Short-term Outcomes of a Randomized Pilot Trial of 2 Treatment Regimens of Transcutaneous Tibial Nerve Stimulation for Fecal Incontinence.

BACKGROUND: Fecal incontinence is a socially disabling condition that affects ≤15% of adults. Neuromodulatory treatments for fecal incontinence are now well established. Less invasive, cheaper, and more ambulatory forms of neuromodulation are under exploration. OBJECTIVE: The purpose of this study was to assess the acceptability and safety of a new ambulatory tibial nerve stimulation device and to determine clinical effect size for 2 differing regimens of therapy. DESIGN: This was a randomized, investigator-blinded, parallel-arm, 6-week pilot trial. SETTINGS: The study was conducted at 7 United Kingdom trial centers. Patients were initially reviewed in the trial center, with subsequent applications of the device performed in the patients home setting. PATIENTS: A total of 43 eligible patients (38 women) who failed conservative management of fecal incontinence were included in the study. INTERVENTION: The study intervention involved twice-weekly, 1- versus 4-hour transcutaneous tibial nerve stimulation for 6 weeks (total of 12 treatments). MAIN OUTCOME MEASURES: Standard fecal incontinence outcome tools (bowel diary, symptom severity score, and generic quality-of-life instruments) were used to collect data at baseline and at 2 weeks posttreatment cessation. RESULTS: A total of 22 patients were randomly assigned to the 1-hour group and 21 to the 4-hour group. Improvements in fecal incontinence outcomes were observed for both groups, including median urge incontinence episodes per week at baseline and posttreatment (1-hour group 2.0 to 0.5 versus 4-hour group 4.0 to 1.0) and deferment time (1-hour group 2.0 to 2.0 minutes versus 4-hour group 0.5 to 5.0 minutes). Accompanying changes were observed in physical functioning domains of quality-of-life instruments. There were no adverse events, and the treatment was highly acceptable to patients. LIMITATIONS: Limitations included the pilot design and lack of control arm in the study. Future trials would need to address these limitations. CONCLUSIONS: This pilot study provides evidence that transcutaneous tibial nerve stimulation with a new ambulatory device is safe and acceptable for the management of fecal incontinence. Additional study is warranted to investigate clinical effectiveness.

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.

Management of colorectal cancer: a role for genetics in prevention and treatment?

Colorectal cancer remains one of the most common cancers in the Western world and amongst the top three causes of cancer morbidity and death. Cancer is caused by genetic mutations, but currently there is little use of genetic information in the clinic with the exception of establishing germline mutations for the uncommon predisposing syndromes. Rapid advances in technologies allowing high throughput analysis of germline and somatic mutations raises the possibility that genetics will find a major role in the clinic distinguishing individuals at low to high risk of cancer, allowing early intervention and stratification of cancers based on mutational pathways for therapeutic interventions. In the future, this will lead to treatment regimes tailored to the individuals and their tumor. Here, we summarize the genetics underlying colorectal cancer and the future role of genetics in prevention, diagnosis, classification and treatment.

Angiopoietin-2 stimulates migration of endothelial progenitors and their interaction with endothelium.

The factors controlling recruitment of endogenous and transplanted endothelial progenitor cells (EPC) to areas of neovascularization are largely unknown. In this study, we have examined the possibility that EPC migration and adhesion could be regulated by angiopoietin-2 (Ang2), a soluble ligand expressed by endothelial cells at sites of vessel remodelling and angiogenesis. We show for the first time that Ang2 causes a marked stimulation of EPC migration. This was specific for EPC as the ligand failed to affect endothelial cell migration. Ang2-stimulated EPC migration was inhibited by soluble Tie2 ectodomain. Furthermore, the ligand stimulated adhesion between EPC and endothelial monolayers.