Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer.

BACKGROUND: MicroRNAs have been suggested to play a vital role in regulating carcinogenesis, tumor progression and invasion. MiR-335 is involved in suppressing metastasis and invasion in various human cancers. However, the mechanisms responsible for the aberrant expression of miR-335 in gastric cancer (GC) remain unknown. METHODS: Expression of miR-335 in four GC cell lines and 231 GC tissues was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). DNA methylation status in the CpG islands upstream of miR-335 in GC cell lines and tissues was determined by methylation-specific PCR and bisulfite sequence-PCR. The effects of the demethylating agent 5-aza-2'-deoxycytidine on cell proliferation, apoptosis, cell cycle, migration, and invasion were investigated in GC cell lines. RESULTS: Cancer-specific methylation was detected in the upstream CpG-rich regions of miR-335, which dramatically silenced its transcriptional activity in GC cell lines and tissues. Low levels of miR-335 expression and high levels of miR-335 methylation in GC tissues were associated with poor clinical features and prognosis. Restoration of miR-335 expression in GC cells promoted cell apoptosis, inhibited tumor cell migration, invasion, and proliferation, and arrested the cell cycle at G0/G1 phase. Overexpression of miR-335 significantly reduced the activity of a luciferase reporter containing the 3' untranslated region of V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL). CONCLUSIONS: MiR-335 functions as a tumor suppressor and may be silenced by promoter hypermethylation. It plays a role in inhibiting tumor cell migration, invasion, and proliferation, arresting the cell cycle at G0/G1 phase, and promoting apoptosis in GC cells through targeting CRKL.

Type D personality is associated with delaying patients to medical assessment and poor quality of life among rectal cancer survivors.

OBJECTIVE: The aim of this research was to explore quality of life (QoL), mental health status, type D personality, symptom duration, and emergency admissions of Chinese rectal cancer patients as well as the relationship between these factors. METHODS: Type D personality was measured with the 14-item Type D Personality Scale (DS14). Mental health status was measured with the Hospital Anxiety and Depression Scale (HADS). The QoL outcomes were assessed longitudinally using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires at the baseline and 6 months after diagnosis. RESULTS: Of the 852 survivors who responded (94 %), 187 (22 %) had a type D personality. The proportion of patients with duration of symptoms >1 month and being diagnosed after emergency admissions in type D group is significantly higher than that in non-type D group. At both of the time points, type D patients reported statistically significant lower scores on most of the functional scales, global health status/QoL scales, and worse symptom scores compared to patients without a type D personality. At the 6-month time point, a higher percentage of patients in the type D group demonstrated QoL deterioration. Clinically elevated levels of anxiety and depression were more prevalent in type D than in non-type D survivors. CONCLUSIONS: Type D personality was associated with poor QoL and mental health status among survivors of rectal cancer, even after adjustment for confounding background variables. Type D personality might be a general vulnerability factor to screen for subgroups at risk for longer symptom duration and emergency admissions in clinical practice.

Higher serum carotenoid concentrations were associated with the lower risk of cancer-related death: Evidence from the National Health and Nutrition Examination Survey.

The study focuses on the association between serum carotenoids and cancer-related death. Using data from the National Health and Nutrition Examination Survey (2001-2006 and 2017-2018), the study encompasses 10,277 participants older than age 20 years, with recorded baseline characteristics and serum carotenoid concentrations (including α-carotene, trans-ß-carotene, cis-ß-carotene, ß-cryptoxanthin, trans-lycopene, and lutein/zeaxanthin). We hypothesized that serum carotenoid concentrations were negatively associated with cancer-related death. The weighted chi-square analyses indicate significant negative correlations between higher serum concentrations of α-carotene, ß-cryptoxanthin, trans-lycopene, and total carotenoids, and the risk of cancer-related deaths. Using weighted Cox regression analysis, this study confirms that α-carotene, ß-cryptoxanthin, trans-lycopene, and total carotenoids, as continuous or categorical variables, are inversely related to cancer mortality (P < .0001). Furthermore, considering competitive risk events, lower concentrations of serum ß-cryptoxanthin (Fine-Gray P = 1.12e-04), trans-lycopene (P = 5.68e-14), and total carotenoids (P = .03) are associated with an increased risk of cancer-related deaths. The research reveals a crucial inverse relationship between serum carotenoid concentrations and cancer-related death.

Neoadjuvant chemotherapy for nonmetastatic esophago-gastric adenocarcinomas: a systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was performed to investigate the efficacy of neoadjuvant chemotherapy for nonmetastatic esophago-gastric adenocarcinomas. METHODS: Electronic databases were searched systematically from January 1980 to July 2012 and a total of 2,587 patients from 17 randomized controlled trials were subjected to meta-analysis. The odds ratios (ORs) for overall survival (OS) and progression-free survival (PFS) were calculated. RESULTS: Seventeen randomized controlled trials were obtained and various comparisons of treatment approaches were performed. Randomized controlled trials detected no differences in these comparisons: R0 resection for neoadjuvant chemotherapy versus none; Preoperative chemotherapy versus surgery alone: 3-year OS, 5-year OS, 5-year OS in Europe, 3-year PFS; Preoperative chemotherapy plus postoperative chemotherapy versus postoperative chemotherapy: 1-year OS, 5-year OS; Preoperative chemotherapy versus preoperative chemoradiotherapy: 3-year OS. Randomized controlled trials detected significant differences in these comparisons: Preoperative chemotherapy plus postoperative chemotherapy versus surgery alone: 3-year and 5-year PFS, 5-year OS; Subgroup analysis examining preoperative chemotherapy versus surgery alone: 5-year OS in Asia; Preoperative chemotherapy versus postoperative chemotherapy: 1-year OS. CONCLUSION: The current limited evidence suggests that preoperative chemotherapy can be applied to patients with nonmetastatic esophago-gastric adenocarcinomas (specifically, advanced esophago-gastric cancer). However, the results should be interpreted with caution because of the statistically low power and the heterogeneity among study designs; therefore, our results need validations in future studies.

Identification and initial validation of maximal tumor area as a novel prognostic factor for overall and disease-free survival in patients with resectable colon cancer: a retrospective study.

BACKGROUND: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer. METHODS: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between the tumor-node-metastasis (TNM) staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P <0.05 was considered statistically significant. RESULTS: A total of 3051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P <0.001; iAUC for DFS, 0.694, P <0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort. CONCLUSIONS: Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with an adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system.

Type D Personality in Gastric Cancer Survivors: Association With Poor Quality of Life, Overall Survival, and Mental Health.

CONTEXT: The associations between Type D personality and poor quality of life, overall survival, and mental health in gastric cancer survivors. OBJECTIVES: The aim of this research was to explore quality of life (QoL), mental health status, Type D personality, symptom duration, and emergency admissions of Chinese gastric cancer patients, as well as the relationship between these factors. METHODS: Eight hundred thirty eligible Chinese patients newly diagnosed with gastric cancer between July 2009 and July 2011 were enrolled in this prospective study. Type D personality was measured with the 14-item Type D Personality Scale (DS14). Mental health status was measured with the Hospital Anxiety and Depression Scale. The QoL outcomes were assessed longitudinally using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Quality of Life Questionnaire-STO22 at baseline and six months after diagnosis. RESULTS: The proportion of patients with symptom duration of more than one month and who were diagnosed after emergency admissions in the Type D group was significantly higher than that in the non-Type D personality group. At both of the time points, Type D patients reported statistically significant lower scores on role, emotional, cognitive, and social functioning (all Ps < 0.001) functional scales, global health status/QoL scales (P < 0.001), and worse symptom scores compared to patients without a Type D personality. During the six-month time frame, a higher percentage of patients in the Type D group demonstrated a considerable QoL deterioration. Clinically elevated levels of anxiety and depression were more prevalent in Type D than in non-Type D survivors (both Ps < 0.001). There was a statistically significant difference in three-year overall survival between the patients in the Type D group and the non-Type D personality group. CONCLUSION: Type D personality is associated with poor QoL, three-year overall survival and mental health status among survivors of gastric cancer, even after adjustment of confounding background variables. The Type D personality group experienced increased levels of pain and fatigue compared to non-Type D patients. Type D personality might be a general vulnerability factor to screen for subgroups at risk of longer symptom duration and emergency admissions in clinical practice.

Prognostic significance of distal subtotal gastrectomy with standard D2 and extended D2 lymphadenectomy for locally advanced gastric cancer.

This study was conducted to investigate prognosis and survival of patients undergoing distal subtotal gastrectomy with D2 and D2+ lymphadenectomy for patients with locally advanced gastric cancer. Overall survival rates of 416 patients with locally advanced gastric cancer were compared between D2 and D2+ lymphadenectomy. Univariate analysis and multivariate analysis was used to identify significant prognostic factors correlated with LN metastasis and prognosis. Univariate analysis identified tumor size, lymphatic vessel invasion, pT stage, pN stage, TNM stage, locoregional recurrence, and distant recurrence, to significantly correlate with prognosis; Tumor size, LVI, and pT stage were identified as independent factors correlating with LN metastasis. Multivariate analysis demonstrated that tumor size, pT stage, pN stage, locoregional recurrence, and distant recurrence were independent prognostic factors; Tumor size and pT stage were independent prognostic factors predicting LN metastasis. When comparing 5-year survival rates of patients who underwent D2 and D2+ lymphadenectomy, as stratified by pT stage and pN stage, a significant difference was found in pN3 patients, but not for pT2-4 and pN0-2 patients, or the patient cohort as a whole. In conclusion, D2 lymphadenectomy for patients with locally advanced gastric cancer undergoing distal subtotal gastrectomy was recommended, especially in eastern Asia.

Factors associated with delaying medical assessment of patients and impacting the prognosis of rectal cancer.

The aims of this study were (a) to compare the clinical presentations and outcomes of patients referred to the hospital from the emergency department (ED) and those referred from non-ED facilities in a Chinese population and (b) to identify the factors influencing delays in medical assessment and prognosis for patients with rectal cancer (RC). Eligible Chinese patients newly diagnosed with RC, admitted to the hospital from the ED, or referred from non-ED sources between 1 January 2008 and 31 December 2009 were enrolled in this prospective study. Associations between symptoms, symptom duration, tumor stage at diagnosis, and 3-year survival were proposed to identify factors associated with delay in the diagnosis of RC and emergency admission. Compared with patients in the non-ED group, patients in the ED group had a significantly longer hospital stay, greater in-hospital mortality, a higher proportion of advanced stage tumor, lower rate of undergoing potentially curative surgery, and a higher proportion of symptom duration longer than 1 month. There was a statistically significant difference in the 3-year overall survival between the patients who underwent emergency operation within 24 h of admission and the patients presenting as emergency who underwent an operation longer than 24 h from admission to operation. Patients who endured symptoms longer than 1 month had a significantly higher proportion of emergency admissions, higher proportion of advanced stage tumor, and lower rate of undergoing potentially curative surgery compared with patients whose symptom duration was less than 1 month. In conclusion, (a) ED referral patients endured significantly longer symptom duration before diagnosis. (b) Emergency operation within 24 h of admission was an independent prognostic indicator of overall survival in patients with RC. A two-stage approach for the management of patients with RC who presented as emergency could enable patients to be transferred to a specialist department of surgical oncology for a definitive radical oncological operation and improve the prognosis.

Extended antimicrobial prophylaxis after gastric cancer surgery: a systematic review and meta-analysis.

AIM: To investigate the efficacy of extended antimicrobial prophylaxis (EAP) after gastrectomy by systematic review of literature and meta-analysis. METHODS: Electronic databases of PubMed, Embase, CINAHL, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register and the China National Knowledge Infrastructure were searched systematically from January 1980 to October 2012. Strict literature retrieval and data extraction were carried out independently by two reviewers and meta-analyses were conducted using RevMan 5.0.2 with statistics tools risk ratios (RRs) and intention-to-treat analyses to evaluate the items of total complications, surgical site infection, incision infection, organ (or space) infection, remote site infection, anastomotic leakage (or dehiscence) and mortality. Fixed model or random model was selected accordingly and forest plot was conducted to display RR. Likewise, Cochrane Risk of Bias Tool was applied to evaluate the quality of randomized controlled trials (RCTs) included in this meta-analysis. RESULTS: A total of 1095 patients with gastric cancer were enrolled in four RCTs. No statistically significant differences were detected between EAP and intraoperative antimicrobial prophylaxis (IAP) in total complications (RR of 0.86, 95%CI: 0.63-1.16, P = 0.32), surgical site infection (RR of 1.97, 95%CI: 0.86-4.48, P = 0.11), incision infection (RR of 4.92, 95%CI: 0.58-41.66, P = 0.14), organ or space infection (RR of 1.55, 95%CI: 0.61-3.89, P = 0.36), anastomotic leakage or dehiscence (RR of 3.85, 95%CI: 0.64-23.17, P = 0.14) and mortality (RR of 1.14, 95%CI: 0.10-13.12; P = 0.92). Likewise, multiple-dose antimicrobial prophylaxis showed no difference compared with single-dose antimicrobial prophylaxis in surgical site infection (RR of 1.10, 95%CI: 0.62-1.93, P = 0.75). Nevertheless, EAP showed a decreased remote site infection rate compared with IAP alone (RR of 0.54, 95%CI: 0.34-0.86, P = 0.01), which is the only significant finding. Unfortunately, EAP did not decrease the incidence of surgical site infections after gastrectomy; likewise, multiple-dose antimicrobial prophylaxis failed to decrease the incidence of surgical site infection compared with single-dose antimicrobial prophylaxis. CONCLUSION: We recommend that EAP should not be used routinely after gastrectomy until more high-quality RCTs are available.