Fast-track surgery in gastrectomy for gastric cancer: a systematic review and meta-analysis

Purpose

Fast-track surgery aims to attenuate the surgical stress response, reduce complications, and shorten hospital stay. The goal of the present meta-analysis is to assess the safety and effectiveness of fast-track surgery in patients undergoing gastrectomy for gastric cancer compared with conventional perioperative care.

Methods

PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared fast-track surgery with conventional perioperative care in patients undergoing gastrectomy for gastric cancer.

Results

Five studies with a total of 400 patients were included in the meta-analysis. Meta-analysis shows that postoperative hospital stay (weighted mean difference (WMD) ?1.87 days, 95 % confidence interval (CI), ?2.46 to ?1.28 days, P?<?0.00001), time to first passage of flatus (WMD ?0.71 days, 95 % CI, ?1.03 to ?0.39 days, P?<?0.0001), and hospital costs (WMD ?505.87 dollars, 95 % CI, ?649.91 to ?361.84 dollars, P?<?0.00001) were significantly reduced for fast-track surgery. No significant differences were found for readmission rates (relative risk (RR), 1.97 95 % CI, 0.37 to 10.64, P?=?0.43) and total postoperative complications (RR, 0.99 95 % CI, 0.56 to 1.76, P?=?0.97).

Conclusions

Fast-track surgery is safe and effective in gastrectomy for gastric cancer. Further randomized trials are needed to strengthen the conclusions.     

LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis.MethodsLipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson's trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score (NAS) was analyzed.ResultsCompared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine (PC) (P-22:0/18:1), sphingomyelin (SM) (d14:0/18:0), SM (d14:0/24:0), SM (d14:0/22:0), phosphatidylethanolamine (PE) (18:0/22:5), PC (O-22:2/12:0), and PC (26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC (14:0/18:2), PE (18:0/22:5) and PC (26:1/11:0)] or plasmalogens [PC (O-22:0/0:0), PC (O-18:0/0:0), PC (O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC (14:0/18:2), phosphatidic acid (18:2/24:4) were positively correlated with NAS; whereas PC (18:0/0:0) was correlated positively with fibrosis score.ConclusionsThe present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.     

Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity

Background and aimsGlomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown.Methods and resultsCross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m². Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (−12%), NEFA (−26%) and uric acid (−22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = −0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05).ConclusionGH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.     

Effect of insulin secretagogues on major cardiovascular events and all-cause mortality: A meta-analysis of randomized controlled trials

Background and aimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs) and all-cause mortality as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin secretagogues (sulfonylureas and glinides) with this respect.Methods and resultsA MEDLINE database search was performed to identify all RCTs, up to January 1st, 2020, with duration≥52 weeks, in which insulin secretagogues (glibenclamide, gliclazide, glimepiride, glipizide, chlorpropamide, repaglinide, nateglinide) were compared with either placebo or active comparators. The principal endpoints were MACE (restricted for RCT reporting MACEs within their outcomes) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Fourteen RCTs were included in the analysis for MACEs (919 in insulin secretagogues and 1,087 in control group). Insulin secretagogues were not significantly associated with an increased risk of MACEs in comparison with controls (MH–OR 1.08 [95% CI 0.96, 1.22], p = 0.20). When considering the 48 RCTs fulfilling criteria for inclusion in the analysis on all-cause mortality, insulin secretagogues were associated with a significantly increased risk of all-cause mortality (MH–OR 1.11 [1.00, 1.23], p = 0.04).ConclusionsThis meta-analysis suggests that insulin secretagogues are associated with an increased risk of all-cause mortality when compared with placebo or other anti-hyperglycaemic drugs.     

Performance of the Steno type 1 risk engine for cardiovascular disease prediction in Italian patients with type 1 diabetes

Background and aimsPremature cardiovascular disease cause excess mortality in type 1 diabetes (T1D). The Steno T1D Risk Engine was developed and validated in northern European countries but its validity in other populations is unknown. We evaluated the performance of the Steno T1D Risk Engine in Italian patients with T1D.Materials and methodsWe included patients with T1D with a baseline visit between July 2013 and April 2014, who were free of cardiovascular disease and had complete information to estimate risk. The estimated cardiovascular risk score was compared with the 5-year rate of cardiovascular events by means of logistic regression.ResultsAmong 223 patients (mean age 43 ± 13 years, 34.5% male, mean duration of diabetes 22 ± 12 years) the mean estimated cardiovascular risk at 5 years was 5.9% (95% C.I. 5.2–6.5%). At baseline, high estimated risk discriminated the presence of asymptomatic atherosclerosis better than microangiopathy, and was not associated with markers of inflammation or endothelial activation. After a mean follow-up of 4.7 ± 0.5 years, only 3 cardiovascular events were observed and nonetheless the risk score was significantly associated with their incidence (OR 1.22; 95% C.I. 1.08–1.39, p = 0.001). However, the observed event rate was significantly lower than the estimated one (3 vs 13; 95% C.I. 12–14; p < 0.001).ConclusionThe Steno T1D Risk Score identified subjects with subclinical atherosclerosis and high cardiovascular risk in an Italian T1D population. However, the absolute risk was significantly overestimated. Further studies in larger population are needed to confirm these results.     

B7-H3 expression in upper tract urothelial carcinoma associates with adverse clinicopathological features and poor survival

B7-H3, a member of the B7 superfamily, is an immune checkpoint molecule. An association between B7-H3 expression and poor survival has been reported in many types of cancer. However, its prognostic value in patients with upper tract urothelial carcinoma (UTUC) has not yet been reported. The aim of this study was to examine the clinical significance of tumor B7-H3 expression in UTUC. B7-H3 positivity was observed in 36 of 271 cases (13 %) by immunohistochemistry and was significantly associated with several adverse clinicopathological features such as tumor grade, tumor stage, and lymph node metastasis. In addition, B7-H3 positivity was significantly associated with shorter metastasis-free survival and cancer-specific survival. We also found that B7-H3/programmed cell death ligand-1 (PD-L1) co-positivity was significantly associated with worse prognosis. These results suggest the utility of B7-H3 positivity and B7-H3/PD-L1 co-positivity as novel prognostic biomarkers in UTUC, and the potential usefulness of B7-H3 targeted therapy for patients with UTUC, the effect of which may be enhanced by combination with programmed cell death-1 /PD-L1 blockade.     

The progression of the tubulointerstitial fibrosis driven by stress-induced “proliferation–death” vicious circle

Several hypotheses have been developed to interpret the progression of tubulointerstitial fibrosis (TF), including senescence, epithelial–mesenchymal transition, inflammation, chronic hypoxia, and reactive oxygen species. All of these hypotheses are based on persistent cell injury and localized cell death. Proliferation of neighboring renal tubular epithelial cells (RTECs) is beneficial for organ function recovery from acute injury. However, compensatory proliferation is not always advantageous, as the proliferating cells are vulnerable to ongoing detrimental stimuli, such as inflammation, endocrine stress, high blood pressure, hypoxia/ischemia, and the like. Cell injury and death promotes secretion of growth factors, which evokes proliferation of RTECs; entering the cell cycle makes the RTECs more vulnerable to injury and death. Under persistent stress, death and proliferation are mutually promoted and form the vicious circle that triggers, maintains, and augments the inflammation and progression of TF. We hypothesize that the “proliferation–death” circle is another important pathophysiologic mechanism of TF onset. Through this hypothesis, this paper interprets the development and progression of TF. Moreover, the vicious circle may be universal, underlying the development of inflammation and fibrosis in various organs and tissues. The hypothesis also suggests a potential therapy strategy for the inhibition of fibrosis.