Coeliac disease screening is suboptimal in a tertiary gastroenterology setting.

BACKGROUND AND AIMS: Coeliac disease (CD) is widely prevalent in North America, but case-finding techniques currently used may not be adequate for patient identification. We aimed to determine the adequacy of CD screening in an academic gastroenterology (GI) practice. METHODS: Consecutive initial visits to a tertiary academic GI practice were surveyed over a 3-month period as a fellow-initiated quality improvement project. All electronic records were reviewed to look for indications for CD screening according to published guidelines. The timing of screening was noted (before or after referral), as well as the screening method (serology or biopsy). Data were analysed to compare CD screening practices across subspecialty clinics. RESULTS: 616 consecutive patients (49±0.6 years, range 16-87 years, 58.5% females, 94% Caucasian) fulfilled inclusion criteria. CD testing was indicated in 336 (54.5%), but performed in only 145 (43.2%). The need for CD screening was highest in luminal GI and inflammatory bowel disease clinics, followed by biliary and hepatology clinics (p<0.0001); CD screening rate was highest in the luminal GI clinic (p=0.002). Of 145 patients screened, 4 patients (2.4%) had serology consistent with CD, of which 2 were proven by duodenal biopsy. Using this proportion, an additional 5 patients might have been diagnosed in 191 untested patients with indications for CD screening. CONCLUSIONS: More than 50% of patients in a tertiary GI clinic have indications for CD screening, but <50% of indicated cases are screened. Case-finding techniques therefore are suboptimal, constituting a gap in patient care and an important target for future quality improvement initiatives.

Hyperdynamic upper esophageal sphincter pressure: a manometric observation in patients reporting globus sensation.

OBJECTIVES: Although globus sensation is a common symptom, its pathogenesis is poorly defined. The aim of this study was to quantify the timing and magnitude of respiratory variation in upper esophageal sphincter (UES) pressure with high-resolution manometry (HRM) in patients with globus sensation, normal controls, and gastroesophageal reflux disease (GERD) patients without globus sensation. METHODS: HRM recordings spanning from the hypopharynx to the stomach were analyzed in 131 consecutive globus patients with normal (64) and abnormal (67) distal esophageal motility. Resting UES pressure was analyzed up to 5 min before 10 5-ml water swallows. Change in UES pressure, its average magnitude between inspiration and expiration, and nadir UES relaxation pressure in globus patients were compared with those in 68 controls and 46 GERD patients without globus. RESULTS: UES pressure typically increased during inspiration in both controls and patients. Respiration-related change in resting UES pressure was significantly amplified in globus patients (37.3 mm Hg) compared with controls (10.6 mm Hg) and GERD patients (13.0 mm Hg) (P<0.0001). A respiratory change in UES pressure>27 mm Hg was found in >60% of globus patients and <15% of controls and GERD patients without globus. This hyperdynamic UES was not associated with other abnormalities of esophageal motor function. CONCLUSIONS: Hyperdynamic respiratory UES pressure changes were prevalent in patients reporting globus sensation irrespective of their deglutitive UES and distal esophageal motility. Although the etiology of this hyperdynamic UES is unclear, it does appear to be a frequent manometric observation in this patient group and may provide a new focus for further studies into pathogenesis and therapy.

Achalasia symptom response after Heller myotomy segregated by high-resolution manometry subtypes.

BACKGROUND: Achalasia is classified into three HRM subtypes that predict outcomes from diverse management strategies. We assessed if symptomatic response varied when a single management strategy-Heller myotomy (HM)-is employed. METHODS: Treatment-naive subjects with achalasia referred for HM were followed in this observational cohort study. Chicago criteria designated achalasia subtypes (subtype I: no esophageal pressurization; subtype II: panesophageal pressurization in ≥20 % swallows; subtype III: premature contractions in ≥20 % swallows). Symptom questionnaires assessed symptom burden before and after HM on five-point Likert scales (0 = no symptoms, 4 = severe symptoms) and on 10-cm visual analog scales (global symptom severity, GSS); satisfaction with HM was recorded similarly. Data were analyzed to determine predictors of GSS change across subtypes. RESULTS: Sixty achalasia subjects (56.1 ± 2.4 years, 55 % female) fulfilled inclusion criteria, 15 % with subtype I, 58 % with subtype II, and 27 % with subtype III achalasia. Baseline symptoms included dysphagia (solids: 85 %, liquids: 73 %), regurgitation (84 %), and chest pain (35 %); mean GSS was 7.1 ± 0.3. Upon follow-up 2.1 ± 0.2 years after HM, GSS declined to 1.9 ± 0.4 (p < 0.001), with surgical satisfaction score of 8.7 ± 0.3 out of 10; these were similar across achalasia subtypes. On univariate analysis, female gender, Eckardt score, severity of transit symptoms, and maximal IRP predicted linear GSS improvement; female gender (p = 0.003) and dysphagia for liquids (p = 0.043) remained predictive on multivariate analysis. CONCLUSIONS: When a uniform surgical approach is utilized, symptomatic outcome and satisfaction with therapy are similar across achalasia subtypes. Female gender and severity of dysphagia for solids may predict better HM outcome.

Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator.

The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on the surface of tumor cells is involved in the activation of proteolytic cascades responsible for the invasiveness of those cells. The diffuse, extensive infiltration of glioblastomas into the surrounding normal brain tissue is believed to rely on modifications of the proteolysis of extracellular matrix components; blocking the interaction between uPA and uPAR might be a suitable approach for inhibiting glioma tumorigenesis. We assessed how expression of an amino-terminal fragment (ATF) of uPA that contains binding site to uPAR affects the invasiveness of SNB19 human glioblastoma cells. SNB19 cells were transfected with an expression plasmid (pcDNA3-ATF) containing a cDNA sequence of ATF-uPA. The resulting ATF-uPA-expressing clones showed markedly less cell adhesion, spreading, and clonogenicity than did control cells. Endogenous ATF expression also significantly decreased the invasive capacity of transfected glioblastoma cells in Matrigel and spheroid-rat brain cell aggregate models. ATF-uPA transfectants were also markedly less invasive than parental SNB19 cells after injection into the brains of nude mice, suggesting that competitive inhibition of the uPA-uPAR interaction on SNB19 cells by means of transfection with ATF cDNA could be a useful therapeutic strategy for inhibiting tumor progression.