Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis.

BACKGROUND: Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. AIMS: To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets. METHODS: Electronic (PubMed/Medline) and manual Google search. RESULTS: The GIT is the most common internal organ involved in SSc. Any part of the GIT from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are nonspecific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the absence of cutaneous disease. Up to 8% of SSc patients develop severe GIT symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the GIT causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of GIT dysmotility mediated by functional anti-muscarinic receptor autoantibodies. CONCLUSIONS: Despite extensive investigation, the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions.

Survey of findings in patients having persistent heartburn on proton pump inhibitor therapy.

In patients with refractory heartburn while on proton pump inhibitor (PPI) therapy, changing drugs or increasing treatment to a twice a day (b.i.d.) dose has become a common practice. This study aims to study patients with persistent heartburn while on PPI therapy and to determine if persistent symptom indicates the need for more aggressive or different therapy. A retrospective review of impedance-pH tracings on PPI therapy (q.d. or b.i.d.) for patients with persistent heartburn was performed. DeMeester score, impedance, and symptom sensitive index (SSI) were used as indices. Statistical analyses were performed using chi-squared test with Yates correction and paired t-test. One hundred consecutive patients, (female 50%, male 50%, mean age 54 [range 16-83] years) were studied on q.d. (n = 45) or b.i.d. PPI (n = 55). Only 20% of the patients had abnormal DeMeester score; 41% had an abnormal impedance score and 56% had abnormal SSI; 29% had all indices normal. There was no difference between patients taking q.d. versus b.i.d. PPI for abnormal DeMeester score (22 vs. 18%), impedance (38 vs. 44%) and SSI (53 vs. 58%); P = 0.80, 0.69, and 0.77, respectively. In 56 patients with positive SSI, symptoms were due to acid reflux in 8 (14%) patients, nonacid reflux in 31 (55%) patients, and combined acid and nonacid reflux in 17 (30%) patients. Patients with persistent heartburn on PPI therapy show a variety of disorders: (i) acid reflux (20%); (ii) nonacid reflux (26%); (iii) positive SSI (56%); (iv) all normal indices (29%). These studies indicate that persistent heartburn on PPI therapy is a complex problem that may not respond to simply increasing acid inhibition.

Prognostic significance of high-grade dysplasia in colorectal adenomas.

AIM: Colonoscopy to detect and remove polyps has contributed to a reduction in colorectal carcinoma. Three-year follow up is recommended for patients considered to be at high risk (at least three adenomas, adenoma ≥ 1 cm, villous or high-grade features). Our study focused on patients diagnosed with high-grade dysplasia with regard to initial management and follow up. METHOD: A search of patients who had had endoscopic removal of a high-grade adenoma was carried out. Patients with the following were excluded: follow up of < 1 year, polyposis syndromes, prior colon cancer and a diagnosis of adenocarcinoma within 6 months following initial diagnosis. RESULTS: Eighty-three patients treated between 1999 and 2007 for high-grade dysplasia (HGD) in a colorectal adenoma were identified. Over a median follow-up period of 4 years, 53 (64%) developed further adenomatous polyps. Among these, 7% had an adenoma with HGD or an adenocarcinoma. In all these patients, the initial high-grade adenoma was > 1 cm in diameter. Initial follow-up colonoscopy was performed on average 7 months following the initial diagnosis. Ten per cent of patients underwent prophylactic segmental resection, and 6% received argon laser therapy. CONCLUSION: The study demonstrates that patients who have a colorectal adenoma > 1 cm with HGD may be at high risk of developing further adenomas with HGD or carcinoma. Close follow up is warranted.

A survey of oesophageal cancer: pathology, stage and clinical presentation.

BACKGROUND: Oesophageal adenocarcinoma is the sixth leading cause of cancer-related mortality worldwide. Previously, oesophageal cancer was mainly squamous cell, presenting late with dysphagia and weight loss. AIMS: To examine the distribution of oesophageal cancer histopathology at a large, urban hospital; to determine the tumour stage and symptoms at presentation; and to evaluate the impact of endoscopic surveillance in Barrett's oesophagus. METHODS: From 1999 to 2004, all patients diagnosed with oesophageal cancer were evaluated retrospectively for demographics and tumour stage at presentation using endoscopic ultrasonography and computerized tomography. RESULTS: A total of 131 patients were included. 81% of tumours were adenocarcinomas; most localized to the distal oesophagus (97%). Patients presented with dysphagia (56%), pain (30%) and/or weight loss (16%). Irrespective of histology, locally advanced lesions accounted for most cases. Thirteen patients had lesions detected in Barrett's surveillance; these were early or intermediate stage in nine patients, but late stage in four patients. CONCLUSIONS: Adenocarcinoma has become the dominant histologic subtype, comprising 81% of proven malignancies. Despite a change in histopathology, most cancers are diagnosed at an advanced stage, presenting with dysphagia, pain and/or weight loss. Endoscopic surveillance of Barrett's oesophagus allows earlier diagnosis of cancer in most, but not all, patients.

The effect of gastro-oesophageal reflux and omeprazole on key sleep parameters.

BACKGROUND: The effect of gastro-oesophageal reflux on sleep and sleep quality is highly controversial. AIM: To determine the temporal relationship of abnormal objective sleep parameters to gastro-oesophageal reflux during acid suppression in patients with self diagnosed sleep disorders. METHODS: Polysomnography during oesophageal pH monitoring was conducted in 16 subjects with and without gastro-oesophageal reflux as determined by a standardized questionnaire. Subjects were studied before and after omeprazole. RESULTS: All reflux events were followed by a sleep arousal or awakening. Nocturnal acid reflux events were not predicted by the Carlsson score. Omeprazole reduced acid reflux-associated arousals from 11.6 +/- 3.8 to 1.5 +/- 0.8 (P < 0.01) and awakenings from 7.7 +/- 1.2 to 3.7 +/- 0.5 (P < 0.05). Sleep efficiency improved from 70.2% to 81.6% in a small subset of subjects with decreased sleep (P < 0.05); rapid eye movement sleep increased from 55.0 +/- 4.5 to 94.5 +/- 18.9 min (P < 0.05); total sleep time increased from 294.0 +/- 15.9 to 345.6 +/- 55.6 min (P < 0.05). Apnoea, hypopnoea and hypoxaemia were not associated with reflux. CONCLUSIONS: In subjects with gastro-oesophageal reflux, sleep arousals and awakenings are closely related to acid reflux events. Reflux-related arousals and awakenings are decreased by acid suppression. Acid suppression in selected subjects with reflux events and reduced sleep efficiency is associated with increased total sleep time, rapid eye movement sleep and sleep efficiency.

A retrospective analysis of medical or surgical therapy in young patients with diverticulitis.

BACKGROUND: Acute diverticulitis is increasingly being recognized in younger patients, but its management remains controversial. AIM: To compare long-term outcomes of young patients treated with surgery vs. medical therapy for their first episode of diverticulitis. METHODS: A retrospective chart analysis at a university and an affiliated community hospital between 1991 and 2002 revealed 149 patients < or = 40 years of age with confirmed diverticulitis. Forty-nine patients (38 males, 11 females) were contacted at least 1 year after their first episode of diverticulitis. Outcomes were compared based on initial therapy--antibiotics or surgical resection. The groups were compared by outcomes, gender, age, white blood cell count, temperature and diet. RESULTS: Three (15%) of 20 surgical patients (mean follow-up 6.89 years), and 16 (55%) of 29 medical patients had a recurrence of diverticulitis (mean follow-up 5.72 years; P = 0.01). The treatment groups did not differ in age, white blood cell count, or temperature. CONCLUSIONS: (i) Surgical treatment is effective initial therapy but disease may recur in a minority of patients; (ii) medical treatment is less effective initial therapy, with recurrence in half of the patients; (iii) initial presentation is not a strong predictor of disease recurrence.

Manometric evaluation of achalasia in the elderly.

BACKGROUND: The effect of ageing on oesophageal motility in patients with achalasia is not well described. Oesophageal contraction amplitude is decreased in otherwise healthy elderly subjects. AIM: To evaluate whether ageing influences the motor function of the oesophagus in achalasia. METHODS: Initial manometry studies of patients with achalasia were reviewed and findings (lower oesophageal sphincter basal and residual pressures and oesophageal body contraction amplitudes) were compared between two groups of patients, those 65 years of age or older (49 patients) and those younger than 65 years (68 patients). The older group was further divided into those > or =70 years and those <70 years. RESULTS: Patients 65 years and older had significantly higher lower oesophageal sphincter basal pressures compared with younger patients (65.6 +/- 4.9 vs. 52.3 +/- 2.7, P = 0.02). At an age cut-off of 70 years, older patients had significantly higher basal (70.7 +/- 1.6 vs. 53.0 +/- 2.4, P = 0.02) and residual (19.7 +/- 1.6 vs. 15.9 +/- 0.7, P = 0.03) lower oesophageal sphincter pressures compared with younger patients. Amplitude of oesophageal contractions was not different between the groups. Across all age groups, there was no linear correlation between age and basal or residual lower oesophageal sphincter pressures (r = 0.28 and 0.12, respectively). CONCLUSIONS: Older patients with achalasia have higher lower oesophageal sphincter pressures, however there is no linear correlation between age and lower oesophageal sphincter pressures. Unlike healthy subjects, advanced age is not associated with a decrease in oesophageal contraction amplitude in patients with achalasia.

The comparison of midazolam and topical lidocaine spray versus the combination of midazolam, meperidine, and topical lidocaine spray to sedate patients for upper endoscopy.

BACKGROUND: Whether an opiate-benzodiazepine combination is superior to benzodiazepine alone for sedation in upper endoscopy is controversial. The purpose of this study was to compare the effectiveness of intravenous midazolam alone versus the combination of intravenous midazolam and intravenous meperidine for the sedation of patients undergoing upper endoscopy. METHODS: One hundred seven patients scheduled for outpatient diagnostic esophagogastroduodenoscopy were randomly assigned to receive 50 mg intravenous meperidine (53 of 107) or placebo (54 of 107). All patients received topical lidocaine spray and as much midazolam as the endoscopist thought the patient needed. Patients and endoscopists were blinded as to assignment. Data collected included intubation time (seconds), procedure time (minutes), pulse, blood pressure, complications, and the need for reversal agents. The endoscopist evaluated the quality of sedation immediately after the procedure (1 = excellent, 2 = good, 3 = fair, and 4 = poor). The patient evaluated the procedure the next day by phone (1 = no discomfort or did not remember, 2 = slightly uncomfortable, 3 = extremely uncomfortable, and 4 = unacceptable). Patients were also asked whether they would agree to another esophagogastroduodenoscopy if their doctor thought it was medically necessary. RESULTS: The intubation time, procedure time and blood pressure were not significantly different between the 2 groups. In comparing the meperidine group versus placebo group, the highest pulse (82.3 vs. 93.7, p = 0.0010), lowest pulse (67.2 vs. 72.3, p = 0.0194) and amount of midazolam used (4.0 vs. 4.8 mg, p = 0.0185 or 0.53 vs. 0.67 mg/kg, p = 0.0083) were significantly different by using a t test analysis. Patient evaluations comparing meperidine versus placebo showed responses of 1 (52 vs. 49), 2 (1 vs. 3), 3 (0 vs. 2) and 4 (0 vs. 0), which were not significantly different. The endoscopists'evaluation comparing meperidine versus placebo gave responses of excellent (44 vs. 27), good (6 vs. 22), fair (3 vs. 5) and poor (0 vs. 0), which were highly significantly different (p < 0.001) by using chi-square statistical techniques. CONCLUSION: The addition of meperidine to midazolam in sedating patients undergoing upper endoscopy adds no benefit from the patient viewpoint, whereas endoscopists favored the use of both medications.

Crohn's disease of the esophagus: Three cases and a literature review.

Three cases of esophageal Crohn's disease (CD) are described, each with dysphagia and/or odynophagia caused by esophageal ulceration. All three patients had associated ileocolitis. One patient followed for a prolonged period responded to treatment with sulfasalazine and prednisone. A computer search back to 1967 produced 72 additional cases of esophageal CD. Among these 75 patients (total), who were, on average, 34 years old, esophageal disease was the presenting disease symptom in 41 patients (55%). The diagnosis was difficult in 13 patients, in whom no distal bowel disease was detected at the time of initial esophageal presentation. The most common presentation was dysphagia associated with aphthous or deeper ulcerations (52 patients). In 11 of these patients, oral aphthous ulcerations were also present. Esophageal stenosis or fistulas to surrounding structures were present in 27 patients and led to surgery in 17 patients. Most of the unfavourable outcomes were in this group of 27 patients with esophageal complications, including five deaths. Fourteen additional patients required surgery for CD of other areas. Responses of uncomplicated ulcerative disease of the esophagus tended to be favourable if the medical regimen included prednisone. Clinical patterns of esophageal CD were divided into three categories: ulcerative, stenosing and asymptomatic (acute disease in children).

End expiration is more accurate than mid respiration in measuring lower esophageal sphincter pressure.

BACKGROUND/AIMS: Two ways popularly used to measure lower esophageal sphincter pressure are the mid-respiratory and end-expiratory methods. The aim of this study was to compare the suitability of these methods in the manometric assessment of patients with endoscopically documented esophagitis. METHODS: Manometry was performed on 22 consecutive patients to determine whether medical therapy or surgery was the more appropriate treatment strategy. Lower esophageal sphincter pressure was measured during a slow station pull-through. End-expiratory lower esophageal sphincter pressure was assessed by measuring the highest trough which coincided with end expiration. Mid-respiratory lower esophageal sphincter pressure was assessed by bracketing the highest pressure over >/=3 respiratory cycles and measuring the mid point. RESULTS: Mid-respiratory lower esophageal sphincter pressure (25.6 mm Hg) was higher (p < 0.0001) than end-expiratory lower esophageal sphincter pressure (15.7 mm Hg). Nine (41%) end-expiratory lower esophageal sphincter pressures were abnormally low (i.e., <10 mm Hg), whereas three (14%) mid-respiratory lower esophageal sphincter pressures were abnormally low (i.e., <14 mm Hg; p = 0.042). CONCLUSIONS Mid-respiratory lower esophageal sphincter pressure measurement includes respiratory artifact and does not accurately measure lower esophageal sphincter pressure. End-expiratory sphincter pressure better identifies potential surgical candidates.

Diarrhea as a side effect of mesalamine treatment for inflammatory bowel disease.

Tablets of coated 5-aminosalicylate (5-ASA) called mesalazines are among the most widely prescribed preparations for the treatment of colitis, including ulcerative, Crohn's disease (CD), collagenous and lymphocytic colitis, and-to a lesser extent-CD of the small bowel. Mesalamines have, to a large extent, replaced the parent drug sulfasalazine because they produce fewer side effects. Although mesalamines have been known from earlier studies to produce occasional diarrhea, the true incidence of this effect is not known and is not always recognized. We are presenting the cases of five patients in whom oral mesalamines produced severe and persistent diarrhea-made worse by increasing doses of the drug-and intensified the colitis in two. Recognition of the problem is by symptom analysis after careful history taking. Changing the therapeutic regimen or discontinuing the medication is usually required to reverse this potentially debilitating and occasionally life-threatening side effect.

American Society for Gastrointestinal Endoscopy-Society of Gastroenterology Nurses and Associates Endoscope Reprocessing Guidelines.

Adequate endoscope reprocessing is one of the most essential functions in any endoscopy setting. Standards and guidelines for reprocessing endoscopes have been established by the Society of Gastroenterology Nurses and Associates (SGNA) and the American Society for Gastrointestinal Endoscopy (ASGE). These standards pertain to any setting in which gastrointestinal endoscopy is performed. Endoscope reprocessing that meets the established standard of practice helps to ensure a patient-ready instrument for all patients, reduces the risk of disease transmission to practitioners and staff, and helps to prolong the life of the endoscope.

Noncompliance with FDA and society guidelines for endoscopic reprocessing: implications for patient care.

Flexible endoscopic instruments are very valuable in the diagnosis and treatment of patients with gastrointestinal diseases. Current guidelines for reprocessing these instruments between patient use are appropriate. Rigid adherence to these guidelines, however, will be necessary to reassure governmental authorities, other medical authorities, and the public that the risk of infection from these procedures is minimal.

GI endoscopic reprocessing practices in the United States.

BACKGROUND: Patient infection from contaminated gastrointestinal (GI) endoscopes can generally be attributed to failure to follow appropriate reprocessing guidelines. Recently, the Food and Drug Administration recommended a 45-minute exposure of GI endoscopes to 2.4% glutaraldehyde solutions heated to 25 degrees C. Simultaneously, the American Society for Gastrointestinal Endoscopy (ASGE), the American Gastroenterological Association, and the Society of Gastroenterology Nurses and Associates endorsed a reprocessing guideline that emphasized manual precleaning and recommended a 20-minute exposure to a 2.4% glutaraldehyde solution at room temperature. Since then, little information has become available regarding actual reprocessing practices in the United States. METHODS: A previously developed questionnaire regarding endoscopic disinfection practices was mailed to randomly selected members of the ASGE. RESULTS: The survey was sent to 730 members and 294 responded (40.3%). Appropriate manual cleaning (suctioning detergent through the accessory channel and brushing the channel and valves) is performed by 90.7% of respondents; 69.9% then use automated reprocessors for disinfection or sterilization. Glutaraldehyde is the most widely used chemical disinfectant; 85.3% use glutaraldehyde as one of their primary disinfectants. The most commonly used disinfection time with 2.4% glutaraldehyde is 20 minutes (83.9%) followed by 45 minutes (11.4%). Only 23.8% of users of 2.4% glutaraldehyde heat their solution; 59.6% of centers test disinfectant concentration daily or more frequently; 74.0% sterilize nondisposable forceps before use; 29.2% of centers re-use disposable endoscopic accessories (which are more frequently disinfected rather than sterilized). Twelve respondents reported cases of endoscopic cross infection. CONCLUSIONS: A significant minority of endoscopy centers still do not completely conform to recent ASGE, American Gastroenterological Association, and the Society of Gastroenterology Nurses and Associates guidelines on disinfection, and they may not be appropriately disinfecting GI endoscopes. Rigid adherence to recommended guidelines is strongly encouraged to ensure patient safety.

Serologic hepatitis B immunity in vaccinated health care workers.

BACKGROUND: Hepatitis B vaccination is recommended for health care workers but has a nonresponse rate of 5% to 32% and an unknown duration of immunity. There is no standardized postvaccination protocol to confirm, monitor, and maintain immunity. OBJECTIVE: To assess the hepatitis B serologic immune status in health care workers who were previously vaccinated. METHODS: A convenience survey and an objective laboratory study, which included testing for hepatitis B surface antigen, core antibody, and qualitative and quantitative surface antibody (anti-HBs), were performed. The data collected included vaccination date, number of doses of vaccine, whether and when titers had previously been checked, titer results, sex of patient, job description, and age at the time of our study and at vaccination. RESULTS: Group A (n = 109, 71%) had detectable anti-HBs titers, and group B (n = 45, 29%) had no detectable anti-HBs titers. Group A was vaccinated 4.80 +/- 0.30 (mean +/- SEM) years prior to our testing, received 2.91 +/- 0.04 (mean +/- SEM) vaccinations, and had a mean +/- SEM titer of 112.91 +/- 5.18 mIU/mL. There was no statistical significance in time since vaccination, number of doses of vaccine, sex, job description, age at the time of our serologic testing, or age at the time of vaccination between groups A and B. Six of 6 subjects given booster doses of vaccine in group B developed anti-HBs. Only 62 subjects (40%) in the entire study population had anti-HBs status previously determined, with 48 (77%) reporting immunity to hepatitis B virus. CONCLUSIONS: Twenty-nine percent of the health care workers who were vaccinated against hepatitis B showed no serologic evidence of hepatitis B immunity. It is unclear whether these subjects are nonresponders, lost immunity, or retained anamnestic potential. Booster vaccination response in 6 of 6 subjects suggests immunity. We recommend (1) postvaccination testing within 1 to 2 months to document immunity, (2) periodic anti-HBs monitoring, and (3) booster vaccination to maintain protective titer levels.

Clinical value of esophageal motility testing.

Esophageal motility testing is the method of choice in evaluating esophageal motor disorders. Some physicians, however, question the clinical utility of esophageal motility testing, since the results are often normal in symptomatic patients. The clinical utility of esophageal motility testing is reviewed for patients with a complaint of noncardiac chest pain, dysphagia or symptoms of gastroesophageal reflux disease. Esophageal motility testing is particularly useful for evaluating patients with dysphagia, but less so for gastroesophageal reflux disease patients, and has little clinical utility in patients with noncardiac chest pain.

Risk to the health care worker of HIV infection and how to minimize It.

Occupational transmission of HIV fortunately is uncommon. The risk of acquiring HIV depends on the mode of exposure, the body fluid involved, and the source patient. Percutaneous injuries carry the greatest risk (approximately 0.3%), and blood is by far the most important source of HIV to which the health care worker is exposed. Universal precautions should be applied to all patients in order to decrease the risk of occupational transmission of HIV. Furthermore, a system must be designed to provide adequate assessment, counselling, and follow-up for exposed health care personnel. Postexposure prophylaxis must be tailored to the specific exposure for each health care worker.

Manometric measurement of anal canal resting tone: comparison of a rectosphincteric balloon probe with a water-perfused catheter assembly.

The purpose of this study was to compare the manometric measurements of a rectosphincteric balloon probe with a water-perfused catheter assembly on anal canal resting tone. Ten normal subjects (9 males, 1 female; mean age: 32 years; range 27-46 years) underwent station pull-through (0.5 cm/3 sec) beginning in the rectum with a water-perfused catheter assembly and a rectosphincteric balloon probe. Both the probe and the catheter were 5 mm in diameter. Three catheter side ports were perfused at 1 ml/min, and the rectal balloon was inflated with 5 ml of air. Measurements were taken on the same day in a counterbalanced manner. Data were analyzed on a computerized system. Mean (+/-SEM) values with the balloon were 82.3 (+/-8.9) mm Hg and 97.1 (+/-9.3) mm Hg with the catheter. These values were not significantly different (P=0.22). A significant order effect (P=0.04) was found where the first measure (101.3+/-10.2 mm Hg) was higher than the second measure (78.1+/-6.6 mm Hg), which was controlled for in the experimental design. A rectosphincteric balloon probe can accurately measure the resting tone of the anal canal compared to a water-perfused catheter assembly. Caution should be used when measuring anal canal resting tone early in an anorectal manometry assessment.