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AIM: Crohn's disease is a chronic inflammatory bowel disease characterized by alternating periods of exacerbation and remission. Surgical resection is not curative and postoperative recurrence (POR) remains a challenge in these patients. The aim of this study was to identify clinical variables that influence the risk of symptomatic anastomotic POR in patients with ileo-colonic Crohn's disease. METHOD: A retrospective study of Crohn's disease patients who had undergone ileo-colic resection between January 2014 and December 2018 was performed. For each patient, data including demographic information, Crohn's disease clinical setting, preoperative radiological data, operative and histological data, pre- and postoperative medication history and postoperative clinical course, including recurrence of disease, were extracted. Symptomatic anastomotic POR was defined as symptoms of Crohn's disease in the presence of confirmed anastomotic POR (endoscopic and/or radiological POR). RESULTS: For the study period, 104 patients were eligible and included for analysis. The cumulative probability of symptomatic anastomotic POR was 14%, 30%, 42%, 50% and 50% at 1, 2, 3, 4 and 5 years, respectively. Two clinical variables on multivariate analysis were associated with increased risk of symptomatic anastomotic POR, namely age <17 years at diagnosis [hazard ratio (HR) 2.17, p = 0.019] and gastrointestinal involvement (extent) >30 cm (HR 1.85, p = 0.048). CONCLUSION: This study describes the natural history of POR after ileo-colic resection for Crohn's disease, as defined by endoscopic, radiological and clinical outcomes. Age <17 years at diagnosis and gastrointestinal involvement (extent) >30 cm were independent risk factors for symptomatic anastomotic POR.

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Up to 80% of patients with rectal cancer undergo sphincter-preserving surgery. It is widely accepted that up to 90% of such patients will subsequently have a change in bowel habit, ranging from increased bowel frequency to faecal incontinence or evacuatory dysfunction. This wide spectrum of symptoms after resection and reconstruction of the rectum has been termed anterior resection syndrome. Currently, no precise definition or causal mechanisms have been established. This disordered bowel function has a substantial negative effect on quality of life. Previous reviews have mainly focused on different colonic reconstructive configurations and their comparative effects on daily function and quality of life. The present Review explores the potential mechanisms underlying disturbed functions, as well as current, novel, and future treatment options.

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BACKGROUND: Sacral nerve stimulation has been shown to be an effective treatment for fecal incontinence and early studies reported success rates of 67% to 100%. However, "success" has been arbitrarily set at a 50% reduction in symptoms, and data are rarely reported with "intention to treat." OBJECTIVE: This study aimed to assess the true efficacy of sacral nerve stimulation for fecal incontinence compared with the published literature. DESIGN: This prospective 5-year study was conducted to assess 50 patients with fecal incontinence treated with sacral nerve stimulation. All analyses were performed on an intention-to-treat basis. SETTINGS: This study took place in a single tertiary referral colorectal department. PATIENTS: Fifty consecutive patients with fecal incontinence refractory to conservative management were included in the study. INTERVENTIONS: The interventions performed were temporary evaluation with or without permanent sacral nerve stimulation. MAIN OUTCOME MEASURES: : Primary outcome measures were 1) attainment of continence, 2) reduction in fecal incontinence episodes, 3) improvement in Cleveland Clinic Fecal Incontinence scores, and 4) improvement in the ability to defer defecation. RESULTS: Thirteen patients (26%) did not respond at the temporary evaluation stage or were dissatisfied with the result. Ten further patients (20%) did not achieve a 50% reduction in symptoms following permanent implantation. The median follow-up was 17 months (range, 2-55), at which time 27 patients (54%) experienced a 50% or more reduction in symptoms, including 13 (26%) who achieved apparent continence. Median fecal incontinence episodes per fortnight reduced from 14 (range, 0-53) to 2 (range, 0-20; P < .0001). Median Cleveland Clinic Fecal Incontinence scores reduced from 15 (range, 3-20) to 8 (range, 0-17; P < .0001). The ability to defer defecation improved significantly (P < .0001). These results compare favorably with the published literature. LIMITATIONS: Quality of life was not assessed. CONCLUSIONS: This study demonstrates that sacral nerve stimulation can be an effective treatment for patients with fecal incontinence; however, when analyzed by intention to treat, the symptoms of fecal incontinence continue in the majority (74%) of patients.

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PURPOSE: Percutaneous tibial nerve stimulation has been shown to be an effective treatment in patients with urinary disorders, but its benefit in fecal incontinence is uncertain. This study aimed to assess the efficacy of percutaneous tibial nerve stimulation in the treatment of urge fecal incontinence. METHODS: This prospective study, conducted over a 14-month period, assessed 31 patients with urge fecal incontinence treated with percutaneous tibial nerve stimulation. The outcomes measured were: 1) reduction in fecal incontinence episodes, 2) improvement in Cleveland Clinic incontinence scores, and 3) improvement in ability to defer defecation. All analysis was performed on an intention-to-treat basis. RESULTS: The median follow-up was 9 months (range, 3-14). Twenty-one (68%) patients improved following percutaneous tibial nerve stimulation and remain satisfied with the clinical response. Median fecal incontinence episodes per week declined from 4 (range, 0-30) to 0 (range, 0-27) (P < .0001). Median Cleveland Clinic incontinence scores declined from 13 (range, 5-20) to 7 (range, 0-20) (P < .0001). Ability to defer defecation was improved significantly (P < .0001). No morbidity was encountered for any patient. CONCLUSION: This preliminary study demonstrates that percutaneous tibial nerve stimulation is an effective and very well tolerated treatment for patients with urge fecal incontinence with particular improvement in reducing fecal urgency.

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BACKGROUND: Sphincter-saving rectal resections have become commonplace in the surgical treatment of malignant rectal pathology. However, restoration of gastrointestinal continuity by means of conventional techniques proves technically challenging in cases of very low rectal pathology, with resultant variable requirements for a permanent stoma. The APPEAR procedure (Anterior Perineal PlanE for Ultralow Anterior Resection of the rectum) is a novel sphincter-saving resection technique to restore gastrointestinal continuity in those who would otherwise require a permanent stoma with conventional abdominal resections. It ensures that the distal rectum is excised and the anastomosis is constructed under direct vision while simultaneously preserving the anal sphincter and its somatic nerve supply in their entirety. INDICATIONS: This procedure is indicated in the following instances: proven lower-third rectal carcinomas where anatomical restrictions prevent satisfactory rectal dissection and/or transection with a potential inadequate distal clearance margin; ileoanal pouch formation for ulcerative colitis or familial adenomatous polyposis where retained rectal tissue is at risk of future malignancy; short or strictured rectal stumps where pelvic dissection is hazardous and thus prevents restoration of gastrointestinal continuity. CONCLUSIONS: The APPEAR technique is a feasible alternative sphincter-saving procedure to further reduce the requirement of permanent stoma in the treatment for ultralow rectal pathology; however, it is appreciated that a larger study group with long-term follow-up is required. This technique should facilitate laparoscopic rectal resection because large and distal tumors can be dissected and excised through the perineal wound, ensuring adequate distal clearance and the anastomosis constructed under vision at an appropriate level. Furthermore, the requirement for an abdominal incision is avoided, improving cosmesis.

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BACKGROUND: Rectal augmentation (RA) with or without electrically stimulated gracilis neosphincter (ESGN) was developed to address the physiologic and anatomic abnormalities present in a subset of patients with incapacitating fecal urgency and associated urge fecal incontinence (UFI). This study evaluated the short- and medium-term clinical and physiologic results. METHODS: Eleven patients with fecal urgency and UFI underwent RA, 6 with concomitant ESGN formation. Patients were evaluated preoperatively, and at a median of 12.5 and 54 months after surgery. RESULTS: At 4.5 years, 7/11 patients had avoided stoma construction. Symptoms recurred leading to permanent stoma formation in 1 patient, whereas one other developed evacuatory difficulty with overflow incontinence. Median ability to defer defecation improved from seconds preoperatively to 10 minutes at 1 year (P = 0.0002), and 15 minutes at 4.5 years (P = 0.002). Median Wexner incontinence scores improved from 15 preoperatively to 3 at 1 year (P = 0.002), and 4 at 4.5 years (P = 0.02). At 1 year, 2 of the rectal sensory thresholds (DDV: P = 0.008; MTV: P = 0.008) and compliance were normalized (P = 0.008), whereas at 4.5 years, all sensation thresholds improved (FCS: P = 0.002; DDV: P = 0.002; MTV: P = 0.002), but changes in compliance were not significant. CONCLUSION: RA with or without ESGN improved reported symptoms and normalized rectal sensation. Improvements were sustained in the medium term. The procedure had no associated morbidity or mortality, and should be considered in the surgical management of a select group of patients presenting with severe urgency and UFI.

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Gene therapy holds promise in preventing the development of many diseases. One of the possible applications is the management of organ transplantation. Over the years, advances in vector development have allowed the clinical progression of this form of therapy to become more attainable. Viral vector technology has proved to be better than non-viral vectors at ferrying therapeutic genes to cells. However, many deficiencies in viral vectors hinder the full realisation of gene-based therapy in transplantation. Here, these deficiencies and their ramifications for the future of viral vector development are fully analysed. The authors propose that the slow progress of gene therapy in transplantation may be related to the deficiencies in viral vectors.

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PURPOSE: Rectal sensory mechanisms are important in the maintenance of fecal continence. Approximately 50 percent of patients with urge incontinence have lowered rectal sensory threshold volumes (rectal hypersensitivity) on balloon distention. Rectal hypersensitivity may underlie the heightened perception of rectal filling; however, its impact on fecal urgency and incontinence is unknown. This study was designed to investigate the impact of rectal hypersensitivity in patients with urge fecal incontinence. METHODS: Prospective and retrospective audit review of all patients (n = 258) with an intact native rectum referred to a tertiary colorectal surgical center for physiologic investigation of urge fecal incontinence during a 7.5-year period. Patients with urge fecal incontinence who had undergone pelvic radiotherapy (n = 9) or rectal prolapse (n = 6) were excluded. RESULTS: A total of 108 of 243 patients (44 percent) were found to have rectal hypersensitivity. The incidence of anal sphincter dysfunction was equal (90 percent) among those with or without rectal hypersensitivity. Patients with urge fecal incontinence and rectal hypersensitivity had increased stool frequency (P < 0.0001), reported greater use of pads (P = 0.003), and lifestyle restrictions (P = 0.0007) compared with those with normal rectal sensation, but had similar frequencies of incontinent episodes. CONCLUSIONS: Urge fecal incontinence relates primarily to external anal sphincter dysfunction, but in patients with urge fecal incontinence, rectal hypersensitivity exacerbates fecal urgency, and this should be considered in the management and surgical decision in patients who present with fecal incontinence.

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BACKGROUND: Local residual tumor predicts poor patient survival after resection for colorectal cancer. The aim of this study was to determine the prevalence of residual tumor in a line of resection in a large prospective series and to identify other pathology variables that may influence survival in the absence of distant metastases in such patients. STUDY DESIGN: This study was based on all patients who had a resection for colorectal cancer at Concord Hospital between 1971 and 2001. Patients were followed up annually until death or December 2002. Survival analysis used the Kaplan-Meier method and log rank test. Proportional hazards regression was used in multivariate modeling. RESULTS: The overall prevalence of residual tumor in a line of resection was 5.9%. Of 12 pathology variables examined, only high grade and apical node metastasis were independently associated with survival in the subset of 120 patients with residual tumor in a line of resection but without distant metastases. The 2-year survival rate for patients with neither of these adverse features was 46.4% (95% CI, 31.7% to 59.9%) as compared with only 7.7% (CI, 0.5% to 29.2%) in those who had both. CONCLUSIONS: These results show that presence of local residual tumor after colorectal cancer resection does not carry a universally poor prognosis. Two specific histopathologic features independently associated with diminished survival were identified.

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PURPOSE: The aim of this study was to assess the morphologic change of the anal canal in patients with rectal prolapse. METHODS: The endoanal ultrasound scans of 18 patients with rectal prolapse were compared with those of 23 asymptomatic controls. The thickness and area of the internal anal sphincter and submucosa were measured at three levels. RESULTS: Qualitatively, patients with rectal prolapse showed a characteristic elliptical morphology in the anal canal with anterior/posterior submucosal distortion accounting for most of the change. Quantitatively, internal anal sphincter (IAS) and submucosa (SM) thicknesses and area were greater in all quadrants of the anal canal (especially upper) in patients with rectal prolapse compared with controls. There was statistical evidence (in a regression model) of a relationship between increases in all measured variables and the finding of rectal prolapse. CONCLUSIONS: The cause of sphincter distortion in rectal prolapse is unknown but may be a response to increased mechanical stress placed on the sphincter from the prolapse or an abnormal response by the sphincter complex to the prolapse. Patients found to have this feature on endoanal ultrasound should undergo clinical examination and defecography to look for rectal wall abnormalities.

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PURPOSE: Currently, rectal sensation may be measured by balloon distention or mucosal electrostimulation. This study investigated the application of a graded heat stimulus to the rectum using a novel thermal probe as a further method of evaluating rectal sensory afferent mechanisms. METHODS: A thermal probe specially designed in our institution was used to test rectal heat sensitivity in 31 healthy subjects. This was compared with all other standard anorectal physiologic measurements. Repeatability studies were also performed. RESULTS: Heat stimulation of the mid rectum elicited sensory responses in all subjects. The most common reported response was not heat but a sharp or prickling sensation. The median rectal heat threshold was similar in males (median, 47 degrees C; range, 44-50 degrees C) compared with females (median, 45 degrees C; range, 43-50 degrees C; P > 0.05). There was a high degree of repeatability with rectal heat and balloon distention thresholds, but not electrostimulation thresholds. A strong correlation was found between rectal heat thresholds and defecatory desire (r = 0.71; P < 0.001) and maximum tolerable volumes (r = 0.8; P < 0.001) measured with balloon distention. CONCLUSION: This is the first demonstration of a repeatable sensory response to heat stimulation in the rectum of normal subjects. Strong correlation between heat thresholds and balloon distention to maximum tolerable volumes and defecatory desire suggest common sensory afferent pathway excitation. Heat stimulation is a simple technique that has a high degree of repeatability and may be an objective assessment of polymodal nociceptor function in the rectum.

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Calcium-activated potassium currents of intermediate conductance (IK1) have been described in the rodent enteric nervous system, where they may regulate afterhyperpolarisation of intrinsic primary afferent neurons. Using specific antibodies for immuno-cytochemistry, we now report IK1-like immunoreactivity for the first time in enteric neurons of human colon, and a significant decrease of IK1-positive cells in myenteric plexus in inflamed colon from patients with Crohn's disease and ulcerative colitis (p = 0.031). Neurotrophin-3 (NT-3), which regulates IK1 expression, was also observed in fewer neurons of the myenteric ganglia in Crohn's bowel (p = 0.048), and in inflamed colonic extracts by Western blotting (p = 0.004); the numbers of neurons expressing the NT-3 high affinity receptor trk C were unchanged. Our findings may explain the diarrhoea and colicky abdominal pain produced by inflammatory bowel disease, and by IK1-blocking pyridine drugs prescribed for neuromuscular disorders.

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PURPOSE: Blunted rectal sensation, or rectal hyposensitivity, has been reported anecdotally in patients with functional disorders of evacuation and continence. The purpose of this study was to determine the prevalence of rectal hyposensitivity and whether the finding of such an abnormality was associated with any clinical impact. METHODS: One thousand three hundred fifty-one patients, referred for anorectal physiologic investigation, were divided according to presenting symptoms into the following categories: constipation (subdivided into infrequency of and/or obstructed defecation), fecal incontinence (subdivided into passive, postdefecation, and urge incontinence), fecal incontinence and constipation, or "other." Rectal hyposensitivity was judged to be present when at least one of the sensory threshold volumes was elevated beyond the normal range (mean plus 2 standard deviations). The prevalence of rectal hyposensitivity was then calculated in each group and in relation to other investigations. RESULTS: Rectal hyposensitivity was present in 16 percent of patients, with males and females equally affected. Twenty-three percent of patients with constipation, 10 percent of patients with fecal incontinence, 27 percent of patients with incontinence associated with constipation, and only 5 percent of patients with other symptoms were found to have rectal hyposensitivity. In patients with obstructed defecation, rectal hyposensitivity was present in 33 percent with rectocele, 40 percent with intussusception, and 53 percent with no mechanical obstruction evident on evacuation proctography. CONCLUSION: Rectal hyposensitivity is common in patients with constipation and/or fecal incontinence and may thus be important in the etiology of such conditions. Although the clinical relevance of this physiologic abnormality is unknown, its presence may have implications regarding the management of hindgut dysfunction and particularly the selection of patients for surgery.

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