• Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.

      Renehan, Andrew G; Tyson, Margaret; Egger, Matthias; Heller, Richard F; Zwahlen, Marcel; Department of Surgery, School of Cancer Studies, University of Manchester, UK. arenehan@picr.man.ac.uk (2008-02-16)
      BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.
    • Breast reconstruction following prophylactic mastectomy for smaller breasts: The superiorly based pectoralis fascial flap with the Becker 35 expandable implant.

      Ross, Gary L; Department of Plastic Surgery, The Christie, Wilmslow Road, Manchester M20 4BX, United Kingdom. (2012-01-09)
      INTRODUCTION: Immediate reconstruction using tissue expander/implants following prophylactic mastectomy for smaller breasts is a reliable means of providing similar size, shape and symmetrical reconstructions. The superiorly based pectoralis fascial flap allows an immediate reconstruction of the inferior pole and may eliminate the need for tissue expansion. METHODS: The superiorly based pectoralis fascial flap and implant was performed on 5 patients (10 breasts). The Becker 35 expandable implant was used in all cases and average size was 349 (range 290-400cc). Average age was 33 (range 21-43). The average BMI was 23 (range 20-26). One patient underwent further tissue expansion of the Becker 35 postoperatively. One patient developed a seroma in the abdominal fascial flap donor site that settled without the need for drainage. There were no other complications. CONCLUSION: The superiorly based pectoralis fascial flap provides a one-stop reconstruction of the lower pole and can eliminate the need for tissue expansion in patients with small breasts.
    • Development and validation of a nomogram for prediction of survival and local control in laryngeal carcinoma patients treated with radiotherapy alone: a cohort study based on 994 patients.

      Egelmeer, A G T M; Velazquez, E R; de Jong, J M A; Oberije, C; Geussens, Y; Nuyts, S; Kremer, B; Rietveld, D; Leemans, C R; de Jong, M; et al. (2011-07)
      To advise laryngeal carcinoma patients on the most appropriate form of treatment, a tool to predict survival and local control is needed.
    • Height and cancer: consistent links, but mechanisms unclear.

      Renehan, Andrew G; School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK. (2011-08)
    • The impact of radiotherapy on swallowing and speech in patients who undergo total laryngectomy.

      De Casso, Carmen; Slevin, Nicholas J; Homer, Jarrod J; University Department of Otolaryngology-Head and Neck Surgery, Manchester Royal Infirmary, Manchester, UK. cdecasso@doctors.org.uk (2008-12)
      OBJECTIVES: Quality of life studies have shown no detrimental effect with radiotherapy (RT) in patients who have a total laryngectomy. We wished to determine the effect of RT (initial or postoperative) specifically on the swallowing and voice function in patients treated by total laryngectomy (TL) for carcinoma of the larynx. DESIGN: Multicenter chart review. SETTING: Multicenter study in the Greater Manchester and Lancashire area. PARTICIPANTS: A total of 121 postlaryngectomy patients all of whom had completed definitive treatment at least 6 months before this study. Twenty-six patients had total laryngectomy as a single modality treatment and 95 had total laryngectomy and radiotherapy. MAIN OUTCOME MEASURES: Swallowing (solid food, soft diet or fluid/PEG) and voice development. RESULTS: Swallowing was better in the group who had no radiotherapy (P = 0.0037). There was no difference in voice function between the two groups. We also demonstrated that females had a worse swallowing outcome (P = 0.0101), as did advanced nodal stage (P = 0.001). CONCLUSIONS: RT adversely affects the swallowing results but not the speech results after TL when given either as initial treatment or postoperatively. This should be kept in mind in the decision-making process in the treatment of patients with carcinoma of the larynx.
    • Initial management through the anal cancer multidisciplinary team meeting.

      Renehan, Andrew G; O'Dwyer, Sarah T; Department of Surgery, Christie NHS Foundation Trust, Manchester, UK. (2011-02)
    • The inpatient burden of abdominal and gynecological adhesiolysis in the US.

      Sikirica, V; Bapat, B; Candrilli, S D; Davis, K L; Wilson, Malcolm S; Johns, A; Shire Pharmaceuticals, Wayne, PA 19087, USA. (2011)
      Adhesions are fibrous bands of scar tissue, often a result of surgery, that form between internal organs and tissues, joining them together abnormally. Postoperative adhesions frequently occur following abdominal surgery, and are associated with a large economic burden. This study examines the inpatient burden of adhesiolysis in the United States (i.e., number and rate of events, cost, length of stay [LOS]).
    • Insulin analogues and cancer risk: the emergence of second-generation studies.

      Renehan, Andrew G; School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. arenehan@picr.man.ac.uk (2012-01)
      A number of observational studies have linked insulin glargine (A21Gly,B31Arg,B32Arg human insulin) with a putative increased cancer risk, particularly breast cancer, but many of these 'first generation' studies had study design and analysis flaws, and were inconclusive. A small number of 'second generation' studies are now emerging in which the applied pharmaco-epidemiological principles are more robust. For example, when Ruitar and colleagues (Diabetologia DOI: 10.1007/s00125-011-2312-4 ) focused specifically on breast cancer rather than all incident cancer risk, they were able to show a positive association with insulin glargine for breast cancer although there was no association with all incident cancer risk. A list of preferred qualities for pharmaco-epidemiological studies is presented.
    • Interpreting the epidemiological evidence linking obesity and cancer: A framework for population-attributable risk estimations in Europe.

      Renehan, Andrew G; Soerjomataram, Isabelle; Leitzmann, Michael F; Department of Surgery, The Christie NHS Foundation Trust, School of Cancer and Enabling Sciences, University of Manchester, UK. arenehan@picr.man.ac.uk (2010-09)
      Standard approaches to estimating population-attributable risk (PAR) include modelling estimates of exposure prevalence and relative risk. Here, we examine the associations between body mass index (BMI) and cancer risk and how effect modifications of these associations impact on PAR estimates. In 2008, sex- and population-specific risk estimates were determined for associations with BMI in a standardised meta-analysis for 20 cancer types. Since then, refinements of these estimates have emerged: (i) absence of menopausal hormonal therapy (MHT) is associated with elevated BMI associations in post-menopausal breast, endometrial and ovarian cancers; (ii) current smoking attenuates the BMI associations in oesophageal squamous cell carcinoma, lung and pancreatic cancers; (iii) prostate screening attenuates BMI associations when all prostate cancers are considered together; and (iv) BMI is differentially associated with different histological subtypes within the same cancer group. Using secondary analyses of the aforementioned meta-analysis, we show 2-3-fold shifts in PAR estimations for breast and endometrial cancers depending on the MHT usage in European countries. We also critically examine how to best handle exposures (in this example, BMI distributions) and relative risk estimates in PAR models, and argue in favour of a counterfactual approach based around BMI means. From these observations, we develop a research framework in which to optimally evaluate future trends in numbers of new cancers attributable to excess BMI. Overall, this framework gives conservative estimates for PAR - nonetheless, the numbers of avoidable cancers across Europe through avoidance of excess weight are substantial.
    • Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

      Alkureishi, Lee W T; Burak, Zeynep; Alvarez, Julio A; Ballinger, James; Bilde, Anders; Britten, Alan J; Calabrese, Luca; Chiesa, Carlo; Chiti, Arturo; de Bree, Remco; et al. (2009-11)
      Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.
    • Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index.

      Harriss, D J; Atkinson, G; George, K; Cable, N Tim; Reilly, Thomas; Haboubi, Najib; Zwahlen, Marcel; Egger, Matthias; Renehan, Andrew G; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Henry Cotton Campus, Liverpool, UK. (2009-07)
      OBJECTIVE: Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta-analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub-site and study characteristics. METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. Random-effects meta-analyses and meta-regressions of study-specific incremental estimates were performed to determine the risk ratio (RR) and 95% confidence intervals (CIs) associated with a 5 kg/m(2) increase in BMI. RESULTS: We analysed 29 datasets from 28 articles, including 67,361 incident cases. Higher BMI was associated with colon (RR 1.24, 95% CIs: 1.20-1.28) and rectal (1.09, 1.05-1.14) cancers in men, and with colon cancer (1.09, 1.04-1.12) in women. Associations were stronger in men than in women for colon (P < 0.001) and rectal (P = 0.005) cancers. Associations were generally consistent across geographic populations. Study characteristics and adjustments accounted for only moderate variations of associations. CONCLUSION: Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic differences, which merit further research.
    • Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity.

      Harriss, D J; Atkinson, G; Batterham, A; George, K; Cable, N Tim; Reilly, Thomas; Haboubi, Najib; Renehan, Andrew G; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK. (2009-09)
      OBJECTIVE: Increased physical activity may decrease the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we performed a systematic review and meta-analysis of prospective observational studies to quantify gender-specific risk associated with increased leisure-time physical activity (LT-PA). METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. We used random-effects meta-analyses to estimate summary risk ratios (RR) and 95% confidence intervals (95% CI) for uppermost vs lowermost categories of physical activity. To investigate dose-response, we explored risks ratios as a function of cumulative percentiles of physical activity distribution. RESULTS: Fifteen datasets from 14 articles, including 7873 incident cases, were identified. For colon cancer, there were inverse associations with LT-PA for men (RR: 0.80; 95% CI: 0.67-0.96) and women (0.86; 0.76-0.98). LT-PA did not influence risk of rectal cancer. The dose-response analysis was consistent with linear pattern reductions in risk of colon cancer in both genders. There was evidence of moderate between-study heterogeneity but summary estimates were broadly consistent across potential confounding factors. CONCLUSION: Increased LT-PA is associated with a modest reduction in colon but not rectal cancer risk; a risk reduction, which previously may have been overstated. LT-PA only interventions in public health cancer prevention strategies are unlikely to impact substantially on colorectal cancer incidences.
    • The long road towards cancer prevention: 4 steps backward and 8 forward.

      Coebergh, Jan-Willem; Martin-Moreno, Jose M; Soerjomataram, Isabelle; Renehan, Andrew G; Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. j.coebergh@erasmusmc.nl (2010-09)
    • Management of local disease relapse.

      Renehan, Andrew G; O'Dwyer, Sarah T; Department of Surgery, Christie NHS Foundation Trust, Manchester, UK. (2011-02)
    • The management of vulval cancer.

      Crosbie, Emma J; Slade, Richard J; Ahmed, Ahmed S; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, United Kingdom. Emma.Crosbie@Manchester.ac.uk (2009-11)
      Referral of women with vulval carcinoma to tertiary centres is now established practise in the UK. The centralisation of care for these women promotes the development of specialist teams of gynaecological oncologists, clinical oncologists, pathologists and clinical nurse specialists with expertise in the management of this relatively rare tumour. The primary care physician plays an essential role in the early detection and subsequent urgent referral of women with suspicious vulval lesions. Improved education and awareness campaigns may encourage women to report vulval symptoms early. Where vulval carcinoma is diagnosed at an early stage, surgical excision is likely to be curative. There is, however, a move away from radical surgery for all patients irrespective of stage of disease towards an individualised approach, which takes into account the size and position of the tumour. The challenge is to reduce morbidity associated with treatment without compromising on cure rates. Restricting groin lymphadenectomy to women with lymph node metastases may be possible with the advent of sentinel node technology and it is anticipated that expertise in this area will show significant advances over the coming years. There is still a place for radical surgery, often in combination with other treatment modalities, in the management of advanced or recurrent disease. This article will review the evidence for the current management of vulval carcinoma.
    • Meta-analysis in medical research: potentials and limitations.

      Zwahlen, Marcel; Renehan, Andrew G; Egger, Matthias; Department of Social and Preventive Medicine, University of Berne, Berne, Switzerland. zwahlen@ispm.unibe.ch (2009-05-12)
      Meta-analysis, the statistical combination of results from several studies to produce a single estimate of a treatment effect or size of an association, continues to attract controversy. We illustrate and discuss the promises and limitations of meta-analysis. Meta-analysis of clinical trials can prevent delays in the introduction of effective treatments or lead to the timely identification of adverse effects. However, meta-analyses are liable to numerous biases, both at the level of the individual study and the selection of studies for inclusion in meta-analysis. The biases and confounding factors that threaten the validity of individual studies will also affect meta-analyses of observational studies. We argue that meta-analyses should only be performed within the framework of systematic reviews that have been prepared using methods that minimize bias and address the combinability of studies.
    • Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.

      Atula, T; Hunter, K D; Cooper, L A; Shoaib, T; Ross, Gary L; Soutar, D S; Canniesburn Plastic Surgery Unit, Jubilee Building, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, United Kingdom. timo.atula@hus.fi (2009-05)
      BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the definitions and clinical significance of MMs and ITCs in SLN biopsy are controversial. We compared the UICC/TNM definitions of MMs and ITCs with our previously published sentinel node protocol to assess how the adoption of the UICC/TNM criteria would affect the staging of nodal micrometastatic disease. METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm intervals, 35 with metastatic tumour were included. Eighty-six SLNs were reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9 SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a further 11 patients (15 out of 25 SLNs were positive) which were reassessed as MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed additional metastases in 46% of patients with MM, whilst one of the ITC patients had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the UICC/TNM classification provides an objective, uniform method of detecting MMs and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common when a micrometastasis was detected in a SLN, indicating need for further treatment of the neck.
    • Mitochondrial DNA mutations in head and neck cancer are infrequent and lack prognostic utility.

      Challen, C; Brown, H; Cai, C; Betts, Guy N J; Paterson, I; Sloan, P; West, Catharine M L; Birch-Machin, M; Robinson, M; Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4BW, UK (2011)
    • Oncoplastic surgery for breast cancer.

      Baildam, Andrew D; University Hospital of South Manchester Foundation Trust and the Christie Hospital, Manchester M20 4BX, UK. aetab2@btinternet.com (2008-01)
    • Perfusion Estimated with Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely with Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study.

      Donaldson, Stephanie B; Betts, Guy N J; Bonington, Suzanne C; Homer, Jarrod J; Slevin, Nicholas J; Kershaw, Lucy E; Valentine, Helen R; West, Catharine M L; Buckley, David L; School of Cancer and Enabling Sciences, University of Manchester, Manchester, United Kindom; North Western Medical Physics, The Christie, Manchester, United Kingdom. (2011-05-04)
      PURPOSE: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. RESULTS: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). CONCLUSIONS: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.