Summary Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo. While intestinal development proceeded normally in the absence of these miRNAs, epithelial regeneration after injury was dramatically impaired. Surprisingly, we found that miR-143/145 are expressed and function exclusively within the mesenchymal compartment of intestine. Defective epithelial regeneration in miR-143/145-deficient mice resulted from dysfunction of smooth muscle and myofibroblasts and was associated with de-repression of the novel miR-143 target Igfbp5, which impaired IGF signaling after epithelial injury. These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer.

Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apc min/+ mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type.

HistoryRectoanal intussusception (RI), also known as internal intussusception, occult rectal prolapse, intrarectal prolapse, and internal procidentia, is a telescoping of the rectal wall during fecal evacuation. 1 Allingham, in the late 1800s, first described what we label today as rectoanal intussusception as the third variety of procidentia recti in which "the upper part of the rectum descends through the lower part, but does not appear outside the anus." 2,3 He diagnosed this with physical exam and symptoms included "obstinate constipation unrelieved by purgatives; a sensation of burning and fullness in the bowel attended with tenesmus, straining, and difficulty in defecation with occasional discharges of blood and mucus." He postulated that the intussusception was caused by a redundant sigmoid or rectal mesentery. Treatment options at that time included cauterizing portions of the intussusception or a sort of rectopexy via a left lower quadrant incision in which a silk suture is passed through the mesentery and secured it to the abdominal wall. 3 Since its first description, advances have been made in the diagnosis and treatment of rectal intussusception. However, there are many unanswered questions and the best treatment option remains unclear. EtiologyThe pathophysiology and etiology of RI is not well elucidated. Existing theories of etiology fall along two general lines of thought: RI is a dynamic anomaly which may progress to rectal prolapse; or RI is secondary to other abnormalities of pelvic floor function. 1,2 Loose fixation of the rectum to the sacrum or connective tissue disorders may contribute to RI. 4 It is hypothesized that symptoms of obstructed defecation due to RI occur owing to the circular infolding of the rectal wall with subsequent occlusion of the rectal lumen.Several studies have examined whether RI progresses to rectal prolapse. Wijffels et al found a positive correlation between grade of prolapse and age, supporting this postulation. 5 However, other studies do not support this hypothesis. Choi et al found that only 1 in 26 patients treated with dietary therapy or biofeedback for large RI ( 10 mm) developed fullthickness rectal prolapse during 45 months of follow-up (range: 12-118 months). 1 Similarly, Mellgren et al studied 38 patients with rectal intussusception on defecography who were treated nonsurgically, and found that only 2 developed rectal prolapse during the follow-up period. 6 A much larger study of 1,014 women with fecal incontinence and/or obstructive defecation found that of the 26 patients with initial rectorectal intussusception, 1 progressed to external rectal AbstractRectoanal intussusception is an invagination of the rectal wall into the lumen of the rectum. Patients may present with constipation, incomplete evacuation, incontinence, or may be asymptomatic. Defecography has been the gold standard for detection. Magnetic resonance imaging defecography and dynamic anal endosonography are alternatives to conventional defecography. However, both methods are not as sens...

Fecal incontinence is a socially debilitating condition that can lead to social isolation, loss of self-esteem and self-confidence, and depression in an otherwise healthy person. After the appropriate clinical evaluation and diagnostic testing, medical management is initially instituted to treat fecal incontinence. Once medical management fails, there are a few surgical procedures that can be considered. This article is devoted to the various surgical options for fecal incontinence including the history, technical details, and studies demonstrating the complication and success rate.