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.

Intratumor heterogeneity may result from the evolution of tumor cells and their continuous interactions with the tumor microenvironment which collectively drives tumorigenesis. However, an appearance of cellular and molecular heterogeneity creates a challenge to define molecular features linked to tumor malignancy. Here we perform multiregional single-cell RNA sequencing (scRNA-seq) analysis of seven liver cancer patients (four hepatocellular carcinoma, HCC and three intrahepatic cholangiocarcinoma, iCCA). We identify cellular dynamics of malignant cells and their communication networks with tumor-associated immune cells, which are validated using additional scRNA-seq data of 25 HCC and 12 iCCA patients as a stable fingerprint embedded in a malignant ecosystem representing features of tumor aggressiveness. We further validate the top ligand-receptor interaction pairs (i.e., LGALS9-SLC1A5 and SPP1-PTGER4 between tumor cells and macrophages) associated with unique transcriptome in additional 542 HCC patients. Our study unveils stable molecular networks of malignant ecosystems, which may open a path for therapeutic exploration.

Chronic lymphocytic leukemia is the most common leukemia in the United States. It is a slowly progressive disease, with an 82% five-year survival rate. The treatment strategies are highly individualized with patients in the early and stable stages typically not requiring treatment. However, those with progressive or clinically advanced disease will require treatment. Cytotoxic drugs, such as the alkylating agents, purine nucleoside antagonists, and immunotherapeutic agents, have been the mainstay of chemotherapeutic treatment in CLL. However, given the lack of therapeutic specificity, these medications (especially older ones) have limited tolerability due to side effects. In this paper, we will discuss the data on the use of phosphatidylinositol 3 kinase inhibitor Idelalisib in the management of patients with chronic lymphocytic leukemia. The preclinical and clinical data thus far demonstrate that Idelalisib produces a dramatic and durable response in patients with chronic lymphocytic leukemia and without causing significant toxicity. Moving forward, the ongoing clinical trials will help address the various questions currently being raised regarding the long-term application and safety of Idelalisib. With greater clinical experience following more widespread use of Idelalisib, we will be able to determine the optimal combination therapies in treatment-naïve and relapsed/refractory patients, resulting in more individualized therapeutic strategies for patients with chronic lymphocytic leukemia.

ImportanceWomen have made substantial advancements in academic surgery, but research funding disparities continue to hamper their progress, and current literature on the status of National Institutes of Health (NIH) funding awarded to women surgeon-scientists appears to be conflicting.ObjectiveTo examine gender-based differences in NIH funding awarded to surgeon-scientists by comparing total grant amounts awarded and the distribution of grants by gender and research type.Design, Setting, and ParticipantsThis cross-sectional study was performed using a previously created database of NIH-funded surgeons from 2010 to 2020. Active physician data from the Association of American Medical Colleges were used to calculate total surgeon populations. This study was performed at the NIH using the NIH internal data platform, iSearch Grants. A total of 715 men and women surgeon-scientists funded by the NIH in 2010 and 1031 funded in 2020 were included in the analysis.Main Outcomes and MeasuresThe main outcome was the number of women among the total number of surgeons who received NIH grants and the total grant amounts awarded to them. Bivariate χ2 analyses were performed using population totals and substantiated by z tests of population proportions.ResultsThis study included 715 physicians (n = 579 men [81.0%]) in 2010 and 1031 physicians (n = 769 men [74.6%]) in 2020. In 2020, women comprised 27.4% of the surgical workforce and 25.4% of surgeons with research funding in the US, but they received only 21.7% of total NIH research funding awarded to all surgeons. The number of funded women surgeon-scientists, however, significantly increased from 2010 to 2020 (262 [25.4%] in 2020 vs 136 [19.0%] in 2010; P < .001) as did their funding ($189.7 million [21.7%] in 2020 vs $75.9 million [12.3%] in 2010; P < .001). Furthermore, the proportion of US women surgeons overall with NIH funding significantly increased in 2020 vs 2010 (0.7% vs 0.5%; P < .001). Basic science, clinical outcomes, and clinical trial R01 grants also increased among women surgeon-scientists. Women and men K grant holders had a similar mean (SD) number of R01 application attempts before success (2.7 [3.01] vs 2.3 [3.15]; P = .60) and similar K-to-R award conversion rates (23.5% vs 26.7%; P = .55).Conclusions and RelevanceThis cross-sectional study found an increasing number of women surgeon-scientists receiving NIH funding in 2020 vs 2010 as well as increases in the median grant amounts awarded. Although these results are promising, a discrepancy remains in the proportion of women in the surgical workforce compared with those funded by the NIH and the total grant amounts awarded to them.