Current aspects and future prospects of total anorectal reconstruction--a critical and comprehensive review of the literature.

PURPOSE: Many rectal cancer patients undergo abdominoperineal excision worldwide every year. Various procedures to restore perineal (pseudo-) continence, referred to as total anorectal reconstruction, have been proposed. The best technique, however, has not yet been defined. In this study, the different reconstruction techniques with regard to morbidity, functional outcome and quality of life were analysed. Technical and timing issues (i.e. whether the definitive procedure should be performed synchronously or be delayed), oncological safety, economical aspects as well as possible future improvements are further discussed. METHODS: A MEDLINE and EMBASE search was conducted to identify the pertinent multilingual literature between 1989 and 2013. All publications meeting the defined inclusion/exclusion criteria were eligible for analysis. RESULTS: Dynamic graciloplasty, artificial bowel sphincter, circular smooth muscle cuff or gluteoplasty result in median resting and squeezing neo-anal pressures that equate to the measurements found in incontinent patients. However, quality of life was generally stated to be good by patients who had undergone the procedures, despite imperfect continence, faecal evacuation problems and a considerable associated morbidity. Many patients developed an alternative perception for the urge to defecate that decisively improved functional outcome. Theoretical calculations suggested cost-effectiveness of total anorectal reconstruction compared well to life with a permanent colostomy. CONCLUSIONS: Many patients would be highly motivated to have their abdominal replaced by a functional perineal colostomy. Given the considerable morbidity and questionable functional outcome of current reconstruction technique improvements are required. Tissue engineering might be an option to design an anatomically and physiologically matured, and customised continence organ.

Outcome of percutaneous tibial nerve stimulation (PTNS) for fecal incontinence: a prospective cohort study.

OBJECTIVES: The aim of this study was to assess the long-term efficacy of percutaneous tibial nerve stimulation (PTNS) in fecal incontinence (FI). BACKGROUND: There is extensive evidence regarding the efficacy of PTNS in urinary incontinence. Data on the efficacy of PTNS for FI are limited to a few small case series with relatively short-follow up. METHODS: A prospective cohort of patients with FI was studied. Incontinence scores were measured using a validated questionnaire (Cleveland Clinic Florida-FI score) at specific time points: before treatment, after completion of a treatment course (12 PTNS sessions), and before the last maintenance ("top-up") therapy. Deferment time and average number of weekly incontinence episodes were also estimated from a prospective bowel dairy kept by the patient at these time points. Quality of life was assessed with the Rockwood Fecal Incontinence Quality of Life questionnaire. RESULTS: A total of 150 patients were recruited to the study between January 2008 and June 2012. Analysis was performed on 115 patients who continued to receive PTNS after a median follow-up of 26 (range, 12-42) months. The baseline Cleveland Clinic Florida-FI score ±SD (12.0 ± 3.9) improved after 12 PTNS sessions (9.4 ± 4.6, P < 0.0001) and after "top-up" treatments (10.0 ± 4.3, P < 0.0001). The increase in the Cleveland Clinic Florida-FI score between the end of the 12th session and the last "top-up" therapy was also significant (P = 0.04). A similar pattern was seen for the deferment time and the quality of life scores. The median time between "top-up" sessions was 12 months (range, 1-40 months), significantly longer than the recommended interval of 6 months. CONCLUSIONS: PTNS is a well-tolerated treatment with high acceptability in the majority of patients. It provides a sustained improvement in FI up to 42 months in a relatively noninvasive manner. The effect of PTNS diminishes with time and additional therapy sessions at 6 monthly intervals may result in greater improvements. PTNS ought to be considered as the first step in all patients with FI refractory to maximum conservative therapies.

Electrically stimulated gracilis neosphincter for end-stage fecal incontinence: the long-term outcome.

BACKGROUND: Electrically stimulated gracilis neosphincter is an established treatment for patients with end-stage fecal incontinence. Few data, however, describe its long-term efficacy. OBJECTIVE: This study aimed to assess the long-term functional outcome associated with this procedure. DESIGN: Patients who underwent gracilis neosphincter construction between1989 and 2001 were identified from a prospectively recorded database. Demographics and pretreatment anorectal physiologic data were available for all patients. SETTINGS: This study was conducted at an academic colorectal unit in a tertiary center. PATIENTS: Sixty patients (median age, 42 years; 46 females) with fecal incontinence and a Williams continence score ≥5 were recruited to the study. The causes of incontinence included obstetric injury (n = 22), anal surgery (n = 17), atresia (n = 7), idiopathic incontinence (n = 6), anorectal excision (n = 4), and ileoanal pouch incontinence (n = 4). MAIN OUTCOME MEASURE: The primary outcomes measured were the Williams continence score and the proportion of patients with a Williams score ≤3 who avoided permanent stoma formation. RESULTS: Continence improved for the cohort postoperatively at 2 years (2(2-5); p < 0.001) but no significant difference was found between continence scores preoperatively and at 13 years (5(3-6); p = not significant). However, a sustained improvement at 13 years was noted for patients in the anal surgery (3(2-5);p < 0.001) and obstetric injury groups (4.5(3-6); p = 0.001). Twenty-six patients (43%) had a Williams score ≤3 and avoided permanent stoma after 13 years. Eighteen patients developed postoperative rectal evacuatory disorder; 10 of them required a conduit to facilitate colonic irrigation. Postoperative evacuatory disorder was more frequent in patients with a history of obstetric injury (p = 0.008). LIMITATIONS: This study was limited by the lack of bowel diaries and quality-of-life scores. CONCLUSION: Gracilis neosphincter is associated with clinically significant and sustained symptom improvement in patients with end-stage fecal incontinence secondary to obstetric injury or anal surgery. These data support the continued use of this procedure in highly selected patients.

Symptom distribution and anorectal physiology results in male patients with rectal intussusception and prolapse.

BACKGROUND: Rectal intussusception and external rectal prolapse are uncommon proctographic findings in men reflecting the lack of studies investigating such patients. The aim of this study was to identify the demographic, clinical, and physiological characteristics of this population with a view to appreciate the mechanism of development of this condition. METHODS: All men, presenting with symptoms of constipation or fecal incontinence, who were diagnosed proctographically with recto-rectal intussusception (RRI)/recto-anal intussusception (RAI) or external rectal prolapse (ERP) between 1994 and 2007 at a tertiary academic colorectal unit were studied. Demographics, relevant comorbidities, distribution and symptom duration, and anorectal physiology results were analyzed retrospectively for each proctographic group and intergroup comparisons performed. RESULTS: Two hundred five men (median age 50 y; range, 13-86) including 155 (75.6%) without any relevant comorbidities were studied. A significant proportion of patients in all proctographic groups reported rectal evacuatory difficulty ([RRI, 46.4%], [RAI, 39.4%], [ERP, 44.8%]; P = 0.38,analysis of variance). Patients also reported a combination of fecal incontinence symptoms (e.g., urge, passive, postdefecatory leakage) that did not differ across the proctographic groups. Anorectal physiological parameters were within normal range and were not found to be statistically different between the proctographic groups with the exception of anal resting pressure, which was lowest in ERP patients (62 cm H2O; range, 14-155) compared with patients with RRI (89 cm H2O; range, 16-250; P = 0.003) and RAI (92 cm H2O; range, 38-175; P = 0.006). CONCLUSIONS: Men with rectal intussusception and prolapse present with a combination of symptoms, predominantly defective rectal evacuation. Anorectal physiological assessment has failed to shed light into the mechanism of development of this condition and thus, the need for large observational studies incorporating integrated defecographic and manometric assessments of the evacuation process.

Prospective clinical audit of two neuromodulatory treatments for fecal incontinence: sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS).

BACKGROUND AND PURPOSE: Two types of neuromodulation are currently practised for the treatment of fecal incontinence (FI): sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS). This study compares these therapies, as no data exist to prospectively assess their relative efficacy and costs. METHODS: The subjects of this study were two distinct cohorts undergoing SNS (between 2003 and 2008) or PTNS (2008-onwards) for FI. Clinical outcomes assessed at 3 months included incontinence scores and the number of weekly incontinence episodes. The direct medical costs for each procedure were calculated from the audited expenditure of our unit. RESULTS: Thirty-seven patients (94.6 % women) underwent permanent SNS and 146 (87.7 % women) underwent PTNS. The mean pre-treatment incontinence score (± SD) was greater in the SNS cohort (14 ± 4 vs. 12 ± 4) and the mean post-treatment incontinence scores were similar for the two therapies (9 ± 5 vs. 10 ± 4), with a greater effect size evident in the SNS patients. In a 'pseudo case-control' analysis with 37 "matched" patients, the effect of both treatments was similar. The cost of treating a patient for 1 year was £ 11,374 ($ 18,223) for permanent SNS vs. £ 1740 ($ 2784) for PTNS. CONCLUSION: Given the lesser cost and invasive nature of PTNS, where both techniques are available, a trial of PTNS could be considered for all patients.

Assessment of female patients with rectal intussusception and prolapse: is this a progressive spectrum of disease?

BACKGROUND: Rectal intussusception may be the initial abnormality of a progressive pelvic floor disorder culminating in external prolapse. The evidence, however, is unclear, and the pathophysiological mechanisms underlying this condition are unknown. OBJECTIVE: The aim of this study is to identify the relationship between age, symptom duration, anorectal physiology parameters, and type of intussusception/prolapse in order to appreciate the natural history of the condition. DESIGN: All female patients diagnosed proctographically with rectorectal/rectoanal intussusception or external prolapse between 1994 and 2007 were studied. Demographics, symptom duration, and anorectal physiology results were compared between these proctographic groups. Patients with repeat proctographic evaluation were also analyzed separately. SETTINGS: This investigation was conducted at a tertiary academic colorectal center. PATIENTS: A total of 1014 women (median age, 51; range, 16-96), including 32 who underwent repeat proctography, were analyzed. MAIN OUTCOME MEASURES: The primary outcomes measured were the differences in median age, symptom duration, and anorectal physiology parameters between the proctographic groups. RESULTS: The cohort exhibited a statistically significant difference (p = 0.0001) in the median age of the proctographic groups with older patients diagnosed with rectoanal rather than rectorectal intussusception, which was supported by uni- and multivariate modeling. Symptom duration was statistically different (p = 0.0002) between the rectorectal intussusception (60 months; range, 1-936) and external rectal prolapse patient groups (36 months; range, 2-732). Patients with external rectal prolapse had statistically lower anal resting (median, 41 versus 77 cmH2O) and squeeze pressures (median 40 versus 56 cmH2O) than patients with rectorectal intussusception. Within 2 years, 19.2% and 3.8% of patients with rectorectal intussusception on the initial proctogram demonstrated progression to rectoanal intussusception and external prolapse. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSION: Rectal intussusception may be an initial abnormality leading to external prolapse, but this appears to happen infrequently. Long-term observational studies are required to fully understand its natural history.

Outcome of sacral nerve stimulation for fecal incontinence in patients refractory to percutaneous tibial nerve stimulation.

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 study of temporary sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity.

OBJECTIVE: 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). BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Efficacy of sacral nerve stimulation for the treatment of fecal incontinence.

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.

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.

Anterior Perineal PlanE for Ultralow Anterior Resection of the Rectum (the APPEAR Technique): a video demonstration.

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.

Percutaneous tibial nerve stimulation for the treatment of urge fecal incontinence.

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.

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 (r = 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.

Anterior Perineal PlanE for Ultra-low Anterior Resection of the Rectum (the APPEAR technique): a prospective clinical trial of a new procedure.

OBJECTIVE: The APPEAR procedure was developed to allow sphincter-preserving rectal resection for both benign and malignant pathology, which would traditionally require abdominoperineal excision or completion proctectomy, if treated by conventional means. This clinical trial (clinicaltrials.gov: NCT00534131) evaluated the short-term clinical and physiological results of this procedure. METHODS: Fourteen patients were enrolled, 7 with neoplasia, 5 with ulcerative colitis, and 2 with traumatic rectal damage. Patients were evaluated preoperatively, and at a median of 2 years after surgery. RESULTS: Nine of 14 patients underwent ileostomy reversal and were followed up for a minimum of 1 year, with 1 patient awaiting closure. Four patients have not yet been considered for ileostomy reversal due to anastomotic perineal fistulae. Transient sexual dysfunction was noted in 3 of 14 patients, but no urological problems occurred. When the APPEAR procedure was performed for neoplasia or trauma, postoperative median Wexner continence score was 5 (range 0-8, n = 6), with a median defecation frequency of 3 (range 1-8/day). All cancers were completely excised with no local recurrence. Following APPEAR with restorative proctocolectomy for ulcerative colitis, median Wexner continence score was 2 (range 0-6, n = 3), with a median daily defecatory frequency of 3 (range 1-5). Preoperative SF-36 scores did not change significantly following ileostomy closure, and anorectal physiological testing was unaltered following perineal dissection. CONCLUSIONS: The APPEAR procedure provides an alternative technique to effect an ultra-low sphincter-saving anastomosis, when this is not possible by conventional surgery. Morbidity was encountered and greater experience will be required to fully assess this approach. Nevertheless, this is a promising new procedure with the potential to reduce the need for a permanent stoma even further than is currently the case.

Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.

BACKGROUND: The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence, for whom the indication for such treatment is unclear. METHODS: After apparently curative resections of colon or rectal cancer, 3239 patients (2963 [91%] with stage II [node negative] disease, 2291 [71%] with colon cancer, median age 63 [IQR 56-68] years) enrolled between May, 1994, and December, 2003, from 150 centres in 19 countries were randomly assigned to receive chemotherapy with fluorouracil and folinic acid (n=1622) or to observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil (370 mg/m2) with high-dose (175 mg) L-folinic acid or low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality. Analyses were done by intention to treat. This trial is registered with the International Clinical Trial Registry, number ISRCTN82375386. FINDINGS: At the time of analysis, 61 (3.8%) patients in the chemotherapy group and 50 (3.1%) in the observation group had missing follow-up. After a median follow-up of 5.5 (range 0-10.6) years, there were 311 deaths in the chemotherapy group and 370 in the observation group; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 (95% CI 0.70-0.95; p=0.008). There were 293 recurrences in the chemotherapy group and 359 in the observation group; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 (0.67-0.91; p=0.001). Treatment efficacy did not differ significantly by tumour site, stage, sex, age, or chemotherapy schedule. Eight (0.5%) patients in the chemotherapy group and four (0.25%) in the observation group died from non-colorectal cancer causes within 30 weeks of randomisation; only one of these deaths was deemed to be possibly chemotherapy related. INTERPRETATION: Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer, although the absolute improvements are small: assuming 5-year mortality without chemotherapy is 20%, the relative risk of death seen here translates into an absolute improvement in survival of 3.6% (95% CI 1.0-6.0).

Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis.

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) x 10(9)/l versus venous 0.26 (0.09-1.6) x 10(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) x 10(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.

Anterior Perineal PlanE for ultra-low Anterior Resection of the rectum (APPEAR) technique: A systematic review.

INTRODUCTION: The Anterior Perineal PlanE for ultra-low Anterior Resection of the rectum (APPEAR) technique utilises a perineal incision to facilitate resection of the distal rectum. The aim of this study was to review use of the APPEAR technique, assessing patient selection, indications, complications and outcomes, both oncological and functional. MATERIALS AND METHODS: A systematic review was carried out to identify studies reporting outcomes following rectal resection via an anterior perineal incision, with no limits on year or language. All studies were included. Quality of studies was assessed using the methodological index for non-randomised studies (MINORS) score. RESULTS: Thirteen studies were identified from 1985 to 2013. 174 patients (102 male), ranging from 21 to 82 years, underwent surgery at eleven centres in seven countries. Maximum experience at one centre is 60 cases. 9 cases were performed for rectal dysplasia, 141 for rectal cancer; 96 resections were R0 (remaining 45 unstated). 14 cases were carried out laparoscopically. 30-day mortality was 2.3% (4 patients); there were 2 further deaths from systemic recurrence. Permanent stoma rate was 8/155 (5%). The most frequent complication was perineal or vaginal fistulation (26 patients): 6 underwent reoperation; 15 healed with conservative management; 5 required a permanent stoma. Functional outcomes were variably reported; median stool frequency was 3/24hrs with average Wexner scores of 5-5.5. CONCLUSION: In selected patients the APPEAR technique offers avoidance of permanent colostomy with good oncological outcomes. The majority of studies had short follow up periods and longer-term outcomes will need evaluation.

Decreased potassium channel IK1 and its regulator neurotrophin-3 (NT-3) in inflamed human bowel.

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.