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2. Outcomes from elective colorectal cancer surgery during the SARS‐CoV‐2 pandemic

Author

Glasbey, James C, Nepogodiev, Dmitri, Simoes, Joana FF, Omar, Omar M, Venn, Mary L, Evans, Jonathan P, Futaba, Kaori, Knowles, Charles H, Minaya‐Bravo, Ana, Mohan, Helen, Chand, Manish, Pockney, Peter, Di Saverio, Salomone, Smart, Neil, Vallance, Abigail, Vimalachandran, Dale, Wilkin, Richard JW, Siaw‐Acheampong, Kwabena, Benson, Ruth A, Bywater, Edward, Chaudhry, Daoud, Dawson, Brett E, Gujjuri, Rohan R, Heritage, Emily, Jones, Conor S, Kamarajah, Sivesh K, Khatri, Chetan, Khaw, Rachel A, Keatley, James M, Knight, Andrew, Lawday, Samuel, Mann, Harvinder S, Marson, Ella J, McLean, Kenneth A, Mckay, Siobhan C, Mills, Emily C, Pellino, Gianluca, Picciochi, Maria, Taylor, Elliott H, Tiwari, Abhinav, Trout, Isobel M, Smart, Neil J, Gallo, Gaetano, Moug, Susan, Pata, Francesco, Vimalchandran, Dale, Abbott, Tom EF, Abukhalaf, Sadi, Adamina, Michel, Ademuyiwa, Adesoji O, Agarwal, Arnav, Akkulak, Murat, Alameer, Ehab, Alderson, Derek, Alakaloko, Felix, Albertsmeiers, Markus, Alser, Osaid, Alshaar, Muhammad, Alshryda, Sattar, Arnaud, Alexis P, Magne Augestad, Knut, Ayasra, Faris, Azevedo, José, Bankhead‐Kendall, Brittany K, Barlow, Emma, Beard, David, Blanco‐Colino, Ruth, Brar, Amanpreet, Breen, Kerry A, Bretherton, Chris, Lima Buarque, Igor, Burke, Joshua, Caruana, Edward J, Chaar, Mohammad, Chakrabortee, Sohini, Christensen, Peter, Cox, Daniel, Cukier, Moises, Cunha, Miguel F, Davidson, Giana H, Desai, Anant, Drake, Thomas M, Edwards, John G, Elhadi, Muhammed, Emile, Sameh, Farik, Shebani, Fiore, Marco, Edward Fitzgerald, J, Ford, Samuel, and Garmanova, Tatiana

Subjects
Digestive Diseases, Patient Safety, Pneumonia, Emerging Infectious Diseases, Clinical Research, Prevention, Cancer, Colo-Rectal Cancer, Lung, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, COVIDSurg Collaborative, COVID-19, SARS-CoV-2, cancer, colon cancer, pandemic, rectal cancer, surgery, surgical oncology, Clinical Sciences, Surgery
Abstract

AimThis study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic.MethodThis was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data.ResultsFrom 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58-14.06), postoperative SARS-CoV-2 (16.90, 7.86-36.38), male sex (2.46, 1.01-5.93), age >70 years (2.87, 1.32-6.20) and advanced cancer stage (3.43, 1.16-10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%).ConclusionSurgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks.

Published
2021

4. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function

Author

Carrington, Emma V, Heinrich, Henriette, Knowles, Charles H, Fox, Mark, Rao, Satish, Altomare, Donato F, Bharucha, Adil E, Burgell, Rebecca, Chey, William D, Chiarioni, Guiseppe, Dinning, Philip, Emmanuel, Anton, Farouk, Ridzuan, Felt‐Bersma, Richelle JF, Jung, Kee Wook, Lembo, Anthony, Malcolm, Allison, Mittal, Ravinder K, Mion, Franҫois, Myung, Seung‐Jae, O’Connell, P Ronan, Pehl, Christian, Remes‐Troche, Jose María, Reveille, R Matthew, Vaizey, Carolynne J, Vitton, Veronique, Whitehead, William E, Wong, Reuben K, Scott, S Mark, and Group, All members of the International Anorectal Physiology Working

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Digestive Diseases, Anal Canal, Gastroenterology, Humans, Intestinal Diseases, Manometry, anorectal function testing, anorectal manometry, balloon expulsion test, functional anorectal disorders, rectal sensory test, All members of the International Anorectal Physiology Working Group, Neurosciences, Medical Physiology, Gastroenterology & Hepatology, Clinical sciences, Medical physiology
Abstract

BackgroundThis manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed.MethodsTwenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018.Key recommendationsThe IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.Conclusions and inferencesThis framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.

Published
2020

5. Combined MRI, high-resolution manometry and a randomised trial of bisacodyl versus hyoscine show the significance of an enlarged colon in constipation: the RECLAIM study.

Author

Wilkinson-Smith, Victoria, Scott, Mark, Menys, Alex, Wiklendt, Lukasz, Marciani, Luca, Atkinson, David, Sansone, Stefano, Zdanaviciene, Ausra, Coupland, Carol, Knowles, Charles H., Dinning, Philip, Taylor, Stuart A., Gowland, Penny, Hoad, Caroline Louise, Corsetti, Maura, and Spiller, Robin C.

Subjects
ANUS, SIGMOID colon, CHRONIC pain, MAGNETIC resonance imaging, MEDICAL sciences, PEER review of students
Published
2025
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6. Local Myoelectric Sensing During Human Colonic Tissue Perfusion.

Author

Ben-David, Matan, Makwana, Raj, Yered, Tal, Sanger, Gareth J., Knowles, Charles H., Wasserberg, Nir, and Shor, Erez

Subjects
ELECTROMYOGRAPHY, ACTION potentials, COLECTOMY, MESENTERIC artery, PROCTOLOGY, TISSUE arrays
Abstract

Objectives: Anastomotic leakage (AL) is one of the most devastating complications after colorectal surgery. The verification of the adequate perfusion of the anastomosis is essential to ensuring anastomosis integrity following colonic resections. This study aimed to evaluate the efficacy of measuring the electrical activity of the colonic muscularis externa at an anastomosis site for perfusion analysis following colorectal surgery. Methods: Strips of human isolated colon were maintained in a horizontal tissue bath to record spontaneous contractions and myoelectric activity and spike potentials (using a bipolar electrode array for the wireless transmission of myoelectric data—the xBar system) from the circular muscle. Intraoperative myoelectric signal assessment was performed by placing the electrode array on the colon prior to and following mesenteric artery ligation, just prior to colonic resection. Results: In human isolated colon, the amplitude, duration, and frequency of contractions were inhibited during hypoxia by >80% for each measurement, compared to control values and time-matched oxygenated muscle. Intraoperative (N = 5; mean age, 64.8 years; range, 54–74 years; 60% females) myoelectric signal assessment revealed a decline in spike rate following arterial ligation, with a mean reduction of 112.64 to 51.13 spikes/min (p < 0.0008). No adverse events were observed during the study, and the device did not substantially alter the surgical procedure. Conclusions: The electrical and contraction force of the human colon was reduced by ischemia, both in vitro and in vivo. These preliminary findings also suggest the potential of the xBar system to measure such changes during intraoperative and possibly postoperative periods to predict the risk of anastomotic viability as a surrogate of evolving dehiscence. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Faecal incontinence in adults

Author

Bharucha, Adil E., Knowles, Charles H., Mack, Isabelle, Malcolm, Allison, Oblizajek, Nicholas, Rao, Satish, Scott, S. Mark, Shin, Andrea, and Enck, Paul

Published
2022
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11. The impact of long‐course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum

Author

Kung, Victor W. S., Broad, John, Makwana, Raj, Palmer, Alexandra, Baidoo, Nicholas, Epton, Sarah, Elahi, Shezan, Chin‐Aleong, Joanne, Thaha, Mohamed, Knowles, Charles H., and Sanger, Gareth J.

Abstract

The long‐term effects of chemoradiotherapy on human rectum are poorly understood. The aims were to investigate changes in inflammatory status, myenteric neuron numbers/phenotype, neuromuscular functions and prokinetic drug efficacy. Macroscopically normal proximal‐to‐mid rectum was obtained from 21 patients undergoing surgery for bowel cancer, 98 days (range: 63–350) after concurrent capecitabine and pelvic radiotherapy, and 19 patients without chemoradiotherapy. Inflammatory status was measured by H&E, CD45 staining and qPCR. Myenteric neurons were examined by immunohistochemistry. Neuromuscular functions and drug efficacy were studied using exogenous agents and electrical field stimulation (EFS) to activate intrinsic nerves. Inflammation was not detected. Numbers of myenteric ganglia/neurons were unchanged (11.7 ± 2.4 vs. 10.3 ± 2.2 neurons/mm myenteric plexus with/without chemoradiotherapy) as were the numbers of cholinergic/nitrergic neurons. EFS stimulated cholinergic and nitrergic neurons so the contractile response of the muscle was the sum of both but dominated by cholinergic (causing contraction) or less often, nitrergic activity (relaxation), followed, after termination of EFS, by neuronally mediated contraction. Inhibition of nitric oxide synthase (by L‐NAME 300 μM) more clearly defined EFS‐evoked contractions. The 5‐HT4agonist prucalopride 10 μM and the cholinesterase inhibitor donepezil 1 µM, respectively increased and greatly increased the composite contractile response to EFS (measured as ‘area‐under‐the curve’) and the contractions isolated by L‐NAME (respectively, by 22 ± 14% and 334 ± 87%; n= 11/8). After chemoradiotherapy, nitrergic‐mediated muscle relaxations occurred more often during EFS (in 29.8 ± 6.1% preparations vs. 12.6 ± 5.1% without chemoradiotherapy, n= 21/18). With L‐NAME, the ability of prucalopride to facilitate EFS‐evoked contraction was lost and that of donepezil approximately halved (contractions increased by 132 ± 36%; n= 8). Several months after chemoradiotherapy, the rectum was not inflamed and myenteric neuron numbers/phenotype unchanged. However, nitrergic activity was increased relative to cholinergic activity, and prokinetic‐like drug activity was lost or greatly reduced. Thus, chemoradiotherapy causes long‐term changes in neuromuscular functions and markedly reduces the efficacy of drugs for treating constipation.

Published
2024
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16. Clinical effectiveness of subsensory sacral neuromodulation in adults with faecal incontinence: the SUBSoNIC crossover RCT and mechanistic study.

Author

Vollebregt, Paul F, Goh, Yan Li, Chan, Claire L, Dudding, Thomas, Furlong, Paul, Hamdy, Shaheen, Haviland, Joanne, Hooper, Richard, Jones, James, McAlees, Eleanor, Norton, Christine, O'Connell, P Ronan, Scott, S Mark, Stevens, Natasha, Tubby, Kerry, Worthen, Sian, Wong, Yuk Lam, and Knowles, Charles H

Published
2024
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25. Constipation

Author

Knowles, Charles H., Arnold, Wolfgang, Series editor, Ganzer, Uwe, Series editor, Herold, Alexander, editor, Lehur, Paul-Antoine, editor, Matzel, Klaus E., editor, and O'Connell, P. Ronan, editor

Published
2017
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26. Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial

Author

Norton, Christine, primary, Bannister, Sybil, additional, Booth, Lesley, additional, Brown, Steve R., additional, Cross, Samantha, additional, Eldridge, Sandra, additional, Emmett, Christopher, additional, Grossi, Ugo, additional, Jordan, Mary, additional, Lacy‐Colson, Jon, additional, Mason, James, additional, McLaughlin, John, additional, Moss‐Morris, Rona, additional, Scott, S. Mark, additional, Stevens, Natasha, additional, Taheri, Shiva, additional, Taylor, Stuart A., additional, Yiannakou, Yan, additional, and Knowles, Charles H., additional

Published
2023
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30. Slow transit constipation : clinical and aetiological studies

Author

Knowles, Charles H.

Subjects
610, Medicine
Abstract

Constipation is the second most commonly self-reported gastrointestinal symptom. On the basis of anorectal physiological investigations and colonic transit studies, a subgroup of patients with several intractable symptoms, but without organic disease will be found to have slow transit constipation (STC). STC is a condition of gut dysmotility which predominantly affects young women, and may result in surgical intervention with variable, often unsatisfactory results. The aetiology remains elusive. New aetiological hypotheses for STC were examined following full clinical and pathophysiological characterisation of a large cohort of 130 patients referred to our institution over the last 10 years. Aspects of nerve and muscle dysfunction were studied. A new scoring system demonstrated some ability of multiple symptoms to discriminate STC from other forms of constipation. Detailed clinical and gastrointestinal physiological studies confirmed the heterogeneity of STC patients. Some significant physiological differences were detectable between clinically defined sub-groups of patients and refuted previous assumptions based on smaller numbers. Detailed neurophysiological studies, including quantitative peripheral sensory and autonomic testing, provided evidence of a small fibre neuropathy in a proportion of patients with STC. Mutational screening of some early-onset cases for a possible congenital pathogenetic mechanism, based on the observation that some STC patients had relatives with Hirschsprung's disease demonstrated that mutation of 2 important genes now implicated in this disorder were not a frequent cause of STC. Serum immunoprecipitation assays showed that anti-neuronal ion channel autoantibodies may have an as yet unrecognised role in the development of STC in a small proportion of acquired cases. An inclusion body myopathy was identifiable in colonic tissue of patients with STC, and this appeared to arise secondary to denervation. Further knowledge of the single or multiple pathogenetic mechanisms leading to this clinical condition may allow more rational or directed therapies aimed at the correction of the disease process or processes themselves.

Published
2000

37. sj-docx-1-tej-10.1177_20417314221139794 – Supplemental material for Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy

Author

Desprez, Charlotte, Danovi, Davide, Knowles, Charles H, and Day, Richard M

Subjects
110599 Dentistry not elsewhere classified, FOS: Clinical medicine, FOS: Biological sciences, 69999 Biological Sciences not elsewhere classified
Abstract

Supplemental material, sj-docx-1-tej-10.1177_20417314221139794 for Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy by Charlotte Desprez, Davide Danovi, Charles H Knowles and Richard M Day in Journal of Tissue Engineering

Published
2023
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39. Pathway Of Low Anterior Resection syndrome relief after Surgery (POLARiS) feasibility trial protocol: a multicentre, feasibility cohort study with embedded randomised control trial to compare sacral neuromodulation and transanal irrigation to optimised conservative management in the management of major low anterior resection syndrome following rectal cancer treatment

Author

Coxon-Meggy, Alexandra Harriet, primary, Vogel, Irene, additional, White, Judith, additional, Croft, Julie, additional, Corrigan, Neil, additional, Meggy, Alun, additional, Stocken, Deborah D, additional, Keller, Deborah, additional, Hompes, Roel, additional, Knowles, Charles H, additional, Quyn, Aaron, additional, and Cornish, Julie, additional

Published
2023
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44. Adult‐onset megacolon with focal hypoganglionosis: A detailed phenotyping and prospective cohort study.

Author

Yoon, Jiyoung, Jung, Kee Wook, Ham, Nam Seok, Kim, Jihun, Do, Yoon Suh, Kim, Seon Ok, Choi, Sang Hyun, Kim, Dong Wook, Hwang, Sung Wook, Park, Sang Hyoung, Yang, Dong‐Hoon, Ye, Byong Duk, Byeon, Jeong‐Sik, Yoon, Yong Sik, Kim, Chan Wook, Yu, Chang Sik, Jung, Hwoon‐Yong, Yang, Suk‐Kyun, Martin, Joanne E., and Knowles, Charles H.

Subjects
LONGITUDINAL method, COHORT analysis, THERAPEUTICS, T cells, SATISFACTION
Abstract

Background: In this prospective cohort study, we evaluated features of "adult‐onset megacolon with focal hypoganglionosis." Methods: We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology. Key results: The median age of the patients with adult‐onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0–74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72–86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7–16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190–338) in the proximal and 95 cells/cm (IQR, 45–213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, −5.4 points (surgery) vs. ‐0.3 points (medical treatment); p < 0.001]. Conclusions and inferences: Adult‐onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Psychophysiological responses to pain identify reproducible human clusters

Author

Farmer, Adam D., Coen, Steven J., Kano, Michiko, Paine, Peter A., Shwahdi, Mustafa, Jafari, Jafar, Kishor, Jessin, Worthen, Sian F., Rossiter, Holly E., Kumari, Veena, Williams, Steven C.R., Brammer, Michael, Giampietro, Vincent P., Droney, Joanne, Riley, Julia, Furlong, Paul L., Knowles, Charles H., Lightman, Stafford L., and Aziz, Qasim

Published
2013
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48. Ex vivo study of human visceral nociceptors

Author

McGuire, Cian, Boundouki, George, Hockley, James R F, Reed, David, Cibert-Goton, Vincent, Peiris, Madusha, Kung, Victor, Broad, John, Aziz, Qasim, Chan, Christopher, Ahmed, Shafi, Thaha, Mohamed A, Sanger, Gareth J, Blackshaw, L Ashley, Knowles, Charles H, and Bulmer, David C

Published
2018
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49. Abnormal Perception of Urge to Defecate: An Important Pathophysiological Mechanism in Women With Chronic Constipation

Author

Vollebregt, Paul F., Wiklendt, Lukasz, Burgell, Rebecca E., Chaichanavichkij, Pam, Dinning, Phil G., Knowles, Charles H., Scott, S. Mark, and Gastroenterology and hepatology

Subjects
Adult, Male, Hepatology, Manometry, Gastroenterology, Rectum, Humans, Bayes Theorem, Female, Perception, Prospective Studies, Defecation, Constipation
Abstract

INTRODUCTION: Although the association of absent or attenuated "call to stool" with constipation is well-recognized, no studies have systematically evaluated the perception of urge to defecate in a well-defined cohort of patients with chronic constipation (CC). METHODS: A prospective study of 43 healthy adult women and 140 consecutive adult women attending a tertiary center for investigation of CC. All participants completed a 5-day viscerosensory questionnaire, and all women with CC also underwent anorectal physiologic investigations. Normal urge perception and abnormal urge perception were defined using a Naive Bayes model trained in healthy women (95% having normal urge). RESULTS: In total, 181 toilet visits in healthy women and 595 in women with CC were analyzed. Abnormal urge perception occurred in 70 (50.0%) women with CC. In this group, the urge to defecate was more often experienced as abdominal sensation (69.3% vs 41.4%; P < 0.0001), and the viscerosensory referral area was 81% larger (median pixels anterior: 1,849 vs 1,022; P < 0.0001) compared to women with CC and normal urge perception. Abnormal (vs normal) urge in women with CC was associated with more severe constipation (Cleveland Clinic constipation score: 19 vs 15 P < 0.0001), irritable bowel syndrome (45.7% vs 22.9% P < 0.0001), and a functional evacuation disorder on defecography (31.3% vs 14.3% P = 0.023). A distinct pattern of abnormal urge was found in women with CC and rectal hyposensitivity. DISCUSSION: Abnormal urge perception was observed in 50% of women with CC and was frequently described as abdominal sensation, supporting the concept that sensory dysfunction makes an important contribution to the pathophysiology of constipation.

Published
2022
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