Diagnostic disagreement between tests of evacuatory function: a prospective study of 100 constipated patients.

BACKGROUND: Evacuatory dysfunction (ED) is a common cause of constipation and may be sub-classified on the basis of specialist tests. Such tests may guide treatment e.g., biofeedback therapy for 'functional' defecatory disorders (FDD). However, there is no gold standard, and prior studies have not prospectively and systematically compared all tests that are used to diagnose forms of ED. METHODS: One hundred consecutive patients fulfilling Rome III criteria for functional constipation underwent four tests: expulsion of a rectal balloon distended to 50 mL (BE50 ) or until patients experienced the desire to defecate (BEDDV ), evacuation proctography (EP) and anorectal manometry. Yields and agreements between tests for the diagnosis of ED and FDD were assessed. KEY RESULTS: Positive diagnostic yields for ED were: BEDDV 18%, BE50 31%, EP 38% and anorectal manometry (ARM) 68%. Agreement was substantial between the two balloon tests (k = 0.66), only fair between proctography and BE50 (k = 0.27), poor between manometry and proctography (k = 0.01), and there was no agreement between the balloon tests and manometry (k = -0.07 for both BE50 and BEDDV ). For the diagnosis of FDD, there was only fair agreement between ARM and EP (k = 0.23), ARM ± BE50 and EP (k = 0.18), ARM and EP ± BE50 (k = 0.30) and ARM ± BE50 and EP ± BE50 (k = 0.23). CONCLUSIONS & INFERENCES: There is considerable disagreement between the results of various tests used to diagnose ED and FDD. This highlights the need for a reappraisal of both diagnostic criteria, and what represents the 'gold standard' investigation.

Traditional measures of normal anal sphincter function using high-resolution anorectal manometry (HRAM) in 115 healthy volunteers.

BACKGROUND: High-resolution anorectal manometry (HRAM) is a relatively new method for collection and interpretation of data relevant to sphincteric function, and for the first time allows a global appreciation of the anorectum as a functional unit. Historically, traditional anal manometry has been plagued by lack of standardization and healthy volunteer data of variable quality. The aims of this study were: (i) to obtain normative data sets for traditional measures of anorectal function using HRAM in healthy subjects and; (ii) to qualitatively describe novel physiological phenomena, which may be of future relevance when this method is applied to patients. METHODS: 115 healthy subjects (96 female) underwent HRAM using a 10 channel, 12F solid-state catheter. Measurements were performed during rest, squeeze, cough, and simulated defecation (push). Data were displayed as color contour plots and analysed using a commercially available manometric system (Solar GI HRM v9.1, Medical Measurement Systems). Associations between age, gender and parity were subsequently explored. KEY RESULTS: HRAM color contour plots provided clear delineation of the high-pressure zone within the anal canal and showed recruitment during maneuvers that altered intra-anal pressures. Automated analysis produced quantitative data, which have been presented on the basis of gender and parity due to the effect of these covariates on some sphincter functions. In line with traditional manometry, some age and gender differences were seen. Males had a greater functional anal canal length and anal pressures during the cough maneuver. Parity in females was associated with reduced squeeze increments. CONCLUSIONS & INFERENCES: The study provides a large healthy volunteer dataset and parameters of traditional measures of anorectal function. A number of novel phenomena are appreciated, the significance of which will require further analysis and comparisons with patient populations.

Evacuation proctography: a reappraisal of normal variability.

AIM: Interpretation of evacuation proctography (EP) images is reliant on robust normative data. Previous studies of EP in asymptomatic subjects have been methodologically limited. The aim of this study was to provide parameters of normality for both genders using EP. METHOD: Evacuation proctography was prospectively performed on 46 healthy volunteers (28 women). Proctograms were independently analysed by two reviewers. All established and some new variables of defaecatory structure and function were assessed objectively: anorectal dimensions; anorectal angle changes; evacuation time; percentage contrast evacuated; and incidence of rectal wall morphological 'abnormalities'. RESULTS: Normal ranges were calculated for all main variables. Mean end-evacuation time was 88 s (95% CI: 63-113) in male subjects and 128 s (95% CI: 98-158) in female subjects; percentage contrast evacuated was 71% (95% CI: 63-80) in male subjects and 65% (95% CI: 58-72) in female subjects. Twenty-six (93%) of 28 female subjects had a rectocoele with a mean depth of 2.5 cm (upper limit = 3.9 cm). Recto-rectal intussusception was found in nine subjects (approximately 20% of both genders); however, recto-anal intussusception was not observed. Only rectal diameter differed significantly between genders. Qualitatively, three patterns of evacuation were present. CONCLUSION: This study defines normal ranges for anorectal dimensions and parameters of emptying, as well as the incidence and characteristics of rectal-wall 'abnormalities' observed or derived from EP. These ranges can be applied clinically for subsequent disease comparison.

Ligation of the intersphincteric fistula tract in the management of anal fistula. A systematic review.

AIM: Over the last 5 years, the ligation of the intersphincteric fistula tract (LIFT) procedure has become increasingly popular as a sphincter-preserving technique for the treatment of anal fistula. The aim of this article was to review the published literature on the LIFT procedure. METHOD: The Cochrane database and EMBASE were searched from January 1980 to November 2012, and PubMed from January 1966 to November 2012. All peer-reviewed studies that investigated the LIFT procedure for the treatment of anal fistula were eligible for inclusion. Technical notes, commentaries, letters and meeting abstracts were excluded. The primary outcome measured was the overall fistula closure rate in relation to the length of follow-up. RESULTS: Twenty-nine articles were originally identified using the search criteria. Thirteen were finally included for analysis. Sample sizes ranged from 18 to 93 patients, with a pooled total of 498. Most fistulae, 494 (99%), were of cryptoglandular aetiology, of which 470 (94%) were transsphincteric. Overall success rates ranged from 40 to 95%, with a pooled success of 71% (352 of 495 patients; 3 of 498 were lost to follow-up). Follow-up ranged from 1 to 55 months, with a reported mean or median of 4 to 19.5 months. One hundred and eighty-three patients were formally assessed for continence, out of whom 11 (6%) had a minor disturbance. CONCLUSION: Overall the systematic review shows that the LIFT procedure appears to be an effective sphincter-conserving approach for the treatment of transsphincteric anal fistula with a pooled healing rate of 71% over a mean or median follow-up period ranging from 4 to 19.5 months.

Assessment of rectal afferent neuronal function and brain activity in patients with constipation and rectal hyposensitivity.

BACKGROUND: Blunted rectal sensation (rectal hyposensitivity: RH) is present in almost one-quarter of patients with chronic constipation. The mechanisms of its development are not fully understood, but in a proportion, afferent dysfunction is likely. To determine if, in patients with RH, alteration of rectal sensory pathways exists, rectal evoked potentials (EPs) and inverse modeling of cortical dipoles were examined. METHODS: Rectal EPs (64 channels) were recorded in 13 patients with constipation and RH (elevated thresholds to balloon distension) and 11 healthy controls, in response to electrical stimulation of the rectum at 10 cm from the anal verge using a bipolar stimulating electrode. Stimuli were delivered at pain threshold. Evoked potential peak latencies and amplitudes were analyzed, and inverse modeling was performed on traces obtained to determine the location of cortical generators. KEY RESULTS: Pain threshold was higher in patients than controls [median 59 (range 23-80) mA vs 24 (10-55) mA; P = 0.007]. Median latency to the first negative peak was 142 (±24) ms in subjects compared with 116 (±15) ms in controls (P = 0.004). There was no difference in topographic analysis of EPs or location of cortical activity demonstrated by inverse modeling between groups. CONCLUSIONS & INFERENCES: This study is the first showing objective evidence of alteration in the rectal afferent pathway of individuals with RH and constipation. Prolonged latencies suggest a primary defect in sensory neuronal function, while cerebral processing of visceral sensory information appears normal.

Novel biological strategies in the management of anal fistula.

BACKGROUND: The mostly widely studied biomaterials for the sphincter sparing treatment of anal fistulas are fibrin glue and the anal fistula plug (AFP). However their overall mean clinical success is only 50-60%. As the understanding of the pathology of anal fistula, wound healing and the host response to materials has improved, so new biological sphincter-sparing strategies have been developed. The aim of this review is to assess the safety and efficacy of these novel techniques. METHOD: PubMed, the Cochrane database and EMBASE were independently searched. All studies that investigated the potential of a biomaterial (defined as any synthetic or biologically derived substance in contact with host tissue) to augment the healing of anal fistula without sphincter division were included. Studies solely describing the role of fibrin glue or an AFP were excluded. Data extraction included type of material, fistula aetiology, treatment of the primary tract, fistula healing, incontinence, duration of follow-up and any specific complications. Systematic quality assessment of the included articles was performed. RESULTS: Twenty-three articles were finally selected for review. These included a variety of biological and synthetic systems that were employed to deliver selected components of the extracellular matrix, growth factors, cytokines, stem cells or drugs to the fistula tract. CONCLUSION: To date no study matches fistulotomy with regard to long-term fistula eradication rate. This is probably due to implant extrusion, inadequate track preparation or an unsuitable material. Future techniques need to address all these issues to ensure success. Success should be validated by MRI or long-term follow-up.

The effects of age and childbirth on anal sphincter function and morphology in 999 symptomatic female patients with colorectal dysfunction.

BACKGROUND AND OBJECTIVES: 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). SETTING: This study was conducted at a specialist surgical colorectal investigation unit in a university teaching hospital. PATIENTS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: Aging predominantly affects anal resting pressures; childbirth, particularly instrumental delivery, is detrimental to the structure and function of the external sphincter.

Learning the hard way: the importance of accurate data.

AIM: The outcome of surgery for colorectal cancer in each unit in the UK is collated by the National Bowel Cancer Audit Project (NBOCAP). In 2008-2009 our unit had a raw 30-day postoperative mortality close to the national average, but when it was nationally adjusted it appeared to be an outlier. The purpose of this study was to identify reasons for this disparity. METHOD: All records were obtained for patients undergoing surgery for colorectal cancer over the 2 years. Data submitted to NBOCAP to determine adjusted rates were compared with actual data. RESULTS: There were major discordances between submitted and actual data for American Society of Anesthesiology grades and timing of surgery. This explained why the unit appeared to be an outlier. CONCLUSION: There is increasing emphasis on outcome of health service delivery, which has important implications. Submission of correct data is essential if objective comparison is to be made on which to base decisions on service delivery among units and within health regions.

Management of idiopathic anal fistula using cross-linked collagen: a prospective phase 1 study.

AIM: Fibrin glue and porcine intestinal submucosa are used in novel sphincter-preserving techniques to heal anal fistulae. However, their success is highly variable and decreases with the length of follow up. The aim of this study was to assess the safety, feasibility and potential efficacy of another novel agent, cross-linked collagen, in two different physical formats, to heal anal fistulae. METHOD: Prospectively recruited patients underwent symptom, continence and anal physiology assessments and magnetic resonance imaging. Patients with secondary tracts or acute sepsis were excluded. At operation, participants were randomized to receiving a solid collagen implant or collagen fibres suspended in fibrin glue. Follow up included repeat symptom, continence and physiological assessments at 3 months, and regular clinical review thereafter. RESULTS: Twenty-nine of 43 entrants were eligible for inclusion. Thirteen patients received the collagen implant, and 16 collagen-fibrin glue. Three months postoperation, no patient experienced acute sepsis or continence disturbance, and sphincter function and integrity were unchanged. At 29 months, 12 of 15 (one lost to follow up) patients treated with collagen-fibrin glue were healed, compared with seven of 13 who received the implant. CONCLUSION: In the short-to-medium term, both techniques are safe and equally effective. The results justify continued research into the use of biomaterials to heal anal fistulae.

Combined vertical reduction rectoplasty and sacral nerve stimulation for rectal evacuatory dysfunction and faecal incontinence associated with previous anorectal malformation.

Functional outcomes following surgery for anorectal malformation are variable, with many children experiencing persisting anorectal dysfunction. We describe a 34-year-old female with previous vestibular fistula who experienced lifelong rectal evacuatory dysfunction and faecal incontinence; she was treated in a two stage process producing efficient defecation and almost total continence.

Pancolonic spatiotemporal mapping reveals regional deficiencies in, and disorganization of colonic propagating pressure waves in severe constipation.

BACKGROUND: The morphology, motor responses and spatiotemporal organization among colonic propagating sequences (PS) have never been defined throughout the entire colon of patients with slow transit constipation (STC). Utilizing the technique of spatiotemporal mapping, we aimed to demonstrate 'manometric signatures' that may serve as biomarkers of the disorder. METHODS: In 14 female patients with scintigraphically confirmed STC, and eight healthy female controls, a silicone catheter with 16 recording sites spanning the colon at 7.5 cm intervals was positioned colonoscopically with the tip clipped to the cecum. Intraluminal pressures were recorded for 24 h. KEY RESULTS: Pan-colonic, 24 h, spatiotemporal mapping identified for the first time in STC patients: a marked paucity of propagating pressure waves in the midcolon (P = 0.01), as a consequence of a significant (P < 0.0001) decrease in extent of propagation of PS originating in the proximal colon; an increase in frequency of retrograde PS in the proximal colon; a significant reduction in the spatiotemporal organization among PS (P < 0.001); absence of the normal nocturnal suppression of PS. CONCLUSIONS & INFERENCES: Pancolonic, 24 h, spatiotemporal pressure mapping readily identifies characteristic disorganization among consecutive PS, regions of diminished activity and absent or deficient fundamental motor patterns and responses to physiological stimuli. These features are all likely to be important in the pathophysiology of slow transit constipation.

Complications of intestinal stomas.

BACKGROUND: Stomal complications are prevalent and associated with considerable morbidity. This study examined the incidence and potential risk factors for their development. METHODS: The time of onset and presence of ten specific complications were recorded for patients with an intestinal stoma over 10 years at two urban hospitals. A database was established with 20 explanatory variables (such as common medical co-morbidities) derived from the stomatherapy and medical records. Univariable and multivariable analyses were performed to identify potential risk factors for the development of complications. RESULTS: Some 1216 patients (mean age 64 years) with a minimum of 2 years' follow-up were included, of whom 544 (44·7 per cent) underwent surgery for malignancy and 647 (53·2 per cent) had a colostomy formed. There were 1219 complications in total; 807 major complications (excluding excoriation and slough) occurred in 564 patients (46·4 per cent), of which the commonest was parastomal hernia (171, 14·1 per cent). On multivariable analysis, musculoskeletal co-morbidity (odds ratio (OR) 1·79, 95 per cent confidence interval 1·05 to 3·07; P = 0·032), cancer (OR 1·48, 1·13 to 1·93; P = 0·004) and high American Association of Anesthesiologists score (OR = 3·80, 2·14 to 6·75; P < 0·001) were associated with an increased risk of complications. Preoperative siting was associated with a reduced risk (OR 0·59, 0·39 to 0·90; P = 0·014). CONCLUSION: Intestinal stomal complications are common, occurring in almost half of patients. There are certain irremediable risk factors, allowing appropriate preoperative counselling.

Joint hypermobility and rectal evacuatory dysfunction: an etiological link in abnormal connective tissue?

BACKGROUND: Previous studies report an association between joint hypermobility (JHM), as a clinical feature of underlying connective tissue (CT) disorder, and pelvic organ prolapse. However, its association with rectal evacuatory dysfunction (RED) has not been evaluated. To investigate the prevalence of JHM in the general population and in patients with symptoms of RED referred for anorectal physiological investigation. METHODS: Bowel symptom and Rome III questionnaires to detect irritable bowel syndrome were sent to 273 patients with RED. Patients then underwent full investigation, including evacuation proctography. A validated 5-point self-reported questionnaire was used to assess JHM in both the patient group and 100 age- and sex-matched controls [87 female, median age 55 (range 28-87)]. KEY RESULTS: Seventy-three patients were excluded from analysis (incomplete questionnaire or investigation). Of 200, 65 patients [32%: 63 female, median age 52 (range 15-80)] and 14% of controls (P = 0.0005 vs patients) had features satisfying criteria for JHM. Overall constipation score (P < 0.0001), abdominal pain (P = 0.003), need for manual assistance (P = 0.009), and use of laxatives (P = 0.03) were greater in the JHM group than the non-JHM group. On proctography, 56 of JHM patients (86%) were found to have significant morphological abnormalities (e.g. functional rectocoele), compared with 64% of the non-JHM group (P = 0.001). CONCLUSIONS & INFERENCES: The greater prevalence of JHM in patients with symptoms of RED, and the demonstration of significantly higher frequencies of morphological abnormalities than those without JHM, raises the possibility of an important pathoaetiology residing in either an enteric or supporting pelvic floor abnormality of CT.

Bowel preparation affects the amplitude and spatiotemporal organization of colonic propagating sequences.

BACKGROUND: Colonic manometry is performed using either colonoscopically assisted catheter placement, after bowel preparation, or nasocolonic intubation of the unprepared bowel. There has been little systematic evaluation of the effects of bowel cleansing upon colonic propagating pressure wave sequences. METHODS: Eight healthy volunteers underwent nasocolonic placement of a water-perfused silicone catheter which recorded pressures at 16 recording sites each spaced 7.5 cm apart in the unprepared colon for 24 h. These measures were compared with those obtained in another eight healthy volunteers in whom the catheter was placed to the caecum at colonoscopy in the prepared colon. KEY RESULTS: The colonic motor responses to meals and morning waking, and the normal nocturnal suppression did not differ between the two groups, nor were the overall frequency, regional dependence nor extent of propagating sequences (PS) influenced by bowel preparation. Bowel preparation did result in a significant increase in the frequency of high amplitude PS (22 +/- 7 vs 8 +/- 4 HAPS/24 h; P = 0.003). Additionally, a number of the measures of spatiotemporal organization among consecutive PS (linkage among sequences and predefecatory stereotypical patterning) were significantly altered by bowel preparation. CONCLUSIONS & INFERENCES: The overall frequency of PSs, the colonic responses to physiological stimuli such a meal and morning waking and nocturnal suppression, are not influenced by prior bowel preparation. However, investigators wishing to study HAPS frequency, or the more complex spatiotemporal relationships among consecutive PSs, should control for bowel preparation when making comparisons among study groups.

The 'straight to test' initiative reduces both diagnostic and treatment waiting times for colorectal cancer: outcomes after 2 years.

AIM: This study aimed to determine whether a 'straight to test'(STT) strategy for 2-week wait (2 wk) referrals for suspected colorectal cancer (CRC) reduced the time to diagnosis and treatment for patients with CRC. METHOD: Consecutive 2-week referrals for suspected CRC over a period of 2 years from February 2007 were analysed. The times to the first diagnostic test and treatment and the cancers identified were analysed for those going to STT or the outpatient clinic. RESULTS: Of 662 patients having a 2 wk referral, 519 (78.4%) were suitable for the hospital colorectal telephone triage service, 121 (18.3%) patients went to STT and 502 (75.8%) were seen in the clinic. Of these 401 (79.8%) underwent diagnostic tests and 25 (6.2%) had CRC and in 12 (2.9%) patients other cancers were detected. In the STT group, 7 (5.8%) patients were diagnosed with CRC. The median time to first diagnostic test was 12 days (IQR 9-13) in the STT pathway, compared with 23 days (17-31) in those seen in the clinic (P < 0.0001). The median time to first treatment was 40 (32-48) days for those via STT, compared to 46 (28-55) days for those seen in the clinic (P = 0.004). A total of 162 CRC were diagnosed during the study period of whom 34 (20.9%) were 2 wk referrals (5.1% of all suspected CRC 2 wk referrals), and 14 (2.1%) other cancers were detected via this pathway. CONCLUSION: STT speeds up the patient pathway by reducing the time to diagnosis and treatment for patients with CRC.

Pathophysiology of evacuation disorders.

This review details our contemporary knowledge of the mechanisms underlying evacuatory disorders. There is confusion concerning terminology and classification, which is based upon both an incomplete understanding of the multiple mechanisms involved in evacuation, and that current tests to investigate it are not physiological. Nevertheless, despite the need for more research, significant advances have been made and current assessments can direct therapy.

Rectal hyposensitivity: pathophysiological mechanisms.

Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. It may occur due to afferent nerve dysfunction and/or secondary to abnormal structural or biomechanical properties of the rectum. The aim of this study was to determine the contribution of these underlying pathophysiological mechanisms by systematically evaluating rectal diameter, compliance and afferent nerve sensitivity in patients with RH, using methodology employed in clinical practice. The study population comprised 45 (33 women; median age 48, range 25-72 years) constipated patients (Rome II criteria) with RH and 20 with normal rectal sensitivity on balloon distension and 20 healthy volunteers. Rectal diameter was measured at minimum distending pressure during isobaric distension under fluoroscopic screening. Rectal compliance was assessed during phasic isobaric distension by measuring the slope of the pressure-volume curve. Electrical stimulation of the rectal mucosa was employed to determine afferent nerve function. Values were compared to normal ranges established in healthy volunteers. The upper limits of normal for rectal diameter, compliance and electrosensitivity were 6.3 cm, 17.9 mL mmHg(-1) and 21.3 mA respectively. Among patients with RH, rectal diameter, but not compliance, was increased above the normal range (megarectum) in seven patients (16%), two of whom had elevated electrosensitivity thresholds. Rectal diameter and compliance were elevated in 23 patients (51%), nine of whom had elevated electrosensitivity thresholds. The remaining 15 patients (33%) with RH had normal rectal compliance and diameter, all of whom had elevated electrosensitivity thresholds. Two-third of the patients with RH on simple balloon distension have elevated rectal compliance and/or diameter, suggesting that impaired perception of rectal distension is due to inadequate stimulation of the rectal afferent pathway. However, a proportion of such patients also appear to have impaired nerve function. In the remaining one-third of the patients, rectal diameter and compliance are normal, while electrosensitivity thresholds are elevated, suggestive of true impaired afferent nerve function. Identification of these subgroups of patients with RH may have implications regarding their management.

Effects of age and gender on three-dimensional endoanal ultrasonography measurements: development of normal ranges.

BACKGROUND: Faecal incontinence is a common and morbid disorder that is often related to anal sphincter dysfunction. High-frequency, three-dimensional (3-D) endoanal ultrasonography (EAUS) allows greater spatial resolution and longitudinal appreciation of the anal canal than conventional 2-D assessment. A robust normal range of values allowing for age and sex is required for subsequent disease comparison. METHODS: A group of 30 healthy male (n=12) and female (n=18) volunteers (median age, 49 years; range, 31-63 years) underwent 3-D EAUS using a high-frequency 10-MHz transducer. A reconstructed data cube was interrogated to measure anal canal structures in 2-D at high, middle and low levels, and in 3-D for longitudinal measurements. RESULTS: Men had a significantly longer 3-D external anal sphincter (EAS) and internal anal sphincter (IAS) than women, especially the anterior EAS (mean in men 2.5 cm, mean in women 1.6 cm, p<0.0001). There were no significant differences between the sexes for anal canal length or by 2-D scanning for the thickness of the EAS and IAS. No significant differences were observed between parous and nulliparous women. Age had no significant effect on 3-D length measurements, but 2-D EAUS measurements of the thickness of both the IAS and EAS increased with age significantly (mid canal, p=0.004). On these bases, normal ranges were generated. CONCLUSIONS: Sphincter measurements, enabled by 3-D reconstruction, vary with age and sex. A normal range incorporating these variations has been produced for future data comparison in disease states.

Normalization of substance P levels in rectal mucosa of patients with faecal incontinence treated successfully by sacral nerve stimulation.

BACKGROUND: Sacral nerve stimulation (SNS) may improve faecal incontinence by modulating rectal sensation. This study measured changes in the peripheral expression of various neural epitopes in response to SNS. METHODS: Rectal mucosal biopsies were taken from 12 patients before and after temporary SNS, and from ten responders at 90 days after permanent stimulation. Sections were immunostained for substance P, transient receptor potential vanilloid (TRPV) 1, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Levels were compared with those in nine continent controls. RESULTS: Baseline levels of percentage area immunoreactivities of substance P (median 0.51 (95 per cent confidence interval 0.31 to 0.73) versus 0.13 (0.07 to 0.27) per cent; P < 0.001) and TRPV1 (0.76 (0.41 to 1.11) versus 0.09 (0.04 to 0.14) per cent; P < 0.001), but not of VIP (1.26 (0.37 to 2.15) versus 1.28 (0.39 to 2.17); P = 0.943), were significantly greater than in controls. Successful SNS resulted in a significant decrease in substance P immunostaining after temporary (0.15 (0.06 to 0.51) per cent; P = 0.051) and permanent (0.17 (0 to 0.46) per cent; P = 0.051) stimulation. Immunoreactivity of TRPV1, VIP, CGRP and neural markers showed no qualitative change. CONCLUSION: Patients with faecal incontinence demonstrate normalization of raised rectal mucosal substance P levels following successful SNS.

Straight to test. Results of a pilot study in a hospital serving an inner city population.

OBJECTIVE: The main aims of the study were to determine the frequency with which two-week wait (2ww) referrals for colorectal cancer (CRC) could proceed directly to straight to test (STT), and the potential improvement in time to diagnosis. METHOD: A telephone interview was attempted in all 2ww referrals not requiring an advocate and under 80 years. Data were assessed according to a test protocol, and where indicated a potential slot for the appropriate investigation was recorded (virtual test). All patients proceeded to clinic, following which differences in time from GP referral to virtual compared with actual requested test, and any discrepancies between virtual and requested tests were analysed. RESULTS: Between 8th January and 16th February 2007, there were 42 2ww referrals. Twenty-one patients were contacted, of whom 14 were suitable for STT: 13 virtual colonoscopies and one CT scan were booked. Following out-patient consultation, eight colonoscopies; three flexible sigmoidoscopies, one barium enema, and two CT scans were actually booked. There was a difference of 15.5 days between the median times of the virtual and actual test. During this 6-week period a total of nine patients were diagnosed with CRC, of whom three were referred via the 2ww pathway, but none were suitable for STT. CONCLUSIONS: This 'straight to test' pilot study suggests a potential strategy for reducing the time to diagnosis and therefore first treatment of those identified with CRC, and offers a methodology for individual hospitals to assess their suitability to employ such a strategy.