S. Mark Scott

Linear discriminant analysis of symptoms in patients with chronic constipation: Validation of a new scoring system (kess)

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.

The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Probiotics have been increasingly investigated in its management. OBJECTIVE The aim was to investigate the effect of probiotics on gut transit time, stool output, and constipation symptoms in adults with functional constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs). DESIGN Studies were identified by searching 4 electronic databases, back-searching reference lists, contacting authors, and hand-searching abstracts. RCTs that reported administration of probiotics in adults with functional constipation were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Outcome data were synthesized by using weighted mean differences (WMDs) or standardized mean differences (SMDs) with the use of a random-effects model. RESULTS A total of 660 records were identified of which 14 were eligible (1182 patients). Overall, probiotics significantly reduced whole gut transit time by 12.4 h (95% CI: -22.3, -2.5 h) and increased stool frequency by 1.3 bowel movements/wk (95% CI: 0.7, 1.9 bowel movements/wk), and this was significant for Bifidobacterium lactis (WMD: 1.5 bowel movements/wk; 95% CI: 0.7, 2.3 bowel movements/wk) but not for Lactobacillus casei Shirota (WMD: -0.2 bowel movements/wk; 95% CI: -0.8, 0.9 bowel movements/wk). Probiotics improved stool consistency (SMD: +0.55; 95% CI: 0.27, 0.82), and this was significant for B. lactis (SMD: +0.46; 95% CI: 0.08, 0.85) but not for L. casei Shirota (SMD: +0.26; 95% CI: -0.30, 0.82). No serious adverse events were reported. Attrition and reporting bias were high, whereas selection bias was unclear due to inadequate reporting. CONCLUSIONS Probiotics may improve whole gut transit time, stool frequency, and stool consistency, with subgroup analysis indicating beneficial effects of B. lactis in particular. However, caution is needed with the interpretation of these data due to their high heterogeneity and risk of bias. Adequately powered RCTs are required to better determine the species or strains, doses, and duration of use of probiotics that are most efficacious.

Systematic Review of Surgical Options for Idiopathic Megarectum and Megacolon

Objective:A subgroup of patients with intractable constipation has persistent dilatation of the bowel, which in the absence of an organic cause is termed idiopathic megabowel (IMB). The aim of this systematic review was to evaluate the published outcome data of surgical procedures for IMB in adults. Methods:Electronic searches of the MEDLINE (PubMed) database, Cochrane Library, EMBase, and Science Citation Index were performed. Only peer-reviewed articles of surgery for IMB published in the English language were evaluated. Studies of all surgical procedures were included, providing they were performed on 3 or more patients, and overall success rates were documented. Studies were critically appraised in terms of design and methodology, inclusion criteria, success, mortality and morbidity rates, and functional outcomes. Results:A total of 27 suitable studies were identified, all evidence was low quality obtained from case series, and there were no comparative studies. The studies involved small numbers of patients (median 12, range 3–50), without long-term follow-up (median 3 years, range 0.5–7). Inclusion of subjects, methods of data acquisition, and reporting of outcomes were extremely variable. Subtotal colectomy was successful in 71.1% (0%–100%) but was associated with significant morbidity related to bowel obstruction (14.5%, range 0%–29%). Segmental resection was successful in 48.4% (12.5%–100%), and recurrent symptoms were common (23.8%). Rectal procedures achieved a successful outcome in 71% to 87% of patients. Proctectomy, the Duhamel, and pull-through procedures were associated with significant mortality (3%–25%) and morbidity (6%–29%). Vertical reduction rectoplasty (VRR) offered promising short-term success (83%). Pelvic-floor procedures were associated with poor outcomes. A stoma provided a safe alternative but was only effective in 65% of cases. Conclusions:Outcome data of surgery for IMB must be interpreted with extreme caution due to limitations of included studies. Recommendations based on firm evidence cannot be given, although colectomy appears to be the optimum procedure in patients with a nondilated rectum, restorative proctocolectomy the most suitable in those with dilatation of the colon and rectum, and VRR in those patients with dilatation confined to the rectum. Appropriately designed studies are required to make valid comparisons of the different procedures available.

Efficacy of sacral nerve stimulation for fecal incontinence in patients with anal sphincter defects.

PURPOSE: Sacral nerve stimulation has traditionally been used to treat patients with fecal incontinence with intact anal sphincters. This rationale has been challenged, but it remains unknown if its efficacy is related to the extent of the sphincter injury. METHODS: This was a prospective study of 15 patients with sphincter defects (9 combined, 2 external only, and 4 internal only) undergoing sacral nerve stimulation for fecal incontinence. Endoanal ultrasound scans were reviewed and defects scored (0–16) with use of a system published by two independent observers. These were correlated with the following outcomes: 1) reduction in fecal incontinence episodes, 2) reduction in soiling, 3) improvement in Cleveland Clinic scores, and 4) improvement in ability to defer defecation. All patients were studied after temporary stimulation and again at three to six months after permanent implantation. RESULTS: Thirteen patients (87%) progressed to permanent stimulation. Median fecal incontinence episodes per two weeks decreased from 15 (range, 1–53) to 3 (range, 0–16; P = 0.01). Median soiling episodes were reduced from 10 (range, 1–14) to 6 (range, 0–14; P = 0.009). Median Cleveland Clinic scores decreased from 12 (range, 9–18) to 9 (range, 4–14; P = 0.0005). The ability to defer defecation was improved significantly (P = 0.05). There were no relationships between sphincter defect scores and outcome measures after sacral nerve stimulation (r2 = 0.001–0.10; P = 0.28–0.94). CONCLUSION: Sacral nerve stimulation is an effective treatment in patients with fecal incontinence who have anal sphincter defects, and outcome is not associated with severity of sphincter disruption.

Rectal hyposensitivity: a disorder of the rectal wall or the afferent pathway? An assessment using the barostat.

OBJECTIVE:Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. Diagnosis on the basis of abnormal threshold volumes on balloon distension alone may be inaccurate due to the influence of differing rectal wall properties. The aim of this study was to investigate whether RH was actually due to impaired afferent nerve function or whether it could be secondary to abnormalities of the rectal wall.METHODS:A total of 50 patients were referred consecutively to a tertiary referral unit for physiologic assessment of constipation (Rome II criteria), 25 of whom had associated fecal incontinence. Thirty patients had RH (elevated threshold volumes on latex balloon distension), and 20 patients had normal rectal sensation (NS). Results were compared with those obtained in 20 healthy volunteers (HV). All subjects underwent standard anorectal physiologic investigation, and assessment of rectal compliance, adaptive response to isobaric distension at urge threshold, and postprandial rectal response, using an electromechanical barostat.RESULTS:Mean rectal compliance was significantly elevated in patients with RH compared to NS and HV (p < 0.001). However, 16 patients with RH (53%) had normal compliance. Intensity of the urge to defecate during random phasic isobaric distensions was significantly reduced in patients with RH compared to NS and HV (p < 0.001). The adaptive response at urge threshold was reduced in patients with RH compared to NS and HV (p < 0.001), although spontaneous adaptation at operating pressure was similar in all three groups studied (p= 0.3). Postprandially, responses were similar between groups.CONCLUSION:In patients found to have RH on simple balloon distension, impaired perception of rectal distension may be partly explained in one subgroup by abnormal rectal compliance. However, a second subgroup exists with normal rectal wall properties, suggestive of a true impairment of the afferent pathway. The barostat has an important role in the identification of these subgroups of patients.

Rectal Hypersensitivity Worsens Stool Frequency, Urgency, and Lifestyle in Patients With Urge Fecal Incontinence

PURPOSERectal 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.METHODSProspective 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.RESULTSA 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.CONCLUSIONSUrge 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.

Rectal Intussusception: Characterization of Symptomatology

PURPOSERectal 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.METHODSA 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.RESULTSThe 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.CONCLUSIONSAlthough 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.

Accurate localization of a fall in pH within the ileocecal region: validation using a dual-scintigraphic technique

Stereotypical changes in pH occur along the gastrointestinal (GI) tract. Classically, there is an abrupt increase in pH on exit from the stomach, followed later by a sharp fall in pH, attributed to passage through the ileocecal region. However, the precise location of this latter pH change has never been conclusively substantiated. We aimed to determine the site of fall in pH using a dual-scintigraphic technique. On day 1, 13 healthy subjects underwent nasal intubation with a 3-m-long catheter, which was allowed to progress to the distal ileum. On day 2, subjects ingested a pH-sensitive wireless motility capsule labeled with 4 MBq (51)Chromium [EDTA]. The course of this, as it travelled through the GI tract, was assessed with a single-headed γ-camera using static and dynamic scans. Capsule progression was plotted relative to a background of 4 MBq ¹¹¹Indium [diethylenetriamine penta-acetic acid] administered through the catheter. Intraluminal pH, as recorded by the capsule, was monitored continuously, and position of the capsule relative to pH was established. A sharp fall in pH was recorded in all subjects; position of the capsule relative to this was accurately determined anatomically in 9/13 subjects. In these nine subjects, a pH drop of 1.5 ± 0.2 U, from 7.6 ± 0.05 to 6.1 ± 0.1 occurred a median of 7.5 min (1-16) after passage through the ileocecal valve; location was either in the cecum (n = 5), ascending colon (n = 2), or coincident with a move from the cecum to ascending colon (n = 2). This study provides conclusive evidence that the fall in pH seen within the ileocolonic region actually occurs in the proximal colon. This phenomenon can be used as a biomarker of transition between the small and large bowel and validates assessment of regional GI motility using capsule technology that incorporates pH measurement.

The Physiology of Human Defecation

Human defecation involves integrated and coordinated sensorimotor functions, orchestrated by central, spinal, peripheral (somatic and visceral), and enteric neural activities, acting on a morphologically intact gastrointestinal tract (including the final common path, the pelvic floor, and anal sphincters). The multiple factors that ultimately result in defecation are best appreciated by describing four temporally and physiologically fairly distinct phases. This article details our current understanding of normal defecation, including recent advances, but importantly identifies those areas where knowledge or consensus is still lacking. Appreciation of normal physiology is central to directed treatment of constipation and also of fecal incontinence, which are prevalent in the general population and cause significant morbidity.

Slow Transit Constipation

Slow transit constipation (STC) is a severe motility disorder, which in the majority of cases is of unknown etiology. In some, symptoms arise de novo in childhood, but a proportion of patients present in later life, including after pelvic surgery or childbirth. Our aims were: (1) to describe our current knowledge of the anatomy and function of the pelvic autonomic nerves with respect to colonic motility (experimental and observational studies); (2) to discuss evidence for pelvic nerve injury in STC arising after pelvic surgery or childbirth; and (3), on the basis that such patients are clinically indistinguishable from patients with chronic idiopathic STC, to evaluate whether there is evidence that pelvic autonomic neuropathy has an etiologic role in patients with chronic idiopathic STC. The outcome was as follows: (1) The clear importance of the pelvic autonomic nerves in colonic motor function is documented. (2) While there is an association between pelvic surgery and childbirth, and the onset of STC, there is little direct anatomical evidence that pelvic denervation occurs in these patients. However the phenotype of these patients is similar to results of experimental and observational studies. (3) Clinical, physiological, and histological similarities exist between patients whose symptoms arose following pelvic intervention and those whose symptoms arise de novo (idiopathic). We further present evidence for possible pathogenetic mechanisms underlying pelvic autonomic neuropathy in chronic idiopathic STC.