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Newsletter 1-15-00  

            Contents of this newsletter:

1. What Really Triggers Your Heartburn?
2. Surgery For Severe Reflux Disease Is Superior to Medical Treatment
3. Omeprazole Test A Sensitive First Step in Evaluation of Reflux
4. Symptomatic Treatment of Reflux Disease Prevents Progression to Stricture
5. Nonulcer Dyspepsia Tied to H. Pylori Infection
6. What Is The Most Effective Imaging Study For Determining The T and N Stages of Esophageal Carcinoma?
7. H. pylori Infection Twice as Likely in Heart Attack Survivors
8. H. Pylori May Not Be As Prevalent in Gastric Ulcer As Previously Thought
9. Nursing Position Affects Symptom Severity in Preterm Infants With Reflux
10. Do You Need Extra B-12?
11. Ulcer Bacteria Linked to Iron Deficiency Anemia
12. Burning Issues In Barrett's Esophagus
13. Painkillers May Add to Heartburn
14. Regular NSAID Use May Raise Reflux Risks


1. What Really Triggers Your Heartburn?    Top

From the publishers of the New England Journal of Medicine

People with heartburn  may be able to pinpoint one or two things that trigger their bouts of searing chest pain, caused by the acidic contents of the stomach splashing up into the esophagus. But many do not know the wide range of foods and lifestyle factors that can cause digestive distress, according to a survey of 2,000 heartburn sufferers published in the July 26 Archives of Internal Medicine. What's more, most survey respondents relied heavily on over-the-counter medications rather than changes in habits to prevent or treat heartburn. Each person who experiences heartburn has a unique set of triggers, but the list below may help you identify more causes of your own heartburn. Your doctor can also suggest lifestyle modifications, such as propping yourself up in bed, that can help you control the burn.

Lifestyle Factors

Specific Food Triggers

Being overweight
Eating a heavy meal
Eating acidic foods
Sitting or lying down after a meal
Stressful or hectic family situations
Stressful, hectic or long workdays
Dining out
Smoking
Traveling
Exercise
Number or timing of meals
Tight clothing around the stomach
Some medications, such as aspirin, that can irritate the stomach

Spicy foods
Fast foods
High-fat foods
Citrus fruits or juices
Tomato products
Caffeinated drinks
Carbonated drinks
Alcoholic drinks
Chocolate
Peppermint
Vinegar

2. Surgery For Severe Reflux Disease Is Superior to Medical Treatment    Top

SAN FRANCISCO, Oct 20 (Reuters Health) - In a presentation at the Annual Clinical Congress of the American College of Surgeons in San Francisco, Dr. Lars Lundell reported for his colleagues in the Nordic GERD Study Group on a 5-year follow-up of 310 patients with chronic severe gastroesophageal reflux disease randomized to treatment with either omeprazole or open antireflux surgery.

"Omeprazole was inferior to antireflux surgery," Dr. Lundell, of Sahlgrenska University Hospital in Goteburg, Sweden, told the audience. "This finding was highly statistically significant." According to his presentation, 83 patients of 122 in the surgery arm were still in remission at 5 years, versus 65 of 133 patients originally assigned to medical management.

In comments made after Dr. Lundell's talk, Dr. Tom R. DeMeester of Los Angeles, California, recounted the history of the "contest" between medical and surgical therapies of reflux disease. Dr. DeMeester told the audience that with the findings presented here by the Scandinavian team, "the game is over."

Next, Dr. Majid Hashemi of the University of Southern California in Los Angeles, California, reported on his team's comparison of outcomes in 54 patients who underwent either laparoscopic or open repair of large type III hiatal hernias. At median follow-up times of 17 months in the laparoscopy group and 35 months in the laparotomy group, hernias had recurred in 42% of patients treated laparoscopically versus 15% of patients who had open procedures.

In his discussion of Dr. Hashemi's presentation, however, Dr. Frederick L. Green of Charlotte, North Carolina, cautioned that nearly 25% of patients had not undergone follow-up video esophagrams, and that "...inclusion of these patients might significantly change the results."

Dr. Guy R. Voeller of the University of Tennessee in Memphis, Tennessee, then described a four-center review of laparoscopic repairs of primary and recurrent ventral hernias in 415 patients. Dr. Voeller and his colleagues concluded that "the laparoscopic approach is safe and effective." Only 8 patients required conversion to an open procedure, he told the audience, and only 14 patients had recurrence of their hernia.

Finally, Dr. Peter W. T. Pisters of the University of Texas M. D. Anderson Cancer Center in Houston, Texas, reported on his team's finding in 300 consecutive patients that preoperative biliary decompression does not increase morbidity after pancreaticoduodenostomy. Their results, Dr. Pisters told the audience, "...have significant implications for the diagnostic evaluation of patients with obstructive jaundice and patients treated with neoadjuvant therapies."

3. Omeprazole Test A Sensitive First Step in Evaluation of Reflux    Top

WESTPORT, Oct 21 (Reuters Health) - The "omeprazole test" is a reliable and cost-effective means of diagnosing gastroesophageal reflux disease (GERD) in patients with symptoms of the disorder.

In fact, "[t]his strategy could result in significant cost savings and decreased use of invasive diagnostic tests," Dr. Ronnie Fass, of the Tucson Veterans Affairs Medical Center, in Arizona, and multicenter colleagues conclude in the October 11th issue of Archives of Internal Medicine.

The team evaluated the diagnostic accuracy of the omeprazole test--a trial of high-dose omeprazole--in 43 patients with suspected GERD who were seen at Veterans Affairs medical centers. Forty-two patients completed the study.

Using standard diagnostic strategies, the team diagnosed 35 of the patients as GERD-positive and seven patients as GERD-negative. Twenty-eight of the GERD-positive patients responded to the omeprazole test, as did three of the GERD-negative patients. The investigators calculated that the sensitivity and specificity of the omeprazole test were 80.0% and 57.1%, respectively.

Dr. Fass and colleagues estimate that the omeprazole test saved nearly $350 per patient evaluated, reducing the need for upper endoscopy by 64% and reducing the number of pH tests by 53%. "Maintenance of antireflux treatment in [GERD-positive] patients with the lowest effective dose of antisecretory medication is the natural next step, which will spare patients from a variety of invasive diagnostic tests."

The team adds that the optimal dosage and duration of omeprazole, as well as the appropriate cut-off for symptom reduction, require further evaluation.

Arch Intern Med 1999;159:2161-2168.

4. Symptomatic Treatment of Reflux Disease Prevents Progression to Stricture    Top

By M. Mary Pennell

PHOENIX, Oct 21 (Reuters Health) - Symptom-driven treatment of gastroesophageal reflux disease (GERD) is sufficient to prevent progression to stricture, according to study results presented here at the 64th annual scientific meeting of the American College of Gastroenterology.

Dr. Stephen Sontag of the Veterans Affairs Hospitals in Hines, Illinois, presented data culled from a population of 2,306 outpatients who were treated for symptoms of GERD between 1979 and 1999 and underwent two or more

endoscopies. "Sixty-seven percent of the patients were unchanged during the 20 years, 22% improved and 11% got worse," Dr. Sontag said.

At baseline endoscopy, 1,317 patients had normal mucosa. The Illinois researcher reported that "...10 of those patients developed stricture in a mean of 8.5 years. What this means is that with normal mucosa on endoscopy, 84% of GERD patients remain the same over 20 years."

Dr. Sontag found that use of proton-pump inhibitors "...was predictive of improvement, while use of NSAIDs [nonsteroidal anti-inflammatory drugs] predicted worsening."

"In conclusion, I think we can say that reflux therapy geared solely toward symptoms is the correct treatment," Dr. Sontag said.

In a second paper presented during a special session on the esophagus, Dr. Allan P. Weston of the Veterans Affairs Medical Center in Kansas City, Kansas, reported that in patients with Barrett's esophagus who have low-grade dysplasia, overexpression of the p53 protein may be a marker for progression to cancer or high-grade dysplasia if it is identified at the time of diagnosis of low grade-dysplasia.

Dr. Weston studied 31 white male patients with Barrett's esophagus, with a mean age of 63.5. Twenty-seven patients had hiatal hernia. "The Barrett's length ranged from 1 to 18 cm with a mean length of 6.4 cm," Dr. Weston said. "The patients were followed for up to 70 months, with the mean follow-up 43.6 months." During the study, each patient underwent an average of 5.2 endoscopies.

The research team established p53 positivity by immunostaining. "Six patients were positive for p53 and half of these patients progressed to either high-grade dysplasia or cancer," Dr. Weston told meeting attendees.

Overall, five patients in the study progressed to cancer, Dr. Weston told Reuters Health in an interview. He said that p53 may be useful as "...a risk factor for progression, but its greatest potential use is as a marker to help stratify risk."

Separately, Dr. Douglas S. Levine, of the University of Washington in Seattle, reported that four-quadrant biopsies taken at 1-cm intervals every 3 months can accurately identify early cancers in patients with Barrett's esophagus and high-grade dysplasia.

Dr. Levine reported on 123 consecutive patients who presented with high-grade dysplasia. Forty-five of the patients progressed to cancer and "...half of the cancers were detected at the first two endoscopies," he said. He said that if

the biopsies had been done at 2-cm intervals, "...only half of the cancers would have been detected, and if only visible lesions were biopsied, only a third of cancers could have been detected."

Using this closely timed surveillance approach, 43 of the 45 cancers were detected at the intramucosal stage, Dr. Levine said.

5. Nonulcer Dyspepsia Tied to H. Pylori Infection    Top

WESTPORT, Oct 21 (Reuters Health) - Helicobacter pylori infection is strongly linked to nonulcer dyspepsia, according to the results of a meta-analysis. Furthermore, dyspeptic symptoms are almost twice as likely to improve in cases where H. pylori infection is eradicated.

In the October 16th issue of the British Medical Journal, Dr. R. Liisa Jaakkimainen of the University of Toronto, Ontario, Canada, and multinational associates report the results of a meta-analysis of 23 observational studies that examined the association between H. pylori and nonulcer dyspepsia. The research team found that study subjects with H. pylori infection were 60% more likely than uninfected subjects to have nonulcer dyspepsia.

Separately, the team conducted a meta-analysis of five randomized studies that investigated whether eradicating H. pylori alleviates dyspeptic symptoms. The results showed that for patients in whom H. pylori was eradicated, dyspeptic symptoms were 90% more likely to improve compared with patients in whom the infection was not eliminated.

Dr. Jaakkimainen and colleagues note that most studies involved patients referred to secondary or tertiary care settings, who presumably had more severe symptoms than patients in the general population.

They suggest that further studies should investigate the magnitude of symptom improvement among primary care patients in whom H. pylori is eradicated, and the cost effectiveness of eliminating the bacterium.

BMJ 1999;319:1040-1044.

6. What is The Most Effective Imaging Study For Determining The T and N Stages of Esophageal Carcinoma?    Top

Endoscopic ultrasonography (EUS) is the single best modality for staging esophageal cancer with respect to depth of tumor infiltration and extent of lymph node involvement using the TNM classification system. The accuracy of EUS for staging patients with esophageal carcinoma who subsequently underwent surgery for confirmation ranged from 59% to 92% (with a mean of 84% in 1154 patients); the accuracy for N staging ranged from 50% to 90% (with a mean of 77% in 1035 patients). Endosonography is superior to CT in the T and N staging of disease.

However, EUS is not a sensitive tool for diagnosing tumor involvement of the trachea and bronchial tree, because these structures contain air. Bronchoscopy should be used for the staging of proximal esophageal cancers. If esophageal cancers obstruct the lumen and the EUS endoscope cannot be advanced through, tumor staging is incomplete.

EUS employs the technology of endoscopy and internally placed high-frequency ultrasound waves to visualize the gastrointestinal wall and adjacent structures. EUS is fast emerging as an important modality for the diagnosis and staging of benign and malignant lesions of the gut wall and the surrounding structures of the mediastinum, abdomen, and pelvis. Interventional applications, such as EUS-guided fine needle aspiration (EUS-FNA) for obtaining tissue/fluid samples, for pseudocyst drainage, and also for delivery of local therapy will likely enhance the clinical utility and cost-effectiveness of this imaging modality.

The widest application of EUS is, however, in the diagnosis and staging of esophageal, gastric, rectal, and pancreaticobiliary carcinoma. While endosonography is the most accurate study available for determining the T and N stages of these neoplasms, EUS-FNA can cytologically confirm the diagnosis and staging of disease with tissue. EUS has been shown to change the approach to clinical management in a significant portion of patients to a less costly, risky, or invasive strategy.

Source: Sze G, Takahashi P, Eysselein VE: Medscape Gastroenterology, 1999.

7. H. pylori Infection Twice as Likely in Heart Attack Survivors    Top

NEW YORK (Reuters Health) -- People who survive a heart attack are twice as likely to be infected with Helicobacter pylori (H. pylori) -- a bacteria known to cause most ulcers -- as people who do not have heart disease, British researchers report.

Although the study findings do not prove that H. pylori causes heart attacks, they suggest that there may be a link between the infection and heart risk, the team writes in the October 30th issue of the British Medical Journal.

8. H. Pylori May Not Be As Prevalent in Gastric Ulcer As Previously Thought    Top

PHOENIX, Oct 25 (Reuters Health) - Only about half of all peptic ulcers may be attributable to Helicobacter pylori, researchers told the 64th annual scientific meeting of the American College of Gastroenterology.

In a series of Medicare and Medicaid patients hospitalized and treated for confirmed peptic ulcer in New York State, the proportion positive for H. pylori ranged from 43% to 49% in the Medicare population and was 61% in the Medicaid population.

Dr. James H. Puleo of the Island Peer Review Organization in Albany, New York, said that the study involved survey responses from 200 hospitals in New York. He told Reuters Health that "...the rate of H. pylori infection in our population among our patients tends to be about 50%, not the 90% reported in clinical trials."

Dr. Puleo's group also checked on the management of H. pylori-positive patients, a year after recommendations were issued in an NIH consensus statement in 1994. He said that 80% of such patients who were not treated in hospital for the infection were put on antibiotics after discharge. The New York investigator said that delayed laboratory results and caution on the part of clinicians accounted for the shortfall in optimal care.

9. Nursing Position Affects Symptom Severity in Preterm Infants With Reflux    Top

WESTPORT, Oct 27 (Reuters Health) - Simply changing an infant's position during feeding can significantly reduce the severity of gastroesophageal reflux in preterm infants.

"Such positioning offers a useful adjunct to the treatment in hospital of preterm infants with gastroesophageal reflux," Dr. A. K. Ewer, of Birmingham Women's Hospital, UK, and colleagues suggest in the November issue of Archives of Disease in Childhood: Fetal and Neonatal Edition.

The investigators studied the effects of nursing position on gastroesophageal reflux duration and frequency in 18 preterm infants with clinically significant reflux. Mothers nursed the infants in the prone, left lateral or right lateral positions for 8 hours each in a randomly assigned order. Gastroesophageal reflux was assessed using 24-hour lower esophageal pH monitoring.

"Our data suggest that a reduction in reflux index of at least one third will be observed if right-sided positioning is avoided," the investigators write.

Specifically, the reflux index was significantly lower when infants were fed in the prone or left lateral positions than in the right lateral position, with median scores of 6.3%, 11.0% and 29.4%, respectively. The duration of the longest reflux episode was reduced significantly in the prone and left lateral positions compared with the right lateral position, with average durations of 8.6, 10.0 and 26.0 min, respectively.

In addition, positioning influenced the median number of reflux episodes during the 8-hour feeding time. There were 41.6 episodes when infants nursed in the right lateral position but only 15.4 and 24.6 episodes when they nursed in the prone and left lateral positions, respectively.

The researchers note that similar findings have already been reported for term infants, but that this is the first report of an association between nursing position and gastroesophageal reflux in preterm infants.

Although the data were obtained on infants nursed in hospital, the data have important implications for advising parents on nursing and sleeping positions after hospital discharge, Dr. Ewer and colleagues conclude.

Arch Dis Child Fetal Neonatal Ed 1999;81:F201-F205.

10. Do You Need Extra B-12?    Top

By Karen Collins, R.D

Oct. 29 — It was once thought that Americans had no problem meeting the recommended intake of vitamin B-12. But now research shows that several groups of people should consider using supplements or fortified foods to meet their needs.

LACK OF B-12 has rarely been a problem in the U.S., since average intake is more than double the recommended dietary allowance (RDA). Vitamin B-12 occurs naturally only in animal products: meat, poultry, seafood and dairy products. But vegetarians are only at risk if they avoid all animal products for an extended time.
Experts used to believe that these vegetarians could rely on seaweed, algae or miso for B-12, but more recent studies have found that they contain a form of B-12 that is not utilized by our bodies. These vegetarians may therefore want to add a fortified food or supplement providing B-12 to their regular diets.
The body uses vitamin B-12 to produce blood cells. Without adequate B-12, people develop anemia and irreversible nerve damage, including tingling in hands and feet, confusion and memory problems.

NEW FINDINGS
Now scientists tell us that adequate B-12 intake can be a concern for another, much larger group of people. Vitamin B-12 occurs in food bound to protein, and must be separated from it in order to be absorbed. Research has shown that 10 to 30 percent of people aged 51 years and older may not produce enough of the stomach acid or enzyme needed to separate B-12 from protein, preventing it from being absorbed by the body. The most recent edition of the RDAs specifically recommends that people over age 50 get all or most of the recommended 2.4 micrograms (mcg) of B-12 in the form of a supplement or fortified food. These synthetic sources of B-12 are not bound to protein, and thus absorption is not a problem.

Foods fortified with B-12 include a few cereals (check labels), fortified soymilk, nutritional yeast, and certain meal replacement foods and drinks. Vitamin B-12 is available alone in supplements or as part of a multiple vitamin/mineral product. The amount of the vitamin provided by supplements and fortified foods is expressed on labels as a percentage of the Daily Value. Daily Values have not yet been updated to reflect the new RDA, and are based on 6 mcg/day. So a serving of a food that contains 50% of the Daily Value would provide 3 mcg, which is more than enough to meet current recommendations.
Some people who have had certain types of stomach or intestinal surgery or certain intestinal diseases cannot absorb any form of B-12. Normally, once B-12 has been separated from protein, it combines with a substance called "intrinsic factor" that is secreted by the stomach, and is then absorbed. People lacking this factor cannot absorb B-12 even from supplements, so periodic injections of vitamin B-12 are needed.

B-12 SUPPLEMENTS
Experts say that a balanced, mostly plant-based diet like that recommended by the American Institute for Cancer Research can meet virtually all our nutritional needs. In fact, centering our eating around vegetables, fruits and grains is the best way to make sure we’re getting the broad range of nutrients and natural phytochemicals that help promote health and lower our risk of developing cancer.
We have learned, however, that as people age vitamin B-12 supplements may be helpful for some. Body stores of vitamin B-12 can last for years, so short-term dietary changes or illnesses are not a problem, and not everyone is affected by a decreased ability to absorb B-12. A reasonable precaution, however, is for those over age 50 to add a fortified food or supplement providing vitamin B-12 to a balanced, plant-based diet.


Karen Collins is a registered dietitian with the American Institute for Cancer Research in Washington, D.C.


11. Ulcer Bacteria Linked to Iron Deficiency Anemia    Top

NEW YORK (Reuters Health) -- Successful treatment of Helicobacter pylori infection -- the bacteria linked to irritation of the stomach lining and stomach ulcers -- may also resolve iron deficiency anemia, according to results of an Italian study published in the November 2nd issue of the Annals of Internal Medicine.

Lead author Dr. Bruno Annibale, a gastroenterologist at Rome's Policlinico Umberto I, Universita La Sapienza, discussed the study with Reuters Health. He explained that, in general, nearly one third of patients "undergoing gastrointestinal investigation for iron deficiency anemia (IDA) remain without a diagnosis," though there has been some association suggested between the presence of H. pylori and iron deficiency anemia, based on epidemiological evidence. Furthermore, several case reports have found that cure of H. pylori infection appears to be accompanied by resolution of IDA. Iron deficiency anemia is characterized by various findings including pallor, gastrointestinal complaints, and abnormal blood test results.

In the current study involving 30 patients, "H. pylori-related gastritis (was) the only pathological finding in a sizeable (number) of patients," Annibale told Reuters Health. No signs of ulcers were found. And, the patients had not responded well to oral iron supplementation, a therapy that would have been expected to improve the anemia.

According to Annibale, the researchers found that "cure of (H. pylori) infection, by a 2-week (eradication) therapy, (led) to long-lasting recovery of anemia with no further need of oral iron (supplementation)." At one year post-treatment, nearly 92% of patients were free of anemia. Interestingly, "most of our patients were premenopausal women in whom IDA (had been) considered by (their) physicians solely due to menstrual blood (losses)," he added.

Given the results achieved in this study, Annibale believes that "H. pylori infection must be considered as a possible cause of IDA... when... other causes have been excluded by... hematological, gynecological, and gastrointestinal... evaluation."

Annibale notes that additional research will be

Annibale notes that additional research will be required to explain why IDA seems to occur in relatively few patients with known H. pylori infection. "The mechanism by which H. pylori determines IDA should also be elucidated," he suggests, "particularly different... strains (of H. pylori) and their effects on... levels of intragastric ascorbic acid."

Ascorbic acid, or vitamin C, is involved in the process of iron absorption and H. pylori is known to "(cause) a considerable decrease in the concentration of ascorbic acid in the gastric (fluids)," Annibale and colleagues write.

Source: Annals of Internal Medicine 1999;131:668-672.

12. Burning Issues In Barrett's Esophagus    Top

M. Brian Fennerty, MD

Introduction

Barrett's esophagus is a premalignant histologic condition of the esophagus that arises in the setting of chronic gastroesophageal reflux disease. Recent evidence indicates that the malignant tumor arising from Barrett's esophagus, esophageal adenocarcinoma, is the most rapidly rising incident tumor of all malignancies. Additionally, recent epidemiological evidence directly links esophageal adenocarcinoma to chronic reflux. Given that 20% of adult Americans have reflux and as many as 10% of individuals with reflux will have Barrett's, the pool of patients requiring surveillance endoscopy and biopsy for Barrett's may be 1%-2% of the adult population. Thus, the issue of Barrett's esophagus has important clinical and economic ramifications.

Barrett's esophagus was thought to be an irreversible premalignant lesion, but recent evidence suggests that this might not be the case. This symposium held at the American College of Gastroenterology 64th Annual Meeting in Phoenix, Ariz, Wednesday, October 20, 1999, was structured to cover the current state-of-the-art knowledge regarding endoscopic ablation/reversal techniques.

Is There a Rationale for Reversal Therapy in Patients With Barrett's Esophagus?

Prateek Sharma, MD, from the University of Kansas, covered the salient historical features of therapy for Barrett's esophagus.[1] Because Barrett's arises in the clinical setting of gastroesophageal reflux disease, it should not seem surprising that the effect of antireflux therapy on Barrett's esophagus has been extensively investigated. Early studies with continuous long-term therapy with H2-receptor antagonists did not demonstrate regression of Barrett's esophagus. Similar negative results have been demonstrated following antireflux surgery. In the multicenter VA Cooperative study, Kim and colleagues[2] demonstrated that there was no decrease in length of Barrett's over a 2-year period (5.7 cm at entry and 6.1 cm at conclusion). In this study, the surgery was performed by skilled antireflux surgeons -- therefore, if surgery alone was to affect the length of Barrett's, it should have been observed in this trial.

In 1989, proton pump inhibitors became clinically available, and given their superior antisecretory potency, these agents were also extensively evaluated for efficacy not only in controlling gastroesophageal reflux symptoms, but as a therapeutic strategy for reversing Barrett's as well. Unfortunately, no clinically relevant reversal has been noted with this class of agents. Sampliner and associates[3] studied the effect of 60 mg of

lansoprazole for 3 years in patients with Barrett's esophagus. At the conclusion of the study, the mean length of Barrett's had not significantly changed (5.3 cm versus 5.7 cm at entry). Thus, pharmacological or surgical control of gastroesophageal reflux does not result in the reversal of Barrett's esophagus.

However, in the course of observing patients treated with these agents, especially those treated with proton pump inhibitors, the appearance of squamous islands within the Barrett's segment was noted. As Barrett's was thought to arise as a result of an abnormal tissue response to injury in an abnormal acid-reflux environment, it was hypothesized that perhaps reversal of this lesion would require not only control of reflux but also a reinjury of the mucosa to effect a reversal of the epithelium. Thus, the stage was set to apply endoscopic methods to test this hypothesis.

Superficial Injury of Barrett's Epithelium: Is it Effective in Reversing Barrett's?

Richard Sampliner, MD, from the University of Arizona, reviewed current data regarding superficial methods of injuring the metaplastic Barrett's epithelium in an attempt to restore the native squamous epithelium.[4] A number of endoscopic thermal methods that only superficially penetrate the epithelium are available and have been evaluated, including multipolar electrocoagulation (MPEC), heater probe (HP), and argon plasma coagulation (APC). The advantage of these modalities is that they are readily available to most gastroenterologists and most gastroenterologists are skilled in the use of one or more of these techniques. Therefore, if successful, this process could be applied without referral to specialty centers, etc. Furthermore, because of their limited depth of injury, morbidity with these techniques should also be minimal.

The first approach studied was MPEC. In a pilot study, Sampliner and associates demonstrated that endoscopic and histologic reversal of Barrett's could be achieved with this device following normalization of intraesophageal acid exposure with omeprazole.[5] What was interesting in this study was that the mean dose of omeprazole needed to achieve esophageal normalization was 56 mg -- a dose much higher than normally used clinically. This finding not only underscored that these techniques were combination therapies (acid control and device "reinjury"), but that prior studies of acid control alone may have undertreated these patients.

Sampliner also presented the preliminary results of the multicenter prospective trial of MPEC therapy involving the University of Arizona, Oregon Health Sciences University, and UCLA.[6] In this study of 54 patients with Barrett's, complete endoscopic reversal was seen in 96% and histologic reversal in 94% of those treated with MPEC, following control of acid secretion with omeprazole 40 mg bid. Only two strictures were noted and both of these patients had had strictures prior to the therapy. Thus, this form of therapy appears potentially effective and associated with little morbidity. These patients are now being prospectively followed for durability of reversal and other clinical outcomes.

APC has also been extensively evaluated in this setting. APC uses argon gas to transmit electrical energy from a probe to the epithelial surface, producing heat. Similar to what has been observed with MPEC, most patients will demonstrate both endoscopic and histologic reversal. While touted as a safe thermal method, 2 patients in an early series[7] were perforated by the procedure and 1 of these patients died. Therefore, the safety of APC in this setting requires further scrutiny.

Heater probe has been less extensively studied as a thermal endoscopic method than has MPEC or APC, but appears to be similarly effective and relatively nonmorbid. Because of the limited depth of injury, these thermal techniques have been mainly applied to patients with nondysplastic Barrett's. Whether they would be similarly effective in dysplastic Barrett's is largely unknown.

What About Deeper Injury Methods to Ablate/Reverse Barrett's?

Ken Wang, MD, of the Mayo Clinic in Rochester, Minn, reviewed data regarding thermal injury with laser and nonthermal injury with photodynamic therapy (PDT).[8] Patients with dysplasia and/or early cancer may require deeper injury to ablate the neoplastic tissue and elicit an epithelial response, restoring the native squamous epithelium. Both laser and PDT have been studied in this regard. Laser in the form of argon, KTP (potassium-titanyl-phosphate), and Nd:YAG all appear effective in limited series of patients and short-term follow-up. However, there is experience in over 100 patients with neoplastic Barrett's using PDT. Overholt and colleagues[9] have published their experience in a single center using porfimer sodium as the photosensitizing agent and laser light from a centering balloon to activate the chemical and produce injury to the abnormal epithelium. In this series, the majority of patients had reversal of their dysplasia and/or cancer.

Although follow-up is limited, this approach appears promising at this time.

However, the deeper injury obtained with these devices also is associated with increased morbidity. One third of patients develop esophageal strictures, phototoxicity is common and requires avoidance of direct sunlight for 30 days, and chest pain requiring analgesics is frequent. Moreover, the cost of this procedure is high. The ongoing prospective, randomized trial of PDT in patients with Barrett's and high-grade dysplasia will determine its place in the treatment of these patients, but unfortunately, these results will not be available for another year.

Should We Do This at All?

M. Brian Fennerty, MD, of the Oregon Health Sciences University, discussed the case against ablation therapy of Barrett's at this time.[10] The two potential beneficial outcomes of reversing Barrett's are: 1) prevention of cancer in the 10% of Barrett's patients who will eventually develop cancer; and 2) elimination of the need for life-long surveillance exams in the 90% who will not ever develop cancer and have benign disease. Additional benefit to these patients is an improved quality of life as they are reassured and no longer "phobic" about their risk of developing cancer. Given the lack of a reliable marker to exclude cancer risk, a reversal technique may have great clinical and/or economic benefit.

Why not apply these techniques then? Or put another way, what don't we know?

Concerning ablative technologies, we don't know the following: the most effective technique, the least morbid technique, and the most cost-effective technique. From a clinical outcomes perspective we don't know: the effect of these endoscopic techniques on functional status or quality of life, morbidity or mortality, and the direct and indirect costs of these approaches. Most important, we do not yet know whether we have eliminated all of the Barrett's and thus eliminated the risk of developing cancer. There are now numerous reports of underlying Barrett's epithelium below the neo-squamous new mucosa. What if we don't lower the risk of cancer with these techniques but instead hamper our ability to survey this epithelium for dysplasia in the future? Then not only have we not done any good, but we have done potential harm as well.[11]

Therefore, while there has been a paradigm shift in our understanding of Barrett's in that it is at least partially reversible, we are still unable to determine whether these techniques are clinically appropriate. Until such data are available, these approaches must remain within the research arena pending proof of their efficacy. The rare exception will be in the patient with high-grade dysplasia who either is not a surgical candidate or who refuses surgery. In these patients we have the potential to improve outcomes with little risk and so ablation therapy may be justified, especially using PDT.

Other Related Abstracts

The long-term outcomes of patients with Barrett's treated with endoscopic ablation techniques were investigated by Landan and colleagues[12] from the Phoenix VA Medical Center. Nine patients with prior ablation using APC were prospectively followed. In 6 of these 9 patients, intestinal metaplasia was demonstrated on a subsequent biopsy. In 1 patient, it was not noted until an exam performed 415 days following apparent reversal. Data such as these, which have also been demonstrated in patients treated with PDT and MPEC, suggest that Barrett's may either return or is not entirely eliminated. If so, these patients may remain at risk for developing adenocarcinoma. Moreover, our ability to monitor these patients for dysplasia is hindered and we may have worsened the situation. These data serve to emphasize the investigational nature of these techniques.

Concluding Commentary

We may be on the brink of a dramatic therapeutic advancement in patients with Barrett's esophagus. However, the lack of demonstrated benefit of endoscopic reversal/ablative techniques dictates that we temper our enthusiasm until definitive data are available. Improvement in outcomes and assurance of no residual Barrett's will be necessary before we incorporate these techniques into clinical practice.

References

  1. Sharma P. The rationale for ablation therapy. Program and abstracts of the American College of Gastroenterology 64th Annual Scientific Meeting; October 16-20, 1999; Phoenix, Ariz.
  2. Kim Sl, Waring JP, Sampliner RE, et al. Effects of antireflux therapy on the extent of Barrett's epithelium. Gastroenterol 1993;104:A118.
  3. Sampliner RE. Effect of up to 3 years of high-dose lansoprazole on Barrett's esophagus. Am J Gastroenterol 1994;89:1844.
  4. Sampliner RE. Superficial injury (MPEC, APC). Program and abstracts of the American College of Gastroenterology 64th Annual Scientific Meeting; October 16-20, 1999; Phoenix, Ariz.
  5. Sampliner RE, Camargo E, Faigel D, et al. Efficacy and safety of reversal of Barrett's esophagus with high-dose omeprazole and electrocoagulation. Gastroenterology 1999;116:A298.
  6. Sampliner RE, Fennerty MB, Garewal HS. Reversal of Barrett's esophagus with acid suppression and multipolar electrocoagulation: preliminary results. Gastrointest Endosc 1996;44:532.
  7. Byrne JP, Armstrong GR, Attwood SEA. Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation. Am J Gastroenterol 1998;93;1810.
  8. Wang K. Deep injury (PDT, Laser). Program and abstracts of the American College of Gastroenterology 64th Annual Scientific Meeting; October 16-20, 1999; Phoenix, Ariz.
  9. Overholt E, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett's esophagus: Follow-up in 100 patients. Gastrointest Endosc 1999;49:1.
  10. Fennerty MB. The case against ablation therapy. Program and abstracts of the American College of Gastroenterology 64th Annual Scientific Meeting; October 16-20, 1999; Phoenix, Ariz.
  11. Fennerty MB. Perspectives on endoscopic eradication of Barrett's esophagus: Who are appropriate candidates and what is the best method? Gastrointest Endosc 1999;49:S24.
  12. Landan D, Ramirez FC. Long-term follow-up of patients with Barrett's Esophagus treated with Argon plasma coagulation (APC). Am J Gastroenterol 1999;94:2590. Program and abstracts of the American College of Gastroenterology 64th Annual Scientific Meeting; October 16-20, 1999; Phoenix, Ariz. Abstract 26.

13. Painkillers May Add to Heartburn    Top

By LAURAN NEERGAARD  AP Medical Writer  NEW ORLEANS

Doctors have long known that popular painkillers like aspirin and ibuprofen can sometimes cause serious stomach ulcers. Now new research suggests the drugs may play a role in chronic heartburn, too. Heartburn, that burning pain in the center of the chest, is one of the nation's most common medical complaints, afflicting millions of Americans at least occasionally. The culprit is gastric acid that bubbles up from the stomach to the delicate esophagus because of a faulty stomach valve. Doctors call it gastroesophageal reflux disease, or GERD. Obesity, smoking and alcohol use are known risk facomach drugs can ease the problem for many people. The new research looked at whether yet another risk factor might be using certain painkillers _ aspirin, ibuprofen and other drugs called nonsteroidal anti-inflammatories, or NSAIDs. University of Georgia scientists compared 12,500 Georgia Medicaid patients whose medical records showed they regularly took prescription-strength NSAIDS with similar Medicaid patients never prescribed painkillers. Although reflux was fairly rare among these Medicaid patients, NSAID users were up to 200 percent more likely to have been diagnosed with it, said lead researcher Jeffrey Kotzan, who presented the study Wednesday at a meeting of the American Association of Pharmaceutical Scientists. The study does not prove painkillers cause heartburn, stressed Kotzan. ``It could very well be that people who have GERD hurt all the time, so they take NSAIDs,'' he said. Other smaller studies have found a link between NSAIDs and heartburn, but none has suggested such a high risk, cautioned Dr. Patrick Waring of Emory University. Waring's own research suggests NSAIDs are linked only to severe heartburn that causes complications that narrowthe esophagus, instead of the more common, milder heartburn. ``It could be that people taking NSAIDs are not more likely to have reflux than the average person, but they are more likely to have a complication,'' he explained. Waring's theory: If someone takes painkillers in a way that lets the drug sit on tender, already irritated tissue _ such as right before lying in bed _ the drug can mix with reflux acid to worsen inflammation. While the new research looked only at prescription-strength NSAIDs, Waring said his own study found the strongest link was daily aspirin use, perhaps because people took the pill shortly before bed. The research is not the first to warn about problems with NSAIDs. These drugs, both prescription and over-the-counter versions, are taken safely by tens of millions of people every year. But they can cause dangerous stomach ulcers and stomach bleeding in some people, particularly long-term users. Indeed, NSAIDs are blamed for hospitalizing 107,000 Americans every year, and killing 16,500. While scientists try to figure out if heartburn really is a concern, what should consumers think? ``It's one more message that these medicines have the potential to injure the intestinal tract,'' said Waring. ``If you take NSAIDs and have reflux, stop taking them, decrease the dose or go talk to a doctor and see if other options are available.''

14. Regular NSAID Use May Raise Reflux Risks    Top

11-19-99

BOSTON (Reuters Health) -- Regular users of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or aspirin are twice as likely as non-users to experience gastroesophageal reflux -- backflow of some of the contents of the stomach into the esophagus, researchers report.

Gastroesophageal reflux -- more commonly called acid reflux -- causes the burning pain in the chest known as heartburn. Especially among women and non-blacks, reflux is strongly associated with NSAID use, according to Dr. Jeffrey Kotzan and colleagues at the University of Georgia, Athens. They presented their findings at the annual meeting of the American College of Rheumatology, held here this week.

The researchers examined the incidence of reflux in just over 12,500 Medicaid recipients who took NSAIDs regularly to treat arthritis, as well as in a similar group of 12,500 individuals who did not use NSAIDs. Reflux symptoms "were twice as prevalent in the NSAID users," Kotzan told Reuters Health in an interview during the meeting. "A two-fold difference is a very large difference" with this disease, he explained.

Women were 57% more likely to develop reflux than men, and non-blacks were 32% more likely to develop symptoms than blacks. The association between NSAID use and reflux was evident only among people who used NSAIDs for at least 6 months continuously, the authors report.

Speaking with Reuters Health, Kotzan speculated that NSAIDs might relax the lower sphincter of the esophagus, permitting the reflux of stomach contents back up into the esophagus.   

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