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Colorectal cancer is the second leading cause of cancer-related death across the world. So far, screening method for colorectal cancer are limited to blood test, imaging test, and digital rectal examination, that are either invasive or ineffective. So, this study aims to explore novel, more convenient and effective diagnostic method for colorectal cancer. First, the experiment cohort was randomly split to train set and test set, and LC-MS-based plasma lipidomics was applied to identify lipid features in colorectal cancer. Second, univariate and multivariate analyses were performed to screen for significantly differentially expressed lipids. Third, single-lipid-based ROC analysis and multiple-lipid-based machine learning modeling were conducted to assess differential lipids' diagnostic performance. Lastly, survival analyses were used to evaluate lipids' prognostic values. In total, 41 differential lipids were screened out, 10 were upregulated and 31 were downregulated in CRC. Only CerP(d15:0_22:0 + O) showed fine predictive accuracy in single-lipid-based ROC analysis. Among the four machine learning models, SVM showed best predictive performance with accuracy (in predicting test set) of 1.0000 (95 %CI: 0.8806, 1.0000), that can be reached by modeling with only 14 lipids. Four lipids had significant prognostic values, that were TG(11:0_18:0_18:0) (HR: 0.34), TG(18:0_18:0_18:1) (HR: 0.34), PC(22:1_12:3) (HR: 2.22), LPC(17:0) (HR: 3.16). In conclusion, this study discovered novel lipid features that have potential diagnostic and prognostic values, and showed combination of plasma lipidomics and machine learning modeling could have outstanding diagnostic performance and may serve as a convenient and more accessible way to aid in clinical diagnosis of colorectal cancer.

Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2) and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ) is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with KIT mutation.

Purpose Our current study was conducted to identify patients' anatomic, pathologic, and clinical factors to predict difficulty of performing laparoscopic abdominoperineal resection for ultra-low rectal cancer. Materials and methods Records of 117 consecutive patients with rectal cancer 2 to 5 cm from the anal verge were retrospectively reviewed. Using univariate and multivariate linear or logistic regression models, standardized operative time and blood loss, as well as postoperative morbidity were utilized as endpoints to screen patients' multiple variables to predict operative difficulty. Results Multivariate linear regression analysis showed body mass index (BMI) (estimate=0.07, P=0.0056), interspinous distance (estimate=-0.02, P=0.0011), tumor distance from anal verge (estimate=-0.17, P=0.0355), prior abdominal surgery (estimate=0.51, P=0.0180), preoperative chemoradiotherapy (estimate=0.67, P=0.0146), and concurrent diseases (hypertension and/or diabetes mellitus) (estimate=0.49, P=0.0122) are predictors for standardized operative time. Age (estimate=0.02, P=0.0208) and concurrent diseases (estimate=0.43, P=0.0476) were factors related to standardized blood loss. BMI (estimate=0.15, P=0.0472) was the only predictor for postoperative morbidity based on logistic regression analysis. Conclusions Age, BMI, interspinous distance, tumor distance from anal verge, prior abdominal surgery, preoperative chemoradiotherapy, and concurrent diseases influence the difficulty of performing laparoscopic abdominoperineal resection for ultra-low rectal cancer. Standardized operative time allows researchers to amass samples by pooling data from all published studies, thus building reliable models to predict operative difficulty for clinical use.

Purpose The aims of this study were to evaluate how the corneal deformation parameters provided by the Corvis ST tonometer (CST) were influenced by pressure-lowering ocular surgery, and to determine the correlations of intraocular pressure (IOP) and axial length (AL) with CST corneal deformation parameters. Methods This prospective 1-month study enrolled 22 subjects (22 eyes) who underwent trabeculectomy combined with mitomycin C. The corneal deformation parameters were measured using the CST. IOP was measured before and after surgery by a Goldmann applanation tonometer and the CST. The central corneal thickness and AL were also recorded. The correlations of the corneal deformation parameters with central corneal thickness, AL, and IOP changes were determined by linear regression analysis. Results IOP decreased significantly after surgery. AL was significantly shorter at 1 week after surgery. There were significant changes in the CST parameters time 1, velocity 1, velocity 2, peak distance highest concavity, and deformation amplitude highest concavity at 1 week and 1 month after surgery and in time highest concavity at 1 week after surgery. The change in time 1 was significantly correlated with preoperative IOP and the IOP reductions, and was positively correlated with the decrease in AL at 1 week. The increase in velocity 1 was negatively correlated with preoperative IOP, and IOP reductions. The change in time highest concavity was negatively correlated with IOP before surgery and the decrease in IOP at 1 week. Conclusion CST is a good choice for measuring IOP, especially when aiming for normalization of IOP after glaucoma surgery.

Aim: This study analyzed clinicopathological features of colorectal mucinous carcinoma and their prognostic values. Patients & method: This study enrolled 265 patients with mucinous colorectal cancer. Clinicopathological information and prognosis were reviewed retrospectively. Kaplan–Meier method, log- rank test and COX proportional hazard regression models were used. Results: In postoperative mucinous carcinoma patients (median age 56, 119 [44.9%] female), advanced tumor stage (odds ratio [OR]: 2.378; 95% CI: 1.512–3.741; p = 0.0002), poor differentiation (OR: 1.896; CI: 1.217–2.955; p = 0.0047) and right-sided tumors (OR: 2.421; CI: 1.145–5.102; p = 0.0206) were associated with shorter overall survival. Appendiceal/ileocecal cecal tumors were not different for prognosis. Conclusion: Mucinous colorectal carcinoma exhibits distinct tumor characteristics. Poor differentiation, advanced stage at presentation and the right side serve as negative prognostic factors.

Objective: The objective of our study was to determine the feasibility and safety of laparoscopic total mesorectal excision (TME) for mid-low rectal cancer following neoadjuvant chemoradiotherapy (nCRT). Methods: We retrospectively reviewed the records of 172 patients with locally advanced rectal cancer who underwent laparoscopic (n = 75) or conventional open (n = 97) surgery with TME following nCRT from June 2009 to October 2015. Perioperative outcomes and related clinical variables were collected and statistically analyzed. Results: Our results showed that patients who underwent laparoscopic surgery had significantly less blood loss and shorter time to pass first flatus and to start a liquid diet compared to those on open surgery. However, other perioperative outcomes, including operative times, postoperative morbidity rates, number of lymph nodes harvested, and sphincter preservation rates, were not significantly different between the two groups. After controlling for surgical approaches, we found that age, gender, tumor stages, and tumor distance to anal verge were significantly correlated with operative times in both groups. Likewise, age, body mass index, tumor T stages, and tumor distance to anal verge were predictors for postoperative morbidity in both groups. Conclusions: We concluded that laparoscopic TME following nCRT is feasible and safe for patients with mid-low rectal cancer. Furthermore, tumor distance to anal verge and age are two important determinants of both operative times and postoperative morbidity, regardless of surgical option.

Normal fibroblasts produce extracellular matrix (ECM) components that form the structural framework of tissues. Cancer-associated fibroblasts (CAFs) with an activated phenotype mainly contribute to ECM deposition and construction of cancer masses. However, the stroma of breast cancer tissues has been shown to be more complicated, and the mechanisms through which CAFs influence ECM deposition remain elusive. In this study, we found that the activated fibroblast marker α-smooth muscle actin (α-SMA) was only present in the stroma of breast cancer tissue, and the CAFs isolated from invasive breast cancer sample remained to be activated and proliferative in passages. To further assess the difference between CAFs and normal breast fibroblasts (NFs), MALDI TOF/TOF‑MS was used to analyze the secretory proteins of primary CAFs and NFs. In total, 2,903 and 3,023 proteins were identified. Mass spectrum quantitative assay and data analysis for extracellular proteins indicated that the CAFs produce less collagens and matrix-degrading enzymes compared with NFs. This finding was confirmed by western blot analysis. Furthermore, we discovered that reduced collagen deposition was present in the stroma of invasive breast cancer. These studies showed that although CAFs from invasive breast cancer possess an activated phenotype, they secreted less collagen and induced less ECM deposition in cancer stroma. In cancer tissue, the remodeling of stromal structure and tumor microenvironment might, therefore, be attributed to the biological changes in CAFs including their protein expression profile.

Background. The interactions between cancer-associated fibroblasts (CAFs) and cancer cells or tumor-infiltrating lymphocytes (TILs) and cancer cells play important roles in cancer progression and metastasis. However, studies related to the crosstalk between CAFs and TILs in tumor microenvironment (TME) are still lacking. In this study, we mainly investigated the interactions between CAFs and TILs. Material and methods. The distribution of TILs rich in regulatory T cells (Tregs) in breast cancer tissues was evaluated using hematoxylin-eosin staining and immunohistochemistry with anti-CD3, anti-Foxp3, and anti-α-smooth muscle actin antibodies. Homologous CAFs/normal fibroblasts (NFs) and TILs cultured in vitro were identified and detected using immunocytochemistry and flow cytometry (FCM). The direct interaction among these cell types was studied via a factorial design in a co-cultured system. Their indirect interaction was assayed using Transwell plates. The cell cycle and apoptosis of CAFs/NFs co-cultured with TILs was analyzed using propidium iodide staining. Results. Histochemistry demonstrated most of the TILs including Tregs, were distributed in the cancer stroma, adjoining to CAFs. This finding implies that both cell types interact closely in the TME. Identification of the cultured cells showed that CAFs maintained their activated phenotype within limited passages in vitro, and that the TILs population contained a high percentage of Tregs. Data analysis of the factorial design suggests significant interactions among CAFs, NFs, and TILs in both direct and indirect contact ways. The CAFs and NFs were suppressed signally by TILs, which are probably induced by the secretory cytokines derived from TILs or Tregs. Although apoptosis was not detected in CAFs/NFs, the cell cycle assay suggested that the CAFs/NFs were arrested in the G2/M phase by the TILs and their secretory cytokines. Conclusion. CAFs and NFs were dramatically suppressed by Tregs-rich TILs. This suggests the interaction between TILs and CAFs might modify the TME in an unknown manner.

To utilize surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to identify potential biomarkers for diagnosis, preoperative pathological classification, staging, and postoperative prognosis in patients with colorectal cancer (CRC), a total of 152 samples were analyzed in this study, including 53 untreated CRC, 12 colorectal adenoma, 15 healthy volunteers, 30 post-treatment CRC patients with stable disease, and 42 post-treatment CRC with progressive disease. The samples were all analyzed by SELDI-TOF-MS and CM10 ProteinChip technology. The proteomic profiles were validated using a bioinformatics tool based on support vector machine (SVM) and undecimated discrete wavelet transform (UDWT) methods. Seven protein peaks were selected as potential biomarkers for CRC, with a specificity of 85.19% and a sensitivity of 96.23%. Four protein peaks were selected as potential markers for colorectal mucinous adenocarcinoma and non-mucinous adenocarcinoma, with a specificity of 95.12% and sensitivity of 83.33%. In addition, SELDI-based serum profiling discriminated between patients with locally advanced (stage I-II) and regionally advanced (stage III) CRC, and between patients with locoregional (stage I-III) and systemic (stage IV) CRC, with high specificity and sensitivity. A protein peak at 5909 Da was identified as a potential marker for tumor progression and prognosis in CRC. In conclusion, we have demonstrated that ProteinChip technology with SELDI-TOF-MS could provide a novel, non-invasive tool for diagnosis, potential preoperative biomarkers for pathological classification, staging, and postoperative prognostic markers for patients with CRC.

Penalized variable selection methods have been extensively studied for standard time-to-event data. Such methods cannot be directly applied when subjects are at risk of multiple mutually exclusive events, known as competing risks. The proportional subdistribution hazard (PSH) model proposed by Fine and Gray (J Am Stat Assoc 94:496-509, 1999) has become a popular semi-parametric model for time-to-event data with competing risks. It allows for direct assessment of covariate effects on the cumulative incidence function. In this paper, we propose a general penalized variable selection strategy that simultaneously handles variable selection and parameter estimation in the PSH model. We rigorously establish the asymptotic properties of the proposed penalized estimators and modify the coordinate descent algorithm for implementation. Simulation studies are conducted to demonstrate the good performance of the proposed method. Data from deceased donor kidney transplants from the United Network of Organ Sharing illustrate the utility of the proposed method.

Metastasis associated in colon cancer-1 (MACC1) is a newly identified oncogene, and increasing evidence has suggested that its overexpression is associated with the development and progression in many tumors. Here, we perform a meta-analysis to assess the relationship between MACC1 overexpression and survival in solid tumors. Eligible studies were searched in Embase, PubMed, and Web of Science databases up to May 2014. Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated to estimate the impact of MACC1 overexpression on survival using a random-effect model. A total of 20 eligible studies dealing with various tumors were included in the analysis: 17 were dealing with overall survival (OS), 7 were with relapse-free survival (RFS), and 3 were with disease-free survival (DFS). Combined results suggested a strong link between the high MACC1 expression and the poor overall survival (HR 2.11, 95 % CI 1.59–2.80, P

To find new biomarkers and establish histopathology protein fingerprint models for early detection of colorectal cancer (CRC), laser capture microdissection (LCM) was utilized to obtain 3 groups of cells of interest--CRC tissues, their adjacent normal colorectal tissues, and their adjacent adenomatous polyps tissues--from the same 12 CRC patients. Each sample was then detected by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology and CM10 protein chip as well as bioinformatics tools. Model 1 formed by 15 protein peaks could be used to distinguish CRC tissues from normal tissues. The diagnostic pattern constructed using support vector machine (SVM) including the 15 proteins showed maximum Youden index (YI). Model 2 formed by 14 protein peaks could be used to distinguish CRC tissues from adenomatous polyps tissues. The two patterns were validated and the results showed that the sensitivity and specificity were both 100.0%. Model 3 formed by 15 protein peaks could distinguish adenomatous polyps tissues from normal tissues with a sensitivity of 92.3% and specificity of 100.0%. The protein peaks m/z 3570 and 5224 were identified in screening for changes during cancer progression. Peak 5224 was significantly upregulated in CRC. However, peak 3570 was significantly downregulated in CRC. LCM technology coupled with SELDI protein chip and bioinformatics approaches could effectively screen the differentially expressed protein profiles and establish molecular diagnosis models with high sensitivity and specificity for CRC.

Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages.

Vascular-targeting agents (VTAs) can be divided into two groups: anti-angiogenesis agents and vascular disrupting agents (VDAs). The purpose of this study was to evaluate the antineoplastic activity of a combination of the anti-angiogenesis agent, Endostar, and the VDA combretastatin, A4 phosphate (CA4P). This study is the first to evaluate the activity of this combination against tumors and the first to investigate the activity of the combination against osteosarcoma. Endostar combined with CA4P had a good anti-tumor effect with no significant toxicity, and was at least not inferior to adriamycin, which is the main drug for osteosarcoma. The use of VDAs combined with anti-angiogenic drugs can result in significantly enhanced anti-tumor effects, providing a novel approach to cancer treatment, which could effectively complement standard treatments. It is believed that this exciting new treatment has the potential to transform the management of cancer.