Ronan Oʼconnell | University College Dublin (original) (raw)

Papers by Ronan Oʼconnell

Indian Journal of Surgery

The Royal College of Surgeons in Ireland (RCSI) was founded primarily to advance the standards of... more The Royal College of Surgeons in Ireland (RCSI) was founded primarily to advance the standards of surgical training and surgical practice in Ireland. Over the course of almost 240 years, the College evolved as a comprehensive University of Medicine and Health Sciences, delivering education not only in Surgery but also in Medicine, Physiotherapy, Pharmacy and Nursing. RCSI today has a large global footprint and runs healthcare education programmes in several international locations. The College works in close collaboration with the other surgical Royal Colleges in Great Britain and the four colleges have a common surgical curriculum. RCSI recognises the increasing challenges facing traditional surgical training models and therefore has developed structured education programmes to support the conventional apprenticeship model. Surgical training in Ireland includes comprehensive training in both technical (operative) skills and non-technical (human factors) skills. RCSI is committed to...

Lynch syndrome is one of the most common cancer susceptibility syndromes. Individuals with Lynch ... more Lynch syndrome is one of the most common cancer susceptibility syndromes. Individuals with Lynch syndrome have a 50%-70% lifetime risk of colorectal cancer, 40%-60% risk of endometrial cancer, and increased risks of several other malignancies. It is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. In a subset of patients, Lynch syndrome is caused by 3' end deletions of the EPCAM gene, which can lead to epigenetic silencing of the closely linked MSH2. Relying solely on age and family history based criteria inaccurately identifies eligibility for Lynch syndrome screening or testing in 25%-70% of cases. There has been a steady increase in Lynch syndrome tumor screening programs since 2000 and institutions are rapidly adopting a universal screening approach to identify the patients that would benefit from genetic counseling and germline testing. These include microsatellite instability testing and/or immunohistochemical testing to identify tumor mismatch repair deficiencies. However, universal screening is not standard across institutions. Furthermore, variation exists regarding the optimum method for tracking and disclosing results. In this review, we summarize traditional screening criteria for Lynch syndrome, and discuss universal screening methods. International guidelines are necessary to standardize Lynch syndrome high-risk clinics.

Neurogastroenterology & Motility, 2020

ACE antegrade continence enema BET balloon expulsion test CC chronic constipation ED evacuation d... more ACE antegrade continence enema BET balloon expulsion test CC chronic constipation ED evacuation disorders FC functional constipation FDD functional defaecation disorders GI gastrointestinal GP general practitioners HR-ARM high-resolution anorectal manometry IBS-C irritable bowel syndrome with constipation MRI magnetic resonance imaging OIC opioid-induced constipation PRO patient-reported outcomes RH rectal hyposensitivity ROM radio-opaque markers SCFA short-chain fatty acids STC slow-transit constipation WMC wireless motility capsule ABSTRACT BACKGROUND Chronic constipation is a prevalent disorder that affects patients' quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009;21(Suppl.2)). This included seven articles, disseminating all themes covered during a preceding two-day meeting held in London, entitled 'Current perspectives in chronic constipation: a scientific and clinical symposium'. In October 2018, the 3 rd London Masterclass, entitled 'Contemporary management of constipation' was held, again over two days. All faculty 4 members were invited to author two new review articles representing a collective synthesis of talks presented and discussions held during this meeting. PURPOSE This article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology and investigation. Clearly not all aspects of the condition can be covered in adequate detail; hence, there is a focus on particular 'hot topics' and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioural, conservative, medical and surgical therapies. AUTHORS' CONTRIBUTIONS: SMS conceived the idea of these review articles. All authors performed the literature search and wrote the manuscript according to the section they were assigned: Introduction:

Clinical and Experimental Gastroenterology, 2018

The epithelial layer within the colon represents a physical barrier between the luminal contents ... more The epithelial layer within the colon represents a physical barrier between the luminal contents and its underlying mucosa. It plays a pivotal role in mucosal homeostasis, and both tolerance and anti-pathogenic immune responses. Identifying signals of inflammation initiation and responses to stimuli from within the epithelial layer is critical to understanding the molecular pathways underlying disease pathology. This study validated a method to isolate and analyze epithelial populations, enabling investigations of epithelial function and response in a variety of disease setting. Materials and methods: Epithelial cells were isolated from whole mucosal biopsies harvested from healthy controls and patients with active ulcerative colitis by calcium chelation. The purity of isolated cells was assessed by flow cytometry. The expression profiles of a panel of epithelial functional genes were investigated by reverse transcription-polymerase chain reaction (PCR) in isolated epithelial cells and corresponding mucosal biopsies. The expression profiles of isolated cells and corresponding mucosal biopsies were evaluated and compared between healthy and inflamed colonic tissue. Results: Flow cytometry identified 97% of cells isolated as intestinal epithelial cells (IECs). Comparisons of gene expression profiles between the mucosal biopsies and isolated IECs demonstrated clear differences in the gene expression signatures. Sixty percent of the examined genes showed contrasting trends of expression between sample types. Conclusion: The calcium chelation isolation method provided a reliable method for the isolation of a pure population of cells with preservation of epithelial cell-specific gene expression. This demonstrates the importance of sample choice when investigating functions directly affecting the colonic epithelial layer.

Mesentery and Peritoneum, 2019

The effect of extending the interval between the end of long-course chemoradiation and total meso... more The effect of extending the interval between the end of long-course chemoradiation and total mesorectal excision on pathological, surgical and oncologic outcomes in patients with rectal cancer: a systematic review and meta-analysis. Mesentery Peritoneum 2019;3:AB059.

Urology, Nov 24, 2016

Sacral neuromodulation (SNM) is a clinically-effective intervention for treatment of urinary and ... more Sacral neuromodulation (SNM) is a clinically-effective intervention for treatment of urinary and bowel disorders. The aim is to establish the hypothesis that there is a common mechanism of action for SNM in both systems. - Therapeutic parameters may be different for the two efficacy measures. - SNM invokes neural circuits that can be observed as neurochemical changes in specific neuroanatomical structures downstream from the therapy delivery site. - There are important central nervous system effects for both therapies. - Clinical observations regarding normal continence sensations as well as physiological measures of continence are different for both therapy areas.

PLOS ONE, 2015

Background Akkermansia muciniphila and Desulfovibrio spp. are commensal microbes colonising the m... more Background Akkermansia muciniphila and Desulfovibrio spp. are commensal microbes colonising the mucus gel layer of the colon. Both species have the capacity to utilise colonic mucin as a substrate. A. muciniphila degrades colonic mucin, while Desulfovibrio spp. metabolise the sulfate moiety of sulfated mucins. Altered abundances of these microorganisms have been reported in ulcerative colitis (UC). However their capacity to bind to human colonic mucin, and whether this binding capacity is affected by changes in mucin associated with UC, remain to be defined. Methods Mucin was isolated from resected colon from control patients undergoing resection for colonic cancer (n = 7) and patients undergoing resection for UC (n = 5). Isolated mucin was purified and printed onto mucin microarrays. Binding of reference strains and three clinical isolates of A. muciniphila and Desulfovibrio spp. to purified mucin was investigated. Results Both A. muciniphila and Desulfovibro spp. bound to mucin. The reference strain and all clinical isolates of A. muciniphila showed increased binding capacity for UC mucin (p < .005). The Desulfovibrio reference strain showed increased affinity for UC mucin. The mucin binding profiles of clinical isolates of Desulfovibrio spp. were specific to each isolate. Two

Health technology assessment (Winchester, England), 2015

Faecal incontinence (FI) is a common condition which is often under-reported. It is distressing f... more Faecal incontinence (FI) is a common condition which is often under-reported. It is distressing for those suffering from it, impacting heavily on their quality of life. When conservative strategies fail, treatment options are limited. Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive outpatient treatment, shown in preliminary case series to have significant effectiveness; however, no randomised controlled trial has been conducted. To assess the effectiveness of PTNS compared with sham electrical stimulation in the treatment of patients with FI in whom initial conservative strategies have failed. Multicentre, parallel-arm, double-blind randomised (1 : 1) controlled trial. Eighteen UK centres providing specialist nurse-led (or equivalent) treatment for pelvic floor disorders. Participants aged > 18 years with FI who have failed conservative treatments and whose symptoms are sufficiently severe to merit further intervention. PTNS was delivered via the Urgent(®) PC...

Genes, 2014

World Journal of Surgery, 2010

Background A pressing need exists to identify factors that predispose to recurrence after termina... more Background A pressing need exists to identify factors that predispose to recurrence after terminal ileal resection for Crohn's disease (CD) and to determine effective prophylactic strategies. This review presents an up-to-date summary of the literature in the field and points to a role for bacterial overproliferation in recurrence. Methods The literature (Medline, Embase, and the Cochrane Library, 1971-2009) on ileal CD and postoperative recurrence was searched, and 528 relevant articles were identified and reviewed. Results Smoking is a key independent risk factor for recurrence. NOD2/CARD15 polymorphisms and penetrating phenotype are associated with aggressive disease and higher reoperation rates. Age at diagnosis, disease duration, gender, and family history are inconsistent predictors of recurrence. Prophylactic 5-aminosalicylic acid therapy and nitromidazole antibiotics are beneficial. Combination therapies with immunosuppressants are also effective. Anti-TNFa-based regimens show benefit but the evidence base is small. Corticosteroid, interleukin-10, and probiotic therapies are not effective. Wider, stapled anastomotic configurations are associated with reduced recurrence rates. Strictureplasty and laparoscopic approaches have similar long-term recurrence rates to open resection techniques. Length of resection and presence of microscopic disease at resection margins do not influence recurrence. A lack of consensus exists regarding whether the presence of granulomas or plexitis affects outcome. Conclusions Current evidence points to defects in mucosal immunity and intestinal dysbiosis of either innate (NOD2/CARD15) or induced (smoking) origin in postoperative CD recurrence. Prophylactic strategies should aim to limit dysbiosis (antibiotics, side-to-side anastomoses) or prevent downstream chronic inflammatory sequelae (antiinflammatory, immunosuppressive, and immunomodulatory therapy).

PLoS ONE, 2013

Objective: The aims of this study were to develop techniques for spatial microbial assessment in ... more Objective: The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes. Design: A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota. Results: Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples. Conclusion: These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities.

International Journal of Gynecology & Obstetrics, 2010

Objective: To assess whether women who underwent forceps delivery were more likely than those who... more Objective: To assess whether women who underwent forceps delivery were more likely than those who delivered either normally (spontaneous vaginal delivery [SVD]) or by cesarean to experience deterioration in fecal continence as they aged. Methods: The study investigated fecal continence assessment among women who gave birth to their first child 10, 20, or 30 years previously. Women who had undergone forceps delivery in the selected years were matched with women who had SVD in the same year. Two additional cohorts (1 premenopausal, 1 postmenopausal), who had only ever delivered by pre-labor cesarean, were identified for comparison. Results: Of the 85 women who participated, 36 had undergone forceps delivery, 35 SVD, and 14 cesarean delivery only. The mode of vaginal delivery had no significant effect on continence scores or manometry pressures. Premenopausal women who had undergone cesarean delivery had significantly higher manometry pressures than those who delivered vaginally, but this protective effect was lost after the menopause. Multivariate analysis of pudendal nerve conduction found that the adverse effect of duration since delivery was greater than the adverse effect of forceps compared with vaginal delivery. Conclusion: Mode of delivery and aging affect pelvic floor function. Women who deliver via cesarean are not immune to age-related deterioration of anal sphincter function.

BJOG: An International Journal of Obstetrics and Gynaecology, 2002

Objective To assess the effects of delayed vs immediate pushing in second stage of labour with ep... more Objective To assess the effects of delayed vs immediate pushing in second stage of labour with epidural analgesia on delivery outcome, postpartum faecal continence and postpartum anal sphincter and pudendal nerve function. Design Prospective, randomised, controlled trial. Setting Tertiary referral maternity teaching hospital. Population One hundred and seventy nulliparous women randomised at full dilatation to immediate or delayed pushing. Methods A total of 178 nulliparous women, all with continuous epidural analgesia, were randomised at full cervical dilatation, but before the fetal head had reached the pelvic floor, to either immediate pushing or 1 hour delayed pushing. Labour outcome was analysed and all women underwent postpartum assessment of anal sphincter function, including anal manometry. Those women who had a normal delivery underwent neurophysiology studies, while those women who had an instrumental delivery underwent endoanal ultrasound. Main outcome measures Mode of delivery; altered faecal continence. Results Ninety women were randomised to immediate pushing and 88 to delayed pushing. The spontaneous delivery rate was 56% (50/90) in the immediate pushing group and 52% (46/88) in the delayed pushing group. Mean duration of labour for the immediate pushing group was 427 minutes compared with 480 minutes for the delayed pushing group (P ¼ 0.005). Eighty-four percent (76/90) of women in the immediate pushing group received oxytocin to augment labour, 21/76 (28%) in the second stage only. Eighty-one percent (71/88) of women in the delayed pushing group received oxytocin to augment labour, 22/71 (31%) in the second stage only. Fetal outcome did not differ between the two groups. Episiotomy rates were 73% and 69% in the immediate pushing and delayed pushing groups, respectively. 26% (23/90) of the immediate pushing group and 38% (33/88) of the delayed pushing group complained of altered faecal continence after delivery (NS). Manometry, ultrasound and neurophysiology studies did not differ significantly between the two groups. Overall, 55% of women after instrumental delivery had endosonographic evidence of damage to the external anal sphincter, while 36% of women after spontaneous delivery had abnormal neurophysiology studies. Conclusions Rates of instrumental delivery were similar following immediate and delayed pushing, in association with epidural analgesia. Delayed pushing prolonged labour by 1 hour but did not result in significantly higher rates of altered continence or anal sphincter injury, when compared with immediate pushing.

… OF DIABETES AND …, 2006

Vaginal delivery is associated with a significant risk of pelvic floor neuropathy and anal sphinc... more Vaginal delivery is associated with a significant risk of pelvic floor neuropathy and anal sphincter dysfunction. Because insulin-dependent diabetes mellitus (IDDM) predisposes to neuropathy, our aim was to determine the incidence of pudendal nerve dysfunction in a cohort of pregnant insulin-dependent diabetic patients and to examine the effect of vaginal delivery on pudendal nerve and anal sphincter function. Materials and Methods: The pudendal nerve was evaluated using electromyography of the anal sphincter (EMG) and clitoral anal reflex (CAR) assessment, during the third trimester in 16 pregnant insulin-dependent diabetic women. Upper limb neurological assessment included median motor, ulnar f-wave, median and ulnar sensory nerve and median transpalmar nerve conduction studies, while the lower limbs were assessed using tibial motor and f-wave studies. Anal manometry and endoanal ultrasound studies were also performed. Thirteen women underwent full reassessment at three months postpartum. Results: An increased sensory threshold (>9mA) on CAR was demonstrable antenatally in 5 women on the right and 8 on the left. Seven women showed prolonged distal latency (>42ms) on the right and in 8 on the left. Five women showed prolongation of median transpalmar nerve conduction studies (>2.2ms), which was associated with diabetes of greater than 12 years duration (p=0.029). The median squeeze pressure was 129mmHg and median resting pressure was 62mmHg. There were no significant changes in nerve conduction or anal manometric pressures postnatally. Discussion: Pregnant women with type 1 IDDM exhibit subtle changes of axonal neuropathy and demyelination, but we found no increased susceptibility to pudendal nerve injury during vaginal childbirth.

Archives of Surgery, 2009

Annals of Surgery, 2005

To assess the role of fibroblasts, transforming growth factor (TGF)-␤, and cell signal pathways i... more To assess the role of fibroblasts, transforming growth factor (TGF)-␤, and cell signal pathways in promoting fibrosis in Crohn's disease (CD). Summary Background Data: Intestinal strictures are a major source of morbidity in CD. Fibroblasts found at sites of stricture promote fibrogenesis. The mechanisms underlying this pro-fibrotic behavior remain elusive. Methods: Fibroblasts were isolated from strictured and macroscopically normal serosa in patients with CD and from normal serosa in patients with colorectal cancer. Whole cell connective tissue growth factor (CTGF) and fibronectin expression were determined by Western blot analysis. Fibroblast type I collagen expression was evaluated by real-time PCR, while fibroblast contractile activity was measured using fibroblast populated collagen lattices. Cells were stimulated with TGF-␤ 1 and inhibitors of the protein kinase C (PKC) and ERK 1/2 mitogen activated protein (MAP) kinase cell signaling pathways. Results: Stricture fibroblasts displayed enhanced constitutive expression of fibronectin. TGF-␤ promoted fibroblast CTGF, fibronectin, and type I collagen expression and enhanced fibroblast contractile activity. Inhibition of PKC reduced basal collagen expression and contractile activity in Crohn's fibroblasts and attenuated the effect of TGF-␤ on fibroblast CTGF, fibronectin, and collagen I expression as well as fibroblast contractility. ERK 1/2 inhibition had a similar effect on TGF-␤-induced CTGF and fibronectin expression. Conclusions: TGF-␤ is a critical pro-fibrotic growth factor in CD, and its effects are mediated via PKC and ERK 1/2 MAP kinase cell signaling. These pathways may represent novel therapeutic targets for patients with CD characterized by recurrent intestinal stricture formation.

American Journal of Physiology-Gastrointestinal and Liver Physiology, 2010

Fibroblasts represent the key cell type in fibrostenosing Crohn's disease (FCD) pathogenesis.... more Fibroblasts represent the key cell type in fibrostenosing Crohn's disease (FCD) pathogenesis. S100A4 is an EF-hand calcium-binding protein family member, implicated in epithelial-mesenchymal transition and as a marker of activated T lymphocytes and fibroblasts in chronic tissue remodeling. The aim of this study was to examine the expression profile of S100A4 in the resected ileum of patients with FCD. Mucosa, seromuscular explants, and transmural biopsies were harvested from diseased and proximal, macroscopically normal margins of ileocecal resections from patients with FCD. Samples were processed for histochemistry, immunohistochemistry, real-time RT-PCR, Western blotting, and transmission electron microscopy. Primary explant cultures of seromuscular fibroblasts were exposed to transforming growth factor (TGF)-β1 (1 ng/ml), and S100A4 expression and scratch wound-healing activity were assessed at 24 h. CCD-18Co fibroblasts were transfected with S100A4 small interfering RNA, tre...