Elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis of patients with primary gastrointestinal stromal tumor.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are considered to reflect the systemic inflammatory response and clinical prognosis. However, the independent prognostic values of the NLR and PLR for patients with gastrointestinal stromal tumor (GIST) remain debatable. This study aims to evaluate the prognostic value of preoperative NLR and PLR in GIST patients. METHODS: We retrospectively reviewed all GIST patients diagnosed and surgically treated at Union Hospital between 2005 and 2018. The preoperative NLR and PLR were calculated to evaluate recurrence-free survival (RFS) and overall survival (OS) by Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were performed to estimate the independent prognostic values. RESULTS: The median follow-up time was 49 months (interquartile range, 22-74 months). The preoperative PLR was significantly increased in the GIST patients with intermediate and high tumor risks. Increases in the NLR (≥2.34) and PLR (≥185.04) were associated with shorter RFS and OS (P < 0.01). Moreover, the multivariate analysis revealed that elevated PLR was an independent factor for shorter RFS (hazard ratio [HR]: 3.041; 95% confidence interval [CI]: 2.001-4.622; P < 0.001) and OS (HR: 1.899; 95% CI: 1.136-3.173; P = 0.014). CONCLUSIONS: The preoperative PLR is a potential biomarker of GIST and is related to the clinical outcome. An elevated preoperative PLR predicts poor prognosis of patients with primary GIST after complete surgical resection.

Clinicopathological features and prognosis of 276 cases of primary small (≤ 2 cm) gastric gastrointestinal stromal tumors: a multicenter data review.

BACKGROUND: Till present, there are still controversies over the epidemiology, pathological features, types of surgical treatment, and prognoses of primary small gastric GISTs (gGISTs). METHODS: From January 1998 to January 2015, patients with primary small gGIST admitted from four high-volume medical centers of the Southern China were enrolled and their data were analyzed to evaluate their clinicopathological features, treatment and prognostic factors to provide evidence-based medical experience for clinical practice. RESULTS: A total of 276 primary small gGIST cases over a period of 18 years were investigated and had a median age of 60 years (range 27-91 years old). Regarding the tumor sites, 24 (8.7%) cases were in the cardia of the stomach, 107 (38.8%) in the fundus, 117 (42.4%) in the gastric body, and 28 (10.1%) in the gastric antrum. Eleven patients (4.0%) underwent a preoperative biopsy. A total of 137 (49.6%), 75 (27.2%), and 64 (23.2%) patients underwent laparoscopic, open resection, and endoscopic resection, respectively. Sixty-four patients (23.2%) had local endoscopic resection, 172 (62.3%) had wedge resection, 7 (2.5%) had proximal gastrectomy, 19 (6.9%) had distal gastrectomy, and 14 (5.1%) had total gastrectomy. Mitotic counts were ≤ 5/50, (5-10)/50, and > 10/50 per HPF in 259 (93.8%), 7 (2.5%), and 10 (3.6%) cases, respectively. There were 259 cases (97.1%) of spindle cell type, 7 (2.5%) epithelial cell types and one case (0.4%) of mixed type. Immunohistochemistry showed 74.6% (206/276), 98.2% (271/276), and 97.4% (269/276) of the patients had co-expression of CD34+, CD117+, and DOG-1+, respectively. Thirty-nine patients underwent genetic testing (39/276, 14.1%). Three patients (1.1%) had positive resection margin. Five high-risk patients received follow-up treatment with imatinib with a median follow-up time of 38 months (range 3-156 months). The overall 1-, 3-, and 5-year overall survival rates were 100%, 99.6%, and 99.1%, respectively. CONCLUSION: Though the incidence of primary small gGISTs increased per annum, the overall survival prognoses were high. Surgery or endoscopic resection was the primary mode of treatment. Pathological features of primary small gGISTs were similar to large gGISTs, and to achieve a timely surgical intervention, the identification of intermediate- and high-risk cases should be a future focus of study.

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.

Ripretinib for the treatment of advanced, imatinib-resistant gastrointestinal stromal tumors.

Discovery of constitutive activation of KIT/PDGFRA tyrosine kinases in gastrointestinal stromal tumors (GISTs) leads to the development of the targeted drug imatinib. However, the inevitable development of imatinib resistance remains a major issue. Ripretinib is a novel targeted drug that inhibits the activities of a broad spectrum of drug-resistant KIT/PDGFRA mutants. It was approved in 2020 and is currently recommended by major international guidelines as the fourth-line and beyond therapy for advanced GISTs. Emerging evidence shows that ripretinib is superior to sunitinib as a second-line treatment for KIT exon 11-mutated GISTs due to its activity against highly heterogeneous frequently occurring secondary mutations. This review summarizes current data on the use of ripretinib to treat advanced imatinib-resistant GISTs. We also propose future research directions to improve the targeted GIST treatment.

Risk Factors of Anastomotic Leakage After Anterior Resection for Rectal Cancer Patients.

OBJECTIVE: Anastomotic leakage (AL) is one of the serious complications after anterior resection for rectal cancer. Defunctioning stoma (DS) is one of the most widely used approaches to prevent it; however, the effect of DS on the occurrence of AL remains controversial. This study aimed to investigate risk factors of AL and assess the effect of DS after anterior resection for rectal cancer patients. METHODS: A retrospective analysis was conducted for the data of 1840 patients who underwent anterior resection for rectal cancer from January 2014 to December 2019. RESULTS: The results showed the overall AL incidence was 7.5%. Multivariate analyses revealed that males [odds ratio (OR) 1.562] and T3-T4 stage (OR 1.729) were independent risk factors for all patients. After propensity score matching analysis, the AL incidence was 14.1% in the group with no DS and 6.4% in the DS group (P<0.001). The clinical AL (grade B + grade C) incidence was 12.4% in no DS group and 4.6% in the DS group (P<0.001). CONCLUSION: The study suggested that males and T3-T4 stage were independent risk factors of AL. In addition, DS could reduce the rate of symptomatic AL.

Short-term Outcomes of Laparoscopy-Assisted vs Open Surgery for Patients With Low Rectal Cancer: The LASRE Randomized Clinical Trial.

Importance: The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established. Objective: To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer. Design, Setting, and Participants: This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022. Interventions: Eligible patients were randomized to receive either laparoscopic or open surgery. Main Outcomes and Measures: The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality. Results: A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days. Conclusions and Relevance: In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT01899547.

Duodenal gastrointestinal stromal tumors: A retrospective study based on a 13 years experience of a single center in China.

AIM: Duodenal gastrointestinal stromal tumors (GISTs) constitute a small rare subset. This study aims to analyze the prognostic differences between duodenal and jejunoileal GISTs and evaluate the clinical treatment and prognostic characteristics of patients with duodenal GISTs. METHODS: Data of patients with primary duodenal or jejunoileal GISTs were collected. Patients were matched through propensity score matching (PSM). Perioperative and long-term outcomes of patients with duodenal GISTs were compared based on surgical approach. RESULTS: Altogether, 101 duodenal and 219 jejunoileal GISTs were identified. In patients with duodenal GISTs, 79 (78%) underwent local resection (LR) and 22 (22%) underwent pancreaticoduodenectomy (PD). Patients undergoing PD had a longer postoperation stay (18.5 vs 13 days, P = 0.001) and more complications (Clavien-Dindo I-II complications for PD vs LR, 31.8 vs 15.2%; Clavien-Dindo III-V complications for PD vs LR, 22.7 vs. 2.5%; P < 0.001). There was no difference in recurrence-free survival (RFS) (P = 0.8) or overall survival (OS) (P = 0.9) when comparing patients who underwent LR versus PD. Multivariable analysis showed that tumor size >5 cm was the only independent predictor of shorter RFS (P = 0.004) and OS (P = 0.012). After matching, there was no significant difference in RFS and OS between patients with duodenal versus jejunoileal GISTs (both P > 0.05). CONCLUSION: The prognosis of duodenal and jejunoileal GISTs are similar. Recurrence and OS of duodenal GISTs primarily depend on tumor size. For duodenal GISTs, LR is associated with comparable long-term survival when compared to PD, but with superior short-term outcomes.

Strategies and recommendations for the management of gastrointestinal surgery during the COVID-19 pandemic: experience shared by Chinese surgeons.

Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public-health pandemic worldwide. Although SARS-CoV-2 has been known to spread primarily through respiratory droplets, recent evidence also supports fecal/oral as an additional route of transmission, raising concerns over gastrointestinal (GI) transmission of the infection. Herein, we, as the front-line Chinese GI surgeons, would like to share our experience and lessons in the combat against COVID-19. It is essential to create science-based, rational, and practical strategies during the outbreak of COVID-19. Here, we provide multi-institutional consensus on minimizing disease transmission while continuing to provide care from all aspects for patients in GI surgery, including outpatient clinics, inpatient units, gastrointestinal endoscopy centers, and adjustments in perioperative care. Our experiences and recommendations are worth sharing and may help to establish specific infection-control and outcome measures.

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.

Enhanced chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil by siRNA recombinant expression vector targeting survivin gene.

OBJECTIVE: To investigate the effects of small interfering RNA (siRNA) recombinant expression vector targeting survivin gene on chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil. METHODS: siRNA recombinant expression vector targeting survivin gene was constructed and transfected into human colon cancer cell lines LOVO. After 48 hours of transfection, cells were harvested for analysis of survivin mRNA and protein expressions using RT-PCR and Western blot. In addition, after human colon cancer cell lines were treated with Survivin siRNA and/or 5-fluorouracil, MTT assay and flow cytometry were used to analyze cell proliferation and apoptosis. RESULTS: Restriction endonuclease analysis confirmed that siRNA recombinant expression vector targeting survivin gene was successfully constructed. Inhibitory ratios of survivin mRNA and protein expressions by Survivin siRNA were 36.33% and 44.65%, respectively. Survivin siRNA combined with 5-fluorouracil significantly increased the cell proliferation inhibitory ratio and apoptosis ratio compared with 5-fluorouracil treating alone (P<0.05). CONCLUSION: The siRNA recombinant expression vector targeting survivin gene can inhibit the expression of survivin gene, and enhance chemotherapy sensitivity of human colon cancer cells to 5-fluorouracil.

[Inhibitory effect of multiple siRNA recombinant expression vector targeting simultaneously Livin and Survivin genes on human colon cancer cells proliferation].

In order to maximize the efficiency and versatility of the vector-based siRNA approach, we have developed a novel siRNA expression vector containing multiple tandem siRNA cassettes to investigate the synergistic inhibitory effect of it on human colon cancer cells proliferation. Multiple siRNA recombinant expression vector targeting simultaneously Livin and Survivin genes was constructed and transfected into human colon cancer cell. The effect of multiple siRNA recombinant expression vector was detected by RT-PCR, Western blotting and flow cytometry. It was confirmed by restriction endonuclease and sequence analysis that multiple siRNA recombinant expression vector targeting simultaneously Livin and Survivin genes was constructed successfully. Livin and Survivin genes inhibition ratio of Livin and Survivin siRNA at mRNA levels were 27.90% and 32.24%, at protein levels were 22.28% and 40.86%, the apoptotic ratio was (11.69 +/- 1.37) %, but the synergistic effect was weaker than Livin and Survivin RNA interference, respectively. The multiple siRNA recombinant expression vector targeting simultaneously Livin and Survivin genes has been constructed successfully. It can inhibit the expression of Livin and Survivin genes in human colon cancer cells, but the synergistic effect was weaker than Livin and Survivin RNA interferences, respectively.

[Effects of magnetic gemcitabine stealth nano-liposomes on the characteristics of breast cancer cell line MCF-7].

The magnetic responsibility and antitumor effect of magnetic gemcitabine stealth nano-liposomes (MGSL) on breast cancer cell line MCF-7 in vitro and in vivo was evaluated. The magnetic response and targeting effect of MGSL in vivo were investigated. Morphological feature and ultrastructure changes of apoptosis of MCF-7 cells were observed. The effect of MGSL on proliferation inhibitory rate of MCF-7 cells was measured with MTT method. The FCM analysis was carried out to examine the cell cycle distribution and cell apoptotic rate. The antitumor effect on human breast cancer xenografts in nude mice was also studied. MGSL was able to converge at the targeting tissue under tridimensional magnetic field and the gemcitabine concentration around it increased, while the amount of gemcitabine in other organs decreased, such as in kidneys and heart. MCF-7 cell line was sensitive to MGSL and the cytotoxity was correlated with the loaded drug dose. The effect of MGSL on apoptosis of MCF-7 was obvious and the rate of apoptosis was 51.62%. The growth speed of tumor in the group of MGSL (+) significantly slowed down than that of other groups. MGSL prepared by reverse-phase evaporation method met with the demand of targeted delivery system, and it might be an effective antitumor agent.

Performance of risk stratification systems for gastrointestinal stromal tumors: A multicenter study.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor type in the gastrointestinal system. Presently, various classification systems to prognosticate GISTs have been proposed. AIM: To evaluate the application value of four different risk stratification systems for GISTs. METHODS: Patients who were diagnosed with GISTs and underwent surgical resection at four hospitals from 1998 to 2015 were identified from a database. Risk of recurrence was stratified by the modified National Institute of Health (NIH) criteria, the Armed Forces Institute of Pathology (AFIP) criteria, the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram, and the contour maps. Receiver operating characteristic (ROC) curves were established to compare the four abovementioned risk stratification systems based on the area under the curve (AUC). RESULTS: A total of 1303 patients were included in the study. The mean age of the patients was 55.77 ± 13.70 yr; 52.3% of the patients were male. The mean follow-up period was 64.91 ± 35.79 mo. Approximately 67.0% the tumors were located in the stomach, and 59.5% were smaller than 5 cm; 67.3% of the patients had a mitotic count ≤ 5/50 high-power fields (HPFs). Thirty-four tumors ruptured before and during surgery. Univariate analysis demonstrated that tumor size > 5 cm (P < 0.05), mitotic count > 5/50 HPFs (P < 0.05), non-gastric location (P < 0.05), and tumor rupture (P < 0.05) were significantly associated with increased recurrence rates. According to the ROC curve, the AFIP criteria showed the largest AUC (0.754). CONCLUSION: According to our data, the AFIP criteria were associated with a larger AUC than the NIH modified criteria, the MSKCC nomogram, and the contour maps, which might indicate that the AFIP criteria have better accuracy to support therapeutic decision-making for patients with GISTs.

Clinicopathological Characteristics and Prognosis of Hepatoid Adenocarcinoma of the Stomach: Evaluation of a Pooled Case Series.

Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique gastric malignancy. The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis. We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016, as well as 294 cases reported prior to 2017 in research databases. Among these patients, 45.6% (115/252) had lesions in the gastric antrum and 77.0% (235/305) were male. Elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (75/93, 80.6%). Vascular invasion (199/286, 69.6%), lymph node metastasis (222/283, 78.4%), and preoperative distant metastasis (121/328, 36.9%) were commonly observed. The 5-year disease-free survival (DFS) and disease-specific survival (DSS) were 20.7% and 29.2%, respectively. DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS: P<0.001, hazard ratio (HR)=-1.831, 95% confidence interval (CI): 0.060-0.429; DSS: P<0.001, HR=-2.185, 95% CI: 0.032-0.401]. In conclusion, HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer. Complete surgery, early pTNM stage, and adjuvant therapy may predict a more favorable prognosis. Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.

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.

[Double sites short hairpin RNAs targeting epidermal growth factor receptor to promote colon cancer cells apoptosis and enhance 5-fluorouracil chemotherapy effect].

OBJECTIVE: To investigate the differences about RNA interference (RNAi) technique which focuses on single or multiple sites to suppress colon cancer LoVo cell line's epidermal growth factor receptor (EGFR) mRNA and protein expression, induce cell apoptosis and enhance 5-fluorouracil (5-FU) sensitivity. METHODS: The human colon cancer LoVo cells were transfected by liposome with pU6-EGFR-shRNA-1 and pU6-EGFR-shRNA-2 expressive vectors which were established by p Genesil-1 plasmid and EGFR short hairpin RNA (shRNA) synthesized in vitro, then were selected for 4 weeks by using G418. Five groups were selected for the study: Group 1: the normal cultured LoVo cells; Group 2: the negative control plasmid HK; Group 3: pU6-EGFR-shRNA-1 plasmid vector; Group 4: pU6-EGFR-shRNA-2 plasmid vector; Group 5: pU6-EGFR-shRNA-1 and pU6-EGFR-shRNA-2, half for each. The mRNA and protein expression were assessed using Real Time PCR and Western blot, the cell apoptosis was determined via flow cytometry, and the suppressive rate and IC(50) to LoVo cells by 5-FU of different concentrations and time points were carried out by using Cell Counting Kit-8 (CCK-8). RESULTS: Expression plasmids encoding shRNA were successfully established and transfected into the LoVo cells. In group 3, 4 and 5, the mRNA expression was decreased by (80.2 +/- 3.4)%, (81.3 +/- 2.8)% and (90.6 +/- 2.8)%, respectively, and protein expression was decreased by (74.1 +/- 4.0)%, (73.4 +/- 2.3)% and (90.4 +/- 3.3)%, respectively; meanwhile, cell apoptosis increased by (10.4 +/- 0.5)%, (10.1 +/- 0.4)% and (14.2 +/- 0.5)%, respectively. The IC(50) of 5-FU and cell suppressive rate analysis demonstrated that there were significant differences among group 5, groups 3 and 4, and groups 1 and 2, but there were no significant difference between group 1 and group 2, as well as group 3 and group 4. CONCLUSIONS: Both pU6-EGFR-shRNA-1 and pU6-EGFR-shRNA-2 were capable of suppressing EGFR expression of LoVo cells, and therefore promoting apoptosis and increasing the cell toxicity of 5-FU. The targeting double combined sites RNAi technique was significantly better than single site interference. The new therapeutic modalities in the treatment of human colon cancer are suggested by this study.

Radiofrequency ablation vs. hepatic resection for resectable colorectal liver metastases.

The treatments of resectable colorectal liver metastases (CRLM) are controversial. This study aimed to evaluate the relative efficacy and safety of hepatic resection (HR) and radiofrequency ablation (RFA) for treating resectable CRLM. Between January 2004 and May 2010, the enrolled patients were given hepatic resection (HR group; n=32) or percutaneous RFA (RFA group; n=21) as a first-line treatment for CRLM. All the tumors had a maximum diameter of 3.5 cm and all patients had five or less tumors. The patient background, tumor characteristics, cumulative survival rate and recurrence-free survival rate were assessed in both groups. There were significantly more patients with comorbidities in the RFA group than those in the HR group (17 in RFA group vs. 10 in HR group; P<0.000). The mean maximum tumor diameter in the HR group and RFA group was 2.25±0.68 and 1.89±0.62 cm (P=0.054), and the mean number of tumors was 2.28±1.05 and 2.38±1.12 (P=0.744), respectively. The 1-, 3- and 5-year cumulative survival rates in the HR group were 87.5%, 53.1% and 31.3%, respectively, and those in the RFA group were 85.7%, 38.1% and 14.2%, respectively with the differences being not significant between the two groups (P=0.062). The 1-, 3- and 5-year recurrence-free survival rates in the HR group were 90.6%, 56.3% and 28.1%, respectively, and those in the RFA group were 76.1%, 23.8% and 4.8%, respectively, with the differences being significant between the two groups (P=0.036). In conclusion, as HR has greater efficacy than RFA in the treatment of resectable CRLM, we recommend it as the first option for this malignancy.

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.

IFN-γ secretion in gut of Ob/Ob mice after vertical sleeve gastrectomy and its function in weight loss mechanism.

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.

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.