Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter Anatomy and Function in a Rat Model at a Time Remote From Injury.

BACKGROUND: We have explored cell-based therapy to aid anal sphincter repair, but a conditioning injury is required to direct stem cells to the site of injury because symptoms usually manifest at a time remote from injury. OBJECTIVE: We aimed to investigate the effect of local electrical stimulation followed by mesenchymal stem cell delivery on anal sphincter regeneration at a time remote from injury. DESIGN AND MAIN OUTCOME MEASURES: With the use of a rat model, electrical stimulation parameters and cell delivery route were selected based on in vivo cytokine expression and luciferase-labeled cell imaging of the anal sphincter complex. Three weeks after a partial anal sphincter excision, rats were randomly allocated to 4 groups based on different local interventions: no treatment, daily electrical stimulation for 3 days, daily stimulation for 3 days followed by stem cell injection on the third day, and daily electrical stimulation followed by stem cell injection on the first and third days. Histology-assessed anatomy and anal manometry evaluated physiology 4 weeks after intervention. RESULTS: The electrical stimulation parameters that significantly upregulated gene expression of homing cytokines also achieved mesenchymal stem cell retention when injected directly in the anal sphincter complex in comparison with intravascular and intraperitoneal injections. Four weeks after intervention, there was significantly more new muscle in the area of injury and significantly improved anal resting pressure in the group that received daily electrical stimulation for 3 days followed by a single injection of 1 million stem cells on the third day at the site of injury. LIMITATION: This was a pilot study and therefore was not powered for functional outcome. CONCLUSIONS: In this rat injury model with optimized parameters, electrical stimulation with a single local mesenchymal stem cell injection administered 3 weeks after injury significantly improved both new muscle formation in the area of injury and anal sphincter pressures.

Current status: new technologies for the treatment of patients with fecal incontinence.

Fecal incontinence is a frequent and debilitating condition that may result from a multitude of different causes. Treatment is often challenging and needs to be individualized. During the last several years, new technologies have been developed, and others are emerging from clinical trials to commercialization. Although their specific roles in the management of fecal incontinence have not yet been completely defined, surgeons have access to them and patients may request them. The purpose of this project is to put into perspective, for both the patient and the practitioner, the relative positions of new and emerging technologies in order to propose a treatment algorithm.

A randomized multicenter trial to compare long-term functional outcome, quality of life, and complications of surgical procedures for low rectal cancers.

INTRODUCTION: Colonic pouches have been used for 20 years to provide reservoir function after reconstructive proctectomy for rectal cancer. More recently coloplasty has been advocated as an alternative to a colonic pouch. However there have been no long-term randomized, controlled trials to compare functional outcomes of coloplasty, colonic J-Pouch (JP), or a straight anastomosis (SA) after the treatment of low rectal cancer. AIM: : To compare the complications, long-term functional outcome, and quality of life (QOL) of patients undergoing a coloplasty, JP, or an SA in reconstruction of the lower gastrointestinal tract after proctectomy for low rectal cancer. METHODS: A multicenter study enrolled patients with low rectal cancer, who were randomized intraoperatively to coloplasty (CP-1) or SA if JP was not feasible, or JP or coloplasty (CP-2) if a JP was feasible. Patients were followed for 24 months with SF-36 surveys to evaluate the QOL. Bowel function was measured quantitatively and using Fecal Incontinence Severity Index (FISI). Urinary function and sexual function were also assessed. RESULTS: Three hundred sixty-four patients were randomized. All patients were evaluated for complications and recurrence. Mean age was 60 +/-12 years, 71% were male. Twenty-three (7.4%) died within 24 months of surgery. No significant difference was observed in the complications among the 4 groups. Two hundred ninety-seven of 364 were evaluated for functional outcome at 24 months. There was no difference in bowel function between the CP-1 and SA groups. JP patients had fewer bowel movements, less clustering, used fewer pads and had a lower FISI than the CP-2 group. Other parameters were not statistically different. QOL scores at 24 months were similar for each of the 4 groups. CONCLUSIONS: In patients undergoing a restorative resection for low rectal cancer, a colonic JP offers significant advantages in function over an SA or a coloplasty. In patients who cannot have a pouch, coloplasty seems not to improve the bowel function of patients over that with an SA.

Prospective, randomized, controlled trial between a pathway of controlled rehabilitation with early ambulation and diet and traditional postoperative care after laparotomy and intestinal resection.

INTRODUCTION: In an era of dwindling hospital resources and increasing medical costs, safe reduction in postoperative stay has become a major focus to optimize utilization of healthcare resources. Although several protocols have been reported to reduce postoperative stay, no Level I evidence exists for their use in routine clinical practice. METHODS: Sixty-four patients undergoing laparotomy and intestinal or rectal resection were randomly assigned to a pathway of controlled rehabilitation with early ambulation and diet or to traditional postoperative care. Time to discharge from hospital, complication and readmission rates, pain level, quality of life, and patient satisfaction scores were determined at the time of discharge and at 10 and 30 days after surgery. Subgroups were defined to evaluate those who derived the optimal benefit from the protocol. RESULTS: Pathway patients spent less total time in the hospital after surgery (5.4 vs. 7.1 days; P = 0.02) and less time in the hospital during the primary admission than traditional patients. Patients younger than 70 years old had greater benefits than the overall study group (5 vs. 7.1 days; P = 0.01). Patients treated by surgeons with the most experience with the pathway spent significantly less time in the hospital than did those whose surgeons were less experienced with the pathway (P = 0.01). There was no difference between pathway and traditional patients for readmission or complication rates, pain score, quality of life after surgery, or overall satisfaction with the hospital stay. CONCLUSIONS: Patients scheduled for a laparotomy and major intestinal or rectal resection are suitable for management by a pathway of controlled rehabilitation with early ambulation and diet. Pathway patients have a shorter hospital stay, with no adverse effect on patient satisfaction, pain scores, or complication rates. Patients younger than 70 years of age derive the optimal benefit, and increased surgeon experience improves outcome.