Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Upregulation of the transmembrane protease serine 3 mRNA level in radioresistant colorectal cancer tissues.

Aim: To investigate the clinical role of transmembrane protease serine 3 (TMPRSS3) in radioresistance and prognosis of colorectal cancer (CRC). Methods: Standardized mean difference (SMD) and summary area under the curve (AUC) of TMPRSS3 were calculated by combining all available high-throughput data globally. The prognostic significance of TMPRSS3 was determined by Kaplan-Meier and Cox regression analyses. Results:TMPRSS3 was remarkably upregulated in 198 CRC radioresistant cases compared with nonradioresistance (SMD = 0.38, AUC = 0.71). Overexpression of TMPRSS3 was observed in 1601 CRC patients compared with control subjects without CRC. TMPRSS3 was a risk factor for disease-free survival of CRC with the summarized hazard ratio 1.28. Conclusion: TMPRSS3 contributes to the radioresistance and unfavorable prognosis of CRC.

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. METHODS: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. RESULTS: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. CONCLUSION: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer.

The "A Disintegrin and Metalloproteinase with Thrombospondin Motif" (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan-Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32-1.14, P < 0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.

Upregulated expression of SAC3D1 is associated with progression in gastric cancer.

SAC3 domain containing 1 (SAC3D1) has been reported to be involved in numerous types of cancer. However, the role of SAC3D1 in GC has not yet been elucidated. In the present study, the mRNA expression level of SAC3D1 between GC and normal tissues were assessed with a continuous variable meta­analysis based on multiple datasets from public databases. The protein expression level of SAC3D1 in GC and normal tissues was assessed by an in­house immunohistochemistry (IHC). The association between SAC3D1 expression and some clinical parameters was assessed based on the TCGA and IHC data. Survival analysis was performed to assess the association between SAC3D1 expression and the survival of GC patients. The co­expressed genes of SAC3D1 were determined by integrating three online tools, and the enrichment analyses were performed to determine SAC3D1­related pathways and hub co­expressed genes. SAC3D1 was significantly upregulated in GC tumor tissues in comparison to normal tissues with the SMD being 0.45 (0.12, 0.79). The IHC results also indicated that SAC3D1 protein expression in GC tissues was markedly higher than in normal tissues. The SMD following the addition of the IHC data was 0.59 (0.11, 1.07). The protein levels of SAC3D1 were positively associated with the histological grade, T stage and N stage of GC (P<0.001). The TCGA data also revealed that the SAC3D1 mRNA level was significantly associated with the N stage (P<0.001). Moreover, prognosis analysis indicated that SAC3D1 was closely associated with the prognosis of patients with GC. Moreover, 410 co­expressed genes of SAC3D1 were determined, and these genes were mainly enriched in the cell cycle. In total, 4 genes (CDK1, CCNB1, CCNB2 and CDC20) were considered key co­expressed genes. On the whole, these findings demonstrate that SAC3D1 is highly expressed in GC and may be associated with the progression of GC.

Application value of nomogram and prognostic factors of gastric cancer patients who underwent D2 radical lymphadenectomy.

BACKGROUND: The aim of this study was to explore the prognostic factors and establish a nomogram to predict the long-term survival of gastric cancer patients. METHODS: The clinicopathological data of 421 gastric cancer patients, who were treated with radical D2 lymphadenectomy by the same surgical team between January 2009 and March 2017, were collected. The analysis of long-term survival was performed using Cox regression analysis. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the 5-year survival rate probability. RESULTS: In the present study, the total overall 3-year and 5-year survival rates were 58.7 and 45.8%, respectively. The results of the univariate Cox regression analysis revealed that tumor staging, tumor location, Borrmann type, the number of lymph nodes dissected, the number of lymph node metastases, positive lymph nodes ratio, lymphocyte count, serum albumin, CEA, CA153, CA199, BMI, tumor size, nerve invasion, and vascular invasion were prognostic factors for gastric cancer (all, P < 0.05). However, merely tumor staging, tumor location, positive lymph node ratio, CA199, BMI, tumor size, nerve invasion, and vascular invasion were independent risk factors, based on the results of the multivariate Cox regression analysis (all, P < 0.05). The nomogram based on eight independent prognostic factors revealed a well-degree of differentiation with a concordance index of 0.76 (95% CI: 0.72-0.79, P < 0.001), which was better than the AJCC-7 staging system (concordance index = 0.68). CONCLUSION: The present study established a nomogram based on eight independent prognostic factors to predict long-term survival in gastric cancer patients. The nomogram would be beneficial for more accurately predicting the prognosis of gastric cancer, and provide important basis for making individualized treatment plans following surgery.

Relationship between celiac artery variation and number of lymph nodes dissection in gastric cancer surgery.

BACKGROUND: Radical D2 lymphadenectomy for advanced gastric cancer as a standard procedure has gained global consensus. Mounting studies have shown that the number of lymph nodes dissection directly affects the prognosis and recurrence of gastric cancer. Our previous study showed that there was no obvious lymph node around the abnormal hepatic artery derived from the superior mesenteric artery. AIM: To investigate the relationship between celiac artery variation and the number of lymph nodes dissection in gastric cancer surgery. METHODS: The clinicopathological data of 421 patients treated with radical D2 lymphadenectomy were analyzed retrospectively. The difference of the number of lymph nodes dissection between the celiac artery variation group and the normal vessels group and the relationship with prognosis were analyzed. RESULTS: Celiac artery variation was found in 110 patients, with a variation rate of 26.13%. Celiac artery variation, tumor staging, and Borrmann typing were factors that affected lymph node clearance in gastric cancer, and the number of lymph nodes dissection in patients with celiac artery variation was significantly less than that of non-variant groups (P < 0.05). Univariate analysis showed that there was no significant difference in survival time between the two groups (P > 0.05). Univariate and multiple Cox regression analysis showed that celiac artery variation was not a prognostic factor for gastric cancer (P > 0.05). Tumor staging, intraoperative bleeding, and positive lymph node ratio were prognostic factors for gastric cancer patients (all P < 0.05). CONCLUSION: The number of lymph nodes dissection in patients with celiac artery variation was reduced, but there was no obvious effect on prognosis. Therefore, lymph nodes around the abnormal hepatic artery may not need to be dissected in radical D2 lymphadenectomy.

Comprehensive evaluation of FKBP10 expression and its prognostic potential in gastric cancer.

FK506 binding protein 10 (FKBP10) has been reported to be dysregulated in numerous types of cancer; however, few reports have investigated FKBP10 in gastric cancer (GC). The aim of the present study was to investigate FKBP10 expression in GC and to analyze its association with the prognosis of patients with GC. FKBP10 mRNA expression was evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The standardized mean differences of the meta­analysis were comprehensively evaluated for FKBP10 expression from a series of GEO datasets. Kaplan­Meier survival and Cox regression analyses were applied to predict the prognostic value of FKBP10 in patients with GC. Additionally, the protein expression levels of FKBP10 were validated by immunohistochemistry (IHC) in 40 GC and adjacent tissues. FKBP10 co­expression network and bioinformatics analyses were then used to explore the potential functional mechanisms of FKBP10. The results revealed that the mRNA expression levels of FKBP10 were significantly increased in GC within the TCGA and GEO databases. Survival analysis revealed that high FKBP10 expression results in poorer overall survival and disease­free survival (P<0.05). Multivariate cox regression analysis indicate FKBP10 as a dependent prognostic factor. The results of IHC indicated that the protein expression levels of FKBP10 were higher in GC tissues than in adjacent non­GC tissues (P<0.001). Co­expression networks and functional enrichment analysis suggested that FKBP10 may be involved in the development of GC via cell adhesion molecules and extracellular matrix­receptor interaction pathways. Therefore, the findings of the present study indicated that FKBP10 is upregulated in GC tissues, and suggests its potential prognostic value. Therefore FKBP10 may be a potential therapeutic target for the treatment of GC.

Prognostic value of small nuclear RNAs (snRNAs) for digestive tract pan- adenocarcinomas identified by RNA sequencing data.

Malignant tumors of the digestive tract include esophageal, gastric, and colorectal carcinomas, which all have high global mortality rates. A clinical role for small nuclear RNA (snRNA), a type of small non-coding RNA, has not yet been documented for digestive tract pan-adenocarcinomas. Therefore, the aim of the study was to identify differentially expressed snRNAs and to explore their prognostic implications in pan-adenocarcinomas from the esophagus, stomach, colon, and rectum. The pan-carcinoma RNA-sequencing data of four types of digestive tract cancers with 1, 102 cases obtained from The Cancer Genome Atlas (TCGA) project were analyzed and the differentially expressed snRNAs were evaluated using the edgeR package. The prognostic value of each of the selected snRNAs was determined by univariate and multivariate Cox regression analyses. All the digestive tract pan-adenocarcinomas showed differential expression of three snRNAs: the up-regulated RNU1-106 P and RNU6-850 P and the down-regulated RNU6-529 P. Interestingly, RNU6-101 P appeared to be a risk factor for esophageal adenocarcinoma (ESAD) and RNVU1-4 was potentially a protective factor for stomach adenocarcinoma (STAD) survival. This consistent finding of differential expression of all three snRNAs in all four types of digestive system cancers suggests potential roles for these snRNAs in the tumorigenesis of digestive system cancers. RNU6-101 P could play a pivotal role in the progression of ESAD and RNVU1-4 could perform a protective role in STAD. However, since the current findings were based on RNA-sequencing data mining, more studies are needed for verification.

Identification of putative drugs for gastric adenocarcinoma utilizing differentially expressed genes and connectivity map.

Gastric adenocarcinoma (GAC) is a challenging disease with dim prognosis even after surgery; hence, novel treatments for GAC are in urgent need. The aim of the present study was to explore new potential compounds interfering with the key pathways related to GAC progression. The differentially expressed genes (DEGs) between GAC and adjacent tissues were identified from The Cancer Genome Atlas (TCGA) and Genotype­Tissue Expression (GTEx) database. Connectivity Map (CMap) was performed to screen candidate compounds for treating GAC. Subsequently, pathways affected by compounds were overlapped with those enriched by the DEGs to further identify compounds which had anti­GAC potential. A total of 843 DEGs of GAC were identified. Via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 13 pathways were significantly enriched. Moreover, 78 compounds with markedly negative correlations with DEGs were revealed in CMap database (P<0.05 and Enrichment <0). Subpathways of cell cycle and p53 signaling pathways, and core genes of these compounds, cyclin B1 (CCNB1) and CDC6, were identified. This study further revealed seven compounds that may be effective against GAC; in particular methylbenzethonium chloride and alexidine have never yet been reported for GAC treatment. In brief, the candidate drugs identified in this study may provide new options to improve the treatment of patients with GAC. However, the biological effects of these drugs need further investigation.

Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data.

BACKGROUND/AIMS: Left- and right-sided colon cancers are considered to be two different diseases and have altered outcomes. However, specific molecules to predict the prognosis of left- and right-sided colon cancers are currently lacking. METHODS: Expression profiling of colon cancer were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of left- and right-sided colon cancers were compared by DESeq analysis. The prognostic values of DEGs were assessed by univariate and multivariate Cox regression. Prognostic index models of two side colon cancers were conducted with prognostic values genes, respectively. Interaction of DEGs was then analyzed by the protein-protein interaction (PPI). Different biology function of two sides of colon cancer was assessed by Gene Set Enrichment Analysis (GSEA). RESULTS: A total of 167 DEGs were identified between left- and right-sided colon cancers based on TCGA data. Using univariate COX regression analysis, five genes (PHACTR3, CKMT2, CYP2W1, ERFE, HOXC4) were related to overall survival in left-sided, and eight distinguishable genes (EREG, ERFE, HOXC6, SLC22A31, TFF1, GFI1, ZG16, RASL10B) in right-sided. Further, left-sided prognostic model was established with PHACTR3 and CKMT2 (HR=2.040; 95%CI=1.004-4.145; P=0.049). Distinguishable prognostic signature for right-sided colon cancer was established based on EREG, ERFE, GFI1, and RASL10B (HR=3.530; 95%CI: 1.934-6.444; P< 0.001) in multivariate analysis. PPI analysis of 167 DEGs showed that CCL5, GNG4, GNLY, GZMH, DRD2, and FASLG genes were at the core of interaction network. In GSEA function analysis, four pathways, including antigen processing and presentation, natural killer cell mediated cytotoxicity, intestinal immune network for Iga production, and type I diabetes mellitus, were significantly enriched in the DEGs of the right-sided colon cancer. CONCLUSIONS: This study constructs a panel of potential prognostic model of left- and right-sided colon cancers, respectively. We also provide molecular biological alterations between left- and right-sided colon cancers.

A meta-analysis of the lymphatic microvessel density and survival in gastric cancer with 1809 cases.

Lymph node metastasis commonly occurs in gastric cancer. Previous studies have demonstrated that the overexpression of lymphatic microvessel density (LVD) is correlated with various malignancies. To evaluate the potential role of LVD in various malignancies, we conducted a systematic review and meta-analysis to thoroughly investigate the association of LVD expression with tumor progression and survival in gastric cancer. We performed a comprehensive search of common databases and selected studies demonstrating the relationship between LVD expression and gastric cancer prognosis. Hazard ratios (HR) were used to determine the value of LVD for predicting gastric cancer metastasis and prognosis. The data were extracted from the included studies and pooled with the appropriate effects model using STATA 12.0. The results showed that high LVD expression obviously impacted the prognosis of gastric cancer, based on an overall survival (OS) HR of 2.58 (95% CI: 1.91-3.48, P < 0.001) and a disease-free survival (DFS) HR of 2.51 (95% CI: 1.35-4.68, P = 0.004) in the univariate analysis. In addition, the results of the multivariate analysis indicated a remarkable relationship between high LVD expression and gastric neoplasm prognosis. The pooled OS HR was 4.12 (95% CI: 3.45-4.91, P < 0.001). The current meta-analysis shows that high LVD is closely related to tumor metastasis and poor prognosis in gastric malignancy. LVD could be a key factor in tumor lymphatic metastasis. Moreover, LVD is likely a potential index and an effective biomarker for the prediction of patient prognosis.

The anticipating value of PLK1 for diagnosis, progress and prognosis and its prospective mechanism in gastric cancer: a comprehensive investigation based on high-throughput data and immunohistochemical validation.

Polo-like kinase 1 (PLK1) is a multi-functional protein and its aberrant expression is a driver of cancerous transformation and progression. To increase our understanding of the clinical value and potential molecular mechanism of PLK1 in gastric cancer (GC), we performed this comprehensive investigation. A total of 25 datasets and 12 publications were finally incorporated. Additional immunohistochemistry was conducted to validate the expression pattern of PLK1 in GC. The pooled standard mean deviation (SMD) indicated that PLK1 mRNA was up-regulated in GC (SMD=1.21, 95% CI: 0.65-1.77, P< 0.001). Similarly, the pooled odds ratio (OR) revealed that PLK1 protein was overexpressed in GC compared with normal gastric tissue (OR=12.12, 95% CI: 5.41-27.16, P<0.001). The area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.86. Furthermore, our results demonstrated that GC patients with PLK1 overexpression were significantly associated with unfavorable overall survival (HR =1.54, 95% CI: 1.30-1.83, P<0.001), lymph node metastasis (OR = 1.78, 95% CI: 1.13-2.80, P=0.013) and advanced TNM stage (OR=1.48, 95% CI: 1.02-2.15, P=0.038). Altogether, 100 similar genes were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and further with gene-set enrichment analysis. These genes were related to gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways relevant to the cell cycle. Gene set enrichment analysis (GSEA) indicated that PLK1 is associated with various cancer-related pathways. Collectively, this study suggests that PLK1 overexpression could play vital roles in the carcinogenesis and deterioration of GC via regulating tumor-related pathways.

Serious neutropenia following neoadjuvant chemotherapy for locally advanced breast cancer: A case report.

Neoadjuvant chemotherapy has been widely used in patients with locally advanced breast cancer (LABC) to increase the chance of breast conservation. Among the most active adjuvant chemotherapy regimens, doxorubicin and cyclophosphamide are the most common drugs used for breast cancer in adjuvant and advanced settings, and taxanes are added to neoadjuvant regimens to improve the pathological complete response rates. However, chemotherapy is often associated with a variety of acute and long-term side effects, and neutropenia is one of the most common chemotherapy-associated toxicities. Lethal neutropenia is rarely reported in clinics. The present study reports the case of a patient with LABC that received 1 cycle of neoadjuvant chemotherapy [intravenous docetaxel (75 mg/m2), pirarubicin (45 mg/m2) and cyclophosphamide (500 mg/m2) on day 2 in 3-weekly intervals] and succumbed to neutropenia and subsequent multiple organ dysfunction syndrome. The present study suggests that neutropenia may be associated with significant mortality if not managed appropriately. Based on the findings of the present study, individual chemotherapy regimens, dosing schedules, effective methods of the prevention and management of neutropenia, and the management of the discharged patient require additional consideration.

Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: The possible role of BRAF(V) (600E) mutation in the diagnosis and prognosis of papillary thyroid carcinoma (PTC) remains controversial. A systematic review to investigate the diagnostic and prognostic role of BRAF(V) (600E) mutation in patients with PTC is urgently needed. METHODS: A systematic review of relevant literatures was performed in PubMed, EMBASE and CENTRAL. The incremental accuracy (IA) of fine needle aspiration biopsy plus BRAF(V) (600E) mutation analysis over fine needle aspiration biopsy alone, and the statistical data about the association of BRAF(V) (600E) mutation and the prognosis of PTC (risk ratios (RR) for dichotomous data, standard mean differences for continuous data and hazard ratios (HRs) for disease-free survival (DFS) were pooled. Subgroup analysis was performed to explain the heterogeneities. RESULTS: A total of 67 studies were included. The pooled IA was 2% (95% confidence interval (CI): 0·5-4%). The pooled RR for gender, multifocality, lymph node metastasis, extrathyroidal invasion and pathological stage was 1·11 (95% CI: 0·98-1·25), 1·17 (95% CI: 1·09-1·24), 1·36 (95% CI: 1·20-1·53), 1·60 (95% CI: 1·41-1·82), and 1·49 (95% CI: 1·33-1·68), respectively. The pooled standard mean differences for age and tumour size were 0·14 (95% CI: 0·04-0·23) and 0·21 (95% CI: 0·1-0·32), respectively. The pooled HR for DFS was 1·96 (95% CI: 1·62-2·37). Subgroup analysis showed that these statistical results were affected by the geographical background of patients, study design and detection methods. CONCLUSIONS: BRAF(V) (600E) mutation analysis can not only be used in the diagnosis of PTC, but can also predict its prognosis.

Study of celiac artery variations and related surgical techniques in gastric cancer.

AIM: To investigate celiac artery variations in gastric cancer patients and the impact on gastric cancer surgery, and also to discuss the value of the ultrasonic knife in reducing the risk caused by celiac artery variations. METHODS: A retrospective analysis was conducted to investigate the difference in average operation time, intraoperative blood loss, number of harvested lymph nodes, average postoperative drainage within 3 d, and postoperative hospital stay between the group with vascular variations and no vascular variations, and between the ultrasonic harmonic scalpel and conventional electric scalpel surgery group. RESULTS: One hundred and fifty-eight cases presented with normal celiac artery, and 80 presented with celiac artery variation (33.61%). The average operation time, blood loss, average drainage within 3 d after surgery in the celiac artery variation group were significantly more than in the no celiac artery variation group (215.7 ± 32.7 min vs 204.2 ± 31.3 min, 220.0 ± 56.7 mL vs 163.1 ± 52.3 mL, 193.6 ± 41.4 mL vs 175.3 ± 34.1 mL, respectively, P < 0.05). In celiac artery variation patients, the average operation time, blood loss, average drainage within 3 d after surgery in the ultrasonic harmonic scalpel group were significantly lower than in the conventional electric scalpel surgery group (209.5 ± 34.9 min vs 226.9 ± 29.4 min, 207.5 ± 57.1 mL vs 235.6 ± 52.9 mL, 184.4 ± 38.2 mL vs 205.0 ± 42.9 mL, respectively, P < 0.05), and the number of lymph node dissections was significantly higher than in the conventional surgery group (25.5 ± 9.2 vs 19.9 ± 7.8, P < 0.05). CONCLUSION: Celiac artery variation increases the difficulty and risk of radical gastrectomy. Preoperative imaging evaluation and the application of ultrasonic harmonic scalpel are conducive to radical gastrectomy.

FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: a meta-analysis.

AIM: To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC). METHODS: A systematic review of relevant literatures in PubMed, Embase and Cochrane Library was performed. The sensitivity and specificity of diagnostic and staging studies, and HRs for prognosis predicting studies were pooled. The bivariate model was used for diagnostic studies and the random-effect model for prognostic studies. Heterogeneity between included studies was tested using χ(2) test, and subgroup analysis was performed to explain the heterogeneities. All of the calculations were performed using Stata version 11.0. RESULTS: A total of 39 studies were included. The pooled sensitivity of PET in diagnosing PC (30 studies, 1582 patients), evaluating N stating (4 studies, 101 patients) and liver metastasis (7 studies, 316 patients) were 0.91 (95%CI: 0.88-0.93), 0.64 (95%CI: 0.50-0.76), and 0.67 (95%CI: 0.52-0.79), respectively; and the corresponding specificity was 0.81 (95%CI: 0.75-0.85), 0.81 (95%CI: 0.25-0.85), and 0.96 (95%CI: 0.89-0.98), respectively. In prognosis analysis (6 studies, 198 patients), significant difference of overall survival was observed between high and low standardized uptake value groups (HR = 2.39, 95%CI: 1.57-3.63). Subgroup analysis showed that PET/CT was more sensitive than PET alone in evaluating liver metastasis of PC, 0.82 (95%CI: 0.48-0.98) and 0.67 (95%CI: 0.52-0.79), respectively. CONCLUSION: PET can be used as a valuable diagnostic and predictive tool for PC, but its effect in the staging of PC remains indeterminate.

CT enterography in obscure gastrointestinal bleeding: a systematic review and meta-analysis.

The objective of this article is to provide a comprehensive and update overview of clinical application of CT enterography (CTE) in the evaluation of obscure gastrointestinal bleeding (OGIB). We performed a systematic review of relevant literatures in PubMed, EMBASE and The Cochrane Library and pooled the yield of CTE and the incremental yield (IY) of CTE over an alternate modality. A total of 18 studies (n = 660) reported the yield of CTE in evaluating OGIB and the pooled yield was 40% (95% confidence interval (CI): 33-49%). Seven studies (n = 279) compared the yield of CTE with capsule endoscopy (CE). The yield for CTE and CE for all findings was 34% and 53%, respectively (IY = -19%, 95% CI = -34% to -4%). When considering the types of identified lesions, the yield was significantly different for vascular and inflammatory lesions but not significantly different for neoplastic or other lesions. Two studies (n = 63) compared the yield of CTE with double-balloon enteroscopy (DBE). The yield for CTE and DBE was 38% and 78%, respectively (IY = -40%, 95% CI = -55% to -25%). Three studies (n = 49) compared the yield of CTE with digital subtraction angiography. The yield for CTE and digital subtraction angiography was 64% and 60%, respectively (IY = 4%, 95% CI = -40% to 47%). CTE is an excellent diagnostic tool in patients with OGIB. It may play a complementary role to CE and can be used as a triage tool prior to DBE in evaluating OGIB.

Polymorphisms in ERCC1, GSTs, TS and MTHFR predict clinical outcomes of gastric cancer patients treated with platinum/5-Fu-based chemotherapy: a systematic review.

BACKGROUND: Despite genetic polymorphism in response to platinum/5-Fu chemotherapy in gastric cancer (GC) has been studied, data reported so far are conflicting and critical consideration is needed before translation to the treatment of GC. METHODS: We performed a meta-analysis by using 20 eligible studies to examine polymorphisms of ERCC1, GSTs, TS and MTHFR in predicting clinical outcomes (response rate, overall survival and toxicity) of GC patients treated with platinum/5-Fu-based chemotherapy. The association was measured using random/fixed effect odds ratios (ORs) or hazard ratios (HRs) combined with their 95% confidence intervals (CIs) according to the studies' heterogeneity. Statistical analysis was performed with the software STATA 9.0 package. RESULTS: No significant association was found between response rate and genetic polymorphism in TS, MTHFR, ERCC1, GSTM1 and GSTP1. However, response rate was higher in GSTT1 (+) genotype compared with GSTT1 (-) genotype (T-/T+: OR=0.67, 95% CI: 0.47-0.97). With regard to long term outcomes, we could observe a significant longer overall survival in TS 3R/3R [(2R2R+2R3R)/3R3R: HR=1.29, 95% CI: 1.02-1.64] and GSTP1 GG/GA [(GG+AG)/AA: HR=0.51, 95% CI: (0.39, 0.67)] genotypes. In addition, significant association was demonstrated between toxicity and genetic polymorphism in TS, MTHFR and GSTP1 in included studies. CONCLUSION: Polymorphisms of ERCC1, GSTs, TS and MTHFR were closely associated with clinical outcomes of GC patients treated with platinum/5-Fu-based chemotherapy. Studies with large sample size using the method of multi-variant analyses may help us to give more persuasive data on the putative association in future.