Systematic review of the clinical effectiveness of neuromodulation in the treatment of faecal incontinence.

BACKGROUND: Over the past 18 years neuromodulation therapies have gained support as treatments for faecal incontinence (FI); sacral nerve stimulation (SNS) is the most established of these. A systematic review was performed of current evidence regarding the clinical effectiveness of neuromodulation treatments for FI. METHODS: The review adhered to the PRISMA framework. A comprehensive search of the literature included PubMed, MEDLINE, Embase and Evidence-Based Medicine Reviews. Methodological quality assessment and data extraction were completed in a systematic fashion. RESULTS: For SNS, 321 citations were identified initially, of which 61 studies were eligible for inclusion. Of studies on other neuromodulation techniques, 11 were eligible for review: seven on percutaneous tibial nerve stimulation (PTNS) and four on transcutaneous tibial nerve stimulation (TTNS). On intention-to-treat, the median (range) success rates for SNS were 63 (33-66), 58 (52-81) and 54 (50-58) per cent in the short, medium and long terms respectively. The success rate for PTNS was 59 per cent at the longest reported follow-up of 12 months. SNS, PTNS and TTNS techniques also resulted in improvements in Cleveland Clinic Incontinence Score and quality-of-life measures. Despite significant use of neuromodulation in treatment of FI, there is still no consensus on outcome reporting in terms of measures used, aetiologies assessed, length of follow-up or assessment standards. CONCLUSION: Emerging data for SNS suggest maintenance of its initial therapeutic effect into the long term. The clinical effectiveness of PTNS is comparable to that of SNS at 12 months, although there is no evidence to support its continued effectiveness after this period. PTNS may be a useful treatment before SNS. The clinical effectiveness of TTNS is still uncertain owing to the paucity of available evidence. A consensus to standardize the use of outcome measures is recommended in order that further reports can be compared meaningfully.

Percutaneous tibial nerve stimulation (PTNS) in females with faecal incontinence: the impact of sphincter morphology and rectal sensation on the clinical outcome.

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is an acceptable second line treatment for patients with faecal incontinence (FI) unresponsive to conservative measures. There is however a paucity of data in the literature regarding its efficacy. The aim of this prospective study was to evaluate the efficacy of PTNS in an exclusively female cohort of patients and to identify factors that may predict treatment response. METHOD: A prospective cohort of female patients with FI underwent evaluation of sphincter morphology, anorectal pressures and rectal sensation as part of their physiologic assessment prior to treatment. PTNS was performed according to a specific departmental protocol. The clinical outcomes measured were: (1) Cleveland Clinic incontinence scores, (2) deferment time and (3) weekly incontinence episodes. Outcomes were compared at baseline and following treatment using appropriate statistical tests. Clinical outcomes were correlated with the results of the anorectal physiology testing (i.e. sphincter morphology, rectal sensation). RESULTS: Eighty-eight female patients with a mean age of 58.0 ± 13.6 years were included in the analysis. FI was predominantly a late consequence of obstetric injury. The mean incontinence score improved from 12.2 ± 4.0 at baseline to 9.1 ± 4.6 following treatment (p < 0.0001). Statistically significant improvements were also seen in the median deferment time and median number of weekly incontinence episodes. Sphincter damage and altered rectal sensation did not appear to influence the outcomes. CONCLUSIONS: PTNS is an effective treatment in female patients with FI. Improvements in clinical outcomes were independent of damage to the anal sphincter complex in patients with normal rectal sensation.

Short-term outcome following percutaneous tibial nerve stimulation for faecal incontinence: a single-centre prospective study.

AIM: Percutaneous tibial nerve stimulation (PTNS) is increasingly being used as a treatment for faecal incontinence (FI). The evidence for its efficacy is limited to a few studies involving small numbers of patients. The aim of the study was to assess the efficacy of PTNS in patients with urge, passive and mixed FI. METHOD: A prospective cohort of 100 patients with FI was studied. Continence scores were determined before treatment and following 12 sessions of PTNS using a validated questionnaire [Cleveland Clinic Florida (CCF)-FI score]. The deferment time and average number of weekly incontinence episodes before and after 12 sessions of treatment were estimated from a bowel dairy kept by the patient. Quality of life was assessed prior to and on completion of 12 sessions of PTNS using a validated questionnaire [Rockwood Faecal Incontinence Quality of Life (QoL)]. RESULTS: One hundred patients (88 women) of median age of 57 years were included. Patients with urge FI (n=25) and mixed FI (n=60) demonstrated a statistically significant improvement in the mean CCF-FI score (11.0 ± 4.1 to 8.3 ± 4.8 and 12.8 ± 3.7 to 9.1 ± 4.4) with an associated improvement in the QoL score. This effect was not observed in patients with purely passive FI (n=15). CONCLUSION: The study demonstrates that PTNS benefits patients with urge and mixed FI, at least in the short term.

Strategies to improve non-viral vectors--potential applications in clinical transplantation.

Prevention of acute rejection has been well controlled with immunosuppressive drugs. However, the long-term control of rejection is less satisfactory and the side effects of chronic usage of these drugs are far from acceptable. Thus, more imaginative options for therapy need to be explored. Gene therapy has potential promise in preserving allografts, preventing rejection and inducing tolerance. Despite this initial promise in many animal models, the translation of gene therapy to the clinical arena has been slow. This may be related in part to the deficiencies in vector development. Existing viral vectors are efficient at transducing allografts, but they induce inflammatory and pathogenic effects. Although the alternative non-viral systems are relatively innocuous, they are less efficient at gene delivery. This review systematically analyses the limitations of non-viral vector technology and the strategies that have been developed to overcome these limitations. Future development of non-viral vectors may have potential application in clinical transplantation.

Local recurrence after curative resection for rectal cancer is associated with anterior position of the tumour.

BACKGROUND: Mobilization of rectal cancer can be difficult if the tumour is located anteriorly and may result in a higher incidence of local recurrence. The aim of this study was to determine whether local recurrence and survival following curative resection of rectal cancer were associated with the position of the tumour. METHODS: Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1990 to December 1998, with follow-up to December 2003. RESULTS: The 5-year local recurrence rate was 15.9 (95 per cent confidence interval (c.i.) 11.0 to 22.8) per cent in 176 patients with tumours that had an anterior component compared with 5.8 (95 per cent c.i. 2.8 to 11.9) per cent in 132 patients with tumours without an anterior component (P = 0.009). This association persisted after adjustment for other factors linked to local recurrence (hazard ratio (HR) 2.4 (95 per cent c.i. 1.1 to 5.4)). Similarly, anterior position had a significant negative independent association with survival (HR 1.4 (95 per cent c.i. 1.0 to 2.00)). CONCLUSION: Anterior position is an independent negative prognostic factor for both local recurrence and survival after curative resection of rectal cancer.

The evolving role of gene-based treatment in surgery.

BACKGROUND: The completion of the sequencing of the human genome in 2003 marked the dawn of a new era of human biology and medicine. Although these remarkable scientific advances improve the understanding of human biology, the question remains how this rapidly expanding knowledge of functional genomics affects the role of surgeons. This article reviews the potential therapeutic application of gene therapy for various surgical conditions. METHODS: The core of this review was derived from a Medline database literature search. RESULTS AND CONCLUSION: The currently available vectors in the field of gene therapy and their limitations for clinical applications were analysed. The achievements of gene therapy in clinical trials and the future ramifications for surgery were also explored. Whether gene therapy takes a major role in surgical practice will depend greatly on the success of future vector development. Advances in viral vector technology to reduce the inflammatory effect, and improvements in the efficiency of gene delivery using non-viral vector technology, would allow this form of therapy to become more clinically applicable.

Radiological appearances in the pelvis following rectal cancer surgery.

Radiology has a significant role in the evaluation of surgery for rectal cancer. With recent developments in surgical techniques, the number of neorectal reservoir configurations has increased. It is important to recognize the normal and abnormal appearances, both early and late, following pelvic surgery. The aim of this pictorial review is to demonstrate the imaging techniques that are used in both the investigation and the follow-up of patients who have undergone uncomplicated or complicated rectal resection.

Rectal sensorimotor dysfunction in patients with urge faecal incontinence: evidence from prolonged manometric studies.

BACKGROUND AND AIMS: Although external anal sphincter dysfunction is the major cause of urge faecal incontinence, approximately 50% of such patients have evidence of rectal hypersensitivity and report exaggerated stool frequency and urgency. The contribution of rectosigmoid contractile activity to the pathophysiology of this condition is unclear, and thus the relations between symptoms, rectal sensation, and rectosigmoid motor function were investigated. METHODS: Fifty two consecutive patients with urge faecal incontinence, referred to a tertiary surgical centre, and 24 volunteers, underwent comprehensive anorectal physiological investigation, including prolonged rectosigmoid manometry. Patients were classified on the basis of balloon distension thresholds into those with rectal hypersensitivity (n = 27) and those with normal rectal sensation (n = 25). Automated quantitative analysis of overall rectosigmoid contractile activities and, specifically, high amplitude contractions and rectal motor complex activity was performed. RESULTS: External anal sphincter dysfunction was similar in both patient groups. Overall, phasic activity and high amplitude contraction frequency were greater, and rectal motor complex variables significantly altered, in those with rectal hypersensitivity. Symptoms, more prevalent in the rectal hypersensitivity group, were also more often associated with rectosigmoid contractile events. For individuals, reduced compliance and increased rectal motor complex frequency were only observed in patients with rectal hypersensitivity. CONCLUSIONS: We have identified a subset of patients with urge faecal incontinence-namely, those with rectal hypersensitivity-who demonstrated increased symptoms, enhanced perception, reduced compliance, and exaggerated rectosigmoid motor activity. Comprehensive assessment of rectosigmoid sensorimotor function, in addition to evaluation of anal function, should be considered in the investigation of patients with urge faecal incontinence.

Contribution of the pudendal nerve to sensation of the distal rectum.

BACKGROUND: Anal and rectal sensory mechanisms and pudendal nerve function are important in the control of faecal continence. The contribution of the pudendal nerve to sensation of the distal rectum was investigated. METHODS: Heat thresholds in the anal canal, distal and mid rectum were measured using a specially designed thermoprobe. Rectal sensory threshold volumes were measured using the balloon distension method. Needle electrodes were inserted into the external anal sphincter. Pudendal nerve block was performed through a perineal approach, and completeness assessed by loss of electromyographic activity. Heat and rectal volume thresholds were measured again following unilateral and bilateral pudendal nerve block. RESULTS: The technique was successful in four of six volunteers. Bilateral pudendal nerve block produced complete anaesthesia to heat in the anal canal (P = 0.029), but had no effect on heat thresholds in the distal or mid rectum. Rectal sensory threshold volumes were also unaffected by pudendal nerve anaesthesia. CONCLUSION: Anal canal sensation is subserved by the pudendal nerve, but this nerve is not essential to nociceptive sensory mechanisms in the distal or mid rectum. The transition between visceral control mechanisms in the lower rectum and somatic mechanisms in the anal canal may have functional importance in the initiation of defaecation and the maintenance of continence.

The surgical management of haemorrhoids--a review.

A number of new surgical treatments have led to a reappraisal of haemorrhoid disease over the last few decades. Despite a range of treatment modalities, the options are limited in their effectiveness and can lead to a number of complications. An inadequate classification system based on appearance rather than symptoms makes the choice of appropriate therapy difficult. More recent techniques have led to a move away from surgical excision. However, further research is required to establish their precise indications and long-term efficacy.

What factors influence survival in patients with unresected synchronous liver metastases after resection of colorectal cancer?

OBJECTIVE: The aim of this study was to determine whether the survival of patients with untreated synchronous liver metastases after resection of a colorectal cancer was associated with any features of the primary tumour. METHODS: Information for 398 consecutive patients with unresected liver metastases in the period 1971-2001 was examined by multivariate survival analysis. RESULTS: Of 19 clinical and pathological variables considered, survival was independently associated only with residual tumour in a line of resection (hazard ratio (HR) 1.95), venous invasion (HR 1.87), right colonic tumour (HR 1.68), lymph node metastasis (HR 1.54), and extra-hepatic metastasis (HR 1.16); 8.3% of patients had none of these adverse features. Their 2-year overall survival rate was 39.2%, compared with only 16.5% (P < 0.001) in those with one or more adverse features. CONCLUSIONS: These findings may assist in selecting patients most likely to benefit from treatment of hepatic metastases and in counselling patients and their relatives.

The anal reflex elicited by cough and sniff: validation of a neglected clinical sign.

BACKGROUND: It is unclear whether contraction of the external anal sphincter (EAS) following a voluntary cough is an integral component of the cough response itself, or a reflex response to the abdominal and pelvic floor dynamics induced by the cough. Clinical experience suggests a reflex origin for this response. OBJECTIVE: To compare motor latencies for intercostal, abdominal, and EAS muscle contraction after transcranial magnetic stimulation with those following voluntary coughing and sniffing. METHODS: A needle electrode inserted into the EAS measured responses, which were confirmed by tonic electromyographic recording. Direct motor latencies from the cerebral cortex to the intercostal, rectus abdominis and EAS muscles were obtained using transcranial magnetic stimulation. Sniff and cough induced responses were also recorded in these muscles. RESULTS: The results suggest that EAS responses following a voluntary cough or sniff represent a polysynaptic reflex. CONCLUSIONS: As the cough induced anal reflex response is consistent and easily elicited, its use in clinical neurological examination is appropriate.

Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency.

BACKGROUND: Faecal urgency and incontinence with rectal hypersensitivity is a distressing, unexplained disorder that is inadequately treated. We aimed to determine whether expression of the heat and capsaicin receptor vanilloid receptor 1 (TRPV1 or VR1) was changed in rectal sensory fibres, and to correlate nerve fibre density with sensory abnormalities. METHODS: We compared full-thickness rectal biopsy samples from nine patients with physiologically characterised rectal hypersensitivity with tissue samples from 12 controls. Sensory thresholds to rectal balloon distension and heating the rectal mucosa were measured before biopsy. We assessed specimens with immunohistochemistry and image analysis using specific antibodies to TRPV1; nerve growth factor (NGF) receptor tyrosine kinase A; glial cell line-derived neurotrophic factor (GDNF); neuropeptides calcitonin gene-related peptide (CGRP) and substance P; the related vanilloid receptor-like protein (VRL) 2; glial markers S-100 and glial fibrillary acid protein (GFAP); and the nerve structural marker peripherin. FINDINGS: In rectal hypersensitivity, nerve fibres immunoreactive to TRPV1 were increased in muscle, submucosal, and mucosal layers: in the mucosal layer, the median% area positive was 0.44 (range 0.30-0.59) in patients who were hypersensitive and 0.11 (0.00-0.21) in controls (p=0.0005). The numbers of peripherin-positive fibres also increased in the mucosal layer (hypersensitive 3.00 [1.80-6.50], controls 1.20 [0.39-2.10]: (p=0.0002). The increase in TRVP1 correlated significantly with the decrease in rectal heat (p=0.03) and the distension (p=0.02) sensory thresholds. The thresholds for heat and distension were also significantly correlated (p=0.0028). Expression of nerve fibres positive for GDNF (p=0.001) and tyrosine kinase A (p=0.002) was also increased, as were cell bodies of the submucosal ganglia immunoreactive to CGRP (p=0.0009). INTERPRETATION: Faecal urgency and rectal hypersensitivity could result from increased numbers of polymodal sensory nerve fibres expressing TRPV1. The triggering factor or factors remain uncertain, but drugs that target nerve terminals that express this receptor, such as topical resiniferatoxin, deserve consideration.