Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. National Institute for Health and Care Research.

Hepatocellular carcinoma (HCC) is the 3rd cause of cancer-related death worldwide. Most cases arise in a background of chronic inflammation, extracellular matrix (ECM) remodeling, severe fibrosis and stem/progenitor cell amplification. Although HCCs are soft cellular tumors, they may contain fibrous nests within the tumor mass. Thus, the aim of this study was to explore cancer cell phenotypes in fibrous nests. Combined anatomic pathology, tissue microarray and real-time PCR analyses revealed that HCCs (n=82) containing fibrous nests were poorly differentiated, expressed Wnt pathway components and target genes, as well as markers of stem/progenitor cells, such as CD44, LGR5 and SOX9. Consistently, in severe liver fibroses (n=66) and in HCCs containing fibrous nests, weighted correlation analysis revealed a gene network including the myofibroblast marker ACTA2, the basement membrane components COL4A1 and LAMC1, the Wnt pathway members FZD1; FZD7; WNT2; LEF1; DKK1 and the Secreted Frizzled Related Proteins (SFRPs) 1; 2 and 5. Moreover, unbiased random survival forest analysis of a transcriptomic dataset of 247 HCC patients revealed high DKK1, COL4A1, SFRP1 and LAMC1 to be associated with advanced tumor staging as well as with bad overall and disease-free survival. In vitro, these genes were upregulated in liver cancer stem/progenitor cells upon Wnt-induced mesenchymal commitment and myofibroblast differentiation. In conclusion, fibrous nests express Wnt target genes, as well as markers of cancer stem cells and mesenchymal commitment. Fibrous nests embody the specific microenvironment of the cancer stem cell niche and can be detected by routine anatomic pathology analyses.

Randomized clinical trials (RCTs) are the building blocks of an evidence-based approach to medicine and surgery. These trials are used as trusted sources of evidence when designing clinical practice guidelines. It is therefore expected that their results are trustworthy and that their conclusions can be verified. Randomized clinical trial data sharing (ie, sharing statistical codes, study protocols, and individual participant data) holds promise for enhancing transparency and maximizing the value of research.¹ Data sharing is supported by patients who also want to share their data in a responsible and secure manner.² In 2018, the International Committee of Medical Journal Editors (ICMJE) required that manuscripts submitted to ICMJE journals as of July 1, 2018, must contain a data sharing statement if they are reporting the results of an RCT. If a trial began enrolling participants on or after January 1, 2019, the article must also include a data sharing plan in the trial’s registration.³ The ICMJE considers that “it is an ethical obligation to responsibly share data generated by interventional clinical trials because participants have put themselves at risk.”⁴

Objective: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. Background: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. Methods: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. Results: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P=0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P=0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. Conclusion: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.

How the side of an extended liver resection impacts the postoperative prognosis of advanced perihilar cholangiocarcinoma (PHC) is still controversial. We compared the outcomes of right (RTS) and left trisectionectomies (LTS) in Bismuth-Corlette (BC) type IV PHC resection. All patients undergoing RTS or LTS for BC type IV PHC in a single tertiary center between January 2012 and December 2019 were compared retrospectively. The endpoints were perioperative outcomes, long-term overall (OS), and disease-free survival (DFS). Among 67 hepatic resections for BC type IV PHC, 25 (37.3%) were LTS and 42 (63.7%) were RTS. Portal vein and artery resection rates were 40% and 52.4% (p = 0.29), and 24% and 0% (p < 0.001) in the LTS and RTS groups, respectively. The severe complication (Clavien–Dindo > IIIa) rate was comparable (36% vs. 21.5%, p = 0.357) while the postoperative liver failure (POLF) rate was lower in the LTS group (16% vs. 38%, p = 0.048). The R0 resection rate was similar between groups (81% vs. 92%; p = 0.154). The five-year OS rate was higher in the LTS group (66% vs. 30%, p = 0.009) while DFS was comparable (43% vs. 18%, p = 0.11). Based on multivariable analysis, the side of the trisectionectomy was an independent predictor of OS. Compared with RTS, LTS is associated with lower POLF and higher overall survival despite more frequent arterial reconstructions in type IV PHC. Although technically more demanding, LTS may be preferred in the treatment of advanced PHC.