The Impact of Pelvic Floor and Lower Gastrointestinal Symptoms on Quality of Life in Women With Systemic Sclerosis.

BACKGROUND: Systemic sclerosis (SSc) patients with gastrointestinal (GI) involvement have a lower quality of life (QoL) and while the impact of upper GI symptoms on QoL in SSc patients has been described few data exist on the presence and impact of lower gastrointestinal (LGI) and pelvic floor symptoms in SSc. Our goal was to assess the prevalence of these symptoms in women with SSc and evaluate their impact on QoL. A secondary hypothesis was that the impact of LGI symptoms on QoL is mediated by depression. STUDY: Women with SSc (n=175) attending an outpatient scleroderma clinic completed multiple validated questionnaires. Pelvic floor and LGI symptoms included fecal incontinence (FI), urinary incontinence (UI), dual incontinence (DI), chronic constipation, diarrhea, and pelvic pain. The Student t tests adjusted for multiple comparisons were used to evaluate group differences at the 0.05 level. RESULTS: Complete data were available for 160 women. FI was reported by 65, UI by 64, DI by 40, chronic constipation by 94, diarrhea by 82, and pelvic pain by 35 of SSc patients. Overall QoL was reduced in SSc patients with FI (0.96 vs. 0.63; P=0.007), UI (0.96 vs. 0.65; P=0.01), DI (1.11 vs. 0.67; P=0.002), and pelvic pain (1.01 vs. 0.70; P=0.04). Antidepressant use was reported by 26%. The negative impact on QoL in patients with pelvic floor symptoms was partially mediated by depression. CONCLUSIONS: Women with SSc suffer from an increased prevalence of LGI and pelvic floor symptoms including FI, UI, diarrhea, constipation, and pelvic pain and this effect seems to be partially mediated by depression.

Chronic constipation in the elderly.

Constipation is one of the most frequent gastrointestinal disorders encountered in clinical practice in Western societies. Its prevalence increases with age and is more frequently reported in female patients. Chronic constipation has been associated with considerable impairment in quality of life, can result in large individual healthcare costs, and represents a burden to healthcare delivery systems. This review will focus on the definition, epidemiology, diagnostic approach, and non-pharmacologic as well as pharmacologic management of chronic constipation in the elderly, including an overview of new medications currently under clinical investigation.

Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) occurs due to alteration of the microbiota within the upper gastrointestinal tract. Proton pump inhibitor (PPI) therapy has been suggested as a risk factor for SIBO; however, the published reports have yielded conflicting results on the association between PPI therapy and risk of developing SIBO. The aim of this study was to compare the prevalence of SIBO as measured by glucose hydrogen breath testing (GHBT) in patients on PPI therapy compared with those not on PPI therapy. METHODS: A retrospective chart review was completed for all patients who underwent GHBT testing from 2004 to 2010. Breath samples for hydrogen (H2) and methane (CH4) were collected before and every 20 min for 120 min following ingestion of a 50-g oral glucose load. We used the following criteria to define a positive GHBT (a) increase in H2 > 20 parts per million (p.p.m.) over baseline, (b) sustained rise H2 > 10 p.p.m. over baseline, (c) CH4 > 15 p.p.m. over baseline, and (d) either rise H2 > 20 p.p.m. over baseline or CH4 > 15 p.p.m. RESULTS: A total of 1,191 patients (70% female) were included, of whom 566 (48%) were on PPI therapy. GHBT positivity did not differ significantly between PPI users and nonusers by any of the diagnostic criteria used and PPI use was not significantly associated with GHBT positivity using any of these criteria. GHBT positivity was associated with older age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.04) and antidiarrheal use (OR 1.99, 95% CI 1.15-3.44) using H2 > 20, older age (OR 1.01, 95% CI 1.00-1.02) and diarrhea (OR 1.53, 95% CI 1.13-2.09) using H2 > 10, and older age (OR 1.01, 95% CI 1.00-1.02) using either H2 > 20 or CH4 > 15. PPI use was not significantly associated with GHBT positivity using any of these criteria. CONCLUSIONS: In this large, adequately powered equivalence study, PPI use was not found to be significantly associated with the presence of SIBO as determined by the GHBT.

A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome.

Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder.

Imaging findings of pelvic venous insufficiency in patients with postural orthostatic tachycardia syndrome.

OBJECTIVES: Some patients with postural orthostatic tachycardia syndrome (POTS) demonstrate improved dysautonomic symptoms following treatment for pelvic venous insufficiency (PVI). This study assessed the prevalence of significant left common iliac vein (LCIV) compression in POTS patients. METHODS: Radiologists retrospectively reviewed CT images of pelvic veins for 216 women (191 with POTS and 25 age-comparable controls).Quantitative vascular analysis identified percent-diameter compression of the LCIV by the right common iliac artery. Significant LCIV compression was defined as >50%. RESULTS: Significant LCIV compression was found in 69% (131/191) of females with POTS versus 40% (10/25) in controls. The hypothesis that venous compression and presence of POTS are independent was rejected (p = .005). CONCLUSIONS: Significant LCIV compression was noted in a majority of female POTS patients, suggesting that incidence of iliac venous obstruction may be higher than the general population. Patients with POTS and symptoms of PVI may benefit from assessment for venous outflow obstruction.

Food Sensitivity Testing and Elimination Diets in the Management of Irritable Bowel Syndrome.

The nonpharmacologic management of irritable bowel syndrome focuses on dietary modification through the concept of food sensitivity or intolerance. Currently, testing for food allergies is not recommended in the absence of a clinical history consistent with an immunoglobulin E-mediated reaction. Objective means of determining food sensitivity, such as individualized diets, are being studied, but testing for food sensitivity is limited to certain food groups. Diets such as the low-FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet may provide benefit.

Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis.

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional disorder. 5-Hydroxytryptamine (5-HT) is a key modulator of gastrointestinal sensorimotor function. Many patients have IBS that can be difficult to treat, which has led to the development of newer agents, such as 5-HT(3) antagonists and 5-HT(4) agonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the efficacy of all available 5-HT agents in IBS. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to June 2008). Trials recruiting adults with IBS in primary, secondary, or tertiary care comparing 5-HT(3) antagonists or 5-HT(4) agonists with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. RESULTS: The strategic search identified 1,593 citations. A total of 29 RCTs were eligible for inclusion; placebo was compared with 5-HT(3) antagonists in 11 RCTs, with tegaserod in 11, and with mixed 5-HT(3) antagonists/5-HT(4) agonists in 7. The study quality was generally high. The RR of IBS symptoms persisting with 5-HT(3) antagonists vs. placebo was 0.78 (95% CI: 0.71-0.86), with a similar benefit for both alosetron and cilansetron. Tegaserod was also superior to placebo (RR=0.85; 95% CI: 0.80-0.90). Renzapride and cisapride had no benefit in IBS. CONCLUSIONS: Alosetron, cilansetron, and tegaserod are all effective in the treatment of IBS. Serious adverse events were rare in the eligible RCTs included in this systematic review.

Serologic profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility.

BACKGROUND & AIMS: Autoimmune gastrointestinal dysmotility is a limited autoimmune dysautonomia occurring idiopathically or in the context of an anatomically remote neoplasm, previously documented or unsuspected. Here we report 24 Mayo Clinic patients in whom the profile of serum autoantibodies aided this diagnosis. METHODS: All patients were ascertained serologically in the course of service evaluation for autoantibodies consistent with neurologic autoimmunity. Review of their histories, motility studies, and laboratory findings revealed that all had presented with subacute gastrointestinal dysmotility. RESULTS: Recorded motility abnormalities included esophageal dysmotility 8 (6 had achalasia), delayed gastric emptying 12, slow small intestinal transit 7, slow colonic transit 4, and pelvic floor dyssynergia 4. Four patients underwent abdominal surgery; 2 commenced total parenteral nutrition. Plasma membrane cation channel autoantibodies were detected in 23 patients: neuronal voltage-gated calcium channel (5 N-type and 1 P/Q-type), acetylcholine receptor (11 ganglionic-type and 4 muscle-type), and neuronal voltage-gated potassium channel autoantibodies (4). Two patients had antineuronal nuclear autoantibodies, type 1. Approximately half of the patients had neural autoantibodies (including skeletal muscle striational and glutamic acid decarboxylase, 65kd isoform) or other antibody markers of organ-specific autoimmunity (thyroid or gastric parietal cell specificities). Neoplasia was diagnosed in 11 patients (9 recent, 2 remote): lung, breast and endometrial, gastrointestinal and thymoma. Moderate to dramatic improvement in gastrointestinal symptoms was reported after immunotherapy in 4 of 4 patients treated and after pyridostigmine treatment in 2 of 2 patients treated. CONCLUSIONS: Autoimmune serology aids the diagnosis of autoimmune gastrointestinal dysmotility, both paraneoplastic and idiopathic, and might guide management.

Endoscopic ultrasound-guided gastric botulinum toxin injections in obese subjects: a pilot study.

BACKGROUND: Gastric injections of botulinum toxin A (BTA) may induce changes in gastric emptying and body weight, but results vary. BTA dose and depth of injection may affect efficacy. This study assessed changes in gastric emptying, satiation, symptoms, and body weight after endoscopic ultrasound (EUS)-guided injection of 100 or 300 U BTA into gastric antral muscularis propria of obese subjects. METHODS: Open label study of ten healthy, obese adults (age = 29-49 years, body mass index = 31-54 kg/m(2)) who received 100 U (n = 4) or 300 U (n = 6) BTA and were followed for 16 weeks. Measures included gastric emptying of solids (by scintigraphy), satiation (by maximum tolerated volume [MTV] during nutrient drink test), gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale), caloric intake (by food frequency questionnaire), and body weight. RESULTS: For the entire cohort, MTV decreased from 1,380 cc (range: 474-2,014) at baseline to 620 cc (range: 256-1,180) 2 weeks after BTA injection; decreases were statistically significant in the subjects receiving 300 U BTA (p = 0.03). Average body weight loss was 4.9 (+/-6.3) kg after 16 weeks. Gastric emptying T(1/2) was prolonged in the 300 U BTA group, but not significantly different from baseline (p = 0.17). BTA injections were well tolerated without significant adverse effects. CONCLUSION: EUS-guided injection of BTA into gastric muscularis propria can be performed safely with minimal adverse effects. A dose of 300 U BTA significantly enhances satiation, is associated with weight loss, and may slow gastric emptying. Further study of higher dose BTA in obese subjects is warranted.

Update on constipation: one treatment does not fit all.

Constipation is a common clinical problem that can be difficult to manage. It has a variety of identifiable causes, but even idiopathic constipation has different possible mechanisms. Often, the key to improvement and patient satisfaction is to understand the mechanism and the patient.

Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS. METHODS: Gene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay. RESULTS: A total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls. CONCLUSIONS: Values for serum 25(OH)D concentrations exhibited a trend towards lower vitamin D levels within the IBS cohort. In addition, the expression of select IBS genetic biomarkers, including tryptophan hydroxylase 1, was modulated by vitamin D. Strikingly, the direction of gene regulation elicited by vitamin D in colonic cells is "opposite" to the gene expression profile observed in IBS patients, suggesting that vitamin D may help "reverse" the pathological direction of biomarker gene expression in IBS. Thus, our results intimate that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency.

Intractable Constipation in the Elderly.

OPINION STATEMENT: Chronic constipation is a common gastrointestinal disorder disproportionately affecting the elderly. Immobility, polypharmacy, and physiologic changes contribute to its increased prevalence in this population. Unidentified and undertreated constipation leads to a significant negative impact on quality of life and an increase in healthcare spending. Careful physical examination and exploration of the clinical history can unmask primary and secondary forms of constipation, guiding diagnostic and therapeutic considerations. Non-pharmacologic treatment options include bowel training and biofeedback as well as the addition of fiber. Laxatives are safe and can be used long term; thus, they remain the mainstay of therapy. Newer agents with specific physiologic targets have proven to be effective in adults with chronic constipation, but data is lacking for safety profile in the elderly. Consideration for surgery in medically refractory cases should be entertained, while use of neuromodulation is not ready for prime time. This is a review of the currently available treatment options for chronic constipation in adults and specifically tailored towards the elderly.

IBS--review and what's new.

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal motility disorder broadly characterized by abdominal pain/discomfort associated with altered bowel habits. The chronic and bothersome nature of IBS symptoms often negatively affects patient quality of life and activity level and places a substantial economic burden on patients and the healthcare system. Advances in research have led to a greater understanding of the underlying pathophysiology of IBS, particularly regarding the role serotonin plays in the gastrointestinal tract; the development of stepwise, symptom-based diagnostic strategies that allow for a diagnosis of IBS to be made without the need for extensive laboratory testing; and the development of treatment options targeting underlying pathophysiologic mechanisms that provide relief of the multiple symptoms associated with IBS. This review highlights recent advances in research and discusses how these findings can be applied to daily clinical practice.

New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists.

Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management. Most patients with irritable bowel syndrome receive outpatient care, but irritable bowel syndrome-related hospitalizations do occur. The pathophysiology of irritable bowel syndrome is multifactorial (i.e. genetics, immune components, changes in the gut microbiota, disturbances in physiologic stress response systems, and psychosocial factors). Management of irritable bowel syndrome can include lifestyle changes, dietary interventions, counseling, psychologic medication, and agents that affect gastrointestinal motility. A number of therapies have emerged in recent years with clinical trial data demonstrating efficacy and safety for patients with irritable bowel syndrome, including agents that target gastrointestinal motility (i.e. linaclotide), gastrointestinal opioid receptors (i.e. asimadoline, eluxadoline), and gut microbiota (i.e. rifaximin). Linaclotide has been shown to significantly improve stool frequency and abdominal pain compared with placebo in constipation-predominant irritable bowel syndrome (number needed to treat, 5.1). Asimadoline shows efficacy in patients with moderate-to-severe irritable bowel syndrome-related pain. Rifaximin provided adequate relief of global irritable bowel syndrome symptoms versus placebo for a significantly greater percentage of patients with diarrhea-predominant irritable bowel syndrome (p < 0.001). Management that encompasses all aspects of irritable bowel syndrome (gastrointestinal symptoms) and comorbid psychologic symptoms (e.g. anxiety or depression) is important for improving overall patient health and well-being.

Multi-society guideline for reprocessing flexible gastrointestinal endoscopes. Society for Healthcare Epidemiology of America.

Flexible gastrointestinal endoscopy is a valuable diagnostic and therapeutic tool for the care of patients with gastrointestinal and pancreaticobiliary disorders. Compliance with accepted guidelines for the reprocessing of gastrointestinal endoscopes between patients is critical to the safety and success of their use. When these guidelines are followed, pathogen transmission can be effectively prevented. Increased efforts and resources should be directed to improve compliance with these guidelines. Further research in the area of gastrointestinal endoscope reprocessing should be encouraged. The organizations that endorsed this guideline are committed to assisting the FDA and manufacturers in addressing critical infection control issues in gastrointestinal device reprocessing.

Constipation: understanding mechanisms and management.

Constipation is a frequently diagnosed gastrointestinal disorder. Symptoms of constipation are common, with the greatest prevalence in the elderly. Evaluation of constipation begins with a detailed medical history and a focused anorectal examination. Diagnostic testing for constipation is not routinely recommended in the initial evaluation in the absence of alarm signs. Key self-management strategies include increased exercise, a high-fiber diet, and toilet training. High-fiber diets can worsen symptoms in some patients who have chronic constipation. Biofeedback is an effective treatment option for patients who have constipation caused by outlet obstruction defecation. A variety of medications are available to remedy constipation.