Fecal DNA testing is an emerging tool to detect colorectal cancer (CRC). Our aims were to estimate the clinical and economic consequences of fecal DNA testing vs. conventional CRC screening.

Placebo-controlled, randomized clinical trials (PC-RCTs) are commonly used to assess therapies for Crohn's disease (CD). Knowledge of the placebo rates of remission and response and understanding of design factors that influence these rates is important for designing future clinical trials evaluating pharmacotherapy of CD. The aims of this study were to estimate rates of remission and response in patients with active CD receiving placebo and to identify factors influencing these rates.

Gastric varices (GV) occur in 20% of patients with portal hypertension either in isolation or in combination with esophageal varices (EV). There is no consensus for optimum treatment of GV and because they comprise an inhomogeneous entity, accurate classification is vital to determine the appropriate management. Gastroesophageal varices (GOV) are classified as GOV1 (EV extending down to cardia or lesser curve) or GOV2 (esophageal and fundal varices). Isolated gastric varices (IGV) may be located in the fundus (IGV1) or elsewhere in the stomach (IGV2). GV possibly bleed less frequently than EV, but GV bleeding is typically difficult to control, associated with a high risk for rebleeding, and high mortality. Fundal varices, large GV (>5 mm), presence of a red spot, and Child's C liver status are associated with a high risk for bleeding. GOV1 have a much lower risk for bleeding. A portosystemic pressure gradient of > or =12 mm Hg is not necessary for GV bleeding, probably related to the high frequency of spontaneous gastrorenal shunts in these patients. GOV1 should be treated as for EV. First-line treatment of bleeding fundal varices is endoscopic variceal obturation. TIPS is currently second-line acute treatment and is used for prevention of rebleeding. The role of some newer interventional radiologic techniques requires further appraisal. This review describes the pathophysiology, diagnosis, natural history, endoscopic, and interventional radiologic treatment options for GV.

Nitric oxide is an intracellular and intercellular messenger with important functions in a number of physiologic and pathobiologic processes within gastroenterology and hepatology, including gastrointestinal tract motility, mucosal function, inflammatory responses, gastrointestinal malignancy, and blood flow regulation. Since the broad review of this topic in Gastroenterology more than 10 years ago, a number of advances have been made in the area of NO biology and its relevance to the gastrointestinal system. The aim of this review is to focus on our expanded understanding of the role NO plays in human gastrointestinal and hepatic physiology and disease processes by drawing on data from relevant in vitro and animal models as well as observational human studies.

The consensus conference "Advancing the Treatment of Fecal and Urinary Incontinence Through Research" had as one of its goals the development of a comprehensive list of research priorities. Experts from all disciplines that treat incontinence-gastroenterology, pediatric gastroenterology, urology, urogynecology, colorectal surgery, geriatrics, neurology, nursing, and psychology-and patient advocates were asked to identify their highest priorities for treatment-related research. Meeting participants were shown the aggregated list and invited to propose additional priorities. Treatments for fecal incontinence (biofeedback, sphincteroplasty, antidiarrheal and laxative medications, and sacral nerve stimulation) require validation by randomized, controlled trials. For urinary incontinence, the greatest need is to compare pharmacological, behavioral, and surgical treatments. Trials assessing combined treatments (e.g., biofeedback plus surgery vs. surgery alone or biofeedback alone) are also needed. New drugs are needed that target anal canal resting pressure in fecal incontinence and hypersensitivity to distention in urge urinary incontinence. It may be possible to substantially reduce the incidence of incontinence through modification of obstetric practices (e.g., avoiding episiotomies or offering elective cesarean delivery to high-risk patients), providing pelvic floor exercises before childbirth, and educating patients to avoid straining during defecation. For the elderly, practical behavioral and pharmacological treatments are needed that can postpone or avoid institutionalization. Social science research may identify ways to counteract the social stigma of fecal incontinence and assist physicians in providing patients with more comprehensive and understandable information on the risks associated with different treatment options.

The International Foundation for Functional Gastrointestinal Disorders (IFFGD) is a nonprofit education and research group. Founded in 1991, the IFFGD provides information and advice to patients around the world with fecal incontinence and other gastrointestinal disorders, educates physicians through medical symposia and other activities, funds and undertakes research, and provides testimony to Congress about the necessity of furthering research activities related to fecal incontinence through the National Institutes of Health. The IFFGD advocates research directed toward more comprehensive identification of quality-of-life issues associated with fecal incontinence and improved assessment and communication of treatment outcomes related to quality of life, standardization of scales to measure incontinence severity and quality of life, assessment of the utility of diagnostic tests for affecting management strategies and treatment outcomes, development of new drug compounds offering new treatment approaches to fecal incontinence, development and testing of strategies for primary prevention of fecal incontinence associated with childbirth, and further understanding of the process of stigmatization as it applies to the experience of individuals with fecal incontinence.

Afferent innervation is important in sensing the degree of bladder fullness and in forming the input limb to involuntary detrusor contractions in neurogenic and probably also non-neurogenic detrusor overactivity. It is likely that homologous mechanisms are involved in control of the bowel. Accumulating evidence now suggests that in conditions of bladder hypersensitivity as well as non-neurogenic detrusor overactivity, there is up-regulation of unmyelinated nerve fibers expressing both the vanilloid receptor and purinergic receptors. The development of a selective neurotoxin that could successfully "deafferent" the bladder would have major therapeutic consequences. Women who respond best to neuromodulation through sacral nerve stimulation are those with a primary disorder of sphincter relaxation and a very large capacity without sensations of urgency or a hyperactive sphincter. For these women, neuromodulation may counteract the inhibitory effects of overactive sphincter afferents on the detrusor, and determination of the central nervous system level at which this response occurs may provide an explanation for the paradoxical finding that both urge incontinence and urinary retention are responsive to this intervention. Experimental evidence suggests that the "procontinence" reaction consists of an inhibitory effect on the detrusor and presumably the lower rectum resulting from contraction of the pelvic floor and the anal or urethral sphincter. Development of methods of enhancing the inhibitory reflex effect could lead to improved voluntary control of micturition and defecation for patients with neurogenic bladder overactivity or spinal cord lesions.

Fecal incontinence affects between 1% and 16% of women, with prevalence increasing with age. The most common cause of fecal incontinence in otherwise healthy women is damage to the anal sphincter(s) during childbirth. As such, the most important tool in the "treatment" of fecal incontinence is its prevention, which should be the first research priority for gynecologists. Routine midline (median) episiotomy has no place in modern obstetrics; when episiotomy must be performed for obstetric indications, use of mediolateral episiotomy should result in fewer anal sphincter injuries than use of midline episiotomy. Additional research questions that gynecologists hope to address are as follows. (1) When anal sphincter injury occurs at delivery, what is the most effective method of repair? Even when repair is performed, women frequently have symptoms of altered bowel function ranging from fecal urgency to frank fecal incontinence. (2) Is it possible to improve the relatively poor results of a strictly surgical repair? Does pelvic muscle rehabilitation (performed either after vaginal delivery or after secondary repair remote from delivery) add significantly to the outcome of women after anal sphincteroplasty? (3) Another more general research priority is to understand the shared and independent factors in the pathophysiology of fecal and urinary incontinence so as to identify modifiable risk factors in women.

Surgical trials differ in several critical aspects from pharmaceutic trials because they are invasive and the procedure itself may carry a significant risk. The surgical procedure cannot be fully specified in advance; although the general approach may be the same, the exact methods used during surgery may differ. Surgeons may have different levels of skill and experience with the techniques; experience is known to affect success rates. Sham surgeries are difficult to justify ethically, yet they have been successful in showing that accepted surgical procedures were not efficacious. Double masking participants in a surgical trial may be difficult; for example, we cannot mask the surgeon. There is also a need to minimize or avoid bias. Therefore, greater flexibility is needed in the design of surgical trials than in the design of pharmaceutic trials. Some of this flexibility is possible through the use of more sophisticated statistical designs. At times, it is necessary to separate the provider of the treatment (the surgeon) from the evaluator of the success of the treatment (a different physician, research nurse, or study coordinator).

There are 4 sources of bias in clinical trials: investigator bias, patient expectation (placebo response), ascertainment bias (inadvertent selection of an unrepresentative sample), and nonspecific effects such as the normal waxing and waning of symptoms over time and the quality of the doctor-patient relationship. In drug trials, these biases are adequately controlled by comparing active to inert pills, randomly assigning subjects to treatments, blinding both the investigator and subject to group assignment, and testing subjects at multiple sites. However, there are special problems with conducting clinical trials of behavioral or psychological interventions that render these controls inadequate. It is impossible to blind the experimenter to which treatment is active, it is difficult to identify a control treatment that is inactive but just as credible to the subject, and doctor-patient relationship variables are more important than in drug trials. The inability to blind the experimenter can be circumvented by having an independent, blinded investigator assess the outcome, and doctor-patient effects can be controlled by using multiple, experienced therapists. The most difficult problem, identifying an appropriate control treatment, can be solved by adhering to 2 principles: the control treatment should be plausible, and it should not have a significant impact on the mechanism that is thought to explain the effectiveness of the investigational treatment. Investigators should confirm that these 2 goals have been achieved by monitoring expectation of benefit with a treatment credibility questionnaire, measuring changes in process variables (variables that reflect the presumed mechanism of treatment), and monitoring differential dropout rates.

Biofeedback techniques used to treat urinary and fecal incontinence lack standardization. Most early protocols used a pressure device placed within the vagina or anal canal, or electromyographic (EMG) sensors in the same locations, to measure the external anal sphincter (EAS) or pelvic floor muscle (PFM) contractile function, and most early studies provided feedback from a single physiological transducer. The goal was to improve bowel and bladder control by improving EAS or PFM contractile function. Protocols that have resulted in the most consistent reductions in urinary incontinent episodes used 2 or more channels of physiological information to reinforce stable abdominal and bladder pressures concurrently with PFM contraction. For fecal incontinence, more significant treatment results were derived when protocols measured (1) patient perception of sensory cues associated with rectal distention and potential loss of stool, (2) short-latency EAS contraction when perceiving rectal distention, (3) inhibition of (extraneous muscle) activity that would increase intra-abdominal pressure during EAS contraction, and (4) reinforcement of sustained (up to 30 seconds) contractions rather than only brief 1- to 2-second contractions. Limited data support the use of surface abdominal EMG measures as indices of extraneous muscle activity associated with increased intra-abdominal pressure and anal or vaginal EMG probes to obtain measures of PFM function. Better results may also be obtained when there are at least 4 training sessions, when daily home exercises are prescribed, and when the therapist is well trained and experienced. These inferences are based for the most part on indirect evidence, and more studies are needed that compare different treatment protocols.

An estimated 15% to 30% of adults over the age of 60 years have urinary incontinence, which is often reported as severe. Although psychological symptoms, especially anxiety and depression, are often associated with urinary incontinence, it seems likely that psychological distress is not a cause but a consequence of suffering from the condition. Cognitive deficits that directly interfere with the neurologic function of the bladder and/or diminish the ability to communicate appear to be important contributors to urinary incontinence. The incidence of fecal incontinence is high in children up to the age of 9 years and ranges from 7% to nearly 10% in adults over the age of 65 years. Although it has been suggested that psychological symptoms can cause fecal incontinence, data are lacking to support a causative association. Psychological disorders and incontinence of urine and feces appear to be common comorbidities. Studies are needed to determine whether the incidence of psychological symptoms in persons with incontinence is comparable for those who seek treatment and those who do not and to compare psychometric and quality-of-life measures before and after treatment to help determine the role of psychological symptoms in persons with fecal and urinary incontinence.