Global academic response to COVID ‐19: Cross‐sectional study

This study explores the response to COVID‐19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross‐sectional bibliometric review of COVID‐19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission‐to‐acceptance time and availability of original data. Publisher‐responsiveness was assessed by measuring the acceptance‐to‐publication time and the provision of open access. Three hundred and ninety‐eight of 2,835 COVID‐19 and 55 of 1,513 MERS search results were eligible. Most COVID‐19 studies were clinical reports (n = 242; 60.8%). The submission‐to‐acceptance [median: 5 days (IQR: 3–11) versus 71.5 days (38–106); P < .001] and acceptance‐to‐publication [median: 5 days (IQR: 2–8) versus 22.5 days (4–48·5‐; P < .001] times were strikingly shorter for COVID‐19. Almost all COVID‐19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open‐access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID‐19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one‐in‐four were published alongside original data, which is a key target for improvement

Patient education about recovery after colorectal surgery: Systematic scoping review

Aim Enhanced recovery after surgery (ERAS) protocols aim to optimize recovery through a series of evidence‐based recommendations. A key component of ERAS is the provision of patient education. Whilst the recommendation for this is strong, the evidence to inform its format, timing and delivery is unclear. The aim of this review was to describe previous educational interventions used to improve recovery after colorectal surgery and to explore opportunities for future research. Methods A systematic scoping review was performed. MEDLINE and Embase databases were searched between 1 January 1990 and 12 February 2020. Studies which described or assessed the effectiveness of a patient education or information resource to improve recovery after colorectal surgery were eligible. Outcomes of interest included the format, timing and delivery of interventions, as well as key features of intervention and study design. A narrative synthesis of data was produced through a process of charting and summarizing key results. Results A total of 1298 papers were inspected, and 11 were eligible for inclusion. Five papers were reports of randomized controlled trials, and others reported a mix of non‐randomized and qualitative studies. The design of educational interventions included audio‐visual resources (n = 3), smartphone device applications (n = 3) and approaches to facilitate person‐to‐person counselling (n = 5). Most of the counselling interventions reported positive outcomes (mainly in length of hospital stay), whereas the other types reported mixed results. Patients and the public were seldom involved as collaborators in the design of interventions. Conclusions Patient education is generally advantageous, but there is insufficient evidence to optimize its design and delivery in the setting of colorectal surgery. Methods: A systematic scoping review was performed. MEDLINE and EMBASE databases were searched between 1st January 1990 and 12th February 2020. Studies which described or assessed the effectiveness of a patient education or information resource to improve recovery after colorectal surgery were eligible. Outcomes of interest included the format, timing, and delivery of interventions, as well as key features of intervention and study design. A narrative synthesis of data was produced through a process of charting and summarising key results. Results: A total of 1,298 manuscripts were inspected and 11 were eligible for inclusion. Five manuscripts were reports of randomised controlled trials and others reported a mix of non‐randomised and qualitative studies. The design of educational interventions included audio‐visual resources (n=3), smartphone device applications (n=3), and approaches to facilitate person‐to‐person counselling (n=5). Most of the counselling interventions reported positive outcomes (mainly in length of hospital stay), whereas the other types reported mixed results. Patients and the public were seldom involved as collaborators in the design of interventions. Conclusions: Patient education is generally advantageous, but there is Insufficient evidence to optimise its design and delivery in the setting of colorectal surgery

The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer

The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC. Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%). Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers

Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting.

BACKGROUND: Colorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-α (FRα) and Epithelial growth factor receptor (EGFR). METHODS: Marker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0-15). Matched positive and negative lymph nodes from 18 patients were also examined. RESULTS: Markers were more highly expressed in tumour tissue than in matched normal tissue in 98.8%, 79.0%, 37.1% and 32.8% of cases for CEA, TAG-72, FRα and EGFR, respectively. Carcinoembryonic antigen showed the greatest differential expression, with tumours scoring a mean of 10.8 points higher than normal tissues (95% CI 10.31-11.21, P<0.001). Similarly, CEA showed the greatest differential expression between positive and negative lymph nodes. Receiver operating characteristic analyses showed CEA to have the best sensitivity (93.7%) and specificity (96.1%) for colorectal cancer detection. CONCLUSION: Carcinoembryonic antigen has the greatest potential to allow highly specific tumour imaging and drug delivery; future translational research should aim to exploit this

Information needs for recovery after colorectal surgery: Patient focus group study

Aim The provision of information to patients is an important part of recovery after colorectal surgery. This study aimed to define patient information needs, barriers to effective understanding, and insights into how information‐provision may be improved. Method A patient focus group was convened. This comprised a broad, convenience sample of eleven participants from across the United Kingdom with experience of major colorectal surgery. A semi‐structured topic guide was used to facilitate discussion about previous experiences of information‐provision and how this may be improved. Data were analysed thematically and are presented as major themes. Results Overall, participants felt that their information needs are poorly prioritised by healthcare professionals. Barriers to understanding and retaining information include highly emotional situations (such as receiving bad news) and inappropriate information design (such as the use of inaccessible language). Participants expressed how information resources should: 1) address patients’ individual information needs; 2) empower patients to take an active role in their recovery; 3) support patients with meaningful education and sign‐posted resources; and 4) recognise patients’ heightened need for information during recovery at home. Conclusions This study provides key insights into the information needs of patients undergoing colorectal surgery. These should inform the development of future information resources, whose format, timing, and design are currently supported by low quality evidence

A novel fluorescent c-met targeted imaging agent for intra-operative colonic tumour mapping: Translation from the laboratory into a clinical trial

Background The c-Met protein is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model. Methods HT-29 SiRNA transfection confirmed specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in BALB/c mice, EMI-137 was injected and biodistribution analysed through in vivo fluorescent imaging. Nine patients, received a single intravenous EMI-137 bolus (0.13 mg/kg), 1–3 h before laparoscopic-assisted colon cancer surgery (NCT03360461). Tumour and LN fluorescence was assessed intraoperatively and correlated with c-Met expression in eight samples by immunohistochemistry. Findings c-Met expression HT-29 cells was silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed up to 6 h post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants, 4/9 showed increased tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited high c-Met protein expression. Interpretation EMI-137, binds specifically to the human c-Met protein, is safe, and with further refinement, shows potential for application in fluorescence-guided surgery

IBD-associated CRC epidemiology and outcomes: an English population-based study

Introduction: People with inflammatory bowel diseases (IBD) of the colon are at an increased risk of colorectal cancer (CRC). This study investigates the epidemiology of IBD-CRC and its outcomes. Methods: Using population data from the English National Health Service (NHS) held in the CORECT-R data repository, all colorectal cancers with and without a prior diagnosis of IBD (Crohn’s, ulcerative colitis, IBD unclassified (IBD-U) and IBD with cholangitis) between 2005 and 2018 were identified. Descriptive analyses and logistic regression models were used to compare the characteristics of the two groups, and their outcomes up to 2 years. Results: 390,614 patients diagnosed with CRC were included, of whom 5,141 (1.3%) also had a previous diagnosis of IBD. IBD-CRC cases were younger (median age at CRC diagnosis (IQR) 66 (54-76) versus 72 (63-79) years (p<0.01)), more likely to be diagnosed with CRC as an emergency (25.1% versus 16.7% (p<0.01)) and have a right-sided colonic tumour (37.4% versus 31.5% (p<0.01)). A total colectomy was performed in 36.3% of those with IBD (15.4% of Crohn’s, 44.1% of ulcerative colitis, 44.5% of IBD-U and 67.7% of IBD with cholangitis). Synchronous (3.2% versus 1.6% p<0.01) & metachronous tumours (1.7% versus 0.9% p<0.01) occurred twice as frequently in individuals with IBD compared to those without IBD. Stage-specific survival up to 2 years was worse for IBD-associated cancers. Conclusion: IBD-associated CRCs occur in younger individuals and have worse outcomes than sporadic CRCs. There is an urgent need to find the reasons for these differences to inform screening, surveillance and treatment strategies for CRC and its precursors in this high-risk group

Is symptom burden a predictor of anxiety and depression in patients with cancer about to commence chemotherapy?

Objectives: To assess the prevalence, severity and distress from physical symptoms and the prevalence of anxiety and depression in patients about to undergo chemotherapy for potentially curable cancers; and to explore the presence of symptom clusters and investigate their relationships with anxiety and depression. Design, participants and setting: Cross-sectional survey of 192 patients with breast or gastrointestinal cancers or lymphoma before first ever chemotherapy treatment with curative intent. Main outcome measures: Hospital Anxiety and Depression Scale to assess anxiety and depression and the Chemotherapy Symptom Assessment Scale to measure physical symptom prevalence, severity and distress ("bother"). Results: Prevalence of anxiety was 45% and depression 25%. The most prevalent physical symptoms were pain (48%), feeling unusually tired (45%) and difficulty sleeping (45%). Physical symptoms rated as most severe were pain (28%), difficulty sleeping (26%) and feeling unusually tired (19%). Physical symptoms causing the most distress were pain (39%), constipation (18%) and nausea (16%). Factor analysis of symptom distress scores indicated that five factors explained 36.7% of the variance and included: gastrointestinal (nausea, vomiting, pain), general malaise (tiredness, feeling weak, headaches), emotional (feeling depressed, feeling anxious), nutritional (changes to appetite, weight loss or gain) and general physical (mouth/throat problems, shortness of breath). Regression analysis indicated that symptom distress for the malaise (β=1.46; PConclusions: Before commencing chemotherapy, patients are already experiencing distressing symptoms and have high scores for anxiety and depression, partially explained by physical symptom distress. Patients should be routinely screened for both emotional and physical needs and appropriate interventions should be developed