The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used. SURGERY: Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation. HEALTH ECONOMICS: There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.

Value of a therapeutic trial to diagnose gastroesophageal reflux disease: step up versus step down therapy.

The 1992 Canadian Association of Gastroenterology consensus conference on gastroesophageal reflux disease (GERD) recommended a therapeutic trial of H2 receptor antagonists as a cost effective approach to the management of patients with typical symptoms of GERD. Omeprazole, with its increased potency and efficacy of acid suppression, appears to be the ideal diagnostic test therapy for GERD. However, there is little evidence in the literature to support this approach. Omeprazole has the potential to mask other disorders such as peptic ulcer disease, thereby delaying appropriate testing for and eradication of Helicobacter pylori. Therefore, omeprazole therapeutic trials should be used with caution in the diagnosis of GERD. The conventional step up therapy is the least costly and reasonably effective approach to treat the majority of patients with mild to moderate symptoms of GERD. For patients who fail therapy or have complications of GERD, the recently proposed step down therapy is probably more effective and appropriate. As physicians become more comfortable with the long term use of proton pump inhibitors, step down therapy may well replace the more conservative step up approach to therapy.

Ambulatory esophageal manometry, pH-metry, and Holter ECG monitoring in patients with atypical chest pain.

Standard Holter electrocardiographic (ECG) monitoring was combined with ambulatory esophageal manometry and pH-metry in 25 patients with atypical chest pain in order to determine whether an association could be found between spontaneous pain episodes and ischemic ECG changes or esophageal dysfunction. Results of ambulatory testing were compared to those obtained with standard esophageal manometry and provocative testing. Twenty-two of the 25 patients experienced a total of 88 pain episodes during ambulatory testing. Although 15 of the 22 patients (68%) experiencing pain during testing had at least one pain episode that correlated temporally with gastroesophageal reflux, esophageal dysmotility or ischemic ECG changes, 65% of all pain episodes were unrelated to abnormal esophageal events or ECG changes. Seventeen percent of pain episodes were associated with gastroesophageal reflux, 15% with esophageal dysmotility, and 2% with a combined acid reflux and esophageal dysmotility event. Only one pain episode was associated with ischemic ECG changes. Twelve of the 15 patients with chest pain episodes associated with reflux or esophageal dysmotility had other identical pain episodes in which there was no correlation. Reproduction of a patient's pain during standard manometry with provocative testing did not predict a strong correlation between the patient's spontaneous pain episodes and esophageal dysfunction during ambulatory recordings. In summary, patients with atypical chest pain have relatively few spontaneous pain episodes that correlate with gastroesophageal reflux, esophageal dysmotility, or ischemic ECG changes. It appears that different stimuli can trigger identical episodes of chest pain, which suggests that many of these patients may have dysfunction of their visceral pain sensory mechanisms.

Transition from nutcracker esophagus to achalasia. A case report.

We report a middle-aged woman with nutcracker esophagus who progressed to classic achalasia in two years. Several previous reports have documented progression of nutcracker esophagus to diffuse esophageal spasm and diffuse esophageal spasm to achalasia, but the only previous report of nutcracker esophagus progressing to achalasia was in a child. Our case suggests that, in some instances, nutcracker esophagus and achalasia may share the same pathogenesis.

Omeprazole in H2 receptor antagonist-resistant reflux esophagitis.

We conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of H2 receptor antagonists to heal their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were on H2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal (grade II) or circumferential (grade III) distal esophageal ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2 antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy. Two of these 14 patients opted for antireflux surgery, whereas the remaining 12 were once again given omeprazole, which again resulted in symptom resolution in all patients. These data suggest that most patients with H2 receptor antagonist-resistant ulcerative esophagitis cannot be successfully maintained on H2 antagonists even after the ulcers have been healed with omeprazole. Further studies are required to determine the role of omeprazole compared to other treatments in the long-term maintenance therapy of these patients.

A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-based lavage solution (Golytely) in the preparation of patients for colonoscopy.

One hundred and two patients were randomized to receive either oral sodium phosphate or standard polyethylene glycol-based lavage solution (Golytely) prior to colonoscopy in order to establish whether the much smaller volume of the former agent enhanced patient tolerance while maintaining or improving effectiveness and safety. Overall, patients found sodium phosphate preparation much easier to complete. In 37 patients who had had a previous colonoscopy prepared with Golytely, 100% of those now receiving sodium phosphate found it easier to complete and over 90% felt it caused less discomfort, compared with their previous experience with Golytely. Colonoscopists, unaware of the type of lavage solution used, scored the degree of colonic cleansing significantly higher for sodium phosphate-prepared colons compared with colons prepared with Golytely. Serial measurements of blood tests and postural pulse and blood pressure changes did not reveal any clinically significant changes in intravascular volume. Hyperphosphatemia was noted with sodium phosphate, but was transient, and no concomitant decrease in calcium was seen. Histological assessment for possible preparation-induced changes revealed no difference between the two agents. Sodium phosphate is significantly less expensive than Golytely. We conclude that, in the group of patients studied, sodium phosphate is a safe colonic cleansing agent that is better tolerated and more effective than Golytely.

Sugar absorption by small bowel biopsy samples from patients with primary lactase deficiency and with adult celiac disease.

The present study was undertaken to compare the 3-O-methyl-D-glucose (3MG) absorption by jejunal biopsies from normal human subjects (N = 3) with that by the jejunum of the rat (N = 8) and of the hamster (N = 8), and to examine whether jejunal biopsies from normal subjects (N = 3), patients with primary lactase deficiency (N = 5) and from patients with celiac sprue (N = 5) follow the same pattern of sugar absorption as usually observed in vivo. The results indicate that under the conditions of our experiments the estimated affinity of carrier for 3MG (ie, apparent Km) in the biopsies from normal subjects did not differ significantly from that in rat or hamster jejunum. The estimated capacity of carriers for 3MG absorption (ie, Vmax) appeared to be similar in biopsies from normal subjects and in hamster jejunum, but significantly lower in rat jejunum. There was no difference in apparent Km between the biopsies from normal subjects and those from the patients with lactase deficiency. Although the Vmax for the lactase deficient patients was substantially higher than that for the normal subjects, the difference was not statistically significant. The absorption of 3MG by the biopsies from patients with celiac sprue did not follow Michaelis-Menten kinetics and was compatible with that of passive diffusion or low saturation conditions. Since the intracellular concentration of 3MG in all biopsies from celiac patients exceeded the concentration of the media, sugar transport could not have occurred by diffusion, and it is concluded that the absence of Michaelis-Menten kinetics was the result of low saturation conditions. This active transport with low saturation kinetics in patients with celiac disease suggests that in these patients not only the number of functioning carrier molecules is diminished but also the affinity of the existing carrier for sugar molecule is reduced. This situation, at least in some patients, seems to improve after treatment with gluten-free diet.

Tests of intestinal function.

The most important tests for investigating the functions of the small bowel are faecal-fat analysis, the determination of xylose tolerance, vitamin-B12 absorption, and 14C-glycoholate transport, barium examination of the small bowel, and small bowel biopsy. With these tests, most disorders of digestion and of absorption can be adequately investigated and diagnosed.

Small-intestinal cell turnover in patients with parasitic infections.

Small-intestinal deoxyribonucleic acid (DNA) loss rates were measured in six patients with Strongyloides stercoralis hyperinfestation, in four patients with hookworm disease, and in eight normal controls. In the four patients with strongyloidiasis having weight loss, hypoproteinaemia, and oedema the mean DNA loss rates were 73.9, 51.6, 58.0, and 62.2 ng atoms DNA-P/min respectively, which was significantly higher than that of patients with hookworm disease (mean 17.3, S.D. 6.6) or in eight control subjects (mean 14.5, S.D. 7.5). In two of three patients with strongyloidiasis the high DNA loss rates fell to normal after treatment, and in two others investigated only after treatment the rates were normal. It is suggested that the high epithelial cell turnover in these patients may result in excessive loss of endogenous substances and that this may be an important mechanism in causing malnutrition and hypoproteinaemia in patients with S. stercoralis hyperinfestation.

Protein loss and cell loss from the small-intestinal mucosa.

Total protein and deoxyribonucleic acid (dna) were measured in small-intestinal washings from rats with normal and high rates of dna (or cell) loss. There was a significant relationship between the loss of these two substances. Preparations of isolated viable epithelial cells contained much less protein in relation to dna than did the intestinal washings. It was calculated that only 8 to 15% of the protein lost by washing the rat small intestine arose from the intracellular protein of exfoliated epithelial cells. The rest was derived from extracellular sources.Protein and dna loss from small-bowel mucosa was measured in six patients. The ratio of protein to dna was similar to that found in the rats. The mean protein loss from 5 cm of human upper small intestine was 956 mug per min or 1.4 g per 24 hours. By calculation, total protein loss from the whole small intestine of man was about 84 g per day, about 10 g coming from within exfoliated cells and the rest arising from extracellular sources. The normal intestine must reabsorb most of this material.