Intraoperative assessment of the curative potential to predict survival after gastric cancer resection: A national cohort study.

BACKGROUND: The surgeon's intraoperative assessment of the curative potential of tumor resection following gastrectomy adds new information that could help clinicians and patients by predicting survival. METHODS: All patients in Sweden undergoing gastric cancer resection between 2006 and 2018 were grouped according to a prospectively registered variable; the surgeon's intraoperative assessment of the curative potential of surgery: curative, borderline curative, or palliative. Factors affecting group allocation were analyzed with multivariable logistic regression, while survival was analyzed using multivariable Cox regression and the Kaplan-Meier method. Positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Of 2341 patients undergoing gastric cancer resection, 1547 (71%) were deemed curative, 340 (15%) borderline curative, and 314 (14%) palliative (140 missing assessments). Advanced stage increased the risk of borderline curative resection (Stage III, odds ratio (OR) = 6.04, 95% confidence interval (CI) = 3.92-9.31), as did emergency surgery OR = 3.31 (1.74-6.31) and blood loss >500 mL; OR = 1.63 (1.06-2.49). Neoadjuvant chemotherapy and multidisciplinary team (MDT) discussion both decreased the risk of borderline curative resection, OR = 0.58 (0.39-0.87) and 0.57 (0.40-0.80), respectively. In multivariable Cox regression, the surgeon's assessment independently predicted worse survival for borderline curative (hazard ratio (HR) = 1.54, 95% CI = 1.29-1.83) and palliative resections (HR = 1.76, 95% CI = 1.45-2.19), compared to curative resections. The sensitivity of the surgeon's assessment of long-term survival was 96.7%. The PPV was 50.7% and the NPV was 92.1%. CONCLUSION: The surgeon's intraoperative assessment of the curative potential of gastric cancer surgery may independently aid survival prediction and is analogous to prognostication by pathologic Staging. Advanced disease, emergency surgery, and a high intraoperative blood loss, increases the risk of a borderline curative or palliative resection. Conversely, neoadjuvant treatment and MDT discussion reduce the risk of borderline curative or palliative resection.

Textbook outcomes for oesophagectomy: A valid composite measure assessment tool for surgical performance in a specialist unit.

INTRODUCTION: In 2017 the Dutch Upper Gastrointestinal Cancer Audit Group proposed a ten-item composite measure for a 'textbook outcome' (TBO) following oesophago-gastric resection. Studies have shown associations between TBO and improved conditional and overall survival. The aim of this study was to evaluate the use of TBO to assess the outcomes from a single specialist unit in a country, with low incidence of disease, allowing comparisons with international specialist centres. MATERIALS AND METHODS: Retrospective analysis of prospectively collected oesophageal cancer surgery data at a single centre, in Australia, between 2013 and 2018. Multivariable logistical regression assessed association between baseline factors and TBO. Post-operative complications were analysed in two separate groups as Clavien-Dindo ≥2 (CD ≥ 2) and Clavien-Dindo ≥3 (CD ≥ 3). Cox-proportional hazards regression analysis determined the association between TBO and survival. RESULTS: 246 patients were analysed, with 50.8% (n = 125) achieving a TBO when complications were defined as CD ≥ 2 and 58.9% (n = 145) when using CD ≥ 3. Patients aged ≥75, and those with a pre-operative respiratory co-morbidity were less likely to achieve a TBO. Overall survival was not influenced by TBO when complications were defined as CD ≥ 2, however it was higher when a TBO was achieved, and complications were defined as CD ≥ 3 (HR 0.54, 95% CI, 0.35 to 0.84, P = 0.007). CONCLUSION: TBO is a multi-parameter metric that allowed benchmarking of the quality of oesophageal cancer surgery in our unit, providing favourable outcomes compared with other published data. There was an association between TBO and improved overall survival when the definition of severe complications was CD ≥ 3.

Improving the working environment for the delivery of safe surgical care in the UK: a qualitative cross-sectional analysis.

OBJECTIVES: The aim of this study was to identify current problems and potential solutions to improve the working environment for the delivery of safe surgical care in the UK. DESIGN: Prospective, questionnaire-based cross-sectional study. SETTING/PARTICIPANTS: Following validation, an electronic questionnaire was distributed to postgraduate local education and training board distribution lists, the Royal College of Surgeons of Edinburgh (RCSEd) mailing lists and trainee organisations. This consisted of a single open-ended question inviting five open-ended responses. Throughout the 13-week study period, the survey was also published on a number of social media platforms. RESULTS: A total of 505 responders completed the survey, of which 35% were consultants, 30% foundation doctors, 17% specialty trainees, 11% specialty doctors, 5% core trainees and <1% surgical nurse practitioners. A total of 2238 free-text answers detailed specific actions to improve the working environment. These responses were individually coded and then grouped into nine categories (staff resources, non-staff resources, support, working conditions, communication and team work, systems improvement, patient centred, training and education, and miscellaneous). CONCLUSIONS: The results of this study have identified a number of key areas that, if addressed, may improve the environment for the delivery of safer surgical care. Common themes that emerged across all grades included: increased front-line staff; a return to a 'firm' structure to improve team continuity; greater senior support; and improved hospital facilities to help staff rest and recuperate. While unlimited funding remains unrealistic, many of the suggestions could be implemented in a cost-neutral fashion and include insightful ideas for remodelling or restructuring the workforce to improve the efficiency of the surgical team. The findings of this study formed the basis of a set of recommendations published by the RCSEd as a discussion paper.

WT1 expression in vessels varies with histopathological grade in tumour-bearing and control tissue from patients with breast cancer.

BACKGROUND: The Wilms' tumour protein (WT1), which influences tumour development and angiogenesis, is a promising therapeutic target in breast cancer. We hypothesised that WT1 expression would vary in endothelial cells in distinct sub-classifications of breast cancer. METHODS: WT1 expression and vascular density were quantified by immunohistochemical analysis of human (n = 57) and murine breast cancers. Human tumours were sub-classified by histopathological grade, ER status and HER2 enrichment. RESULTS: WT1 was identified in endothelial (and epithelial and smooth muscle) cells in tumours and tumour-free tissues (controls) from patients and mice with breast cancer. WT1 expression was higher in tumours than in controls, but this was not due to increased endothelial WT1. Vascular WT1 in cancers decreased as histopathological grade increased. WT1 was higher in ER-positive versus ER-negative cancers. Strikingly, reduced WT1 expression in controls correlated with an increased Nottingham Prognostic Index score. CONCLUSIONS: Expression of WT1 is increased in breast cancers but this is not limited to the vascular compartment. The association between reduced WT1 in tumour-free tissue and poor prognosis suggests a protective role for WT1 in the healthy breast.

In Vivo Assays for Assessing the Role of the Wilms' Tumor Suppressor 1 (Wt1) in Angiogenesis.

The Wilms' tumor suppressor gene (WT1) is widely expressed during neovascularization, but it is almost entirely absent in quiescent adult vasculature. However, in vessels undergoing angiogenesis, WT1 is dramatically upregulated. Studies have shown Wt1 has a role in both tumor and ischemic angiogenesis, but the mechanism of Wt1 action in angiogenic tissue remains to be elucidated. Here, we describe two methods for induction of in vivo angiogenesis (subcutaneous sponge implantation, femoral artery ligation) that can be used to assess the influence of Wt1 on new blood vessel formation. Subcutaneously implanted sponges stimulate an inflammatory and fibrotic response including cell infiltration and angiogenesis. Femoral artery ligation creates ischemia in the distal hindlimb and produces an angiogenic response to reperfuse the limb which can be quantified in vivo by laser Doppler flowmetry. In both of these models, the role of Wt1 in the angiogenic process can be assessed using histological/immunohistochemical staining, molecular analysis (qPCR) and flow cytometry. Furthermore, combined with suitable genetic modifications, these models can be used to explore the causal relationship between Wt1 expression and angiogenesis and to trace the lineage of cells expressing Wt1. This approach will help to clarify the importance of Wt1 in regulating neovascularization in the adult, and its potential as a therapeutic target.

Bronchial flap closure of the right lower lobe bronchus.

We describe a novel method for closure of the bronchus intermedius, after right lower lobectomy, using a flap derived from the lower lobe apical segmental bronchus. We have successfully used this technique in an endobronchial carcinoid tumor occurring in a young man. It allowed middle lobe preservation despite a very proximal tumor position within the basal trunk bronchus. Adequate tumor margins were confirmed by on-table frozen section examination. This technique may have particular use in carcinoids or benign tumors.

The utility of functional interaction and cluster analysis in CNS proteomics.

Proteomic studies offer enormous potential for gaining insight into cellular dynamics and disease processes. An immediate challenge for enhancing the utility of proteomics in translational research lies in methods of handling and interpreting the large datasets generated. Publications rarely extend beyond lists of proteins, putatively altered derived from basic statistics. Here we describe two additional distinct approaches (with particular strengths and limitations) that will enhance the analysis of proteomic datasets. Arithmetic and functional cluster analyses have been performed on proteins found differentially regulated in human glioma. These two approaches highlight (i) subgroups of proteins that may be co-regulated and play a role in glioma pathophysiology, and (ii) functional protein interactions that may improve comprehension of the biological mechanisms involved. A coherent proteomic strategy which involves both arithmetic and functional clustering, (together with careful consideration of conceptual limitations), is imperative for quantitative proteomics to deliver and advance the biological understanding of disease of the CNS. A strategy which combines arithmetic analysis and bioinformatics of protein-protein interactions is both generally applicable and will facilitate the interpretation of proteomic data.