Why do the published data fail to clarify the relationship between gastroesophageal reflux and asthma?

The relationship between gastroesophageal reflux (GER) and asthma has troubled physicians for centuries and has been a source of debate among pulmonologists, allergists, and gastroenterologists for decades. Attempting to tie together the pieces of the puzzle, numerous investigators have struggled to show that in patients with asthma, GER symptoms occur too frequently, gastric acid dwells for too long in the esophageal lumen, and refluxed gastric acid injures the esophageal mucosa more than expected. Unfortunately, all of the work done by these fine investigators has failed to demonstrate a "cause and effect" relationship. Although they have succeeded in convincing us that GER occurs more frequently in asthmatics than in nonasthmatics, they still must continue until we all know how to predict which patients have gastroesophageal-induced or gastroesophageal-exacerbated asthma.

Gastroesophageal reflux and asthma.

The medical literature has been deluged with articles on the relation between gastroesophageal reflux (GER) and asthma. In an effort to piece together the complex puzzle, investigators from all disciplines have gathered their patients with wheezing and heartburn and studied the epidemiology, the possible cause or effect mechanisms and the therapeutic response to GER treatment. Indeed, since humans first began to hunker down and work together to discuss interesting observations, the world has begun to breathe easier. Epidemiological evidence for a GER/asthma association suggests that about three-fourths of asthmatics, independent of the use of bronchodilators, have acid GER, increased frequency of reflux episodes, or heartburn; and 40% have reflux esophagitis. Physiological studies suggest that 2 separate mechanisms are involved in the GER/asthma relationship: (1) a vagally mediated pathway and (2) microaspiration. In any given patient, however, there is no acceptable diagnostic method available to confirm the presence or absence of GER-induced asthma. Clinical trials, using antireflux medical therapy and antireflux surgery have begun to provide some clues about GER-related pulmonary symptoms. The trials of medical therapy using acid suppressing drugs (e.g. histamine-2 receptor antagonists) have ranged from no benefit to modest improvement of only nocturnal asthma symptoms. Studies with proton-pump inhibitors are underway. In uncontrolled surgical studies, antireflux surgery has resulted in partial or complete remission of asthma symptoms in a large proportion of patients. Despite the uncontrolled nature of these studies, many patients have had dramatic subjective improvement in pulmonary symptoms. It appears for now that clinical trials are the only available means to assess whether medical or surgical treatment of GER in patients with both GER and asthma improves the symptoms of asthma and decreases the need for pulmonary medications. One conclusion is certain: We no longer can ignore the important co-existent nature of these 2 afflictions.

Preventing death of Barrett's cancer: does frequent surveillance endoscopy do it?

Patients experiencing gastroesophageal reflux may be predisposed to developing Barrett's esophagus, which is thought to be a precursor for the development of esophageal cancer. Currently, endoscopic surveillance is recommended for patients with Barrett's esophagus in the hope that esophageal cancer may be detected or even prevented. However, the frequency of endoscopic evaluations is a matter of debate. This article will examine whether regular endoscopic surveillance can prevent death of Barrett's cancer. The issues that are evaluated include the death rate from esophageal cancer, the need to scope all patients with reflux, the need to perform surveillance on all patients with Barrett's esophagus, survival data for Barrett's patients, and the incidence of nonsymptomatic Barrett's cancer.

Prostaglandins in peptic ulcer disease. An overview of current status and future directions.

Naturally occurring prostaglandins almost certainly play an important role in maintaining the integrity of the gastrointestinal mucosa. Clinical evidence available to date indicates that synthetic analogues of prostaglandins heal gastroduodenal ulcer only in doses that suppress gastric acid. However, non-antisecretory doses of prostaglandins may eventually have a role in the treatment of ulcer disease by maintaining ulcer healing and preventing recurrence. This possibility along with the potential of prostaglandins to prevent gastroduodenal mucosal injury caused by NSAIDs, alcohol, aspirin and stress, if supported by the results of ongoing clinical trials, may prove to be a major therapeutic advance for the treatment of acid peptic disease.

Walking and chewing reduce postprandial acid reflux.

BACKGROUND: Gastro-oesophageal reflux is worse after meals, and antacids are usually consumed after dietary indiscretion. AIM: To investigate whether walking or gum chewing affect meal-induced gastro-oesophageal reflux. METHODS: The study population comprised 12 case subjects with gastro-oesophageal reflux disease and 24 healthy controls. Each subject was studied using pH-metry for 5 h on 3 separate days. After baseline recording of pH for 1 h, all subjects were fed a standard breakfast over a 20-min period. On one of the days, oesophageal pH was recorded after the 20-min eating period for an additional 4 h in the sitting position. On another day, postprandial oesophageal pH was recorded for the first hour whilst walking, and for 3 subsequent hours whilst sitting. During a third day, oesophageal pH was recorded for the first postprandial hour whilst gum-chewing, followed by 3 h of sitting. RESULTS: Food intake promoted gastro-oesophageal reflux in case subjects with GERD as well as in healthy controls, although postprandial reflux was more pronounced amongst the refluxers than amongst the controls. Chewing gum for 1 h after the meal reduced the acid contact time in both groups, with a more profound effect in refluxers than in controls. Whilst the beneficial effect of 1-h of gum-chewing lasted for up to 3 h in both groups, the beneficial effect of 1-h of walking was apparent only in refluxers, only to a mild degree, and only for a short duration. CONCLUSIONS: Chewing gum after a meal helps to reduce postprandial oesophageal acid exposure.

There are no reliable symptoms for erosive oesophagitis and Barrett's oesophagus: endoscopic diagnosis is still essential.

AIMS: To evaluate the sensitivity and specificity of different symptoms in erosive reflux oesophagitis and Barrett's oesophagus. METHODS: The presence of reflux symptoms was compared between a case population of 306 patients with endoscopically determined erosive reflux oesophagitis, 235 patients with biopsy-proven Barrett's oesophagus and a control population of 198 subjects without reflux disease. RESULTS: Heartburn at any time and heartburn at night represented the only two symptoms to be simultaneously sensitive and specific. Symptoms that were induced by various foods, such as fat, tomato, chocolate, citrus or spices, tended to cluster in the same sub-group of patients. Similarly, heartburn induced by exercise, lying down or bending over tended to occur in the same sub-groups. The frequency of symptoms was influenced more by the presence of mucosal erosions than by the presence of Barrett's oesophagus. Reflux symptoms occurred more frequently in the presence rather than the absence of Barrett's oesophagus, and in long segment rather than short segment of Barrett's mucosa. CONCLUSIONS: Endoscopic inspection of the oesophageal mucosa remains the only certain method by which to reliably diagnose erosive reflux oesophagitis and Barrett's oesophagus.

Reflux symptoms are associated with psychiatric disease.

AIMS: To evaluate the frequency of reflux symptoms in patients with a diagnosed psychiatric disorder and to assess potential risk factors for symptom occurrence. METHODS: The presence of reflux symptoms was compared between a case population of 94 psychiatric patients and a control population of 198 non-psychiatric patients. RESULTS: Heartburn, exercise-induced heartburn, cough and dysphagia were all reported significantly more frequently by subjects with psychiatric disorders than by control subjects. The presence of any psychiatric diagnosis exerted an increased risk for both heartburn (odds ratio, 2.71; 95% confidence interval, 1.01-7.30) and exercise-induced heartburn (3.34; 1.12-9.96). The type of psychiatric disorder, the type of psychotropic medication and the lifestyle did not influence the presence of reflux symptoms. CONCLUSIONS: Reflux symptoms occur more frequently in patients with than without a diagnosed psychiatric disorder. The reflux symptoms are not associated with any specific type of medication and may reflect a generally reduced threshold for or distorted perception of symptoms.

Inguinal hernia is not a sign of colon cancer: results of a prospective screening trial.

BACKGROUND: It has been suggested that patients with an inguinal hernia harbour an increased risk for colorectal cancer. METHODS: In a prospective clinical trial, we compared the prevalence of colonic neoplasms in 100 cases with inguinal hernia and 100 controls without inguinal hernia. The number, size, histology type, and the location of all colorectal lesions found during a screening flexible sigmoidoscopy were recorded. RESULTS: Not a single case of colorectal cancer was detected in the patients with inguinal hernia pending surgical repair. In the asymptomatic control subjects, one Dukes A and one Dukes B1 colon cancer were detected. Polypectomy was performed in 15% and 17% of the case and control subjects, respectively. During a 5-year period following the initial screening procedure, none of the case or control subjects was diagnosed with colon cancer. CONCLUSIONS: The decision for or against performing an endoscopic procedure in a patient with inguinal hernia should be guided by the general principles of screening for colorectal cancer. The mere presence of an inguinal hernia does not automatically increase the risk of colorectal cancer.

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux. AIM: To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus. METHODS: An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2-4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8. RESULTS: The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups. CONCLUSION: In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

The significance of intraepithelial eosinophils in the histologic diagnosis of gastroesophageal reflux.

Detection of intraepithelial eosinophils in esophageal mucosal biopsies has been suggested as histologic evidence of symptomatic gastroesophageal reflux (GER) disease in both children and adults. Previous studies have primarily examined symptomatic persons, and only one study included a comparison with normal controls. In the present study, the authors examined esophageal mucosal biopsies obtained by the hydraulic suction technic for the presence of intraepithelial eosinophils from 73 adult patients with subjective and objective evidence of GER disease and 12 asymptomatic adult volunteers in whom a series of esophageal function tests were normal. Intraepithelial eosinophils were identified in 23 (31.5%) of adult patients and in 4 (33.3%) of the asymptomatic volunteers. No clinical aspects in the GER patients correlated with the presence of eosinophils. By crude quantitation, rare eosinophils added little to more conventional assessment of histologic esophagitis and were present in one-third of normal subjects. The authors conclude that rare eosinophils in esophageal biopsies may not be a reliable criterion for the histologic assessment of GER disease.

Fecal occult blood testing: a false sense of security?

BACKGROUND: Recent screening studies with fecal occult blood testing (FOBT) report that one of three patients with colorectal cancer (CRC) can be cured of the disease; minimal attention has been given to the two of three patients who despite repeated screening go on to die of silent CRC. We report the known "miss rate" (known false negatives) of our 14-year ongoing program of FOBT that was organized in 1979 to detect early CRC. METHODS: From October 1979 through December 1993, 36,034 FOBT kits were distributed to patients who were without gastrointestinal complaints at Hines Veterans Affairs Hospital. The test was considered positive if at least one result of the six tests was positive and negative if the test result was equivocal. Patients with negative FOBT received a new test kit each year by mail. A positive test was followed by full colonoscopy or an air contrast barium enema if a full colonoscopy was not possible. RESULTS: The overall return rate was 47.8%. CRC was detected in 115 patients: 94 had a favorable and 21 had an unfavorable Duke's C or D or lymphoma prognosis. Of 21 patients 13 (62%) had initially tested FOBT negative (missed lesion). Of the 21 cases of advanced CRC 15 (71.43%) were in the descending, sigmoid, or rectosigmoid colon or rectum. CONCLUSIONS: (1) The majority (82%) of all CRC detected by FOBT screening are diagnosed at a favorable stage. (2) The majority of known advanced CRC (62%) escape early detection with FOBT. (3) Five (62.5%) of eight of the advanced CRC cases discovered on initial FOBT and 10 (76.9%) of 13 of advanced CRC cases missed on initial FOBT but detected in subsequent years were in the left colon and most likely in the range of the flexible sigmoidoscope. (4) FOBT as a sole screening test may provide a false sense of security, especially in patients with advanced left-side CRC.

Cholecystectomy in cirrhotic patients: a formidable operation.

Cholecystectomy and common bile duct exploration in cirrhotic patients is associated with an 83 percent mortality if prothrombin time is prolonged 2.5 seconds over control. The causes of death are related to complications of liver disease such as hepatic encephalopathy, ascites, sepsis and hemorrhage. If the prothrombin time is prolonged, major intraoperative blood loss can be anticipated, and blood and plasma transfusion requirements may be massive. Jaundice in the presence of cirrhosis requires careful preoperative evaluation and is most frequently due to hepatocellular disease rather than extrahepatic biliary obstruction. Cholecystectomy and common duct exploration in cirrhotic patients should be performed only for life-threatening complications of biliary tract disease such as empyema, perforation and ascending cholangitis.

Risk factors of oesophagitis in arthritic patients.

BACKGROUND: The risk factors that precipitate the occurrence of oesophageal mucosal injury in patients on continuous nonsteroidal anti-inflammatory drug (NSAID) therapy are unknown. METHODS: Outpatients who regularly consumed NSAIDs for osteoarthritis were recruited from a rheumatology clinic into a prospective case-control study. All patients answered a structured interview and underwent upper gastrointestinal endoscopy. RESULTS: Of 450 eligible patients, 195 (43%) consented to be interviewed and undergo upper gastrointestinal endoscopy. Oesophagitis was diagnosed in 41 of these 195 patients (21%). The occurrence of gastric or duodenal ulcer in individual patients did not predict the concomitant damage of the oesophageal mucosa. Young age (odds ratio: 1.79 per decade of life; 95% confidence interval: 1.11-2.86) and hiatus hernia (odds ratio: 3.72; 95% confidence interval: 1.63-8.49) both increased the risk of developing oesophagitis. When questioned, all oesophagitis patients revealed at least one gastrointestinal symptom, heartburn being named most frequently (odds ratio: 4.78; 95% confidence interval: 2.04-11.17). The type of anti-inflammatory medication, the use of alcohol and the use of nicotine were not associated with any significant risk for erosive oesophagitis. CONCLUSIONS: Patients on chronic NSAID therapy for rheumatological disease suffer frequently from erosive oesophagitis. While the risk may be higher in patients with a pre-existing tendency for gastro-oesophageal reflux, any concomitant history of NSAID-induced peptic ulcer disease does not add to the risk. Erosive oesophagitis should be considered especially in patients on NSAIDs who complain of heartburn.

The cause of leg cramps and knee pains: an hypothesis and effective treatment.

Cramps and pains of the lower extremities along with stiffness and pains in the knees are common complaints in the general population. Because the etiology and development of these disorders are poorly understood, treatment has been haphazard, for the most part unsuccessful, and occasionally dangerous. The diagnosis of "arthritis" is often incorrect; when osteoarthritis is present it is frequently not the cause of the pain. We name these maladies the "stiff leg syndrome" and hypothesise that they are caused by muscle and tendon shortening which came about as a direct result of modern civilization; the popular practice of squatting close to the ground to defecate, cook and eat was replaced by a more "civilized" practice of sitting high on toilets and chairs. We discuss several simple stretching exercises which mimic the effects of squatting and frequently result in immediate and dramatic relief of symptoms.

Transarterial chemoembolization for HCC in patients with extensive liver transplantation waiting times.

The treatment of hepatocellular cancer (HCC) with transarterial chemoembolization (TACE) prior to orthotopic liver transplant (OLT) is of increasing importance due to the rise in HCC incidence and donor shortage. This single-center study examines 28 patients treated with TACE and 7 patients not treated with TACE, with HCC prior to OLT between 1999 and 2008. The overall 1- and 5-year survival of all transplanted patients with HCC was 94% (33 of 35) and 80% (28 of 35). There was no difference in survival (P = .99) between patients who underwent transplantation immediately (median 95 days) and patients who had significantly longer wait times (median 308 days) when treated with TACE. During extensive wait times for OLT, TACE can be used to keep patients with HCC on the waiting list by preventing tumor progression, with similar outcomes compared with those who underwent transplantation immediately.