Sacral nerve stimulation for fecal incontinence related to external sphincter atrophy.

BACKGROUND: Atrophy of the external anal sphincter, a pathologic muscle volume anomaly associated with fecal incontinence, has been shown to be a negative predictor of the outcome of surgery for defects of the external anal sphincter. It is unclear whether external anal sphincter atrophy also affects the outcome of sacral nerve stimulation for fecal incontinence. OBJECTIVE: Our aim was to assess the effectiveness of sacral nerve stimulation in patients with fecal incontinence and external anal sphincter atrophy and to determine whether severity of atrophy and concomitant presence of a sphincter defect are negative predictors of outcome. DESIGN: This was a prospective observational study of treatment outcome. SETTING: The study was conducted from November 2004 through November 2010 at a regional hospital in Italy. PATIENTS: Consecutive patients with fecal incontinence and external anal sphincter atrophy were included. By means of MRI, patients were determined to have either moderate (<50%) or severe (≥ 50%) thinning of and/or replacement of sphincter muscle by fat. The concomitant presence of defects of the external anal sphincter was also detected by MRI. INTERVENTION: All patients underwent sacral nerve stimulation through a staged implantation procedure. MAIN OUTCOME MEASURES: The main outcome measures were improvement in the Cleveland Clinic Florida Fecal Incontinence Scale (Wexner score), number of episodes of incontinence per week, and the Fecal Incontinence Quality of Life Scale. RESULTS: A total of 28 patients underwent definitive implantation of the sacral nerve stimulation device. Wexner scores decreased from a median of 16 (range, 10-20) at baseline to 3 (range, 0-8) at 6-month follow-up (p < 0.001). Weekly incontinence episodes decreased from a mean (SD) of 14.7 (12.5) to 0.40 (0.82); p < 0.001. Improvement was significantly related to severity of fecal incontinence (r = 0.86; p < 0.001). Overall quality-of-life scores improved from a mean of 1.8 (0.6) to 3.8 (0.4);p < 0.001. Sacral nerve stimulation was effective in both moderate (n = 16) and severe (n = 12) atrophy and in patients with (n = 8) or without (n = 20) external anal sphincter defects. LIMITATIONS: The study was limited by its observational nature and relatively small sample size. CONCLUSIONS: Sacral nerve stimulation can be effective in restoring continence and improving quality of life in patients with fecal incontinence related to atrophy of the external anal sphincter, regardless of the severity of atrophy. Moreover, the presence of EAS atrophy does not influence the success of the outcome of SNS in patients with a sphincter defect. These findings are consistent with the hypothesis that the effects of SNS are not achieved solely by its action on the anal sphincter complex.

The value of high-resolution three-dimensional endorectal ultrasonography in the management of submucosal invasive rectal tumors.

PURPOSE: The aims of this prospective study were 1) to evaluate the accuracy of high-resolution three-dimensional endorectal ultrasonography in distinguishing slight from massive submucosal invasion of early rectal tumors, and 2) to determine the technology's role in treatment selection. METHODS: A total of 142 consecutive patients with clinically possible pT1 rectal cancers underwent three-dimensional endorectal ultrasonography. Slight or massive irregularity of the hyperechoic submucosal layer was considered to characterize uT1-slight or uT1-massive tumors. Treatment was selected on the basis of ultrasonographic findings: endoscopic resection or full-thickness transanal local excision was selected for uT1-slight lesions, and radical resection was selected for uT1-massive tumors. Ultrasonographic staging was compared with histopathologic staging. RESULTS: One hundred twenty-six patients were included in the final analyses. Three-dimensional endorectal ultrasonography staged 77 lesions as uT0, 25 as uT1-slight, 20 as uT1-massive, and 4 as uT2. Histologically, adenomas were found in 75 patients and tumor invasion was found in 44 lesions (24 pT1-slight, 16 pT1-massive, 4 pT2). The overall kappa for the concordance between ultrasonographic and histopathologic stagings was 0.81 (95% confidence interval, 0.72-0.89). No invasive carcinomas remained undetected. The depth of invasion was correctly determined in 87.2% of both pT1-slight and pT1-massive lesions. Considering the complete series of 126 patients, the accuracy of this modality in selecting appropriate management was 95.2% (kappa, 0.84; 95% confidence interval, 0.71-0.96). Adequate surgery was performed in 87.5% of pT1 tumors. CONCLUSION: Three-dimensional endorectal ultrasonography is useful for assessing the depth of submucosal invasion in early rectal cancer and for selecting therapeutic options.

Effects of cryopreservation and coculture with pancreatic ductal epithelial cells on insulin secretion from human pancreatic islets.

Long-term storage methods, such as cryopreservation and long-term in vitro culture, hinder the therapeutical application of pancreatic islet transplantation, because they decrease islet viability. Pancreatic ductal epithelial cells (DEC) are putative stem cells for islets, which may secrete specific factors supporting islet growth and function. Hence, we studied the effect of coculture with DEC on the viability of fresh and cryopreserved human pancreatic islets. Islets and DEC were isolated from the pancreas of an organ donor, and part of them were cryopreserved. Fresh and cryopreserved-thawed islets were cultured alone or in the presence of DEC for 14 days at 33 degrees C or 37 degrees C. At day 1 and day 14 of culture, insulin secretion was stimulated by two sequential 45-min exposures to low and high glucose concentrations (3.3 and 16.7 mmol/l, respectively). Insulin concentrations were measured by radio-immunoassay, and the ratio between the insulin responses to high and low glucose was calculated (insulin stimulation index, ISI). After 14 days of culture, some fresh islets were processed for scanning electron microscopy (SEM). At day 14, ISI was markedly reduced in both fresh and cryopreserved islets with respect to 1 day cultures. Cryopreservation reduced ISI at day 1 and day 14, but in the latter case only when cultures were maintained at 37 degrees C. Coculture with DEC did not affect ISI of fresh islets at day 1, and enhanced it at day 14, but only at a culture temperature of 33 degrees C. Conversely, coculture raised ISI of cryopreserved islets at both day 1 and day 14, independently of the culture temperature. SEM showed that at day 14 of culture, the morphology of fresh islets displayed the best preservation when cocultured with DEC at 33 degrees C. Our findings confirm that both long-term culture and cryopreservation decrease viability of human pancreatic islets. Moreover, they indicate that coculture of islets with DEC at 33 degrees C represents a valuable tool to improve the survival and functional activity of islets, especially in the case of cryopreserved material.