This trial tested the influence of aspirin or resistant starch on the incidence of colorectal cancer or colonic adenomas in patients with the Lynch syndrome (hereditary nonpolyposis colon cancer). ...Neither intervention influenced the incidence of colorectal neoplasms in the Lynch syndrome.
Neither aspirin or resistant starch influenced the incidence of colorectal neoplasms in the Lynch syndrome.
The regular use of aspirin or aspirin-like agents is associated with a moderate reduction in the risk of colonic polyps and colorectal cancer.
1
–
4
Randomized trials of high-fiber diets have not shown a reduction in the risk of adenomas or colorectal cancer,
5
but none have investigated the effects of resistant starch. There is epidemiologic evidence of a negative correlation between colon cancer and starch intake.
6
Resistant starches escape digestion in the upper gut; colonic fermentation yields short-chain fatty acids, including butyrate, which has antineoplastic properties.
7
In carcinogen-treated rats, resistant starch reduces the development of intestinal tumors
8
,
9
and the production . . .
Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes ...(mean follow-up 55·7 months SD 31·4) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population.
In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 82% from Europe, 112 13% from Australasia, 38 4% from Africa, and four <1% from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990.
Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43–0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39–0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years' intervention gave an HR of 0·56 (0·34–0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31–0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43–0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously.
The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results.
Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.
Objective To systematically evaluate the effects of physical activity in adult patients after completion of main treatment related to cancer.Design Meta-analysis of randomised controlled trials with ...data extraction and quality assessment performed independently by two researchers.Data sources Pubmed, CINAHL, and Google Scholar from the earliest possible year to September 2011. References from meta-analyses and reviews.Study selection Randomised controlled trials that assessed the effects of physical activity in adults who had completed their main cancer treatment, except hormonal treatment.Results There were 34 randomised controlled trials, of which 22 (65%) focused on patients with breast cancer, and 48 outcomes in our meta-analysis. Twenty two studies assessed aerobic exercise, and four also included resistance or strength training. The median duration of physical activity was 13 weeks (range 3-60 weeks). Most control groups were considered sedentary or were assigned no exercise. Based on studies on patients with breast cancer, physical activity was associated with improvements in insulin-like growth factor-I, bench press, leg press, fatigue, depression, and quality of life. When we combined studies on different types of cancer, we found significant improvements in body mass index (BMI), body weight, peak oxygen consumption, peak power output, distance walked in six minutes, right handgrip strength, and quality of life. Sources of study heterogeneity included age, study quality, study size, and type and duration of physical activity. Publication bias did not alter our conclusions.Conclusions Physical activity has positive effects on physiology, body composition, physical functions, psychological outcomes, and quality of life in patients after treatment for breast cancer. When patients with cancer other than breast cancer were also included, physical activity was associated with reduced BMI and body weight, increased peak oxygen consumption and peak power output, and improved quality of life.
Summary Background & aims Patients undergoing gastrointestinal operations are at risk of malnutrition which may increase the chance of adverse surgical outcomes. This prospective study aimed at ...correlating nutritional status of patients having gastrointestinal operations with their short-term surgical outcomes captured by a territory-wide Surgical Outcomes Monitoring and Improvement Program. Methods The preoperative malnutrition risk of Chinese adult patients undergoing elective/emergency ultra-major/major gastrointestinal operations in two surgical departments over a 12-month period were assessed by Chinese version of Malnutrition Universal Screening Tool. Their perioperative risk factors and clinical outcomes, including length of hospital stay, mortality and morbidity, were retrieved from the above mentioned program. Correlation of malnutrition risk with clinical outcomes was assessed by logistic regression analysis after controlling for known confounders. Results 943 patients (58% male; mean age 65.9 ± 14.8 years) underwent gastrointestinal operations (40.3% emergency operation; 52.7% ultra-major procedures; 66.9% bowel resections) had analyzable data. 15.8% and 17.1% of patients were at medium and high risk of malnutrition, respectively. Malnutrition risk score according to the screening tool was an independent predictor of length of hospital stay, 30-day mortality, 60-day mortality and minor medical complications. Similar correlations were found for various sub-scores of malnutrition risk. Weight loss sub-score was predictive of 30-day mortality, 60-day mortality and minor medical complications. Body mass index was predictive of mortality (30- and 60- day) whereas the acute disease sub-score was predictive of length of hospital stay. Conclusions Preoperative malnutrition was an important predictor of poor clinical outcomes in patients undergoing gastrointestinal operations in Hong Kong.
PURPOSE:
METHODS:
RESULTS:A total of 1,417 patients were studied and anastomotic leakage occurred in 25 patients (1.8 percent). Twenty-two patients (88 percent) required reoperation for anastomotic ...leakage. The hospital stay (28 vs. 10 days, P < 0.001) and mortality rate (32 vs. 4 percent, P < 0.001) of patients with anastomotic leakage were significantly increased compared with those without leakage. Multivariate analysis showed that American Society of Anesthesiologists Grade 3 to 5 (P = 0.04; odds ratio, 5.6; 95 percent confidence interval, 1.6-15.3) and emergency operation (P = 0.03; odds ratio, 4.6; 95 percent confidence interval, 1.9-9.8) were independent factors associated with anastomotic leakage. The risk of anastomotic leakage was 8.1 percent (odds ratio, 10.5; 95 percent confidence interval, 2.7-26.8) if both factors were present.
CONCLUSIONS:
In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This ...prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS).
Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months.
During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03).
Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.
Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict ...psychological resilience in adults undergoing genetic testing for HCRC.
A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points.
Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 +/- 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression (B = -0.24, p < 0.01 for depression); and anxiety (B = -0.11, p = 0.05 for anxiety).
The current findings suggest that hopefulness may predict resilience after HCRC genetic testing in Hong Kong Chinese. Interventions to increase the level of hope may be beneficial to the psychological adjustment of CRC genetic testing recipients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To assess the effects of dietary and physical activity (PA) interventions on generic and cancer-specific quality of life (QoL), anxiety, and depression levels among adult Chinese colorectal ...cancer (CRC) survivors.
Methods
Two-hundred twenty-three adult CRC survivors within 1 year of completion of primary cancer treatment were randomized to receive dietary, PA or combined intervention, or usual care for a 12 monthduration, under a 2 (diet vs usual care) × 2 (PA vs usual care) factorial design. Generic and cancer-specific QoL was assessed using a Chinese version 12-Item Short Form Health Survey (SF-12) and the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale, respectively. Anxiety and depression was assessed using the Hospital Anxiety and Depression Scale at baseline, 6, 12, 18, and 24 months. Linear mixed models were used for examining the intervention effects.
Results
Participants receiving dietary intervention experienced a significant improvement in the generic measure of QoL (SF-6D utility scores, mean difference 0.042, 95%CI 0.03 to 0.081) at 12 months, the cancer-specific QoL scores (mean difference 3.09, 95%CI 0.13 to 6.04), and levels of depression (
P
= 0.015) at both 12 and 24 months follow-up. Participants receiving PA intervention only demonstrated a significant improvement in SF-6D utility index (mean difference 0.039, 95%CI 0.002 to 0.077) and physical functioning (mean difference 2.85, 95%CI 1.00 to 4.70) at 6 months.
Conclusions
Dietary intervention improved the generic and cancer-specific QoL and depression in CRC survivors.
Trial registration
The study was prospectively registered on 17 October 2012 at
ClinicalTrials.gov
(NCT01708824).
Implications for Cancer Survivors
CRC survivors can benefit from dietary interventions in alleviating depression and improving overall health-related QoL.
This study aimed to investigate the impact of postoperative complications on long-term survival and disease recurrence in patients who underwent curative resection for colorectal cancer.
Patients who ...underwent radical resection for colorectal cancer with curative intent from January 1996 to December 2004 were included. Operative mortality and morbidity were documented prospectively. Factors that might affect long-term outcome were analyzed with multivariate analysis.
Curative resection was performed in 1657 patients (943 men), and the median age was 70 years (range: 24-94 years). The 30-day mortality was 2.4%, and the complication rate was 27.3%. Age over 70 years (P < .001, odds ratio: 2.06, 95% CI: 1.63-2.61), male gender (P = .001, odds ratio: 1.49, 95% CI: 1.19-1.88), emergency operation (P < .001, odds ratio: 3.14, 95% CI: 2.26-4.35) and rectal cancer (P < .001, odds ratio: 1.41, 95% CI: 1.25-1.61) were associated with a significantly higher complication rate. With exclusion of patients who died within 30 days, the median follow-up of the surviving patients was 45.3 months. The 5-year overall survival was 64.9%, and the overall recurrence rate was 29.1%. The presence of postoperative complications was an independent factor associated with a worse overall survival (P = .023, hazard ratio: 1.26; 95% CI: 1.03-1.52) and a higher overall recurrence rate (P = .04, hazard ratio: 1.26; 95% CI: 1.01-1.57).
The presence of postoperative complication not only affects the short-term results of resection of colorectal cancer, but the long-term oncologic outcomes are also adversely affected. Long-term outcomes can be improved with efforts to reduce postoperative complications.
The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g ...resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS.
Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.
PDF
