Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers.

Patients with newly diagnosed, early stage estrogen receptor positive (ER+) breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K) pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE) tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies

Biological validation of the breast cancer gene expression assay using samples of known immunohistochemical subtype.

<p>(A) Hierarchical clustering of thirty FFPE breast cancer tumor samples with known ER, PR and HER2 status run on the breast cancer gene expression assay. Blue =  triple negative, Pink  =  ER+, Yellow = HER2+ (red = high expression, green = low expression) (B) Box-plots indicating genes that showed statistically significant differential expression in the ER+ subtype, (C) ER+ and HER2+ subtype, (D) HER2+ subtype and (E) triple negative subtype samples (3N) (p-values indicated).</p

PI3K pathway alterations in primary and metastatic ER+ breast cancers.

<p>(A) Distribution of alterations in <i>PIK3CA</i>, <i>AKT1</i> and PTEN across 75 matched primary and metastatic ER+ breast cancers. PTEN null status denotes total absence of PTEN protein in neoplastic cells determined by immunohistochemistry. Arrows indicate patients with alterations in both <i>PIK3CA</i> and PTEN. (B) Frequency and overlap of PI3K pathway alterations in ER+ breast cancer samples. Biomarker frequencies calculated only from patients where tissue was evaluable for all biomarker assays. The data from the single <i>PIK3CA</i> exon 4 mutant sample was pooled with the exon 9 data, and the data from the exon 9/20 double mutant samples were pooled with exon 20 data. (C) Scatterplot of PTEN protein levels indicated by H-score in primary and metastatic samples. The solid diagonal line (y = x) and the dashed lines (y = x±50, y = x±100) are shown to highlight the magnitude of the absolute differences between x and y axes.</p

Ki67 protein and gene expression analysis.

<p>(A) <i>MKI67</i> mRNA expression levels and relationship to Ki67 protein staining levels as determined by IHC. (B) Differentially expressed genes associated with Ki67 high or low protein staining levels (p-values indicated). Ki67 ≤ 15%, N = 16, Ki67 > 15%, N = 48.</p

PIK3CA, AKT1, PTEN and Ki67 status across a collection of 77 matched ER+ breast cancers.

<p>MND - Mutation not detected; E545X - E545A, G, D, K; Q546X - Q546E, K, R, L; Positive - PTEN positive, unable to determine H-Score; NA - Not available.</p

Gene expression correlations between matched primary and metastatic ER+ breast cancer tumor samples.

<p>(A) Gene expression correlations between 61 matched primary and metastatic tumor samples for 90 genes from the breast cancer gene expression assay. Each dot represents the mean fold change between primary and metastatic samples for a single gene. (B) Correlation plots of genes that showed a greater than 1.5 fold difference in expression between matched primary and metastatic samples (FDR-adjusted P<0.05). Each dot represents the fold change between primary and metastatic samples for a single patient. The solid diagonal line (y = x) and the dashed lines (y = x±1) are shown to highlight the magnitude of the absolute differences between x and y axes.</p