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Article: Pre-, pro- and synbiotics in cancer prevention and treatment-a review of basic and clinical research.

Scott, Alasdair J / Merrifield, Claire A / Younes, Jessica A / Pekelharing, Elizabeth P

Ecancermedicalscience

2018 Volume 12, Page(s) 869

Abstract: There is a growing appreciation of the role of the human microbiota in the pathophysiology of cancer. Pre-, pro- and synbiotics are some of the best evidenced means of manipulating the microbiota for therapeutic benefit and their potential role in the ... ...

Abstract	There is a growing appreciation of the role of the human microbiota in the pathophysiology of cancer. Pre-, pro- and synbiotics are some of the best evidenced means of manipulating the microbiota for therapeutic benefit and their potential role in the prevention and treatment of cancer has garnered significant interest. In this review, we discuss how these agents may have oncosuppressive effects by maintaining intestinal barrier function, immunomodulation, metabolism and preventing host cell proliferation. We highlight the epidemiological and trials-based evidence supporting a role for pre-, pro- and synbiotics in the prevention of cancer. Ultimately, there is more evidence in support of these agents as adjuncts in the treatment of cancer. We discuss their roles in optimising the efficacy and/or minimising the adverse effects of chemotherapy and radiotherapy, antibiotics and surgery. Although we see significant promise in the application of pre-, pro- and synbiotics for clinical benefit in oncology patients, the field is very much in its infancy and oncologists face substantial challenges in advising their patients appropriately.
Language	English
Publishing date	2018-09-05
Publishing country	England
Document type	Journal Article ; Review
ISSN	1754-6605
ISSN	1754-6605
DOI	10.3332/ecancer.2018.869
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Article: Colorectal carcinogenesis: an archetype of gut microbiota-host interaction.

Alexander, James L / Scott, Alasdair J / Pouncey, Anna L / Marchesi, Julian / Kinross, James / Teare, Julian

Ecancermedicalscience

2018 Volume 12, Page(s) 865

Abstract: Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology ... ...

Abstract	Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as
Language	English
Publishing date	2018-09-05
Publishing country	England
Document type	Journal Article ; Review
ISSN	1754-6605
ISSN	1754-6605
DOI	10.3332/ecancer.2018.865
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Article ; Online: Patient-related risk factors for urinary retention following ambulatory general surgery: a systematic review and meta-analysis.

Mason, Sam E / Scott, Alasdair J / Mayer, Erik / Purkayastha, Sanjay

American journal of surgery

2016 Volume 211, Issue 6, Page(s) 1126–1134

Abstract: Background: Postoperative urinary retention (POUR) is a source of avoidable patient harm. The aim of this review is to identify and quantify the role of patient-related risk factors in the development of POUR following ambulatory general surgery.: ... ...

Abstract	Background: Postoperative urinary retention (POUR) is a source of avoidable patient harm. The aim of this review is to identify and quantify the role of patient-related risk factors in the development of POUR following ambulatory general surgery. Methods: Studies published until December 2014 were identified by searching MEDLINE, EMBASE, and PsycINFO databases. Risk factors assessed in 3 or more studies were meta-analyzed. Results: Twenty-one studies were suitable for inclusion consisting of 7,802 patients. The incidence of POUR was 14%. Increased age and the presence of lower urinary tract symptoms significantly increased risk with odds ratios [ORs] of 2.11 (95% confidence interval [CI] 1.15 to 3.86) and 2.83 (1.57 to 5.08), respectively. Male sex was not associated with developing POUR (OR .96, 95% CI .62 to 1.50). Preoperative α-blocker use significantly decreased the incidence of POUR with an OR of .37 (95% CI .15 to .91). Conclusions: Increased age and the presence of lower urinary tract symptoms increase the risk of POUR, while α-blocker use confers protection. Male sex was not associated with POUR. These findings assist in preoperative identification of patients at high risk of POUR.
MeSH term(s)	Adult ; Age Factors ; Aged ; Ambulatory Surgical Procedures/adverse effects ; Ambulatory Surgical Procedures/methods ; Comorbidity ; Female ; General Surgery/methods ; Humans ; Incidence ; Lower Urinary Tract Symptoms/epidemiology ; Male ; Middle Aged ; Postoperative Complications/diagnosis ; Postoperative Complications/epidemiology ; Risk Assessment ; Surgical Procedures, Operative/adverse effects ; Surgical Procedures, Operative/methods ; Survival Analysis ; Urinary Retention/diagnosis ; Urinary Retention/epidemiology
Language	English
Publishing date	2016-06
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2015.04.021
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Article: Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5-6 September 2017, London, UK.

Scott, Alasdair J / Merrifield, Claire A / Alexander, James L / Marchesi, Julian R / Kinross, James M

Ecancermedicalscience

2017 Volume 11, Page(s) 791

Abstract: The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education ... ...

Abstract	The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5-6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research. Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers-such as lung and urogenital tract-was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics. On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a 'healthy' microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite 'interactome' between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may be exploited for therapeutic benefit in cancer and the safety implications of performing such research in oncology patients.
Language	English
Publishing date	2017-12-20
Publishing country	England
Document type	Journal Article
ISSN	1754-6605
ISSN	1754-6605
DOI	10.3332/ecancer.2017.791
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Article ; Online: Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-monoinfection.

Maurice, James B / Patel, Amee / Scott, Alasdair J / Patel, Krish / Thursz, Mark / Lemoine, Maud

AIDS (London, England)

2017 Volume 31, Issue 11, Page(s) 1621–1632

Abstract: Objective: To identify the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and fibrosis in HIV-monoinfected patients.: Design: Systematic review and meta-analysis.: Methods: We searched ... ...

Abstract	Objective: To identify the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and fibrosis in HIV-monoinfected patients. Design: Systematic review and meta-analysis. Methods: We searched Medline and Embase and included studies that enrolled HIV-monoinfected patients with NAFLD defined by imaging and/or liver histology. Data on prevalence and risk factors for NAFLD, NASH and fibrosis were collected for meta-analysis using random effects models. Results: Ten studies were included from the United States of America (n = 4), Canada (n = 1), France (n = 2), Italy (n = 1), Japan (n = 1) and China (n = 1). The prevalence of NAFLD (Imaging studies), NASH and fibrosis (biopsied populations) were 35% [95% confidence interval (CI) 29-42], 42% (95% CI 22-64) and 22% (95% CI 13-34), respectively. Meta-analysis of risk factors showed that high BMI, waist circumference, type 2 diabetes, hypertension, triglycerides and high CD4 cell count were associated with NAFLD, whereas HIV viral load, duration of HIV infection, duration of antiretroviral therapy and CD4 cell count nadir were not. Patients with high BMI [mean difference (MD) 1.38, 95% CI 0.04-2.71 P = 0.04], fasting glucose (MD 0.80, 95% CI 0.47-1.13 P < 0.00001) and AST level (MD 13.00, 95% CI 4.34-21.65 P = 0.003) were at increased risk of significant liver fibrosis. Conclusion: NAFLD is frequently observed in HIV-monoinfected patients, and NASH is a common cause of unexplained abnormal liver function in patients selected for liver biopsy. Metabolic disorders are key risk factors independently of HIV parameters. Future trials on pharmacological interventions in NASH with fibrosis should include patients with HIV.
MeSH term(s)	Canada/epidemiology ; China/epidemiology ; Cross-Sectional Studies ; France/epidemiology ; HIV Infections/epidemiology ; HIV Infections/physiopathology ; Humans ; Italy/epidemiology ; Japan/epidemiology ; Liver Cirrhosis/epidemiology ; Liver Cirrhosis/physiopathology ; Liver Cirrhosis/virology ; Non-alcoholic Fatty Liver Disease/epidemiology ; Non-alcoholic Fatty Liver Disease/physiopathology ; Non-alcoholic Fatty Liver Disease/virology ; Prevalence ; Risk Factors ; United States/epidemiology
Language	English
Publishing date	2017-04-11
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000001504
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Article ; Online: Impact of the COVID-19 Pandemic on Emergency Adult Surgical Patients and Surgical Services: An International Multi-center Cohort Study and Department Survey.

Winter Beatty, Jasmine / Clarke, Jonathan M / Sounderajah, Viknesh / Acharya, Amish / Rabinowicz, Simon / Martin, Guy / Warren, Leigh R / Yalamanchili, Seema / Scott, Alasdair J / Burgnon, Elizabeth / Purkayastha, Sanjay / Markar, Sheraz / Kinross, James M

Annals of surgery

2021 Volume 274, Issue 6, Page(s) 904–912

Abstract: Objectives: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort.: Background: High mortality rates were reported for surgical patients ... ...

Abstract	Objectives: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. Background: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. Methods: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. Results: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. Conclusion: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.
MeSH term(s)	Adult ; Aged ; COVID-19/epidemiology ; Comorbidity ; Emergencies/epidemiology ; Emergency Service, Hospital/statistics & numerical data ; Female ; Follow-Up Studies ; General Surgery/statistics & numerical data ; Global Health ; Hospital Mortality/trends ; Humans ; Male ; Middle Aged ; Pandemics ; SARS-CoV-2 ; Surveys and Questionnaires
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000005152
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Article ; Online: Insights from a global snapshot of the change in elective colorectal practice due to the COVID-19 pandemic.

Mason, Sam E / Scott, Alasdair J / Markar, Sheraz R / Clarke, Jonathan M / Martin, Guy / Winter Beatty, Jasmine / Sounderajah, Viknesh / Yalamanchili, Seema / Denning, Max / Arulampalam, Thanjakumar / Kinross, James M

PloS one

2020 Volume 15, Issue 10, Page(s) e0240397

Abstract: Background: There is a need to understand the impact of COVID-19 on colorectal cancer care globally and determine drivers of variation.: Objective: To evaluate COVID-19 impact on colorectal cancer services globally and identify predictors for ... ...

Abstract	Background: There is a need to understand the impact of COVID-19 on colorectal cancer care globally and determine drivers of variation. Objective: To evaluate COVID-19 impact on colorectal cancer services globally and identify predictors for behaviour change. Design: An online survey of colorectal cancer service change globally in May and June 2020. Participants: Attending or consultant surgeons involved in the care of patients with colorectal cancer. Main outcome measures: Changes in the delivery of diagnostics (diagnostic endoscopy), imaging for staging, therapeutics and surgical technique in the management of colorectal cancer. Predictors of change included increased hospital bed stress, critical care bed stress, mortality and world region. Results: 191 responses were included from surgeons in 159 centers across 46 countries, demonstrating widespread service reduction with global variation. Diagnostic endoscopy was reduced in 93% of responses, even with low hospital stress and mortality; whilst rising critical care bed stress triggered complete cessation (p = 0.02). Availability of CT and MRI fell by 40-41%, with MRI significantly reduced with high hospital stress. Neoadjuvant therapy use in rectal cancer changed in 48% of responses, where centers which had ceased surgery increased its use (62 vs 30%, p = 0.04) as did those with extended delays to surgery (p<0.001). High hospital and critical care bed stresses were associated with surgeons forming more stomas (p<0.04), using more experienced operators (p<0.003) and decreased laparoscopy use (critical care bed stress only, p<0.001). Patients were also more actively prioritized for resection, with increased importance of co-morbidities and ICU need. Conclusions: The COVID-19 pandemic was associated with severe restrictions in the availability of colorectal cancer services on a global scale, with significant variation in behaviours which cannot be fully accounted for by hospital burden or mortality.
MeSH term(s)	Betacoronavirus/physiology ; COVID-19 ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/therapy ; Coronavirus Infections/epidemiology ; Elective Surgical Procedures/statistics & numerical data ; Female ; Gastroenterology/organization & administration ; Gastroenterology/statistics & numerical data ; Health Care Rationing ; Health Services Needs and Demand ; Humans ; Male ; Pandemics ; Patient Safety ; Pneumonia, Viral/epidemiology ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-10-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0240397
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Article ; Online: Longitudinal analysis of serum oxylipin profile as a novel descriptor of the inflammatory response to surgery.

Wolfer, Arnaud M / Scott, Alasdair J / Rueb, Claudia / Gaudin, Mathieu / Darzi, Ara / Nicholson, Jeremy K / Holmes, Elaine / Kinross, James M

Journal of translational medicine

2017 Volume 15, Issue 1, Page(s) 83

Abstract: Background: Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the ... ...

Abstract	Background: Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile. Methods: Adults patients undergoing elective laparoscopic or open colorectal resections were included. Primary outcomes were serum oxylipin profile quantified by ultra high-performance liquid chromatography-mass spectrometry, serum white cell count and C-reactive protein concentration. Serum samples were taken at three time-points: pre-operative (day zero), early post-operative (day one) and late post-operative (day four/five). Results: Some 55 patients were included, of which 33 (60%) underwent surgery that was completed laparoscopically. Pre-operative oxylipin profiles were characterised by marked heterogeneity but surgery induced a common shift resulting in more homogeneity at the early post-operative time-point. By the late post-operative phase, oxylipin profiles were again highly variable. This evolution was driven by time-dependent changes in specific oxylipins. Notably, the levels of several oxylipins with anti-inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at the early post-operative point before returning to baseline by the late post-operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the early post-operative phase while levels of anti-thrombotic mediators (9-HODE and 13-HODE) fell; concentrations of all three oxylipins then remained fairly static from early to late post-operative phases. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had lower levels of some anti-inflammatory oxylipins (8,9-DHET and 17-HDoHE) in addition to reduced concentrations of anti-thrombotic mediators (9-HODE and 13-HODE) with increased concentration of their pro-thrombotic counterpart (TxB2). Conclusions: Serum oxylipin profile is modified by surgical intervention and may even be sensitive to the degree of surgical trauma and therefore represents a novel descriptor of the surgical systemic inflammatory response.
MeSH term(s)	Aged ; C-Reactive Protein/metabolism ; Demography ; Fatty Acids, Unsaturated/blood ; Female ; Humans ; Inflammation/blood ; Laparoscopy ; Leukocyte Count ; Longitudinal Studies ; Male ; Middle Aged ; Oxylipins/blood ; Principal Component Analysis ; Time Factors
Chemical Substances	Fatty Acids, Unsaturated ; Oxylipins ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2017-04-26
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-017-1171-2
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Article ; Online: Robotic surgery: disruptive innovation or unfulfilled promise? A systematic review and meta-analysis of the first 30 years.

Tan, Alan / Ashrafian, Hutan / Scott, Alasdair J / Mason, Sam E / Harling, Leanne / Athanasiou, Thanos / Darzi, Ara

Surgical endoscopy

2016 Volume 30, Issue 10, Page(s) 4330–4352

Abstract: Background: Robotic surgery has been in existence for 30 years. This study aimed to evaluate the overall perioperative outcomes of robotic surgery compared with open surgery (OS) and conventional minimally invasive surgery (MIS) across various surgical ... ...

Abstract	Background: Robotic surgery has been in existence for 30 years. This study aimed to evaluate the overall perioperative outcomes of robotic surgery compared with open surgery (OS) and conventional minimally invasive surgery (MIS) across various surgical procedures. Methods: MEDLINE, EMBASE, PsycINFO, and ClinicalTrials.gov were searched from 1990 up to October 2013 with no language restriction. Relevant review articles were hand-searched for remaining studies. Randomised controlled trials (RCTs) and prospective comparative studies (PROs) on perioperative outcomes, regardless of patient age and sex, were included. Primary outcomes were blood loss, blood transfusion rate, operative time, length of hospital stay, and 30-day overall complication rate. Results: We identified 99 relevant articles (108 studies, 14,448 patients). For robotic versus OS, 50 studies (11 RCTs, 39 PROs) demonstrated reduction in blood loss [ratio of means (RoM) 0.505, 95 % confidence interval (CI) 0.408-0.602], transfusion rate [risk ratio (RR) 0.272, 95 % CI 0.165-0.449], length of hospital stay (RoM 0.695, 0.615-0.774), and 30-day overall complication rate (RR 0.637, 0.483-0.838) in favour of robotic surgery. For robotic versus MIS, 58 studies (21 RCTs, 37 PROs) demonstrated reduced blood loss (RoM 0.853, 0.736-0.969) and transfusion rate (RR 0.621, 0.390-0.988) in favour of robotic surgery but similar length of hospital stay (RoM 0.982, 0.936-1.027) and 30-day overall complication rate (RR 0.988, 0.822-1.188). In both comparisons, robotic surgery prolonged operative time (OS: RoM 1.073, 1.022-1.124; MIS: RoM 1.135, 1.096-1.173). The benefits of robotic surgery lacked robustness on RCT-sensitivity analyses. However, many studies, including the relatively few available RCTs, suffered from high risk of bias and inadequate statistical power. Conclusions: Our results showed that robotic surgery contributed positively to some perioperative outcomes but longer operative times remained a shortcoming. Better quality evidence is needed to guide surgical decision making regarding the precise clinical targets of this innovation in the next generation of its use.
MeSH term(s)	Blood Loss, Surgical/statistics & numerical data ; Blood Transfusion/statistics & numerical data ; Humans ; Laparoscopy ; Laparotomy ; Length of Stay/statistics & numerical data ; Minimally Invasive Surgical Procedures ; Operative Time ; Postoperative Complications/epidemiology ; Prospective Studies ; Robotic Surgical Procedures ; Surgical Procedures, Operative
Language	English
Publishing date	2016-02-19
Publishing country	Germany
Document type	Comparative Study ; Journal Article ; Meta-Analysis ; Review ; Systematic Review
ZDB-ID	639039-0
ISSN	1432-2218 ; 0930-2794
ISSN (online)	1432-2218
ISSN	0930-2794
DOI	10.1007/s00464-016-4752-x
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Article ; Online: Insights from a global snapshot of the change in elective colorectal practice due to the COVID-19 pandemic

Mason, Sam E. / Scott, Alasdair J. / Markar, Sheraz R. / Clarke, Jonathan M. / Martin, Guy / Winter Beatty, Jasmine / Sounderajah, Viknesh / Yalamanchili, Seema / Denning, Max / Arulampalam, Thanjakumar / Kinross, James M.

PLOS ONE

2020 Volume 15, Issue 10, Page(s) e0240397

Keywords	General Biochemistry, Genetics and Molecular Biology ; General Agricultural and Biological Sciences ; General Medicine ; covid19
Language	English
Publisher	Public Library of Science (PLoS)
Publishing country	us
Document type	Article ; Online
ISSN	1932-6203
DOI	10.1371/journal.pone.0240397
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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