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.

AIMTo investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODSAGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTSAGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively.CONCLUSIONIn addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.

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Gastrointestinal cancers (gastric, pancreatic and colorectal) are life-threatening diseases, which easily spread to peritoneal cavity (Juhl et al. in Int J Cancer 57:330-335, 1994; Schneider et al. in Gastroenterology 128:1606-1625, 2005; Geer and Brennan in Am J Surg 165:68-72 1993). Application of hyperthermal intraperitoneal chemotherapy (HIPEC) is one of the choices treating these malignancies and prolonging patient survival time. Despite numbers of clinical trials showing positive effects of HIPEC against various types of cancer, the question whether hyperthermia significantly potentiate the cytotoxicity of cisplatin remains unanswered. Little information is available on the HIPEC effect at the level of mitochondria. To define the effect of hyperthermia (40 °C and 43 °C) to cisplatin treated human gastric AGS, pancreatic T3M4 and colorectal Caco-2 cancer cells, we established an in vitro experiment, which mimics clinical HIPEC conditions. Giving the importance of mitochondrial energy metabolism in cancer, we investigated the effect of cisplatin and hyperthermia on mitochondrial Complex-I (glutamate/malate) and complex-II (succinate) dependent respiratory rates, the coupling of oxidative phosphorylation, the proton permeability of mitochondrial inner membrane and on the integrity of mitochondrial outer membrane in Caco-2, AGS and T3M4 cancer cell lines. Our main findings are: 1) treatment of cells with cisplatin causes the impairment of mitochondrial functions - the increase in the proton permeability of mitochondrial inner membrane and decrease in the oxidative phosphorylation efficiency in Caco-2, AGS and T3M4 cancer cells; 2) hyperthermia (40 °C and 43 °C) increased state 2 respiration rate only in AGS cells without any effects on Caco-2 and T3M4 cells; 3) hyperthermia in combination with cisplatin doesn't enhance cisplatin effect neither in Caco-2 and T3M4 nor in AGS cells. Thus, our results show the different mitochondrial response of gastric AGS, pancreatic T3M4 and colorectal Caco-2 cancer cells to cisplatin or/and hyperthermia - treatment. Further studies are needed to find the mechanisms of cell line - specific mitochondrial response to cisplatin and hyperthermia.