A comparison of the prognostic value of composite ratios and cumulative scores in patients with operable rectal cancer

The aim of this study was to directly compare the prognostic value of cumulative scores and composite ratios in patients with operable rectal cancer. Within a single surgical unit preoperative differential blood cell results including neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, as well as CRP (C) and albumin (A) levels were recorded. These results were used to construct a series of composite ratios (NLR, PLR, LMR, CAR) and cumulative scores (NLS, PLS, LMS, NPS, mGPS). The relationship between composite ratios and the cumulative scores and clinicopathological characteristics, cancer specific survival (CSS) and overall survival (OS) were examined. A total of 413 patients were included. When adjusted for TNM stage, surgical approach, time of surgery and margin involvement mGPS (p < 0.05) was associated with CSS. In addition, most composite ratios/scores showed correlations with neoadjuvant therapy (p < 0.001). When a direct comparison between NPS (myeloid) and mGPS (liver) was carried out they showed similar associations with both CSS and OS. Therefore, both composite ratios and cumulative scores have been shown to be prognostic in patients with operable rectal cancer

The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores

Introduction: The systemic inflammatory response has been proven to have a prognostic value. There are two methods of assessing the systemic inflammatory response composite ratios (R) and cumulative scores (S). The aim of this study was to compare the prognostic value of ratios and scores in patients undergoing surgery for colon cancer. Methods: Patients were identified prospectively in a single surgical unit. Preoperative neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, CRP (C) and albumin (A) levels were recorded. The relationship between composite ratios neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), C-reactive protein albumin ratio (CAR) and the cumulative scores neutrophil– lymphocyte score (NLS), platelet–lymphocyte score (PLS), lymphocyte–monocyte score (LMS), neutrophil– platelet score (NPS), modified Glasgow prognostic score (mGPS) and clinicopathological characteristics, cancer-specific survival (CSS) and overall survival (OS), were examined. Results: A total of 801 patients were examined. When adjusted for tumour node metastasis (TNM) stage, NLR >5 (p < 0.001), NLS (p < 0.01), PLS (p < 0.001), LMR <2.4 (p < 0.001), LMS (p < 0.001), NPS (p < 0.001), CAR >0.22 (p < 0.001) and mGPS (p < 0.001) were significantly associated with CSS. In patients undergoing elective surgery (n = 689), the majority of the composite ratios/scores correlated with age (p < 0.01), BMI (p < 0.01), T stage (p < 0.01), venous invasion (p < 0.01) and peritoneal involvement (p < 0.01). When NPS (myeloid) and mGPS (liver) were directly compared, their relationship with CSS and OS was similar. Conclusions: Both composite ratios and cumulative scores had prognostic value, independent of TNM stage, in patients with colon cancer. However, cumulative scores, based on normal reference ranges, are simpler and more consistent for clinical use

Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer : a study protocol of a randomised phase II trial (PRIME-RT)

Acknowledgements We are grateful to Mr George Davidson and Ms Monica Jeffers for their input with writing the PRIME-RT protocol and patient information sheet. This study is co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde. Funding PRIME-RT is funded by Astrazeneca and receives core funding from CRUK Clinical Trials Unit Glasgow for the purposes of trial set-up and data collection. The trial is co-sponsored by the University Of Glasgow and NHS Greater Glasgow and Clyde.Peer reviewedPublisher PD

The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer

Background The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy. Methods Two cohorts were utilised; 862 TNM I–III CRC validation cohort, and 2912 TNM II–III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction. Results GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85–5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39–3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19–4.16, p = 0.012). Conclusions This study validates the GMS as a prognostic tool for patients with stage I–III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX

Alcohol use and misuse: What are the contributions of occupation and work organization conditions?

<p>Abstract</p> <p>Background</p> <p>This research examines the specific contribution of occupation and work organization conditions to alcohol use and misuse. It is based on a social-action model that takes into account agent personality, structures of daily life, and macro social structures.</p> <p>Methods</p> <p>Data come from a representative sample of 10,155 workers in Quebec, Canada. Multinomial regression models corrected for sample design effect have been used to predict low-risk and high-risk drinking compared to non-drinkers. The contribution of occupation and work organization conditions (skill used, decision authority, physical and psychological demands, hours worked, irregular work schedule, harassment, unionization, job insecurity, performance pay, prestige) have been adjusted for family situation, social network outside the workplace, and individual characteristics.</p> <p>Results</p> <p>Compared to non-qualified blue-collars, both low-risk and high-risk drinking are associated with qualified blue-collars, semi-qualified white-collars, and middle managers; high-risk drinking is associated with upper managers. For constraints-resources related to work organization conditions, only workplace harassment is an important determinant of both low-risk and high-risk drinking, but it is modestly moderated by occupation. Family situation, social support outside work, and personal characteristics of individuals are also associated with alcohol use and misuse. Non-work factors mediated/suppressed the role of occupation and work organization conditions.</p> <p>Conclusion</p> <p>Occupation and workplace harassment are important factors associated with alcohol use and misuse. The results support the theoretical model conceptualizing alcohol use and misuse as being the product of stress caused by constraints and resources brought to bear simultaneously by agent personality, structures of daily life, and macro social structures. Occupational alcohol researchers must expand their theoretical perspectives to avoid erroneous conclusions about the specific role of the workplace.</p

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

The TREAT-NMD DMD Global Database: Analysis of more than 7,000 Duchenne Muscular Dystrophy mutations

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations)

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (&lt;50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, &lt;50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified