Two different mutational types of familial gastrointestinal stromal tumors: Two case reports.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and cases of GISTs tend to be of the disseminated type, with a global incidence of 10 to 15 cases/million each year. The rarer familial GISTs, which often represent a population, differ in screening, diagnosis, and treatment. Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs. However, whether the same genetic family has different phenotypes has not been reported. CASE SUMMARY: We report two cases of rare GISTs in the same family: A male patient with the V561D mutation in exon 12 of the PDGFRA gene, who has been taking the targeted drug imatinib since undergoing surgery, and a female patient diagnosed with wild-type GIST, who has been taking imatinib for 3 years since undergoing surgery. The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy, and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease. CONCLUSION: Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

Advances in immunotherapy of M2 macrophages and gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the GI tract. They can occur throughout the GI tract, and the survival time of some patients can be improved by first-line targeted therapy with imatinib. However, there are some limitations with imatinib treatment. Immunotherapy for GIST has attracted much attention in recent years, and as one of the most abundant cells in the GIST microenvironment, M2 macrophages play an important role in disease progression. They have unique anti-inflammatory and pro-tumorigenic effects and are one target for immunotherapy. This review summarizes the connection between different factors and the programmed death receptor-1/programmed death ligand-1 pathway and M2 macrophages to reactivate or enhance anti-tumor immunity and improve imatinib efficacy, and to provide new ideas for GIST immunotherapy.

Recent developments in antibacterial or antibiofilm compound coating for biliary stents.

Cholestasis of the indwelling biliary stents usually leads to stone recurrence after endoscopic retrograde cholangio pancreatoraphy (ERCP). Biliary stents, including metallic and none-degradable plastic stents are widely used in clinical settings due to their many excellent properties. However, conventional biliary stents still suffer from poor antibacterial activity and anti-bile-adhesion, which lead to injured, local fibroblasts proliferating. Currently, various coatings for biliary stents have been prepared to meet the clinical demands. In this review, we start by summarizing and discussing classifications of biliary stents and antibacterial/antibiofilm mechanism. Then, the latest advances about developing antibacterial and antibiofilm coatings for improving the properties of biliary stents are reviewed and discussed in detail. Lastly, we list several possible directions for future development of biliary stents coatings and biliary stent, such as anti-bile-adhesion coating, multifunctional coating, drug-eluting biodegradable biliary stents and 3D printed biliary stents.

Can T-tube drainage be replaced by primary suture technique in laparoscopic common bile duct exploration? A meta-analysis of randomized controlled trials.

BACKGROUND: Although laparoscopic common bile duct exploration (LCBDE) is considered the best treatment and has the advantages of being minimally invasive for common bile duct (CBD) stones, the choice of T-tube drainage (TTD) or primary duct closure (PDC) after LCBDE is still controversial. Therefore, the aim of the study was to compare the superiority of PDC versus TTD after LCBDE for choledocholithiasis. METHODS: All potential studies which compare the surgical effects between PDC with TTD were electronically searched for in PubMed, Web of Science, and the Cochrane library databases up to November 2019. Data synthesis and statistical analysis were carried out using RevMan 5.3 software. RESULTS: In total, six randomized controlled trials with 604 patients (307 in the PDC group and 297 in the TTD group) were included in the current meta-analysis. As compared with the TTD group, the pooled data showed that PDC group had shorter operating time (WMD = -24.30; 95% CI = -27.02 to -21.59; p < 0.00001; I2 = 0%; p < 0.88), less medical expenditure (WMD = -2255.73; 95% CI = -3330.59 to -1180.86; p < 0.0001; I2 = 96%; p < 0.00001), shorter postoperative hospital stay (OR = -2.88; 95% CI = -3.22 to -2.54; p < 0.00001; I2 = 60%; p < 0.03), and lower postoperative complications (OR = 0.49; 95% CI = 0.31 to 0.78; p = 0.77; I2 = 0%; p = 0.003). There were no significant differences between the two groups concerning bile leakage (OR = 0.74; 95% CI = 0.36 to 1.53; p = 0.42; I2 = 0%; p = 0.90) and retained stones (OR = 0.96; 95% CI = 0.36 to 2.52; p < 0.93; I2 = 0%; p < 0.66). CONCLUSIONS: LCBDE with PDC should be performed as a priority alternative compared with TTD for choledocholithiasis.

In vitro and in vivo antitumor activity of neochlorogenic acid in human gastric carcinoma cells are complemented with ROS generation, loss of mitochondrial membrane potential and apoptosis induction.

PURPOSE: The main aim of the study was to evaluate in vitro and in vivo the anticancer and apoptotic effects of neochlorogenic acid in human gastric carcinoma cell death and the underlying mechanism of apoptosis induction, reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), m-TOR/PI3K/AKT signalling pathway, cell migration and cell invasion suppression. METHODS: Fluorescence microscopy using DAPI and annexin V/PI staining in combination with flow cytometry was used to study the apoptotic effects induced by neochlorogenic acid on gastric cancer cells. The effects on ROS and MMP were studied by flow cytometry. Western blot assay was used to evaluate the effects of neochlorogenic acid on m-TOR/PI3/Akt signaling pathway. To examine the anti-cancer activity of neochlorogenic acid in vivo, we used the nude mice xenograft model. RESULTS: The results indicated that neochlorogenic acid exhibited an IC50 of 20 µM in these cells. The study also showed that apoptosis was due to loss of MMP and increased intracellular ROS production. Neochlorogenic acid downregulated the expression of key proteins of m-TOR/PI3/Akt signaling pathway. After 6 weeks of neochlorogenic acid administration to mice, the average tumor volumes and growth for the untreated control group were significantly higher than the treated groups. CONCLUSION: Based on these results, we propose that neochlorogenic acid can be a prospective anti-cancer therapeutic lead for the management of human gastric carcinoma.

Prognostic impact of preoperative neutrophil-lymphocyte ratio for surgically resected gastrointestinal stromal tumors.

Neutrophil-lymphocyte ratio (NLR) was shown to be prognostic value in various malignancies. There are limited data about predictive or prognostic role of NLR during gastrointestinal stromal tumors (GISTs) patients. This study evaluated the prognostic significance of preoperative NLR in patients with GIST.We retrospectively enrolled 72 primary GIST patients who received initial curative surgical resection with or without adjuvant imatinib therapy. The preoperative NLR in the peripheral blood was calculated. Univariate and multivariate Cox proportional hazard regression models were used to identify potential predictors of tumor outcomes.The NLR cut-off value of 4.18 was selected. Multivariate analysis revealed that high NLR was associated with a unfavorable prognosis of GISTs (P < .05). Tumor size, tumor location, and age were significantly correlated with the NLR (P < .05).High NLR was an unfavorable prognostic factor of overall survival in GISTs and may be a useful preoperative biomarker of the prognosis of GISTs.

Efficacy and safety of laparoscopic holmium laser lithotripsy in the treatment of complicated biliary calculus: A PRISMA-compliant systematic reviews and meta-analysis.

BACKGROUD: The aim of this study was to assess the efficacy and safety of laparoscopic holmium laser lithotripsy (LHLL) in the treatment of complicated biliary calculus. METHODS: We systematically searched the electronic database (PubMed, EMBASE, Cochrane library, Web of science, and Chinese Biomedical Literature Database) up to May 2018 to identify case-controlled studies that compared LHLL with laparoscopic bile duct exploration (LBDE) for complicated biliary calculus. RESULTS: Five case-controlled studies were included, with 541 patients (273 in the LHLL group and 268 in the LBDE group). Compared with LBDE, LHLL was associated with shorter operative time (weighted mean difference [WMD] = -40.04, P < .001) and lower estimated blood loss (EBL) (WMD = -56.42, P < .001), lesser duration of hospitalization (WMD = -3.93, P < .001) and lower rate of residual stone (OR = 0.13, P < .001). There was no statistically significant differences in bile leakage (OR = 0.48, P = .23) and hemobilia (OR = 0.49, 0.41). CONCLUSION: Current evidence suggests that the efficacy of LHLL is superior to that of LBDE but they are similarly safe for the treatment of complicated biliary calculus. Limited by the quantity and quality of the studies included, these conclusions need to be verified by more high-quality studies.

Prognostic value of MAGE-A9 expression in patients with colorectal cancer.

MAGE-A9 is a novel member of the melanoma-associated antigen (MAGE) family and is expressed in testicular cancer. The present study investigated MAGE-A9 expression as a potential biomarker in colorectal cancer (CRC). Immunohistochemical analysis was used to determine the expression of MAGE-A9 in 201 cases CRC tissues. We used quantitative real-time polymerase chain reaction (RT-PCR) and western blot analysis to further verify the results. The correlation between MAGE-A9 expression, clinicopathological features and prognosis of CRC patients was analyzed. The results showed that MAGE-A9 was predominantly localized in the cytoplasm of cancer cells and stromal cells. Compared to normal adjacent tissues, the high expression rate of MAGE-A9 in CRC tissues was significantly increased (P<0.001). High MAGE-A9 expression was significantly associated with venous invasion (P=0.008) and lymph node metastasis (P<0.001). The survival rate of the CRC patients who were positive for MAGE-A9 expression was significantly lower than that of CRC patients with negative MAGE-A9 expression. Moreover, univariate and multivariate analyses showed that high MAGE-A9 expression was a poor prognostic factor for CRC patients. Hence, MAGE-A9 is expected to become a new target for CRC treatment.

Association of Romo1 gene genetic polymorphisms with risk of gastric cancer in northwestern Chinese population.

Increased expression of reactive oxygen species modulator 1 protein-triggered reactive oxygen species production was reported in the mitochondria of various cancer cell lines. To date there is no report on association between Romo1 gene polymorphisms and gastric cancer risk. To investigate the relationship between Romo1 gene polymorphisms and GC risk, we conducted a case-control study in a population from northwest China (358 GC patients and 412 healthy controls). The genotypes of two SNPs were determined with PCR-denaturing high-performance liquid chromatography and direct DNA sequencing. We found that the genotype and allele distributions of two polymorphisms were significantly different in GC patients compared with controls, When the wild type of two loci were served as the reference group, respectively, significantly increased risk for gastric cancer were associated with rs6060566 TC genotype (Adjusted OR = 1.525, 95 % CI =1.126-2.138), rs6060567 GC genotype (Adjusted OR = 1.641, 95 % CI =1.238-2.291) and CC genotype (Adjusted OR = 1.594, 95 % CI =1.102-2.973). This effect was more pronounced in patients with smoking, alcohol consumption, H.pylori infection,and male patients subgroups. Haplotypes analysis of two genetic variants showed that the most common haplotype TG displayed the strongest evidence of association with GC (corrected P = 9.30 × 10(-5)), and was associated with protection against GC (OR = 0.584). Whereas the CC haplotypes had significant correlation with GC risk (OR = 1.732). These findings suggested genetic polymorphisms of Romo1 gene were associated with significant risk of GC in Northwestern Chinese population, which is strengthened by alcohol use, smoking, H.pylori infection or male patients.

[Effect of colon cancer cell-derived IL-1α on the migration and proliferation of vascular endothelial cells].

OBJECTIVE: To explore the effect of colon cancer cell-derived interleukin-1α on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1α and IL-1ra in the angiogenesis process. METHODS: Western blot was used to detect the expression of IL-1α and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential. We also examined how IL-1α and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively. Double layer culture technique was used to detect the effect of IL-1α on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells. RESULTS: Western blot analysis showed that IL-1α protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9±3.6) and 1 ng/ml rIL-1α group (23.2±4.2), 10 ng/ml rIL-1α group (31.7±4.5), and 100 ng/ml rIL-1α group (38.6±4.9), showing that it was positively correlated with the increasing concentration of rIL-1α (P<0.01 for all). The proliferation assay showed that the absorbance values were 1.37±0.18 in the control group, and 1.79±0.14 in the 1 ng/ml rIL-1α group, 2.14±0.17 in the 10 ng/ml rIL-1α group, and 2.21±0.23 in the 100 ng/ml rIL-1α group, showing a positive correlation with the increasing concentration of rIL-1α(P<0.01 for all). IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P<0.01). The levels of VEGF protein were (1.697±0.072) ng/ml, (3.507±0.064)ng/ml and (4.139±0.039)ng/ml in the control, HUVECs+ IL-1α and HUVECs+ HT-29 co-culture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1α groups and between the control and HUVECs+ HT-29 groups (P<0.01 for both). CONCLUSIONS: Our findings indicate that colon cancer cell-derived IL-1α plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1α and inhibit the angiogenesis in colon cancer.

Lack of Association of the CD247 SNP rs2056626 with Systemic Sclerosis in Han Chinese.

Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors. A recent genome-wide association study (GWAS) indicated that CD247 was strongly associated with SSc, which was subsequently confirmed in a SSc cohort of European population. However, genetic heterogeneity in different ethnic populations may significantly impact the complex trait of SSc. The studies herein aimed to examine whether the SSc-associated SNP rs2056626 of CD247 identified in Caucasian is also associated with Han Chinese SSc. A Han Chinese cohort consisting of 387 SSc patients and 523 healthy controls were examined in the studies. TaqMan assays were performed to examine the SNP. Exact p-values were obtained (Fisher's test) from 2x2 tables of allele counts and disease status. The results showed that there was no association between rs2056626 of CD247 and SSc or any SSc subtypes of Han Chinese. The negative results are important in understanding genetics of SSc in different ethnic populations, which further suggest complex nature of genetics of SSc.

Perioperative immunonutrition for gastrointestinal cancer: a systematic review of randomized controlled trials.

BACKGROUND: To improve the clinical outcome, immunonutrition (IN) was usually used in the patients undergoing elective gastrointestinal caner surgery. However, its effectiveness remains uncertain. METHODS: Randomized controlled trials (RCTs) published between 1995 and 2011 were identified and extracted by two reviewers independently from electronic databases, including PubMed, EMBASE, and Cochrane Library. The quality of included trials was assessed according to the handbook for Cochrane reviewer (V5.0.1). Statistical analysis was carried out with RevMan software. RESULTS: Nineteen RCTs involving a total of 2331 patients were included in our meta-analysis. The results showed perioperative IN significantly reduced length of hospital stay (WMD, -2.62; 95% CI, -3.26 to -1.97; P < 0.01) and morbidity of postoperative infectious complication (RR, 0.44; 95% CI, 0.32 to 0.60; P < 0.01) compared with standard diet. Moreover, perioperative IN also significantly decreased morbidity of postoperative non-infectious complication in comparison with standard diet (RR, 0.72; 95% CI, 0.54 to 0.97; P = 0.03). CONCLUSION: Perioperative IN is effective and safe to reduce postoperative infection, non-infection complication and length of hospital stay.

Octreotide for advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the effectiveness of octreotide in advanced hepatocellular carcinoma participants on the basis of randomized controlled trials. METHODS: We searched the Cochrane Center Register of Controlled Trials in The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database, China Journal Full-text Database, Chinese Scientific Journals Database up to June 2008 in any language. Randomized controlled trials of octreotide for advanced hepatocellular carcinoma were selected and evaluated by two investigators. Any disagreement was solved by discussion. Analyses were performed using Review Manager 4.2. RESULTS: Six randomized controlled trials totaling 352 participants were included. The median survival time was reported in four randomized controlled trials. The results between the octreotide group and the control group (the placebo or best supportive care group) were as follows: 13.0 versus 4.0 months, 1.93 versus 1.97 months, 4.7 versus 5.3 months, and 7.0 versus 2.5 months. Three randomized controlled trials reported 6-month survival rates and 12-month survival rates and meta-analysis results in these two outcomes [(RR 1.35, 95% CI 0.92-1.97); (RR 1.35, 95% CI 0.66-11.16) respectively] were not found to be statistically significant by random-effects model. When we analyzed 6-month survival rates by fixed-effect model (RR 1.30, 95% CI 1.02-1.66), meta-analysis result reached statistical significance. CONCLUSIONS: As for the limitations of the included trials, the result may not demonstrate a significant superiority of octreotide administration in participants with advanced hepatocellular carcinoma from the available evidence.