Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial.

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases.

PURPOSE: The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans. METHODS: Mice underwent MRI twice weekly for up to 31 d following intracardiac injection of the brain-homing breast cancer cell line MDA-MB231-BR. Patients with small cell lung cancer underwent quarterly MRI for 1 year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time point and in registered regions at earlier time points. Texture analysis and linear discriminant analysis were performed to detect metastasis-containing slices. RESULTS: Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time point. Some lesions were visible at earlier time points on the MTR and ADC maps: 24% of these were not visible on corresponding T2 -weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time point, with 77% sensitivity 2-4 d earlier and 46% 5-8 d earlier. Only 2 of 16 patients developed metastases, and their penultimate scans were normal. CONCLUSIONS: Some brain metastases may be detected earlier on MTR than conventional T2 ; however, the small gain is unlikely to justify "predictive" MRI. Magn Reson Med 77:1987-1995, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A systematic review of contextual factors relating to smokeless tobacco use among South Asian users in England.

INTRODUCTION: Certain types of smokeless tobacco (ST) are popular among some people of South Asian origin in England; however, little is known about the contextual factors surrounding use in this population. This systematic review explores the factors associated with ST use among people of South Asian origin in England. METHODS: An iterative search strategy in targeted databases and grey literature sources was conducted in the summer of 2011. Data extractions and quality assessments were completed and verified by two reviewers, and results were presented as a narrative. RESULTS: A total of 2,968 references were screened by two reviewers who agreed on the inclusion of 14 studies. ST use is more prevalent among older participants who may have started chewing in India; however, the evidence suggests that some younger English-born South Asians are using ST as well. Reasons for chewing included the use of these products in times of stress, boredom or simply to relax. Traditional health messages and prior held beliefs may lead them to chew these products because of misconceptions about their health benefits, since very few people were aware of the health risks. Many expressed a desire to quit, however found it difficult to go without ST. CONCLUSION: This review examines the complex factors that underpin and influence ST use among South Asians in England with the potential of informing targeted interventions and health policy.

Caught on camera: a video assessment of suspected concussion and other injury events in women's rugby union.

OBJECTIVES: The objective of this study was to identify and report the incidence and mechanisms of suspected injury and concussion in women's rugby union. DESIGN: A cross-sectional video analysis study. METHODS: Using video analysis of non-professional, single-angle footage, cases of suspected injury and concussion were identified and reported, based on content validation and consensus by eight rugby-specific researchers, therapists, and sport medicine physicians. RESULTS: There were 225 suspected injuries recorded in 48 games [Suspected injury rate (IR) = 117.5/1000 h (95 % CI;102.6-133.9) or 4.7 suspected injuries per match]. The on-field medical attention IR was 95.0/1000 h (95 % CI;81.7-109.9: 3.8 per game). Suspected concussions accounted for 26 % of injuries (30.8/1000 h: 95 % CI;23.5-39.7: 1.2 per game). The attacking team sustained 64 % of suspected injuries. Permanent removal from play was observed for 29 % of suspected injuries. The most common suspected injury locations were head/neck (28.4 %) and lower extremity (27.6 %). The tackle accounted for 67.1 % of all suspected injuries, with a propensity of 11.2/1000 tackle events (95 % CI;9.5-13.2) or 3.1 tackle-related injuries/game. Of tackle-related injuries, 63.6 % were to the ball carrier while 52.2 % of tackle-related concussions were to the ball carrier. CONCLUSION: This study adds to the growing body of literature examining women's rugby. The rate of suspected injury is high compared with other studies. It is acknowledged that these are suspected injuries not supported by prospective injury surveillance. The high proportion of suspected injuries that are tackle-related warrants specific attention to identify tackle characteristics associated with injury and concussion.

MRI & MRS assessment of the role of the tumour microenvironment in response to therapy.

MRI and MRS techniques are being applied to the characterisation of various aspects of the tumour microenvironment and to the assessment of tumour response to therapy. For example, kinetic parameters describing tumour blood vessel flow and permeability can be derived from dynamic contrast-enhanced MRI data and have been correlated with a positive tumour response to antivascular therapies. The ongoing development and validation of noninvasive, high-resolution anatomical/molecular MR techniques will equip us with the means to detect specific tumour biomarkers early on, and then to monitor the efficacy of cancer treatments efficiently and reliably, all within a clinically relevant time frame. Reliable tumour microenvironment imaging biomarkers will provide obvious advantages by enabling tumour-specific treatment tailoring and potentially improving patient outcome. However, for routine clinical application across many disease types, such imaging biomarkers must be quantitative, robust, reproducible, sufficiently sensitive and cost-effective. These characteristics are all difficult to achieve in practice, but image biomarker development and validation have been greatly facilitated by an increasing number of pertinent preclinical in vivo cancer models. Emphasis must now be placed on discovering whether the preclinical results translate into an improvement in patient care and, therefore, overall survival.

Small cell carcinoma of the urinary bladder: a 15-year retrospective review of treatment and survival in the Anglian Cancer Network.

OBJECTIVE: To report the clinical experience and management of patients with small cell carcinoma (SCC) of the bladder, treated in the Anglia Cancer network from 1992 to 2007, and to review published studies, as SCC is a rare condition, accounting for <1% of all bladder tumours, and there is no established treatment strategy for managing these patients. PATIENTS AND METHODS: We analysed retrospectively data from all patients diagnosed with SCC of the urinary bladder between 1992 and 2007, with an emphasis on stage, treatment and overall survival. RESULTS: Twenty patients were identified with primary bladder SCC (male: female ratio 3:1; mean age 68 years; mean follow-up 15.8 months). Nine patients (45%) had extensive-stage disease at diagnosis. Four patients received best supportive care, three had a radical cystectomy, one radical radiotherapy and six sequential chemo-radiotherapy. In all, 13 patients were treated with chemotherapy, with six receiving cyclophosphamide, doxorubicin and vincristine, three receiving carboplatin and etoposide, and the remainder receiving alternative platinum-based regimens. For 12 patients with assessable disease, six had a complete response, three a partial response and three had progressive disease after chemotherapy. No patient received prophylactic cranial irradiation (PCI). At the time of analysis, 14 (70%) patients had died, with one (5%) developing brain metastasis. The median survival was 33 months for patients receiving chemotherapy, vs 3 months with no chemotherapy. CONCLUSIONS: SCC of the bladder tends to occur in an older population, more commonly in men. It is an aggressive tumour with a propensity for early metastasis. The response rate to chemotherapy is high but the overall prognosis is poor. Brain secondaries are less common than for SCC of the lung and currently the role of PCI is unclear. As there is no standard of care for these patients, they are treated according to local protocols. Further efforts should be made to develop more effective treatments and the role of PCI should be assessed in the setting of a clinical trial, in conjunction with other extrapulmonary SCCs.

New Model for Estimating Glomerular Filtration Rate in Patients With Cancer.

Purpose The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method. Methods We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%. Results Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)-adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated. Conclusion In a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care.

Identifying evidence for public health guidance: a comparison of citation searching with Web of Science and Google Scholar.

AIM: To examine how effectively forwards citation searching with Web of Science (WOS) or Google Scholar (GS) identified evidence to support public health guidance published by the National Institute for Health and Care Excellence. METHOD: Forwards citation searching was performed using GS on a base set of 46 publications and replicated using WOS. OUTCOMES: WOS and GS were compared in terms of recall; precision; number needed to read (NNR); administrative time and costs; and screening time and costs. Outcomes for all publications were compared with those for a subset of highly important publications. RESULTS: The searches identified 43 relevant publications. The WOS process had 86.05% recall and 1.58% precision. The GS process had 90.7% recall and 1.62% precision. The NNR to identify one relevant publication was 63.3 with WOS and 61.72 with GS. There were nine highly important publications. WOS had 100% recall, 0.38% precision and NNR of 260.22. GS had 88.89% recall, 0.33% precision and NNR of 300.88. Administering the WOS results took 4 h and cost £88-£136, compared with 75 h and £1650-£2550 with GS. CONCLUSION: WOS is recommended over GS, as citation searching was more effective, while the administrative and screening times and costs were lower.

Prostatic relapse of an undifferentiated teratoma 24 years after orchidectomy.

BACKGROUND: Non-seminomatous germ cell tumours make up about 40 % of all germ cell tumours, which in turn are the most common tumours in men aged 15-44 years. Low risk stage I non-seminomatous germ cell tumours, which are confined to the testes, are commonly treated by orchiectomy and surveillance. Up to 20 % of patients with this diagnosis relapse, usually within 1-2 years of follow up, but very rarely after more than 5 years. The most common sites of relapse are the retroperitoneal lymph nodes, the mediastinum, and the lungs. We describe a case of relapse in the prostate over 20 years after initial diagnosis, which has not been described in the literature so far. CASE PRESENTATION: This report presents a 49-year-old white British man with relapsed testicular non-seminomatous germ cell tumour 22 years after initial treatment with orchidectomy only. He relapsed with a prostatic mass, haematospermia and back pain. His prostate specific antigen levels were within normal range. Alpha feto-protein and lactate dehydrogenase levels were elevated, and his human chorionic gonadotrophin levels were normal. A biopsy confirmed undifferentiated malignant tumour, shown immunohistochemically to be a yolk sac tumour. The patient was initially treated with bleomycin, etoposide and cisplatin chemotherapy, but developed bleomycin-related pulmonary side effects after two cycles. His treatment was changed and he completed four cycles of chemotherapy by receiving two cycles of etoposide, ifosfamide, and cisplatin. Post treatment blood tumour markers were normal, but a follow up computed tomography showed a mass in the base of the prostate, the trigone and the left distal ureter which was surgically resected. The histology from the surgical resection was of necrotic tissue. The patient is now in follow up at 3 years after treatment with no evidence of residual disease on computed tomography. His Alpha feto-protein, beta human chorionic gonadotrophin and lactate dehydrogenase levels are normal. CONCLUSIONS: Very late relapse in stage I non-seminomatous germ cell tumours is extremely rare and the prostate is a highly unusual site of relapsed disease. For diagnosis of late relapse, this case confirms the value of serum biomarkers in germ cell tumours, in particular non-seminomatous germ cell tumours.

Impact of anti-angiogenic treatments on metastatic renal cell carcinoma.

Patients with metastatic renal cell cancer (mRCC) have traditionally had poor responses to systemic therapies. Recent developments in molecular biology have increased our understanding of the oncogenic processes and pathways in clear-cell mRCC. The development of drugs that target these pathways has expanded treatment options, improved prognosis and changed standard management of patients with clear-cell mRCC. Sunitinib, sorafenib and pazopanib (oral tyrosine kinase inhibitors) as well as everolimus and temsirolimus (mTOR inhibitors) and interferon with bevacizumab (an antibody to VEGF) have improved patient outcomes in large Phase III trials. These drugs have been incorporated into standard practice. Sunitinib has been adopted as first-line standard of care. Many agents are in development for treatment of mRCC, including axitinib in Phase III trials. We will review these treatments, their toxicities and how these targeted agents have impacted on mRCC.