Summary Background 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov , NCT03471494 . Findings Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding National Institute for Health Research Global Health Research Unit.

Background: Effective screening for colorectal cancer can reduce mortality by early detection of tumours and colonic polyps. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a potential non-invasive diagnostic tool for detection of cancer. The aim of this study was to evaluate the reliability of breath-testing for colorectal cancer screening and early diagnosis using an advanced breath sampler. Methods: The exhaled breath of patients with colorectal cancer and non-cancer controls with negative findings on colonoscopy was collected using the ReCIVA ® Breath Sampler. This portable device is able to capture the alveolar breath fraction without environmental contamination. VOCs were desorbed thermally and analysed by gas chromatography-mass spectrometry. The discriminatory ability of VOCs in detecting colorectal cancer was evaluated by receiver operating characteristic (ROC) curve analysis for each VOC, followed by cross-validation by the leave-one-out method, and by applying stepwise logistic regression analysis. Results: The study included 83 patients with colorectal cancer and 90 non-cancer controls. Fourteen VOCs were found to have significant discriminatory ability in detecting patients with colorectal cancer. The model with the diagnosis of cancer versus no cancer resulted in a statistically significant likelihood of discrimination of 173⋅45 (P < 0⋅001), with an area under the ROC curve of 0⋅979. Cross-validation of the model resulted in a true predictive value for colorectal cancer of 93 per cent overall. Reliability of the breath analysis was maintained irrespective of cancer stage. Conclusion: This study demonstrated that analysis of exhaled VOCs can discriminate patients with colorectal cancer from those without. This finding may eventually lead to the creation of a smart online sensory device, capable of providing a binary answer (cancer/no cancer) and directing to further screening.

Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called “ideal biomarkers”, for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.

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