Gastroesophageal reflux as a reversible cause of allograft dysfunction after lung transplantation.

Gastroesophageal reflux (GER) is increasingly recognized as contributing to a number of pulmonary disorders. The relationship of GER to pulmonary allograft dysfunction after lung transplantation is unknown. In this report, we describe a lung transplant recipient who developed an acute decline in pulmonary function several months after a retransplantation for chronic rejection. A pulmonary workup at that time, including bronchoscopy with biopsy, revealed bronchial inflammation with no allograft rejection or infection. Because of increasing GI symptoms after retransplantation, the patient also underwent additional testing, which revealed severe acid reflux. The treatment of this patient's acid reflux with Nissen fundoplication surgery resulted in a prompt and sustained improvement in his pulmonary function. We suggest that GER should be considered among the potential causes of allograft dysfunction after lung transplantation.

Rapid progression to high-grade dysplasia in Barrett's esophagus after liver transplantation.

There is an increased incidence of malignancies in transplant recipients. Accelerated progression from a premalignant lesion to carcinoma has been reported in transplant recipients with skin cancer and colon cancer. Whereas Barrett's esophagus is a common premalignant condition in the normal population, rapid progression to severe dysplasia or carcinoma has not been widely reported in transplant recipients. We report on a liver transplant recipient who developed rapid progression from Barrett's esophagus without dysplasia to high-grade dysplasia within 9 months after transplantation.

Endoscopic discrimination of gastric ulcers.

Because endoscopists are concerned about misidentifying a gastric neoplasm as a benign gastric ulceration (GU), routine endoscopic biopsy and documentation of GU healing has been recommended. With the decreasing incidence of gastric cancer in the United States, the increased use of nonsteroidal anti-inflammatory drugs, and the concern over medical care costs, this practice standard has been questioned. To study the utility of endoscopic GU follow-up, we reviewed all cases of GU in the Duke GI-Trac database over a 7-year period. We found 1,189 patients diagnosed with GU who underwent 1,698 upper endoscopies. Of these, 130 patients underwent serial esophagogastroduodenoscopy until GU healing was documented. We identified 19 cases of gastric neoplasm. Endoscopic impression correlated with histology as follows: positive predictive value, 36%; negative predictive value, 99.3%; specificity, 90%; and sensitivity, 84%. Two of the three cases of GU in which the endoscopist's impression was benign but histology revealed malignancy occurred in the setting of an acute gastrointestinal bleed. We conclude that more than 99% of the time an endoscopist's initial impression that a GU is benign is correct. Using the Medicare reimbursement scheme, approximately $150,000 would be spent to detect one early gastric cancer. Our results further question the utility of serial endoscopic evaluation of GUs until healing.

Patterns of esophageal motility in patients with stable bulimia.

OBJECTIVES: A high prevalence of GI motility disturbances, including deranged esophageal motility, has previously been reported in patients with eating disorders; altered esophageal and gastric motility have been suggested to play an important role in these disease processes. We sought to confirm this association in an independent patient population. METHODS: We performed esophageal manometry in 12 patients with eating disorders (eight patients with bulimia and four with overlap syndromes, including both anorexia and bulimia features) and 12 sex-matched controls. All subjects completed a symptom questionnaire. Motility testing was performed in the standard fashion using a low compliance water perfusion catheter and computerized digital data capture. Coded tracings were interpreted in a blinded fashion. RESULTS: All 24 studies showed normal motility patterns [95% confidence interval for abnormal esophageal motility in eating disorders patients (0, 0.27)]. Mean lower esophageal sphincter pressure was 24.4 mm Hg in patients and 21.8 in controls; all relaxed normally. Mean esophageal body contraction amplitude 3 cm above the lower esophageal sphincter was 82.6 mm Hg in patients and 84.3 in controls; waveform morphology and progression met normal criteria in all studies. Eight of 12 patients reported dysphagia, odynophagia, or both, compared with 1 of 12 controls; patients demonstrated a pattern of increased overall GI symptomatology compared to controls. CONCLUSIONS: We conclude that disordered esophageal motility is uncommon among stable eating disorder outpatients with bulimic features, and that dysphagia and odynophagia are rarely associated with disordered motility in this group.

Evidence that CCK-58 has structure that influences its biological activity.

Many biologically active peptides exist in multiple molecular forms, but the functional significance of regions outside the region of bioactivity is unknown. The biological and immunological data presented in this study indicate that cholecystokinin-58 (CCK-58), unlike other forms of cholecystokinin, has structure that influences its bioactivity. CCK-58 was purified from acid extracts of canine intestinal mucosa until a single absorbance peak was obtained during reverse-phase chromatography. Amino acid analysis precisely determined the peptide concentrations of purified CCK-58 and synthetic CCK-8. Our hypothesis was that if the amino terminus of CCK-58 influences its bioactivity then its activity would be modified when this region was removed from the peptide. To evaluate the importance of the amino terminus of CCK-58 to influence its biological activity, the abilities of CCK-58 and CCK-8 to release amylase from pancreatic acini were compared before and after tryptic digestion. Tryptic digestion of CCK-58 decreased the half-maximal stimulation (EC50) for amylase release from 96 to 28 pM. The EC50 for digested CCK-58 was similar to that for CCK-8 (17 pM). These results suggest that CCK-58 has a structure that shields its bioactive carboxyl terminus. This is further supported by the finding that carboxyl fragments generated from CCK-58 by trypsin or by partial acid hydrolysis were greater than twofold more immunoreactive than the intact CCK-58. The diminished activity of CCK-58 SK shields the carboxyl terminus, which is important to its biological and immunological activities.

Predicting the presence of choledocholithiasis in patients with symptomatic cholelithiasis.

OBJECTIVES: Accurate preoperative prediction of choledocholithiasis is essential in order to minimize patient risk and curtail health care expenditures. This study was designed to identify independent risk factors for choledocholithiasis in patients who had undergone cholecystectomy for symptomatic cholelithiasis and to develop a predictive model based on those factors. METHODS: The charts of 1264 consecutive patients who had undergone cholecystectomy at one of three North Carolina hospitals between January 1, 1989 and December 31, 1991 were reviewed; 465 of these patients had confirmed presence or absence of choledocholithiasis by cholangiography and/or common bile duct exploration and were eligible for analysis. Candidate predictor variables included age and maximum preoperative values for each of the following: temperature, alkaline phosphatase, bilirubin, AST, amylase, white blood cell count, and common bile duct diameter. Model development and validation were conducted using standard data-splitting (60% "training," 40% "test") and logistic regression techniques. RESULTS: Choledocholithiasis was confirmed in 115 (25%) of the 465 eligible patients. Univariate analysis identified bilirubin, common bile duct diameter, AST, temperature, alkaline phosphatase, and age as predictors. Multivariable analysis subsequently identified bilirubin, common bile duct diameter, AST, alkaline phosphatase, and age as independent predictors of choledocholithiasis. A final model containing these variables (except age, whose contribution to the model was small) accurately predicted choledocholithiasis (c-index = 0.76). CONCLUSIONS: Accurate estimates of choledocholithiasis risk can be made using maximum preoperative bilirubin, common bile duct diameter, AST, and alkaline phosphatase values. Use of the model may help physicians select those patients with symptomatic cholelithiasis who would most likely benefit from further investigation to exclude choledocholithiasis.

Periprocedural myocardial ischemia in patients with severe symptomatic coronary artery disease undergoing endoscopy: prevalence and risk factors.

PURPOSE: To determine the prevalence of and risk factors for periprocedural myocardial ischemia associated with gastrointestinal endoscopy in patients with severe symptomatic coronary artery disease. PATIENTS AND METHODS: In this prospective observational study, myocardial ischemia (ST segment change > 100 microV in any 2 leads or > 200 microV in any 1 lead, lasting > 60 seconds) was assessed using a continuous 12-lead digital electrocardiographic monitor before, during, and after gastrointestinal endoscopy. RESULTS: Between June 1992 and May 1993, 1,084 esophagogastroduodenoscopies and 588 colonoscopies were performed during 1,438 consecutive endoscopies on patients admitted to a university hospital. Seventy (18%) of 252 patients with prior angiography had significant coronary artery disease. Fifty-two (74%) were successfully enrolled, and satisfactory electrocardiographic recordings were obtained from 49 (median age 65 years, interquartile range 58 to 74). Thirty-six were men, 12 had myocardial infarctions within the 6 weeks (median 12.5 days, interquartile range 8 to 18), and 25 had unstable angina. The coronary artery disease involved 1 vessel in 14 subjects, 2 vessels in 21, and 3 vessels in 14. Nineteen episodes of ischemia (4 pre-, 6 intra-, 9 postprocedure) were detected in 8 patients (16%; 95% confidence interval, 6% to 26%) during the recording period (median duration 322 min, interquartile range 227 to 429). One patient became symptomatic with a myocardial infarction. Multivariable logistic regression showed that women experienced more periprocedural ischemia compared to men (31% versus 11%; P = 0.058). CONCLUSIONS: Myocardial ischemia occurs during the periprocedural period in 16% of hospitalized patients with severe coronary artery disease undergoing gastrointestinal endoscopy. Endoscopy is safe in hemodynamically stable patients with recent myocardial infarction and/or unstable angina. Women appear to be at greater risk for periprocedural ischemia associated with endoscopy.

Botulinum toxin for suspected pseudoachalasia.

We describe a 74-yr-old man with stage III adenocarcinoma of the lung who presented with suspected malignancy-induced secondary achalasia and responded clinically to intrasphincteric injections of botulinum toxin type A (Botox, Allergen Inc., Irvine, CA). We discuss the use of botulinum toxin in this setting, as well as diagnostic strategies to differentiate achalasia from pseudoachalasia.

Effect of different coffees on esophageal acid contact time and symptoms in coffee-sensitive subjects.

The purpose of this study was to correlate the effects of different coffees on esophageal acid contact, heartburn, and regurgitation in patients with coffee-sensitivity. Twenty volunteers with coffee-sensitivity were studied in a double-blind, 3 period, crossover study examining the effect of three regular (caffeinated) coffees (a coffee from the USA--"A"; a "treated" coffee from Europe--"B"; and an "untreated" coffee from Europe--"C") before and after a high-fat test meal. The median acid contact times for coffees A, B, and C were 6.5%, 9%, and 10.5%, respectively (A vs. C, p = 0.005). Significantly fewer patients reported any symptoms with coffee A compared with coffee C (p < 0.05). Symptoms were usually more frequent and severe after the test meal. There was a trend toward fewer and less severe symptoms with the treated coffee (B) compared with its untreated counterpart (C). Our conclusions are as follows: (a) Different coffees induce variations in gastroesophageal reflux in coffee-sensitive individuals. (b) Coffee can be treated in a manner which decreases heartburn symptoms by 75% while decreasing acid contact by only 14%. (c) Gastroesophageal reflux and symptoms of coffee sensitivity increase with the concomitant ingestion of food. (d) Symptoms of dyspepsia appear to be influenced by variations in both the coffee itself and characteristics of susceptible individuals. (e) Although gastroesophageal reflux is important in the genesis of coffee-sensitivity, there must be other factors which act in concert with reflux to produce symptoms of coffee-sensitivity.

Complications of upper gastrointestinal endoscopy and their management.

The tremendous growth in the use of gastrointestinal endoscopy has necessarily produced complications of the procedures. In general, overall reported complication rates for diagnostic endoscopy are extremely low (0.13%-0.24%) reflecting these procedures' overall safety. However, many of these reports are likely to underestimate the true complication rate. Therapeutic procedures have substantially higher complication rates, the most frequent of which is perforation. Esophageal dilation, achalasia pneumatic dilation, and esophageal endoprosthesis placement carry the highest risk of perforation, 0.25%, 3.3%, and 7% to 15%, respectively. The outcomes research movement will revolutionize the future practice of endoscopy. Practice guidelines for endoscopy will not be determined by expert panels, but will be established empirically by outcomes research. Accurate complication rates will be determined from studies with complete and timely collection of intervention, confounding factors, and outcome. Finally, risk factors will be established by studies of appropriate design and power.

Clinical trials. How should they be designed?

The fundamental principles of clinical trial design include (1) a priori formulation of a specific research question, (2) precise description of the population to be studied, (3) limitation of the effects of chance by predetermining the study hypothesis and using methods that account for multiple statistical testing, (4) calculation of the sample size necessary to answer the research question, and (5) limitation of the potential bias whenever possible through blinding and random allocation of subjects to treatment and control groups (Table 2). Although the randomized controlled trial is regarded as the gold standard for determination of efficacy of therapy, cost and sample size are frequently rate-limiting. Other techniques have been developed to supplement clinical trials and include meta-analysis, data base (observational) research, and decision analysis. In the current climate of concern over staggering health care costs and variable practice patterns, research emphases are shifting from cost containment to maximizing value of health-related services and assessing patient outcomes.

Laparoscopic Nissen fundoplication: operative results and short-term follow-up.

The operative results, outcome, and short-term follow-up after laparoscopic exploration for Nissen fundoplication were evaluated in 35 patients with symptomatic gastroesophageal reflux and reflux-induced pulmonary disease. There were 19 female and 16 male patients, ranging in age from 17 to 72 years (mean: 42 years, SD: 11.6 years). In 20 patients, the symptoms were predominantly of regurgitation and heartburn; the remaining 15 patients had mixed regurgitation/heartburn and pulmonary symptoms. All patients underwent 24-hour pH monitoring, upper endoscopy, and manometry. The indication for surgery was medical failure or the need for long-term medical management with omeprazole. The operation, which was performed laparoscopically, is identical to the conventional Nissen fundoplication. There was a mortality rate of 0% and a morbidity rate of 25.7%. Five patients required conversion to open Nissen fundoplication, which was due to hemodynamic instability secondary to presumed pneumothorax in three patients and colotomy and a distal esophageal perforation in the other two patients. Thirty patients underwent laparoscopic Nissen fundoplication. Three patients developed early dysphagia, and one patient experienced a perforation of the piriform sinus due to nasogastric tube manipulation under anesthesia. All these patients had an uncomplicated postoperative course, and there was no long-term disability. The total surgical time of laparoscopic Nissen fundoplication was on average 107 minutes (SD: 35.3 minutes). Discharge usually occurred on the evening of postoperative day 2 (mean: 3.3 days; SD: 1.5 days). Twenty-six of the 30 patients who underwent laparoscopic Nissen fundoplication described the outcome as excellent and good (87%); however, 4 patients (13%) were unsatisfied. Fifteen patients (50%) had difficulty belching or vomiting, and moderate dysphagia was described by 7 patients (24%) in follow-up. Regurgitation and heartburn were cured in 96%, whereas reflux-induced pulmonary disease was cured in 50%. The results of laparoscopic Nissen fundoplication compare favorably with those of conventional Nissen fundoplication with respect to mortality, complications, and outcome.