Liying Zhao

Laparoscopic vs open D2 gastrectomy for locally advanced gastric cancer: a meta-analysis.

AIM To conduct a meta-analysis comparing laparoscopic (LGD2) and open D2 gastrectomies (OGD2) for the treatment of advanced gastric cancer (AGC). METHODS Randomized controlled trials (RCTs) and non-RCTs comparing LGD2 with OGD2 for AGC treatment, published between 1 January 2000 and 12 January 2013, were identified in the PubMed, Embase, and Cochrane Library databases. Primary endpoints included operative outcomes (operative time, intraoperative blood loss, and conversion rate), postoperative outcomes (postoperative analgesic consumption, time to first ambulation, time to first flatus, time to first oral intake, postoperative hospital stay length, postoperative morbidity, incidence of reoperation, and postoperative mortality), and oncologic outcomes (the number of lymph nodes harvested, tumor recurrence and metastasis, disease-free rates, and overall survival rates). The Cochrane Collaboration tools and the modified Newcastle-Ottawa scale were used to assess the quality and risk of bias of RCTs and non-RCTs in the study. Subgroup analyses were conducted to explore the incidence rate of various postoperative morbidities as well as recurrence and metastasis patterns. A Beggs test was used to evaluate the publication bias. RESULTS One RCT and 13 non-RCTs totaling 2596 patients were included in the meta-analysis. LGD2 in comparison to OGD2 showed lower intraoperative blood loss [weighted mean difference (WMD) = -137.87 mL, 95%CI: -164.41--111.33; P < 0.01], lower analgesic consumption (WMD = -1.94, 95%CI: -2.50--1.38; P < 0.01), shorter times to first ambulation (WMD = -1.03 d, 95%CI: -1.90--0.16; P < 0.05), flatus (WMD = -0.98 d, 95%CI: -1.30--0.66; P < 0.01), and oral intake (WMD = -0.85 d, 95%CI: -1.67--0.03; P < 0.05), shorter hospitalization (WMD = -3.08 d, 95%CI: -4.38--1.78; P < 0.01), and lower postoperative morbidity (odds ratio = 0.78, 95%CI: 0.61-0.99; P < 0.05). No significant differences were observed between LGD2 and OGD2 for the following criteria: reoperation incidence, postoperative mortality, number of harvested lymph nodes, tumor recurrence/metastasis, or three- or five-year disease-free and overall survival rates. However, LGD2 had longer operative times (WMD = 57.06 min, 95%CI: 41.87-72.25; P < 0.01). CONCLUSION Although a technically demanding and time-consuming procedure, LGD2 may be safe and effective, and offer some advantages over OGD2 for treatment of locally AGC.

Immunoscore Signature: A Prognostic and Predictive Tool in Gastric Cancer

Objective: We postulated that the ImmunoScore (IS) could markedly improve the prediction of postsurgical survival and chemotherapeutic benefits in gastric cancer (GC). Summary Background Data: A prediction model for GC patients was developed using data from 879 consecutive patients. Methods: The expression of 27 immune features was detected in 251 specimens by using immunohistochemistry, and a 5-feature-based ISGC was then constructed using the LASSO Cox regression model. Testing and validation cohorts were included to validate the model. Results: Using the LASSO model, we established an ISGC classifier based on 5 features: CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, and CD66bIM. Significant differences were found between the high-ISGC and low-ISGC patients in the training cohort in 5-year disease-free survival (45.0% vs. 4.4%, respectively; P <0.001) and 5-year overall survival (48.8% vs. 6.7%, respectively; P <0.001). Multivariate analysis revealed that the ISGC classifier was an independent prognostic factor. A combination of ISGC and tumor, node, and metastasis (TNM) had better prognostic value than TNM stage alone. Further analysis revealed that stage II and III GC patients with high-ISGC exhibited a favorable response to adjuvant chemotherapy. Finally, we constructed 2 nomograms to predict which patients with stages II and III GC might benefit from adjuvant chemotherapy after surgery. Conclusions: The ISGC classifier could effectively predict recurrence and survival of GC, and complemented the prognostic value of the TNM staging system. Moreover, the ISGC might be a useful predictive tool to identify stage II and III GC patients who would benefit from adjuvant chemotherapy.

Interleukin-17-producing neutrophils link inflammatory stimuli to disease progression by promoting angiogenesis in gastric cancer.

Purpose: Elevated levels of neutrophils have been associated with poor survival in various cancers, but direct evidence supporting a role for neutrophils in the immunopathogenesis of human cancers is lacking. Experimental Design: A total of 573 patients with gastric cancer were enrolled in this study. Immunohistochemistry and real-time PCR were performed to analyze the distribution and clinical relevance of neutrophils in different microanatomic regions. The regulation and function of neutrophils were assessed both in vitro and in vivo. Results: Increased neutrophil counts in the peripheral blood were associated with poor prognosis in gastric cancer patients. In gastric cancer tissues, neutrophils were enriched predominantly in the invasive margin, and neutrophil levels were a powerful predictor of poor survival in patients with gastric cancer. IL17+ neutrophils constitute a large portion of IL17-producing cells in human gastric cancer. Proinflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines. Moreover, neutrophils at the invasive margin were a major source of matrix metalloproteinase-9, a secreted protein that stimulates proangiogenic activity in gastric cancer cells. Accordingly, high levels of infiltrated neutrophils at the invasive margin were positively correlated with angiogenesis progression in patients with gastric cancer. Conclusions: These data provide direct evidence supporting the pivotal role of neutrophils in gastric cancer progression and reveal a novel immune escape mechanism involving fine-tuned collaborative action between cancer cells and immune cells in the distinct tumor microenvironment. Clin Cancer Res; 23(6); 1575–85. ©2016 AACR.

miR-221 and miR-222 Simultaneously Target RECK and Regulate Growth and Invasion of Gastric Cancer Cells

Background Although Helicobacter pylori infection is necessary for development of gastric adenocarcinoma (GAC), the underlying mechanism remains poorly defined. This study aimed to explore how miR-221 and miR-222 are dysregulated after H. pylori infection and how these 2 miRNAs are involved in pathological development of gastric cancer. Material/Methods qRT-PCR analysis was performed to quantify miR-221 and miR-222 expression in patients with H. pylori – induced chronic gastritis, H. pylori-negative healthy controls, and in gastric cancer tissues and the corresponding adjacent normal tissues. Cell models were used to verify the expression profile. Dual luciferase assay was performed to verify putative binding between miR-221 or miR-222 and RECK. A loss-and-gain function study was performed to assess the miR-221/miR-222-RECK axis in gastric cancer cells. Results H. pylori infection leads to significantly higher miR-221 and miR-222 expression. MiR-221 and miR-222 can bind the same sequence of RECK 3′UTR, thereby modulating its expression. Through simultaneous regulation over RECK, miR-221 and miR-222 can promote gastric cancer cell growth and invasion. Conclusions The miR-221/miR-222-RECK axis might be an important path modulating H. pylori infection-related gastric cancer development.

Systematic review and meta-analysis of single-incision versus conventional laparoscopic appendectomy in children ☆

BACKGROUND Increasing evidence has indicated that single-incision laparoscopic appendectomy (SILA) is a safe procedure that has a comparable clinical outcome to conventional multiport laparoscopic appendectomy (CLA) in adult patients. Nevertheless, the use of SILA in pediatric patients is still controversial, and systematic reviews that compare SILA and CLA in children are lacking in the current literature. METHODS A literature search in MEDLINE, EMBASE, Cochrane library, and ClinicalTrials.gov was performed to identify eligible studies that were conducted between January 1998 and September 2014. Primary outcome measures were total postoperative complications, wound infection, intra-abdominal abscess, ileus, and wound hematoma. Secondary outcome measures were operative time, length of hospital stay and the frequency of use of additional analgesics. The random effect model was used for the meta-analysis. RESULTS The literature search identified 2 randomized clinical trials and 12 nonrandomized clinical trials that met the inclusion criteria for the meta-analysis. These studies included a total of 2249 patients: 744 who underwent SILA and 1505 who underwent CLA. No significant differences were observed between the groups with respect to the incidence of total postoperative complications, intraabdominal abscess, ileus, wound hematoma, length of hospital stay, or the frequency of use of additional analgesics. However, SILA was associated with a higher incidence of wound infection (OR=2.25; 95%=1.21-4.17; P=0.01) compared with CLA and required a longer operative time (WMD=5.73 minutes; 95% CI=4.17-7.28; P<0.00001). CONCLUSIONS SILA seems to be a relatively feasible and safe procedure without any superiority to CLA. Thus, SILA may not be a better approach for pediatric patients.

Techniques and feasibility of laparoscopic extended right hemicolectomy with D3 lymphadenectomy

AIM To illustrate the critical techniques and feasibility of laparoscopic extended right hemicolectomy (LERH), according to our previous experience. METHODS Anatomical relationship and operative techniques were demonstrated. One hundred and five consecutive patients who underwent extended right hemicolectomy with D3 lymphadenectomy between January 2008 and May 2011 were included in the present study [laparoscopic group (n = 48) vs open group (n = 57)]. RESULTS The right retrocolic space was the main surgical plan of the LERH. The superior mesenteric vein was the most important anatomical landmark for vascular dissection. The medial-to-lateral dissection approach made the LERH performed efficiently. Compared with the open group, the LERH group had less blood loss (111.7 ± 127.8 mL vs 170.2 ± 49.7 mL, P = 0.023), faster return of flatus (3.0 ± 1.6 d vs 3.7 ± 1.3 d, P = 0.019), and earlier diet (4.2 ± 1.4 d vs 5.0 ± 1.2 d, P = 0.005). Five patients (10.4%) underwent conversion during laparoscopic surgery. The cancer recurrence rates between the two groups were comparable (laparoscopic vs open, 8.6% vs 9.1%, P = 0.335). CONCLUSION For an advanced tumor located at the hepatic flexure or proximal transverse colon, LERH with D3 lymphadenectomy using a medial-to-lateral approach seems to be safe and feasible when the superior mesenteric vein serves as the main anatomical landmark and the right retrocolic space severed as the surgical plan.

Comparative effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in advanced gastric cancer: A meta-analysis of randomized controlled trials

Background & Aims Platinum-based drugs are the most significant chemotherapy for advanced gastric cancer. The study aims to compare the efficacy and safety of oxaliplatin-based therapy versus cisplatin-based therapy in patients with advanced gastric cancer. Materials and Methods An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in patients with advanced gastric cancer were eligible. The primary endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). The second endpoint was the adverse events. Results Five phase II or III RCTs involving a total of 2,046 patients were identified. The results showed that there were no significant difference in ORR (OR = 1.17, 95% CI = 0.98–1.40, p = 0.08, I2 = 0%), PFS (HR = 0.92, 95% CI = 0.84–1.01, p = 0.09, I2 = 0%) and OS (HR = 0.91, 95% CI = 0.82–1.01, p = 0.07, I2 = 0%) between oxaliplatin-based therapy and cisplatin-based therapy. In addition, oxaliplatin-based therapy had lower risk of neutropenia, anemia, nausea, alopecia, thromboembolism, stomatitis and creatinine increased at all grades, and neutropenia, anemia, leukopenia and alopecia at 3–4 grades than cisplatin-based therapy. However, oxaliplatin-based therapy was associated with increased risk of neurosensory toxicity and thrombocytopenia. Conclusions Our meta-analysis showed that there were no significant difference in ORR, PFS and OS between oxaliplatin-based therapy and cisplatin-based therapy. The oxaliplatin-based therapy could generally decrease the risk of adverse effects except neurosensory toxicity and thrombocytopenia.

Circ-104916 is downregulated in gastric cancer and suppresses migration and invasion of gastric cancer cells

Circular RNAs are a large class of noncoding RNA that have shown huge capabilities as gene regulators. Recent evidence suggest that circular RNAs are associated with many diseases, especially cancer. However, little attention has been focused on the expression and function of circular RNA in gastric cancer (GC). In this study, we demonstrate that the expression of circ-104916 is downregulated in GC tissues and cell lines. A lower expression of circ-104916 appeared in deeper invasion depth, higher tumor stage and more frequent lymphatic metastasis patients. Overexpression of circ-104916 effectively inhibited the proliferation, migration and invasion abilities of GC cells in vitro. Western blot showed that circ-104916 overexpression upregulated E-cadherin and downregulated N-cadherin, Vimentin and Slug, indicating that circ-104916 was involved in the epithelial–mesenchymal transition process. Our results revealed that circ-104916 might be a novel potential tumor suppressor and biomarker of GC.

Oxaliplatin/fluorouracil‐based adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery: a systematic review and meta‐analysis of randomized controlled trials

Previous randomized controlled trials and meta‐analyses have demonstrated the ineffectiveness of fluorouracil‐based adjuvant chemotherapy for patients with rectal cancer who have undergone neoadjuvant chemoradiotherapy and subsequent surgery. The role of oxaliplatin/fluorouracil‐based adjuvant chemotherapy in such patients is unknown. We performed a meta‐analysis to evaluate the efficacy of oxaliplatin/fluorouracil‐based adjuvant chemotherapy based on a comparison with fluorouracil‐based adjuvant chemotherapy for patients with rectal cancer.

Association of Adjuvant Chemotherapy With Survival in Patients With Stage II or III Gastric Cancer

Importance The current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy. Objective To construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. Design, Setting, and Participants In this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study’s inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016. Main Outcomes and Measures Concordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival. Results Of the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P < .05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual’s net survival gain attributable to adjuvant chemotherapy. Conclusions and Relevance The survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.