1021772
editorial2021
GUTXXX10.1177/26345161211021772ForegutGrimsley et al
Invited Article
Refractory Gastroesophageal Reflux
Disease: Surgical Perspective from a
Multi-Disciplinary Practice
Emily Grimsley1, Logan Meyer1, and Vic Velanovich1
From the medical perspective, “refractory” gastroesopha-
geal reflux disease (GERD) is symptomatic pathologic
acid reflux that is not responsive to medical management,
usually in the form of proton pump inhibitors (PPI). The
basis of this approach is not to eliminate volume reflux,
but to make reflux imperceptible by eliminating the stom-
ach’s ability to produce acid. Refractory, in this view,
means that elimination of gastric acid does not lead to
elimination of symptoms. GERD is protean in its mani-
festations and severity, both from the standpoint of symp-
toms, but also pathological manifestations, such as
esophagitis, Barrett’s esophagus, and eventual esopha-
geal adenocarcinoma. The constellation of GERD mani-
festations, both typical and atypical, can have varying
effects on the patient’s quality of life.1 Most quality of life
decline is generally driven by symptoms, however other
aspects can also contribute, such as the need to take medi-
cation indefinitely, medications’ possible untoward
effects, and concerns about neoplasia development. The
only way to truly “cure” both acid and volume reflux is
surgical. Therefore, from the surgical perspective, refrac-
tory GERD is diagnosed in the patient for whom reflux
has produced such a detriment in their quality of life that
they wish something more than medication.
The purpose of this article is to discuss who should be
considered for anti-reflux surgery (ARS), selection of
operation, and pitfalls in patient selection. Our opinion is
informed by our multidisciplinary approach to esopha-
geal and swallowing disorders at the Joy McCann
Culverhouse Center for Swallowing Disorders at the
University of South Florida.
Who is a Candidate for Anti-Reflux
Surgery?
The ideal candidate for ARS is the patient with symptoms
and/or organ pathology directly attributable to GERD,
without other functional or psycho-emotional disorders,
which can produce patient-perceived poor outcomes.2
Identification of a patient with pathologic reflux requires
both an understanding of the symptoms caused by GERD
and the objective testing to confirm the pathology. The
symptoms of GERD are quite varied (Table 1).3 Sorting
Foregut
2021, Vol. 1(2) 152­–156
© The Author(s) 2021
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/26345161211021772
https://doi.org/10.1177/26345161211021772
journals.sagepub.com/home/gut
out which symptoms are actually caused by GERD can be
vexing, especially for the atypical symptoms.4 Therefore,
at our center we careful correlate symptoms with objec-
tive testing to insure that an ARS will lead to symptom-
atic and pathologic improvement, with minimal side
effects.
Once a diagnosis of “refractory” GERD is established,
and other concomitant diagnoses are assessed, namely, a
patient’s overall fitness for surgery and general anesthe-
sia. Age, by itself, should not exclude anyone from an
ARS. Co-existing cardiopulmonary disease needs to be
evaluated with appropriate preoperative consultations
and inventions performed. Any patient with a diagnosis
of GERD who desires to discontinue antacid medica-
tions, cannot afford life-long antacid medications, or is
having treatment failure with antacid medications should
be considered for surgery.
What Predicts Surgical Success?
Surgical success can be defined by symptom ameliora-
tion, resolution of any anatomic pathologies (eg, esopha-
gitis), lack of significant complications, and minimal
operation-related side effects. The best way to achieve
this goal is proper patient selection, operation selection,
operation execution, and postoperative care.
With respect to appropriate patient selection, the best
predictor of successful operation is establishing the diag-
nosis of GERD. In general, patients with typical symp-
toms will get more relief after surgery than patients with
atypical symptoms, which likely stems from the fact that
atypical symptoms can be due to etiologies other than
GERD. Patients who responded to antacid therapy, even
transiently, will have better results post-operatively as the
treatment of their reflux is known to provide them
symptom relief. Beware of the patient with no symptom
1
University of South Florida, Tampa, FL, USA
Corresponding Author:
Vic Velanovich, Division of Gastrointestinal Surgery, Morsani College
of Medicine, University of South Florida, 5 Tampa General Circle,
Suite 740, Tampa, FL 33606, USA.
Email: vvelanov@usf.edu
Grimsley et al 153
Table 1.  Patient-Perceived Symptoms of GERD.
Typical Atypical (extra-esophageal)
Heartburn Throat clearing
Regurgitation Hoarseness
Waterbrash/pyrosis Chronic cough
Dysphagia Asthma
  Chest pain
  Idiopathic pulmonary fibrosis
  Aspiration pneumonia/pneumonitis
  Globus
  Dental erosions
relief even with “double-dose” PPI’s. In general, patients
with “typical” supine, nocturnal reflux respond better to
ARS than those with upright, daytime reflux.5
Who Should Not Undergo Surgery?
There are few absolute contraindications to ARS.
Contraindications include patients unfit for general anes-
thesia or intra-peritoneal insufflation, patients with diag-
noses masquerading as GERD, such as achalasia or
esophageal adenocarcinoma, or patients unable to partici-
pate in their own care. Despite few absolute contraindica-
tions, there are several factors we think warrant
consideration as they can greatly impact patient-per-
ceived surgical success.
Certain preoperative conditions will affect patient-
perceived success. If preoperative symptoms can also be
interpreted as a postoperative side effects from ARS, and
if these symptoms are not improved with surgery; that is,
if patients continue to have preoperative symptoms of
bloating, gassiness, nausea, emesis, or dysphagia pre-
operatively, they will interpret there continued presence
as a failure of the operation.6 Therefore, caution should
be taken with patients that have concomitant functional
gastrointestinal disorders such as irritable bowel syn-
drome, delayed gastric emptying, and gastroparesis. In
addition, patients with chronic pain disorders, such as
fibromyalgia, or psycho-emotional issues such, as depres-
sion and anxiety, will frequently interpret postoperative
symptoms not related to GERD negatively and be dissat-
isfied with their outcome.7,8 For these patients, there
should be a thorough discussion between surgeon and
patient to establish realistic expectations on what symp-
toms will improve, which will not change, and overall
how the patient may feel post-operatively.9 There has also
been described a population at risk for the “Nocebo phe-
nomenon,” which is when the patient perceives things as
side effects from a medication or procedural/operative
intervention that are not pharmacologically possible or
anatomically/physiologically attributable to the opera-
tion. These patients have been found to present with a
long list of medication “allergies” and should be exten-
sively counseled on what to expect postoperatively.10
Lastly, obese patients with hiatal hernia (HH) and
GERD should be counseled to lose weight prior to pro-
ceeding with ARS and hiatal hernia repair (HHR) as
recurrence rates for HH are higher in obese patients. In
fact, if these patients are candidates for bariatric surgery,
the should have the opportunity to discussed such an
option with a bariatric surgeon. The option of performing
bariatric surgery, specifically Roux-en-Y gastric bypass
which is an excellent anti-reflux operation, concomi-
tantly with HHR is highly effective.11
How to Choose among the
Operations Available?
There are many options for ARS (Table 2).12 Properly
choosing an operation requires knowledge of the patient’s
anatomic and physiologic status and of the anatomical
and physiological effects of the operation. At present, the
most commonly used ARS has been the laparoscopic
“floppy” Nissen fundoplication, usually the Rosetti mod-
ification. Patients who most benefit from this procedure
are those with “typical” symptoms and good esophageal
motility as determined by high-resolution esophageal
manometry. Some surgeons have adopted a robotic
approach, despite being found to be more expensive, less
widely available, with longer surgical time.13-17 That said,
robotic surgery has been demonstrated to be safe and the
complication rates are similar to laparoscopy.13-16,18-21 A
randomized trial of robotic versus laparoscopic fundopli-
cations found at 6 months post-operatively, patients had
similar rates of reflux based on objective pH probe test-
ing.18 However, very similar to the learning curve that
was seen 1990s with the uptake of laparoscopy, a recent
study by Benedix et al,16 showed that while the operative
time for robotic cases was significantly longer, the sur-
geons did demonstrate improvement (shorter operative
time) over the course of a 2-year period.
Overall, laparoscopy remains the gold standard for
ARS. For simplicity, we will only list laparoscopic ver-
sions of each procedure—please keep in mind that the
indications and contraindications for each below men-
tioned procedure are the same performed laparoscopic or
robotically.
Laparoscopic Nissen Fundoplication
First developed by Dr. Rudolph Nissen in 1955, this pro-
cedure combines closing the diaphragmatic crura and cre-
ating a short, floppy, wrap of the fundus around the lower
esophagus in order decrease reflux and prevent recur-
rence. The Nissen is ideal for those with typical and atyp-
ical symptoms, and pathologic acid reflux or volume
154 Foregut 1(2)

Table 2.  Types of Antireflux Operations in Present Use.

Year Surgeon Salient features Present indications

1951 Allison Reduction of hiatal hernia with Hiatal hernia where a fundoplication is
approximation of diaphragmatic crura impossible or detrimental due to the
patient’s condition
1956 Nissen 360° wrap of the gastroesophageal junction Typical or atypical symptoms in patient
with the anterior and posterior surfaces with adequate motility
of the gastric fundus 4-6 cm in length
1957 Collis Tubularization of the stomach by division Presents of a foreshortened esophagus and
at the angle of His to “lengthen” the where fundoplication is impossible or
esophagus with approximation of detrimental to the patient’s condition
diaphragmatic crura
1962 Dor 180° anterior partial fundoplication using Presents of severe esophageal motility
anterior surface of the fundus disorders (eg, achalasia) or if posterior
fundoplications impossible or detrimental
1963 Toupet 270° posterior partial fundoplication using Typical or atypical symptoms in patients
the anterior and posterior surfaces of the with severe motility disorders or poor
stomach with fixation to the esophagus motility with dysphagia
and diaphragmatic crura
1967 Hill Approximation of diaphragmatic crura with Typical or atypical symptoms where a
fixation of the gastroesophageal junction fundoplication is impossible but the
to the arcuate ligament of the diaphragm arcuate ligament can be exposed
1967 Belsy Transthoracic partial invagination of distal Typical or atypical symptoms where a
esophagus into anterior and posterior trans-abdominal approach is impossible
surfaces of the stomach or hazardous
1968 Rossetti Modification of the Nissen fundoplication Typical or atypical symptoms in patient
to use only the anterior surface of the with adequate motility
fundus
1969 Gaurner 270° posterior partial fundoplication Typical or atypical symptoms in patients
6-8 cm in length without fixation to the with severe motility disorders or poor
diaphragmatic crura motility with dysphagia
1978 Orringer “Collis-Nissen”: the Collis lengthening Presents of a foreshortened esophagus
procedure with Nissen-Rossetti associated with typical or atypical
fundoplication symptoms
1985/1986 Donahue/DeMeester Modification of the Nissen-Rossetti Typical or atypical symptoms in patient
fundoplication into a shorter with adequate motility
(approximately 2 cm) “floppy” (over
larger dilators) wrap
1991 Dallemagne The laparoscopic approach to antireflux In patients in whom a laparoscopic
operations approach is feasible
1991 Watson Anterior plication of fundus to the left Typical or atypical symptoms in patient
anteriolateral border of the esophagus with adequate or poor motility

From reference #11.

reflux diagnosed by impedance testing. Hiatal hernia
repair should nearly always be done in conjunction with a
Nissen fundoplication, regardless of hernia size. There is
some controversy as to whether a Nissen fundoplication
should be done in the face of poor esophageal motility. In
general, having normal esophageal motility as deter-
mined by high-resolution manometry preoperatively,
and, more specifically, ruling out motility disorders such
as achalasia can give one more confidence that a Nissen
fundoplication will not lead to postoperative dysphagia.
However, others have documented that decreased esoph-
ageal body peristalsis, especially when preoperative
dysphagia is not present, does not lead to an increased
risk of postoperative dysphagia after a Nissen
fundoplication.22
Laparoscopic Partial Fundoplication—Toupet
and Dor fundoplications
Partial fundoplications, either a 270° posterior Toupet or
an 180° anterior Dor, are performed when a 360° Nissen
may lead to dysphagia. The symptomatic indications for
these fundoplications is similar to the Nissen fundoplica-
tion—namely, typical and atypical GERD symptoms, in
Grimsley et al 155
the face of poor esophageal motility. Although the demar-
cation between “adequate” esophageal motility and poor
motility is nebulous and varies among surgeons, our center
considers ineffective esophageal motility and collagen-
vascular diseases, such as scleroderma, especially in asso-
ciation with preoperative dysphagia, as indications for a
partial fundoplication. However, these partial fundoplica-
tions are generally considered not as durable as a Nissen
fundoplication,23 while some authors suggests the recur-
rence rates are not statistically higher when a partial fundo-
plication is performed, but robust long term data is still
being gathered.24-29
Laparoscopic Magnetic Sphincter
Augmentation (MSA)
The LinxR device is a bracelet of rare-earth metal magnets
that is clasped around the gastroesophageal junction.
LinxR was approved by the Food and Drug Administration
in 2012 for use as a medical implant for the treatment of
GERD. The magnetic beads on the ball-end links augment
the lower esophageal sphincter (LES), preventing reflux,
while a swallowed food bolus generates enough force that
the magnets to separate, essentially “relaxing” the mag-
netic sphincter. Unlike fundoplication, the LinxR has a
smaller range of presently-accepted indications. These
include patients with typical symptoms of GERD with
non-erosive GERD or LA grade A or B esophagitis.30
Contraindications at present are patients with dysphagia,
esophageal dysmotility, or impaired peristalsis. It is rela-
tively contraindicated in patients with prior upper abdomi-
nal surgery or prior endoluminial ARS, and absolutely
contraindicated in patients with nickel-titanium metal
allergies, pacemakers, or defibrillators.
Endoluminal Antireflux Procedures
Of the many endoluminal procedures developed, only the
transoral esophagogastric incisionless fundoplication
(TIF) using the EsophyXR device, a similar procedure
using the MuseR device, and radiofrequency energy con-
traction of the gastroesophageal junction using the
StrettaR device are still available. Although initially
promising, there are concerns with durability. When com-
pared to proton pump inhibitor (PPI) treatment and
Nissen fundoplication, TIF was found to be less cost-
effective, when calculating cost per quality-adjusted life
years gained—over a 30 year period,31 and a meta-analy-
sis revealed higher return to PPI treatment after TIF, com-
pared to other ARS.32 Using a network meta-analysis,
Richter et al33 found it to be inferior to a Nissen fundopli-
cation. However, others report long-lasting symptomatic
relief, undoubtedly reflecting the difficulty in achieving
expertise with this device.34
Adjuncts to Antireflux Surgery
If patients have delayed gastric emptying or gastropare-
sis, especially in association with preoperative bloating, a
pyloroplasty should also be strongly considered with the
index operation.35 Although certainly controversial and
not indicated in all repair, it is our practice that in large or
recurrent HH, biological mesh can be used in an effort to
reduce recurrence.36
Conclusions
In summary, our multi-disciplinary approach to the opti-
mal management of patients with GERD is based on an
accurate diagnosis of the causes of the patient’s symptoms,
assessing physiologic fitness for surgery and anesthesia,
identifying associated gastrointestinal disorders or psycho-
emotional disorders that can adversely affect patient-per-
ceived outcomes, in a patient who desires surgical treatment
and has a realistic expectations. There are many ways to
perform ARS, and those are best guided by patient charac-
teristics, associated pathology, and surgeon experience.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
References
1. Kamolz T, Pointner R, Velanovich V. The impact of gastro-
esophageal reflux disease on quality of life. Surg Endosc.
2003;17:1193-1199.
2. Velanovich V. Secrets for successful laparoscopic anti-
reflux surgery: predictors. Ann Laparosc Endosc Surg.
2017;2:27.
3. Bennett RD, Straughan DM, Velanovich V. Gastro­
esophageal reflux disease, hiatal hernia, and barrett esopha-
gus. In: Zinner MJ, Ashley SW, Hines OJ eds. Maingot’s
Abdominal Operations. 13th ed. McGraw-Hill Education;
2019:351-371.
4. Katzka DA, Kahrilas PJ. Advances in the diagnosis and
management of gastroesophageal reflux disease. BMJ.
2020;371:m3786.
5. Stefanidis D, Hope WW, Kohn GP, et al. Guidelines for
surgical treatment of gastroesophageal reflux disease. Surg
Endosc. 2010;24:2647-2669.
6. Richter JE. Gastroesophageal reflux disease treatment:
side effects and complications of fundoplication. Clin
Gastroenterol Hepatol. 2013;11:465-471.
7. Velanovich V, Karmy-Jones R. Psychiatric disorders affect
outcomes of antireflux operations for gastroesophageal
reflux disease. Surg Endosc. 2001;15:171-175.
156 Foregut 1(2)
8. Kamolz T, Granderath FA, Pointner R. Does major depres-
sion in patients with gastroesophageal reflux disease affect
the outcome of laparoscopic antireflux surgery? Surg
Endosc. 2003;17:55-60.
9. Velanovich V. The effect of chronic pain syndromes and
psychoemotional disorders on symptomatic and quality-
of-life outcomes of antireflux surgery. J Gastrointest Surg.
2003;7:53-58.
10. Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific
medication side effects and the nocebo phenomenon.
JAMA. 2002;287:622-627.
11. Rohof WO, Bisschops R, Tack J, Boeckxstaens GE.
Postoperative problems 2011: fundoplication and obesity
surgery. Gastroenterol Clin North Am. 2011;40:809-821.
12. Velanovich V. Practice-changing milestones in anti-reflux
and hiatal hernia surgery: a single surgeon perspective
over 27 years and 1200 operations. J Gastrointest Surg.
Published online February 2, 2021. doi:10.1007/s11605-
021-04940-3
13. Morino M, Pellegrino L, Giaccone C, Garrone C, Rebecchi
F. Randomized clinical trial of robot-assisted versus lapa-
roscopic Nissen fundoplication. Br J Surg. 2006;93:553-
558.
14. Nakadi IE, Melot C, Closset J, et al. Evaluation of da Vinci
Nissen fundoplication clinical results and cost minimiza-
tion. World J Surg. 2006;30:1050-1054.
15. Heemskerk J, van Gemert WG, Greve JW, Bouvy ND.
Robot-assisted versus conventional laparoscopic Nissen
fundoplication: a comparative retrospective study on costs
and time consumption. Surg Laparosc Endosc Percutan
Tech. 2007;17:1-4.
16. Benedix F, Adolf D, Peglow S, Gstettenbauer LM, Croner
R. Short-term outcome after robot-assisted hiatal hernia
and anti-reflux surgery-is there a benefit for the patient?
Langenbecks Arch Surg. Published online January 6, 2021.
17. Higgins RM, Frelich MJ, Bosler ME, Gould JC. Cost anal-
ysis of robotic versus laparoscopic general surgery proce-
dures. Surg Endosc. 2017;31:185-192.
18. Draaisma WA, Rijnhart-de Jong HG, Broeders IA, Smout
AJ, Furnee EJ, Gooszen HG. Five-year subjective and
objective results of laparoscopic and conventional Nissen
fundoplication: a randomized trial. Ann Surg. 2006;244:34-
41.
19. Draaisma WA, Ruurda JP, Scheffer RC, et al. Randomized
clinical trial of standard laparoscopic versus robot-assisted
laparoscopic Nissen fundoplication for gastro-oesophageal
reflux disease. Br J Surg. 2006;93:1351-1359.
20. Hartmann J, Menenakos C, Ordemann J, Nocon M, Raue
W, Braumann C. Long-term results of quality of life after
standard laparoscopic vs. robot-assisted laparoscopic fun-
doplications for gastro-oesophageal reflux disease. A com-
parative clinical trial. Int J Med Robot. 2009;5:32-37.
21. Jensen JS, Antonsen HK, Durup J. Two years of experi-
ence with robot-assisted anti-reflux surgery: a retrospective
cohort study. Int J Surg. 2017;39:260-266.
22. Patti MG, Robinson T, Galvani C, Gorodner MV, Fisichella
PM, Way LW. Total fundoplication is superior to partial
fundoplication even when esophageal peristalsis is weak. J
Am Coll Surg. 2004;198(6):863-869.
23. Horvath KD, Jobe BA, Herron DM, Swanstrom LL.
Laparoscopic Toupet fundoplication is an inadequate pro-
cedure for patients with severe reflux disease. J Gastrointest
Surg. 1999;3:583-591.
24. Hajibandeh S, Hajibandeh S, Pugh M, et al. Impact of
Toupet versus Nissen fundoplication on dysphagia in
patients with gastroesophageal reflux disease and associ-
ated preoperative esophageal dysmotility: a systematic
review and meta-analysis. Surg Innov. Published online
September 12, 2018. doi:10.1177/1553350618799549
25. Shan CX, Zhang W, Zheng XM, Jiang DZ, Liu S, Qiu
M. Evidence-based appraisal in laparoscopic Nissen and
Toupet fundoplications for gastroesophageal reflux dis-
ease. World J Gastroenterol. 2010;16:3063-3071.
26. Tian ZC, Wang B, Shan CX, Zhang W, Jiang DZ, Qiu M.
A meta-analysis of randomized controlled trials to com-
pare long-term outcomes of Nissen and Toupet fundo-
plication for gastroesophageal reflux disease. PLoS One.
2015;10(6):e0127627.
27. Hoshino M, Omura N, Yano F, et al. Comparison of laparo-
scopic Nissen and Toupet fundoplication using a propensity
score matching analysis. Surg Today. 2017;47:1195-1200.
28. Walle KV, Funk LM, Xu Y, et al. Persistent dysphagia rate
after antireflux surgery is similar for Nissen fundoplication
and partial fundoplication. J Surg Res. 2019;235:52-57.
29. Ugliono E, Seno E, Allaix ME, Rebecchi F, Morino M.
Results after minimally invasive Toupet fundoplication
technique: a narrative review. Laparosc Surg. 2021;5:5.
30. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assess-
ment of oesophagitis: clinical and functional correlates and
further validation of the Los Angeles classification. Gut.
1999;45:172-180.
31. Funk LM, Zhang JY, Drosdeck JM, Melvin WS, Walker
JP, Perry KA. Long-term cost-effectiveness of medical,
endoscopic and surgical management of gastroesophageal
reflux disease. Surgery. 2015;157:126-136.
32. Huang X, Chen S, Zhao H, et al. Efficacy of transoral inci-
sionless fundoplication (TIF) for the treatment of GERD:
a systematic review with meta-analysis. Surg Endosc.
2017;31:1032-1044.
33. Richter JE, Kumar A, Lipka S, Miladinovic B, Velanovich
V. Efficacy of laparoscopic Nissen fundoplication vs tran-
soral incisionless fundoplication or proton pump inhibitors
in patients with gastroesophageal reflux disease: a system-
atic review and network meta-analysis. Gastroenterology.
2018;154:1298-1308.e7.
34. Testoni PA, Testoni S, Distefano G, Mazzoleni G, Fanti
L, Passaretti S. Transoral incisionless fundoplication with
EsophyX for gastroesophageal reflux disease: clinical
efficacy is maintained up to 10 years. Endosc Int Open.
2019;7:E647-E654.
35. Maqusi S, Velanovich V. Pyloroplasty with fundoplication
in the treatment of combined gastroesophageal reflux dis-
ease and bloating. World J Surg. 2007;31:332-336.
36. Keville S, Rabach L, Saad AR, Montera B, Velanovich
V. Evolution from the U-shaped to the keyhole-shaped
mesh configuration in repair of paraesophageal and recur-
rent hiatal hernia. Surg Laparosc Endosc Percutan Tech.
2020;30:339-344.