• Bacteraemia during transurethral resection of the prostate: what are the risk factors and is it more common than we think?

      Mohee, Amar Raj; Gascoyne-Binzi, D; West, R; Bhattarai, S; Eardley, I; Sandoe, J; Department of Urology, The Christie NHS Foundation Trust, 550 Wilmslow Road (2016)
      The aim of this work was to investigate the microbial causes, incidence, duration, risk factors and clinical implications of bacteraemia occurring during transurethral resection of the prostate (TURP) surgery to better inform prophylaxis strategies. An ethically approved, prospective, cohort study of patients undergoing TURP was conducted. Clinical information and follow-up details were collected using standardized data collection sheets. Blood was obtained for culture at 6 different time points peri-procedure. Standard of care antibiotic prophylaxis was given prior to surgery. Bacteriuria was assessed in a pre-procedure urine sample. Histopathology from all prostate chips was assessed for inflammation and malignancy. 73 patients were consented and 276 blood samples obtained. No patients developed symptomatic bacteraemia during the procedure, 17 patients developed asymptomatic bacteraemia (23.2%). Enterococcus faecalis and Pseudomonas aeruginosa were the most common organisms cultured. 10 minutes after the start of the TURP, the odds ratio (OR) of developing bacteraemia was 5.38 (CI 0.97-29.87 p = 0.05), and 20 minutes after the start of the procedure, the OR was 6.46 (CI 1.12-37.24, p = 0.03), compared to before the procedure. We also found an association between the development of intra-operative bacteraemia and recent antibiotic use (OR 4.34, CI 1.14-16.62, p = 0.032), the presence of a urinary catheter (OR 4.92, CI 1.13-21.51, p = 0.034) and a malignant histology (OR 4.90, CI 1.30-18.46, p = 0.019). There was no statistical relationship between pre-operative urine culture results and blood culture results. This study shows that asymptomatic bacteraemia is commonly caused by TURP and occurs in spite of antibiotic prophylaxis. Our findings challenge the commonly held view that urine is the primary source of bacteraemia in TURP-associated sepsis and raise the possibility of occult prostatic infection as a cause of bacteraemia. More work will be needed to determine the significance of transient bacteraemia in relation to more serious complications like infective endocarditis and malignancy.
    • Bad neighbours: hypoxia and genomic instability in prostate cancer

      Ashton, Jack; Bristow, Robert G; Translational Oncogenomics, CRUK Manchester Institute and CRUK Manchester Centre, Manchester, (2020)
      Prostate cancer (PCa) is a clinically heterogeneous disease and has poor patient outcome when tumours progress to castration-resistant and metastatic states. Understanding the mechanistic basis for transition to late stage aggressive disease is vital for both assigning patient risk status in the localised setting and also identifying novel treatment strategies to prevent progression. Subregions of intratumoral hypoxia are found in all solid tumours and are associated with many biologic drivers of tumour progression. Crucially, more recent findings show the co-presence of hypoxia and genomic instability can confer a uniquely adverse prognosis in localised PCa patients. In-depth informatic and functional studies suggests a role for hypoxia in co-operating with oncogenic drivers (e.g. loss of PTEN) and suppressing DNA repair capacity to alter clonal evolution due to an aggressive mutator phenotype. More specifically, hypoxic suppression of homologous recombination represents a 'contextual lethal' vulnerability in hypoxic prostate tumours which could extend the application of existing DNA repair targeting agents such as poly-ADP ribose polymerase inhibitors. Further investigation is now required to assess this relationship on the background of existing genomic alterations relevant to PCa, and also characterise the role of hypoxia in driving early metastatic spread. On this basis, PCa patients with hypoxic tumours can be better stratified into risk categories and treated with appropriate therapies to prevent progression.
    • Balancing Risks in Developing a Personalised Approach to the Treatment of Early Hodgkin Lymphoma: Have We Got the Balance Right?

      Illidge, Timothy M; Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester, UK. Electronic address: tmi@manchester.ac.uk (2015-08)
    • Balancing the economics and ethics of personalised oncology.

      Flaum, Nicola; Hall, P; McCabe, C; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK (2018-09)
      The cost of personalised medicine in oncology is increasing. The varied and contrasting priorities of the pharmaceutical industry, local and national governments, international medical community, and patients need to be reviewed and balanced. In addition to the economic and political standpoints on this issue, the ethical considerations from physicians' viewpoints need to be considered to optimise cancer patients' care. In this paper we discuss the way research and development (R&D) of these drugs is carried out and reimbursed, and how this needs to change. We describe frameworks assessing the value of these treatments which been developed. Physicians need to develop their knowledge and understanding of these issues to best meet their dual responsibilities of advocating for their patients and promoting public health.
    • Balancing the efficacy and toxicity of chemotherapy in colorectal cancer.

      Braun, Michael S; Seymour, M T; Consultant, Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK. (2011-01)
      As the therapeutic options for the treatment of colorectal cancer have expanded over the past 20 years, so has the complexity of decision making. The goals of treatment in the palliative, adjuvant and neoadjuvant settings vary and it is not only the efficacy of drugs that influence treatment decisions. Age, performance status, the presence of significant comorbidities and the different treatment regimens and strategies provide medical oncologists with an array of options to attempt to maximize patients' quality of life and longevity.
    • Balancing therapeutic impact of treatment strategies with quality of life and pain experience in multiple myeloma: New insights into influence of genetic variants.

      Ahmedzai, S; Snowden, J; Cairns, D; Williams, C; Hockaday, A; Cavenagh, J; Parrish, C; Yong, K; Cavet, James; Hunter, H; et al. (2016)
    • Balancing toxicity and efficacy: learning from trials and treatment using antiresorptive therapy in prostate cancer.

      Clarke, Noel W; The Christie and Salford Royal Hospitals, Manchester, UK. Electronic address: noel.clarke@srft.nhs.uk. (2013-07-26)
    • Balloon cell malignant melanoma of the urethra - a case report and literature review.

      Iavazzo, Christos; Gynaecological Oncology, The Christie NHS Foundation Trust, Manchester (2015)
    • Balloon cell urethral melanoma: differential diagnosis and management.

      McComiskey, Mark; Iavazzo, Christos; Datta, Meghna; Slade, Richard J; Winter-Roach, Brett; Lambe, Gerard F; Sangar, Vijay K; Smith, Michael; Gynaecological Oncology Department, Christie Hospital, Manchester M20 4BX, UK (2015)
      Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas) that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.
    • Bariatric surgery leads to a reduction in antibodies to apolipoprotein A-1: a prospective cohort study

      Adam, Safwaan; Ho, Jan H; Liu, Y.; Siahmansur, T.; Iqbal, Z.; Pagano, S.; Azmi, S.; Dhage, Shaishav S; Donn, R.; Ammori, B. J.; et al. (2021)
    • Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity

      Azmi, S.; Ferdousi, M.; Liu, Y.; Adam, Safwaan; Iqbal, Z.; Dhage, Shaishav; Ponirakis, G.; Siahmansur, T.; Marshall, A.; Petropoulos, I.; et al. (2021)
      Introduction: Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. Methods: Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. Results: Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). Conclusion: Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.
    • Barium paste: useful for primary tumour localization in oral cancer.

      Yap, Beng K; Slevin, Nicholas J; Ahamad, A; Department of Clinical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK. (2004-02)
    • Basal cell carcinoma: 10-year experience with electrochemotherapy

      Campana, L; Marconato, R; Valpione, Sara; Galuppo, S; Alaibac, M; Rossi, C; Mocellin, S; Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, Padua (2017-05-31)
    • Basal serum dehydroepiandrosterone sulphate concentration does not predict the cortisol response to provocative testing.

      Littley, M D; Pollock, A; Kane, J; Shalet, Stephen M; Department of Endocrinology, Christie Hospital, Withington, Manchester, UK. (1990-11)
      The concentration of dehydroepiandrosterone sulphate (DHEAS) was measured in the plasma of 104 patients aged 16-78 years (48 men) undergoing routine assessment of anterior pituitary reserve. A fasting plasma sample was collected at 0900 h on the same day that either an insulin tolerance test or a glucagon stimulation test was performed. Serum cortisol, DHEAS and prolactin were measured by radioimmunoassay. DHEAS levels between 0.5 and 14 nmol/L were significantly but negatively correlated with age but there was no significant correlation with basal cortisol, maximum stimulated cortisol, the increment in cortisol or basal prolactin. The correlation of DHEAS with age was also observed when results for women were analysed separately but this did not hold for men. For male and female results separately, there was again no correlation of basal DHEAS with basal cortisol, maximum stimulated cortisol, increment of cortisol or basal prolactin. The age and sex related reference range and other factors affecting basal DHEAS concentration make it a cumbersome and unreliable measure of hypothalamic-pituitary-adrenal axis reserve.
    • Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial

      Brown, JE; Handforth, C; Walsh, J; Pezaro, C; Sydes, MR; Clarke, Noel W; James, ND; McCloskey, E; Oncology and Metabolism, Academic Unit of Clinical Oncology, University of Sheffield, Sheffield (2019)
    • Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

      Öcal, O.; Schütte, K.; Kupčinskas, J.; Morkunas, E.; Jurkeviciute, G.; de Toni, E. N.; Ben Khaled, N.; Berg, T.; Malfertheiner, P.; Klümpen, H. J.; et al. (2021)
      Purpose: To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods: A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results: Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9-8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2-4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22-7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02-4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion: IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.
    • Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO

      Westphalen, C. B.; Karapetyan, A.; Beringer, A.; Bochtler, T.; Chalabi, N.; Cook, Natalie; Duran-Pacheco, G.; Golding, S.; Hoglander, E.; Losa, F.; et al. (2021)
      Background NCCN guidelines consider next-generation sequencing important in guiding therapeutic decision-making in CUP. CUPISCO (NCT03498521) is an ongoing, phase II randomised study of targeted therapy/cancer immunotherapy vs platinum-based chemotherapy in pts with unfavourable CUP, defined per ESMO guidelines. We present a preliminary, descriptive molecular analysis of ?50% of pts designated for enrolment. Methods Upon enrolment, comprehensive genomic profiling, including determination of microsatellite instability and tumour mutational burden (TMB), was performed on formalin-fixed, paraffin-embedded tissues using the F1CDx assay. Gene alterations (GAs) found in ?3% of pts were analysed using multiple correspondence analyses and hierarchical clustering to identify co-occurrences. Results Median age was 61.5 years (n = 346 [Apr 2021]; range: 22�84); median TMB was 2.5 mutations/Mb (0�63.0). In our analysis, 30% of patients carried a potentially targetable GA. Most frequent GAs were TP53 (44%), CDKN2A (32%), KRAS (21%; 2% G12C alterations), CDKN2B (21%), ARID1A (13%), STK11 (13%), MTAP (12%), PIK3CA (10%), MYC (8%), PBRM1 (8%), BAP1 (8%) and FGFR2 (8%). Beyond PIK3CA and FGFR2, other targetable GAs were identified in EGFR (2%), ERBB2 (6%), ALK (0.3%), ROS1 (1%), MET (2%), NTRK1 (1%) and BRAF (6%). The frequency of microsatellite instability and TMB-high (>16 mutations/Mb) samples was 3% and 9%, respectively. Based on hierarchical clustering of co-mutational profiles, multiple clusters were identified in the study cohort, each characterised by specific GA co-occurrences. Conclusions This descriptive analysis sheds further light on the molecular landscape in pts with poor-prognosis CUP. Our analyses demonstrate that CUP cases can be clustered based on molecular profiling; further studies are needed to determine if these clusters carry clinical relevance. Our early results suggest that comprehensive genomic profiling of CUP samples identifies therapeutically relevant GAs in a significant proportion of patients and could thus guide personalised treatment of these tumours.
    • Baseline mutational profiles of patients with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO

      Mileshkin, L.; Karapetyan, A. R.; Beringer, A.; Bochtler, T.; Chalabi, N.; Cook, Natalie; Duran-Pacheco, G.; Golding, S.; Hoglander, E.; Losa, F.; et al. (2021)
      Aims: NCCN guidelines consider next-generation sequencing important in therapeutic decision-making in CUP. CUPISCO (NCT03498521) is an ongoing, phase II, randomized study of targeted therapy/cancer immunotherapy vs platinum-based chemotherapy in ESMO-guideline-defined unfavourable CUP. We present a preliminary, descriptive molecular analysis of ∼50% of patients designated for enrollment. Methods: Upon enrollment, comprehensive genomic profiling, including determination of microsatellite instability and tumour mutational burden (TMB), was performed on formalin-fixed, paraffin-embedded issues using the F1CDx assay. Gene alterations (GAs) found in ≥3% of patients were analyzed using multiple correspondence analyses and hierarchical clustering to identify co-occurrences. Results: Median age was 61.5 years (n = 346 [Apr 2021]; range: 22– 84); median TMB, 2.5 mutations/Mb (0–63.0). In our analysis, 30% of patients carried a potentially targetable GA. Most-frequent GAs were TP53 (44%), CDKN2A (32%), KRAS (21%; 2% G12C alterations), CDKN2B (21%), ARID1A (13%), STK11 (13%), MTAP (12%), PIK3CA (10%), MYC (8%), PBRM1 (8%), BAP1 (8%), and FGFR2 (8%). Beyond PIK3CA and FGFR2, other targetable GAs were identified in EGFR (2%), ERBB2 (6%), ALK (0.3%), ROS1 (1%), MET (2%), NTRK1 (1%), and BRAF (6%). The frequency of microsatellite instability- and TMB-high (> 16 mutations/Mb) samples was 3% and 9%, respectively. Based on hierarchical clustering of co-mutational profiles, multiple clusters were identified in the study cohort, each characterized by specific GA cooccurrences. Conclusions: This descriptive analysis sheds further light on the molecular landscape in patients with poor-prognosis CUP. Our analyses demonstrate that CUP cases can be clustered based on molecular profiling; further studies are needed to determine if these clusters carry clinical relevance. Our early results suggest that comprehensive genomic profiling of CUP samples identifies therapeutically relevant GAs in a significant proportion of patients and could thus guide personalized treatment of these tumors.
    • Baseline shifts towards the heart after IGRT are linked to overall survival in lung SABR patients

      Johnson-Hart, C; Price, Gareth J; Vasquez Osorio, Eliana; Faivre-Finn, Corinne; van Herk, Marcel; University of Manchester Radiotherapy Related Research, Manchester (2019)
    • Baseline status of paediatric oncology care in ten low-income or mid-income countries receiving My Child Matters support: a descriptive study.

      Ribeiro, Raul C; Steliarova-Foucher, Eva; Magrath, Ian; Lemerle, Jean; Eden, Tim O B; Forget, Caty; Mortara, Isabel; Tabah-Fisch, Isabelle; Divino, Jose Julio; Miklavec, Thomas; et al. (2008-08)
      BACKGROUND: Childhood-cancer survival is dismal in most low-income countries, but initiatives for treating paediatric cancer have substantially improved care in some of these countries. The My Child Matters programme was launched to fund projects aimed at controlling paediatric cancer in low-income and mid-income countries. We aimed to assess baseline status of paediatric cancer care in ten countries that were receiving support (Bangladesh, Egypt, Honduras, Morocco, the Philippines, Senegal, Tanzania, Ukraine, Venezuela, and Vietnam). METHODS: Between Sept 5, 2005, and May 26, 2006, qualitative face-to-face interviews with clinicians, hospital managers, health officials, and other health-care professionals were done by a multidisciplinary public-health research company as a field survey. Estimates of expected numbers of patients with paediatric cancer from population-based data were used to project the number of current and future patients for comparison with survey-based data. 5-year survival was postulated on the basis of the findings of the interviews. Data from the field survey were statistically compared with demographic, health, and socioeconomic data from global health organisations. The main outcomes were to assess baseline status of paediatric cancer care in the countries and postulated 5-year survival. FINDINGS: The baseline status of paediatric oncology care varied substantially between the surveyed countries. The number of patients reportedly receiving medical care (obtained from survey data) differed markedly from that predicted by population-based incidence data. Management of paediatric cancer and access to care were poor or deficient (ie, nonexistent, unavailable, or inconsistent access for most children with cancer) in seven of the ten countries surveyed, and accurate baseline data on incidence and outcome were very sparse. Postulated 5-year survival were: 5-10% in Bangladesh, the Philippines, Senegal, Tanzania, and Vietnam; 30% in Morocco; and 40-60% in Egypt, Honduras, Ukraine, and Venezuela. Postulated 5-year survival was directly proportional to several health indicators (per capita annual total health-care expenditure [Pearson's r(2)=0.760, p=0.001], per capita gross domestic product [r(2)=0.603, p=0.008], per capita gross national income [r(2)=0.572, p=0.011], number of physicians [r(2)=0.560, p=0.013] and nurses [r(2)=0.506, p=0.032] per 1000 population, and most significantly, annual government health-care expenditure per capita [r(2)=0.882, p<0.0001]). INTERPRETATION: Detailed surveys can provide useful data for baseline assessment of the status of paediatric oncology, but cannot substitute for national cancer registration. Alliances between public, private, and international agencies might rapidly improve the outcome of children with cancer in these countries.