The impact of gastroesophageal reflux disease symptoms in scleroderma: effects on sleep quality.

Systemic scleroderma/sclerosis (SSc) is an autoimmune connective tissue disease, which can lead to esophageal motor dysfunction and gastroesophageal reflux disease (GERD). Nocturnal GERD symptoms may be associated with sleep disturbances, which in turn can drastically affect well-being and fatigue levels. We hypothesized that GERD symptoms would be associated with poorer sleep in patients with SSc. Rheumatologist established SSc patients completed the following questionnaires: the UCLA scleroderma clinical trial consortium gastrointestinal tract instrument (GIT) 2.0 questionnaire; the Pittsburgh sleep quality index (PSQI); the fatigue severity scale (FSS); the multidimensional gastrointestinal symptom severity index (GSSI). Poor sleep quality was defined by a PSQI total score >5. Questionnaires were completed by 287 patients [mean (SD) age = 59 (14) years; female = 243]. Poor sleep quality was identified in 194 (68%) patients. Patients with poor sleep quality reported less sleep time and increased fatigue compared to those with normal sleep scores. SSc patients with poor sleep had significantly higher GIT Reflux scores (P < .001), and poor sleep was more frequent in those with moderate/severe versus mild/no heartburn on GISSI (P < .001). Narcotic and antidepressant use was significantly more frequent in SSc patients with poor sleep quality. Multivariable logistic regression supported the association between GERD symptoms and poor sleep after controlling for age, sex, and body mass index (BMI) (2.53, 95% confidence interval (CI) 1.52-4.25; P < .001). The association remained after controlling for narcotic and antidepressant use (2.20, 95% CI 1.29-3.73; P < .001). SSc patients who reported GERD symptoms were also more likely to report poor sleep quality. Future studies should examine mechanisms underlying nocturnal GERD symptoms in SSc patients, and the impact of improved GERD symptom control on sleep quality.

Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood. AIMS: Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology. METHODS: This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS). RESULTS: In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02). CONCLUSIONS: Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.

Clinical utility of gastric emptying scintigraphy: Patient and physician perspectives.

BACKGROUND: The use of gastric emptying scintigraphy (GES) in the evaluation of patients with dyspeptic symptoms is controversial. Our aim was to investigate objective and subjective parameters of clinical utility of GES from the perspectives of both the patient and the ordering physician. METHODS: Socio-demographic features, healthcare resource utilization, gastroparetic symptoms and quality of life (QoL) were obtained from consecutive patients referred for GES immediately prior to GES and again 4 months later. The ordering physician received a brief survey 2 weeks after the GES regarding their perceptions on whether the test provided them with clinically useful information. KEY RESULTS: One hundred and seventy-two (mean age ± SD 52.0 ± 17.9; 78% female) of 266 patients enrolled completed both the baseline and follow-up questionnaires and comprised our study population. At baseline, patients with abnormal GES had significantly higher gastroparesis symptom scores and reduced QoL. At the 4-month follow-up, an improvement in symptoms and QoL was seen, but the degree of improvement was not significantly different between those with a normal or abnormal GES. One hundred and ninety-seven ordering physicians completed the survey and perceived that GES, particularly when abnormal, provided new information (91%) and resulted in a change in diagnosis (58%) and management (60%). CONCLUSIONS & INFERENCES: Although patients with an abnormal GES generally had worse symptoms and lower QoL, the results of GES did not help to identify those with improved or worsened symptoms or QoL at follow-up. Nevertheless, the ordering physicians generally felt that the results of GES were helpful in managing these patients.

The relationship among gastroparetic symptoms, quality of life, and gastric emptying in patients referred for gastric emptying testing.

BACKGROUND: Symptoms suggestive of gastroparesis are non-specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying. METHODS: Gastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing (GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates. KEY RESULTS: Two hundred and sixty-six patients participated (195 females; mean age, 49.1 ± 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity. CONCLUSIONS & INFERENCES: In patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying.

Psychological distress in Rome III functional dyspepsia patients presenting for testing of gastric emptying.

BACKGROUND: There have been conflicting results from studies that have evaluated psychological disturbances in functional dyspepsia (FD). We conducted a comprehensive survey of psychological measures in patients undergoing gastric emptying testing (GET) in order to determine the relationship among psychological distress, gastric emptying, and dyspeptic symptoms. METHODS: Consecutive patients referred for GET were prospectively enrolled. Details regarding patient characteristics, health care utilization, dyspeptic symptoms, quality of life, and psychological dysfunction were obtained. Depression, anxiety, somatization, stress, positive and negative affect, and alexithymia were queried using validated questionnaires. We compared those dyspeptic patients who met Rome III criteria for FD to those who did not meet these criteria. KEY RESULTS: Two hundred and nine patients (160 female; mean age 46.6 years ± 17.3 years) participated. Around 151 patients (72%) met Rome III criteria for FD. In the entire group, a high level of depression, anxiety, somatization, and perceived stress was present compared to population norms. Health care seeking behavior and symptom severity were greater in those with FD and quality of life was lower compared to non-FD. Gastric emptying did not differentiate the two groups and similar degrees of psychological distress were present whether emptying was delayed or normal. CONCLUSIONS & INFERENCES: In patients referred for GET, substantial psychological distress is present. The degree of distress was similar regardless of whether the patient met Rome III FD criteria or not. Further evaluation of psychological dysfunction in FD patients may lead to improved diagnosis and determination of the most appropriate treatment.

The impact of obesity on oesophageal acid exposure time on and off proton pump inhibitor therapy.

BACKGROUND: Obesity is associated with increased oesophageal acid exposure time (AET) in patients with gastro-oesophageal reflux (GER), and may decrease the effects of proton pump inhibitors (PPIs). AIM: To evaluate the effects of increased body mass on the ability of PPI therapy to decrease AET in patients with reflux symptoms. METHODS: Acid exposure time profiles collected from adult patients using wireless pH-metry while on or off PPI therapy was retrospectively reviewed. Patients were separated into five body mass index (BMI) categories as defined by the World Health Organization. A multivariable logistic regression evaluated the association between abnormal AET and BMI groups while controlling for age, gender and pH capsule placement methods. RESULTS: The study group comprised 968 patients with 336 (34.7%) studied on a PPI and 632 (65.3%) studied off PPI therapy. AET (total greater than 5.3%) was found more frequently in the overweight (67%) and obese classes (74-80%) compared to those who were normal weight (40%) while off acid-suppressing medications (P < 0.001). No significant differences were found between these groups when studied on acid-suppressing medications, and the proportion of patients with abnormal AET across BMI classes was similar regardless of taking a PPI either once or twice daily. CONCLUSIONS: This is the largest study to report on the relationship between BMI and oesophageal acid exposure time in patients with GER on and off PPI therapy. We conclude that obesity is related to increased acid exposure time, but with no significant difference in acid exposure time among different weight-based groups when taking a once or twice-daily PPI.

Polyethylene glycol induces apoptosis in HT-29 cells: potential mechanism for chemoprevention of colon cancer.

Recent experimental evidence suggests that polyethylene glycol (PEG) is a highly effective chemopreventive agent against colon cancer; however, the mechanism(s) remain largely unexplored. To further elucidate this issue, we evaluated the effect of PEG on two human colon cancer cell lines. PEG treatment resulted in a dose- and time-dependent reduction in cell number without alteration in markers of cell proliferation. However, there was a dramatic and specific, concentration-dependent induction of apoptosis, with 50 mM PEG rendering approximately half the cells apoptotic. This corresponded with a 17-fold induction in the expression of the pro-apoptotic protein, prostate apoptosis response-4. Our data suggest that induction of apoptosis may be responsible, at least in part, for the ability of PEG to prevent experimental colon cancer.

Endoscopic therapy for gastroesophageal reflux disease: can it replace antireflux surgery?

This article addresses emergent endoluminal technologies currently available for the treatment of gastroesophageal reflux disease (GERD) and compares it to the laparoscopic Nissen fundoplication. To date the mainstay of GERD therapy has been achieved with either open or laparoscopic fundoplication or life-long medical treatment. Endoluminal treatment modalities attempt to augment the gastroesophageal junction (GEJ) function by various techniques. We searched the Medline database from 1980 to 2004 for studies on endoscopic GERD techniques and laparoscopic fundoplications. Product investigators were contacted for data presented in abstract form only. Endoluminal management of GERD include using radiofrequency energy, injection of biocompatible polymers and endoluminal sutures to alter the GEJ and reduce reflux. Early results while encouraging, should be evaluated thoroughly and with caution before widespread use can be advocated. Endoscopic treatment of GERD has future promise, however, more experience and perhaps further refinement in techniques and technology must occur before widespread clinical application can be encouraged.

Review article: current treatment options and management of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89-90%), postprandial fullness (75-88%), and early satiety (50-82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive. AIM: To present current management options for the treatment of FD (therapeutic gain/response rate noted when available). RESULTS: The utility of Helicobacter pylori eradication for the treatment of FD is modest (6-14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7-10% therapeutic gain), histamine-type-2-receptor antagonists (8-35% therapeutic gain), prokinetic agents (18-45%), tricyclic antidepressants (TCA) (response rates of 64-70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies. CONCLUSIONS: A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti-nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.

Observational study of the frequency of use and perceived usefulness of ancillary manoeuvres to facilitate colonoscopy completion.

BACKGROUND: A paucity of information exists regarding the frequency of use and usefulness of ancillary manoeuvres such as applying abdominal pressure and changing patient position to successfully complete colonoscopy. This information would be useful to understand and improve colonoscopy technique. AIM: We sought to determine the frequency, type and perceived success of ancillary manoeuvres used when performing colonoscopy during routine clinical practice. PATIENTS AND METHODS: A prospective, observational study was conducted at an outpatient endoscopy centre with a diverse group of colonoscopists. Our hypothesis was that ancillary manoeuvres would be used frequently by endoscopists of varying levels of experience and would be helpful in achieving successful caecal intubation. Information collected included patient and staff characteristics, procedural information and use of ancillary manoeuvres. Additional descriptive information was obtained when a manoeuvre was performed. RESULTS: One thousand three hundred and twenty-seven patients participated (691 women; mean age 62.5+/-12.3). The caecum was reached in 94% of cases. One or more ancillary manoeuvres were used in 73% of cases. Whilst one or two manoeuvres were helpful to achieve caecal intubation, increased manoeuvres were associated with an increased risk of incomplete colonoscopy. CONCLUSION: These data suggest that ancillary manoeuvres are used frequently but are not necessarily predictive of successful caecal intubation. Additional data from prospective, randomised studies are needed to address the overall utility and optimal application of individual manoeuvres.

Patient characteristics, clinical, endoscopic, and histologic findings in adult eosinophilic esophagitis: a case series and systematic review of the medical literature.

The objective of our study is to describe patient characteristics, clinical, endoscopic, and pathologic features and management of adult eosinophilic esophagitis (EE). A retrospective review of adults with EE (20 or more eosinophils per high-power field) diagnosed between 1997 and 2006, and a systematic review of the medical literature was performed. Forty-two patients (31 male; 11 female) had EE. Mean (SD) age at diagnosis was 44 (15.8) years, with highest prevalence (48%) at age 20-39. Predominant symptoms were dysphagia (81%); median duration, 8 years; range, 1-30 years and food impaction (55%). Forty-three percent had allergy or atopy, 36% had asthma, 54% had peripheral eosinophilia, and 10% had a first-degree relative with dysphagia. Endoscopic findings included ringed esophagus (55%), linear furrows (33%), narrow esophagus (10%), normal esophagus (7%), and esophageal strictures (38%). Mean number of dilations was 2 (range, 1-5). There were no perforations, but superficial mucosal tears occurred in 31% of dilations. Nine patients were treated with topical fluticasone with clinical improvement in all four (100%) patients who were seen in follow-up. Pathologic findings included 20 or more eosinophils per high-power field from proximal or mid-esophageal biopsy specimens. A systematic review of 14 studies (11 manuscripts, 2 abstracts, and this case series) with 212 patients showed similar findings. EE should be suspected in young men with unexplained dysphagia or food impaction even in the absence of typical endoscopic findings of rings or corrugations, linear furrows, and narrow esophagus; diagnosis is confirmed by 20 or more eosinophils per high-power field on proximal or mid-esophageal biopsies; EE is associated with allergic or atopic disorders; topical steroids are effective in the management of EE; dilation of esophageal strictures is reasonably safe in EE.

Does gastroesophageal reflux contribute to the development of chronic sinusitis? A review of the evidence.

Although recent studies suggest that gastroesophageal reflux disease (GERD) may contribute to a variety of ear, nose and throat and pulmonary diseases, the cause-and-effect relationship for the vast majority remains far from proven. In this article, the evidence supporting a possible causal association between GERD and chronic sinusitis has been reviewed. The evidence would suggest that: (i) a higher prevalence of GERD and a different esophagopharyngeal distribution of the gastric refluxate occurs in patients with chronic sinusitis unresponsive to conventional medical and surgical therapy compared to the general population; (ii) a biologically plausible pathogenetic mechanism exists whereby GERD may result in chronic sinusitis; and (iii) clinical manifestations of chronic sinusitis respond variably to antireflux therapy. While these findings suggest that GERD may contribute to the pathogenesis of chronic sinusitis in some patients, it is apparent that the quality of the evidence supporting each of these three lines of evidence is low and therefore does not conclusively establish a cause-and-effect relationship. A number of unresolved issues regarding prevalence, pathophysiological mechanism, diagnosis and treatment exist that deserve further investigation in order to solidify the relationship between GERD and chronic sinusitis. In conclusion, given the possible relationship between GERD and chronic sinusitis, until more convincing data are available, it may be prudent to investigate for GERD as a potential cofactor or initiating factor in patients with chronic sinusitis when no other etiology exists, or in those whose symptoms are unresponsive to conventional therapies.

Lymphoma and tracheoesophageal fistula: Indication for a removable esophageal stent.

Mediastinal lymphoma is a rare cause of tracheoesophageal fistula (TEF). While most reports described in the literature have been related to prior or concurrent chemoradiation therapy, TEF has rarely been reported as the initial presentation of lymphoma. We report on a young woman found to have Hodgkin's disease complicated by TEF that required emergent placement of an esophageal stent. The lymphoma was successfully treated and, due to stent-related symptoms, removal was desired but not technically possible. We discuss options that may prevent this predicament in the future.

Fatal diffuse invasive gastrointestinal candidiasis masking as ileus after bone marrow transplantation.

High-dose cytotoxic chemotherapy has increased the incidence of candidal infections that make neutropenic patients very sick and may kill them. We report fatal invasive candidiasis involving the entire alimentary tract after autologous bone marrow transplantation in a young woman with breast cancer. Illustrated are the significance of fungal infections in this patient population, the potential for Candida albicans to invade the entire gastrointestinal tract, and the potential role of endoscopy in the early diagnosis of these often catastrophic infections. We also suggest that diffuse, invasive candidiasis should be considered in the differential diagnosis of ileus in the immunocompromised patient.

Steatorrhea and weight loss in a 72-year-old man: primary biliary cirrhosis? Celiac disease? Bacterial overgrowth? What else?

Unintentional weight loss is an ominous sign, particularly when it occurs in the elderly; concern for malignancy is especially worrisome. In this report, we describe a 72-yr-old man who presented with weight loss and was found to have massive steatorrhea. An extensive evaluation revealed evidence of primary biliary cirrhosis (PBC), celiac disease, and small intestinal bacterial overgrowth. No malignancy was identified. The weight loss was attributed to severe steatorrhea due, in part, to intraluminal bile salt deficiency, small bowel mucosal disease, and bacterial overgrowth. Several points are discussed regarding gastrointestinal function in elderly patients with chronic liver disease secondary to PBC. The rare association between PBC and celiac disease in adults is also discussed. Finally, we suggest that bacterial overgrowth plays a significant role in the development of steatorrhea in some persons with PBC and that an assessment for bacterial overgrowth should be performed on persons with steatorrhea and PBC.

Efficacy of prolonged administration of intravenous erythromycin in an ambulatory setting as treatment of severe gastroparesis: one center's experience.

Intravenous erythromycin is a potent gastric prokinetic with demonstrated efficacy in the acute therapy of gastroparesis; long-term oral therapy has been limited by tolerance and modest efficacy. Our aim was to review our experience with prolonged administration of intravenous erythromycin in an ambulatory setting as therapy for severe gastroparesis, refractory to usual dietary and oral prokinetic regimens. We conducted a retrospective analysis of patients with gastroparesis treated with intravenous erythromycin for at least 1 month. Information on demographics; origin of gastroparesis; dosage, duration, and route of administration; clinical outcome in the short- and longer-term; and complications were determined. Eleven patients received a total of 14 courses of intravenous erythromycin for a median of 6.5 months (range, 1 to 19 months) at a median dosage of 300 mg/day (range, 150 to 1,000 mg/day). One patient received no benefit, two had complete responses, and all others reported some benefit. Two had dramatic relapse on cessation of therapy and subsequently improved on its resumption. Parenteral nutrition could be discontinued in one of four patients. There were four episodes of line sepsis; two required catheter removal. A nonocclusive thrombus developed at the site of a central line in one patient. Secondary infections or antibiotic resistance were not encountered. Prolonged administration of intravenous erythromycin in an ambulatory setting is feasible, well tolerated, and effective in patients with severe gastroparesis.