Search

Barium defecography can assess structural and functional abnormalities in patients with chronic constipation.The purpose of this study was to determine the prevalence of individual and overlapping defecographic findings in this setting.This was a cross-sectional study.The study was conducted at a university hospital tertiary GI physiology department.Consecutive examinations of 827 consecutive patients presenting over a 30-month period with well-defined symptom severity (≥12 points on the Cleveland Clinic Constipation score) were included. Systematic evaluation of images with results stratified by sex is described.Six individual functional or anatomic (intussusception, rectocele, enterocele, megarectum, excessive dynamic perineal descent) defecographic observations were defined a priori, thus permitting 26 possible combinations of findings (ie, 63 abnormal types + 1 normal).Patients with constipation (mean symptom score = 19) were predominantly female (88%), with median age of 49 years (range, 17-98 y) . All 6 individual radiologic findings were identified with a total of 43 combinations found in the cohort; the 14 most prevalent of these accounted for85% of patients. Only 136 patients (16.4%) had a normal defecography (34.3% males vs 13.9% females; p0.0001). Overall, 612 patients (74.0%) had structural (n = 508 (61.4%)) or functional (n=104 (12.6%)) abnormalities in isolation, with 79 (9.6%) others exhibiting combinations of both. Functional abnormalities in isolation were more common in males compared with females (22.5% vs11.2%; p = 0.025) as opposed to structural abnormalities (57.8% vs 85.7%; p0.0001). Expulsion time was longer in females compared with males (110 s (60-120 s) vs 90 s (60-120 s); p = 0.049).The study was limited by its lack of multiorgan opacification.These results provide a contemporary atlas of defecographic findings in constipation. Several individual structural and functional features have been systematically classified, with overlap greater than previously acknowledged and profound differences among sexes that carry implications for tailoring management. See Video Abstract at http://links.lww.com/DCR/B552.ANTECEDENTES:La defecografía con bario puede evaluar anomalías estructurales y funcionales en pacientes con estreñimiento crónico.OBJETIVO:Determinar la prevalencia de hallazgos defecográficos individuales y superpuestos en este entorno.DISEÑO:Transversal.ENTORNO CLINICO:Hospital Universitario de tercer nivel, departamento de fisiología gastrointestinal.PACIENTES:Exploraciones consecutivas de 827 pacientes consecutivos que se presentaron durante un período de 30 meses con una gravedad de los síntomas bien definida (≥12 puntos en la escala de estreñimiento de la Cleveland Clinic): evaluación sistemática de imágenes con resultados estratificados por sexo.PRINCIPALES MEDIDAS DE VALORACION:Se definieron a priori seis observaciones defecográficas individuales, funcionales o anatómicas (intususcepción, rectocele, enterocele, megarecto, descenso perineal dinámico excesivo), lo que permitió 26 combinaciones posibles de hallazgos (es decir, 63 tipos anormales + 1 normal).RESULTADOS:Los pacientes con estreñimiento (puntuación media de síntomas, 19) eran predominantemente mujeres (88%) con una edad mediana de 49 (17-98) años. Se identificaron 6 hallazgos radiológicos individuales con un total de 43 combinaciones encontradas en la cohorte; los 14 más predominantes de éstos representaron85% de los pacientes.Solo 136 (16,4%) pacientes tuvieron una defecografía normal (34,3% hombres vs. 13,9% mujeres; P0,0001). En general, 612 (74,0%) pacientes tenían anomalías estructurales (n = 508 [61,4%]) o funcionales (n = 104 [12,6%]) de forma aislada, y otros 79 (9,6%) presentaban combinaciones de ambas. Las anomalías funcionales aisladas fueron más comunes en los hombres en comparación con las mujeres (22,5% vs. 11,2%, P = 0,025) en comparación con las anomalías estructurales (57,8 vs. 85,7%, P0,0001). El tiempo de expulsión fue mayor en las mujeres en comparación con los hombres (110 [60-120] vs. 90 [60-120] segundos; P = 0,049).LIMITACIONES:Falta de opacificación multiorgánica.CONCLUSIONES:Estos resultados proporcionan un atlas contemporáneo de hallazgos defecográficos en estreñimiento. Varias características individuales, estructurales y funcionales; se han clasificado sistemáticamente, con una superposición mayor que la reconocida anteriormente y con grandes diferencias entre los sexos que tienen implicaciones para adaptar su tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B552.

INTRODUCTION Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. METHODS Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. RESULTS Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a "functional" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). DISCUSSION RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).(Equation is included in full-text article.).

Objectives\ud Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation.\ud Patients and methods\ud A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months.\ud Results\ud A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe.\ud Conclusion\ud ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection.

Background Percutaneous tibial nerve stimulation and sacral nerve stimulation are both second-line treatments for fecal incontinence, but the comparative efficacy of the 2 therapies is unknown. In our institution, patients with refractory fecal incontinence are generally treated with percutaneous tibial nerve stimulation before being considered for sacral nerve stimulation. Objective The aim of this study was to assess the outcome associated with this treatment algorithm in order to guide future management strategies. Design All patients with fecal incontinence treated over a 3-year period with tibial nerve stimulation before receiving sacral nerve stimulation were identified from a prospectively recorded database. Demographics and pretreatment anorectal physiological data were available for all patients. Settings This study was conducted at an academic colorectal unit in a tertiary center. Patients Twenty patients (17 female:3 male, median age 55 (33-79) years) were identified to be refractory to percutaneous tibial nerve stimulation. Main outcome measures Clinical outcome data were collected prospectively before and after treatment, including 1) Cleveland Clinic Florida-Fecal Incontinence scores and 2) number of incontinence episodes per week. Results The mean (±SD) pretreatment incontinence score (11.7 ± 3.5) did not differ from the mean incontinence score after 12 sessions of tibial nerve stimulation (10.9 ± 3.6, p = 0.42). All patients were subsequently counseled for sacral nerve stimulation, and 68.4% of them reported a significant therapeutic benefit with an improved incontinence score (7.7 ± 4.1, p = 0.014). Limitations This was a nonrandomized study with a relatively small number of patients Conclusion Sacral nerve stimulation appears to be an effective treatment for patients who do not gain an adequate therapeutic benefit from percutaneous tibial nerve stimulation and, thus, should be routinely considered for this patient cohort.

Prospective randomized double-blind placebo-controlled crossover trial of 14 female patients (median age 52 [30-69] years) with proctographically defined evacuatory dysfunction (ED) and demonstrable rectal hyposensitivity (elevated thresholds to balloon distension in comparison with age- and sex-matched controls).Sacral nerve stimulation (SNS) is an evolving treatment for constipation. However, variable outcomes might be improved by better patient selection. Evidence that the effect of SNS may be mediated by modulation of afferent signaling promotes a role in patients with ED associated with rectal hyposensation.SNS was performed by the standard 2-stage technique (temporary then permanent implantation). During a 4-week period of temporary stimulation, patients were randomized ON-OFF/OFF-ON for two 2-week periods. Before insertion (PRE), and during each crossover period, primary (rectal sensory thresholds) and secondary (bowel diaries, constipation, and GIQoL [gastrointestinal quality of life] scores) outcome variables were blindly assessed.Thirteen patients completed the trial. Following stimulation, defecatory desire volumes to rectal balloon distension were normalized in 10 of 13 patients (PRE: mean 277 mL [234-320] vs ON: 163 mL [133-193] vs OFF: 220 mL [183-257 mL]; P = 0.006) and maximum tolerable volume in 9 of 13 (PRE: mean 350 mL [323-377] vs ON: 262 mL [219-305] vs OFF: 298 mL [256-340 mL]; P = 0.012). There was a significant increase in the percentage of successful bowel movements (PRE: median 43% [0-100] vs ON: 89% [11-100] vs OFF: 83% [11-100]; P = 0.007) and Wexner constipation scores improved (PRE: median 19 [9-26] vs ON: 10 [6-27] vs OFF: 13 [5-29]; P = 0.01). There were no significant changes in disease-specific or generic quality of life measures. Eleven patients progressed to permanent stimulation (9/11 success at 19 months).Most patients with chronic constipation secondary to ED with rectal hyposensitivity responded to temporary SNS. The physiological results presented support a mechanistic role for rectal afferent modulation.

Conflicting data exist on the contributions of advancing age and childbirth on the structure and function of the anal sphincter. This study aimed to examine the relative contributions of age and childbirth in a large cohort of women referred for investigation of symptoms of colorectal dysfunction (fecal incontinence and constipation).This study was conducted at a specialist surgical colorectal investigation unit in a university teaching hospital.Retrospective analysis was performed on prospectively collected demographic, symptom profile, and physiologic data from 3686 female patients. Strict exclusion criteria were applied, leaving 999 patients for univariate, multivariate, and logistic statistical modeling.The effects of independent variables alone and in combination on anal sphincter pressures (resting and squeeze increment) and the presence of sphincter defects (internal and external) were expressed as regression coefficients and odds ratios.Median age was 42 years (range, 16-88), and parity was 2 (range, 0-11); 16% were nulliparous. Three hundred sixty patients had fecal incontinence, 352 had constipation, and 287 had combined symptoms. Anal resting tone decreased with age by 0.66 cm H2O per year, and by 4.3 cm H2O per birth, and was associated with both internal and external anal sphincter defects (p = 0.0001 for both). Squeeze increment pressures decreased by 0.3 cm H2O per year, and by 3.8 cm H2O per birth; decreased pressures were, however, only significantly associated with external anal sphincter defects (p = 0.0001) as a result of childbirth. Cesarean delivery was protective against both reduced anal pressures and sphincter defects. Pudendal nerve terminal motor latencies increased bilaterally with age and with vaginal delivery; the impact of both was greater on the left nerve. Rectal sensation was unaffected by age or parity.Aging predominantly affects anal resting pressures; childbirth, particularly instrumental delivery, is detrimental to the structure and function of the external sphincter.

Background and aims Inflammation and thrombosis are closely related processes, which may play a role in the pathogenesis, as well as complications, of inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte aggregation are increased and platelet aggregation is known to occur in the mesenteric vasculature in IBD. The aims of this study were to test the hypotheses that platelet-leucocyte aggregation, platelet activation and neutrophil activation occur in the mesenteric vessels of patients with ulcerative colitis (UC). Patients and methods Platelet-leucocyte aggregates (PLAs), platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression, which decreases on neutrophil activation) were assessed flow cytometrically in mesenteric arterial, and venous blood sampled in eight patients with UC and eight controls with colonic carcinoma undergoing intestinal resections. Results In the patients with UC, the number of PLAs in the mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02). In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) × 10 9 /l versus venous 0.26 (0.09-1.6) x10 9 /l (P= 0.02). The median percentage increase was 45%. Mesenteric PLA formation did not occur in patients with colonic carcinoma [arterial 0.06 (0.03-0.49) x 10 9 /l vs. venous 0.05 (0.02-0.35) x10 9 /l; P=0.55]. The median percentage change was + 45% for UC patients and - 5% for controls. No arteriovenous gradient was observed in P-selectin expression, but L-selectin expression (arbitrary units), increased in the mesenteric vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035); P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous 850 (546-957); P=0.04]. The median percentage change was + 4% for UC and - 7% for controls. Conclusion The finding of increased numbers of PLAs in the venous mesenteric circulation supports the hypothesis that activated vascular endothelium stimulates PLA formation in UC.

The term "gastrointestinal neuromuscular disease" can be interpreted variably and encompasses a spectrum of paediatric and adult conditions including achalasia, pseudoobstruction, idiopathic constipation, irritable bowel syndrome, megacolon, and Hirschsprung disease. Although progress has been made in the understanding of the pathophysiology of some conditions, the aetiopathogenesis has been elucidated only in the rare minority. This review critically considers the available evidence for possible pathogenic mechanisms in these disorders.

b c espite advances in adjuvant and neoadjuvant treatent, surgery will remain the cornerstone of rectal caner treatment for the foreseeable future. The standard phincter-saving resection technique for cancer of the id and distal rectum is anterior resection, with total esorectal excision performed by the abdominal aproach using modern stapling methods. As low rectal esection techniques have improved over time, several rocedures have been described for ultra-low anastomois, eg, transsphincteric, abdominotransanal, abdominoranssphincteric, or more recently, transanal interphincteric resection. Despite each of these being more echnically difficult to perform than standard anterior esection, their adoption has allowed greater numbers of atients to be cured of rectal cancer with maintenance of astrointestinal continuity. Rectal resection results in loss of the rectal “reservoir” unction, which is fundamental to the maintenance of ontinence, and can also be associated with possible nadvertent sphincter injury. Straight anastomosis to he anal canal, unfortunately, does not afford either opimal reservoir function or important rectal continence echanisms (eg, discriminatory sensory function, comlex biomechanical properties), and conceptual modifiations, such as reservoir construction, have been develped to try to improve functional outcomes. Little ublished evidence has investigated whether neorectal ontinence mechanisms are truly present. This is exremely pertinent in individuals who might well have

Rectal intussusception is a common finding at evacuation proctography; however, its significance has been debated. This study was designed to characterize clinically and physiologically a large group of patients with rectal intussusception and test the hypothesis that certain symptoms are predictive of this finding on evacuation proctography. A total of 896 patients underwent evacuation proctography from which three groups were identified: those with isolated rectal intussusception (n = 125), those with isolated rectocele (n = 100), and those with both abnormalities (n = 152). Multivariate analyses were used to identify symptoms predictive of findings by evacuation proctography. The symptoms of anorectal pain and prolapse were highly predictive of the finding of isolated intussusception over rectocele (odds ratio, 3.6, P = 0.006; odds ratio, 4.9, P < 0.001) or combined intussusception and rectocele (odds ratio, 2.9, P = 0.02; odds ratio, 2.4, P = 0.03). The symptom of “toilet revisiting” was associated with the finding of rectoanal intussusception (odds ratio, 3.55, P = 0.04). Although patients with mechanically obstructing intussuscepta evacuated slower and less completely (P < 0.001) than those with nonobstructing intussuscepta, no symptom was predictive of this finding on evacuation proctography. Although certain symptoms are predictive of the finding of rectal intussusception, there is a wide overlap with symptoms of rectocele, another common cause of evacuatory dysfunction. Furthermore, the observation that “obstruction to evacuation” made on proctography had no impact on the incidence of evacuatory symptoms suggests that beyond simply demonstrating the presence of an intussusception, analysis of proctography and subclassifying intussusception morphology seems of little clinical significance, and selection for surgical intervention on the basis of proctographic findings may be illogical.

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.

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°C; range, 44–50°C) compared with females (median, 45°C; range, 43–50°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.

Objectives Acid-sensing ion channels (ASICs) are expressed by rat sensory neurons and may mediate pain associated with tissue acidosis after inflammation or injury. Our aim was to examine the molecular forms and localization of ASICs in human intestine and dorsal root ganglia using immunochemical techniques, and to measure the effects of inflammation and injury. Design and methods Inflamed Crohn's disease intestine and injured human dorsal root ganglia, with appropriate controls, were studied by Western blotting and immunohistochemistry, using specific affinity-purified ASIC antibodies. Results In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers. There was a corresponding trend for an increased immunoreactive density and increased number of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed intestine. In dorsal root ganglia, immunoreactivity for all ASICs was restricted to a sub-population (about 50%) of small-diameter (nociceptor) sensory neurons, and was generally less intense after injury. Conclusions Increased ASIC-3 in inflamed intestine suggests a role in pain or dysmotility, for which ASICs represent new therapeutic targets.

PURPOSE: The aim of this study was to devise a symptom scoring system to assist in diagnosing constipation and in discriminating among pathophysiologic subgroups. METHOD: A structured symptom scoring questionnaire (11 questions) was completed by 71 chronically constipated patients and by 20 asymptomatic controls. The symptom score was correlated with a previously validated constipation score (Cleveland Clinic Score). All patients underwent colonic transit studies, standard anorectal physiology testing, and evacuation proctography. On the basis of these investigations alone, an observer blinded to the questionnaire results allocated patients to one of three pathophysiologic subgroups: slow-transit constipation, rectal evacuatory disorder, or mixed (slow-transit constipation and rectal evacuatory disorder). Linear discriminant analysis was used to assess the ability of different questionnaire symptoms to discriminate among these subgroups. RESULTS: Total symptom score was strongly correlated with the Cleveland Clinic Score (r=0.9). The median total score in constipated patients was 20 (range, 11–35) compared with a median of 2 in controls (range, 0–6). Discriminant analysis using cross validation estimated that pathophysiology could be predicted correctly for 55 percent (95 percent confidence interval =43–67 percent) of patients using just five symptoms. The discriminant function rarely misclassified patients with rectal evacuatory disorder as slow-transit constipation andvice versa, but could not effectively discriminate between patients with single and mixed pathologies. CONCLUSION: This new scoring system is a valid technique to assist in the diagnosis of constipation and is the first study using appropriate statistical methodology to demonstrate a discriminatory ability of multiple symptoms in constipation. At present, symptom analysis does not adequately differentiate major pathophysiologic subgroups for use in clinical practice.

PURPOSE: Idiopathic slow-transit constipation is a severe disorder of unknown cause. The onset in early childhood and history of constipation or Hirschsprung's disease in close family relatives suggest that slow-transit constipation could have a genetic basis. Several germline mutations have been described in Hirschsprung's disease, including mutations ofRET and the gene encoding its ligand glial cell-derived neurotrophic factor. The aim of this study was to screen a panel of 16 cases of familial idiopathic slow-transit constipation, including 4 families in which there were relatives with Hirschsprung's disease, forRET and glial cell-derived neurotrophic factor mutations previously identified in Hirschsprung's disease. METHODS: Genomic DNA from 16 patients with slow-transit constipation and four relatives with Hirschsprung's disease was analyzed using single strand and heteroduplex conformation polymorphism analysis at two conditions and by direct DNA sequencing using the fluorescent dideoxy terminator method. RESULTS: Although common sequence polymorphisms were demonstrated with a frequency comparable with published data, no published or new mutation was seen in any of the exons ofRET or glial cell-derived neurotrophic factor. CONCLUSIONS: Mutation ofRET or glial cell-derived neurotrophic factor is not a frequent cause of idiopathic slow-transit constipation.