Screening and identifying of biomarkers in early colorectal cancer and adenoma based on genome-wide methylation profiles.

BACKGROUND: Colorectal cancer is one of the most common malignant tumors worldwide with high morbidity and mortality. This study aimed to identify different methylation sites as new methylation markers in CRC and colorectal adenoma through tissue detection. METHODS: DNA extraction and bisulfite modification as well as Infinium 450K methylation microarray detection were performed in 46 samples of sporadic colorectal cancer tissue, nine samples of colorectal adenoma, and 20 normal samples, and bioinformatic analysis was conducted involving genes enrichments of GO and KEGG. Pyrosequencing methylation detection was further performed in 68 sporadic colorectal cancer tissues, 31 samples of colorectal adenoma, and 49 normal colorectal mucosae adjacent to carcinoma to investigate the differentially methylated genes obtained from methylation microarray. RESULTS: There were 65,535 differential methylation marker probes, among which 25,464 were hypermethylated markers and 40,071 were hypomethylated markers in the adenoma compared with the normal group, and 395,571 were differentially methylated markers in patients with sporadic colorectal cancer compared with the normal group, including 21,710 hypermethylated markers and 17,861 hypomethylated markers. Five hypermethylated genes including ZNF471, SND1, SPOCK1, FBLIM1, and OTX1 were detected and confirmed in 68 cases of colorectal cancer, 31 cases of adenoma, and 49 cases of normal control group. CONCLUSIONS: Hypermethylated genes of ZNF471, SND1, SPOCK1, FBLIM1, and OTX1 were obtained from methylation chip detection and further confirm analysis in colorectal cancer and adenoma compared with normal tissue, which may be promising diagnostic markers of colorectal cancer and colorectal adenoma.

Propensity score-matched comparison between totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction and conventional laparoscopic surgery with mini-laparotomy in the treatment of ascending colon cancer (with video).

BACKGROUND AND AIMS: Now that the debate about the safety and effectiveness of laparoscopic versus open surgery is over, attention has turned to innovations that can verify whether minimizing the impact of laparoscopy on the abdominal wall can further reduce pain, improve patient comfort, lead to superior cosmesis, and reduce morbidity. The aim of this study was to further explore the application value of totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction (NOSE) and to evaluate the short-term efficacy of transcolonic NOSE surgery for resecting specimens of ascending colon cancer. METHODS: From January 2016 to May 2017, a retrospective study was conducted in Guangxi. Propensity score matching was used to minimize the bias from nonrandomized treatment assignment. Patients were followed up through May 2020. RESULTS: Forty-nine patients underwent totally laparoscopic right hemicolectomy with transcolonic NOSE and 116 patients laparoscopic right hemicolectomy with mini-laparotomy (ML) procedures at our institution. After propensity score matching, each group included 45 patients, and all covariate imbalances were alleviated. The transcolonic NOSE group and the ML group did not differ significantly in terms of baseline clinical characteristics. The transcolonic NOSE group was associated with a shorter time to first flatus (NOSE vs ML: 1.8 ± .5 vs 3.2 ± .8, P = .032), a shorter length of hospital stay (11.3 ± 2.5 days vs 13.0 ± 3.1 days, P = .034), a shorter time to first liquid intake (2.6 ± .8 vs 3.8 ± .9, P = .068), less pain (1.8 ± .8 vs 4.2 ± .7, P = .013), less analgesia requirement (6 [13.3%] vs 21 [46.7%], P = .001), and lower C-reactive protein levels on postoperative day 1 (3.6 ± 1.7 vs 8.2 ± 2.2, P = .001) and postoperative day 3 (NOSE 2.4 ± 1.4 vs M: 4.6 ± 1.7 [P = .013]) than the ML group. The median follow-up was 28.4 months (interquartile range, 18.0-36.0). The 3-year overall survival rates were similar between the transcolonic NOSE group and the ML group. CONCLUSIONS: In total, laparoscopic right hemicolectomy with transcolonic specimen extraction appears to be safe for selected patients with ascending colon cancer as a minimally invasive surgery.

Siva­1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF­κB pathway.

Siva­1 is a well­known anti­apoptosis protein that serves a role in multiple types of cancer cells. However, whether Siva­1 affects multidrug resistance via the NF­κB pathway in gastric cancer is currently unknown. The present study aimed to determine the possible involvement of Siva­1 in gastric cancer anticancer drug resistance in vitro. A vincristine (VCR)­resistant KATO III/VCR gastric cancer cell line with stable Siva­1 overexpression was established. The protein expression levels of Siva­1, NF­κB, multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1) were detected via western blotting. The effect of Siva­1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5­fluorouracil and doxorubicin. The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. Additionally, colony formation, wound healing and Transwell assays were used to detect the proliferation, migration and invasion of cells, respectively. The results of the current study revealed that the Siva­1­overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5­fluorouracil and doxorubicin. The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva­1. The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva­1 overexpression. Additionally, Siva­1 overexpression increased the migration and invasion of KATO III/VCR cells in vitro. Western blot analysis determined that Siva­1 overexpression increased NF­κB, MDR1 and MRP1 levels. The current study demonstrated that overexpression of Siva­1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells via promotion of NF­κB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. These data provided novel insight into the molecular mechanisms of gastric cancer, and may be of significance for the clinical diagnosis and therapy of patients with gastric cancer.

Ingested toothpick retrieved through a lumbar approach: a case report.

BACKGROUND: Ingested toothpick may cause severe complications if there is no intervention timely. Toothpicks that required surgical intervention often retrieved through exploratory laparotomy or laparoscopic exploration surgery under general anesthesia, while, those through lumbar approach have been rarely reported. Herein, authors report a case of ingested toothpick which removed through the lumbar surgical approach under local anesthesia and the patient has gained a considerable recovery. CASE PRESENTATION: A 57-year-old man was admitted to our hospital with distending pain in the right flank for more than 20 days. He had a history of accidental toothpick ingestion. Abdominal computed tomography (CT) scan and Color Doppler Ultrasound of the superficial tissue (right flank pain area) consistently revealed a linear lesion -corresponding to the toothpick- was located at the right flank next to the body surface. Surgery via lumbar approach was then successfully performed to retrieve the toothpick under local anesthesia. The post-procedural course was uneventful, and the patient was discharged on the third day after surgery, no complications were noted at the 18-month follow-up. CONCLUSION: When a foreign body that causes perforation of the digestive tract remains for a relative long time (non-acute stage) and the perforation is close to the body surface, a local anesthesia surgery through the corresponding body surface may be a considerable choice.

p33ING1b methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions.

The present study aimed to investigate the feasibility of detecting p33 inhibitor of growth 1b (p33ING1b) gene methylation in fecal DNA as a screening method for colorectal carcinoma (CRC) and precancerous lesions. The methylation of p33ING1b was analyzed in fecal samples from 61 patients with CRCs, 27 patients with precancerous lesions (advanced adenoma) and 20 normal individuals by nested methylation-specific polymerase chain reaction (nMSP) and fecal occult blood test. Methylated p33ING1b was detected in 73.77% of CRC patients and 62.96% of adenoma patients. By contrast, only 5% of normal individuals had methylated p33ING1b. These results indicated 73.77% sensitivity for detecting CRC, 62.96% sensitivity for detecting precancerous lesions and 95% specificity of the assay for detecting CRCs and precancerous lesions. The detection of p33ING1b methylation status by incubation of DNA contained in agarose beads for bisulfite modification, followed by nMSP, is a promising non-invasive screening method for CRCs and precancerous lesions.