Role of Ursodeoxycholic Acid in the Prevention of Gallstones Formation in Bariatric Patients-a Systematic Review and Meta-Analysis of Randomised Trials.

The aim of this meta-analysis was to assess whether treatment with ursodeoxycholic acid (UDCA) in patients who have undergone bariatric surgery reduces gallstone formation. A systematic literature search was performed using electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, PROSPERO, Google Scholar and the WHO International Clinical Trials Registry platform). RCTs without restrictions on study language, year, status of publication and patient's age were used. Pooled risk ratios were calculated using a random-effects model. Subgroup analyses for drug dose, duration and procedure types were performed. Sensitivity analyses and a summary of findings table were generated to assess the robustness and the level of evidence provided, respectively. Fourteen trials were included (3619 patients, 2292 in UDCA vs 1327 in control group). Procedures included SG, RYGB, OAGB, AGB and Gastroplasty. UDCA dose ranged from 300 to 1200 mg per day. Gallstone formation occurred in 19.3% (8.3% in UDCA vs 38.1% in the control group). UDCA significantly reduced the risk of gallstone formation (14 trials, 3619 patients; RR 0.27, 95% CI 0.18-0.41; P < 0.001). UDCA significantly reduced the risk of symptomatic gallstone disease (6 trials, 2458 patients; RR 0.30, 95% CI 0.21-0.43; P < 0.001). No subgroup difference was found for different doses, duration and type of procedure performed. Oral UDCA treatment significantly reduces the risks of developing gallstones in postoperative bariatric patients from 38 to 8%. The use of 500 to 600 mg UDCA for 6 months is effective and should be implemented in all patients post-bariatric surgery.

Differences in the transcriptome response in the gills of sea lamprey acutely exposed to 3-trifluoromethyl-4-nitrophenol (TFM), niclosamide or a TFM:niclosamide mixture.

Sea lamprey (Petromyzon marinus) control in the Laurentian Great Lakes of North America makes use of two pesticides: 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide, which are often co-applied. Sea lamprey appear to be vulnerable to these agents resulting from a lack of detoxification responses with evidence suggesting that lampricide mixtures produce a synergistic effect. However, there is a lack of information pertaining to the physiological responses of sea lamprey to niclosamide and TFM:niclosamide mixtures. Here, we characterized the transcriptomic responses of the sea lamprey to TFM, niclosamide, and a TFM:niclosamide (1.5 %) mixture in the gill. Along with a control, larval sea lamprey were exposed to each treatment for 6 h, after which gill tissues were extracted for measuring whole-transcriptome responses using RNA sequencing. Differential gene expression patterns were summarized, which included identifying the broad roles of genes and common expression patterns among the treatments. While niclosamide treatment resulted in no differentially expressed genes, TFM- and mixture-treated fish had several differentially expressed genes that were associated with the cell cycle, DNA damage, metabolism, immune function, and detoxification. However, there was no common differential expression among treatments. For the first time, we characterized the transcriptomic response of sea lamprey to niclosamide and a TFM:niclosamide mixture and identified that these agents impact mRNA transcript abundance of genes associated with the cell cycle and cellular death, and immune function, which are likely mediated through mitochondrial dysregulation. These results may help to inform the production of more targeted and effective lampricides in sea lamprey control efforts.

A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. Evidence acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. Evidence synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. Patient summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups.

Transcriptomic impacts and potential routes of detoxification in a lampricide-tolerant teleost exposed to TFM and niclosamide.

Sea lamprey (Petromyzon marinus) control in the Laurentian Great Lakes of North America often relies on the application of 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide mixtures to kill larval sea lamprey. Selectivity of TFM against lampreys appears to be due to differential detoxification ability in these jawless fishes compared to bony fishes, particularly teleosts. However, the proximate mechanisms of tolerance to the TFM and niclosamide mixture and the mechanisms of niclosamide toxicity on its own are poorly understood, especially among non-target fishes. Here, we used RNA sequencing to identify specific mRNA transcripts and functional processes that responded to niclosamide or a TFM:niclosamide mixture in bluegill (Lepomis macrochirus). Bluegill were exposed to niclosamide or TFM:niclosamide mixture, along with a time-matched control group, and gill and liver tissues were sampled at 6, 12, and 24 h. We summarized the whole-transcriptome patterns through gene ontology (GO) term enrichment and through differential expression of detoxification genes. The niclosamide treatment resulted in an upregulation of several transcripts associated with detoxification (cyp, ugt, sult, gst), which may help explain the relatively high detoxification capacity in bluegill. Conversely, the TFM:niclosamide mixture resulted in an enrichment of processes related to arrested cell cycle and growth, and cell death alongside a diverse detoxification gene response. Detoxification of both lampricides likely involves the use of phase I and II biotransformation genes. Our findings strongly suggest that the unusually high tolerance of bluegill to lampricides is due to these animals having an inherently high capacity and flexible detoxification response to such compounds.

Freshwater protected areas can preserve high-performance phenotypes in populations of a popular sportfish.

Recreational fishing has the potential to cause evolutionary change in fish populations; a phenomenon referred to as fisheries-induced evolution. However, detecting and quantifying the magnitude of recreational fisheries selection in the wild is inherently difficult, largely owing to the challenges associated with variation in environmental factors and, in most cases, the absence of pre-selection or baseline data against which comparisons can be made. However, exploration of recreational fisheries selection in wild populations may be possible in systems where fisheries exclusion zones exist. Lakes that possess intra-lake freshwater protected areas (FPAs) can provide investigative opportunities to evaluate the evolutionary impact(s) of differing fisheries management strategies within the same waterbody. To address this possibility, we evaluated how two physiological characteristics (metabolic phenotype and stress responsiveness) as well as a proxy for angling vulnerability, catch-per-unit-effort (CPUE), differed between populations of largemouth bass (Micropterus salmoides) inhabiting long-standing (>70 years active) intra-lake FPAs and adjacent, open access, main-lake areas. Fish from FPA populations had significantly higher aerobic scope (AS) capacity (13%) and CPUE rates compared with fish inhabiting the adjacent main-lake areas. These findings are consistent with theory and empirical evidence linking exploitation with reduced metabolic performance, supporting the hypothesis that recreational fishing may be altering the metabolic phenotype of wild fish populations. Reductions in AS are concerning because they suggest a reduced scope for carrying out essential life-history activities, which may result in fitness level implications. Furthermore, these results highlight the potential for unexploited FPA populations to serve as benchmarks to further investigate the evolutionary consequences of recreational fishing on wild fish and to preserve high-performance phenotypes.

Variation in the Transcriptome Response and Detoxification Gene Diversity Drives Pesticide Tolerance in Fishes.

Pesticides are critical for invasive species management but often have negative effects on nontarget native biota. Tolerance to pesticides should have an evolutionary basis, but this is poorly understood. Invasive sea lamprey (Petromyzon marinus) populations in North America have been controlled with a pesticide lethal to them at lower concentrations than native fishes. We addressed how interspecific variation in gene expression and detoxification gene diversity confer differential pesticide sensitivity in two fish species. We exposed sea lamprey and bluegill (Lepomis macrochirus), a tolerant native species, to 3-trifluoromethyl-4-nitrophenol (TFM), a pesticide commonly used in sea lamprey control. We then used whole-transcriptome sequencing of gill and liver to characterize the cellular response in both species. Comparatively, bluegill exhibited a larger number of detoxification genes expressed and a larger number of responsive transcripts overall, which likely contributes to greater tolerance to TFM. Understanding the genetic and physiological basis for pesticide tolerance is crucial for managing invasive species.

The Effect of Pre-operative Exercise Intervention on Patient Outcomes Following Bariatric Surgery: a Systematic Review and Meta-analysis.

This systematic review aimed to assess the effect of a pre-operative exercise intervention on short- and long-term health and clinical outcomes for adult patients undergoing bariatric surgery (BS). We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), SPORTDiscus and reference lists of relevant papers, through March 2021. Five randomised controlled trials were included (n = 199 patients). Modest increases in cardiorespiratory fitness (VO2max) were found at both pre-operative (0.73 mL kg-1 min-1, P ≤ 0.001) and maximum follow-up time points (0.98 mL kg-1 min-1, P ≤ 0.04). There was no significant effect of an exercise intervention on percentage total weight loss (%TWL). Pre-operative exercise can induce significant short- and long-term improvements in fitness in individuals with obesity. There is insufficient evidence to determine whether pre-operative training impacts other post-operative clinical outcomes.

Contrasting physiological responses between invasive sea lamprey and non-target bluegill in response to acute lampricide exposure.

Control of invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes of North America uses lampricides, which consist of 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide. Lampricides are thought to inhibit aerobic energy synthesis, with TFM having a relatively greater selective action against lampreys. While the toxicity and physiological effects of TFM are known, the impacts associated with exposure to niclosamide and TFM:niclosamide mixtures are poorly characterized in fishes. Therefore, focusing on energy metabolism, we quantified the physiological responses of larval sea lamprey and bluegill (Lepomis macrochirus), a non-target, native species. Exposures consisted of each lampricide alone (TFM at the species-specific 24 h LC10; niclosamide at 1.5% of the mixture's TFM concentration) or a mixture of the two (larval sea lamprey at TFM 24 h LC10 + 1.5% niclosamide; bluegill at sea lamprey's TFM 24 h LC99.9 + 1.5% niclosamide) for 24 h. Tissues (brain, skeletal muscle, and liver) were sampled at 6, 12, and 24 h of exposure and assayed for concentrations of ATP, phosphocreatine, glycogen, lactate, and glucose and tissue lampricide levels. In larval sea lamprey, TFM had little effect on brain and skeletal muscle, but niclosamide resulted in a depletion of high energy substrates in both tissues. Mixture-exposed lamprey showed depletion of high energy substrates, accumulation of lactate, and high mortality rates. Bluegill were largely unaffected by toxicant exposures. However, bluegill liver showed lower glycogen and lactate under all three toxicant exposures suggesting increased metabolic turnover. Bluegill also had lower concentrations of TFM and niclosamide in their tissues when compared to lamprey. Our results indicate that lampricide toxicity in sea lamprey larvae is mediated through a depletion of high energy substrates because of impaired aerobic ATP synthesis. We also confirmed that non-target bluegill showed high tolerance to lampricide exposure, an effect potentially mediated through a high detoxification capacity relative to lampreys.

Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

BACKGROUND: Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS: This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS: Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION: Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

The Impact of the Largest National Joint Registry on Current Knee Replacement Longevity Estimates: An Analysis and Review of Knee Prosthesis Brand and Fixation Technique.

BACKGROUND: The UK National Joint Registry is the single largest joint registry in the world enrolling 1.3 million patients and recently reaching 17 years of follow-up data. Current knee prosthesis longevity estimates are based off smaller sized international registries and the impact of fixation type on prosthesis survival remains unclear. METHODS: We used the UK National Joint Registry 17th annual report to calculate pooled mean survival estimates of total knee replacements (TKRs), unicondylar knee replacements (UKRs), and patellofemoral knee replacements at 10 and 15 years based on both construct brand and fixation technique (cemented vs uncemented). Independent t-testing was performed for significance. RESULTS: All-cause survivorship of TKRs at 10 and 15 years is 96.7% and 95.4%, respectively. For UKRs it is 89.8% and 80.7% and for patellofemoral knee replacements it is 81.6% and 76.5%. In regard to fixation technique, cemented and uncemented TKRs show similar survivorship at both time points. For UKRs uncemented constructs showed improved survivorship compared to cemented at 10 years (92.7% vs 88.2%, P < .001). This was greatest among those <65 years of age. In fact, all construct types regardless of fixation showed increased rate of revision in those <65 years vs those ≥65 years. CONCLUSION: We provide more accurate estimations for knee prosthesis survival and highlight that younger patients, particularly those receiving UKRs, are prone to greater revision risks. This data also suggests that uncemented fixation may offer improved joint survival in these patients.

Validation of an online risk calculator for the prediction of anastomotic leak after colon cancer surgery and preliminary exploration of artificial intelligence-based analytics.

BACKGROUND: Recently published data support the use of a web-based risk calculator ( www.anastomoticleak.com ) for the prediction of anastomotic leak after colectomy. The aim of this study was to externally validate this calculator on a larger dataset. METHODS: Consecutive adult patients undergoing elective or emergency colectomy for colon cancer at a single institution over a 9-year period were identified using the Binational Colorectal Cancer Audit database. Patients with a rectosigmoid cancer, an R2 resection, or a diverting ostomy were excluded. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve (AUROC) was derived and compared with that of the American College of Surgeons National Surgical Quality Improvement Program® (ACS NSQIP) calculator and the colon leakage score (CLS) calculator for left colectomy. Commercially available artificial intelligence-based analytics software was used to further interrogate the prediction algorithm. RESULTS: A total of 626 patients were identified. Four hundred and fifty-six patients met the inclusion criteria, and 402 had complete data available for all the calculator variables (126 had a left colectomy). Laparoscopic surgery was performed in 39.6% and emergency surgery in 14.7%. The anastomotic leak rate was 7.2%, with 31.0% requiring reoperation. The anastomoticleak.com calculator was significantly predictive of leak and performed better than the ACS NSQIP calculator (AUROC 0.73 vs 0.58) and the CLS calculator (AUROC 0.96 vs 0.80) for left colectomy. Artificial intelligence-predictive analysis supported these findings and identified an improved prediction model. CONCLUSIONS: The anastomotic leak risk calculator is significantly predictive of anastomotic leak after colon cancer resection. Wider investigation of artificial intelligence-based analytics for risk prediction is warranted.

A simple web-based risk calculator (www.anastomoticleak.com) is superior to the surgeon's estimate of anastomotic leak after colon cancer resection.

BACKGROUND: Anastomotic leak can be a devastating complication, and early prediction is difficult. The aim of this study is to prospectively validate a simple anastomotic leak risk calculator and compare its predictive value with the estimate of the primary operating surgeon. METHODS: Consecutive patients undergoing elective or emergency colon cancer surgery with a primary anastomosis over a 1-year period were prospectively included. A recently published anastomotic leak risk nomogram was converted to an online calculator ( www.anastomoticleak.com ). The calculator-derived risk of anastomotic leak and the risk estimated by the primary operating surgeon were recorded at the completion of surgery. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve analysis (AUROC) was performed for both risk estimates. RESULTS: A total of 105 patients were screened for inclusion during the study period, of whom 83 met the inclusion criteria. The overall anastomotic leak rate was 9.6%. The anastomotic leak calculator was highly predictive of anastomotic leak (AUROC 0.84, P = 0.002), whereas the surgeon estimate was not predictive (AUROC 0.40, P = 0.243). CONCLUSIONS: A simple anastomotic leak risk calculator is significantly better at predicting anastomotic leak than the estimate of the primary surgeon. Further external validation on a larger data set is required.

Production of nabumetone nanoparticles: Effect of molecular weight, concentration and nature of cellulose ether stabiliser.

The ability of a range of hydrophilic nonionic cellulose ethers (CEs) (namely methylhydroxethylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose) to prepare stable nabumetone nanoparticles (<1000nm, as measured by laser diffraction) using wet-bead milling has been investigated. Due to the limited range of CE molecular weights commercially available, the CEs were degraded using ultrasonication for varying lengths of time to yield CEs of lower molecular weight. Of the CEs tested, only hydroxyethylcellulose was found not to stabilise the production of nabumetone nanoparticles at any of the molecular weights tested, namely viscosity average molecular weights (Mv) in the range of 236-33kg/mol. All other CEs successfully stabilised nabumetone nanoparticles, with the lower molecular weight/viscosity polymers within a series being more likely to result in nanoparticle production than their higher molecular weight counterparts. Unfortunately due to the nature of the ultrasonication process, it was not possible to compare the size of nabumetone particles produced using polymers of identical Mv. There was, however, enough similarity in the Mv of the various polymers to draw the general conclusion that there was no strong correlation between the Mv of the various polymers and their ability to produce nanoparticles. For example hydroxypropylcellulose of 112.2kg/mol or less successfully produced nanoparticles while only ethylhydroxyethylcellulose and hydroxypropylmethyl polymers of 52 and 38.8kg/mol or less produced nanoparticles. These results suggest that polymer molecular weight is not the only determinant of nanoparticle production and that structure of the polymer is at least as important as its molecular weight. In particular the hydrophobic nature of the CE was thought to be an important factor in the production of nabumetone nanoparticles: the more hydrophobic the polymer, the stronger its interaction with nabumetone and the greater its ability to produce nanoparticles. In this context HPC was the most hydrophobic polymer and HEC the least hydrophobic.

Effects of exercise intensity on clot microstructure and mechanical properties in healthy individuals.

BACKGROUND: Exercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development. METHODS: df was measured in 24 healthy individuals prior to, after 5min of submaximal exercise, following maximal exercise, 45min of passive recovery and following 60min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. RESULTS: Significantly increased df was observed following exercise, returning to resting values following 60min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. CONCLUSION: This study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.

Stratum corneum lipid matrix: Location of acyl ceramide and cholesterol in the unit cell of the long periodicity phase.

The extracellular lipid matrix in the skin's outermost layer, the stratum corneum, is crucial for the skin barrier. The matrix is composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs) and involves two lamellar phases: the short periodicity phase (SPP) and the long periodicity phase (LPP). To understand the skin barrier thoroughly, information about the molecular arrangement in the unit cell of these lamellar phases is paramount. Previously we examined the molecular arrangement in the unit cell of the SPP. Furthermore X-ray and neutron diffraction revealed a trilayer arrangement of lipids within the unit cell of the LPP [D. Groen et al., Biophysical Journal, 97, 2242-2249, 2009]. In the present study, we used neutron diffraction to obtain more details about the location of lipid (sub)classes in the unit cell of the LPP. The diffraction pattern revealed at least 8 diffraction orders of the LPP with a repeating unit of 129.6±0.5Å. To determine the location of lipid sub(classes) in the unit cell, samples were examined with either only protiated lipids or selectively deuterated lipids. The diffraction data obtained by means of D2O/H2O contrast variation together with a gradual replacement of one particular CER, the acyl CER, by its partly deuterated counterpart, were used to construct the scattering length density profiles. The acyl chain of the acyl CER subclass is located at a position of ~21.4±0.2Å from the unit cell centre of the LPP. The position and orientation of CHOL in the LPP unit cell were determined using tail and head-group deuterated forms of the sterol. CHOL is located with its head-group positioned ~26±0.2Å from the unit cell centre. This allows the formation of a hydrogen bond with the ester group of the acyl CER located in close proximity. Based on the positions of the deuterated moieties of the acyl CER, CHOL and the previously determined location of two other lipid subclasses [E.H. Mojumdar et al., Biophysical Journal, 108, 2670-2679, 2015], a molecular model is proposed for the unit cell of the LPP. In this model CHOL is located in the two outer layers of the LPP, while CER EOS is linking the two outer layers with the central lipid layers. Finally the two other lipid subclasses are predominantly located in the central layer of the LPP.

Laparoscopic versus open gastrectomy for gastric cancer.

BACKGROUND: Gastric cancer is the third most common cause of cancer-related mortality in the world. Currently there are two surgical options for potentially curable patients (i.e. people with non-metastatic gastric cancer), laparoscopic and open gastrectomy. However, it is not clear whether one of these options is superior. OBJECTIVES: To assess the benefits and harms of laparoscopic gastrectomy or laparoscopy-assisted gastrectomy versus open gastrectomy for people with gastric cancer. In particular, we planned to investigate the effects by patient groups, such as cancer stage, anaesthetic risk, and body mass index (BMI), and by intervention methods, such as method of anastomosis, type of gastrectomy and laparoscopic or laparoscopically-assisted gastrectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov and the WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) until September 2015. We also screened reference lists from included trials. SELECTION CRITERIA: Two review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full text articles for selected references. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful. MAIN RESULTS: In total, 2794 participants were randomised in 13 trials included in this review. All the trials were at unclear or high risk of bias. One trial (which included 53 participants) did not contribute any data to this review. A total of 213 participants were excluded in the remaining trials after randomisation, leaving a total of 2528 randomised participants for analysis, with 1288 undergoing laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the participants were suitable for major surgery.There was no difference in the proportion of participants who died within thirty days of treatment between laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta-analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10; risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11; I(2) = 0%; low quality evidence). There were no events in either group for short-term recurrence (participants = 103; studies = 3), proportion requiring blood transfusion (participants = 66; studies = 2), and proportion with positive margins at histopathology (participants = 28; studies = 1). None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term mortality (HR 0.94, 95% CI 0.70 to 1.25; participants = 195; studies = 3; I(2) = 0%; very low quality evidence), serious adverse events within three months (laparoscopic gastrectomy (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR 0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I(2) = 0%; very low quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30; participants = 162; studies = 4; very low quality evidence), adverse events within three months (laparoscopic gastrectomy (204/268: adjusted proportion = 16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01; participants = 2490; studies = 11; I(2) = 38%; very low quality evidence), quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38; participants = 143; studies = 2; I(2) = 0%; very low quality evidence), length of hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies = 6; I(2) = 83%; very low quality evidence), and number of lymph nodes harvested (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I(2) = 40%; very low quality evidence) were imprecise. There was no alteration in the interpretation of the results in any of the subgroups. AUTHORS' CONCLUSIONS: Based on low quality evidence, there is no difference in short-term mortality between laparoscopic and open gastrectomy. Based on very low quality evidence, there is no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy. However, the data are sparse, and the confidence intervals were wide, suggesting that significant benefits or harms of laparoscopic gastrectomy cannot be ruled out. Several trials are currently being conducted and interim results of these trials have been included in this review. These trials need to perform intention-to-treat analysis to ensure that the results are reliable and report the results according to the CONSORT Statement.