical management strategies. The tumor burden score (TBS) is a prognostic indicator of the cumulative effect of tumor size and tumor number on survival; however, the score is not perfect because bilobar spread of colorectal liver metastases (CRLM) is neglected. This article reports a modified TBS that unifies three parameters (CRLM size, CRLM number, and unilobar/bilobar metastasis) and development of a more comprehensive and practical prognostic scoring system—the Comprehensive Evaluation of Relapse Risk (CERR) score. [ABSTRACT FROM AUTHOR]

Background: This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy and chemoradiotherapy in stage II or stage III thoracic esophageal squamous cell carcinoma (TESCC) patients who underwent curative (R0) esophagectomy. Methods: A total of 272 TESCC patients who underwent radical esophagectomy from 2007 to 2016 were included in this retrospective analysis. All cases were pathologically confirmed with stage II or III disease and 148 patients received postoperative chemoradiotherapy (CRT), while the remaining 124 patients received postoperative radiotherapy (RT) alone. Results: In CRT and RT groups, the three‐year overall survival rates were 51.3 versus 31.5% (P < 0.01) and the median overall survival (OS) was 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively (P = 0.213). Three‐year disease‐free survival rates (DFS) were 30.5% versus 15.9% (P = 0.008), while the median DFS times were 26 months (95% CI, 17.7 to 34.3 months) and 19 months (95% CI, 16.4 to 21.6 months), respectively (P = 0.156). Univariate and multivariate analyses showed AJCC (American Joint Committee on Cancer seventh edition) stage and N stage were independent prognostic factors for overall survival, while the N stage was an independent prognostic factor for disease‐free survival. Conclusions: Postoperative chemoradiotherapy led to one‐ and three‐year overall survival benefits along with an obvious increase in treatment side effects for stage II to III TESCC patients, with no further improvement in five‐year survival. However, the chemoradiotherapy benefits mainly favor stage III,number of resected lymph nodes less than 15, younger (less than 60 years old) and smoking patients. [ABSTRACT FROM AUTHOR]

Background We compared the efficacy of postoperative chemoradiation ( POCRT) and surgery alone ( SA) in patients with stage II-III esophageal squamous cell carcinoma ( ESCC). Methods We analyzed the records of 265 patients with stage II-III ESCC who had undergone transthoracic esophagectomy and lymphadenectomy; 105 patients received POCRT, while 160 had SA. Results The median disease-free survival ( DFS) of the whole cohort was 22 months (95% confidence interval [ CI], 19.2-24.8), while the median overall survival ( OS) was 29 months (95% CI 25.5-32.5). The median DFS of the SA group was 21 months (95% CI 17.9-24.0), while that of the POCRT group was 29 months (95% CI 18.8-31.2; P = 0.048). Consistently, patients in the POCRT group had significantly longer median OS than patients in the SA group (34 vs. 26 months, respectively). Subgroup analysis showed that in patients with positive lymph nodes, pathological stage III, T3-4 stage, and poorly differentiated carcinoma, POCRT was apparently more effective than SA at improving OS and decreasing the rates of local recurrence and distant metastasis. Multivariate analysis demonstrated that lymph node involvement and treatment with POCRT were independent prognostic factors. Conclusion Compared with SA, POCRT may be more effective in improving OS and decreasing the rates of local recurrence and distant metastasis, particularly in stage III or positive lymph node stage II-III ESCC patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this trial was to compare the Enhanced Recovery After Surgery (ERAS) program with conventional perioperative management in patients who underwent radical resection for colorectal cancer. Methods: A combination of evidence-based and consensus methodology was used to develop the ERAS protocol. Five hundred ninety-seven consecutive patients who underwent elective colorectal resection were randomized to either the ERAS ( n = 299) or the control group ( n = 298). Outcomes relating to nutrition and metabolism index, stress index, and recovery index were measured and recorded. Results: Demographic and operative data were similar between the two groups. Patients in the ERAS group showed improved nutritional status when compared with those of the control group. On postoperative day (POD) 1, the HOMA-IR (insulin resistance index) of the ERAS group was lower than that of the control group ( p < 0.001). The cortisol level of the control group was elevated on both POD 1 ( p = 0.007) and POD 5 ( p = 0.002) compared to the preoperative level. However, the cortisol level of the ERAS group was not increased until POD 5 ( p = 0.001). Reduced levels of TNF-α, IL-1β, IL-6, and IFN-γ in the ERAS group indicated less postoperative stress responses. In addition, ERAS was associated with accelerated recovery of gastrointestinal function. The postoperative length of stay ( p < 0.001) and expense ( p < 0.001) for the ERAS group were reduced in comparison to the controls. Twenty-eight cases in the control group and twenty-nine in the ERAS group suffered complications, which was not significantly different. Conclusion: The ERAS protocol attenuates the surgical stress response and accelerates postoperative recovery without compromising patient safety. [ABSTRACT FROM AUTHOR]

Background: The existence of cancer stem cells in hepatocellular carcinoma (HCC) has been verified by characterizing side population (SP) cells based on efflux of Hoechst 33342 dye from stem cells. Recent advances in microRNA (miRNA) biology have revealed that miRNAs play an important role in embryonic development and tumorigenesis. However, it is still unclear which miRNAs participate in the neoplastic transformation of liver cancer stem cells (LCSCs) during hepatocarcinogenesis. Methods: To identify the unique set of miRNAs differentially regulated in LCSCs, we applied SP sorting to primary cultures of F344 rat HCC cancer cells treated with diethylnitrosamine (DEN) and normal syngenic fetal liver cells, and the stem-like characteristics of SP cells were verified through detecting expression of CD90.1, AFP and CK-7. Global miRNA expression profiles of two groups of SP cells were screened through microarray platform. Results: A total of 68 miRNAs, including miR-10b, miR-21, miR-470*, miR-34c-3p, and let-7i*, were identified as overexpressed in SP of HCC cells compared to fetal liver cells. Ten miRNAs were underexpressed, including miR- 200a* and miR-148b*. These miRNAs were validated using stem-loop real-time reverse transcriptase polymerase chain reaction (RT-PCR). Conclusions: Our results suggest that LCSCs may have a distinct miRNA expression fingerprint during hepatocarcinogenesis. Dissecting these relationships will provide a new understanding of the function of miRNA in the process of neoplastic transformation of LCSCs. [ABSTRACT FROM AUTHOR]

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Background: N6-methyladenosine (m6A) modification plays crucial roles in cancers. However, its alteration in colorectal cancer (CRC) is still poorly described. The purpose of this study is to explore the change of m6A modification and the function of m6A binding protein YTHDC2 in CRC. Methods: The global level of m6A modification was detected by mass spectrometry and dot blotting assay. The expression of YTHDC2 was investigated using The Cancer Genome Atlas and using real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry based on CRC tissues. Kaplan–Meier analysis and Cox proportional hazards regression were performed to analyze the prognostic value of YTHDC2. RNA immunoprecipitation (RIP)-seq and m6A immunoprecipitation (MeRIP)-seq were used to explore the direct targets of YTHDC2. Gene oncology (GO) and Gene Set Enrichment Analysis (GSEA) were used to explore the pathways that could be influenced by YTHDC2. Results: No significant difference was observed in the global level of m6A modification on total RNA or mRNA between CRC and adjacent nontumor tissues. We further found a significant decreasing of YTHDC2 in CRC tissues. Kaplan–Meier analysis indicated that lower expression of YTHDC2 was related to the worse disease-free survival and overall survival. In addition, lower expression of YTHDC2 was an independent worse prognostic factor in univariate and multivariate Cox regression analysis. Using YTHDC2-RIP-seq and MeRIP-seq, we identified that YTHDC2 could participate in several important biological signal pathways. Conclusions: In summary, this study suggested that the global level of m6A did not change in CRC and identified that lower YTHDC2 as a prognostic marker for worse survival of CRC. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) progression is frequently detected in patients with favorable initial responses to first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), but data are incomplete with respect to clinical features and prognostic factors of CNS failure in this population. We retrospectively evaluated 420 advanced nonsmall cell lung cancer (NSCLC) patients treated with first-generation EGFR-TKI for over 3 months. We analyzed CNS progression of these patients, defining as newly developed CNS metastases or progression of preexisting brain lesions after EGFR-TKI treatment. Of the 420 patients, 99 (23.6%) with CNS progression after EGFR-TKI initiation were identified. The median time to CNS progression was 12 months (95% confidence interval [CI] 10.5-13.5). Patients with L858R mutation were more likely to experience CNS failure than those with exon 19 deletion (p = 0.008). For patients with previous brain metastases (BM), the median time to CNS progression of patients with EGFR-TKI and local CNS therapy was significantly longer than those treated with EGFR-TKI alone (14.0 months vs. 11.2 months; p = 0.016). The median survival time after CNS progression was 11.2 months (95% CI 8.8-13.5). L858R mutation, multiple BM progression and CNS with other site failures were negative prognostic factor, while localized CNS therapy was the only significant favorable prognostic factor for overall survival after CNS progression. For advanced NSCLC patients treated successfully with first-generation EGFR-TKI, careful monitoring for CNS progression should be considered, especially for those with L858R mutation. Localized CNS therapy should be considered for CNS progression. [ABSTRACT FROM AUTHOR]