Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatmentof acute pediatric pancreatitis. The preferred reporting items for systematic review(PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (Pub Med: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly(SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.

Intralesional steroid is beneficial in benign refractory esophageal strictures:A meta-analysis

AIM To analyze the effect of intralesional steroid injections in addition to endoscopic dilation of benign refractory esophageal strictures.METHODS A comprehensive search was performed in three databases from inception to 10 April 2017 to identify trials, comparing the efficacy of endoscopic dilation to dilation combined with intralesional steroid injections. Following the data extraction, meta-analytical calculations were performed on measures of outcome by the randomeffects method of Der Simonian and Laird. Heterogeneity of the studies was tested by Cochrane's Q and I^2 statistics. Risk of quality and bias was assessed by the Newcastle Ottawa Scale and JADAD assessment tools.RESULTS Eleven articles were identified suitable for analyses, involving 343 patients, 235 cases and 229 controls in total. Four studies used crossover design with 121 subjects enrolled. The periodic dilation index(PDI) was comparable in 4 studies, where the pooled result showed a significant improvement of PDI in the steroid group(MD:-1.12 dilation/month, 95% CI:-1.99 to -0.25 P = 0.012; I^2 = 74.4%). The total number of repeat dilations(TNRD) was comparable in 5 studies and showed a non-significant decrease(MD:-1.17, 95%CI:-0.24-0.05, P = 0.057; I^2 = 0), while the dysphagia score(DS) was comparable in 5 studies and did not improve(SMD: 0.35, 95%CI:-0.38, 1.08, P = 0.351; I^2 = 83.98%) after intralesional steroid injection.CONCLUSION Intralesional steroid injection increases the time between endoscopic dilations of benign refractory esophageal strictures. However, its potential role needs further research.

Network meta-analysis of randomized controlled trials on esophagectomies in esophageal cancer:The superiority of minimally invasive surgery

BACKGROUND Previous meta-analyses,with many limitations,have described the beneficial nature of minimal invasive procedures.AIM To compare all modalities of esophagectomies to each other from the results of randomized controlled trials(RCTs)in a network meta-analysis(NMA).METHODS We conducted a systematic search of the MEDLINE,EMBASE,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and CENTRAL databases to identify RCTs according to the following population,intervention,control,outcome(commonly known as PICO):P:Patients with resectable esophageal cancer;I/C:Transthoracic,transhiatal,minimally invasive(thoracolaparoscopic),hybrid,and robot-assisted esophagectomy;O:Survival,total adverse events,adverse events in subgroups,length of hospital stay,and blood loss.We used the Bayesian approach and the random effects model.We presented the geometry of the network,results with probabilistic statements,estimated intervention effects and their 95% confidence interval(CI),and the surface under the cumulative ranking curve to rank the interventions.RESULTS We included 11 studies in our analysis.We found a significant difference in postoperative pulmonary infection,which favored the minimally invasive intervention compared to transthoracic surgery(risk ratio 0.49;95%CI:0.23 to 0.99).The operation time was significantly shorter for the transhiatal approach compared to transthoracic surgery(mean difference-85 min;95%CI:-150 to-29),hybrid intervention(mean difference-98 min;95%CI:-190 to-9.4),minimally invasive technique(mean difference-130 min;95%CI:-210 to-50),and robot-assisted esophagectomy(mean difference-150 min;95%CI:-240 to-53).Other comparisons did not yield significant differences.CONCLUSION Based on our results,the implication of minimally invasive esophagectomy should be favored.

Chronic kidney disease severely deteriorates the outcome of gastrointestinal bleeding: A meta-analysis

AIM To understand the influence of chronic kidney disease(CKD) on mortality, need for transfusion and rebleeding in gastrointestinal(GI) bleeding patients.METHODS A systematic search was conducted in three databases for studies on GI bleeding patients with CKD or endstage renal disease(ESRD) with data on outcomes of mortality, transfusion requirement, rebleeding rate and length of hospitalization(LOH). Calculations were performed with Comprehensive Meta-Analysis software using the random effects model. Heterogeneity was tested by using Cochrane's Q and I2 statistics. Mean difference(MD) and OR(odds ratio) were calculated.RESULTS1063 articles(EMBASE: 589; PubM ed: 459; Cochrane: 15) were found in total. 5 retrospective articles and 1 prospective study were available for analysis. These 6 articles contained data on 406035 patients, of whom 51315 had impaired renal function. The analysis showed a higher mortality in the CKD group(OR = 1.786, 95%CI: 1.689-1.888, P < 0.001) and the ESRD group(OR = 2.530, 95%CI: 1.386-4.616, P = 0.002), and a rebleeding rate(OR = 2.510, 95%CI: 1.521-4.144, P < 0.001) in patients with impaired renal function. CKD patients required more unit red blood cell transfusion(MD = 1.863, 95%CI: 0.812-2.915, P < 0.001) and spent more time in hospital(MD = 13.245, 95%CI: 6.886-19.623, P < 0.001) than the controls.CONCLUSION ESRD increases mortality, need for transfusion, rebleeding rate and LOH among GI bleeding patients. Prospective patient registries and observational clinical trials are crucially needed.