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Professor Charles Knowles, MBBChir, PhD, FRCS, FRCS (Gen Surg)

Charles

Professor of Surgery, Deputy Director of Research and Director of National Bowel Research Centre

Centre: Neuroscience and Trauma Centre

Email: c.h.knowles@qmul.ac.uk
Telephone: +44 20 7882 8757

Profile

Prof Knowles undertook his preclinical training at Cambridge University and then moved to the London Hospital Medical College, qualifying in 1992. Prior to specialist training, he undertook research based at Barts & the London and, funded by the Royal College of Surgeons of England, leading to the degree of PhD at the University of London in 2000. He entered the Specialist Register in 2005 as a general and colorectal surgeon. In 2006, he was appointed Senior Lecturer in Colorectal Surgery on the basis of a prestigious award from HEFCE. He holds an Honorary Consultant appointment at Barts Health NHS Trust.

 Senior president of Barts and the London Student Running Club

Summary

Professor Knowles is Director of the NIHR Enteric Healthcare Technology Cooperative, Director of the National Bowel Research Centre and Surgical Specialty Lead for North Thames NIHR CRN. He holds research positions in the European Society of Coloproctology and Association of Coloproctology of Great Britain and Ireland. He is Chair to UEG-led international working groups in anorectal physiology and GI neuromuscular diseases. He serves as a member of the Rome IV committee for anorectal disorders and is on the global expert panel for Medtronic. He is a panel member for NIHR i4i and is on the editorial board of two journals. He has authored over 150 peer-reviewed publications as well as contributing several book chapters to major colorectal and general surgical texts.

 

Teaching

  • Lecturer on the final MB revision and preparation for practice courses: Barts & the London SMD
  • Lecturer on MSc, Intercalculated BSc and higher surgical training courses locally and internationally
  • Lecturer on Cass University (nursing) coloproctology masterclass course
  • Co-author or editor of 4 books related to examination technique, revision style and knowledge base
  • Author of chapters in core surgical texts in the UK (Bailey and Love) and USA (American College of Surgery textbook)
  • Internal and external (Imperial College) surgical examiner annually
  • Student Mentor (years 3-5) and Academic Scheme Mentor: Barts & the London SMD
  • Approved Educational Supervisor to ST programme at Homerton Hospital
  • Local lead for Academic Clinical Fellowships and prev. national surgical advisor to Walport scheme
  • Representative on the NE Thames London Deanery Specialist Training & Academic Steering Committees
  • National trainee surgical research network pilot steering group member
  • Senior advisor (and founder) or the London Surgical Research Group (trainee led)

Topics for PhD supervision:

  • A randomised mixed methods pilot (phase II exploratory trial) of sacral and percutaneous tibial nerve stimulation for faecal incontinence (N Thin)
  • Role of hypermobility and connective tissue disease in disorders of GI function (A Fikree)
  • Study of central afferent neural mechanisms of sacral nerve stimulation (E Carrington)
  • A translational study of voltage-gated sodium channels in visceral afferent signalling (G Boundouki)
  • Further development of human visceral afferent recordings (C McGuire)
  • CONtrol of Faecal Incontinence using Distal NeuromodulaTion (CONFIDeNT) study (E Horrocks)

Research

Research Interests:

His main clinical interests are in the surgical management of:

  1. Functional colorectal disorders e.g. chronic constipation
  2. Pelvic floor disorders including prolapse and faecal incontinence
  3. Complex proctology e.g. anal fistula

His main research interests are:

  1. Evaluation of new technologies for the treatment of chronic gastrointestinal (GI) diseases with a focus on neuromodulation
  2. Development and evaluation of GI diagnostics for deeper phenotyping and treatment stratification;
  3. Pathology and management of rare gastrointestinal neuromuscular diseases
  4. Development of new trial methodology for evaluation of complex interventions with a focus on surgery

 

Overview

  • The use of advanced colorectal physiology to guide surgical treatment, in particular the evolving use of neuromodulation
  • Cellular and molecular basis of peripheral visceral afferent function particularly in relation to visceral pain, using both in vivo and in vitro human models
  • Characterisation of the neuropathology and aetiology of severe primary and secondary gastrointestinal neuromuscular disease
  • Neuromuscular pathological aspects of gastrointestinal motility disorders
  • The molecular basis of gut sensorimotor dysfunction, particularly in relation to visceral hypersensitivity and pain
  • The role of autoantibody-mediated disease in gut motility disorders
  • The role of clinical tests of colorectal physiology in guiding therapy

Recent and ongoing research projects

  • Development of the first international classification of GI neuromuscular pathology
  • Prospective randomized double-blind study of sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity
  • In vitro human visceral afferent recordings
  • A randomised mixed methods pilot (phase II exploratory trial) of sacral and percutaneous tibial nerve stimulation for faecal incontinence (NIHR RfPb)
  • CONtrol of Faecal Incontinence using Distal NeuromodulaTion (CONFIDeNT) study (NIHR HTA)
  • GI neuromuscular disease international database
  • Study of central afferent neural mechanisms of sacral nerve stimulation
  • Pilot randomised study of ambulatory transcutaneous tibial nerve stimulation for overactive bladder and faecal incontinence
  • IMmediate Pharmacological intervention in Acute Colonic pseudo-obstrucTION (IMPACTION) – randomised trial of single dose 2mg prucalopride
  • Development of a UK evidence-based algorithm for management of chronic constipation (NIHR PDG)
  • Selective nerve stimulation for chronic abdominal pain

Publications

Horrocks EJ, Chadi S, Stevens N, Wexner S, Knowles CH. Predictors of efficacy of percutaneous tibial nerve stimulation for fecal incontinence: a post-hoc analysis of a randomized trial" (CGH-D-17-00954). Clinical Gastroenterology and Hepatology 2017 (epub ahead of print).

McGuire C, Boundouki G, Hockley JR, Reed D, Cibert-Goton V, Peiris M, Kung V, Broad J, Aziz Q, Chan C, Ahmed S, Thaha MA, Sanger GJ, Blackshaw LA, Knowles CH, Bulmer DC. Ex vivo study of human visceral nociceptors. Gut. 2016 Sep 21. pii:gutjnl-2016-311629. doi: 10.1136/gutjnl-2016-311629. [Epub ahead of print]

Rao SS, Bharucha AE, Chiarioni G, Felt-Bersma R, Knowles C, Malcolm A, Wald A. Functional Anorectal Disorders. Gastroenterology 2016 Mar 25 [Epub ahead of print].

Grossi U, Carrington EV, Bharucha AE, Horrocks EJ, Scott SM, Knowles CH. Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defaecation. Gut 2016; 65: 447-55.

Hockley JR, Tranter MM, McGuire C, Boundouki G, Cibert-Goton V, Thaha MA, Blackshaw LA, Michael GJ, Baker MD, Knowles CH, Winchester WJ, Bulmer DC. P2Y Receptors Sensitize Mouse and Human Colonic Nociceptors. J Neurosci. 2016; 36:2364-76.

Thaha MA, Abukar AA, Thin NN, Ramsanahie A, Knowles CH. Sacral nerve stimulation for faecal incontinence and constipation in adults. Cochrane Database Syst Rev 2015 Aug 24;8:CD004464.

Knowles CH, Horrocks EJ, Bremner SA, Stevens N, Norton C, O'Connell PR, Eldridge S; CONFIDeNT study group. Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial. Lancet 2015; 386(10004):1640-8.

Altomare DF, Giuratrabocchetta S, Knowles CH, Muñoz Duyos A, Robert-Yap J, Matzel KE; the European SNS Outcome Study Group. Long-term outcomes of sacral nerve stimulation for faecal incontinence. Br J Surg. 2015; 102:407-415.

Thin N, Taylor SJC, Bremner SA, Emmanuel AV, Hounsome N, Williams NS, Knowles CH. Randomized clinical trial of sacral and percutaneous tibial nerve stimulation in patients with faecal incontinence. Br J Surg 2015; 102: 349-358.

Evers J, Devane L, Carrington EV, Scott SM, Knowles CH, O'Connell PR, Jones JF. Effects of stimulation frequency and intensity in sacral neuromodulation on anorectal inputs to the somatosensory cortex in an experimental model. Br J Surg 2014; 101:1317-28.

Hockley JR, Boundouki G, Cibert-Goton V, McGuire C, Yip PK, Chan C, Tranter M, Wood JN, Nassar MA, Ashley Blackshaw L, Aziz Q, Michael GJ, Baker MD, Winchester WJ, Knowles CH, Bulmer DC. Multiple Roles for Na(V)1.9 in the Activation of Visceral Afferents by Noxious Inflammatory, Mechanical and Human Disease Derived Stimuli. Pain. 2014;155: 1962-75

Botha C, Farmer AD, Nilsson M, Brock C, Gavrila AD, Drewes AM, Knowles CH, Aziz Q. Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015; 64:611-7.

Hayat JO, Gabieta-Somnez S, Yazaki E, Kang JY, Woodcock A, Dettmar P, Mabary J, Knowles CH, Sifrim D. Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease. Gut 2014 64(3):373-80.

Hotouras A, Murphy J, Walsh U, Allison M, Curry A, Williams NS, Knowles C, Chan CL. Outcome of Percutaneous Tibial Nerve Stimulation (PTNS) for Fecal Incontinence: A Prospective Cohort Study. Ann Surg. 2014; 259:939-43.

Athanasakos EP, Kemal KI, Malliwal RS, Scott SM, Williams NS, Aziz Q, Ward HC, Knowles CH. A controlled study of clinical and psychosocial functioning in adolescents and young adults with anorectal malformations and chronic idiopathic constipation. Br J Surg 2013; 100: 832-9.

Knowles CH, Panza E, Lindberg G, De Giorgio R. New perspectives in the diagnosis and management of enteric neuropathies. Nat Rev Gastroenterol Hepatol 2013;10:206-18.

Knowles CH, Thin N, Gill K, Bhan C, Grimmer K, Lunniss PJ, Williams NS, Scott M. Prospective randomized double-blind study of sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity. Ann Surg 2012; 255: 643-9.

Peiris M, Bulmer D, Baker M, Boundouki G, Sinha S, Hobson A, Lee K, Aziz Q, Knowles CH. Human visceral afferent recordings: preliminary report. Gut 2011; 60: 204-8.

Knowles CH, Thin N, Gill K, Bhan C, Grimmer K, Lunniss PJ, Williams NS, Scott M. Prospective randomized double-blind study of sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity. In press: Ann Surg July 2011.

Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Gershon MD, Hutson J, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T. The London Classification of GI Neuromuscular disease. Gut 2010; 59: 882-887.

Knowles CH, Aziz Q. Basic and clinical aspects of gastrointestinal pain. Pain 2009; 141: 191-209.

Nastro P, Knowles CH, McGrath A, Heyman B, Porrett TR, Lunniss PJ. Complications of intestinal stomas. Br J Surg. 2010; 97: 1185-9.

Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Gershon MD, Hutson J, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T. Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group. Acta Neuropathol 2009; 118: 271-301.

Martin JE, Hester TW, Aslam H, Sinha S, Knowles CH. Discordant practice and limited histopathological assessment in gastrointestinal neuromuscular disease. Gut 2009; 58: 1703-5.

Hubball A, Lang B, De Giorgio R, Martin JE, Knowles CH. The role of humoral autoimmunity in Gastrointestinal neuromuscular disease. Prog Neurobiol 2008; 87: 10-20.

Gooneratne M, Facer P, Knowles CH, Frye J, Chan C, Anand P, Williams NS. Elevated rectal mucosal substance P levels in patients with faecal incontinence are normalised by successful sacral nerve stimulation. Br J Surg 2008; 95: 477-83.

Knowles CH, Veress B, Tornblom H, Wallace S, Paraskevas P, Darzi A, Martin JE, Nyborg B, Lindberg G. Safety and diagnostic yield of laparoscopically assisted full-thickness bowel biospy. Neurogastroenterol Motil 2008; 20: 774-9.

Williams NS, Murphy J, Knowles CH. The Anterior Perineal PlanE for ultra low Anterior Resection (the APPEAR technique): a pilot study. Ann Surg 2008; 247: 750-758.


View all Charles Knowles's Research Publications at: http://www.researchpublications.qmul.ac.uk

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