56 results on '"O'Connell P. R."'
Search Results
2. Sacral nerve stimulation for faecal incontinence and constipation: a European consensus statement.
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Maeda, Y., O'Connell, P. R., Lehur, P.‐A., Matzel, K. E., and Laurberg, S.
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SACRAL nerves , *FECAL incontinence , *DEFECATION disorders , *CONSTIPATION , *INTESTINAL diseases , *PROCTOLOGY - Abstract
Aim In Europe during the last decade sacral nerve stimulation ( SNS) or sacral neuromodulation ( SNM) has been used to treat faecal incontinence ( FI) and constipation. Despite this, there is little consensus on baseline investigations, patient selection and operative technique. A modified Delphi process was conducted to seek consensus on the current practice of SNS/ SNM for FI and constipation. Method A systematic literature search of SNS for FI and constipation was conducted using PubMed. A set of questions derived from the search and expert opinion were answered on-line on two occasions by an international panel of specialists from Europe. A 1-day face-to-face meeting of the experts finalized the discussion. Results Three hundred and ninety-three articles were identified from the literature search, of which 147 fulfilled the inclusion criteria. Twenty-two specialists in FI and constipation from Europe participated. Agreement was achieved on 43 (86%) of 50 domains including the set-up of service, patient selection, baseline investigations, operative technique and programming of the device. The median of agreement was 95% (35-100%). Conclusion Consensus was achieved on the majority of domains of SNS/ SNM for FI and constipation. This should serve as a benchmark for safe and quality practice of SNS/ SNM in Europe. [ABSTRACT FROM AUTHOR]
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- 2015
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3. What should surgeons write?
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O’Connell, P. R.
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PHYSICIANS as authors , *SURGERY - Abstract
Focuses on possible articles to be written by surgeon writers in Great Britain. Review on surgical experiences of individuals; Innovations on surgical techniques; Discussion for a formulation of a surgically relevant hypothesis.
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- 2000
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4. Sacral nerve stimulation for constipation ( Br J Surg2013; 100: 174-181).
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O'Connell, P. R.
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SACRAL nerves , *CONSTIPATION , *COMPARATIVE studies , *NEURAL stimulation , *MEDICINE - Abstract
The article informs of the application of sacral nerve stimulation (SNS) for the treatment of patients with constipation resistant to conservative treatment. It also mentions SNS appears to be an effective treatment for constipation. It also emphasizes the need of comparative analysis of SNS with other available surgeries in the field of medicine.
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- 2013
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5. A European survey of bowel preparation in colorectal surgery.
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Devane, L. A., Proud, D., O'Connell, P. R., and Panis, Y.
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BOWEL preparation (Procedure) , *PROCTOLOGY , *META-analysis , *COLON surgery , *ANTIBIOTICS , *CHI-squared test - Abstract
Aim Meta-analysis has shown that mechanical bowel preparation ( MBP) does not improve outcomes in colonic surgery; however, there is uncertainty regarding MBP use in laparoscopic and rectal surgery and the addition of oral antibiotic regimens. The aim of this study was to assess current use of bowel preparation among European surgeons. Method An online survey was circulated to members of the European Society of Coloproctology. Chi-squared analysis was used to compare subgroups. Results A total of 426 surgeons responded to the survey. MBP is routinely prescribed by 29.6% of respondents prior to colonic surgery and in 77.0% prior to rectal surgery. In the cohort performing > 30% of colorectal operations laparoscopically ( n = 294), routine use of MBP in colonic surgery was significantly lower (19.7% vs 51.5%, P < 0.01). Less than 10% prescribe oral antibiotic bowel preparation whereas 96% prescribe perioperative intravenous antibiotics. Conclusion Among the majority of respondents to this survey, MBP is used routinely for rectal operations. For colonic surgery, laparoscopic surgeons have a significantly lower use of MBP. Use of oral antibiotic bowel preparation remains uncommon. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow-transit constipation ( Br J Surg 2012; 99: 1002-1010).
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O'Connell, P. R.
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CONSTIPATION , *NEURAL stimulation , *SACRAL nerves , *INTESTINAL diseases , *ELECTRIC stimulation - Abstract
The article discusses a study which evaluated the colonic motor response to subsensory and suprasensory sacral nerve stimulation (SNS) in patients with slow-transit constipation. Patients with confirmed slow-transit constipation who participated in the study were implanted with a temporary electrode transcutaneously in the S3 sacral nerve foramen. It found no motor response to subsensory stimulation compared with sham stimulation.
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- 2012
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7. Anal intraepithelial neoplasia: a single centre 19 year review.
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Cotter, M. B., Kelly, M. E., O'Connell, P. R., Hyland, J., Winter, D. C., Sheahan, K., and Gibbons, D.
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ANAL diseases , *DYSPLASIA , *IMMUNOHISTOCHEMISTRY , *EOSIN , *SQUAMOUS cell carcinoma - Abstract
Aim There is debate about whether the traditional three-tiered grading of anal intraepithelial neoplasia ( AIN) should be replaced by a more reproducible two-tiered system. In this study, we review our experience with AIN to determine the most suitable classification system. Method We performed a retrospective review of all histological reports over a 19 year period. All specimens were graded on haemataloxin and eosin appearance and those with dysplasia had immunohistochemistry for p16 and Ki67 performed. Results Cases included 25 condyloma acuminata, 11 dysplastic cases and 24 invasive squamous cell carcinomas. On review, 18 were classified as condyloma acuminata without dysplasia. Seven had AIN I, five had AIN II and six had AIN III when using a three-tiered system. All cases classified as dysplastic ( n = 18) showed an increased proliferation index as measured by Ki67. p16 positivity was seen in all AIN III, two AIN II and none of the AIN I cases. Recurrence was not observed in any of the AIN I cases. Five of eleven AIN II and AIN III cases recurred or persisted at a similar, higher or lower grade. Both of the AIN II cases which recurred or persisted were p16 positive. None of the AIN II cases that were p16 negative recurred. Three of the p16-positive AIN III cases did not recur. None of the 18 AIN cases progressed to carcinoma. Conclusion The findings support the slow progression of AIN as described in the literature. In our small series, a two-tiered system with further subclassification of the traditional AIN II group using p16 appears to be clinically useful. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Effect of injury on S1 dorsal root ganglia in an experimental model of neuropathic faecal incontinence.
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Peirce, C., O'Herlihy, C., O'Connell, P. R., and Jones, J. F. X.
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GANGLIA , *FECAL incontinence , *NEUROPATHY , *TRANSCRIPTION factors , *ALTERNATIVE medicine , *WOUNDS & injuries - Abstract
Background: An experimental model of neuropathic faecal incontinence has recently been established. This study aimed to quantify and compare the effect of crush and compression injury on first-order sensory neurones of the inferior rectal nerve (IRN) using a nuclear marker of axonal injury, activating transcription factor (ATF) 3. Methods: Eighteen Wistar rats were allocated to three groups: an unoperated control group, an IRN crush group (positive control) and a retrouterine balloon compression group. Five days after surgery, all animals were anaesthetized and perfused with fixative, and S1 dorsal root ganglia (DRG) were harvested. The tissue was sampled and neuronal nuclear ATF-3 expression calculated. Results: Estimated total S1 DRG ATF-3 nuclear labelling was higher in the nerve crush (median (interquartile range) 171 (60-824) cells) and balloon compression (59 (20-274) cells) groups, compared with that in the unoperated control group (9 (3-24) cells) (P = 0·001 and P = 0·008 respectively). In all groups, most neurones displaying the marker of injury were of the C-fibre class. Conclusion: This study confirmed the presence of axonal injury in a pelvic compression model of obstetric injury. C-fibre afferent pathways appeared to be most vulnerable. Neuromodulation may function through augmentation of residual C-fibre pathways. [ABSTRACT FROM AUTHOR]
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- 2011
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9. Ileal pouch-anal anastomosis.
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McGuire, B. B., Brannigan, A. E., and O'Connell, P. R.
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RESTORATIVE proctocolectomy , *COLON surgery , *COLITIS treatment , *ULCERATIVE colitis , *RECTAL surgery , *SURGICAL complications , *OPERATIVE surgery - Abstract
Background: Since 1977, restorative proctocolectomy with ileoanal anastomosis (IAA) has evolved into the surgical treatment of choice for most patients with intractable ulcerative colitis. Construction of an ileal pouch reservoir is now standard, usually in the form of a J pouch (IPAA). The aim of this report is to review selection criteria for, and functional outcomes, follow-up and management of complications of IPAA after 30 years of widespread clinical application. Methods and results: Literature published in English on the clinical indications, surgical technique, morbidity, complications and outcome following IAA and IPAA was sourced by electronic search, performed independently by two reviewers who selected potentially relevant papers based on title and abstract. Additional articles were identified by cross-referencing from papers retrieved in the initial search. Conclusion: The functional results of IPAA are good. Pouchitis, irritable pouch syndrome and cuffitis are specific long-term complications but rarely result in failure. Pouch salvage is possible in selected patients with poor functional outcomes. One-stage operations are increasingly performed. [ABSTRACT FROM AUTHOR]
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- 2007
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10. Does the angle of episiotomy affect the incidence of anal sphincter injury?
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Eogan, M., Daly, L., O'Connell, P. R., and O'Herlihy, C.
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EPISIOTOMY , *OBSTETRICS surgery , *TEARS (Body fluid) , *WOMEN'S hospitals - Abstract
Objective Mediolateral episiotomy is associated with lower rates of significant perineal tears than midline episiotomy. However, the relationship between precise angle of episiotomy from the perineal midline and risk of third-degree tear has not been established. This study quantifies this relationship. Design Case–control study. Setting National Maternity Hospital, Dublin, Ireland. Sample One hundred primiparous women who had undergone right mediolateral episiotomy 3 months previously. Methods Two groups of primiparous women were compared. Cases had sustained clinically apparent anal sphincter injury during delivery, while controls had not. The angle of episiotomy measured from the midline was marked on a superimposed sheet of transparent plastic film and measured using a protractor. Data were analysed using Student's t test, chi-square test and logistic regression analysis. Main outcome measures Angle of mediolateral episiotomy from the perineal midline. Results Fifty-four cases and 46 controls were assessed. Cases were more likely to have undergone assisted delivery and consequently to have been delivered by an obstetrician than by a midwife. The mean angle of episiotomy measured significantly smaller in cases (30°, 95% CI 28–32°) than in controls (38°, 95% CI 35–41°; P < 0.001). Analysis showed a 50% relative reduction in risk of sustaining third-degree tear for every 6° away from the perineal midline that an episiotomy was cut. Conclusions These results show that a larger angle of episiotomy is associated with a lower risk of third-degree tear and mediolateral episiotomy incisions should be made at as large an angle as possible to minimise the risk of sphincter disruption. [ABSTRACT FROM AUTHOR]
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- 2006
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11. Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.
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Ong, K., Bordeianou, L., Brunner, M., Buntzen, S., Collie, M.H.S., Hanly, A., Hunt, C. W., Matzel, K. E., O'Connell, P. R., Rydningen, M., Savitt, L., Totaro, A., Vaizey, C. J., and Maeda, Y.
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ANUS , *ARTIFICIAL sphincters , *SACRAL nerves , *SPHINCTERS , *NEURAL stimulation , *NEUROMODULATION - Abstract
Aim: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. Method: This was a multi‐centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow‐up of 5 years, complications and requirement for further interventions were recorded. Results: A total of 461 patients (median age 56 years, range 24–90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re‐siting or removal). At the time of last follow‐up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow‐up 32 patients (18.1%) crossed over to SNM. Comparing two 4‐year periods (2000–2003 and 2007–2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). Conclusion: The paradigm of surgical intervention for FI has changed with increasing use of SNM. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Clinicopathological features and oncological outcomes of patients with young‐onset rectal cancer.
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Zaborowski, A. M., Murphy, B., Creavin, B., Rogers, A. C., Kennelly, R., Hanly, A., Martin, S. T., O'Connell, P. R., Sheahan, K., and Winter, D. C.
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HEREDITARY nonpolyposis colorectal cancer , *RECTAL cancer , *SURGICAL excision , *AGE groups , *CHEMORADIOTHERAPY , *ADJUVANT treatment of cancer , *PROGRESSION-free survival - Abstract
Background: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. Methods: Disease‐specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. Results: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. Clinical stage did not differ between the two age groups. Patients aged less than 50 years were more likely to have microsatellite instability (9 versus 1·6 per cent; P = 0·003) and Lynch syndrome (7 versus 0 per cent; P < 0·001). Younger patients were also more likely to receive neoadjuvant chemoradiotherapy (67 versus 53·3 per cent; P = 0·003) and adjuvant chemotherapy (41 versus 24·2 per cent; P = 0·006). Five‐year overall survival was better in those under 50 years old (80 versus 72 per cent; P = 0·013). The 5‐year disease‐free survival rate was 81 per cent in both age groups (P = 0·711). There were no significant differences in the development of locoregional recurrence or distant metastases. Conclusion: Despite accessing more treatment, young patients have disease‐specific outcomes comparable to those of their older counterparts. [ABSTRACT FROM AUTHOR]
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- 2020
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13. Minimally invasive approaches to the management of anastomotic leakage following restorative rectal cancer resection.
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Creavin, B., Ryan, É. J., Kelly, M. E., Moynihan, A., Redmond, C. E., Ahern, D., Kennelly, R., Hanly, A., Martin, S. T., O'Connell, P. R., Brophy, D. P., and Winter, D. C.
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ONCOLOGIC surgery , *SURGICAL drainage , *PROGRESSION-free survival , *LEAKAGE , *DRAINAGE - Abstract
Aim: Management of anastomotic leakage (AL) following rectal resection has evolved with increasing use of less invasive techniques. The aim of this study was to review the management of AL following restorative rectal cancer resection in a tertiary referral centre. Method: A retrospective review of a prospectively maintained database was performed. The primary outcome was successful management of AL. The secondary outcome was the impact of AL on oncological outcome. Results: Five hundred and two restorative rectal cancer resections were performed during the study period. The incidence of AL was 9.9% (n = 50). AL occurred more commonly following neoadjuvant chemoradiotherapy (n = 31/252, 12.3%) than in those who did not receive neoadjuvant chemoradiotherapy (n = 19/250, 7.6%; P = 0.107); however, this was not statistically significant. Successful minimally invasive drainage was achieved in 28 patients (56%, radiological n = 24, surgical n = 4). Trans‐rectal drainage was the most common drainage method (n = 14). The median duration of drainage was longer in the neoadjuvant group (27 vs 18 days). Surgical intervention was required in 11 patients, with anastomotic takedown and end‐colostomy formation was most commonly required. Successful management of AL with drainage (maintenance of the anastomosis without the need for further intervention) was achieved in 26 of the 28 patients. There were no significant differences in overall or disease‐free survival when patients with AL were compared with patients without AL (69.4% vs 72.6%, P = 0.99 and 78.7% vs 71.3%, P = 0.45, respectively). Conclusion: In selected patients, AL following restorative rectal resection can be effectively controlled using minimally invasive radiological or surgical drainage without the need for further intervention. [ABSTRACT FROM AUTHOR]
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- 2019
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14. Meta‐analysis of the effect of extending the interval after long‐course chemoradiotherapy before surgery in locally advanced rectal cancer.
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Ryan, É. J., O'Sullivan, D. P., Kelly, M. E., Syed, A. Z., Neary, P. C., O'Connell, P. R., Kavanagh, D. O., Winter, D. C., and O'Riordan, J. M.
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RECTAL cancer , *CHEMORADIOTHERAPY , *META-analysis , *ODDS ratio , *SURGERY , *LYMPH nodes - Abstract
Background: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long‐course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6–8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. Methods: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8‐week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence‐free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta‐analysis was performed using the Mantel–Haenszel method. Results: Twenty‐six publications, including four RCTs, with 25 445 patients were identified. A minimum 8‐week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). Conclusion: A minimum 8‐week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence‐free survival without compromising surgical morbidity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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15. The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.
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Brown, S. R., Epstein, J. C., Soop, M., Evans, M. D., George, B. D., Guy, R. J., Hill, J., Limdi, J. K., O'Connell, P. R., Pinkney, T. D., Sagar, P. M., Singh, B., Terry, H., Fearnhead, N. S., Davies, R. J., Walsh, C. J., Williams, A. B., Williams, G. L., Faiz, O. D., and Clark, S. K.
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Aim: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. Methods: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. Results: All aspects of surgical care for IBD have been included along with 157 recommendations for management. Conclusion: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery. [ABSTRACT FROM AUTHOR]
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- 2018
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16. IntAct: intra‐operative fluorescence angiography to prevent anastomotic leak in rectal cancer surgery: a randomized controlled trial.
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Armstrong, G., Croft, J., Corrigan, N., Brown, J. M., Goh, V., Quirke, P., Hulme, C., Tolan, D., Kirby, A., Cahill, R., O'Connell, P. R., Miskovic, D., Coleman, M., and Jayne, D.
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RECTAL cancer , *CANCER patients , *ETIOLOGY of cancer , *LAPAROSCOPY , *HUMAN microbiota - Abstract
Abstract: Aim: Anastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, the rates of AL have remained static, at around 10–15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (indocyanine green) and near‐infrared laparoscopy can minimize the rate of AL leak compared with conventional white‐light laparoscopy. Two mechanistic sub‐studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies. Method: IntAct is a prospective, unblinded, parallel‐group, multicentre, European, randomized controlled trial comparing surgery with intra‐operative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end‐point is rate of clinical AL at 90 days following surgery. Secondary end‐points include all AL (clinical and radiological), change in planned anastomosis, complications and re‐interventions, use of stoma, cost‐effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over 3 years, 880 patients from 25 European centres will be recruited and followed up for 90 days. Discussion: IntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning. [ABSTRACT FROM AUTHOR]
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- 2018
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17. A systematic review examining quality of life following pelvic exenteration for locally advanced and recurrent rectal cancer.
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Rausa, E., Kelly, M. E., Bonavina, L., O'Connell, P. R., and Winter, D. C.
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RECTAL cancer diagnosis , *RECTAL cancer patients , *QUALITY of life , *EXENTERATION , *TUMORS - Abstract
Aim Pelvic exenteration is a complex surgical procedure associated with considerable morbidity. Quality of life (QoL) is a crucial metric of surgical outcome. The aim of this review was to assess the QoL following pelvic exenteration for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC). Method A comprehensive search of studies published between 2000 and 2016 that examined QoL outcome following pelvic exenteration was performed. Functional Assessment of Cancer Therapy - Colorectal (FACT-C), SF-36 version 2, European Organization for Research and Treatment of Cancer QLQ-C30, and Brief Pain Inventory assessments from these studies were reviewed. Results Seven studies reporting on 382 patients were included. Baseline QoL was the strongest predictor of postoperative QoL. Female gender, total pelvic exenteration with or without bone resection, and positive surgical margins were associated with a reduced QoL. In the majority of patients, QoL gradually improved between 2 and 9 months post-operation. Conclusion QoL is an important patient-reported outcome. This review highlights factors associated with reduced postoperative QoL that should be borne in mind when surgical resection is being considered. [ABSTRACT FROM AUTHOR]
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- 2017
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18. Altered defaecatory behaviour and faecal incontinence in a video-tracked animal model of pudendal neuropathy.
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Devane, L. A., Lucking, E., Evers, J., Buffini, M., Scott, S. M., Knowles, C. H., O'Connell, P. R., and Jones, J. F. X.
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FECAL incontinence , *PUDENDAL nerve , *LABORATORY rats , *COLOSTOMY , *DEFECATION disorders - Abstract
Aim The aim was to develop a behavioural animal model of faecal continence and assess the effect of retro-uterine balloon inflation ( RBI) injury. RBI in the rat causes pudendal neuropathy, a risk factor for obstetric related faecal incontinence in humans. Method Video-tracking of healthy rats ( n = 12) in a cage containing a latrine box was used to monitor their defaecatory behaviour index ( DBI) over 2 weeks. The DBI (range 0-1) was devised by dividing the defaecation rate (pellets per hour) outside the latrine by that of the whole cage. A score of 0 indicates all pellets were deposited in the latrine. Subsequently, the effects of RBI ( n = 19), sham surgery ( n = 4) and colostomy ( n = 2) were determined by monitoring the DBI for 2 weeks preoperatively and 3 weeks postoperatively. Results The DBI for healthy rats was 0.1 ± 0.03 with no significant change over 2 weeks ( P = 0.71). In the RBI group, 13 of 19 rats (68%) showed no significant change in DBI postoperatively (0.08 ± −0.05 vs 0.11 ± −0.07) while in six rats the DBI increased from 0.16 ± −0.09 to 0.46 ± 0.23. The negative control, sham surgery, did not significantly affect the DBI (0.09 ± 0.06 vs 0.08 ± 0.04, P = 0.14). The positive control, colostomy, increased the DBI from 0.26 ± 0.03 to 0.86 ± 0.08. Conclusions This is the first study showing a quantifiable change in defaecatory behaviour following injury in an animal model. This model of pudendal neuropathy affects continence in 32% of rats and provides a basis for research on interventions for incontinence. [ABSTRACT FROM AUTHOR]
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- 2017
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19. The lymph node ratio does not provide additional prognostic information compared with the N1/N2 classification in Stage III colon cancer.
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Mohan, H. M., Walsh, C., Kennelly, R., Ng, C. H., O'Connell, P. R., Hyland, J. M., Hanly, A., Martin, S., Gibbons, D., Sheahan, K., and Winter, D. C.
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COLON cancer treatment , *LYMPH nodes , *TUMOR classification , *COLON cancer patients , *CANCER-related mortality - Abstract
Aim The ratio of positive nodes to total nodes, the lymph node ratio ( LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer. Method Patients with Stage III colon cancer were identified from a prospectively maintained database (1996-2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut-off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000-fold was performed. This was then repeated for disease-specific survival. Results The specificity and sensitivity of the N1/N2 classification in predicting 3-year overall survival in this cohort ( n = 402) was 62.2% and 52.1%, respectively. The cut-off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease-specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44). Conclusion Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease-specific survival for a given cut-off point. [ABSTRACT FROM AUTHOR]
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- 2017
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20. Organ preservation with local excision or active surveillance following chemoradiotherapy for rectal cancer.
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Creavin, B, Ryan, E, Martin, S T, Hanly, A, O'Connell, P R, Sheahan, K, and Winter, D C
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Background: Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality, and to improve functional outcome.Methods: Locally advanced non-metastatic rectal cancers were identified from a prospective database. Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy (CRT) (50-54 Gy and 5-fluorouracil), and were reassessed 6-8 weeks post treatment. An active surveillance programme ('watch and wait') was offered to patients who were found to have a complete endoluminal response. Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm. Patients were followed up clinically, endoscopically and radiologically to assess for local recurrence or disease progression.Results: Of 785 patients with rectal cancer between 2005 and 2015, 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT. Sixty out of three hundred and sixty-two (16.5%) patients were treated with organ-preserving strategies - 10 with 'watch and wait' and 50 by transanal excision. Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings. There was no significant difference in overall survival (85.6% vs 93.3%, P=0.414) or disease-free survival rate (78.3% vs 80%, P=0.846) when the outcomes of radical surgery were compared with organ preservation. Tumour regrowth occurred in 4 out of 45 (8.9%) patients who had organ preservation.Conclusions: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT. Transanal excision defines the pathological response and refines decision-making. [ABSTRACT FROM AUTHOR]- Published
- 2017
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21. A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery.
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Vallance, A., Wexner, S., Berho, M., Cahill, R., Coleman, M., Haboubi, N., Heald, R. J., Kennedy, R. H., Moran, B., Mortensen, N., Motson, R. W., Novell, R., O'Connell, P. R., Ris, F., Rockall, T., Senapati, A., Windsor, A., and Jayne, D. G.
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PROCTOLOGY , *DISEASE incidence , *MEDICAL care , *HUMAN microbiota , *ROUTINE diagnostic tests , *HEALTH outcome assessment - Abstract
The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed. [ABSTRACT FROM AUTHOR]
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- 2017
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22. Reversal of sensory deficit through sacral neuromodulation in an animal model of fecal incontinence.
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Evers, J., Devane, L., Carrington, E. V., Scott, S. M., Knowles, C. H., O'Connell, P. R., and Jones, J. F. X.
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TREATMENT of fecal incontinence , *SACRAL nerves , *ELECTRIC stimulation , *ANIMAL models in research , *PUDENDAL nerve , *BRAIN physiology , *CEREBRAL cortex - Abstract
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 effects of 14 Hz and 2 Hz SNM on sensory cortical activation were studied. In 32 anesthetized rats, anal canal evoked potentials ( EPs) were recorded over the primary somatosensory cortex. Pudendal nerve injury was produced by 1-hour inflation of two intra-pelvic balloons. Four groups were studied: balloon injury, balloon injury plus either 14 Hz or 2 Hz SNM, sham operation. Immunohistochemistry for the neural plasticity marker polysialylated neural cell adhesion molecule ( PSA- NCAM) positive cells (numerical density and location) in the somatosensory cortex was performed. Key Results Anal EP amplitudes diminished during balloon inflation; 14 Hz SNM restored diminished anal EPs to initial levels and 2 Hz SNM to above initial levels. Evoked potential latencies were prolonged during balloon inflation. The numerical density of PSA- NCAM positive cells increased in the SNM groups, but not in sham or balloon injury without SNM. Stimulated cortices showed clusters of PSA- NCAM positive cells in layers II, IV, and V. Post SNM changes were similar in both SNM groups. Conclusions & Inferences Sacral neuromodulation augments anal representation in the sensory cortex and restores afferent pathways following injury. PSA- NCAM positive cell density is increased in stimulated cortices and positive cells are clustered in layers II, IV, and V. [ABSTRACT FROM AUTHOR]
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- 2016
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23. Does anal sphincter injury preclude subsequent vaginal delivery?
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Fitzpatrick, M., Cassidy, M., Barassaud, M.L., Hehir, M.P., Hanly, A.M., O’Connell, P.R., O’Herlihy, C., O'Connell, P R, and O'Herlihy, C
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SPHINCTERS , *DELIVERY (Obstetrics) , *SYMPTOMS , *ULTRASONIC imaging , *CESAREAN section , *LONGITUDINAL method , *FOLLOW-up studies (Medicine) , *WOUNDS & injuries , *COMPLICATIONS of birth injuries , *ANUS , *BIRTH injuries , *FECAL incontinence , *LABOR (Obstetrics) , *LABOR complications (Obstetrics) - Abstract
Objective: To assess continence and anal sphincter integrity during a subsequent pregnancy and delivery in women known to have a previous anal sphincter injury.Design: Prospective observational study.Setting: The National Maternity Hospital, Dublin, Ireland.Population: Antenatal patients with a documented obstetric anal sphincter injury at a previous delivery.Methods: Women underwent symptom scoring, endoanal ultrasound and manometry.Main Outcome Measures: Recommended and actual mode of delivery, continence scores and endoanal ultrasound findings after index delivery.Results: 557 women were studied. 293 (53%) had no symptoms of faecal incontinence, 189 (34%) had mild symptoms and 75 (13%) moderate or severe symptoms. 408 (73%) had an endoanal ultrasound. 383(94%) had a normal or small (<1 quadrant) defect in the internal anal sphincter and 390 (96%) had a scar or small (<1e quadrant) defect in the external anal sphincter. 393 (70%) delivered vaginally. 164 (30%) were delivered by caesarean section. 197/557 (35%) returned for follow-up. There was no significant change in continence following either vaginal or caesarean delivery. 20 (5.1%) women had a recognised second anal sphincter tear during vaginal delivery.Conclusions: The majority of women who sustain a third degree tear have minimal or no symptoms of faecal incontinence when assessed antenatally in a subsequent pregnancy. 70% go on to have a vaginal delivery, with little impact on faecal continence. These findings provide reassurance for patients and clinicians about the safety of vaginal delivery following anal sphincter injury in appropriately selected patients. [ABSTRACT FROM AUTHOR]- Published
- 2016
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24. Balloon tamponade to control haemorrhage following transanal rectal surgery.
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McGuinness, J., Winter, D. C., and O'Connell, P. R.
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SURGICAL instruments , *HEMORRHAGE , *RECTAL surgery , *HEMOSTASIS ,ANAL surgery - Abstract
Background. Bleeding following transanal rectal surgery can be difficult to manage. Case. We report a case where a Minnesota tube was used to achieve haemostasis in a patient with severe bleeding after transanal excision of a large dysplastic polyp. [ABSTRACT FROM AUTHOR]
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- 2004
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25. A systematic review of sacral nerve stimulation mechanisms in the treatment of fecal incontinence and constipation.
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Carrington, E. V., Evers, J., Grossi, U., Dinning, P. G., Scott, S. M., O'Connell, P. R., Jones, J. F. X., and Knowles, C. H.
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TREATMENT of fecal incontinence , *CONSTIPATION , *THERAPEUTICS , *NEURAL stimulation , *SACRAL nerves , *DISEASE management , *DEFECATION disorders , *ANIMAL models in research - Abstract
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 settings, but interpretation is difficult due to the multitude of techniques used and heterogeneity of reported findings. The aim of this study was to systematically review available evidence on the mechanisms of SNS in the treatment of FI and constipation. Methods Two systematic reviews of the literature (performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses framework) were performed to identify manuscripts pertaining to (a) clinical and (b) physiological effects of SNS during the management of hindgut dysfunction. Key Results The clinical literature search revealed 161 articles, of which 53 were deemed suitable for analysis. The experimental literature search revealed 43 articles, of which nine were deemed suitable for analysis. These studies reported results of investigative techniques examining changes in cortical, gastrointestinal, colonic, rectal, and anal function. Conclusions & Inferences The initial hypothesis that the mechanism of SNS was primarily peripheral motor neurostimulation is not supported by the majority of recent studies. Due to the large body of evidence demonstrating effects outside of the anorectum, it appears likely that the influence of SNS on anorectal function occurs at a pelvic afferent or central level. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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26. Effects of stimulation frequency and intensity in sacral neuromodulation on anorectal inputs to the somatosensory cortex in an experimental model.
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Evers, J., Devane, L., Carrington, E. V., Scott, S. M., Knowles, C. H., O'Connell, P. R., and Jones, J. F. X.
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FECAL incontinence , *EVOKED potentials (Electrophysiology) , *SOMATOSENSORY evoked potentials , *PUBLIC health , *MEDICAL care - Abstract
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 anal canal cortical evoked potentials ( EPs) in an animal model. Methods In female Wistar rats, anal canal EPs were recorded over the primary somatosensory cortex using a flexible multielectrode array, and the effect of SNM was studied. SNM was applied at 0·1-100 Hz and a frequency response curve plotted. The data were fitted to a quadratic equation. Results The magnitude of potentiation of anal canal EPs caused by SNM depended significantly on stimulation frequency ( P < 0·001). The frequency-potentiation relationship was parabolic in form, with a clear optimum at 2 Hz. The SNM must be applied for at least 3 min. The theoretical maximal potentiation predicted by the model was not found to be statistically different to actual data recorded ( P = 0·514-0·814). The response depended on stimulation amplitude in an 'all-or-nothing' fashion. EPs were augmented when the SNM intensity was 0·5 times the motor threshold to tail twitch or greater, but values below this intensity failed to affect the EPs. Conclusion The effect of SNM in this animal model is governed principally by frequency, with an optimum of 2 Hz. If animal data can be translated to humans, optimization of SNM frequency may offer a clinically relevant improvement in the efficacy of SNM. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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27. Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive.
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O'Toole, A, Michielsen, A J, Nolan, B, Tosetto, M, Sheahan, K, Mulcahy, H E, Winter, D C, Hyland, J M, O'Connell, P R, Fennelly, D, O'Donoghue, D, O'Sullivan, J, Doherty, G A, and Ryan, E J
- Abstract
Background: Tumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs.Methods: Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA.Results: TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs.Conclusion: Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC. [ABSTRACT FROM AUTHOR]- Published
- 2014
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28. Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive.
- Author
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O'Toole, A, Michielsen, A J, Nolan, B, Tosetto, M, Sheahan, K, Mulcahy, H E, Winter, D C, Hyland, J M, O'Connell, P R, Fennelly, D, O'Donoghue, D, O'Sullivan, J, Doherty, G A, and Ryan, E J
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COLON cancer diagnosis , *COLON cancer patients , *IMMUNOSUPPRESSION , *DENDRITIC cells , *CANCER invasiveness , *LIPOPOLYSACCHARIDES - Abstract
BackgroundTumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs.Methods:Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA.Results:TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs.Conclusion:Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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29. Correlations between colonic crypt mucin chemotype, inflammatory grade and Desulfovibrio species in ulcerative colitis.
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Lennon, G., Balfe, Á., Bambury, N., Lavelle, A., Maguire, A., Docherty, N. G., Coffey, J. C., Winter, D. C., Sheahan, K., and O'Connell, P. R.
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MUCINS , *DESULFOVIBRIO , *ULCERATIVE colitis , *BLUE stain , *POLYMERASE chain reaction , *HYDROGEN sulfide - Abstract
Aim The colonic mucus gel layer is composed of mucins that may be sulphated or sialyated. Sulphated mucins predominate in health while in ulcerative colitis ( UC) sulphation is reduced. These differences result directly from inflammatory events. It may also be hypothesized that they arise in part from alterations in the colonic microbiota, particularly changes in the burden of sulphated mucin-metabolizing species, such as Desulfovibrio ( DSV) bacteria. The aim of this study was to correlate colonic mucin chemotypes and inflammatory scores in health and UC and relate these changes to changes in the colonization of colonic crypts by DSV. Method Paired colonic biopsies from 34 healthy controls ( HC) and 19 patients with active UC were collected for the purpose of parallel histological and microbiological assessment. High-iron diamine and Alcian blue staining and haematoxylin and eosin of mucosal biopsy specimens were used to assess histological changes within the clinical spectrum of UC. Quantitative real-time polymerase chain reaction analysis was employed to determine the total and DSV copy number within the colonic crypts. Results Compared with HC, the mucin chemotype in UC was less sulphated and inversely correlated with the degree of mucosal inflammation. A weak but significant negative correlation was found between the abundance of sulphated mucins and DSV burden. Conclusion Mucin composition strongly correlates with the degree of mucosal inflammation, and to a lesser extent with DSV burden. These data suggest that mucin chemotype and DSV burden are linked phenomena and highlight the need to consider changes in mucin chemotype in the setting of microbial dysbiosis occurring within the colitic colon. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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30. Circulating fibrocytes and Crohn's disease.
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Sahebally, S. M., Burke, J. P., Chang, K. H., Kiernan, M. G., O'Connell, P. R., and Coffey, J. C.
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FIBROBLASTS , *CROHN'S disease , *DISEASE relapse , *PATHOLOGICAL physiology , *EXTRACELLULAR matrix proteins , *FIBROSIS , *CELL differentiation - Abstract
Background Despite advances in medical therapy, there remains no effective preventive or non-surgical therapeutic option for fibrostenotic Crohn's disease ( CD). Symptomatic recurrences are common, necessitating reintervention. Intestinal fibroblasts mediate stricture formation, but their exact source is unclear. Recent evidence indicates that circulating fibrocytes drive fibrosis through differentiation into fibroblasts and the production of extracellular matrix proteins. The aim of this review is to describe current understanding of the pathophysiology underlying fibrosis in CD, the cellular and molecular biology of fibrocytes and their role in CD. Methods The electronic literature (January 1972 to December 2012) on 'circulating fibrocytes' and 'Crohn's fibrosis' was reviewed. Results Circulating fibrocytes appear universally involved in organ fibrosis. A complex array of cytokines, chemokines and growth factors regulate fibrocyte biology, and these are associated with fibrogenesis in CD. The cytokines transforming growth factor β1, connective tissue growth factor and interleukin 13, overexpressed in the strictured Crohn's intestine, promote fibrocyte generation and/or differentiation. Conclusion Levels of circulating fibrocytes are raised in conditions marked by exaggerated fibrosis. These and other observations prompt a characterization of fibrocyte activity in CD with a view to investigating a pathogenic role. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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31. Is there a nitrergic modulation of the rat external anal sphincter?
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Evers, J., Buffini, M., Craven, S., O’Connell, P. R., and Jones, J. F. X.
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ANUS , *NITRIC oxide , *STRIATED muscle , *NERVE fibers , *NEURAL transmission - Abstract
Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter (EAS) is unknown. The aim of this study was to investigate whether there is a nitrergic nerve plexus that modulates the EAS, similar to that found in oesophageal striated muscle. An in vitro ring preparation of rat anal canal was used to evaluate the effects of the nitric oxide synthase inhibitor Nω-nitro- l-arginine ( l-NNA) and the NO donor sodium nitroprusside (SNP) on the EAS in conditions of neuromuscular blockade and the effect of SNP on nerve-evoked contractions. Immunohistological experiments were conducted to determine whether the neuronal isoform of nitric oxide synthase (nNOS) is present in the EAS. During direct muscle stimulation neither l-NNA ( P= 0.32) nor SNP ( P= 0.19) significantly changed the EF50, which is the frequency at which 50% of maximal contraction is reached, compared with a time-dependent control. Nerve-evoked contractions were also not altered by addition of SNP to the tissue bath. Immunohistohistological experiments clearly showed co-localization of nNOS-positive nerve fibres at motor endplates of the oesophagus but not in the EAS. The internal anal sphincter was richly innervated by nitrergic fibres, but these did not extend into the EAS. In conclusion, there are no nitrergic motor fibres innervating the EAS, neurotransmission at the motor endplates is not affected by NO, and NO does not affect muscle force directly in conditions of neuromuscular blockade. There is, therefore, no evidence that EAS contraction is directly modulated by NO or by pudendal nitrergic fibres or diffusion from neighbouring nitrergic plexuses of the anal canal. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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32. Authors' reply: Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts (Br J Surg 2010; 97: 1126-1134).
- Author
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Burke, J. P., Coffey, J. C., and O'Connell, P. R.
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LETTERS to the editor , *ENDOTOXINS , *FIBROBLASTS - Abstract
A response by J. P. Burke, J. C. Coffey and P. R. O'Connell to a letter to the editor about their study "Bacterial Lipopolysaccharide Promote Profibriotic Activation of Intestinal Fibroblasts," which appeared in a 2010 issue of the "British Journal of Surgery," is presented.
- Published
- 2010
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33. Letter to the editor.
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Joyce, M. R., Ryan, J. D., and O’Connell, P. R.
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LETTERS to the editor , *ANATOMICAL organ diseases - Abstract
A letter to the editor is presented which focuses on the definition of professor Oliver Armstrong regarding relevant anatomy of the canal of Nuck and its clinical correlation.
- Published
- 2010
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34. The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy.
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Smith, F. M., Chang, K. H., Sheahan, K., Hyland, J., O'Connell, P. R., and Winter, D. C.
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RECTAL cancer , *RADIOTHERAPY , *CANCER patients , *CANCER treatment , *LYMPH node diseases - Abstract
Background: Local excision of rectal cancer after neoadjuvant chemoradiotherapy (CRT) has been proposed as an alternative to radical surgery in selected patients. However, little is known about the significance of the morphological and histological features of residual tumour. Methods: Patients who had undergone CRT at the authors' institution between 1997 and 2010 were identified. Multiple features were assessed as putative markers of pathological response. These included: gross residual disease, diameter of residual mucosal abnormalities, tumour differentiation, presence of lymphovascular/perineural invasion and lymph node ratio. Results: Data from 220 of 276 patients were suitable for analysis. Diameter of residual mucosal abnormalities correlated strongly with pathological tumour category after CRT (ypT) ( P < 0·001). Forty of 42 tumours downstaged to ypT0/1 had residual mucosal abnormalities of 2·99 cm or less after CRT. Importantly, 19 of 31 patients with a complete pathological response had evidence of a residual mucosal abnormality consistent with an incomplete clinical response. The ypT category was associated with both pathological node status after CRT ( P < 0·001) and lymph node ratio ( P < 0·001). Positive nodes were found in only one of 42 patients downstaged to ypT0/1. The risk of nodal metastases was associated with poor differentiation ( P = 0·027) and lymphovascular invasion ( P < 0·001). Conclusion: In this series, the majority of patients with a complete pathological response did not have a complete clinical response. In tumours downstaged to ypT0/1 after CRT, residual mucosal abnormalities were predominantly small and had a 2 per cent risk of positive nodes, thus potentially facilitating transanal excision. The presence of adverse histological characteristics risk stratified tumours for nodal metastases. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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35. Comparison of the motor discharge to the voluntary sphincters of continence in the rat.
- Author
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Buffini, M., O'Halloran, K. D., O'Herlihy, C., O'Connell, P. R., and Jones, J. F. X.
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ANUS , *URETHRA diseases , *ELECTROMYOGRAPHY , *MYOSIN , *URINATION - Abstract
Background The rat external anal sphincter (EAS) and external urethral sphincter (EUS) are voluntary muscles of continence that can display similar synchronous electromyographic (EMG) activity patterns. However, the two sphincters are quite different in structure and function. The EUS is a fast twitch muscle and contains fibers expressing type 2B myosin. In contrast, the EAS exhibits slower kinetics and lacks type 2B fibers. This striking contrast in kinetics and fiber type profiles may be shaped by differences in the basal motor drive that each sphincter receives. Methods A double EMG approach was used to obtain spontaneously active single motor unit action potentials from the EUS and EAS simultaneously and compare their basal discharge frequencies in urethane anaesthetized rats. Key Results The basal firing rates of motor units of the EUS and EAS were not significantly different (3.9 ± 0.9 Hz vs. 3.1 ± 1.6 Hz, respectively, n = 7 animals, P = 0.32, paired Student's t-test). However, auto-correlogram analysis showed that EUS is driven by neurons with faster instantaneous firing frequencies: 30.5 ± 2.4 Hz vs 14.3 ± 0.9 Hz in the EAS ( P = 0.03, paired Student's t-test). Conclusions & Inferences The oscillator(s) driving the EUS operate(s) at a frequency twice that of the EAS. This may explain the presence of type 2B fibers in the EUS. In the inter-micturition periods no cross correlation was found in motor discharge to the sphincters suggesting that the two muscles do not share a common central drive to sustain the continent tonus of the two outlet tracts. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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36. Use of an electrothermal bipolar sealing device in ligation of major mesenteric vessels during laparoscopic colorectal resection.
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Martin, S. T., Heeney, A., Pierce, C., O'Connell, P. R., Hyland, J. M., and Winter, Desmond C.
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FURNACE atomic absorption spectroscopy , *BLOOD coagulation , *LIGATURE (Surgery) , *RIGHT hemicolectomy , *TRANSURETHRAL prostatectomy ,LAPAROSCOPIC surgery complications - Abstract
Background: A variety of approaches are available for division of major vascular structures during laparoscopic colorectal resection. Ultrasonic coagulating shears (UCS), vascular staplers, plastic or titanium clips and electrothermal bipolar vessel sealing (EBVS) are currently available. We report our experience with an EBVS device, LigaSure™ (Covidien AG), used in division of the ileocolic, middle colic and inferior mesenteric arteries during laparoscopic colorectal resection. Methods: We report the immediate outcome of 802 consecutive unselected patients who underwent elective laparoscopic colorectal cancer resection performed with use of the LigaSure™ (5 and 10 mm) at our institution over a 5-year period. Operative procedures included right hemicolectomy ( n = 180), left hemicolectomy ( n = 96), sigmoid colectomy ( n = 347) and anterior resection ( n = 179). Data were collected from a prospectively maintained cancer database and operative records. The procedures were performed primarily by three consultant surgeons with an interest in laparoscopic colorectal resection. Results: Of 802 cases in which the LigaSure™ device was employed to divide major vascular structures, immediate effective vessel sealing was achieved in 99.8% ( n = 800). Two patients experienced related adverse events both following division of the inferior mesenteric artery with a 5 mm LigaSure™. Both patients had immediate uncontrolled haemorrhage that required laparotomy. Conclusions: Use of the LigaSure™ device to seal and divide the major mesenteric vessels during laparoscopic colorectal resection is very effective, with a high success rate of 99.8%. Caution should be exercised in elderly atherosclerotic patients, particularly when using the 5-mm LigaSure™ device. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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37. Sacral nerve stimulation increases activation of the primary somatosensory cortex by anal canal stimulation in an experimental model.
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Griffin, K. M., Pickering, M., O'Herlihy, C., O'Connell, P. R., and Jones, J. F. X.
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SACRAL nerves , *NEURAL stimulation , *ANUS , *FECAL incontinence , *ELECTRIC stimulation - Abstract
Background: [ABSTRACT FROM AUTHOR]
- Published
- 2011
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38. Atrophy of the sphincters of continence in an experimental model.
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Banahan, M., Peirce, C., Buffini, M., O'Herlihy, C., O'Connell, P. R., and Jones, J. F. X.
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FECAL incontinence , *SPHINCTERS , *ANUS , *DEHYDROGENASES , *ANIMAL models in research - Abstract
Background Pudendal nerve injury during childbirth may result in external anal sphincter (EAS) atrophy. Recently, balloon compression of the pelvic side wall has been shown to result in EAS atrophy in an experimental model. The aim of this study was to determine whether other sphincters of continence are similarly affected. Method Sixteen adult female virgin Wistar rats (eight controls) were studied 4 weeks after surgery. Anal and urethral canals were dissected, snap frozen and sectioned using a cryostat (100 lm thickness). Masses of EAS, internal anal sphincter (IAS) and external urethral sphincter (EUS) were calculated stereologically and stained with succinate dehydrogenase histochemistry to differentiate striated from smooth muscle. Sphincter length was determined and total sphincter mass calculated. Data were analysed with an unpaired Student's t-test. Results Atrophy of EAS (30.9 ± 1.7 to 21.3 ± 1.7 mg / kg, P = 0.001), IAS (98.1 ± 11.3 to 67.1 ± 5.0 mg / kg, P = 0.01) and EUS (9.6 ± 0.98 to 7.4 ± 0.8 mg / kg, P = 0.05) was found 4 weeks after the injury. Conclusion In an experimental model of obstetric pudendal nerve injury, significant atrophy of striated and smooth muscle sphincters of continence occurs and may contribute to altered continence following vaginal childbirth. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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39. Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.
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Burke, J. P., Cunningham, M. F., Watson, R. W. G., Docherty, N. G., Coffey, J. C., and O'Connell, P. R.
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ENDOTOXINS , *FIBROBLASTS , *NF-kappa B , *CONNECTIVE tissue growth factor , *COLLAGEN - Abstract
The article presents a study on lipopolysaccharide (LPS) and its effect on intestinal fibroblast activation. It explains the assessment of toll-like receptor (TLR) 4, nuclear factor kB (NFkB) pathway activation, connective tissue growth factor (CTGF), and the measurement of fibroblast contractility. Results showed several effects of LPS such as the NFkB activation, initiation of collagen contraction, and reduction of the TGF-ß1 inhibitor call smad-7.
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- 2010
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40. Endoglin negatively regulates transforming growth factor β1--induced profibrotic responses in intestinal fibroblasts.
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Burke, J. P., Watson, R. W. G., Mulsow, J. J., Docherty, N. G., Coffey, J. C., and O'Connell, P. R.
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FIBROBLASTS , *TRANSFORMING growth factors , *CROHN'S disease , *CYTOLOGICAL research , *GLYCOPROTEINS - Abstract
The article details a study which examined the effect of endoglin on transforming growth factor Β1-induced profibrotic responses in intestinal fibroblasts. The study cultured intestinal fibroblast from seromuscular biopsies of patients undergoing intestinal resection for Crohn's disease (CD) strictures or from control patients. It found that fibroblasts from strictures in CD express increase constitutive endoglin. In addition, the study discovered that endoglin is a negative regulator of transforming growth factor Β1.
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- 2010
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41. Simvastatin impairs smad-3 phosphorylation and modulates transforming growth factor 131 -mediated activation of intestinal fibroblasts.
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Burke, J. P., Watson, R. W. G., Murphy, M., Docherty, N. G., Coffey, J. C., and O'Connell, P. R.
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STATINS (Cardiovascular agents) , *COLON cancer patients , *INTESTINAL cancer , *FIBROSIS , *TRANSFORMING growth factors , *PHOSPHORYLATION , *SURGICAL excision , *CANCER treatment , *THERAPEUTICS - Abstract
The article presents a study which investigates the impact of Rho/Rho-associated coiled kinase (Rho/ROCK) pathway inhibitor simvastatin on transforming growth factor (TGF) β1-mediated activation of intestinal fibroblast. Intestinal fibroblast cultures obtained from eight elderly colorectal cancer patients receiving intestinal resection were activated by TGF β1. The study shows that simvastatin suppresses Smad-3 phosphorylation and is a potential treatment for intestinal fibrosis.
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- 2009
- Full Text
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42. Sulphate-reducing bacteria and hydrogen sulphide in the aetiology of ulcerative colitis.
- Author
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Rowan, F. E., Docherty, N. G., Coffey, J. C., and O'Connell, P. R.
- Subjects
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ULCERATIVE colitis , *ETIOLOGY of diseases , *BACTERIA , *HYDROGEN sulfide , *SULFATES - Abstract
The article examines the role of sulphate-reducing bacteria (SRB) and hydrogen sulphide in the etiology of ulcerative colitis. A literature search was conducted using the PubMed database and search terms "sulphate reducing bacteria," "hydrogen sulphide," "ulcerative colitis," "mucous gel layer" and "trans-sulphuration." According to the article, there is evidence to implicate SRB as an environmental factor in ulcerative colitis.
- Published
- 2009
- Full Text
- View/download PDF
43. External anal sphincter fatigue is not improved by N-acetylcysteine in an animal model.
- Author
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Healy, C. F., McMorrow, C., O'Herlihy, C., O'Connell, P. R., and Jones, J. F. X.
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OXIDATIVE stress , *ANUS , *FATIGUE (Physiology) , *HEALTH , *THERAPEUTICS - Abstract
Oxidative stress is associated with skeletal muscle fatigue. This study tests the hypotheses that N-acetylcysteine (NAC) reduces fatigue and accelerates recovery of the rat external anal sphincter (EAS). Fifteen female Wistar rats were killed humanely. The EAS was mounted as a ring preparation and electrically stimulated with 50 Hz trains of 200 ms in duration every 4 s for three and a half minutes. Three groups were analysed: a control group ( n = 5), a group pretreated with NAC (10−4 mol L−1; n = 5) and a group pretreated with NAC (10−3 mol L−1; n = 5). A novel fatigue index was formulated and was compared to a conventional method of expressing fatigue. There was no significant difference at concentrations of NAC (10−4 mol L−1; P > 0.05). At high concentrations of NAC (10−3 mol L−1) there was a significant depression in peak twitch amplitude before fatigue ( P = 0.04). N-Acetylcysteine in both concentrations used, did not alter fatigue or recovery of the rat EAS. There was a significant positive correlation between the two methods of expressing fatigue but the conventional method produced a higher fatigue index (22.4% on average). N-Acetylcysteine does not ameliorate fatigue or accelerate recovery of the EAS and may not be a useful medical therapy for faecal incontinence. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
44. Randomised clinical trial of a laxative alone versus a laxative and a bulking agent after primary repair of obstetric anal sphincter injury.
- Author
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Eogan, M., Daly, L., Behan, M., O'Connell, P. R., and O’Herlihy, C.
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ANUS , *LAXATIVES , *WOMEN , *OBSTETRICAL diagnosis , *LACTULOSE , *FECAL incontinence , *POSTNATAL care , *CLINICAL trials , *WOUNDS & injuries - Abstract
Objective To compare two postpartum laxative regimens in women who have undergone primary repair of obstetric anal sphincter injury. Design Randomised controlled trial. Setting National Maternity Hospital, Dublin. Population A total of 147 postpartum women who had sustained anal sphincter injury at vaginal birth. Methods Women were randomised to receive either lactulose alone thrice daily for the first three postpartum days followed by sufficient lactulose to maintain a soft stool over the following 10 days (lactulose group, n= 77) or the lactulose regimen combined with a sachet of ispaghula husk daily for the first 10 postpartum days (Fybogel™ group, n= 70). All patients kept a diary of bowel habit for the first 10 postpartum days and were invited to return for review at 3 months postpartum. Main outcome measures Patient discomfort with first postpartum bowel motion, incidence of postnatal constipation and incontinence and incontinence score in postnatal period. Results Pain scores were similar in the two treatment groups; but incontinence in the immediate postnatal period was more frequent with the two preparations compared with lactulose alone (32.86% versus 18.18%, P= 0.03). Conclusions This study does not support routine prescribing of a stool-bulking agent in addition to a laxative in the immediate postnatal period for women who have sustained anal sphincter injury at vaginal delivery. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
45. Rectovaginal fistula repair – a video vignette.
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Climent, M., McCawley, N., Hanly, A. M., and O'Connell, P. R.
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VIGNETTES , *FISTULA , *COLPORRHAPHY , *ANUS - Abstract
Intra-operatively, the external anal sphincter appeared grossly intact and did not require repair. A further advantage of performing levatorplasty is that the sequential sutures towards the perineum naturally lead to the deep external anal sphincter, which can be plicated or repaired as indicated. Advantages of a posterior fourchette incision in anal sphincter repair. [Extracted from the article]
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- 2020
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46. Expression and regulation of connective tissue growth factor by transforming growth factor β and tumour necrosis factor α fibroblasts isolated from strictures in patients with Crohn's disease.
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Beddy, D., Mulsow, J., Watson, R. W. G., Fitzpatrick, J. M., and O'Connell, P. R.
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CONNECTIVE tissue development , *GROWTH factors , *TUMOR necrosis factors , *FIBROBLASTS , *CROHN'S disease - Abstract
Background: Connective tissue growth factor (CTGF) stimulates fibroblast proliferation and extracellular matrix production. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of CTGF. Stricturing that occurs in patients with Crohn's disease after treatment with anti-tumour necrosis factor (TNF) α may be due to dysregulation of CTGF homeostasis. The aim of this study was to examine CTGF expression and regulation in fibroblasts isolated from patients with Crohn's disease. Methods: Fibroblasts were isolated by a primary explant technique from serosal biopsies of strictured segments of bowel in eight patients undergoing resection for Crohn's disease and from normal colon in seven patients having resection for benign or malignant colorectal disease. Cells were stimulated with transforming growth factor (TGF) β and TNF-α. CTGF protein and mRNA expression were measured by western blotting and real-time polymerase chain reaction respectively. Results: Mean(s.d.) CTGF protein expression in strictured Crohn's fibroblasts was higher than that in normal fibroblasts (56.5(9.7) versus 17.0(10.0) respectively; P = 0.011). In normal and strictured Crohn's fibroblasts, culture with TGF-β increased CTGF protein and mRNA expression. Co-culture of normal fibroblasts with TNF-α suppressed TGF-β-stimulated CTGF expression. Conclusion: Increased expression of CTGF in strictured Crohn's fibroblasts underlies its role in fibrosis. TNF-α suppresses fibrosis by downregulating fibroblast CTGF expression, an effect that may be lost following anti-TNF-α treatment, thereby promoting stricture formation. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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- View/download PDF
47. Anal vector volume analysis complements endoanal ultrasonographic assessment of postpartum anal sphincter injury.
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Fynes, M. M., Behan, M., O'herlihy, C., and O'connell, P. R.
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ANUS , *ULTRASONIC imaging , *WOUNDS & injuries - Abstract
Summary Background The aim of this study was to determine the role of anal vector manometry in the assessment of postpartum anal sphincter injury and to establish the most suitable method of anal vector volume analysis for identifying significant external anal sphincter (EAS) injury in an at-risk parous population. Methods A total of 101 consecutive women with a history of instrumental or traumatic vaginal delivery was recruited. Anal ultrasonography and anal vector manometry were performed. Receiver–operator characteristic curves were used to determine the usefulness of anal manometry and anal vector volume analysis in the identification of significant EAS disruption (full thickness, more than one quadrant involved) detected by ultrasonography. Results Seventeen women had significant EAS disruption identified by anal ultrasonography. Anal vector manometry provided complementary functional information. Anal vector symmetry index (VSI), determined by analysis of mean maximum squeeze pressure, yielded 100 per cent sensitivity for significant EAS disruption, with a positive predictive value of 61 per cent. Conclusion Anal vector manometry complements endoanal ultrasonography. VSI, determined by means of the squeeze pressure profile, correlates best with significant EAS disruption identified at anal ultrasonography. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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48. Metabolic substrate utilization differs in ileal faecal and urinary reservoirs.
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Duffy, M. M., Regan, M. C., Harrington, M. G., Fitzpatrick, J. M., and O'Connell, P. R.
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ILEUM , *GLUTAMINE , *METABOLISM - Abstract
Background Construction of an ileal faecal or urinary reservoir profoundly alters ileal luminal ecology and availability of mucosal metabolic substrates. The aims of this study were to measure mucosal metabolic flux of butyrate and glutamine in histologically normal (control) ileum and to determine the effect of reservoir construction on metabolic fluxes in patients with ileal pouch–anal anastomosis and ileocystoplasty. Methods Endoscopic biopsy samples were obtained from normal ileum (n=10), ileum of patients with ulcerative colitis (n=10), ileal pouch–anal anastomosis (n=7), ileocystoplasty (n=7) and ileal conduit (n=7). Using a closed microculture technique, biopsy utilization of 14C-labelled butyrate and glutamine was measured as [14C]carbon dioxide production. Biopsy DNA content was measured and [14C]carbon dioxide evolution expressed as picomoles [14C]carbon dioxide per microgram DNA per hour. Results The metabolic flux of both butyrate and glutamine was reduced in ileal pouch mucosa compared with that of ileal mucosa in patients with ulcerative colitis. In contrast, the metabolic flux of buyrate alone was reduced in ileal mucosa from ileocystoplasty and ileal conduit compared with that in normal ileal mucosa, while the metabolic flux of glutamine remained unchanged. Conclusion Ileal mucosal metabolic fluxes measured in vitro are altered by changing luminal ecology in vivo. These changes may affect the health and mucosal integrity of ileum used to construct these reservoirs. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
49. An Unusual Left Upper Quadrant Mass: A Bronchopulmonary Foregut Malformation.
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McDermott, R. L., Kavanagh, D. O., Bartosik, W., Quinn, C., and O'Connell, P. R.
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LUNG abnormalities , *FOREGUT , *PERIODIC health examinations , *DIAPHRAGM (Anatomy) , *HISTOPATHOLOGY , *EMBRYOLOGY , *RARE diseases , *SURGERY - Abstract
We report a case of a lady who presented with epigastric discomfort. Physical examination revealed a large left upper quadrantmass filling the left upper quadrant. Following extensive preoperative evaluation, she underwent resection of this 9 × 10 × 11 centimeter mass with en bloc excision of a portion of the left hemidiaphragm. She made an uneventful postoperative recovery. Histopathology revealed a bronchopulmonary foregut malformation with pulmonary sequestration. This developmental anomaly of the foregut typically occurs in the thoracic cavity; however, it can occur below the diaphragm. Herein we report a case and a detailed review of the embryology, clinical features, and management of these extremely rare clinical entities. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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50. Haematoma in a hydrocele of the canal of Nuck mimicking a Richter's hernia.
- Author
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Ryan JD, Joyce MR, Pierce C, Brannigan A, O'Connell PR, Ryan, J D, Joyce, M R, Pierce, C, Brannigan, A, and O'Connell, P R
- Abstract
We report a haematoma in a hydrocele of the canal of Nuck in a 69-year-old female. She presented with a right-sided groin swelling, the differential for which included an irreducible inguinal hernia or haematoma given her aspirin and clopidegrel use. Successful treatment involved evacuation of the haematoma with excision of the sac. Despite a high index of suspicion for a haematoma, these swellings should ideally be explored given the potential for co-existence of a hernia. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
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