Xiaonan Yin

Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

Background/Aims This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). Results The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Methods Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Conclusions Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

Comparative effectiveness of preoperative, postoperative and perioperative treatments for resectable gastric cancer: A network meta-analysis of the literature from the past 20 years

BACKGROUND Different preoperative, postoperative or perioperative treatment strategies, including chemotherapy or chemoradiotherapy, are available for patients with gastric cancer, but conventional meta-analyses that assess two alternative treatments are unable to compare differences in overall survival. Thus, we performed a network meta-analysis to identify the best treatment strategy. METHODS We systematically searched and assessed studies for eligibility and extracted data. We then pooled the data and conducted a Bayesian network meta-analysis to combine direct comparisons with indirect evidence. The node-splitting method was used to assess the inconsistency. Rank probabilities were assessed by the probability of treatment rankings. RESULTS Thirty-three eligible randomized controlled trials were included in the network meta-analysis. Four treatments that had significantly improved prognoses when compared with surgery only were postoperative chemotherapy [HR = 0.80 with 95% CrI: (0.73, 0.88)], postoperative chemoradiotherapy [HR = 0.73 with 95% CrI: (0.61, 0.87)], preoperative chemoradiotherapy [HR = 0.77 with 95% CrI: (0.62, 0.98)] and perioperative chemotherapy [HR = 0.69 with 95% CrI: (0.55, 0.84)]. Preoperative chemotherapy, however, did not significantly improve survival when compared with surgery alone [HR = 0.94 with 95% CrI: (0.71, 1.2)]. There was no statistically significant difference between postoperative chemotherapy, postoperative chemoradiotherapy, preoperative chemoradiotherapy and perioperative chemotherapy in terms of overall survival. Chemoradiotherapy after D2 lymphadenectomy did not significantly improve OS when compared with postoperative chemotherapy [HR = 0.95 with 95% CrI: (0.73, 1.3)]. CONCLUSION Among patients with operable gastric cancer, perioperative chemotherapy had the highest probability of being the best treatment. Further clinical resources may be required to assess the efficacy and safety of perioperative chemotherapy for patients with gastric cancer.

Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials

Background Regorafenib is a novel multikinase inhibitor (MKI) approved for use in the treatment of metastatic colorectal cancer (CRC), treatment-refractory gastrointestinal stromal tumors, and other solid tumor malignancies. However, the adverse events (AEs) associated with regorafenib have not been systematically investigated. Hence, we performed a meta-analysis to identify AEs associated with regorafenib in patients with advanced solid tumors. Methods The databases of PubMed, MEDLINE, and Embase and abstracts presented in American Society of Clinical Oncology annual meetings were searched for relevant publications from January 2004 to September 2017. Eligible studies were limited to prospective randomized controlled trials (RCTs) that evaluate the use of regorafenib in patients with advanced solid tumors. Incidence, relative risk (RR), and 95% CIs were calculated using a random or fixed effects model on the basis of the heterogeneity of the included studies. Results A total of 2,065 patients from six RCTs were included, and 1,340 of them received regorafenib and 725 received a placebo. Sixteen all-grade AEs and 15 high-grade AEs were investigated for their association with regorafenib. Results showed that hand–foot skin reaction (HFSR; 54%), diarrhea (33%), fatigue (32%), hypertension (31%), oral mucositis (28%), and anorexia (23%) were the most frequent clinical AEs. The most common high-grade (grade, ≥3) AEs were HFSR (16%), hypertension (13%), fatigue (6%), increased aspartate aminotransferase (AST; 6%), and hypophosphatemia (6%). Pooled RR showed that the use of regorafenib was associated with an increased risk of developing AEs. Subgroup analysis based on the prior MKI treatment showed that prior MKI treatment was associated with an increased incidence of all-grade anorexia (P=0.03) and a reduced incidence of high-grade increased AST (P=0.04). However, subgroup analysis based on the tumor type showed that no significant differences were found when comparing the RR of all-grade and high-grade AEs in patients with CRC or non-CRC. Conclusion The meta-analysis systematically investigated regorafenib-associated AEs. Knowledge of these AEs is essential for minimizing treatment-related toxicities and improving clinical outcomes.

Role of surgical resection for patients with recurrent or metastatic gastrointestinal stromal tumors: A systematic review and meta-analysis

BACKGROUND The role of surgical resection for patients with recurrent or metastatic gastrointestinal stromal tumors is still controversial. This meta-analysis aims to investigate the clinical outcomes of surgery combined with tyrosine kinase inhibitors among patients with recurrent or metastatic gastrointestinal stromal tumors. METHODS We systematically searched PubMed, EMBASE, the Cochrane Library and Wanfangdata without language restriction. Random effect models were used to estimate pooled hazard ratio and the corresponding 95% confidence intervals. Subgroup analyses, sensitivity analysis and trim and fill analysis were also performed. RESULTS A total of 1416 patient from 9 studies were finally enrolled in this meta-analysis. The summary results showed that surgery combined with tyrosine kinase inhibitors showed a tendency of a longer overall survival compared with tyrosine kinase inhibitors treatment alone (HR by random-effects model 0.68, 95% CI 0.54-0.85, I2 = 44.7%) and improved progress-free survival (HR by random-effects model 0.50,95% CI, 0.33-0.76, I2 = 17.9%). The trim and fill analysis and sensitive analysis indicated the relatively robust result. CONCLUSION Surgery combined with tyrosine kinase inhibitors therapy is associated with a better overall survival and progression free survival for patients with recurrent or metastatic gastrointestinal stromal tumors as compared with TKIs treatment alone.

Comparative effectiveness of neoadjuvant treatments for resectable gastroesophageal cancer: a network meta-analysis

Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%]. Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.

Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors

BackgroundMalignant growth and metastasis of gastrointestinal stromal tumors (GIST) occur in some patients even during the course of treatment, but their mechanisms remains poorly understand at the molecular level so far.MethodsProfiles of protein expression in gastric GIST tissues were explored using protein microarray analysis, down-regulation of SPARCL1 (secreted protein acidic and rich in cysteine-like protein 1) was validated by RT-qPCR, western blot and immunohistochemistry. The effect of specific shRNA-induced SPARCL1 downregulation on the biological traits of GIST 882 cell was investigated. We then employed a mouse xenograft model to investigate whether the low-expression of SPARCL1 impact the metastasis ability of GIST cells in vivo.ResultsSPARCL1 was significantly downregulated in the gastric GIST with high-grade malignance as compared with low-grade malignance, its expression was closely correlated with tumor size, mitotic index, distant metastasis at the time of initial diagnosis and tumor progression of GIST (P < 0.05). Moreover, results of the Cox analysis showed that expression of SPARCL1 is an independent prognostic predictors for gastric GIST (P = 0.008; HR 0.157, 95% CI 0.040~ 0.612). Downregulation of SPARCL1 promoted cell migration and invasion, but did not affect proliferation, cell cycle and apoptosis of GIST 882 cells. In mouse xenograft model, GIST cells with the decreased expression of SPARCL1 presented an enhanced ability of liver metastasis (P < 0.05).ConclusionsTaken together, our present study demonstrated that SPARCL1 have a certain degree of malignancy-suppressing potential through inhibiting the metastasis of gastric GIST.

Prognoses in patients with primary gastrointestinal neuroendocrine neoplasms based on the proposed new classification scheme

The aim of this study is to investigate the clinicopathological characteristics, as well as explore the prognostic accuracy of the proposed new classification in gastrointestinal NENs (GI‐NENs) patients.