C. H. Knowles's research while affiliated with Queen Mary, University of London and other places
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Publications (129)
Purpose:
There remains uncertainty as to which risk factors are important for the development of defaecatory problems as a result of heterogeneity of published evidence. Understanding the impact of risk factors may be important in selecting targets for disease prevention or reversal. The aim of this study was to identify and evaluate risk factors...
Introduction
The influence of risk factors on the development of defaecatory problems is difficult to ascertain due to heterogeneity of published evidence. An understanding of the impact of these risk factors is important in selecting targets for disease prevention.
Methods
Risk factors for chronic constipation and faecal incontinence were anonymo...
Background Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multi...
Background
Colectomy remains a treatment option for a minority of patients with slow-transit constipation (STC) refractory to conservative treatment. However careful patient selection is essential to maximize benefits and minimize risk of adverse outcome. This study determined the proportion of patients with chronic constipation that would meet cri...
Aim This 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. Method This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicio...
Aim Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients...
Objectives
Randomised trials comparing surgical techniques for rectal prolapse are not always feasible. We assessed whether non‐randomised comparisons of those who have had surgery with those still waiting would be confounded baseline health status.
Study Design and Setting
Prospective cohort study in seven UK hospitals. Participants ≥18 years list...
The COVID‐19 crisis has undoubtedly taken a toll on the care of patients with colorectal disease. Elective services, be that face to face contact, endoscopy or operating all but ceased during the pandemic
Aim
Dyssynergic defaecation (DD) is characterised by inappropriate co‐ordination of the pelvic floor muscles during defaecation, resulting in impaired stool expulsion. The mainstay of treatment is biofeedback and alternative therapies are limited in those who do not respond. This systematic review evaluated Botulinum toxin type A injection (BTXA) a...
Background:
Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery.
Methods:
A prospective multicentre cohort study was delivered by an international, student-...
While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory con...
We welcome the comments by Buskens & Bemelman in their recent editorial (1). As in many countries there are maximum waiting times in the UK for patients needing cancer treatment. The ‘2 week wait’ speeds up diagnosis and 31/62 day target streamline waiting times for treatment. For non-cancer patients the National Health Service policy stipulates th...
Background
The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up.
Methods
The randomized...
Background
Patients with IBD have difficulty revealing concerns about bowel control problems to clinicians,¹ who do not actively ask about this symptom² despite clinical guidelines recommending active-case finding in high-risk populations.³ With no available evidence to advise clinicians on how to ask, we aimed to determine the results of face-to-f...
The following position statement forms part of a response to the current concerns regarding use of mesh to perform rectal prolapse surgery. It highlights the actions being pursued by the Pelvic Floor Society (TPFS) regarding clinical governance in relation to ventral mesh rectopexy (VMR). The following are summary recommendations. Available evidenc...
Aim:
This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR).
Methods:
Summary of review data, development of GPR and fu...
Aim:
To assess the outcomes of rectal suspension procedures (forms of rectopexy) in adults with chronic constipation.
Method:
Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxf...
Aim:
This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice.
Method:
PRISMA guidance was adhered to throughout. A literature search was performed in...
Aim:
To assess the outcomes of rectal excisional procedures in adults with chronic constipation.
Method:
Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Eviden...
Aim:
To assess the outcomes of colectomy in adults with chronic constipation (CC).
Method:
Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements (SES) with a summative Oxford Centre for Evidence-Based...
Aim:
To assess the outcomes of recto-vaginal reinforcement procedures in adults with chronic constipation.
Method:
Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre...
Aim:
To assess the outcomes of sacral nerve stimulation in adults with chronic constipation.
Method:
Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-B...
The cover image, created by Faaria Khan and Dania Khan, is based on the Original article, The association between Ehlers-Danlos syndrome—hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study, by QASIM AZIZ et al., DOI 10.1111/nmo.12942.
Background:
Ano-rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM betwee...
Background:
Patients with Ehlers-Danlos syndrome-hypermobility type (EDS-HT) have increased prevalence of gastrointestinal (GI) symptoms, particularly reflux and dyspepsia. EDS-HT is associated with dysautonomia, psychopathology, and chronic pain which can be associated with GI symptoms. The association between GI symptoms and EDS-HT in a 'non-pat...
Background:
Evacuatory dysfunction (ED) is a common cause of constipation and may be sub-classified on the basis of specialist tests. Such tests may guide treatment e.g., biofeedback therapy for 'functional' defecatory disorders (FDD). However, there is no gold standard, and prior studies have not prospectively and systematically compared all test...
Background:
Fecal incontinence (FI) is a common and socially disabling condition with obstetric trauma considered the principal etiological factor. This study aimed to systematically evaluate symptom presentation and anorectal function in both females and males with FI.
Methods:
One hundred males (M) and 100 age-matched females (F) with FI prese...
Background:
Sacral neuromodulation (SNM) is a treatment option for intractable fecal incontinence. The mechanism of action is unclear, however, increasing evidence for afferent somatosensory effects exists. This study's aim was to elucidate effects of acute SNM on the cerebral cortex in a rodent model of pudendal nerve injury.
Methods:
The effec...
Background:
Chronic intestinal pseudo-obstruction (CIPO) is characterized by dilatation of the bowel lumen and abnormal motility. In this study, we aimed to quantify small bowel dysmotility in CIPO using a validated pan-intestinal motility assessment technique based on motion capture magnetic resonance imaging (MRI) compared to normal controls. In...
Background:
Sacral nerve stimulation has become a first line treatment for fecal incontinence, however, its effect on the motor function of the anorectum is uncertain. The aim of this study was to apply acute lumbosacral nerve stimulation in an animal model and to determine its effect on the external and internal anal sphincter forces, the rectoan...
Background:
Normal defaecation involves activation of anorectal mechanoreceptors responsive to pressure and stretch. The aim of this study was to develop selective anal and rectal mucosal light-touch stimulation suitable for measurement of cortical evoked potentials (EPs) in order to explore the sensory arm of these pathways.
New method:
A novel...
Introduction The most widely-used validated questionnaires for assessing constipation are the Patient Assessment of Constipation Symptoms (PAC-SYM) and the Cleveland Clinic Constipation Score (CCCS). We aimed to assess patients’ reported symptoms of constipation, preferred terminology, and quality of life (QoL) issues, and whether these are reflect...
Introduction Percutaneous Tibial Nerve Stimulation (PTNS) is a relatively new ambulatory therapy for faecal incontinence. Case series data suggest beneficial outcomes in 50–80% patients however the effectiveness of PTNS vs. sham has not been trialled. We aimed to assess the short-term efficacy of PTNS compared to sham electrical stimulation in adul...
Introduction Preoperative chemoradiotherapy may impair anorectal functions. Its effect on neuromuscular functions was investigated in human rectum ex-vivo.
Method Following informed consent, 3 groups of patients undergoing surgery for anorectal cancer were studied: 13 patients treated by surgery alone (Group I); 13 with long course neoadjuvant chem...
AimSacral nerve stimulation (SNS) may be offered to patients with constipation who have failed to improve with conservative treatment. The response to SNS is variable with a significant loss of efficacy in some patients. An increased frequency of stimulation may improve the efficacy of SNS for faecal incontinence. This study aimed to see if alterat...
Background
The overlap of unexplained gastrointestinal (GI) and somatic symptoms is well established in patients with functional gastrointestinal disorders (FGID). Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder associated with GI and somatic symptoms. We aimed to determine whether there is an association between...
The enzyme guanosine triphosphate-cyclohydrolase-1 (GCH-1) is a rate limiting step in the de novo synthesis of tetrahydrobiopterin (BH4) a co-factor in monoamine synthesis and nitric oxide production. GCH-1 is strongly implicated in chronic pain based on data generated using the selective GCH-1 inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP), and...
Background
Sacral nerve stimulation (SNS) has proven short- to medium-term effectiveness for the treatment of faecal incontinence (FI); fewer long-term outcomes have been presented and usually in small series. Here, the long-term effectiveness of SNS was evaluated in a large European cohort of patients with a minimum of 5 years' follow-up.Methods
P...
Background
Sacral nerve stimulation (SNS) is a well established therapy for faecal incontinence (FI). Percutaneous tibial nerve stimulation (PTNS) is a newer, less invasive, treatment. The effectiveness and acceptability of these treatments have not been compared systematically.Methods
An investigator-blinded randomized pilot trial of PTNS versus S...
Introduction
Although sacral neuromodulation (SNM) is an established treatment for faecal incontinence, stimulation parameters have been derived empirically and only one frequency (14 Hz) is employed clinically. The aim of this study was to test a range of stimulation frequencies to establish an optimal frequency of SNM for maximum augmentation of...
Background
Sacral nerve stimulation (SNS) is now well established as a treatment for fecal incontinence (FI) resistant to conservative measures and may also have utility in the management of chronic constipation; however, mechanism of action is not fully understood. End organ effects of SNS have been studied in both clinical and experimental settin...
Introduction Current diagnostic tests for GORD have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an “office-based” method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in a large cohort of healthy asymptomatic subjects and to deter...
Introduction The Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder with a prevalence of 20%. It is characterised by joint hypermobility,chronic pain, fibromyalgia (FM) and dysautonomia. Gastrointestinal (GI) symptoms e.g., dyspepsia, reflux, bloating and constipation are present in up to 80% of affected individuals...
Two forms of tibial nerve stimulation are used to treat faecal incontinence (FI): percutaneous (PTNS) and transcutaneous (TTNS) tibial nerve stimulation. This article critically appraises the literature on both procedures.
A systematic review was performed adhering to the PRISMA framework. A comprehensive literature search was conducted, with syste...
Background
High-resolution anorectal manometry (HRAM) is a relatively new method for collection and interpretation of data relevant to sphincteric function, and for the first time allows a global appreciation of the anorectum as a functional unit. Historically, traditional anal manometry has been plagued by lack of standardization and healthy volun...
Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects.
20 Rome III defined FCP patients (nine m...
Over the past 18 years neuromodulation therapies have gained support as treatments for faecal incontinence (FI); sacral nerve stimulation (SNS) is the most established of these. A systematic review was performed of current evidence regarding the clinical effectiveness of neuromodulation treatments for FI.
The review adhered to the PRISMA framework....
Cholinesterase inhibitors such as neostigmine are used for acute colonic pseudo-obstruction, but cardio-bronchial side-effects limit use. To minimise side-effects, lower doses could be combined with a 5-HT4 receptor agonist, which also facilitates intestinal cholinergic activity. However, safety concerns, especially in the elderly, require drugs wi...
Introduction The joint hypermobility syndrome (JHS) is a common non-inflammatory connective tissue disorder characterised by joint hyperflexibility and skin hyperelasticity. A validated 5 point hypermobility questionnaire screens for the presence or absence of JHS; formal diagnosis requires fulfilment of the Brighton criteria. Previous small cohort...
Introduction Functional Gastrointestinal Disorders (FGID) are common, but their cause is unknown. Joint hypermobility syndrome (JHS) is a common non-inflammatory connective tissue disorder characterised by joint hyperflexibility. It is associated with gastrointestinal (GI) symptoms (1), in particular unexplained symptoms (2). The association betwee...
Introduction Faecal incontinence and urgency are well-recognised sequelae of obstetric injury, however there is a paucity of literature describing the co-existence of symptoms of rectal evacuatory dysfunction (RED) and faecal incontinence (FI). This study aims to analyse and quantify these symptoms in patients referred for anorectal investigations...
Faecal incontinence (FI) and constipation occur following corrective surgery for anorectal malformations (ARMs) and in children or adults with chronic constipation without a structural birth anomaly (chronic idiopathic constipation, CIC). Such symptoms may have profound effects on quality of life (QoL). This study systematically determined the burd...
Background: Cases series suggest joint hypermobility (JH) is a risk factor for musculoskeletal pain in childhood, but this has not been
supported by epidemiological studies. However, the latter have largely comprised small samples, and prospective data based
on large cohorts are lacking. We aimed to exploit the Avon Longitudinal Study of Parents an...
to 197 days). 78% of patients responded to the questionnaire with 15 patients suffered from rectal prolapse and 7 patients ODS). Eight patients underwent LVMR following perineal repair, of these 1 reported recurrence of prolapse and faecal leakage. The mean score for CCCS and SMIS were compared pre and post-operatively. Both showed a reduction in s...
Autoantibodies directed against specific neuronal antigens are found in a significant number of patients with gastrointestinal neuromuscular diseases (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal antibodies in idiopathic GINMD and GINMD secondary to South American Trypanosomiasis. The GI distribution of voltage-g...
Conflicting data exist on the contributions of advancing age and childbirth on the structure and function of the anal sphincter. This study aimed to examine the relative contributions of age and childbirth in a large cohort of women referred for investigation of symptoms of colorectal dysfunction (fecal incontinence and constipation).
This study wa...
Acid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown.
To study the effects of pregabalin on development of secondary oesophageal hypersensitivity in...
Percutaneous tibial nerve stimulation (PTNS) is increasingly being used as a treatment for faecal incontinence (FI). The evidence for its efficacy is limited to a few studies involving small numbers of patients. The aim of the study was to assess the efficacy of PTNS in patients with urge, passive and mixed FI.
A prospective cohort of 100 patients...
Introduction Immunoreactive nerves and epithelial markers have been studied in the context of acid induced oesophageal hypersensitivity. Increase in immunoreactive TRPV1 nerves are associated with presence of oesophagitis1 2 as well as acid exposure time.3 ASIC3 was identified in epithelium of rat oesophagus and ASIC inhibitor (Amitidine) prevented...
IntroductionPatients with Functional Gastrointestinal Disorders (FGID) often display persistent and heightened pain sensitivity to experimental gut stimulation, a phenomenon known as Visceral Pain Hypersensitivity (VPH). Current management of pain in FGID involves the use of either antispasmodics or antidepressants; both are often unsatisfactory. T...
Sacral nerve stimulation (SNS) has become an established option in the management of defaecatory disorders. There are many data on the end-organ effects of SNS, but limited consensus on its mechanism of action. The objective of this review was to determine the effect of sacral nerve stimulation (SNS) on anorectal function.
Systematic literature rev...
Background Patients with gastrointestinal neuromuscular diseases may undergo operative procedures that yield tissue appropriate to diagnosis of underlying neuromuscular pathology. Critical to accurate diagnosis is the determination of limits of normality based on the study of control human tissues. Although robust diagnostic criteria exist for many...
Stomal complications are prevalent and associated with considerable morbidity. This study examined the incidence and potential risk factors for their development.
The time of onset and presence of ten specific complications were recorded for patients with an intestinal stoma over 10 years at two urban hospitals. A database was established with 20 e...
Introduction The ability of drugs to affect gastrointestinal (GI) motility may be predicted in vitro by studying how they modify changes in muscle tension evoked by motor nerve activation with electrical field stimulation (EFS). In human tissues, variations in types of response to EFS make the technique difficult unless only one type is studied, ig...
Introduction Oesophageal acid infusion in humans induces primary and secondary hyperalgesia due to peripheral and central sensitisation, respectively.1 Pregabalin is a centrally acting modulator of voltage-sensitive calcium channels which reduces neuropathic pain by attenuating the release of multiple neurotransmitters2 in the CNS. Its efficacy in...
