Search

Background: Postoperative mortality after colorectal cancer surgery varies across hospitals and countries. The aim of this study was to test the Association of Coloproctologists of Great Britain and Ireland (ACPGBI) models as predictors of 30-day mortality in an Australian cohort., Methods: Data from patients who underwent surgery in six hospitals between 1996 and 2015 (CRC data set) were reviewed to test ACPGBI models, and patients from 79 hospitals in the Bi-National Colorectal Cancer Audit between 2007 and 2016 (BCCA data set) were analysed to validate model performance. Recalibrated models based on ACPGBI risk models were developed, tested and validated on a data set of Australasian patients., Results: Of 18 752 patients observed during the study, 6727 (CRC data set) and 3814 (BCCA data set) were analysed. The 30-day mortality rate was 1·1 and 3·5 per cent in the CRC and BCCA data sets respectively. Both the original and revised ACPGBI models overestimated 30-day mortality for the CRC data set (observed to expected (O/E) ratio 0·17 and 0·21 respectively). Their ability to correctly predict mortality risk was poor (P < 0·001, Hosmer-Lemeshow test); however, the area under the curve for both models was 0·88 (95 per cent c.i. 0·85 to 0·92) showing good discriminatory power to classify 30-day mortality. The recalibrated original model performed well for calibration and discrimination, whereas the recalibrated revised model performed well for discrimination but not for calibration. Risk prediction was good for both recalibrated models. On external validation using the BCCA data set, the recalibrated models underestimated mortality risk (O/E ratio 3·06 and 2·98 respectively), whereas both original and revised ACPGBI models overestimated the risk (O/E ratio 0·48 and 0·69). All models showed similar good discrimination., Conclusion: The original and revised ACPGBI models overpredicted risk of 30-day mortality. The new Australasian calibrated ACPGBI model needs to be tested further in clinical practice., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Background: Lymph node yield (LNY) of 12 or more in resection of colorectal cancer is recommended in current international guidelines. Although a low LNY (less than 12) is associated with poorer outcome in some studies, its prognostic value is unclear in patients with early-stage colorectal or rectal cancer with a complete pathological response following neoadjuvant therapy. Lymph node ratio (LNR), which reflects the proportion of positive to total nodes obtained, may be more accurate in predicting outcome in stage III colorectal cancer. This study aimed to identify factors correlating with LNY and evaluate the prognostic role of LNY and LNR in colorectal cancer., Methods: An observational study was performed on patients with colorectal cancer treated at three hospitals in Melbourne, Australia, from January 2010 to March 2016. Association of LNY and LNR with clinical variables was analysed using linear regression. Disease-free (DFS) and overall (OS) survival were investigated with Cox regression and Kaplan-Meier survival analyses., Results: Some 1585 resections were analysed. Median follow-up was 27·1 (range 0·1-71) months. Median LNY was 16 (range 0-86), and was lower for rectal cancers, decreased with increasing age, and increased with increasing stage. High LNY (12 or more) was associated with better DFS in colorectal cancer. Subgroup analysis indicated that low LNY was associated with poorer DFS and OS in stage III colonic cancer, but had no effect on DFS and OS in rectal cancer (stages I-III). Higher LNR was predictive of poorer DFS and OS., Conclusion: Low LNY (less than 12) was predictive of poor DFS in stage III colonic cancer, but was not a factor for stage I or II colonic disease or any rectal cancer. LNR was a predictive factor in DFS and OS in stage III colonic cancer, but influenced DFS only in rectal cancer.

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640., (© 2016 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Abnormal embryos that arose in our in-vitro fertilization programme were cultured in serum-free minimum essential medium (MEM), and those that developed into blastocysts were cultured up to day 14 after fertilization to study the influence of various supplements on chorionic gonadotrophin (CG) secretion. Human cord serum, at a concentration of 1%, was found to be one of the most effective stimulants for initiating and maintaining CG production. A mixture of insulin+transferrin+selenium (ITS) stimulated CG secretion in serum-free MEM, although the output of hormone began to decline after approximately 3 days. Platelet-derived growth factor (PDGF) produced a similar response to ITS. Stimulation of blastocyst CG secretion in the absence of serum could also be induced with 8-bromo-cAMP. All stimulants were able to evoke CG secretion in day 7-8 blastocysts. These studies have shown that multiple factors were capable of inducing CG production by early blastocysts. On the basis of these and other studies it was postulated that receptors for insulin, transferrin and PDGF were expressed in preimplantation blastocysts.