Long-Term Outcomes After Colorectal Surgery in Patients with Ulcerative Colitis-Associated Colorectal Cancer Versus Sporadic Colorectal Cancer.

BACKGROUND: Ulcerative colitis is associated with a higher risk for developing colorectal cancer. It is unknown whether this translates into a worse prognosis when malignancy occurs. The goal of this study was to compare long-term outcomes between patients with ulcerative colitis-associated colorectal cancer and sporadic colorectal cancer. METHODS: All patients who underwent surgery with curative intent for colorectal cancer in Denmark between January 2004 and June 2016 were included in the study. Patients diagnosed with ulcerative colitis were identified and matched 1:5 with patients with sporadic colorectal cancer using propensity score matching. The primary outcome was disease-free survival, with recurrence-free survival and all-cause mortality as secondary outcomes. In order to relate the results of the study to the existing literature, a systematic review with meta-analysis was conducted. RESULTS: A total of 1332 patients, 222 with ulcerative colitis and 1110 with sporadic colorectal cancer were included in the study. Disease-free survival was similar between the two groups with a hazards ratio (HR) 1.06 [95% confidence interval (CI) 0.85-1.32], as was recurrence-free survival HR 1.14 (95% CI 0.86-1.53) and all-cause mortality HR 1.15 (95% CI 0.89-1.48). The results of the systematic review identified seven other relevant studies. Meta-analysis showed a HR 1.67 (95% CI 0.61-4.56) for recurrence-free survival and HR 1.21 (95% CI 0.93-1.56) for all-cause mortality. CONCLUSIONS: There were no significant differences in long-term outcomes between ulcerative colitis-associated and sporadic colorectal cancer. However, the current results are limited by possible residual confounding and the meta-analysis by heterogeneity in confounding adjustment.

Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial.

Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077-0.80]), giving a NNT of 3.0 [95 % CI 1.7-11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.

The prognostic value of tumour-infiltrating lymphocytes in pancreatic cancer: a systematic review and meta-analysis.

IMPORTANCE: Tumour-infiltrating lymphocytes (TILs) have previously been found to influence patient prognosis in other gastrointestinal cancers, for instance in colorectal cancer. An immunosuppressive phenotype often characterizes pancreatic cancer with a low degree of immune cell infiltration. Cytotoxic CD8+ T cell infiltration in tumours is found to be the best predictive variable for response to immune checkpoint inhibitor therapy, emphasizing the importance of investigating TILs in pancreatic cancer, especially focussing on CD8+ T cells. OBJECTIVE: Here, we systematically review the literature and perform meta-analyses to examine the prognostic value of TILs in human pancreatic ductal adenocarcinomas (PDAC). Secondarily, we review the literature regarding the histological localization of TILs and the impact on survival in PDAC. EVIDENCE REVIEW: A literature search was conducted on PubMed, Embase, The Cochrane Library and Web of Science. Studies examining patients with PDAC and the impact of high vs. low infiltration of immune cells on long-term oncological survival measures were included. Time-to-event meta-analysis and frequency analysis were conducted using a random effects model. The risk of bias was assessed using the Newcastle-Ottowa Scale. Quality of the cumulative evidence was evaluated using the GRADE approach for prognostic studies. FINDINGS: In total, 1971 articles were screened, of which 43 studies were included in the systematic review and 39 in the meta-analysis. High infiltration of CD8+ lymphocytes was significantly associated with improved overall survival (OS) [hazard ratio (HR) = 0.58, 95% confidence intervals (CIs): 0.50-0.68], disease-free survival (DFS) [HR = 0.64, 95% CI: 0.52-0.78], progression-free survival [HR = 0.66, 95% CI: 0.51-0.86] and cancer-specific survival [HR = 0.56, 95% CI: 0.32-0.99]. A high infiltration of CD3+ T cells was correlated with increased OS [HR = 0.58, 95% CI: 0.50-0.68] and DFS [HR = 0.74, 95% CI: 0.38-1.43]. Infiltration of CD4+ lymphocytes was associated with improved 12-months OS [risk ratio = 0.59, 95% CI: 0.35-0.99] and DFS [risk ratio = 0.68, 95% CI: 0.53-0.88]. High expression of FoxP3+ lymphocytes was associated with poor OS [HR = 1.48, 95% CI: 1.20-1.83]. The greatest impact on survival was observed in the CD8+ T cell and OS group, when infiltration was located to the tumour centre [HR = 0.53, 95% CI: 0.45-0.63]. However, subgroup analysis on the impact of the histological location of infiltration revealed no significant differences between the subgroups (tumour centre, invasive margin, stroma and all locations) in any of the examined cell types and outcomes. CONCLUSIONS AND RELEVANCE: Subsets of TILs, especially CD3+, CD8+ and FoxP3+ T cells are strongly associated with long-term oncological outcomes in patients with PDAC. To our knowledge, this is the first systematic review and meta-analysis on the prognostic value of TILs in pancreatic cancer.

Prophylactic antidepressant treatment following acute coronary syndrome: A systematic review of randomized controlled trials.

Major depressive disorder is significantly increased in patients following acute coronary syndrome resulting in twofold increased mortality compared with patients without depression. The depression diagnosis is often missed leading to considerable undertreatment. This systematic review assesses the current evidence of primary prophylactic treatment of depression in patients after acute coronary syndrome. The study protocol was prospectively registered at PROSPERO (registration number CRD42015025587). A systematic review were conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran Library was searched. Two independent reviewers screened the records. The inclusion criteria were randomized controlled trials on adult patients with acute coronary syndrome treated prophylactically with an antidepressant intervention of any kind. A validated assessment tool should measure depression and depressive symptoms. Languages were limited to articles written in English. Six articles were included. Four studies utilized different components of case and disease management, health coaching, or relaxational audiotapes as intervention compared with usual care or with no formal program of rehabilitation. None of the studies showed any significant prophylactic effect against depression. One study with a program of health education and counselling and another study with a pharmacological antidepressant showed significant prophylactic effect on depression and depressive symptoms. All six included studies were associated with high risk of bias. There is not strong evidence of the effects of any type of routine antidepressant prophylaxis in patients following acute coronary syndrome. Further high quality studies are warranted.

Actigraphy for measurements of sleep in relation to oncological treatment of patients with cancer: a systematic review.

Sleep disturbances are a prevalent and disabling problem for patients with cancer. Sleep disturbances are present throughout the cancer trajectory, especially during oncological treatment. Previously sleep disturbances have primarily been quantified with subjective rating scales. Actigraphy is an easy to use, non-invasive method for objective measurement of sleep. We systematically reviewed the literature for studies using actigraphy to measure sleeping habits of patients with cancer, undergoing oncological treatment. Our study furthermore reviewed studies with interventions designed to reduce sleep disturbances in the patient population. 19 studies were included in the final review of which 13 had a descriptive study design and six included some kind of intervention. The studies were primarily performed in patients with breast cancer undergoing chemotherapy. We found that sleep disturbances are prevalent, and persistent in patients with cancer. The sleep disturbances seem to be aggravated by chemotherapy treatment and accumulate as the treatment continues. Sleep disturbances need further attention among clinicians working with patients with cancer.

Actigraphy for measurement of sleep and sleep-wake rhythms in relation to surgery.

STUDY OBJECTIVES: Patients undergoing surgery have severe sleep and sleep-wake rhythm disturbances resulting in increased morbidity. Actigraphy is a tool that can be used to quantify these disturbances. The aim of this manuscript was to present the literature where actigraphy has been used to measure sleep and sleep-wake rhythms in relation to surgery. METHODS: A systematic review was performed in 3 databases (Medline, Embase, and Psycinfo), including all literature until July 2012. RESULTS: Thirty-two studies were included in the review. Actigraphy could demonstrate that total sleep time and sleep efficiency was reduced after surgery and number of awakenings was increased in patients undergoing major surgery. Disturbances were less severe in patients undergoing minor surgery. Actigraphy could be used to differentiate between delirious and non-delirious patients after major surgery. Actigraphy measurements could determine a differential effect of surgery based on the patient's age. The effect of pharmacological interventions (chronobiotics and hypnotics) in surgical patients could also be demonstrated by actigraphy. CONCLUSION: Actigraphy can be used to measure sleep and sleep-wake rhythms in patients undergoing surgery.