Metachronous colorectal cancer metastasis: Who, what, when and what to do about it.

Metachronous colorectal cancer (CRC) metastasis occurs due to micrometastatic disease, in up to 23% of patients who have undergone curative-intent treatment. Metachronous metastasis tends to occur within 2 years of initial treatment. Diagnosis relies on posttreatment surveillance strategies. Care for patients with metachronous CRC metastasis is complex and requires careful multidisciplinary consideration. Those with isolated and technically resectable diseases are recommended to undergo metastasectomy with adjunct chemotherapy, however, survival, even after curative-intent resection, is poor.

The promoting physical activity in regional and remote cancer survivors (PPARCS) trial: Physical activity maintenance.

INTRODUCTION: The study examined whether increased physical activity (PA) in nonmetropolitan cancer survivors was maintained 12 weeks following the PPARCS intervention. METHODS: PA outcomes were assessed using an accelerometer at baseline, end of the intervention, and at 24 weeks. Linear mixed models were used to examine between-group changes in PA outcomes. RESULTS: The increased moderate-to-vigorous PA (MVPA) following intervention was maintained with significantly higher MVPA in the intervention group at 24 weeks (vs. controls) compared to baseline nett change of 52.5 min/week (95% CI 11.0-94.0.4). CONCLUSIONS: Distance-based interventions using wearables and health coaching may produce MVPA maintenance amongst nonmetropolitan cancer survivors.

PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

BACKGROUND: The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c+ DC co-expressing the immunoinhibitory molecule PD-L1 and their spatial relationship with CD8+ T-cells in patients treated for stage III colon cancer. METHODS: Tissue microarrays containing representative cores of central tumor, leading edge, and adjacent normal tissue from 221 patients with stage III colon cancer were immunostained for CD8, CD11c, PD-L1, and cytokeratin using immunofluorescent probes. Cells were quantified using StrataQuest digital image analysis software, with intratumoral and stromal regions analyzed separately. Kaplan-Meier estimates and Cox regression were used to assess survival. RESULTS: Intratumoral CD8+ cell density (HR = .52, 95% confidence interval [CI] .33-.83, P = .007), stromal CD11c+ cell density (HR = .52, 95% CI .33-.83, P = .006), intratumoral CD11c+ PD-L1+ cell density (HR = .57, 95% CI .35-.92, P = .021), and stromal CD11c+ PD-L1+ cell density (HR = .48, 95% CI .30-.77, P = .003) on leading-edge cores were all significantly associated with good survival. CD8+ cell density was positively correlated with both CD11c+ cell density and CD11c+ PD-L1+ cell density in tumor epithelium and stromal compartments. CONCLUSION: Here we showed that PD-L1-expressing DC in the tumor microenvironment are associated with improved survival in stage III colon cancer and likely reflect an immunologically "hot" tumor microenvironment. Further investigation into the expression of immunomodulatory molecules by tumor-associated DC may help to further elucidate their prognostic value.

Psychological correlates of physical activity and exercise preferences in metropolitan and nonmetropolitan cancer survivors.

OBJECTIVE: Interventions to increase physical activity (PA) in cancer survivors have often adopted a "one-size-fits-all" approach and may benefit from being tailored to psychological constructs associated with behavior. The study objective was to investigate the exercise preferences and psychological constructs related to PA among cancer survivors. METHODS: Posttreatment colorectal, endometrial, and breast cancer survivors (n = 183) living in metropolitan and nonmetropolitan areas completed survey measures of PA, exercise preferences, attitudes, self-efficacy, perceived behavioral control (PBC), and intention toward PA. RESULTS: A structural equation model with adequate fit and quality indices revealed that instrumental attitude and self-efficacy were related to PA intention. Intention was related to behavior and mediated the relationship between self-efficacy and behavior. Preferred exercise intensity was related to self-efficacy, PBC, attitudes, and intention, while preferred exercise company was related to self-efficacy and PBC. Participants preferred moderate-intensity PA (71%), specifically self-paced (52%) walking (65%) in an outdoor environment (58%). CONCLUSIONS: Since instrumental attitude and self-efficacy were associated with PA, incorporating persuasive communications targeting attitudes in PA interventions may promote PA participation. As cancer survivors who prefer low-intensity exercise and exercising with others report lower self-efficacy and PBC, interventions targeting confidence and successful experience in this group may also be warranted.

"To be there for my family" and "Keep my independence": Metropolitan and Non-Metropolitan Cancer Survivors' Health Behaviour Motives.

PURPOSE: Cancer survivors are at risk of comorbidities and mortality, and those living outside of metropolitan areas are particularly susceptible given poorer socioeconomic, health and support resources. As engagement in health behaviours is affected by participants' autonomous motives, investigation of the motives of cancer survivors in metropolitan and non-metropolitan areas could elucidate the values and reasons for practising health behaviours, allowing programs to be tailored to these motives. METHODS: Metropolitan (n = 103) and non-metropolitan (n = 80) Australian cancer survivors completed a survey item by describing their motives for physical activity and healthy diet change. Inductive thematic analysis of responses was performed to establish themes across health behaviour motives. RESULTS: Analyses revealed four themes: to be able to, longevity, psychological health and appearance. Survivors primarily referred to being able to enjoy family, leisure activities, travel and staying independent, with these motives often linked to longevity. Motives were similar across locations; however, those in non-metropolitan locations reported continuation of work and pain relief more frequently. Female survivors more often reported weight loss. CONCLUSIONS: A predominant motive for health behaviour change in cancer survivors across geographical location was the ability to enjoy family and engage in leisure and work activities. Programs aiming to promote health behaviours in cancer survivors might consider framing interventions accordingly by emphasizing benefits of longevity and maintaining independence.

Primary local excision of stage 1 rectal cancer is not associated with worse oncological outcomes when compared with major resection.

PURPOSE: Primary local excision (PLE) for early rectal cancers is associated with decreased surgical morbidity and mortality compared with major resection (MR). However, it is thought to be associated with poorer oncological outcomes. There is a paucity of data regarding PLE within the Australasian population. We present comparative post-operative and survival outcomes for stage 1 rectal cancers treated with PLE or MR from three Western Australian hospitals. METHODS: A retrospective analysis was performed on a prospectively maintained database of patients undergoing PLE or MR for stage 1 rectal cancers between February 1996 and May 2019. RESULTS: Of the 533 patients, 81 underwent PLE. Median post-operative admission was shorter for those undergoing PLE, with no significant difference in post-operative complication rate. Five-year overall survival was greater following MR (89.6% CI 86.1-92.3) compared with PLE (84.6% CI 73.8-91.2; p = 0.0003). There was no significant difference in 5-year cancer-specific survival (MR, 94.4% CI 91.5-96.3; PLE, 95.3% CI 86.0-98.5; p = 0.98) or 5-year disease-free survival (MR, 92.3% CI 89.1-94.7; PLE, 89.1% CI 78.5-94.7; p = 0.36). Local excision provided poorer local tumour control with an inferior 5-year local recurrence rate (MR, 2.16% CI 1.08-4.28; PLE, 10.9% CI 5.30-21.6; p = 0.0002). After controlling for confounders, PLE was significantly associated with worse local recurrence but did not significantly impact overall survival, cancer-specific survival, overall recurrence, or metastatic recurrence. CONCLUSION: Local excision of early rectal cancer remains a viable alternative, in those unwilling or unable to undergo MR. Patients should be informed that while PLE is associated with poorer local pelvic control, this does not translate to worse survival.

A randomized controlled trial of WATAAP to promote physical activity in colorectal and endometrial cancer survivors.

OBJECTIVE: The objective of this study was to ascertain whether wearable technology coupled with action planning was effective in increasing physical activity (PA) in colorectal and endometrial cancer survivors at cardiovascular risk. METHODS: Sixty-eight survivors who had cardiovascular risk factors and were insufficiently active were randomized to intervention and control arms. Intervention participants were given a wearable tracker for 12 weeks, two group sessions, and a support phone call. Participants in the control arm received print materials describing PA guidelines. Assessments at baseline and 12 weeks measured triaxial and uniaxial estimates of moderate-vigorous physical activity (MVPA), sedentary behaviour, blood pressure, and body mass index (BMI). RESULTS: The intervention group significantly increased MVPA by 45 min/wk compared with a reduction of 21 min/wk in the control group. Group by time interactions were significant for minutes of MVPA (F1,126  = 5.14, P = 0.025). For those with diastolic hypertension, there was a significant group by time interaction (F1,66  = 4.89, P = 0.031) with a net reduction of 9.89 mm Hg in the intervention group. CONCLUSIONS: Significant improvements in MVPA were observed following the intervention. The results display promise for the use of pragmatic, low-intensity interventions using wearable technology.

Long-term Outcomes of Surgery for Colorectal Cancer: A 20-Year Study.

BACKGROUND: Colorectal cancer is a common and potentially deadly diagnosis. Surgery is the treatment of choice. Data of outcomes beyond 10 y are sparse. This study attempts to identify factors influencing long-term survival. METHODS: This cohort study examines a prospectively collected database of patients undergoing colorectal resections from January 1996 to May 2006. Variables were analyzed by plotting Kaplan-Meier survival curves and Cox regression analysis to identify independent predictors of survival. RESULTS: Six hundred fifty-seven patients were included in this analysis. Three hundred sixty underwent resection for rectal cancer. Median follow-up time was 11.7 y (interquartile range 2.8-15.4). Metachronous cancers occurred following 5.4% (confidence intervals [CI] 3.4-8.4) of resections for colorectal malignancy at 15 y. Mean age at death was higher in patients with higher Australian clinicopathological score (A: 82.4, B: 78.9, C: 75.5, D: 68.9). Multivariable analysis revealed age at diagnosis (hazard ratio [HR] 1.02, CI 1.01-1.03), Australian clinicopathological score (B: HR 1.47, CI 1.08-2.01; C: 2.11, CI 1.51-2.93; D: HR 11.12, CI 8.12-15.13), American Society of Anesthesiology score (ASA2: HR 1.66, CI 1.03-2.67; ASA3: HR 2.00, CI 1.20-3.34; ASA4: HR 3.39, CI 1.95-6.25), and operating for locoregional recurrence (HR 1.82, CI 1.21-2.76) to be associated with increased mortality. Adjuvant chemotherapy was associated with improved survival (HR 0.64, CI 0.49-0.84). CONCLUSIONS: Age at diagnosis, American Society of Anesthesiology score, and stage of disease were the principal predictors of long-term survival. Adjuvant chemotherapy was found to improve survival. Metachronous cancers occurred in a minority of patients.

Barriers to physical activity participation in colorectal cancer survivors at high risk of cardiovascular disease.

BACKGROUND: Lifestyle factors including inadequate physical activity may contribute to increased risk of developing cardiovascular disease in colorectal cancer survivors. Identification of the barriers to physical activity is important for forming an evidence base of factors to target in future physical activity programs aimed at improving cardiovascular health in this population. METHODS: Colorectal cancer survivors (N = 24) from St. John of God Subiaco Hospital participated in semi-structured interviews about their current physical activity behaviors and perceived barriers to physical activity. RESULTS: Inductive thematic analysis of interviews revealed 5 overarching themes relating to barriers to physical activity: psychological barriers, environmental barriers, knowledge of guidelines, lack of practitioner support, and energy/age barriers. CONCLUSIONS: Novel findings revealed participants' dependence on practitioner support, including a reliance on practitioners to recommend lifestyle change. Survivors also revealed that regular checkups to monitor cardiovascular risk replaced the need for healthy lifestyle changes. IMPLICATIONS: With survivors holding the advice of clinicians in high regard, an opportunity exists for clinicians to facilitate lifestyle change. Health care professionals such as nurses can implement motivational strategies and provide additional health information during follow-up visits, to ensure long-term adherence. Individuals who reported psychological, motivational, and environmental barriers may benefit from interventions to improve self-regulation, planning, and problem-solving skills.

A qualitative study exploring health perceptions and factors influencing participation in health behaviors in colorectal cancer survivors.

PURPOSE: The purpose of the study was to explore colorectal cancer survivors' health perceptions following cessation of active treatment for cancer and to explore the factors influencing participation in health-promoting behaviors that may help reduce cardiovascular disease risk. METHODS: Face-to-face interviews were conducted with participants that had completed active treatment for cancer within the previous 2 years. Participants were colorectal cancer survivors (N = 24, men = 11, women = 13, M age = 69.38 years, SD = 4.19) recruited from a private hospital in Perth, Australia on the basis that they had existing morbidities that put them at increased risk of cardiovascular disease. Interview transcripts were analyzed using thematic analysis. RESULTS: Five main themes emerged: back to normal; the pleasures in life: 'is it worth it?'; beliefs about health behavior; skepticism of eating guidelines; and lack of motivation. The majority of participants felt they were in good health and had made a full recovery. Participants questioned whether it was worth changing their lifestyle given their life stage and referred to the desire to enjoy life. Lay health beliefs, skepticism of eating guidelines, and a lack of motivation were barriers to change. CONCLUSIONS: Interventions should target lay beliefs and skepticism in relation to health behaviors in order to reinforce the importance and value of participating in health-related behavior. IMPLICATIONS FOR CANCER SURVIVORS: Findings may inform the development of effective, patient-centered interventions that target lay health beliefs and build motivation for health behavior change. Copyright © 2016 John Wiley & Sons, Ltd.

Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil­based chemotherapy.

BACKGROUND & AIMS: Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses than patients with tumors without MSI, but have a poor response to 5-fluorouracil­based chemotherapy. A dominant-negative form of heat shock protein (HSP)110 (HSP110DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T(17) intron repeat, sensitizes the cells to 5-fluorouracil and oxaliplatin.We investigated whether HSP110 T(17) could be used to identify patients with colorectal cancer who would benefit from adjuvant chemotherapy with 5-fluorouracil and oxaliplatin. METHODS: We characterized the interaction between HSP110 and HSP110DE9 using surface plasmon resonance. By using polymerase chain reaction and fragment analysis, we examined how the size of somatic allelic deletions in HSP110 T(17) affected the HSP110 protein expressed by tumor cells. We screened 329 consecutive patients with stage II­III colorectal tumors with MSI who underwent surgical resection at tertiary medical centers for HSP110 T(17). RESULTS: HSP110 and HSP110DE9 interacted in a1:1 ratio. Tumor cells with large deletions in T(17) had increased ratios of HSP110DE9:HSP110, owing to the loss of expression of full-length HSP110. Deletions in HSP110 T(17) were mostly biallelic in primary tumor samples with MSI. Patients with stage II­III cancer who received chemotherapy and had large HSP110 T(17) deletions (≥5 bp; 18 of 77 patients, 23.4%) had longer times of relapse-free survival than patients with small or no deletions (≤4 bp; 59 of 77 patients, 76.6%) in multivariate analysis (hazard ratio, 0.16; 95% confidence interval, 0.012­0.8; P = .03). We found a significant interaction between chemotherapy and T17 deletion (P =.009). CONCLUSIONS: About 25% of patients with stages II­III colorectal tumors with MSI have an excellent response to chemotherapy, due to large, biallelic deletions in the T(17) intron repeat of HSP110 in tumor DNA.

Peer review of cancer multidisciplinary teams: is it acceptable in Australia?

OBJECTIVE: To develop a peer-review model for assessment and quality improvement of cancer multidisciplinary teams (MDTs) and qualitatively assess its feasibility and acceptability in Australia. DESIGN, SETTING AND PARTICIPANTS: A peer-review methodology was developed, based on the United Kingdom's National Health Service peer-review model and a comprehensive literature review. This was pilot tested in three mature MDTs in different settings. Semi-structured interviews were conducted between December 2012 and July 2013 with all five peer reviewers and 17 MDT members. Thematic analysis was undertaken using a framework approach. RESULTS: Peer reviewers and MDT members found the process reasonable, constructive and useful; however, those involved in the preparation for the review found it time-consuming. Most MDT members considered the final report accurate and reflective of their service. Recommendations in the report were met with mixed reactions: several MDT members perceived some recommendations to be particularly relevant, while others viewed the same recommendations as impractical or of limited value. Many participants were unsure if recommendations would be fully implemented. The majority saw value in the process and expressed support for its implementation locally and nationally; however, feedback suggests the most appropriate format is yet to be established. CONCLUSIONS: Peer review of cancer MDTs is feasible and acceptable. We describe valuable lessons learnt and recognise that further development of the proposed peer-review model and national benchmarking of MDTs against established outcome measures is required if this process is to be widely implemented.

Population-based screening for Lynch syndrome in Western Australia.

We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994-2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2-3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.

A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors (PPARCS).

BACKGROUND: Physical activity (PA) is important for cancer survivors. Trials of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer survivors. The objective of this study was to ascertain whether wearable technology, coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in Australia. METHODS: Cancer survivors from 5 states were randomized to intervention and control arms. Intervention participants were given a Fitbit Charge 2TM and received up to 6 telephone health coaching sessions. Control participants received PA print materials. Accelerometer assessments at baseline and 12 weeks measured moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior. RESULTS: Eighty-seven participants were recruited (age = 63 ± 11 years; 74 (85%) female). There was a significant net improvement in MVPA of 49.8 min/week, favoring the intervention group (95% confidence interval (95%CI): 13.6-86.1, p = 0.007). There was also a net increase in MVPA bouts of 39.5 min/week (95%CI: 11.9-67.1, p = 0.005), favoring the intervention group. Both groups improved light PA and sedentary behavior, but there were no between-group differences. CONCLUSION: This is the first study to demonstrate that, when compared to standard practice (i.e., PA education), a wearable technology intervention coupled with distance-based health coaching, improves MVPA in non-metropolitan cancer survivors. The results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors.

Locally performed postoperative circulating tumour DNA testing performed during routine clinical care to predict recurrence of colorectal cancer.

BACKGROUND: Identifying patients at high risk for colorectal cancer recurrence is essential for improving prognosis. In the postoperative period, circulating tumour DNA (ctDNA) has been demonstrated as a significant prognostic indicator of recurrence. These results have been obtained under the strict rigours of clinical trials, but not validated in a real-world setting using in-house testing. We report the outcomes of locally performed postoperative ctDNA testing conducted during routine clinical care and the association with the recurrence of colorectal cancer. METHODS: We recruited 36 consecutive patients with newly diagnosed colorectal cancer between 2018 and 2020. Postoperative plasma samples were collected at the first outpatient review following resection. Tumour-informed ctDNA analysis was performed using droplet digital polymerase chain reaction or targeted next-generation sequencing. RESULTS: At the time of surgery, there were 24 patients (66.7%) with localized cancer, nine (25%) with nodal spread, and three (8.3%) with metastatic disease. The median time from surgery to plasma sample donation was 22 days (IQR 20-28 days). At least one somatic mutation was identified in primary tumour tissue for 28 (77.8%) patients. Postoperative ctDNA was detected in five patients (13.9%). The median duration of follow-up was 32.0 months (IQR 27.2-38.1 months). Two patients (5.56%) developed metastatic recurrence. However, neither had detectable postoperative ctDNA. There were no instances of loco-regional recurrence. CONCLUSION: Analysis of postoperative ctDNA testing can be performed locally, however this study did not reproduce the adverse association between detectable postoperative ctDNA and the development of colorectal cancer recurrence seen in clinical trials.

FOXP3+ cell density in lymphoid follicles from histologically normal mucosa is a strong prognostic factor in early stage colon cancer.

There are few clearly established prognostic factors available to guide the use of adjuvant chemotherapy in early stage colon cancer patients. Some of the most promising candidates include the invasion of extramural blood vessels by tumour cells and the densities of FOXP3+ T regulatory cells (Tregs) in tumour and adjacent normal colonic mucosal tissue. The aim of our study was to evaluate the prognostic significance of these markers in AJCC stage II colon cancer, with particular reference to lymphoid follicles in the mucosa. Histopathological review for the presence of vascular and serosal invasion was conducted on a series of 165 stage II colon cancers treated by surgery alone. Immunohistochemical staining for FOXP3 was performed on tumour tissue and histologically normal colonic mucosa from the surgical margin. Image analysis software was used to evaluate the density of FOXP3+ cells in the tumour core, invading margin and lymphoid follicles from the colonic mucosa. For survival analysis, cases were classified into high- or low-density of FOXP3+ cells according to the median value. The mean density of FOXP3+ Tregs in lymphoid follicles was twofold and fivefold higher than in the invading margin and tumour core, respectively. Multivariate analysis identified extramural vascular invasion (HR, 2.47; 95% CI: 1.00-6.07; P = 0.05) and high FOXP3+ cell density in lymphoid follicles (HR, 4.22; 95% CI: 1.49-11.91; P = 0.007) as independent factors for worse survival, whereas a high frequency of lymphoid follicles in histologically normal colonic mucosa was associated with better survival (HR, 0.31; 95% CI: 0.12-0.79; P = 0.014). Our data suggest that host factors related to the immune system have major prognostic significance in early stage colon cancer. The density of FOXP3+ cells within lymphoid follicles and the frequency of these structures in normal colonic mucosa represent novel and independent prognostic factors.

Non-resection versus resection for an asymptomatic primary tumour in patients with unresectable stage IV colorectal cancer.

BACKGROUND: In a majority of patients with stage IV colorectal cancer, the metastatic disease is not resectable and the focus of management is on how best to palliate the patient. How to manage the primary tumour is an important part of palliation. A small proportion of these patients present with either obstructing or perforating cancers and require urgent surgical care. However, a majority are relatively asymptomatic from their primary cancer. Chemotherapy has been shown to prolong survival in this group of patients, and a majority of patients would be treated this way. Nonetheless, A recent meta-analysis (Stillwell 2010) suggests an improved overall survival and reduced requirement for emergency surgery in those patients who undergo primary tumour resection. This review was also able to quantify the mortality and morbidity associated with surgery to remove the primary. OBJECTIVES: To determine if there is an improvement in overall survival following resection of the primary cancer in patients with unresectable stage IV colorectal cancer and an asymptomatic primary who are treated with chemo/radiotherapy. SEARCH METHODS: In January 2012 we searched for published randomised and non-randomised controlled clinical trials without language restrictions using the following electronic databases: CENTRAL (the Cochrane Library (latest issue)), MEDLINE (1966 to date), EMBASE (1980 to date), Science Citation Index (1981 to date), ISI Proceedings (1990 to date), Current Controlled Trials MetaRegister (latest issue), Zetoc (latest issue) and CINAHL (1982 to date). SELECTION CRITERIA: Randomised controlled trials and non-randomised controlled studies evaluating the influence on overall survival of primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who are treated with palliative chemo/radiotherapy. DATA COLLECTION AND ANALYSIS: We conducted the review according to the recommendations of The Cochrane Collaboration and the Cochrane Colorectal Group. "Review Manager 5" software was used. MAIN RESULTS: A total of 798 studies were identified following the initial search. No published or unpublished randomised controlled trials comparing primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who were treated with chemo/radiotherapy were identified. Seven non-randomised studies, potentially eligible for inclusion, were identified: 2 case-matched studies, 2 CCTs and 3 retrospective cohort studies. Overall, these trials included 1.086 patients (722 patients treated with primary tumour resection, and 364 patients managed first with chemotherapy and/or radiotherapy). AUTHORS' CONCLUSIONS: Resection of the primary tumour in asymptomatic patients with unresectable stage IV colorectal cancer who are managed with chemo/radiotherapy is not associated with a consistent improvement in overall survival. In addition, resection does not significantly reduce the risk of complications from the primary tumour (i.e.  obstruction, perforation or bleeding). Yet there is enough doubt with regard to the published literature to justify further clinical trials in this area. The results from an ongoing high quality randomised controlled trial will help to answer this question.

Fusobacterium nucleatum and Bacteroides fragilis detection in colorectal tumours: Optimal target site and correlation with total bacterial load.

BACKGROUND: Mucosal infiltration by certain bacterial species may contribute to the development and progression of colorectal cancer (CRC). There is considerable variation in reported detection rates in human CRC samples and the extent to which bacterial infiltration varies across regions of the primary tumour is unknown. This study aimed to determine if there is an optimal site for bacterial detection within CRC tumours. METHODS: Presence of target bacterial species was assessed by quantitative real-time PCR (qPCR) in 42 human CRC tumours. Abundance in primary tumour regions, normal epithelium and at metastatic sites was investigated in an expanded cohort of 51 patients. Species presence/absence was confirmed by diversity profiling in five patients. Correlation with total bacterial load and clinicopathological features was assessed. RESULTS: Fusobacterium nucleatum and Bacteroides fragilis were detected in tumours from 43% and 24% of patients, respectively (17% positive for both species). The optimal detection site was the tumour luminal surface (TLS). Patients testing positive at the TLS frequently tested negative at other sites, including central tumour and invasive margin. F. nucleatum was detected at a higher frequency in tumour versus normal epithelium (p < 0.01) and was associated with more advanced disease (p = 0.01). Detection of both species correlated with total bacterial load. However, corroboration of qPCR results via diversity profiling suggests detection of these species may indicate a specific microbial signature. CONCLUSIONS: This study supports a role for F. nucleatum in CRC development. Presence of F. nucleatum and B. fragilis varies across primary tumour regions, with the TLS representing the optimal site for bacterial detection.

Timing and intensity of recreational physical activity and the risk of subsite-specific colorectal cancer.

PURPOSE: Although there is convincing evidence that physical activity reduces colon cancer risk, there are important questions that remain unanswered about the association. These include the timing and intensity of activity required to optimally reduce risk, and whether physical activity has a different effect on cancers at different sites within the colon. We conducted a case-control study to investigate these issues. METHODS: A case-control study of colorectal cancer was conducted in Western Australia in 2005-2007. Data were collected on various risk factors. The estimated effects of recreational physical activity on the risk of cancers of the distal colon, proximal colon, and rectum were analyzed using multinomial logistic regression. This analysis included 870 cases and 996 controls. RESULTS: The risk of distal colon cancer was reduced by performing a high level of vigorous-intensity activity between the ages 19 and 34 years (women), 35 and 50 years (men), after the age of 51 years (men and women), and consistently over the adult lifetime (men and women). The risk of rectal cancer was reduced by performing a high level of vigorous activity between the ages 35 and 50 years (men), and consistently over the adult lifetime (men). Proximal colon cancer risk was not associated with physical activity in any of the age periods or over the adult lifetime. Moderate intensity activity did not reduce the risk of colorectal cancer. CONCLUSION: Physical activity may have a greater effect on the risk of distal colon cancer than proximal colon cancer. Vigorous physical activity is required to reduce colorectal cancer risk.