Prognostic Value of Computed Tomography : Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers

Professor Graeme Murray, Department of Pathology, University of Aberdeen provided us access to the colorectal cancer pathology databases from which the colorectal component of the research was based. Conflict of interest There are no conflicts of interest.Peer reviewedPublisher PD

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The effect of Arginine on gastric cancer cell behaviour : molecular mechanisms of action

The effect of arginine on gastric cancer cell behaviour: Molecular mechanisms of action – Abstract of thesis In gastric cancer patients undergoing surgical resection, the immunosuppression associated with surgery together with the malnutrition, which these patients often have, contribute substantially to a 40% risk of major peri-operative morbidity. Standard nutritional support in these patients has had mixed results. However, the ingestion of key nutrients, which modulate immune, inflammatory and metabolic pathways, also known as immunonutrition, offers a therapeutic modality, by reducing infectious complications by approximately 50%. However, studies have shown that arginine a key nutrient included in immunonutritional regimens not only has immune-enhancing effects but also has the ability to both stimulate and inhibit tumour growth. Therefore concerns remain with regard to the peri-operative use of arginine with regard to tumour growth and dissemination around the time of surgery. The aims of this study were to evaluate the in vitro effects of arginine on gastric cancer cell growth and invasion and the potential molecular mechanisms underlying any changes. A feasibility study was conducted to evaluate the influence of immunonutrition on gastric cancer patients by way of effect on expression of genes involved with tumour growth and invasion. The in vitro data confirmed that both stimulation of apoptosis associated with an increase in caspase 8 expression and cell cycle arrest at G2 phase independent of the effects of both p21 and p53 were associated with inhibition of AGS cell growth. No significant effect on invasion was demonstrated on AGS cells treated with arginine. The feasibility study demonstrated the challenges associated with extracting adequate quantity and quality of RNA from gastric tumour tissue. However, a total of 668 genes demonstrating a two fold change in gene expression were identified in the gastric tumour biopsies following feeding with immunonutrition. In summary, our data confirms inhibition of gastric cancer cell growth with arginine supplementation. However, the peri-operative use of arginine enriched nutritional support in patients with gastric cancer requires further assessment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The effect of Arginine on gastric cancer cell behaviour : molecular mechanisms of action

The effect of arginine on gastric cancer cell behaviour: Molecular mechanisms of action – Abstract of thesis In gastric cancer patients undergoing surgical resection, the immunosuppression associated with surgery together with the malnutrition, which these patients often have, contribute substantially to a 40% risk of major peri-operative morbidity. Standard nutritional support in these patients has had mixed results. However, the ingestion of key nutrients, which modulate immune, inflammatory and metabolic pathways, also known as immunonutrition, offers a therapeutic modality, by reducing infectious complications by approximately 50%. However, studies have shown that arginine a key nutrient included in immunonutritional regimens not only has immune-enhancing effects but also has the ability to both stimulate and inhibit tumour growth. Therefore concerns remain with regard to the peri-operative use of arginine with regard to tumour growth and dissemination around the time of surgery. The aims of this study were to evaluate the in vitro effects of arginine on gastric cancer cell growth and invasion and the potential molecular mechanisms underlying any changes. A feasibility study was conducted to evaluate the influence of immunonutrition on gastric cancer patients by way of effect on expression of genes involved with tumour growth and invasion. The in vitro data confirmed that both stimulation of apoptosis associated with an increase in caspase 8 expression and cell cycle arrest at G2 phase independent of the effects of both p21 and p53 were associated with inhibition of AGS cell growth. No significant effect on invasion was demonstrated on AGS cells treated with arginine. The feasibility study demonstrated the challenges associated with extracting adequate quantity and quality of RNA from gastric tumour tissue. However, a total of 668 genes demonstrating a two fold change in gene expression were identified in the gastric tumour biopsies following feeding with immunonutrition. In summary, our data confirms inhibition of gastric cancer cell growth with arginine supplementation. However, the peri-operative use of arginine enriched nutritional support in patients with gastric cancer requires further assessment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Optimized response prediction in esophagogastric junction adenocarcinomas (EGJAc) with combination of molecular biomarkers and FDG-PET.

1 Background: Predictive biomarkers (BMs) for EGJAc would optimise treatment selection and avoid ineffective therapy. Metabolic response (MR) defined as &gt;35% decrease in tumour FDG Standardized Uptake Value (SUV) between day 0 &amp; 14 after starting chemotherapy has a high negative predictive value (95%) for response, but limited positive predictive value (50%). Combining molecular BMs with FDG-PET may optimise response prediction. We used global gene expression profiling (GEP) to identify molecular BMs that when combined with FDG-PET would improve predictive accuracy. Methods: 28 patients with locally advanced or metastatic EGJAc received platinum based chemotherapy (PBC). FDG PET CT scans were at day 0 and day 14 and GEP (Affymetrix ST1.0 Exon Genechips) on day 0 tumour biopsies. A tissue microarray comprising an independent set of 154 OGJAc who underwent surgery +/− neoadjuvant PBC was used with immunohistochemistry (IHC) for qualification of GEP results. Radiological response was assessed after 3/ 4 cycles of PBC by RECISTv1.1. Results: We identified a gene expression signature (86 genes) that separated FDG PET MR patients(&gt;35% fall SUV day 0 to14) into those that do and do not go on to have a RECIST response. In cross validation, this signature correctly predicted response in 28/28. Pathway analysis on GEP data identified potential novel mechanisms of response, including the Leptin pathway. Leptin mRNA was higher in FDG metabolic responders who did not have a RECIST response compared to those that did. In the independent set, high Leptin protein by IHC was strongly associated with lack of histopathologic response to neoadjuvant PBC (n=64, p=0.002). High Leptin expression also had a therapy independent prognostic effect with longer survival in the absence of histopathologic response or with no neoadjuvant PBC and in low Leptin patients poor survival was mitigated to a certain extent by neoadjuvant PBC (n=154, Kaplan-Mieier, log rank p=0.041 &amp; Cox MVA p=0.040). Conclusions: Molecular biomarkers (Leptin in particular) combine with FDG PET to optimise response prediction in EGJAc. Further investigation of this combined molecular and imaging approach is warranted. </jats:p

Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world

Use of Telemedicine for Post-discharge Assessment of the Surgical Wound: International Cohort Study, and Systematic Review with Meta-analysis

Objective: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardised assessment tools are needed. Summary background data: Surgical site infection is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery. Methods: The primary outcome of this study was surgical site infection reported up to 30-days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analysed primary data from an international cohort study of adult patients undergoing abdominal surgery who were discharged from hospital before 30-days after surgery. The second part combined this data with the results of a systematic review to perform a meta-analysis of all available data conducted in accordance with PRIMSA guidelines (PROSPERO:192596). Results: The cohort study included 15,358 patients from 66 countries (8069 high, 4448 middle, 1744 low income). Of these, 6907 (45.0%) were followed up using telemedicine. The SSI rate reported using telemedicine was slightly lower than with in-person follow-up (13.4% vs. 11.1%, P&lt;0.001), which persisted after risk adjustment in a mixed-effects model (adjusted odds ratio: 0.73, 95% confidence interval 0.63-0.84, P&lt;0.001). This association was consistent across sensitivity and subgroup analyses, including a propensity-score matched model. In nine eligible non-randomised studies identified, a pooled mean of 64% of patients underwent telemedicine follow-up. Upon meta-analysis, the SSI rate reported was lower with telemedicine (odds ratio: 0.67, 0.47-0.94) than in-person (reference) follow-up (I2=0.45, P=0.12), although there a high risk of bias in included studies. Conclusions: Use of telemedicine to assess the surgical wound post-discharge is feasible, but risks underreporting of SSI. Standardised tools for remote assessment of SSI must be evaluated and adopted as telemedicine is upscaled globally