Body mass index and Barrett's oesophagus in women.

OBJECTIVE: Excess body mass is associated with symptoms of gastro-oesophageal reflux disease, and cross-sectional studies suggest an association between body mass index (BMI) and Barrett's oesophagus. The present study sought prospectively to examine the influence of BMI and other anthropomorphic measures on the risk for Barrett's oesophagus among women. METHODS: This was a prospective study of 15 861 women who participated in the Nurses' Health Study, without a history of cancer, who underwent upper gastrointestinal endoscopy for any reason between 1986 and 2004. The main outcome measures were 261 cases of pathologically confirmed specialised intestinal metaplasia within the oesophagus (Barrett's oesophagus). Self-reported data on weight were collected from biennial questionnaires. Self-reported height was collected in 1976, and self-reported waist and hip circumferences were collected in 1986. RESULTS: Compared with women with a BMI of 20-24.9 kg/m(2), women with a BMI of 25-29.9 had a multivariate OR for Barrett's oesophagus of 0.92 (95% CI 0.66 to 1.27), women with a BMI > or =30 had a multivariate OR of 1.52 (95% CI 1.02 to 2.28) and women with a BMI <20 had a multivariate OR of 0.92 (95% CI 0.65 to 1.31). Results were similar when controlling for symptoms of gastro-oesophageal reflux, and among the entire Nurses' Health Study cohort (n = 93 609) regardless of a history of endoscopy. In contrast, waist-to-hip ratio, waist circumference and height did not appear to be associated with Barrett's oesophagus. CONCLUSIONS: Obese, but not overweight, women appear to be at increased risk for Barrett's oesophagus.

The inaccuracy of ICD-9-CM Code 530.2 for identifying patients with Barrett's esophagus.

Barrett's esophagus (BE) is a chronic complication associated with gastroesophageal reflux disease. The ICD-9-CM code used for BE, 530.2, is also used for patients with 'ulcer of the esophagus.' We aimed to determine if the ICD-9-CM code of 530.2 is reliable for identifying cases of Barrett's esophagus within databases for research purposes. We reviewed the records of all patients assigned code 530.2 at two university medical center hospitals and a veterans' administration hospital over a cumulative 16-year period. Billing records provided information about where the code was assigned, whether it was a major or minor diagnosis, and if the code was assigned on multiple occasions for each patient. Histology and endoscopy records were reviewed to confirm the diagnosis of Barrett's esophagus. Among 435 patients with code 530.2 in their records, 354 (82%) had an esophageal biopsy reported and 393 (90%) had an endoscopy report available for review. Only 182 (42%) had specialized intestinal metaplasia documented in a biopsy from an area of salmon-colored mucosa arising above the esophagogastric junction (51% of those with histology available). There were 288 patients (66%) with an endoscopic diagnosis of Barrett's esophagus (73% of those with an endoscopy reported). Variables associated with documented specialized intestinal metaplasia were age > or = 60 (OR 2.3; 95% CI 1.4-3.7), multiple assignments of 530.2 (OR 3.2; 95% CI 2.0-5.0), and assignment of 530.2 in a gastrointestinal (GI) clinic or an endoscopy unit (OR 3.5; 95% CI 2.0-6.3). The positive predictive value of the code being assigned in a GI location was 48% (95% CI 43-54%). Therefore, ICD-9-CM code of 530.2 is not specific for the diagnosis of Barrett's esophagus. The usage of code 530.2 in a GI setting was not sufficiently predictive of BE to be reliable for rigorous epidemiological studies.

Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy.

BACKGROUND AND STUDY AIMS: The widespread use of cholangioscopy in the management of difficult choledocholithiasis has been limited by the need for two expert operators. This report describes the use of a technique of single-operator duodenoscope-assisted cholangioscopy (SODAC) in the successful management of 75 patients with choledocholithiasis. PATIENTS AND METHODS: The single-operator technique, allowing simultaneous control of both the duodenoscope and cholangioscope, was prospectively studied between June 1999 and June 2001 in the diagnosis and treatment of choledocholithiasis. RESULTS: A total of 109 SODAC procedures were conducted in 75 patients to manage choledocholithiasis. The indications were: firstly, SODAC-guided electrohydraulic lithotripsy (EHL) of stones in which conventional methods, including mechanical lithotripsy, had not been successful (52 SODAC procedures in 26 patients); and secondly, direct visualization of the biliary tree after cholangiography to assess the presence of stones (57 SODAC procedures in 49 patients). The locations and numbers of the stones, but not their size, were predictive of the number of SODAC-guided lithotripsy sessions required. All of the patients were free of stones at the end of the study period, and no complications were recorded. CONCLUSIONS: Single-operator SODAC-guided electrohydraulic lithotripsy was effective in the treatment of difficult cases of choledocholithiasis in which conventional methods had previously failed. The technique may allow increased use of cholangioscopy in the management of choledocholithiasis.

Hypotension during ERCP is common but not a risk factor for post-ERCP pancreatitis.

BACKGROUND: In patients undergoing cardiopulmonary bypass, hypotension is a risk factor for developing acute pancreatitis. Hypotension in animal models can also induce pancreatitis. We sought to determine whether or not relative hypotension during ERCP is a risk factor for developing acute pancreatitis. PATIENTS AND METHODS: A nested, case-control study reviewed all cases of post-ERCP pancreatitis resulting from ERCPs performed at this institution between May 1993 and May 1998. Post-ERCP pancreatitis was defined as abdominal pain requiring hospitalisation and elevation of serum amylase or lipase more than four times the upper limit of normal 24 hours or more after ERCP. Non-invasive blood pressure measurements were recorded automatically at least every 5 min during ERCP. Hypotension was defined as any systolic blood pressure (SBP) <100 mmHg, diastolic blood pressure (DBP) <60 mmHg, or mean blood pressure (MBP) <80 mmHg. Controls were chosen randomly from ERCPs performed on the same or the nearest day as each index case. RESULTS: In total, 1854 ERCPs were reviewed from the study period.There were 96 cases of post-ERCP pancreatitis,giving an incidence of 5.2%. The average age of cases was 48 years, while that of controls was 55 years (p < 0.003).There were no differences between the groups regarding gender, ERCP findings, need for sphincterotomy nor acinar filling on the pancreatogram (acinarisation). At least one episode of hypotension was recorded in 32% of cases and 30% of controls (p = 0.75). There were no differences between cases and controls comparing mean pre- and intra-procedure SBP, DBP and MBPs, or lowest procedure SBP, DBP and MBP. DISCUSSION: Episodes of acute hypotension are common during ERCP but are not a risk factor for developing post-ERCP pancreatitis.

The indications, utilization and safety of gastrointestinal endoscopy in an extremely elderly patient cohort.

BACKGROUND: In developed nations, increasing proportions of the population now reach advanced age. Physicians may be reluctant to refer such patients for non-critical diagnostic and therapeutic interventions, on the basis of perceived diminution of tolerance, safety and substantive benefits in these patients. We aimed to review the utility and safety of gastrointestinal endoscopy in an extremely elderly cohort. METHODS: The study involved 214 consecutive participants aged 85 years or more, between 1995 and 1997. They were identified using a prospective database linked to the endoscopy reporting system. Procedure type, indication, use of sedation, complications, and outcomes were evaluated. RESULTS: The median age was 87 (85-94, sigma = 2). The female:male ratio was 3:2; 185 had undergone one procedure and 29 two or more; and 65% of procedures were performed on an outpatient basis. Of the inpatient procedures, 10% of all procedures were performed emergently, predominantly for upper gastrointestinal hemorrhage. Midazolam was administered to 129 patients (60%), at a median dose of 2 mg (range 1-11); of these, 75 (35%) also received a median dose of 25 microg fentanyl (range 12.5-125). Colonoscopy (n = 95) was the most frequently performed procedure, followed by esophagogastroduodenoscopy (EGD) (n = 64) and endoscopic retrograde cholangiopancreatography (ERCP) (n = 21). There was no procedure-related mortality. The incidence of post-ERCP pancreatitis was 5%, colonic perforation 1%, and cardiopulmonary complications in sedated patients, 0.6%. The majority underwent procedures which related to active management of ongoing medical problems, and procedures were performed for palliative indications in only 15 (7%) patients. CONCLUSIONS: Gastrointestinal endoscopy is extremely safe and well tolerated in extremely elderly patients. Age alone should not influence decisions relating to its utilization.

Thrombin and histamine rapidly stimulate the phosphorylation of the myristoylated alanine-rich C-kinase substrate in human umbilical vein endothelial cells: evidence for distinct patterns of protein kinase activation.

Human alpha-thrombin and histamine each stimulates protein phosphorylation in human umbilical vein endothelial cells (HUVEC). We have identified the most prominent of these phosphoproteins by immunoprecipitation as the human homolog of the widely distributed myristoylated alanine-rich C-kinase substrate (MARCKS). Stimulation by 0.1-10 U/ml of alpha-thrombin produces a time-dependent, sustained (plateau 3-5 min) level of MARCKS phosphorylation. MARCKS phosphorylation requires thrombin catalytic activity but not receptor binding and is also seen in response to stimulation by a peptide, TR (42-55), that duplicates a portion of the thrombin receptor tethered ligand created by thrombin proteolytic activity. One micromolar histamine, like alpha-thrombin, produces sustained phosphorylation of MARCKS (plateau 3-5 min). In contrast, 100 microM histamine results in rapid but transient MARCKS phosphorylation (peak 1-3 min). HUVEC treated with 100 microM histamine for 5 min can be restimulated by alpha-thrombin but not fresh histamine, suggesting that the histamine receptor was desensitized. MARCKS phosphorylation can also be induced by several exogenous protein kinase C (PKC) activators and both alpha-thrombin- and histamine-induced MARCKS phosphorylation are inhibited by the PKC antagonist staurosporine. However, while prolonged PMA pretreatment ablates histamine-induced MARCKS phosphorylation, the ability of thrombin to induce MARCKS phosphorylation is retained. These findings provide evidence for agonist-specific pathways of protein kinase activation in response to thrombin and histamine in HUVEC.

The nature of after-hours telephone medical practice by GI fellows.

OBJECTIVE: Gastroenterology fellows on-call often serve as the initial or only contact for patients calling "after hours" with questions and symptoms. These fellows are rarely trained specifically in how to handle these calls. The aim of this study was to determine whether there are particular topics in telephone medicine that ought to be covered in new fellow training. Therefore, we sought to evaluate the nature of after-hours pages initiated by patients and to document the advice given by fellows. METHODS: The content of 100 patient-initiated telephone calls with GI fellows was recorded prospectively over 7 months. We included pages received between 5 PM and 8 AM daily as well as daytime calls on weekends. Fellows documented the time and length of the call, the issue raised by the patient, the advice given, and the patient's gender and attending gastroenterologist. When a particular patient paged more than once in a 24-h period, the repeat calls were not counted toward the 100-call tally. RESULTS: Twenty-two percent of calls occurred between 11 PM and 7 AM. Eighty-three percent of calls lasted less than 10 min. Sixty-seven percent of patients called because of symptoms. Only 30% of patients calling with symptoms were referred to the emergency room. Although only 1 of 13 patients with procedure-related (i.e., postendoscopy) symptoms required admission to the hospital, 18 of 54 (33%) patients with nonprocedure-related symptoms required admission either immediately or within a month of calling after hours. CONCLUSIONS: Most after-hours calls from patients are related to symptoms. Patients calling with postprocedure symptoms rarely require admission to the hospital. Conversely, a significant number of patients calling with non-procedure-related symptoms require admission within 30 days. Fellowship directors should consider providing training to fellows in the evaluation of symptoms over the telephone.

Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells.

BACKGROUND: The peptido-leukotrienes (LTs) and lipoxins (LX) are produced by platelets through the transcellular conversion of leukocyte-derived LTA4 at sites of vascular inflammation and injury, such as during coronary artery balloon angioplasty. We studied the actions of these eicosanoids on vascular endothelium. METHODS AND RESULTS: We found that stimulation of cultured human umbilical vein endothelial cells (EC) with LTC4 and LTD4 resulted in the release of high-molecular-weight multimers of von Willebrand factor (vWF) in a concentration- and time-dependent fashion, as measured by ELISA. Neither LXA4 nor LXB4 stimulated vWF release. LTC4 and LTD4 also stimulated a rapid increase in the surface expression of P-selectin indicated by increased binding of anti-P-selectin monoclonal antibody-coated beads. Fluorescence cytometry detected prolonged peaks of [Ca2+]i in EC in response to concentrations of thrombin and LTD4 that induce near-maximal vWF secretion. In contrast, concentrations of LTC4 that induce similar levels of vWF secretion produced only asynchronous oscillations of [Ca2+]i in most EC and rarely induced prolonged peaks of [Ca2+]i. Depletion of external Ca2+ had no apparent impact on LT-stimulated [Ca2+]i transients and vWF secretion, implicating an intracellular pool as the source of this response. Staurosporine, sphingosine, and H-7 each had only modest effects on peptido-LT-induced vWF secretion, suggesting that protein kinase C is not a primary mediator of peptido-LT-induced exocytosis. Inhibitors of cyclooxygenase and platelet-activating factor had no effect on peptido-LT-mediated vWF secretion. CONCLUSIONS: Through the induction of vWF secretion and P-selectin surface expression, peptido-LTs are likely to play an important role in the interrelated processes of hemostasis and inflammation.

Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction.

BACKGROUND: The endoscopically placed enteral stent has emerged as a reasonable alternative to palliative surgery for malignant intestinal obstruction. This is a report of our experience with the use of enteral stents for nonesophageal malignant upper GI obstruction. METHODS: Data on all patients who had undergone enteral stent placement were reviewed. Those with a diagnosis of pancreatic cancer were compared with another similar cohort of patients who underwent palliative gastrojejunostomy. RESULTS: Thirty-one procedures were performed on 29 patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%), third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%) procedures were successful and good clinical outcome was achieved in 25 (80.6%). Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days. The median survival time for patients with pancreatic cancer who underwent enteral stent placement compared with those who underwent surgical gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and duration of hospitalization was 4 and 14 days, respectively (latter 2 differences with p value < 0.005). CONCLUSION: Endoscopic enteral stent placement of nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost-effective procedure with good clinical outcome, lower charges, and shorter hospitalization period than the surgical alternative.

Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the potential of 3 spectroscopic techniques (fluorescence, reflectance, and light-scattering spectroscopy) individually and in combination, for evaluating low- and high-grade dysplasia in patients with Barrett's esophagus (BE). METHODS: Fluorescence spectra at 11 excitation wavelengths and a reflectance spectrum were acquired in approximately 1 second from each site before biopsy using an optical fiber probe. The measured fluorescence spectra were combined with the reflectance spectra to extract the intrinsic tissue fluorescence. The reflectance spectra provided morphologic information about the bulk tissue, whereas light-scattering spectroscopy was used to determine cell nuclear crowding and enlargement in Barrett's epithelium. RESULTS: Significant differences were observed between dysplastic and nondysplastic BE in terms of intrinsic fluorescence, bulk scattering properties, and levels of epithelial cell nuclear crowding and enlargement. The combination of all 3 techniques resulted in superior sensitivity and specificity for separating high-grade from non-high-grade and dysplastic from nondysplastic epithelium. CONCLUSIONS: Intrinsic fluorescence, reflectance, and light-scattering spectroscopies provide complementary information about biochemical and morphologic changes that occur during the development of dysplasia. The combination of these techniques (Tri-Modal Spectroscopy) can serve as an excellent tool for the evaluation of dysplasia in BE.