Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

BACKGROUND: The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA). METHODS: We genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in gastric cancer was explored in clinical samples and cell culture studies. RESULTS: Multivariable analysis showed that patients with the CT + TT genotype at SLC39A6 rs1050631 were at greater risk of recurrence (hazard ratio, HR 1.387, p = 0.004) and death (HR 1.429, p = 0.002) than patients with CC genotype. Median recurrence-free and overall survival were significantly shorter in patients with the CT + TT genotype (20, 27 months) than in patients with the CC genotype (36, 43 months, p = 0.001, p < 0.001). Patients with the CT + TT genotype who were male or ≥ 60 years, or who had a tumor ≥5 cm or a moderately differentiated tumor were at significantly higher risk of recurrence and death. SLC39A6 was overexpressed in tissues from GA patients and in GA cell lines, and SLC39A6 knockdown in GA cell lines inhibited their proliferation, migration and invasion. CONCLUSION: SLC39A6 rs1050631 correlates with post-resection prognosis of GA patients and SLC39A6 may participate in GA onset or progression.

LncRNA Expression Profiling in Advanced Resected Gastric Adenocarcinoma Tissues.

BACKGROUND: Long noncoding RNAs (lncRNAs) are the chief products of human transcriptomes and have a major function in mediating gene expression. Abnormal lncRNA levels have been detected in gastric cancer. However, changes in lncRNA expression in advanced gastric adenocarcinoma (GA) are largely unexplored. METHODS: We studied the expression of lncRNAs and mRNAs in 6 advanced resected GA (ARGA) tissues using a lncRNA microarray chip. RESULTS: Among 22,870 lncRNAs expressed in ARGA and paired nonneoplastic tissues (non-GA), 1,769 and 1,710 were up- or downregulated, respectively, in all 6 ARGA tissues (≥ 2.0-fold, p < 0.05). The expression of 5 differentially expressed lncRNAs, HNF1A-AS1, RP11-62F24.2, GAS5, MALAT1, and H19 were randomly selected to be measured in 47 patients using real-time quantitative reverse transcription PCR (qRT-PCR), and the data were consistent with those obtained from the microarray chip. Analysis of their nearby coding genes (mRNAs) revealed that the main associated GO (gene ontology) classes were genes that regulate cellular metabolic processes, protein binding and receptor binding, whereas the main associated pathways were MAPK signaling, which regulates cell proliferation and differentiation and the apoptosis pathway, which is cancer-related. Some (n = 37) differentially expressed lncRNAs had direct annotated functions; among these lncRNAs, 27 were associated with cancer, cancer pathways, oncogenes, and tumor suppressor genes and with cell development and differentiation. CONCLUSIONS: Expression differences in lncRNAs exist between advanced GA and noncancerous gastric tissues, so lncRNA expression patterns may explain gastric carcinogenesis and progression as well as serve as candidate biomarkers for the treatment of GA.

The rs2839698 Single Nucleotide Polymorphism of lncRNA H19 is Associated with Post-Operative Prognosis in T3 Gastric Adenocarcinoma.

BACKGROUND: It has been widely demonstrated that long non-coding RNA H19 (lncRNA H19) plays an important role in the progression of various human cancers. However, the associations of common genetic variations with recurrence and survival in gastric adenocarcinoma in this lncRNA remain largely unknown. METHODS: The rs2839698 single nucleotide polymorphism (SNP) of H19 was genotyped in tissue samples from 441 patients with T3 gastric adenocarcinoma who had surgical operations between 2004 to 2009, and the relationships between the different genotypes and recurrence and survival after surgery alone (n = 156) or surgery plus chemotherapy (n = 285) were assessed using 3 different statistical-methods. RESULTS: Based on the final day of investigation (November 2014), the GA genotype was significantly associated with recurrence and survival in patients treated with surgery alone, but not in patients treated with surgery plus chemotherapy. In patients treated with surgery alone, individuals with the GA genotype had significantly lower risks of recurrence and death [adjusted hazard ratio (HR) 0.57, 95% CI 0.37 - 0.88; adjusted HR: 0.58, 95% CI 0.38 - 0.88] than the GG genotype (p = 0.010 and p = 0.010), respectively. More importantly, patients treated with surgery alone who carried the GA genotype achieved significantly longer median disease-free survival time and overall survival than carriers of the GG genotype (45 vs. 26 months, p = 0.010; 44 vs. 23 months, p = 0.013). CONCLUSIONS: The rs2839698 SNP of H19 may have potential as a novel prognostic factor for survival in T3 gastric adenocarcinoma after surgery alone; these finding have special relevance to patients who are not suitable for postoperative chemotherapy.

Mapping of DNA Hypermethylation and Hypomethylation induced by Folate Deficiency in Sporadic Colorectal Cancer and Clinical Implication Analysis of Hypermethylation Pattern in CBS Promoter.

BACKGROUND: Aberrant DNA methylation patterns play a major role in tumorigenesis and the effects of nutrients, especially folate in the diet, on methylation changes is of great importance in colorectal cancer (CRC). Folate deficiency would disrupt methylation patterns; however, its exact effects on DNA methylation patterns in CRC are unclear. This study was performed to gain insight into the methylation changes induced by folate deficiency and the putative role of methylation pattern diversities of related genes in the clinical outcome of CRC. METHODS: The NimbleGen MeDIP chip (Methylated DNA Immunoprecipitation chip) assay was used in high-resolution mapping of DNA methylation patterns in the normal human colon mucosal epithelial cell line, NCM460 cultured with or without folate. Aberrant CpG island methylation patterns in the promoter of genes were identified by chip assay and then were confirmed in paired colorectal tissues and corresponding non-malignant tissues obtained from patients by bisulfate sequencing PCR (BSP). Of the total, the expression of cystathionine-beta-synthase (CBS) involved in methyl metabolism and its important substrate, homocysteine, were all detected by realtime RT-PCR and immunostaining. We also analyzed the data of its hypermethylation level statistically correlated with pathological parameters and the clinical outcome in malignant tissues. RESULTS: The chip assay showed that there are 17 genes with hyper or hypomethylation in CpG islands of promoter on chromosome 21, and 8 of them seemed to be associated with tumorigenesis. Among the total, a hypermethylation patterns existed in the promoter of CBS in CRC (p < 0.001), and the hypermethylation is related with the down-regulation of CBS and the accumulation of homocysteine in vitro and vivo (p < 0.001). Univariate analysis showed CBS hypermethylation level is correlated with age (p < 0.001), pT stage (p = 0.008), pN stage (p = 0.038), liver metastasis (p = 0.017), pTNM stage (p = 0.032), Dukes' stage (p = 0.022), recurrence (p = 0.041), five-year survival (p = 0.034), recurrence-free probability (p = 0.011), and overall survival (p = 0.018). Multivariate analysis showed that CBS hypermethylation level significantly correlated with recurrence rate (p = 0.039) and overall survival (p = 0.012) independent of pT stage, pN stage, and liver metastasis. CONCLUSIONS: Folate deficiency could induce aberrant DNA methylation patterns and gene expressions in CRC. CBS plays a critical role in tumorigenesis and could serve as a prognostic marker for tumor progression.

Overexpression of HER-2 Protein is a High-Risk Factor for Patients with Surgically-Resected Stage T3 Gastric Adenocarcinoma.

BACKGROUND: Factors associated with tumor recurrence and death in stage T3-gastric adenocarcinoma (GA) after surgical resection remain unclear. In this study, we investigated whether patients with overexpression of epidermal growth factor receptor 2 (HER-2) comprised a high-risk group. METHODS: The immunohistochemistry data of HER-2 protein expression from 633 surgically-resected T3-GA tissues were collected and then retrospectively analyzed by Chi-square test, Kaplan-Meier curve, and log rank test as well as univariate and multivariate analyses. RESULTS: Patients with HER-2 overexpression had increased recurrence rates and decreased median recurrence free survival times (MRFST) compared to those with low expression of HER-2 (76.3% vs. 65.4%, p = 0.004; and 18 vs. 26 months, p = 0.002, respectively). Conversely, overall survival rates and median overall survival times (MOST) were decreased in these patients (23.3% vs. 35.7%, p = 0.001 and 26 vs. 36 months, p = 0.001, respectively). HER-2 overexpression, lymph node metastasis (pN1-pN3), distant metastasis, and R1 resection margin were identified as independent prognostic factors for shorter MRFST and MOST in patients with surgically-resected T3-GA. CONCLUSIONS: Overexpression of HER-2 is a simple and reliable predictor for increased recurrence and poorer survival in patients with T3-GA following surgical resection. As such, these patients may benefit from trastuzumabbased therapy.

"Fast track" rehabilitation after gastric cancer resection: experience with 80 consecutive cases.

BACKGROUND: To evaluate the safety, efficacy and outcomes of fast-track rehabilitation applied to gastric cancer proximal, distal and total gastrectomy. METHODS: Eighty consecutive patients undergoing gastric cancer resection performed by a single surgeon, received perioperative multimodal rehabilitation. Demographic and operative data, gastrointestinal function, postoperative hospital stays, surgical and general complications and mortality were assessed prospectively. RESULTS: Of the 80 patients (mean age 56.3 years), 10 (12.5%) received proximal subtotal gastrectomy (Billroth I), 38 (47.5%) received distal (Billroth II), and 32 (40%) received total gastrectomy (Roux-en-Y). Mean operative time was 104.9 minutes and intraoperative blood loss was 281.9 ml. Time to first flatus was 2.8 ± 0.5 postoperative days. Patients were discharged at a mean of 5.3 ± 2.2 postoperative days; 30-day readmission rate was 3.8%. In-hospital mortality was 0%; general and surgical complications were both 5%. CONCLUSIONS: Fast-track multimodal rehabilitation is feasible and safe in patients undergoing gastric cancer resection and may reduce time to first flatus and postoperative hospital stays.

Hypoxia-ameliorated photothermal manganese dioxide nanoplatform for reversing doxorubicin resistance.

Drug resistance is a huge hurdle in tumor therapy. Tumor hypoxia contributes to chemotherapy resistance by inducing the hypoxia-inducible factor-1α (HIF-1α) pathway. To reduce tumor hypoxia, novel approaches have been devised, providing significant importance to reverse therapeutic resistance and improve the effectiveness of antitumor therapies. Herein, the nanosystem of bovine serum albumin (BSA)-templated manganese dioxide (MnO2) nanoparticles (BSA/MnO2 NPs) loaded with doxorubicin (DOX) (DOX-BSA/MnO2 NPs) developed in our previous report was further explored for their physicochemical properties and capacity to reverse DOX resistance because of their excellent photothermal and tumor microenvironment (TME) response effects. The DOX-BSA/MnO2 NPs showed good biocompatibility and hemocompatibility. Meanwhile, DOX-BSA/MnO2 NPs could greatly affect DOX pharmacokinetic properties, with prolonged circulation time and reduced cardiotoxicity, besides enhancing accumulation at tumor sites. DOX-BSA/MnO2 NPs can interact with H2O2 and H+ in TME to form oxygen and exhibit excellent photothermal effect to further alleviate hypoxia due to MnO2, reversing DOX resistance by down-regulating HIF-1α expression and significantly improving the antitumor efficiency in DOX-resistant human breast carcinoma cell line (MCF-7/ADR) tumor model. The hypoxia-ameliorated photothermal MnO2 platform is a promising strategy for revering DOX resistance.

The effects of propranolol on the biology and Notch signaling pathway of human umbilical vein endothelial cells.

BACKGROUND: Propranolol is the first choice for treating infantile hemangioma (IH). How propranolol works in IH remains unclear. Infantile hemangioma endothelial cells (HemECs) express Notch1, Jagged, Hey1, and other molecules in the Notch pathway, suggesting that Notch pathway-related molecules play an important role in affecting vascular endothelial cell proliferation. Whether propranolol can affect the Notch signaling pathway in IH treatment is unclear. METHODS: We performed this study to observe the effect of propranolol on the expression of Notch signaling pathway molecules in human umbilical vein endothelial cells (HUVECs) and to explore the therapeutic mechanism of propranolol on IH. HUVECs cultured in vitro were exposed to 60, 120, 240, 360, or 480 µM propranolol. The morphological changes of the HUVECs were observed under an inverted microscope. HUVECs proliferation was detected with Cell Counting Kit-8 (CCK-8). The effects of propranolol on HUVECs apoptosis were detected by flow cytometry. The role of Notch in propranolol inhibition of HUVEC proliferation was analyzed with real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Propranolol reduced HUVECs numbers and altered their morphology. The inhibitory effect of propranolol on cell proliferation was dependent on the reaction time and drug concentration. Propranolol upregulated Jagged1, Notch1, and Hey1 expression and downregulated delta-like ligand4 (DLL4) expression. CONCLUSIONS: Propranolol may play a role in IH treatment by increasing Jagged1 expression in endothelial cells, activating the Notch pathway and inducing the upregulation of the downstream target gene HEY1.

Analysis of safety and efficacy of conservative treatment and endovascular treatment in patients with spontaneous isolated mesenteric artery dissection.

Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare disease with abdominal pain as the main clinical manifestation, but its optimal treatment strategy has not yet been determined. Based on this, this study explored a safe and effective treatment method by analyzing and comparing the safety and efficacy of conservative treatment and endovascular treatment in SISMAD patients. Methods: The clinical and imaging data and treatment effects of 85 patients with SISMAD who were admitted to the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to December 2020 were retrospectively analyzed. Two groups were treated, the data of patients in conservative treatment group and endovascular treatment group were analyzed, and a safe and effective treatment method for SISMAD was discussed. Results: The mean follow-up time was 36.58 ± 25.03 months. The success rate of interventional operation was 86.11% (31/36), and the operation failed because the guide wire could not enter the true lumen in four cases. One case was terminated due to poor physical condition of the patient who could not tolerate surgery. There were no significant differences in gender, body mass index, clinical manifestations, and past history between conservative treatment and endovascular treatment (P > 0.05), but in age, superior mesenteric artery-distal aorta angle, distance from the superior mesenteric artery opening to dissection, dissection length, and true lumen stenosis. There was a statistical difference between the two groups in the rate and Yun classification (P < 0.05). Conclusions: Conservative treatment is effective for most symptomatic SISMAD patients, and close monitoring is required; for patients with persistent symptoms and severe true lumen stenosis (especially Yun classification type III), endovascular treatment is preferred; endovascular treatment is mainly based on endovascular bare stent placement. Patients receiving stent implantation may suffer from stent stenosis or occlusion in the long term, and most of them have no obvious symptoms of intestinal ischemia; the prognosis is good.

[The role of mesenteric lymph in pathogenesis of systemic inflammatory response syndrome and systemic complications following severe acute pancreatitis in rats].

OBJECTIVE: To observe the effect of mesenteric lymph duct ligation (MLDL) on systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis (SAP) in rats. METHODS: Twenty-four Sprague-Dawley (SD) male rats were randomly divided into sham operation group, SAP group, and SAP+MLDL group, with 8 rats in each group. Sham operation group underwent laparotomy only. SAP complicated with multiple organ injury model was reproduced by retrograde injection of sodium taurocholate into the pancreatic duct in SD rats. In SAP+MLDL group MLDL was performed before reproduction of SAP. Rats were sacrificed at 24 hours after operation. The terminal ileum were collected for examination under light microscope. The samples of pancreas, lung and liver were collected for measuring the level of myeloperoxidase (MPO). The mesenteric lymph nodes were harvested for standard bacteriologic culture. The blood levels of diamine oxidase (DAO), D-lactate, endotoxin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were also measured. RESULTS: The blood levels of DAO [(0.64 + or - 0.17) kU/L vs. (0.37 + or - 0.07) kU/L], D-lactate [(8.16 + or - 1.79) ng/L vs. (3.24 + or - 1.00) ng/L], endotoxin [(0.068 + or - 0.019) kEU/L vs. (0.033 + or - 0.009) kEU/L], TNF-alpha [(65.21 + or - 13.38) ng/L vs. (22.16 + or - 5.04) ng/L] and IL-6 [(7.95 + or - 1.83) ng/L vs. (4.26 + or - 1.23) ng/L] in SAP group were increased significantly comparing with those in sham operation group (all P<0.01). The contents of pulmonary tissue [(9.07 + or - 2.52) U/g vs. (4.38 + or - 1.29) U/g], pancreatic [(5.14 + or - 1.24) U/g vs. (2.88 + or - 0.75) U/g] and liver [(6.36 + or - 1.63) U/g vs. (3.19 + or - 0.96) U/g] MPO were increased significantly in SAP group comparing with those in sham operation group (all P<0.01). The rate of bacterial translocation to mesenteric lymph nodes in SAP group was significantly higher than that of the sham operation group (75.0% vs. 0, P< 0.01). Compared to SAP group, the contents of DAO [(0.50 + or - 0.13) kU/L], D-lactate [(6.23 + or - 1.25) ng/L] , endotoxin [(0.048 + or - 0.014) kEU/L], TNF-alpha [(48.50 + or - 13.23) ng/L] and IL-6 [(6.06 + or - 1.64) ng/L] were significantly decreased in SAP+MLDL group (P<0.05 or P<0.01). The levels of pulmonary [(6.58 + or - 1.96) U/g], pancreatic [(4.01 + or - 1.05) U/g] and liver [(4.64 + or - 1.34) U/g] MPO, as well as the rate of bacterial translocation to mesenteric lymph nodes (12.5%) were significantly lower in SAP+MLDL group than those in SAP group (all P<0.05). CONCLUSION: MLDL decreases bacteria/ endotoxin translocation and reduces the systemic inflammatory response by interrupting the lymph flow from the injured gut into the bloodstream. This procedure may protect the small intestine mucosal barrier function and other organs by reducing the neutrophil aggregation and the release of cytokines.

[Effect of blood glucose control after small intestine exclusion surgery in Goto-Kakizaki rat with type 2 diabetes mellitus].

OBJECTIVE: To evaluate the effect of diabetic control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with type 2 diabetes mellitus. METHODS: GK type 2 diabetic rats underwent duodenal bypass (Group A, n = 8) creating a shortcut for ingested nutrients with bypassing duodenum alone, or duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB excluding duodenum and proximal jejunum, or duodenum and total jejunum exclusion (Group C, n = 8), or sub-total small intestine exclusion (Group D, n = 8) creating a shortcut for ingested nutrients with bypassing duodenum, jejunum and sub-total ileum. Controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO, n = 8). Rats were observed for 24 weeks after surgery. Fasting blood glucose (FBG) level was determined on a Surestep plus blood glucose meter (Lifescan) at 0, 1, 3, 6, 12, 24 week. Hemoglobin A1c (HbA1c) level was measured at 0, 12, 24 week on VARIANT Hemoglobin A1c Program (Bio-Ray) with high performance liquid chromatography (HPLC) method. RESULTS: The fasting blood glucose and HbA1c levels significantly decreased after surgery in all the operative groups through the entire follow-up period [Group B (FBG before surgery and 1 week after: (162 +/- 44) mg/dl vs (80 +/- 19) mg/dl; HbAlc before surgery and 12 week after: (8.2 +/- 2.2)% vs (5.1 +/- 1.5)%, P < 0.05 or P < 0.01]; while FBG had no differences before 12 week and significantly increased at 12 week (164 +/- 44) mg/dl and 24 week (180 +/- 42) mg/dl in group SO [preoperative (145 +/- 35) mg/dl, P < 0.01]. As compared with sham-operated rats, all the operative groups showed reduced blood-glucose and HbA1c levels through the entire follow-up period (P < 0.05 or P < 0.01). The FBG and HbA1c levels in Group B significantly decreased versus Group A [24 week (FBG: (82 +/- 21) mg/dl vs (111 +/- 27) mg/dl; HbA1c: (3.9 +/- 0.9)% vs (5.4 +/- 1.2)%, P < 0.05], indicating that duodenal-jejunal bypass had markedly a better effect of diabetic control. But Groups B, C and D were similar to one another (P > 0.05), suggesting that a potential role of proximal gut in the pathogenesis of disease. CONCLUSION: In spontaneous type 2 diabetes mellitus rats, all the small intestinal exclusion including proximal gut are effective in glucose control. In terms of intestinal nutrient absorption, duodenal-jejunal bypass may be an ideal surgery for clinical diabetic control. These findings suggest a potential role of proximal intestine in pathogenesis of type 2 diabetes mellitus.

[Effect of diabetes control after small intestine exclusion surgery in Goto-Kakizaki rat with non-obese type 2 diabetes mellitus].

OBJECTIVE: To evaluate the effect and possible mechanisms of diabetes control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with non-obese type 2 diabetes mellitus. METHODS: Forty GK rats with non-obese type 2 diabetes mellitus underwent duodenal bypass (Group A, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum alone; duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB that excludes the duodenum and proximal jejunum; duodenum and total jejunum exclusion (Group C, n = 8); sub-total small intestine exclusion (Group D, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum, jejunum and sub-total ileum; controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO, n = 8). The rats were observed for 24 weeks after surgery. Body weight, food intake and fasting blood glucose level were tested at 0, 1, 3, 6, 12, 24 weeks after the operation in those groups. The concentrations of insulin and glucagon-like peptide-1 (GLP-1) concentrations were measured before (baseline) and then 30, 60, 120, and 180 minutes after OGTT at 0, 12, 24 weeks after the operation. RESULTS: Mean operating time of all groups was similar. The mean body weight and food intake decreased significantly at 1 week after surgery (P < 0.01) and with no differences among the groups. Fasting blood glucose level decreased significantly after surgery in all the operation groups through the entire follow-up period (P < 0.05). No significant changes in fasting blood glucose level in SO group was found in 12 weeks after the operation, and it increased at 12 and 24 weeks after. Fasting blood glucose levels in group B decreased significantly compared with group A (P < 0.05), but no difference was found among group B, C and D (P > 0.05). Oral glucose-stimulated peak (30 min) levels of blood insulin and GLP-1 increased markedly in operation groups (A, B, C and D) after surgery (P < 0.01). Compared with group A, peak levels of blood insulin and GLP-1 in group B were strikingly higher (P < 0.05), but no difference was found when compared with group C or D (P > 0.05). CONCLUSIONS: In spontaneously non-obese type 2 diabetes mellitus rats, small intestinal exclusion including proximal gut is effective in terms of glucose control and has no direct relation with body weight and food intake loss. Restoration of the first-phase insulin secretion and high secretion of GLP-1 in type 2 diabetic subjects after gastrointestinal bypass surgery seem to be helpful to diabetes control. Taking intestinal nutrient absorption into consideration, duodenal-jejunal bypass may be a better surgery for diabetes control.

[Effect of nano carbon tattooing on the lesion localization in the early colon cancer for additional surgical procedure after endoscopic resection].

OBJECTIVE: To explore the effect of nano carbon tattooing on the lesion localization in the early colon cancer for additional surgical procedure after endoscopic resection. METHODS: Thirty-five patients with early colon cancer accepted additional surgical procedures after endoscopic resection in Fuzhou General Hospital of PLA from May 2014 to November 2016. All the patients underwent nano carbon tattooing before the end of endoscopic resection: 0.1 ml carbon nanoparticles suspension was respectively injected into the normal intestinal submucosa from 1 cm outside the 4 sites (upper, lower, left and right) of the lesion border by colonoscopy, marking the original lesion location and guiding the subsequent additional surgery. Data of these 35 cases were summarized. RESULTS: All the 35 cases, including 22 males and 13 females, with a mean age of 46.5 years(range 35-70), completed the endoscopic disposable carbon nano marking, and the mean operative time was 7.5 minutes(range 5-10). No bleeding, no perforation and no adverse reaction occurred. Four to 21(10±3.5) days after endoscopic resection, the patients received the additional surgery as a result of pathological specimens of endoscopic resection in 10 cases of vascular invasion, 7 cases of severe submucosal infiltration, 7 cases of more than grade G2 in tumor budding, 6 cases of poorly differentiated adenocarcinoma and undifferentiated carcinoma, and 5 cases of positive margin. All the patients underwent laparoscopic surgery. The mean time of intraoperative detection and lesion location was 3.0 minutes(range 1-5). All tattooings were clearly visible under the naked eye. The colon wedge resection were performed in 5 cases, colon segment resection in 14 cases, and radical resection of colon cancer in 16 cases. The operative time was 45 to 180(120±30) min, and the blood loss was 50 ~ 200(50±15) ml. There was no intraoperative complications. The first gas passage time was 12 to 48(24±8) h. The postoperative hospital stay was 10 to 3(6.5±2.5) d. There was no postoperative complication and no perioperative mortality. CONCLUSION: Nano carbon tattooing is helpful for the accurate location of primary lesions in the additional surgical operation after endoscopic resection of early colon cancer, and it can improve the safety and precision of surgical procedures, especially for laparoscopic surgery.

High expression of EGFR predicts poor survival in patients with resected T3 stage gastric adenocarcinoma and promotes cancer cell survival.

Epidermal growth factor receptor (EGFR) is an essential regulator and biomarker of several types of cancer. However, the association between its expression and prognosis in patients with resected T3 stage gastric adenocarcinoma (RT3-GA) remains to be determined. In total, 683 patients with resectable T3-GA who underwent surgery were retrospectively included in the present study, and their immunohistochemical data for EGFR expression were collected. The associations between the patients' clinicopathologic characteristics and EGFR immunohistochemistry data were analyzed by multiple statistical methods. Annexin V apoptosis and MTT cell viability assays were performed to explore the effect of EGFR on AGS gastric adenocarcinoma cell survival. EGFR expression levels were categorized into two groups: low (406 cases) and high (277 cases). High EGFR was demonstrated to be significantly associated with distant metastasis (P=0.043) and severely decreased median overall survival time (MOST) and recurrence-free survival time (MRFST). MOST and MRFST in the low EGFR group were 39 and 37 months, respectively; whereas in the high EGFR group these values were only 18 and 13 months (P=3.10×10-9 and P=6.74×10-8, respectively). Multivariate analysis confirmed that high EGFR expression levels were associated with poor survival, which was associated with significantly increased recurrence risk and ~2-fold elevation in mortality risk [hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.43-2.10; P=2.37×10-8 and HR, 1.80; 95% CI, 1.50-2.17; P=3.80×10-10]. Inhibiting EGFR with AG1478 suppressed its effect on promoting AGS cell survival. These results suggest that high EGFR expression indicates poor survival in patients with RT3-GA, which may be correlated with EGFR promoting GA cell survival.

[Nutritional support for critical ill patients in gastrointestinal surgery].

Nutrition support is an important part of the comprehensive treatment for the critically ill patients with the pathophysiology changes of stress responses related to hypercatabolism, immunity inflammatory reaction disordered and organ dysfunction. Compared with other critical illness, gastrointestinal surgical critically ill patients have the complex characteristics of altered gastrointestinal anatomy and (or) function. Therefore, the nutritional support especially the enteral nutrition support for critical illness patients in gastrointestinal surgery is more difficult and demanding. Mastering the principles, including the timing, route, type and amount of nutrients delivered, and developing an individualized nutritional plan according to the patient's own characteristics, may help to improve its safety and tolerance. Early nutrition support, especially early enteral nutrition, can reduce complications and mortality, enhance recovery and improve outcome for gastrointestinal surgical severely ill patients.

High Tumor Vascular Endothelial Growth Factor Expression Is Associated With Poorer Clinical Outcomes in Resected T3 Gastric Adenocarcinoma.

OBJECTIVES: To investigate the clinical and prognostic significance of high vascular endothelial growth factor (VEGF) expression in resected T3 gastric adenocarcinoma (GA). METHODS: Data of VEGF expression on 453 patients with resected T3 GA were collected from a single institute in Fuzhou, China. VEGF expression in the resected tumor tissues was evaluated by immunohistochemistry (IHC). Associations between VEGF expression outcomes and prognosis were investigated using by the χ(2) test, Kaplan-Meier plus log-rank test, and univariate and multivariate Cox models. RESULTS: In total, 48.6% (220/453) patients had low VEGF expression (IHC score ≤2+). Patients with high VEGF expression (IHC>2+; 233/453, 51.4%) had significantly poorer median recurrence-free survival time (20 vs 55 months, P < 001) and median overall survival time (28 vs 58 months; P < 001) than patients with low VEGF. High VEGF was associated with higher overall recurrence (68.2% vs 51.4%, P = 2.675 × 10(-4)), poorer overall survival (27.5% vs 47.3%, P = 1.719 × 10(-5)), and increased risk of recurrence (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.33-2.19; P = 2.43 × 10(-5)) and death (HR, 1.80; 95% CI, 1.41-2.3; P = 2.19 × 10(-6)). CONCLUSIONS: High VEGF expression is associated with a higher risk of recurrence and shorter survival in resected T3 GA. These findings may provide a foundation for evaluating VEGF-targeted molecular therapies in T3 GA.

[Application of combined laparoscopic endoscopic procedures in the treatment of colorectal neoplasms].

Combined laparoscopic endoscopic procedures (CLEP) is a technical advance in minimally invasive approaches, combining the advantages of both laparoscopy and endoscopy. CLEP expands the use of minimally invasive surgery, and improves the safety, precision and efficacy in the treatment of colorectal neoplasms.Endoscopy-assisted laparoscopic surgery (EALS), laparoscopy- assisted endoscopic surgery (LAES), and laparoscopy endoscopy cooperative surgery (LECS) are being used. The combined application of laparoscopy and colonoscopy or transanal endoscopic microsurgery (TEM) provides a new minimally invasive approach for the treatment of colorectal benign and malignant tumors, especially suitable for the patients undergoing single laparoscopic or endoscopic surgery with greater difficulty and higher risk, or those who would have undergone open operation in the past. CLEP enhances the safety and efficacy of minimally invasive surgery, and achieves the minimal invasiveness and maximal preservation of physiological function at the same time. To a large extent, the integrated operating room and multidisciplinary team help to promote the development of these new minimally invasive procedures.