Clinicopathologic features and prognosis of primary gastrointestinal stromal tumor patients under 35 years of age: A 10-year retrospective study.

OBJECTIVES: To investigate gastrointestinal stromal tumor (GIST) clinicopathologic characteristics in young adults. METHODS: Clinicopathologic data from GIST patients under 35 years diagnosed at our hospital from January 2005 to December 2014 were retrospectively collected. RESULTS: Thirty-one (5.3%, 31/585) patients were included; 17 (54.8%) were female. The most common presentation and primary tumor site were gastrointestinal bleeding (n = 18, 58.1%) and the small intestine (n = 13, 41.9%), respectively. Fifteen (48.4%) GISTs were classified as having a high relapse risk; two (6.4%), intermediate; nine (29.0%), low; and five (16.1%), very low. All patients underwent tumor resection. With a median follow-up of 51 months for 20 (64.5%) patients, 12 (60%) were given imatinib methylate as adjuvant therapy. One (5%) patient died of peritoneal GIST dissemination, four (20%) developed abdominal recurrences, two (10%) had hepatic metastasis, and thirteen (65%) were disease free. The 5-year disease-free survival rate was 51.2%. CONCLUSIONS: GISTs rarely occur in young adults. The most common location is the small intestine. A slight female predominance was observed in the current study. Adjuvant therapy longer than the recommended duration may be beneficial for GISTs with a high relapse risk. Combined targeted therapy and surgery is appropriate for recurrent and metastatic GISTs in select patients. J. Surg. Oncol. 2016;114:977-981. © 2016 Wiley Periodicals, Inc.

Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China.

The incidence of colorectal cancer (CRC) is increasing in China, with high mortality. Here, we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China. The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively. KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction (q-PCR) in 410 CRC patients, with mutation frequencies of KRAS, NRAS and BRAF of 47.56%, 2.93% and 4.15%, respectively. The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed. The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes. The BRAF gene mutation was also associated with cancer thrombosis in blood vessels. Cox regression analysis showed that there was no statistically significant difference in the overall survival (OS) between patients with KRAS, NRAS mutants and wild-type CRC patients, while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients. It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

Transcriptional inactivation of ERbeta gene is mediated by the induction of promoter hypermethylation in a rat colonic epithelial cell model.

BACKGROUND: To construct a primary rat colonic epithelial cell model for treatment with specific methylated oligonucleotides (MOs) and to determine whether the transcriptional inactivation of ERbeta mRNA is mediated by the induction of hypermethylation of the ERbeta gene promoter. METHODS: Suckling rat colonic epithelial cells were cultured in DMEM. Two methylated oligonucleotides complementary to the promoter regions of ERbeta were synthesized and applied to the cultured cells to induce promoter hypermethylation of the ERbeta gene. Methylation-specific PCR (MSP) was used to determine the methylation status of the ERbeta promoter in the cultured cells. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the expression of ERbeta mRNA after treatment with MOs. RESULTS: Suckling rat colonic epithelial cells were successfully cultured in vitro. The MOs and unmethylated oligonucleotides (UMOs) we designed, synthesized, successfully transfected into the colonic epithelial cells, and assembled in the nuclei of the cells, which had extremely elevated proliferative activity. RT-PCR demonstrated that the expression of ERbeta mRNA was significantly suppressed in the cells treated with MOs, whereas its expression in the control cells treated with UMOs was not. MSP analysis showed that the promoter of ERbeta in the cells treated with MOs was hypermethylated compared with that of the control cells. CONCLUSION: The transcriptional inactivation of ERbeta mRNA in rat colonic epithelial cells may be mediated by the hypermethylation of the ERbeta gene promoter. Our model markedly simulates the epigenetic modification of the ERbeta gene in colonic cancer cells.

The prognostic value of AGR2 expression in solid tumours: a systematic review and meta-analysis.

The prognostic value of anterior gradient-2 (AGR2) in tumours remains inconclusive. Here, we systematically reviewed the literature evidence and assessed the association between AGR2 expression and prognosis in solid tumours. The primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS). All analyses were performed by STATA 12.0, with the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) as the effect size estimate. A total of 20 studies containing 3285 cases were included. Pooled analyses revealed that AGR2 overexpression had an unfavourable impact on OS (HR 1.93, 95% CI 1.32-2.81) and time to tumour progression (TTP) (DFS/RFS/PFS) (HR 1.60 95% CI 1.06-2.40) in solid tumour patients. Subgroup analyses indicated that AGR2 overexpression in breast cancer patients was significantly associated with poor OS (HR 3.02, 95% CI 1.03-8.81) and TTP (HR 1.93, 95% CI 1.17-3.20). Excluding breast cancer, AGR2 overexpression was also found to have a significant correlation with poor OS in the remaining solid tumour patients (HR 1.51, 95% CI 1.04-2.19). Overall, AGR2 might be a potential biomarker to predict prognosis in solid tumour patients.

Anatomical basis and clinical research of pelvic autonomic nerve preservation with laparoscopic radical resection for rectal cancer.

The clinical effect of laparoscopic rectal cancer curative excision with pelvic autonomic nerve preservation (PANP) was investigated. This study evaluated the frequency of urinary and sexual dysfunction of 149 male patients with middle and low rectal cancer who underwent laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP) from March 2011 to March 2013. Eighty-four patients were subjected to laparoscopic surgery, and 65 to open surgery respectively. The patients were followed up for 12 months, interviewed, and administered a standardized questionnaire about postoperative functional outcomes and quality of life. In the laparoscopic group, 13 patients (18.37%) presented transitory postoperative urinary dysfunction, and were medically treated. So did 12 patients (21.82%) in open group. Sexual desire was maintained by 52.86%, un-ability to engage in intercourse by 47.15%, and un-ability to achieve orgasm and ejaculation by 34.29% of the patients in the laparoscopic group. Sexual desire was maintained by 56.36%, un-ability to engage in intercourse by 43.63%, and un-ability to achieve orgasm and ejaculation by 33.73% of the patients in the open group. No significant differences in urinary and sexual dysfunction between the laparoscopic and open rectal resection groups were observed (P>0.05). It was concluded that laparoscopic rectal cancer radical excision with PANP did not aggravate or improve sexual and urinary dysfunction.

The Diagnostic Performance of Stool DNA Testing for Colorectal Cancer: A Systematic Review and Meta-Analysis.

This meta-analysis was designed to evaluate the diagnostic performance of stool DNA testing for colorectal cancer (CRC) and compare the performance between single-gene and multiple-gene tests.MEDLINE, Cochrane, EMBASE databases were searched using keywords colorectal cancers, stool/fecal, sensitivity, specificity, DNA, and screening. Sensitivity analysis, quality assessments, and performance bias were performed for the included studies.Fifty-three studies were included in the analysis with a total sample size of 7524 patients. The studies were heterogeneous with regard to the genes being analyzed for fecal genetic biomarkers of CRC, as well as the laboratory methods being used for each assay. The sensitivity of the different assays ranged from 2% to 100% and the specificity ranged from 81% to 100%. The meta-analysis found that the pooled sensitivities for single- and multigene assays were 48.0% and 77.8%, respectively, while the pooled specificities were 97.0% and 92.7%. Receiver operator curves and diagnostic odds ratios showed no significant difference between both tests with regard to sensitivity or specificity.This meta-analysis revealed that using assays that evaluated multiple genes compared with single-gene assays did not increase the sensitivity or specificity of stool DNA testing in detecting CRC.

Effects of carbon dioxide and nitrogen on adhesive growth and expressions of E-cadherin and VEGF of human colon cancer cell CCL-228.

AIM: To study the effects of carbon dioxide on the metastatic capability of cancer cells, and to compare them with that of nitrogen. METHODS: The colon cancer cell CCL-228 was treated with 100 % carbon dioxide or nitrogen at different time points and then cultured under normal condition. Twelve hours after the treatment, the survival rates of suspension cells and the expressions of e-cadherin and VEGF were examined. RESULTS: After 60 min of carbon dioxide and longer time of nitrogen treatment, the suspended cells increased and the expression of e-cadherin decreased while the expression of VEGF was enhanced significantly. And the effects of nitrogen were similar to, but weaker than, those of carbon dioxide. CONCLUSION: Carbon dioxide may improve the metastatic capability of cancer cells and its effects are significantly stronger than that of nitrogen. A sequential use of carbon dioxide and nitrogen in pneumoperitoneum may take the advantage of both gases.

Estrogen inhibits colon polyp formation by reducing angiogenesis in a carcinogen-induced rat model.

Objective. To study the effects of estrogen on colon polyp formation, proliferation, and angiogenesis on a rat model of colon cancer induced by dimethylhydrazine (DMH). Methods. Thirty-six female ovariectomized (OVX) rats were randomly divided into 3 groups: (I) control group (administrated with vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH + E2 group (administrated with DMH and 17ß-estradiol weekly). The incidence, volumes, and multiplicity of colon polyps in each group were evaluated. The microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen (PCNA), and the expressions of HIF-1 α and VEGF in polyps were detected in each group. Results. Estrogen reduced the multiplicity, volumes, and the PCNA expressions of DMH-induced colon polyps. The MVD in DMH + E2 group was significantly lower than that in DMH group. Estrogen treatment decreased the HIF-1 α and VEGF expressions at both mRNA and protein level. Conclusion. Estrogen replacement was protective for ovariectomized rats from DMH-induced carcinogenesis, and one of the mechanisms for this was due to estrogen's inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1 α expressions.