A systematic review and meta-analysis of the 2007 WCRF/AICR score in relation to cancer-related health outcomes.

BACKGROUND: We conducted a systematic literature review and meta-analysis of observational studies investigating adherence to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations for cancer prevention and health outcomes. PATIENTS AND METHODS: We searched PubMed and the in-house database of the WCRF Continuous Update Project for publications up to June 2019. Cross-sectional studies were only narratively reviewed given their heterogeneity while findings of cohort/case-control studies were synthesized in umbrella reviews and meta-analyses. Summary relative risks (RRs) and 95% confidence intervals (CI) were estimated using a random-effects model when at least two studies reported results on a specific outcome. RESULTS: Thirty-eight articles (17 prospective, 8 case-control, and 13 cross-sectional studies) were included. The summary RR per each point increment in the 2007 WCRF/AICR score was 0.90 (95% CI: 0.87-0.93, n = 11) for breast cancer, regardless of hormone receptor and menopausal status, 0.86 (95% CI: 0.82-0.89, n = 10) for colorectal cancer, and 0.93 (95% CI: 0.89-0.96, n = 2) for lung cancer risk. No statistically significant associations were reported for prostate (n = 6) and pancreatic cancers (n = 2). Adherence to the recommendations was associated with lower overall mortality (RR = 0.90, 95% CI 0.84-0.96, n = 3) and cancer-specific mortality (RR = 0.91, 95% CI 0.89-0.92; n = 3) in healthy populations, as well as with higher survival in cancer patients (n = 2). In cross-sectional studies, a healthier plasma marker profile and lower cancer risk factors in the general population and a better health status and quality of life in cancer patients/survivors were reported. CONCLUSIONS: Adhering to the 2007 WCRF/AICR recommendations is associated with lower risks of cancer incidence, namely breast and colorectal cancers, and mortality. Primary prevention of cancer should emphasize modification of multiple lifestyle factors. Upcoming studies examining the recently updated 2018 guidelines will further clarify such associations.

Impact of BD Kiestra InoqulA streaking patterns on colony isolation and turnaround time of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacterale surveillance samples.

OBJECTIVES: To determine if using alternative streaking patterns on the BD Kiestra InoqulA can impact colony isolation and improve turnaround time (TAT) of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) screening samples. METHODS: A total of 1571 positive MRSA screening samples were studied, of which 755 screening plates were streaked by the standard pattern (4-Quadrant uniform S200) and 816 plates were streaked by an alternative pattern (Zigzag 3.5-1 S200). A total of 424 CRE-positive screening samples were studied, of which 211 screening plates were streaked by the standard pattern (Zigzag 2.5-1 inoc S200) and 213 plates were streaked by an alternative customized pattern (Zigzag 3.5-1 vertstreak s200). RESULTS: There was a reduction in the number of MRSA screening plates with insufficient isolated colonies for confirmatory testing from 75 plates (9.9%) when using the standard pattern to 18 plates (2.2%) when using the alternative streaking pattern. MRSA cases with a TAT above 36 hours also reduced significantly from 144 (19.1%) to 20 (2.4%). The number of CRE screening plates with insufficient colonies for same-day confirmatory testing reduced from 16 (7.6%) when using the standard pattern to two plates (1.1%) when using the alternative customized pattern. CRE cases with a TAT above 36 hours also reduced from 16 (7.6%) to seven (3.3%). CONCLUSIONS: The change in streaking patterns resulted in more plates with sufficient isolated colonies as well as reduced man-hours and materials required to perform subculture of mixed colonies and overall improvements in TAT.

Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies.

BACKGROUND: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. METHOD: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs). RESULTS: Our findings showed BMI, and BMI in early adulthood (aged 18-21 years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. CONCLUSION: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.

Re-visiting the ATA 2015 sonographic guidelines - who are we missing?: A retrospective review.

BACKGROUND: The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic biopsy be based on ultrasound findings (i.e. size and nodule characteristics). The overall effect of these changes results in fewer nodules requiring biopsy. This study was conducted to determine if the changes to the guidelines will result in overlooked thyroid cancers, specifically malignancies with aggressive characteristics measuring between 1 and 1.49 cm. METHODS: Patients (n = 2083) with thyroid nodules who underwent total or subtotal/hemi thyroidectomy with or without neck dissection by a single surgeon between 2006 and 2016 were retrospectively enrolled. Demographic information and nodule characteristics were collected for all patients. Ultrasonography and final pathology reports were reviewed for patients with thyroid nodules between the sizes of 1-1.49 cm (n = 155). RESULTS: 45% (n = 70) of patients with nodules between 1 and 1.49 cm were "low suspicion" nodules according to ultrasound. 47 of these nodules contained malignancies on final histopathological examination, 100% of which were of the papillary subtype. 21% (n = 10) of these malignant nodules demonstrated extrathyroidal extension and 34% (n = 16) were associated with regional metastases. CONCLUSIONS: Reliance on sonographic patterns alone could result in missed cancer diagnoses in patients with thyroid nodules measuring between 1 and 1.49 cm. Moreover, a portion of these malignancies may be associated with aggressive features. The effect of this finding on long-term outcomes is unclear.

Outcomes after laparoscopic anti-reflux surgery related to obesity: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic Anti-Reflux Surgery (LARS) is an established alternative treatment to pharmacological therapy for patients with Gastro Osophageal Reflux Disease (GORD), yet its safety and efficacy in obese patients is controversial. A systematic review and meta-analysis was performed to compare LARS related to obesity. METHODS: Embase, MEDLINE and the Cochrane Library (January 1970 to July 2017) were searched for studies reporting clinical outcomes of LARS in patient cohorts stratified by Body Mass Index (BMI). Data was grouped according to BMI, <30 kg/m2 (non-obese) and ≥30 kg/m2 (obese). Primary outcome measures were reflux recurrence, operative morbidity, re-intervention (redo surgery and endoscopic dilatation), conversion to open surgery, and early return to theatre. Results were pooled in meta-analyses as Odds Ratios (OR). RESULTS: Thirteen eligible observational studies comparing LARS in non-obese (n = 6246) and obese (n = 1753) patients were identified. Recurrence of reflux was significantly lower in the non-obese cohort (OR 0.28, 95% C.I. 0.13 to 0.61, p = 0.001), however no significant differences were observed in rates of operative morbidity (OR 0.82, 0.54 to 1.23, p = 0.33), redo surgery (OR 0.94, 0.51 to 1.72, p = 0.84), endoscopic dilatation (OR 0.98, 0.45 to 2.17, p = 0.97), conversion to open surgery (OR 0.96, 0.50 to 1.85, P = 0.90), or early return to theatre (OR 0.77, 0.43 to 1.38, p = 0.39). CONCLUSIONS: LARS can be performed safely in obese patients, but risks higher GORD recurrence. Clinicians and patients should be aware that obesity may adversely affect LARS outcome and careful consideration be given in the consent process inherent within the optimal management of GORD.

An update of the WCRF/AICR systematic literature review and meta-analysis on dietary and anthropometric factors and esophageal cancer risk.

BACKGROUND: In the 2007 World Cancer Research Fund/American Institute for Cancer Research Second Expert Report, the expert panel judged that there was strong evidence that alcoholic drinks and body fatness increased esophageal cancer risk, whereas fruits and vegetables probably decreased its risk. The judgments were mainly based on case-control studies. As part of the Continuous Update Project, we updated the scientific evidence accumulated from cohort studies in this topic. METHODS: We updated the Continuous Update Project database up to 10 January 2017 by searching in PubMed and conducted dose-response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) using random effects model. RESULTS: A total of 57 cohort studies were included in 13 meta-analyses. Esophageal adenocarcinoma risk was inversely related to vegetable intake (RR per 100 g/day: 0.89, 95% CI: 0.80-0.99, n = 3) and directly associated with body mass index (RR per 5 kg/m2: 1.47, 95% CI: 1.34-1.61, n = 9). For esophageal squamous cell carcinoma, inverse associations were observed with fruit intake (RR for 100 g/day increment: 0.84, 95% CI: 0.75-0.94, n = 3) and body mass index (RR for 5 kg/m2 increment: 0.64, 95% CI: 0.56-0.73, n = 8), and direct associations with intakes of processed meats (RR for 50 g/day increment: 1.59, 95% CI: 1.11-2.28, n = 3), processed and red meats (RR for 100 g/day increment: 1.37, 95% CI: 1.04-1.82, n = 3) and alcohol (RR for 10 g/day increment: 1.25, 95% CI: 1.12-1.41, n = 6). CONCLUSIONS: Evidence from cohort studies suggested a protective role of vegetables and body weight control in esophageal adenocarcinomas development. For squamous cell carcinomas, higher intakes of red and processed meats and alcohol may increase the risk, whereas fruits intake may play a protective role.

Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project.

OBJECTIVE: As part of the World Cancer Research Fund International Continuous Update Project, we updated the systematic review and meta-analysis of prospective studies to quantify the dose-response between foods and beverages intake and colorectal cancer risk. DATA SOURCES: PubMed and several databases up to 31 May 2015. STUDY SELECTION: Prospective studies reporting adjusted relative risk estimates for the association of specific food groups and beverages and risk of colorectal, colon and rectal cancer. DATA SYNTHESIS: Dose-response meta-analyses using random effect models to estimate summary relative risks (RRs). RESULTS: About 400 individual study estimates from 111 unique cohort studies were included. Overall, the risk increase of colorectal cancer is 12% for each 100 g/day increase of red and processed meat intake (95% CI = 4-21%, I2=70%, pheterogeneity (ph)<0.01) and 7% for 10 g/day increase of ethanol intake in alcoholic drinks (95% CI = 5-9%, I2=25%, ph = 0.21). Colorectal cancer risk decrease in 17% for each 90g/day increase of whole grains (95% CI = 11-21%, I2 = 0%, ph = 0.30, 6 studies) and 13% for each 400 g/day increase of dairy products intake (95% CI = 10-17%, I2 = 18%, ph = 0.27, 10 studies). Inverse associations were also observed for vegetables intake (RR per 100 g/day =0.98 (95% CI = 0.96-0.99, I2=0%, ph = 0.48, 11 studies) and for fish intake (RR for 100 g/day = 0.89 (95% CI = 0.80-0.99, I2=0%, ph = 0.52, 11 studies), that were weak for vegetables and driven by one study for fish. Intakes of fruits, coffee, tea, cheese, poultry and legumes were not associated with colorectal cancer risk. CONCLUSIONS: Our results reinforce the evidence that high intake of red and processed meat and alcohol increase the risk of colorectal cancer. Milk and whole grains may have a protective role against colorectal cancer. The evidence for vegetables and fish was less convincing.

Adult weight gain and colorectal adenomas-a systematic review and meta-analysis.

BACKGROUND: Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. METHODS: We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. RESULTS: For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. CONCLUSIONS: Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer.

Meta-analysis of antegrade continence enema in adults with faecal incontinence and constipation.

BACKGROUND: Faecal incontinence and constipation affects up to 20 per cent of the general population, and can be a significant source of distress. The antegrade continence enema (ACE) procedure has been shown to be an effective alternative treatment option for children, but its use in adults requires clarification. A systematic review and meta-analysis was performed to determine outcomes of the ACE procedure in adults with faecal incontinence and constipation. METHODS: PubMed, MEDLINE and the Cochrane Library (from January 1990 to January 2015) were searched for studies that reported outcomes of ACE in adults with faecal incontinence and constipation. The primary outcome measure was successful use of ACE in the management of symptoms, as determined by continued use at follow-up. RESULTS: Seventeen observational studies involving 426 patients (265 female patients; median age 42 (range 17-84) years) with faecal incontinence (165 patients), constipation (209) or both (52), who had undergone the ACE procedure, were analysed. At a median follow-up of 39 months, the pooled success rate was 74·3 (95 per cent c.i. 66·1 to 82·6) per cent (P < 0·001). For patients with faecal incontinence the pooled success rate was 83·6 (75·0 to 92·1) per cent, compared with 67·7 (55·1 to 80·3) per cent in patients with constipation (both P < 0·001). CONCLUSION: The ACE procedure is an effective long-term treatment option in patients with faecal incontinence and constipation, and should be considered before performing a definitive colostomy. Patients with faecal incontinence appear to respond better than those with constipation.

Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is the most common cause of cancer death. Fruits and vegetables containing carotenoids and other antioxidants have been hypothesized to decrease lung cancer risk. As part of the World Cancer Research Fund International Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies. METHODS: We searched PubMed and several databases up to December 2014 for prospective studies. We conducted meta-analyses comparing the highest and lowest intakes and dose-response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and examine possible non-linear associations. We combined results from the Pooling Project with the studies we identified to increase the statistical power of our analysis. RESULTS: When comparing the highest with the lowest intakes, the summary RR estimates were 0.86 [95% CI 0.78-0.94; n (studies) = 18] for fruits and vegetables, 0.92 (95% CI 0.87-0.97; n = 25) for vegetables and 0.82 (95% CI 0.76-0.89; n = 29) for fruits. The association with fruit and vegetable intake was marginally significant in current smokers and inverse but not significant in former or never smokers. Significant inverse dose-response associations were observed for each 100 g/day increase: for fruits and vegetables [RR: 0.96; 95% CI 0.94-0.98, I(2) = 64%, n = 14, N (cases) = 9609], vegetables (RR: 0.94; 95% CI 0.89-0.98, I(2) = 48%, n = 20, N = 12 563) and fruits (RR: 0.92; 95% CI 0.89-0.95, I(2) = 57%, n = 23, N = 14 506). Our results were consistent among the different types of fruits and vegetables. The strength of the association differed across locations. There was evidence of a non-linear relationship (P < 0.01) between fruit and vegetable intake and lung cancer risk showing that no further benefit is obtained when increasing consumption above ∼400 g per day. CONCLUSIONS: Eliminating tobacco smoking is the best strategy to prevent lung cancer. Although residual confounding by smoking cannot be ruled out, the current evidence from prospective studies is consistent with a protective role of fruit and vegetables in lung cancer aetiology.

Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

BACKGROUND: Greater body mass index (BMI) has been convincingly related to increased endometrial cancer risk, however, whether adiposity earlier in life or abdominal fatness is an independent risk factor and whether weight gain or greater height increases the risk is not clear. METHODS: As part of the Continuous Update Project of the World Cancer Research Fund International, we conducted a systematic review and meta-analysis of prospective studies of the association between anthropometric measures and endometrial cancer risk and searched PubMed and several other databases up to February 2015. Summary relative risks (RRs) were calculated using a random-effects model. RESULTS: Thirty prospective studies of BMI and endometrial cancer risk with 22 320 cases among 6 445 402 participants were included. The summary RR for a 5-unit increment was 1.54 [95% confidence interval (CI) 1.47-1.61, I(2) = 81%]. Although the test for non-linearity was significant, Pnon-linearity < 0.0001, and the curve was steeper within the overweight and obese BMI ranges, there was evidence of increased risk even within the high normal BMI range. The summary RR was 1.45 (95% CI 1.28-1.64, I(2) = 76%) per 5 BMI units for BMI in young adulthood, 1.18 (95% CI 1.14-1.23, I(2) = 67%) per 5 kg increase of weight, and 1.16 (95% CI 1.12-1.20, I(2) = 51%) per 5 kg of weight gained between young adulthood and study baseline, 1.27 (95% CI 1.17-1.39, I(2) = 71%) per 10 cm increase in waist circumference, 1.21 (95% CI 1.13-1.29, I(2) = 0%) per 0.1-unit increment in waist-to-hip ratio and 1.30 (95% CI 1.19-1.41, I(2) = 0%) per 10-cm increase in hips circumference. The summary RR was 1.15 (95% CI 1.09-1.22, I(2) = 61%) for a 10-cm increase in height. CONCLUSIONS: All measures of adiposity were associated with increased risk of endometrial cancer, and in addition increasing height was associated with increased risk.

Laparoscopic common bile duct exploration.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is a safe and effective single-stage treatment for choledocholithiasis in the elective setting. The outcomes after LCBDE in the emergency setting are unknown. The aim of this study was to compare the outcomes following elective and emergency LCBDE for choledocholithiasis. METHODS: Details of all patients who underwent LCBDE for choledocholithiasis between August 2003 and August 2013 were analysed retrospectively. The primary outcome measure was common bile duct (CBD) stone clearance rate. Secondary outcome measures were conversion rate, morbidity, mortality and length of hospital stay. RESULTS: Some 215 consecutive patients (57 male; median age 65 (range 14-92) years) underwent LCBDE. Some 121 procedures were performed electively and 94 as an emergency. Forty-five patients (48 per cent) presented with obstructive jaundice or cholangitis in the emergency LCBDE group compared with 15 (12·4 per cent) in the elective group (P < 0·001). The CBD stone clearance rate was similarly high in both groups (96 versus 96·7 per cent respectively; P = 0·557). There were no significant differences in conversion rate (6 versus 4·1 per cent), morbidity (5 versus 6·6 per cent), mortality (2 versus 0 per cent) or median length of stay (3 days) between groups. Two patients died, both following emergency LCBDE. CONCLUSION: LCBDE can be performed safely and effectively in both elective and emergency settings.

Identification of a natural product-like STAT3 dimerization inhibitor by structure-based virtual screening.

STAT3 regulates a variety of genes involved with cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, inflammation, and immunity. The purpose of this study was to apply molecular docking techniques to identify STAT3 inhibitors from a database of over 90000 natural product and natural product-like compounds. The virtual screening campaign furnished 14 hit compounds, from which compound 1 emerged as a top candidate. Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with selectivity over STAT1 and with comparable potency to the well-known STAT3 inhibitor S3I-201. Furthermore, compound 1 inhibited STAT3 dimerization and decreased STAT3 phosphorylation in cells without affecting STAT1 dimerization and phosphorylation. Compound 1 also exhibited selective anti-proliferative activity against cancer cells over normal cells in vitro. Molecular docking analysis suggested that compound 1 might putatively function as an inhibitor of STAT3 dimerization by binding to the SH2 domain. This study also validates the use of in silico techniques to identify inhibitors of protein-protein interactions, which are typically considered difficult to target with small molecules.

Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies.

BACKGROUND: Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised. METHODS: We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations. RESULTS: Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29-1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02-1.12) for overweight (BMI 25.0-<30.0) and 1.10 (95% CI 0.92-1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26-2.41) for pre-menopausal and 1.34 (95% CI 1.18-1.53) for post-menopausal breast cancer. For each 5 kg/m(2) increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively. CONCLUSIONS: Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer.

Influence of a regional centralised upper gastrointestinal cancer service model on patient safety, quality of care and survival.

AIMS: The aim of this study was to determine outcomes of a reconfigured centralised upper gastrointestinal (UGI) cancer service model, allied to an enhanced recovery programme, when compared with historical controls in a UK cancer network. MATERIALS AND METHODS: Details of 606 consecutive patients diagnosed with UGI cancer were collected prospectively and outcomes before (n = 251) and after (n = 355) centralisation compared. Primary outcome measures were rates of curative treatment intent, operative morbidity, length of hospital stay and survival. RESULTS: The rate of curative treatment intent increased from 21 to 36% after centralisation (P < 0.0001). Operative morbidity (mortality) and length of hospital stay before and after centralisation were 40% (2.5%) and 16 days, compared with 45% (2.4%) and 13 days, respectively (P = 0.024). The median and 1 year survival (all patients) improved from 8.7 months and 39.0% to 10.8 months and 46.8%, respectively, after centralisation (P = 0.032). On multivariate analysis, age (hazard ratio 1.894, 95% confidence interval 0.743-4.781, P < 0.0001), centralisation (hazard ratio 0.809, 95% confidence interval 0.668-0.979, P = 0.03) and overall radiological TNM stage (hazard ratio 3.905, 95% confidence interval 1.413-11.270, P < 0.0001) were independently associated with survival. CONCLUSION: These outcomes confirm the patient safety, quality of care and survival improvements achievable by compliance with National Health Service Improving Outcomes Guidance.

Systematic review and meta-analysis of the influence of circumferential resection margin involvement on survival in patients with operable oesophageal cancer.

BACKGROUND: The prognostic role and definition of circumferential resection margin (CRM) involvement in operable oesophageal cancer remain controversial. The College of American Pathologists (CAP) and Royal College of Pathologists (RCP) define CRM involvement as tumour found at the cut resection margin and within 1 mm of the cut margin respectively. This systematic review and meta-analysis was performed to determine the influence of CRM involvement on survival in operable oesophageal cancer. METHODS: PubMed, MEDLINE and the Cochrane Library (January 1990 to June 2012) were searched for studies correlating CRM involvement with 5-year mortality. Statistical analysis of dichotomous variables was performed using the odds ratio (OR) as the summary statistic. RESULTS: Fourteen studies involving 2433 patients with oesophageal cancer who had undergone potentially curative oesophagectomy were analysed. Rates of CRM involvement were 15·3 per cent (173 of 1133) and 36·5 per cent (889 of 2433) according to the CAP and RCP criteria respectively. Overall 5-year mortality rates were significantly higher in patients with CRM involvement compared with CRM-negative patients according to both CAP (OR 4·02, 95 per cent confidence interval (c.i.) 2·25 to 7·20; P < 0·001) and RCP (OR 2·52, 1·96 to 3·25; P < 0·001) criteria. CRM involvement between 0·1 and 1 mm was associated with a significantly higher 5-year mortality rate than CRM-negative status (involvement more than 1 mm from CRM) (OR 2·05, 95 per cent c.i. 1·41 to 2·99; P < 0·001). CONCLUSION: CRM involvement is an important predictor of poor prognosis. CAP criteria differentiate a higher-risk group than RCP criteria, but overlook a patient group with similar poor outcomes.

Prognostic significance of 18-FDG PET/CT and EUS-defined tumour characteristics in patients with oesophageal cancer.

AIM: To determine the correlation between 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) defined maximum standardized uptake value (SUVmax) and endoluminal ultrasound-defined tumour volume (EDTV) in patients with oesophageal cancer (OC) and their relative prognostic significance. MATERIALS AND METHODS: One hundred and eighty-five consecutive patients with OC were staged using CT, endoscopic ultrasound (EUS), and PET/CT. The maximum potential EDTV was calculated (πr(2)L, where r = tumour thickness and L = total length of disease including proximal and distal lymph node metastases). Primary outcome measure was survival from diagnosis. RESULTS: Ninety-one percent of patients (168/185) had FDG-avid tumours on PET/CT. SUVmax correlated positively and significantly with EDTV (Spearman's rho = 0.339, p = 0.001). On univariate analysis, survival was inversely related to the PET/CT lymph node metastasis count (LNMC, p = 0.015), EUS N stage (p = 0.002), EDTV (<48 cm(3), p = 0.001), EUS total length of disease (p = 0.001), SUVmax (p = 0.002), PET/CT N stage (p < 0.0001), and EUS LNMC (p < 0.0001). On multivariate analysis two factors were significantly and independently associated with survival: EDTV (HR, 3.118; 95% CI: 1.357-7.167; p = 0.007), and PET/CT N stage (HR, 0.496; 95% CI: 0.084-1.577; p = 0.022). CONCLUSION: EDTV and PET/CT N stage were important predictors of survival and further research is needed to identify critical prognostic values.

A cyclometallated iridium(III) complex as a c-myc G-quadruplex stabilizer and down-regulator of c-myc oncogene expression.

A new cyclometallated iridium(III) complex with the 2,2'-biquinoline N-donor ligand has been synthesized and characterized. The interaction and affinity of the complex towards c-myc G-quadruplex and duplex DNA have been investigated using UV/Vis spectroscopy and gel mobility shift assay. These studies revealed that complex 1 binds to c-myc G-quadruplexes (Pu22 and Pu27) with high affinity but does not interact with duplex DNA either by intercalation or groove binding. The ability of 1 to stabilize c-myc G-quadruplex DNA in vitro has also been examined through a PCR stop assay and a cell-based luciferase reporter assay. Complex 1 displays promising cytotoxic activity against the HeLa cell line with sub-micromolar potency.