ABSTRACT
BACKGROUND: For patients with asymptomatic, incurable, metastatic colorectal cancer, palliative, systemic treatment can be started immediately, or can be delayed until disease-related symptoms occur. How the potential survival benefit of starting palliative, systemic treatment immediately after diagnosis weighs up against the potential side effects is currently under debate, and was investigated in this review. OBJECTIVES: To assess the effects of immediate versus delayed chemotherapy, with or without targeted therapy, on overall survival, toxicity, quality of life, progression-free survival, and compliance with chemotherapy for individuals with asymptomatic, metastatic, incurable colorectal cancer. SEARCH METHODS: We searched CENTRAL; 2018, Issue 8, MEDLINE Ovid, Embase Ovid, PsycINFO, the World Health Organization International Clinical Trials Registry Platform, and Clinicaltrials.gov, from inception to 23 August 2018. We did not apply limitations based on language or date of publication. We searched the reference lists of all included studies to identify trials that may not have been identified from the electronic searches. SELECTION CRITERIA: Randomised controlled trials evaluating immediate versus delayed chemotherapy in persons with asymptomatic, metastatic, incurable colorectal cancer. DATA COLLECTION AND ANALYSIS: We applied standard methodological procedures, according to the recommendations of Cochrane and Cochrane Colorectal Cancer. Two review authors independently reviewed the studies identified by literature searches, selected relevant trials, extracted data, and assessed risk of bias of the included studies. We used the Cochrane tool to assess risk of bias, Review Manager 5 software for meta-analysis, GRADE methods to evaluate the quality of the evidence, and GRADEpro GDT software to develop a 'Summary of findings' table. MAIN RESULTS: We included three randomised controlled trials (351 participants) investigating immediate versus delayed chemotherapy in people diagnosed with asymptomatic, metastatic, incurable colorectal cancer. Giving immediate versus delayed chemotherapy may make little or no difference to overall survival (hazard ratio (HR) 1.17, 95% confidence interval (CI) 0.93 to 1.46; 3 studies, 351 persons; low-quality evidence). For toxicity, giving immediate versus delayed chemotherapy may make little or no difference to the risk of grade 3 or 4 nausea and vomiting (risk ratio (RR) 0.84, 95% CI 0.31 to 2.25; 2 studies, 140 persons; very low-quality evidence), stomatitis (RR 1.10, 95% CI 0.47 to 2.55; 2 studies, 140 persons; very low-quality evidence), or diarrhoea (RR 0.69, 95% CI 0.34 to 1.40; 2 studies, 140 persons, very low-quality evidence). We are uncertain whether delayed chemotherapy made a difference to quality of life (very low-quality evidence), progression-free survival (low-quality evidence), or compliance with chemotherapy (low-quality evidence), as we had insufficient data to pool for these outcomes. AUTHORS' CONCLUSIONS: Based on a limited number of trials, very sparse data, and uncertainty of the evidence, this review was unable to establish whether there was a difference in overall survival or other clinically relevant outcomes, between immediate or delayed chemotherapy in persons with metastatic, incurable, colorectal cancer. The results should be interpreted with caution.
Subject(s)
Antineoplastic Agents/therapeutic use , Asymptomatic Diseases/therapy , Colonic Neoplasms/drug therapy , Colonic Neoplasms/mortality , Palliative Care/statistics & numerical data , Rectal Neoplasms/drug therapy , Rectal Neoplasms/mortality , Time-to-Treatment , Antineoplastic Agents/adverse effects , Colonic Neoplasms/pathology , Confidence Intervals , Diarrhea/chemically induced , Drug Administration Schedule , Humans , Nausea/chemically induced , Proportional Hazards Models , Randomized Controlled Trials as Topic , Rectal Neoplasms/pathology , Stomatitis/chemically induced , Survival Analysis , Vomiting/chemically inducedABSTRACT
BACKGROUND: Anastomotic leakage is a severe complication after low anterior resection for rectal cancer. With a global increase in registration initiatives, adapting uniform definitions and grading systems is highly relevant. OBJECTIVE: This study aimed to provide clinical parameters to categorize anastomotic leakage into subcategories according to the International Study Group of Rectal Cancer. DESIGN: All of the patients who underwent a low anterior resection in the Netherlands with primary anastomosis were included using the population-based Dutch Surgical Colorectal Audit. SETTINGS: Data were derived from the Dutch Surgical Colorectal Audit. MAIN OUTCOME MEASURES: The development of grade B anastomotic leakage (requiring invasive treatment but no surgery) versus grade C anastomotic leakage (requiring reoperation) was measured. RESULTS: Overall, 4287 patients underwent low anterior resection with primary anastomosis. A total of 159 patients (4%) were diagnosed with grade B anastomotic leakage versus 259 (6%) with grade C. Hospital stay and intensive care unit visits were significantly higher in patients with grade C anastomotic leakage compared with patients with grade B leakage. Mortality in patients with grade C leakage was higher compared with grade B leakage, although nonsignificant (5.8% vs 2.5%; p = 0.12). Multivariate analysis showed that patients with diverting stomas (n = 2866) had a decreased risk of developing grade C leakage compared with grade B (OR = 0.17 (95% CI, 0.10-0.29)). Male patients had an increased risk of developing grade C anastomotic leakage, and patients receiving neoadjuvant treatment before surgery had an increased risk of developing grade B anastomotic leakage. LIMITATIONS: Some possibly relevant variables, such as smoking and nutritional status, were not recorded in the database. CONCLUSIONS: Anastomotic leakage after low anterior resection for rectal cancer was a frequent observed complication in this cohort. Differences in clinical outcome suggest that grade B and C leakage should be considered separate entities in future registrations. In patients with a diverting stoma, the chances of experiencing grade C anastomotic leakage were reduced. See Video Abstract at http://links.lww.com/DCR/A315.
Subject(s)
Anastomotic Leak/classification , Digestive System Surgical Procedures , Rectal Neoplasms/surgery , Rectum/surgery , Age Factors , Aged , Anastomotic Leak/therapy , Case-Control Studies , Chemoradiotherapy/statistics & numerical data , Colostomy/statistics & numerical data , Databases, Factual , Female , Humans , Laparoscopy , Laparotomy , Male , Medical Audit , Mortality , Multivariate Analysis , Neoadjuvant Therapy/statistics & numerical data , Neoplasm Staging , Netherlands , Postoperative Complications/classification , Radiotherapy/statistics & numerical data , Rectal Neoplasms/pathology , Risk Factors , Severity of Illness Index , Sex FactorsABSTRACT
Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03-2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13-3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma/genetics , Colonic Neoplasms/genetics , DNA Methylation , Long Interspersed Nucleotide Elements , Aged , Aged, 80 and over , Carcinoma/pathology , Colonic Neoplasms/pathology , Female , Humans , Male , Middle Aged , Survival AnalysisABSTRACT
OBJECTIVE: The aim of this study was to explore local practices and perceptions of effective nurse-resident communication during shifts. Subsequently, effective communication was sought to be reinforced by implementing an initiative for improvement. DESIGN: A mixed-methods study was performed, combining a questionnaire with focus groups. Following qualitative analysis, 3 initiatives for improvement of nurse-resident communication were scrutinized, after which 1 initiative was implemented. Overall contentment with the implementation and effectiveness of communication was reassessed through a questionnaire at 3 months postimplementation. SETTING: This study took place between 2022 and 2023 at the Department of Surgery of the Leiden University Medical Center, a tertiary center in the Netherlands. PARTICIPANTS: All surgical nurses (nâ¯=â¯150) and residents (nâ¯=â¯20) were invited to participate, by responding to the questionnaire and take part in the focus groups. A total of 38 nurses (response rate 25.3%) and 12 residents (60%) completed the questionnaire, and 31 nurses and 13 residents participated in the focus groups. RESULTS: The themes "clarity," "mutual respect," "accessibility" and "approach" were critical for effective communication, in which there were interdisciplinary differences in the interpretation and needs regarding "clarity." In response, structured moments for interdisciplinary consultation during shifts were implemented, which were foremostly useful according to nurses (73.9%), compared to residents (40.0%). A majority of the nurses agreed that communication during shifts improved through fixed moments (60.9%). CONCLUSION: Differences in the perception of critical elements for efficient nurse-resident communication during shifts can be found, which could possibly be explained by differences in training and culture. Mutual awareness for each other's tasks, responsibilities and background seems vital for the ability to deliver good patient care during shifts. To improve interprofessional practice and overcome concerns of quality of care, attention for local practices is imperative. Practical arrangements, such as fixed moments for peer communication, can strengthen partnership during shift work.
Subject(s)
Focus Groups , Internship and Residency , Humans , Netherlands , Male , Surveys and Questionnaires , Female , Communication , Adult , Interprofessional Relations , Shift Work Schedule , Nursing Staff, Hospital/psychology , Attitude of Health Personnel , Qualitative ResearchABSTRACT
In 1971 the first study appeared that suggested a relationship between aspirin and cancer. Currently publications on the subject of aspirin and cancer are numerous, with both a beneficial effect of aspirin on cancer incidence and a beneficial effect on cancer survival. This review focusses on the relation between the use of aspirin and improved survival in colorectal cancer patients. Various study designs have been used, with the main part being observational studies and post hoc meta-analyses of cancer outcomes in cardiovascular prevention trials. The results of these studies are unambiguously pointing towards an effect of aspirin on colorectal cancer survival, and several randomised controlled trials are currently ongoing. Some clinicians feel that the current evidence is conclusive and that the time has come for aspirin to be prescribed as adjuvant therapy. However, until this review, not much attention has been paid to the specific types of bias associated with these studies. One of these biases is confounding by indication, because aspirin is indicated for patients as secondary prevention for cardiovascular disease. This review aims to provide perspective on these biases and provide tools for the interpretation of the current evidence. Albeit promising, the current evidence is not sufficient to already prescribe aspirin as adjuvant therapy for colorectal cancer.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/mortality , Bias , Cardiovascular Diseases/drug therapy , Confounding Factors, Epidemiologic , Meta-Analysis as Topic , Observational Studies as Topic , Randomized Controlled Trials as Topic , Research Design , Survival RateABSTRACT
BACKGROUND: Use of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis. METHODS: A random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used. RESULTS: Aspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44-0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57-2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival. CONCLUSION: Low-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future.
Subject(s)
Aspirin/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Aged, 80 and over , Colon/drug effects , Colon/metabolism , Colon/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/mortality , Female , Gene Expression , Humans , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Survival AnalysisABSTRACT
Several studies have suggested an association between use of metformin and an increased overall survival in patients diagnosed with pancreatic cancer, however with several important methodological limitations. The aim of the study was to assess the association between overall survival, pancreatic cancer, and metformin use.A retrospective cohort study of 1111 patients with pancreatic cancer was conducted using data from The Netherlands Comprehensive Cancer Organization (1998-2011). Data were linked to the PHARMO Database Network containing drug-dispensing records from community pharmacies. Patients were classified as metformin user or sulfonylurea derivatives user from the moment of first dispensing until the end of follow up. The difference in overall survival between metformin users and nonusers was assessed, and additionally between metformin users and sulfonylurea derivatives users. Univariable and multivariable parametric survival models were used and use of metformin and sulfonylurea derivatives was included as time-varying covariates.Of the 1111 patients, 91 patients were excluded because of differences in morphology, 48 patients because of using merely metformin before diagnosis, and 57 metformin-users ever used contemporary sulfonylurea derivatives and were therefore excluded. Lastly, 8 patients with a survival of zero months were excluded. This resulted in 907 patients for the analysis. Overall, 77 users of metformin, 43 users of sulfonylurea derivatives, and 787 nonusers were identified. The adjusted rate ratio for overall survival for metformin users versus nonusers was 0.86 (95% CI: 0.66-1.11; Pâ=â0.25). The difference in overall survival between metformin users and sulfonylurea derivatives users showed an adjusted rate ratio of 0.90 (95% CI: 0.59-1.40; Pâ=â0.67).No association was found between overall survival, pancreatic cancer, and metformin use. This was in concordance with 2 recently published randomized controlled trials. Future research should focus on the use of adjuvant metformin in other cancer types and the development or repurposing of other drugs for pancreatic cancer.