Long-term Outcome of Medical and Surgical Therapies for
Gastroesophageal Reflux Disease
Follow-up of a Randomized Controlled
Trial
Stuart Jon Spechler, MD; Edward Lee, MD; Dennis Ahnen, MD; Raj K.
Goyal, MD; Ikuo Hirano, MD; Francisco Ramirez, MD; Jean-Pierre Raufman, MD;
Richard Sampliner, MD; Thomas Schnell, MD; Stephen Sontag, MD; Z. Reno
Vlahcevic, MD; Renee Young, MD; William Williford, PhD
Context Severe gastroesophageal reflux disease (GERD) is a lifelong
problem that can be complicated by peptic esophageal stricture and
adenocarcinoma of the esophagus.
Objective To determine the long-term outcome of medical and surgical
therapies for GERD.
Design and Setting Follow-up study conducted from October 1997 through October 1999
of a prospective randomized trial of medical and surgical antireflux treatments
in patients with complicated GERD. Mean (median) duration of follow-up was 10.6
years (7.3 years) for medical patients and 9.1 years (6.3 years) for surgical
patients.
Participants Two hundred thirty-nine (97%) of the original 247 study patients
were found (79 were confirmed dead). Among the 160 survivors (157 men and 3
women; mean [SD] age, 67 [12] years), 129 (91 in the medical treatment group
and 38 in the surgical treatment group) participated in the follow-up.
Main Outcome
Measures Use of antireflux
medication, Gastroesophageal Reflux Disease Activity Index (GRACI) scores,
grade of esophagitis, frequency of treatment of esophageal stricture, frequency
of subsequent antireflux operations, 36-item Short Form health survey (SF-36)
scores, satisfaction with antireflux therapy, survival, and incidence of
esophageal adenocarcinoma, compared between the medical antireflux therapy
group and the fundoplication surgery group. Information on cause of death was
obtained from autopsy results, hospital records, and death certificates.
Results Eighty-three (92%) of 90 medical patients and 23 (62%) of 37
surgical patients reported that they used antireflux medications regularly (P<.001). During a 1-week period after
discontinuation of medication, mean (SD) GRACI symptom scores were
significantly lower in the surgical treatment group (82.6 [17.5] vs 96.7 [21.4]
in the medical treatment group; P
= .003). However, no significant differences between the groups were found in
grade of esophagitis, frequency of treatment of esophageal stricture and
subsequent antireflux operations, SF-36 standardized physical and mental
component scale scores, and overall satisfaction with antireflux therapy.
Survival during a period of 140 months was decreased significantly in the
surgical vs the medical treatment group (relative risk of death in the medical
group, 1.57; 95% confidence interval, 1.01-2.46; P = .047), largely because of excess deaths from heart
disease. Patients with Barrett esophagus at baseline developed esophageal
adenocarcinomas at an annual rate of 0.4%, whereas these cancers developed in
patients without Barrett esophagus at an annual rate of only 0.07%. There was
no significant difference between groups in incidence of esophageal cancer.
Conclusion This study suggests that antireflux surgery should not be advised
with the expectation that patients with GERD will no longer need to take
antisecretory medications or that the procedure will prevent esophageal cancer
among those with GERD and Barrett esophagus.
JAMA. 2001;285:2331-2338
Gastroesophageal reflux disease (GERD) is one of
the most common chronic disorders of the gastrointestinal tract.1, 2 Surveys have shown
that approximately 20% of US adults experience GERD symptoms such as heartburn
and acid regurgitation at least once per week.3, 4 GERD and its sequela,
Barrett esophagus, are strong risk factors for esophageal adenocarcinoma,5, 6 a malignancy that has
nearly quadrupled in frequency during the past 2 decades.7 Medical treatment of
GERD involves long-term administration of antacids and antisecretory agents,8 and patients in the
United States may spend as much as an estimated $5 billion annually on
antireflux medicines.9 Antireflux surgery
(fundoplication) has become an increasingly popular form of therapy for GERD
since minimally invasive (laparoscopic) surgical approaches have been
developed.10, 11 It has been estimated
that 29 000 and 34 800 laparoscopic Nissen fundoplications were
performed in the United States in 1998 and 1999, respectively (Synergy, a
division of Quintiles Informatics, Waltham, Mass, unpublished data, March
2000).
Modern medical and surgical antireflux therapies
are highly effective in controlling GERD symptoms,8 but few published data
support the efficacy of any treatment in preventing GERD complications such as
adenocarcinoma.12 Some reports
have suggested that fundoplication (which creates a barrier to reflux of all
gastric contents) might be more effective than medical therapy (which is
directed primarily at decreasing gastric acid secretion) for preventing both
peptic and neoplastic complications of GERD.13-16 Two small
studies(that had methodological limitations) involving patients with Barrett
esophagus who received medical and surgical therapies for GERD have provided
weak support for this contention by reporting fewer cases of dysplasia and
cancer among surgically treated patients.17, 18 Some have proposed
that medical treatment of GERD with antisecretory agents might predispose to
cancer, perhaps by promoting reflux of deconjugated bile acids,19, 20 and that increasing
use of these drugs may be contributing to the increasing frequency of
esophageal adenocarcinoma.21 However, the limited
studies that have addressed this issue directly have found no significant
association between esophageal adenocarcinoma and use of antisecretory agents
per se.22, 23
Although severe GERD is judged to be a lifelong problem,
few data are available on the long-term outcome of any antireflux therapy. One
study of patients with severe GERD treated with omeprazole for a mean of 6.5
years found that relapses occurred frequently and that patients often required
increasing dosages of omeprazole (up to 120 mg/d).24 Such observations
have raised questions regarding the long-term utility and cost of medical
therapy for GERD. Successful antireflux surgery might obviate the inconvenience
and expense of lifelong medical treatment. Some investigators have reported
success rates that exceed 90% at 10 to 20 years after open fundoplication,25, 26 whereas others have
described return of reflux esophagitis in more than 50% of cases within 6
years.27 However,
without additional meaningful, consistent, long-term data, it is difficult to
make a rational choice between medical and surgical therapy.
In the late 1980s, the Department of Veterans
Affairs (VA) Cooperative Studies Program conducted a randomized trial of
medical and surgical antireflux treatments for 247 patients with complicated
GERD.28 For the 2-year
duration of the study, surgery (open Nissen fundoplication) was found to be
significantly better than medical therapy (antacids, histamine2
receptor blockers, metoclopramide, sucralfate) for controlling the symptoms and
signs of GERD. This study is one of the few randomized trials of medical and
surgical antireflux therapies ever reported.29, 30 To determine the
long-term outcome of GERD therapies, we conducted a follow-up study of this
well-defined cohort of patients.
METHODS
From July 1986 through October 1988, the VA
conducted a cooperative study of medical and surgical therapies for GERD.
Patients with complicated GERD (243 men and 4 women) were instructed to
implement antireflux lifestyle modifications, stratified into 1 of 5 risk
groups (Table 1),
and then randomly assigned by concealed allocation to 1 of 3 treatment groups:
(1) continuous medical therapy consisting of antacid (2 tablets 1 and 3 hours
after meals) and ranitidine (150 mg twice daily) regardless of symptoms, with
metoclopramide (10 mg 4 times daily) and sucralfate (1 g dissolved in 10 mL of
warm water, after meals) added when necessary for persistent symptoms; (2)
symptomatic medical therapy consisting of the medications described for the
previous group but given only when necessary to control symptoms; or (3)
surgical therapy consisting of open Nissen fundoplication. Treatments were
continued for the duration of the study (12 to 28 months). On completion of the
study, patients returned to their primary care physicians for nonstandardized
GERD management.
The present follow-up study was conducted from
October 1997 through October 1999. Prior to enrolling patients, all
investigators met as a group to standardize procedures and evaluation methods.
We determined the whereabouts of the original study patients using the VA
computer database and a professional search agency (Business Information
Systems, Smyrna, Ga). For patients who had died, we obtained information
regarding the cause of death from all available autopsy results, hospital
records, and death certificates. Surviving patients were contacted and invited
to participate in the follow-up study.
GERD Symptom Scoring
The Gastroesophageal Reflux Disease Activity Index (GRACI) score used in the
original study was used to assess the severity of GERD symptoms in the
follow-up study. GRACI was developed in a prospective investigation that used
multiple regression analysis techniques to correlate clinical data with an
experienced physician's assessment of GERD activity. These were the same
methods used to develop the Crohn Disease Activity Index. Details regarding
development, validation, and use of the GRACI score have been published
elsewhere.28, 31 Briefly, patients
maintain a standardized diary of GERD symptoms every day for 1 week, and the
GRACI score is calculated by assigning weighted numerical values to certain
symptoms (eg, the percentage of each day that the patient had heartburn,
general severity of heartburn for that day, episodes of odynophagia, episodes
of coughing or wheezing that awakened the patient from sleep). The GRACI score
can range from 74 (no symptoms) to 172 (worst symptoms); published mean scores
for patients with mild, moderate, and severe symptoms are 93, 110, and 125,
respectively.31
Patients in this study had GRACI scores
determined during 2 consecutive weeks. For the first week, patients were
instructed to continue, without modification, whatever antireflux regimen they
had been using on a regular basis. No new antireflux therapies were started,
and patients were instructed not to alter their routine lifestyle practices.
For the second week, patients were instructed to discontinue all antireflux
medications. No new antireflux therapies were started, and patients were
instructed not to alter their routine lifestyle practices. Antacids were
allowed for relief of intolerable heartburn.
Endoscopic Examination
Patients were asked to discontinue all antireflux medications for 1 week prior
to the procedure. Endoscopic severity of esophagitis was graded using the scale
used in the original study (grade 1, no evidence of inflammation; grade 2,
erythema, friability, or both; grade 3, esophageal erosions; and grade 4,
esophageal ulcers). For patients with a columnar-lined esophagus, esophageal biopsy
specimens were obtained at 1-cm intervals from the squamocolumnar junction
(Z-line) to the gastroesophageal junction (the most proximal level of the
gastric folds). Biopsy specimens were evaluated by the study pathologist (E.L.)
for epithelial type and presence of neoplasia.
24-Hour Esophageal pH
Monitoring
All antireflux medications were discontinued for 72 hours before the monitoring
period. The studies were performed according to standard procedures for the
monitoring systems used at each of the 8 participating centers.
Completion of Follow-up
Questionnaire and SF-36
Patients were questioned regarding the frequency with which they had used
medications specifically for treatment of GERD since completion of the original
study. We also obtained data regarding any subsequent antireflux operations
performed, symptoms of gas-bloat syndrome, satisfaction with antireflux
therapies, treatments for esophageal stricture, and development of esophageal
cancer.
The 36-item Short Form general health and
well-being survey (SF-36) assesses 8 health issues: limitations in physical
activities due to health problems, limitations in usual role activities due to
physical health problems, bodily pain, general health perception, vitality,
limitations in social activities due to physical or emotional problems,
limitations in usual role activities due to emotional problems, and general
mental health.
Statistical Analysis
At the time of randomization into the original study, there were no significant
differences among the 3 treatment groups in demographic or functional status (Table 1).
The committee that planned the original study thought that it would be
unethical to include a placebo treatment for patients with complicated GERD
and, instead, included a control group of patients who would be treated
medically only as necessary for relief of symptoms (the symptomatic medical
treatment group). Those patients quickly became symptomatic when medical
therapy was stopped and, consequently, the 2 medical groups received the same
medications in similar dosages for the 2-year duration of the original study.
The 2 medical treatment groups did not differ significantly in any outcome
measured in that study, and all patients received nonstandardized GERD
management after the study ended in 1988. Since the continuous and symptomatic
medical treatment groups were virtually identical in baseline characteristics,
study treatments, study outcomes, and subsequent management, we have combined
these 2 groups into 1 medical treatment group to simplify analyses in the
present follow-up study.
Primary statistical analyses in both the
original and present studies were based on the intention-to-treat principle. All
tests of statistical significance are 2-sided. A log-rank statistic was used to
compare survival distributions between the medical and surgical treatment
groups. Kaplan-Meier analysis was used to construct life-table plots.
The study was approved by the Human Rights
Committee of the VA Cooperative Studies Program Coordinating Center (Perry
Point, Md) and the institutional review boards at each of the 8 participating
VA medical centers. Patients who agreed to participate provided written
informed consent.
RESULTS
We determined the whereabouts of 239 (97%) of
247 patients in the original study. Seventy-nine patients were confirmed to be
dead; the 160 remaining patients (157 men and 3 women) were contacted and
invited to participate in the follow-up study. The mean (SD) age of surviving
patients at the time of contact was 67 (12) years. Thirty-one of the 160
patients (21 [19%] of 112 medical patients and 10 [21%] of 48 surgical
patients) either refused or were unable to participate in the follow-up study;
129 patients (91 medical patients and 38 surgical patients) participated in at
least some of the follow-up procedures. Thus, specific follow-up data were
obtained for 208 (84%; 129 survivors and 79 deaths) of the original 247
patients. Mean and median durations of follow-up (from termination of the
original study to death or last contact) were 10.6 and 7.3 years, respectively,
for medical patients and 9.1 and 6.3 years, respectively, for surgical
patients.
Survival
There were no surgery-related deaths in the original study. The 79 deaths that
occurred during follow-up involved 33 (40%) of the 82 patients randomized to
the surgical group and 46 (28%) of the 165 patients randomized to receive
medical treatment. In an intention-to-treat analysis, the Cox proportional
hazards model showed that survival during a period of 140 months was decreased
significantly in the surgical group compared with the medical group (relative
risk of death in the medical group [RR], 1.57; 95% confidence interval [CI],
1.01-2.46; P = .047) (Figure 1).
In the original study, 24 of the 82 patients randomized to surgery and 16 of
the 165 patients randomized to medical therapy refused to accept the treatments
to which they were assigned. When the survival analysis was limited to the 207
patients who actually received their assigned treatments, the observed
difference between the groups was greater (RR, 1.89; 95% CI, 1.14-3.13; P = .01) (Figure 1).
Causes of Death
Causes of death in the treatment groups are shown in Table 2.
Heart disease was the cause of 20% and 48% of deaths in the medical and
surgical groups, respectively (P
= .004). Although deaths due to all types of heart disease were significantly
more common in the surgical group, the groups did not differ significantly in
frequency of any individual cardiac cause of death. Also, there were no significant
differences between groups in the frequency of deaths due to any other major
category of disease, including cancer of all types and esophageal cancer. There
were only 2 deaths from esophageal cancer in the entire study group.
Cigarette smoking is a major factor that could
influence mortality from heart disease. The observed excess mortality from
heart disease was not anticipated and, consequently, data on cigarette smoking
were not collected in the follow-up study. During the original study, however,
there were no significant differences between the groups in the frequency of
cigarette smoking (34% of the medical patients and 39% of the surgical patients
were smokers; P = .45).
Esophageal Cancer
Five patients (all white men; 4 medical patients and 1 surgical patient)
developed esophageal adenocarcinoma after a mean follow-up of 7.1 years (range,
4-12 years). There was no significant difference in the rate of esophageal
cancer development between the medical and surgical groups (P = 1.0 by Fisher exact test). However, we
calculated that a study designed to demonstrate a 50% relative reduction in
risk of esophageal cancer during this period would have required a sample size
of 460 patients in each treatment group (assuming a baseline cancer incidence of
0.5% per year; power = 80%; P =
.05). Therefore, our study did not have sufficient statistical power to detect
potentially important differences between groups in the rate of cancer
development.
Four patients were known to have developed
esophageal adenocarcinomas before the follow-up study was initiated, and 1
asymptomatic patient had cancer discovered when he underwent endoscopic
evaluation as part of the follow-up study. Four of the 5 patients who developed
cancer had Barrett esophagus with specialized intestinal metaplasia at
baseline. One patient who died of metastatic esophageal adenocarcinoma had no
evidence of Barrett esophagus either at baseline endoscopy or during 2
subsequent endoscopies performed at weeks 6 and 52 of the original study.
Thirteen months before death, this patient's tumor was resected. We obtained
the pathologic specimens from the resection and reviewed the gross photographs
and histologic slides. The tumor was 8 cm in length and crossed the
gastroesophageal junction, but the bulk of the adenocarcinoma (>75%) was
located in the distal esophagus. Review of multiple sections revealed no
specialized intestinal metaplasia in the esophagus, but the large neoplasm
conceivably may have obliterated any such metaplasia. Our assessment was that
the adenocarcinoma most likely originated in the distal esophagus, but the
possibility that the neoplasm arose from the proximal stomach could not be
excluded, as is the case for virtually any adenocarcinoma that crosses the
gastroesophageal junction.32
In the original study, 108 patients had Barrett
esophagus with specialized intestinal metaplasia at entry. These 108 patients
were followed up for a total of 1037 patient-years, and 4 developed
adenocarcinoma of the esophagus, for an incidence rate of 1 esophageal cancer
per 259 patient-years of follow-up (0.4% per year). The 139 patients who had
severe GERD without apparent Barrett esophagus were followed up for a total of
1357 patient-years, and 1 developed adenocarcinoma, for an incidence rate of 1
esophageal cancer per 1357 patient-years of follow-up (0.07% per year).
Long-term Outcomes of GERD
Table 3
summarizes the results of some long-term outcome measures of GERD. GRACI
symptom scores were significantly lower in the surgical treatment group during
the week when antireflux medications were discontinued. For comparison, mean
(SD) GRACI scores were 89 (2) for the medical treatment group and 78 (2) for
the surgical treatment group at the time of completion of the original study
(after 104 weeks of therapy). After 1 week without antireflux medications,
there was no significant difference in the endoscopic grade of esophagitis
between the medical and surgical treatment groups.
The mean (SD) duration of acid reflux was
greater in the medical treatment group (while not receiving therapy) than in
the surgical treatment group (31.0% [61.6%] vs 17.1% [41.1%] of the 24-hour
monitoring period), but the difference was not statistically significant. These
results are based on a relatively small sample size (because most patients
refused 24-hour esophageal pH monitoring), and the SDs are large. Consequently,
our data on 24-hour esophageal pH monitoring are inconclusive.
Overall, 92% of patients in the medical
treatment group and 62% of those in the surgical treatment group reported that
they had used antireflux medications regularly since completion of the original
study (P<.001). Nine medical
patients (10%) and 6 surgical patients (16%) had had 1 or more antireflux
operations since the end of the original study (P = .38). Esophageal strictures requiring treatment were
reported by 8% and 14% of patients in the medical and surgical treatment
groups, respectively (P = .46).
The majority of patients in both groups were
either very satisfied (67% of medical and 58% of surgical patients; P = .42) or satisfied (29% of medical and
31% of surgical patients; P =
.83) with the antireflux treatments they had received since completion of the
original study. When patients in the surgical group were asked to rate their
satisfaction specifically with the results of the original operation, 72% said
they were very satisfied, 14% were satisfied, 10% were dissatisfied, and 3%
were very dissatisfied. When these same patients were asked if they would still
have the operation if they could do it over again, 89% answered yes.
Patients in both treatment groups were questioned
regarding symptoms that have been attributed to postfundoplication gas-bloat
syndrome. There were no significant differences between groups in the frequency
of any of these symptoms, including increased abdominal girth (36% of medical
and 34% of surgical patients), abdominal fullness (41% of medical and 42% of
surgical patients), inability to belch (20% of medical and 29% of surgical
patients), and inability to vomit (20% of medical and 32% of surgical
patients).
SF-36 General Health and
Well-being
There were no significant differences between groups for any profile on the
SF-36 except bodily pain, which was significantly better in surgical patients
(mean [SD] score, 51.7 [25.2] for medical patients vs 64.0 [28.9] for surgical
patients [P = .02]; a higher
score in this profile represents less bodily pain). No significant differences
between groups were noted for the overall physical and mental component scores.
COMMENT
This study is unique in providing data on the
long-term outcome of a well-defined cohort of patients who participated in a
randomized trial of medical and surgical treatments for GERD. Compared with the
medical treatment group, surgical patients exhibited a significant decrease in
survival during the 10- to 13-year follow-up. Surgery was not the direct cause
of death, and the excess late mortality resulted largely from a significant
increase in deaths due to heart disease. The shortened life expectancy in
surgical patients was an unexpected finding, and the study was not designed to
investigate mechanisms underlying a difference in mortality rates.
Consequently, the explanation for the observed excess mortality due to heart
disease after fundoplication is not clear. While this issue requires further
investigation, it seems prudent to advise patients who are to undergo or who
have had antireflux surgery to make extra efforts to control their risk factors
for cardiovascular disease.
GERD and Barrett esophagus are both risk factors
for esophageal adenocarcinoma.5, 6 In this study,
patients with Barrett esophagus developed adenocarcinoma at the rate of 1
esophageal cancer per 259 patient-years (0.4% per year). The reported annual
incidence of cancer with Barrett esophagus has ranged from 0.2% to 1.9%, 33-36 and, by pooling
data from these studies, 1 widely quoted report has estimated the cancer risk
in patients with this condition at 1% per year.33 However, a recent
report has suggested that the cancer risk associated with Barrett esophagus has
been overestimated because of publication bias.37 The authors of that
report have estimated the annual risk of cancer in patients with Barrett
esophagus at approximately 0.5%, a rate close to the 0.4% annual incidence
observed in our study and in 2 recent, prospective US studies of Barrett
esophagus.33, 38 Acceptance of this
low rate of cancer incidence could have a profound influence on recommendations
regarding endoscopic surveillance for patients with Barrett esophagus. Current
recommendations, based on an assumed annual cancer incidence of approximately
1%, call for endoscopic surveillance at intervals of every 2 to 3 years.39 A recent study using
a computer model to explore the value of different surveillance strategies
found that if the risk of cancer in patients with Barrett esophagus is 0.4%
annually, endoscopy every 5 years would be the only reasonable surveillance
strategy.40
The Practice Parameters Committee of the
American College of Gastroenterology has recommended endoscopic screening for
Barrett esophagus of older patients who have chronic GERD symptoms.41 The purpose of such
screening is to reduce mortality from esophageal cancer. However, 1 of the 5
patients in our study who developed esophageal adenocarcinoma had no evidence
of Barrett esophagus on 3 earlier endoscopic examinations performed by study
endoscopists who were specifically seeking evidence of the disorder. It is not
clear whether short-segment Barrett esophagus was missed on those examinations
or whether the patient indeed developed esophageal adenocarcinoma without
Barrett esophagus. Nevertheless, if a substantial proportion of patients who
develop esophageal adenocarcinoma do so without having endoscopically apparent
Barrett esophagus, endoscopic screening programs designed to look for Barrett
esophagus will have limited impact in decreasing mortality from esophageal
cancer.
In our study, the cancer incidence among
patients who had severe GERD without Barrett esophagus was only 0.07% per year.
Furthermore, except for 2 deaths from esophageal cancer, none of the deaths in
the entire study population appeared to be a direct consequence of GERD. Thus,
we found GERD to be an uncommon cause of mortality, even in our elderly population
of patients with severe reflux esophagitis. We found no significant differences
between treatment groups in incidence of esophageal adenocarcinoma but, with
such a low incidence of this neoplasm, our study did not have sufficient
statistical power to detect such differences. Even if antireflux surgery could
prevent esophageal adenocarcinoma for patients with GERD, however, its use
solely for this purpose cannot be sanctioned because the surgical mortality
rate (at least 0.2%)10 exceeds the annual
incidence of cancer (0.07%).
We found that GERD symptoms were significantly
less severe in the surgical treatment group when drug therapy was discontinued
but not when patients were permitted to take antireflux medications in their
usual fashion. There was no significant difference in the mean endoscopic grade
of esophagitis between groups, and the mean grade was in the mild category for
both medical and surgical patients. However, patients had discontinued
medications for only 1 week before endoscopy, and this may have been an
insufficient amount of time for visible esophagitis to occur. The majority
(92%) of patients in the medical treatment group continued to take antireflux
medications regularly during the follow-up period, and regular use of these
medications was significantly less common in the surgical treatment group.
Nevertheless, 62% of surgical patients were taking antireflux medications on a
regular basis. This suggests that antireflux surgery should not be advised with
the expectation that patients will no longer take antisecretory medications.
During the follow-up period, a substantial
number of patients in both groups had 1 or more antireflux operations (10% of
medical patients and 16% of surgical patients; P
= .38) and had treatment for esophageal stricture (8% of medical patients and
14% of surgical patients; P =
.46). No significant differences between the groups were noted for overall
physical and mental well-being as assessed by SF-36 scores. Most patients in
both groups were satisfied or very satisfied with their antireflux therapy (96%
of medical patients and 89% of surgical patients; P = .24).
The original VA Cooperative Study predated the
widespread availability of proton pump inhibitors (released for general use in
the United States in 1989) and laparoscopic fundoplication (introduced in
1991). Nevertheless, the results of this follow-up study are relevant for a
number of reasons. First, proton pump inhibitors were available to all patients
and used by most during the follow-up period, albeit in a nonstandardized
fashion. Next, open fundoplication remains the surgical standard by which
laparoscopic fundoplication is judged. Although the operative approaches
differ, the technique of laparoscopic Nissen fundoplication is virtually
identical to that of the open procedure.42 The laparoscopic
approach has become popular not because it produces a better functional result
than the open procedure but because of proposed advantages in the degree of
postoperative discomfort, duration of hospital stay, and cosmetic outcome.43 Two recent randomized
trials of laparoscopic and open Nissen fundoplication found no significant
differences in the functional results of the 2 procedures (ie, relief of GERD
symptoms, reduction in esophageal acid exposure).44, 45 However, 1 of those
studies was terminated prematurely because an interim analysis showed an excess
of adverse outcomes (primarily postoperative dysphagia) in the laparoscopically
treated group.45 Furthermore,
at least 1 study has shown that the primary factor involved in overall patient
satisfaction with antireflux surgery is relief of GERD symptoms, not operative
approach.46 Therefore, our
study on the long-term outcome of open fundoplication remains highly relevant,
even in this era of laparoscopic surgery.
In summary, during a follow-up period of 10 to
13 years, we found that patients with complicated GERD who were treated with
antireflux surgery were significantly less likely to take antireflux
medications regularly, and, when those medicines were discontinued, their GERD
symptoms were significantly less severe than those of medically treated
patients. However, 62% of surgical patients took antireflux medications on a
regular basis, and there were no significant differences between the medical
and surgical treatment groups in rates of neoplastic and peptic complications
of GERD, overall physical and mental well-being scores, and satisfaction with
antireflux therapy. Patients with Barrett esophagus developed esophageal
adenocarcinoma at an annual rate of 0.4%, whereas the annual rate for patients
who had severe GERD without Barrett esophagus was only 0.07%. Furthermore,
esophageal cancer was an uncommon cause of death. Fundoplication unexpectedly
was associated with a significant decrease in long-term survival.
We conclude that antireflux surgery should not
be advised with the expectation that patients will no longer take antisecretory
medications or that it is clearly a cancer-preventing procedure for patients
with GERD and Barrett esophagus. The low rates of esophageal cancer development
and mortality due to GERD found in this prospective study call for a
reevaluation of current screening and surveillance guidelines for Barrett
esophagus. These findings also suggest that the first requisite for any
antireflux therapy must be safety.
Author/Article Information
Author Affiliations: Department of
Veterans Affairs Medical Center, Dallas, Tex (Drs Spechler and Lee); Department
of Veterans Affairs Medical Center, Denver, Colo (Dr Ahnen); Department of
Veterans Affairs Medical Center, West Roxbury, Mass (Drs Goyal and Hirano);
Department of Veterans Affairs Medical Center, Phoenix, Ariz (Dr Ramirez);
Department of Veterans Affairs Medical Center, Little Rock, Ark (Dr Raufman);
Department of Veterans Affairs Medical Center, Tucson, Ariz (Dr Sampliner);
Department of Veterans Affairs Medical Center, Hines, Ill (Drs Schnell and
Sontag); Department of Veterans Affairs Medical Center, Richmond, Va (Dr
Vlahcevic); Department of Veterans Affairs Medical Center, Omaha, Neb (Dr
Young); and Department of Veterans Affairs Medical Center, Perry Point, Md (Dr
Williford). Dr Vlahcevic is deceased.
Corresponding Author and Reprints:
Stuart Jon Spechler, MD, Division of Gastroenterology (111B1), Department of
Veterans Affairs Medical Center, 4500 S Lancaster Rd, Dallas, TX 75216 (e-mail:
[log in to unmask]).
Author Contributions: Study concept and design:
Spechler, Ahnen, Goyal, Hirano, Raufman, Vlahcevic.
Acquisition of data: Spechler, Ahnen, Hirano, Ramirez, Raufman, Sampliner, Schnell,
Sontag, Vlahcevic, Young, Williford.
Analysis and interpretation of
data: Spechler, Lee, Ahnen,
Goyal, Raufman, Williford.
Drafting of the manuscript: Spechler, Sontag, Williford.
Critical revision of the
manuscript for important intellectual content: Spechler, Lee, Ahnen, Goyal, Hirano, Ramirez, Raufman, Sampliner,
Schnell, Young.
Statistical expertise: Williford.
Obtained funding: Spechler, Ahnen, Goyal.
Administrative, technical, or
material support: Spechler, Goyal,
Hirano, Raufman, Schnell, Sontag, Young, Williford.
Study supervision: Spechler, Ahnen, Hirano, Raufman, Sampliner.
Funding/Support: This work was supported by grants from the Department of Veterans
Affairs Medical Research Service Cooperative Studies Program (CSP 277A), and
Ethicon Endo-Surgery, Cincinnati, Ohio.
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Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.