What GI Doctors Should Know About Anti-Reflux Surgery

This is a useful review -with helpful diagrams: Full text Ten Things Every Gastroenterologist Should Know About Antireflux Surgery (S Park et al. Clin Gastroenterol Hepatol 2020; 18: 1923-1929)

A couple excerpts:

Selecting Patients for Surgery: Current guidelines fall short in determining appropriate patients who would benefit most from surgery. For instance, the recommendation that a desire to discontinue PPI therapy is a suitable indication for antireflux surgery fails to recognize that 62% of patients end up back on PPIs within 9 years. Furthermore, indicating that those patients who failed medical management would benefit from surgery neglects the fact that the patients who respond best to antireflux surgery are those who have responded well to PPI therapy in the first place

Complications: Late postoperative complaints are more common and often are referred back to the referring gastroenterologist for diagnosis and management. These include late-onset dysphagia (3%–24%), recurrent heartburn (up to 62%), gas-bloat syndrome (up to 85%), and diarrhea (18%–33%).  Anatomic failure of the fundoplication (Figure Below) can present a unique challenge to the clinician because the symptoms and patient presentation (postoperative dysphagia, regurgitation, and heartburn) can be clinically indistinct from the issues seen commonly after this surgery even in the best of circumstances.  Therefore, the gastroenterologist should assess symptoms carefully in a stepwise approach with upper endoscopy, barium swallow, esophageal manometry, and/or ambulatory pH monitoring when appropriate and plan any interventions based on objective findings from focused testing.

Other points:
  • Antireflux Surgery Has No Significant Impact on the Progression of Barrett’s Esophagus to Esophageal Adenocarcinoma: Endoscopic Ablation of Dysplastic Barrett’s Esophagus Still Is Recommended
  • Medical Therapy Is More Cost Effective Than Surgical Treatment if the Cost of the Drug Is Low
  • Several New, Less-Invasive Surgical and Endoscopic Antireflux Procedures Are Now Food and Drug Administration Approved, Available, and Appear Promising

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More Data on Magnetic Sphincter Augmentation for Gastroesophageal Reflux

In adults with gastroesophageal reflux, there is more data that magnetic sphincter augmentation (MSA) is a good option for many.  R Bell et al. Clin Gastroenterol Hepatol 2020; 18: 1736-1743. Full Text: Magnetic Sphincter Augmentation Superior to Proton Pump Inhibitors for Regurgitation in a 1-Year Randomized Trial)

Methods: Patients with moderate to severe regurgitation (assessed by the foregut symptom questionnaire) despite once-daily PPI therapy (n = 152) were randomly assigned to groups given twice-daily PPIs (n = 102) or laparoscopic MSA (n = 50) at 20 sites.

Key findings:

  • MSA resulted in control of regurgitation in 72/75 patients (96%); regurgitation control was independent of preoperative response to PPIs. It is noted that none of the patients in this study had grade C or grade D esophagitis.
  • Only 8/43 patients receiving PPIs (19%) reported control of regurgitation.
  • In the MSA group, MSA, 61 (81%) had improvements in GERD health-related quality of life improvement scores (greater than 50%) and 68 patients (91%) discontinued daily PPI use. The Demeester scores improved from 33.4 to 3.5 at 6 months post implanation
  • Esophageal acid exposure time decreased from 10.7% to 1.3% (P < .001) from study entry to 1-year after MSA.
  • Safety: No serious perioperative adverse events occurred in any arm of the study. Although 19 (39.6%) MSA patients and 10 (33.3%) MSA crossover patients reported instances of dysphagia, MSA patients reported less dysphagia at 6 and 12 months than at baseline

Discussion points from authors:

  • Relatively limited duration of follow-up, though “other studies of MSA have documented little decrease in efficacy between 1 and 5 years of follow-up”
  • The American College of Gastroenterology guidelines indicate “that surgical therapy is not recommended for patients who do not respond to PPI therapy. However, the basis for these recommendations and the types of symptoms evaluated for response to PPI therapy is unclear. Three prospective cohort studies have compared the effectiveness of laparoscopic fundoplication between PPI responsive and  nonresponsive populations and found significant symptom improvement with laparoscopic fundoplication in PPI nonresponders, though not quite as much as in PPI responders”
  • Increased bloating which is common after laparoscopic fundoplication was not evident with MSA which found a decrease from baseline.  “. Continued ability to belch was reported in 99% (n = 74 of 75) of all patients who received MSA at 12 months.”

In the associated editorial, JE Richter (Clin Gastroenterol Hepatol 2020; 18: 1685-1687 Full text: Laparoscopic Magnetic Sphincter Augmentation: Potential Applications and Safety Are Becoming More Clear—But the Story Is Not Over) notes that “erosion and migration of the MSA device have been a rare event thus far. In a total of nearly 10,000 device placements, there were 29 reported cases of erosions…Smaller devices were associated with higher rates of erosions. The 12-bead device was responsible for 18 of 29 erosions (62%) and is no longer available for implantation…To an admitted skeptic about new antireflux treatments, the available data about the symptomatic and
physiological effectiveness, durability, and safety of MSA are very impressive. I believe this procedure now deserves to be routinely done as an alternative surgical procedure to traditional fundoplication for patients with mild-moderate GERD….patients with severe GERD and structural sphincter dysfunction still need the traditional fundoplication”

My take: This study and others shows that MSA (aka Linx) is an effective treatment option for many adult patients with medically-refractory regurgitative reflux.

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It is surprising to me that almost half of the U.S. thnk that we have handled the pandemic well

New Agent for Refractory Reflux

In the June issue of Gastroenterology (158: 2015-16), a tribute to George Sachs (1935-2019) recognizes his work in the field of gastroenterology and his development of proton pump inhibitors (PPIs).

Much more work remains as ~30% of patients with gastroesophageal reflux remain symptomatic despite PPI therapy.   In the same issue, IW-3718, a bile acid sequestrant colsevelam with a gastric-retentive formulation was studied in 280 patients (MF Vaez et al. Gastroenterol 2020; 158: 2017-19).

Methods: The authors performed a multicenter, double-blind, placebo-controlled 8-weel treatment trial (2016-17); patients received the study drug (500, 1000, 1500 mg) or placebo twice daily.  The authors enrolled symptomatic patients (≥4 times per week) with erosive esophagitis or pathologic reflux based on Bravo study (pH<4 for ≥4.2% during at least one 24-hour period). They continued PPI therapy which they had been receiving for a minimum of 8 weeks prior to starting study medication.

Key findings:

  • Improvement in heartburn severity scores for placebo, 500, 1000, and 1500 mg groups: 46%, 49%, 55%, and 58%.  The 11.9% difference between 1500 mg group compared to placebo reached statistical significance (P=.04)
  • There was an improvement in weekly regurgitation frequency score as well from baseline to week 8 in 1500 mg group of 17.5% compared to placebo.
  • No serious drug related serious adverse events were identified.  Constipation was noted in 8% of study drug recipients compared 7% for placebo recipients.

Limitations: lack of a centralized review for endoscopy images, high placebo response rate, once daily use of PPI in study, and problems with overlap of functional symptoms

My take: This study shows why a placebo control is needed in reflux studies.  While IW-3718 at higher doses was effective, its response appears much less notable when compared with placebo-recipients.

Job Security Study: Lots of People Have Reflux Symptoms & COVID-19 Due To Singing

A recent study (SD Delshad, CV Almario et al. Gastroenterol 2020; 158: 1250-61) used survey data from an APP, MyGiHealth, to assess prevalence of reflux symptoms and symptoms that had not responded to proton pump inhibitor treatment.

Key findings:

  • In 2015, among 71,812 participants, 32,878 (44.1%) reported reflux symptoms previously and 23,039 (30.9%) reported reflux symptoms in previous week
  • 35% with reflux symptoms were currently receiving treatment: 55% PPIs, 24% H2RAs, and 24% antacids
  • Of the 3229 taking daily PPIs, 54% reported persistent reflux symptoms (≥2 days per week)
  • Age range of respondents was 33% for 18-29, 27% for 30-39, 17% for 40-49, 15% for 50-59, and 8% ≥60

Limitations: 

  • Potential selection bias as there was only a 5.5% response rate among the entire eligible population of 1.3 million
  • Reflux symptoms frequently is not due to reflux disease

My take: There are a lot of folks with reflux symptoms and many have ongoing symptoms despite treatment; hence, lots of opportunity to help (and job security)

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Also from NY Times: Coronavirus Ravaged a Choir. But Isolation Helped Contain It.

“One sick singer attended choir practice, infecting 52 others, two of whom died. A study released by the C.D.C. shows that self-isolation and tracing efforts helped contain the outbreak.”  Only 8 of the 61 choir members did not get sick.

Graphical Abstract

Gastroesophageal Reflux Phenotypes and “Where Rome, Lyon, and Montreal Meet”

A useful review (DA Katzka et al. Clin Gastroenterol Hepatol 2020; 18: 767-76) discusses the phenotypes of gastroesophageal reflux and related disorders.   The authors note that consensus initiatives (Montreal, Rome, and Lyon) have looked at these disorders from different perspectives and their goal was to merge their perspectives.

Table 1 lists the major phenotypes:

  • Nonerosive reflux disease
  • Reflux hypersensitivity
  • Functional heartburn
  • Erosive esophagitis (low grade and high grade).  LA grade A esophagitis “can be found in approximately 6% of asymptomatic controls”
  • Barrett’s esophagus
  • Reflux chest pain syndrome
  • Regurgitation-dominant reflux disease: “need to differentiate from rumination and achalasia”
  • Laryngopharyngeal reflux
  • Chronic cough  “although reflux may contribute, it is rarely the dominant pathophysiology… more amenable to GERD therapy when accompanied by typical reflux symptoms”

Figure 1 provides a model for the pathogenesis of GERD. Figure 2 describes the relationship between reflux phenotypes and PPI responsiveness:

In those with typical reflux symptoms: 

  • esophagitis healing 84% with PPI Rx compared to 28% with placebo (NNT =1.8)
  • heartburn relief (with and without esophagitis) 56% with PPI Rx compared to 16% with placebo (NNT =4.4)
  • heartburn relief without esophagitis 40% with PPI Rx compared to 13% with placebo (NNT =3.7)
  • regurgitation relief (with and without esophagitis) 47% with PPI Rx compared to 30% with placebo (NNT =5.9)

In those with atypical reflux symptoms:

  • chest pain relief with objective GERD 74% with PPI Rx compared to 20% with placebo (NNT =1.6) (Studies used a 50% reduction in pain as opposed to complete elimination…opens the door for a greater placebo response)
  • chest pain relief without objective GERD 29% with PPI Rx compared to 23% with placebo (NNT =16.7) (Studies used a 50% reduction in pain as opposed to complete elimination…opens the door for a greater placebo response)
  • chronic cough with objective GERD 33% with PPI Rx compared to 9% with placebo (NNT =4.2)
  • chronic cough without objective GERD 31% with PPI Rx compared to 27% with placebo (NNT =25)
  • reflux laryngitis (without heartburn, complete resolution) 15% with PPI Rx compared to 16% with placebo
  • poorly-controlled asthma (without heartburn)-exacerbations per year: 2.5 with PPI Rx compared to 2.3 with placebo 
  • *references for this figure provided

Other useful points:

  • “An exception to the de-emphasizing the relationship of GERD to an extraesophageal syndrome is with lung transplantation, which …has unique considerations…the sequelae of untreated GERD …may lead to accelerated mortality from allograft injury…data have suggested that PPIs may be effective at prolonging allograft survival.”
  • The authors state that escalating PPI/antisecretory treatments for esophagitis is often effective but this approach has limited applicability for other indications and can result in overuse. “Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, and visceral and central hypersensitivity on symptom severity has greatly oversimplified the problem.”

My take (borrowed in part from authors): PPIs work well for esophagitis and documented reflux; “the broad spectrum of syndromes [are] much less amenable to PPI therapy in any dose.”

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Curbside Humor

 

Impedance May Help in Borderline Reflux Disease Assessment

A recent retrospective study (A Rengarajan et al. Clin Gastroenterol Hepatol 2020; 18: 589-95), with a cohort of 371 patients (mean age 54 years) shows how impedance testing may help identify patients who are likely to respond to reflux management when pH probe testing is equivocal.  The cohort included adults with persistent reflux symptoms.  Response to antireflux therapy was defined as >50% improvement in esophageal symptoms.

Key points:

  • 107 (28.8%) had pathologic acid exposure time (AET) (pH<4 for >6%)
  • 234 (63.1%) had abnormal mean nocturnal baseline impedance (MNBI) (<2292 ohms). MNBI was calculated using baseline values at 10-minute periods between 1-3 am from the 5 cm channel to correspond to total distal AET.
  • Figure 1, shows the combined use of AET and MNBI.  Only 106/107 patients with AET>6, had an abnormal MNBI.  In the borderline category of AET 4-6%, 62/68 (91.2%) had abnormal MNBI values. In those with AET <4, MNBI was abnormal in 66/196 (33.7%)

Response to Treatment:

  • Among patients with AET >6, 66/89 (74%) responded to medical therapy and 18/23 (78%) responded to surgical therapy; among patients with AET 4-6%, 37/56 (66%) responded to medical therapy and 14/17 (82%) responded to surgical therapy. In those with AET <4, 39/185 (21%) responded to medical therapy and 16/23 (70%) responded to surgical therapy
  • Among patients with a low MNBI, 119/198 (60%) responded to medical therapy and 41/50 (82%) to surgical therapy.  In those with a normal MNBI, 23/132 (17%) responded to medical therapy and 7/13 (54%) responded to surgical treatment
  • In those with AET >6, 84/111 (76%) responded to treatment. For those with AET 4-6%, of those with low MNBI, 49/67 (73%), responded (similar to those with AET >6%).  In those with low MNBI and AET <4, 27/70 (39%) responded to treatment
  • 28/138 (20.2%) with normal AET <4 and with normal MNBI responded to treatment

My take: The big takeaway is that all of our tests for pathologic reflux are highly flawed; impedance may (to a small degree) help stratify patients with equivocal evaluation based on AET.  Normal tests do not exclude response treatment (especially surgery).

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Blaming Reflux for BRUEs -Not Changing Despite Guideline Recommendations

Briefly noted: DR Duncan et al. J Pediatr 2019; 211: 112-9.

In this retrospective cohort study of infants with brief resolved unexplained events (BRUEs) at Boston Children’s Hospital, the authors examined guideline implementation among 359 subjects in the year before and the year after AAP guidelines.

Key findings:

  • There were no significant changes in practice after guideline publication
  • Only 13% had videofluoroscopic swallow study performed; 72% of these showed aspiration/penetration
  • No subject had reflux testing, “yet reflux was implicated as the cause” for BRUE in 40%. Children continued to be “discharged on acid suppression despite lack of efficacy”

My take: The pendulum is (slowly) starting to swing back from blaming everything (including BRUEs) on reflux but this change is not evident in this study.

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Which Symptom is Best for Indicating Reflux in Infants?

A recent study (CR Collins et al. J Pediatr 2019; 206; 240-7) showed that symptoms alone are not able to predict the degree/presence of reflux in infants.

Methods: The authors recruited ‘symptomatic’ infants with median 41 weeks postmenstrual age (median 29 weeks at birth) and employed a combination of 24-hour pH-impedance to determine acid reflux index (ARI) and subsequently used provocative esophageal infusions (with air, water then apple juice) to assess manometry and symptoms. In total, they analyzed 2635 separate esophageal stimula in 74 infants.

The authors considered ARI <3% as normal, 3-7% as indeterminate ARI, and >7% as abnormal ARI.

Symptoms that they recorded included arching, irritability, cough, gag, sneeze, gasp, bradycardia, desaturation, throat clearing, startle, grimace, grunting, mouthing, and yawning.

Key findings:

  • “The presence of physical symptoms (ARI <3: 80%; ARI 3-7: 77%; ARI >7: 81%; P=0.4), cardiorespiratory symptoms (ARI <3: 27%; ARI 3-7: 40%; ARI >7: 26%; P=0.4),or sensory symptoms (ARI <3: 26%; ARI 3-7: 22%; ARI >7: 35%; P=0.3) were also not significantly different by ARI groups”
  • All infants had a normal symptom index (SI) for acid, nonacid, or total reflex.
  • Accepted metrics, SI, SSI, and SAP, had higher association with nonacid events compared with acid events.
  • Cardiorespiratory symptoms are more likely to be elicited by esophageal infusions with both water and apple juice than air.  “Symptoms are indicators of esophageal dysmotility and maladaptive aerodigestive protective mechanisms.”
  • The authors in their discussion state that “GERD severity plays no role in the generation of symptoms.”

My take: All infants with and without reflux have a lot of “symptoms.”  Nonacid reflux is much more likely to provoke symptoms in this population than acid reflux reinforcing the idea that acid suppression is likely ineffective and potentially harmful.  “The findings of this study challenge the rationale for instituting anti-GERD therapies in neonates based on either symptoms alone or the existing acid-reflux indices or pH-impedance metrics.”

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Link to article cited below from The Onion: Dog Feels Like He Always Has To Be ‘On’ Around Family Thanks to Jennifer for this reference.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

Do Acid Blockers Given to Infants Increase the Risk of Allergic Disease?

A recent retrospective study (Mitre E, et al. JAMA Pediatr. 2018;doi:10.1001/jamapediatrics.2018.0315) suggests that acid blockers, both histamine receptor antagonists and proton pump inhibitors increase the risk of developing allergic disease.  Since this is a retrospective study, this association with allergic diseases has NOT been proven to have a causal relationship; thus, an alternative explanation would be that infants who are likely to develop allergic diseases could be prescribed these agents more frequently due to symptoms attributed to reflux.

Here is an excerpt from a summary of this study (from Healio):  Acid-suppressor, antibiotic use in infancy tied to later allergic disease

Of the 792,130 children included in the study (49.9% female), 7.6% were prescribed a histamine-2 receptor antagonist (H2RA) and 1.7% were prescribed a proton pump inhibitor (PPI) within the first 6 months of life. Antibiotics also were prescribed for 16.6% of infants included in the study during this time. Mitre and colleagues noted that data continued to be collected on these infants for a median of 4.6 years…

When children were prescribed an H2RA, the researchers noted adjusted HRs of 2.18 (95% CI, 2.04-2.33) for food allergy, 1.70 (95% CI, 1.60-1.80) for medication allergy, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) for allergic rhinitis and 1.25 (95% CI, 1.21-1.29) for asthma.

Infants who were prescribed PPIs had comparable aHRs, which the researchers observed at 2.59 (95% CI, 2.25-3.00) for food allergy, 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.45 (95% CI, 1.22-1.73) for anaphylaxis and 1.44 (95% CI, 1.36-1.52) for asthma.

Mitre and colleagues also calculated the aHRs related to later allergic disease in children who were prescribed antibiotics within the first 6 months of life. They observed these rates at 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis.

My take: This study is another reminder that these agents may be more detrimental than beneficial in the vast majority of infants.

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Better to Do a Coin Toss than an ENT Examination to Determine Reflux

A recent study (R Rosen et al. J Pediatr 2017; 183: 127-31) adds additional data to the literature which has shown that ENT doctors are NOT able to tell if there is reflux by examining the airway.

Prior post on this topic: Accuracy of ENT diagnosis of Reflux Changes

This prospective, cross-sectional cohort study of 77 children correlated ENT examinations with “reflux finding score” (RFS) by three blinded otolaryngologists with objective measures of reflux: pH-metry and impedance.  All children had chronic cough and underwent bronchoscopy and esophagogastroduodenoscopy.

Key findings:

  • “There was no correlation between pH-MII variables and mean RFS”
  • The concordance correlation for RFS between ENT doctors was low (intraclass correlation coefficient =0.32)
  • Using pH-metry as a gold standard, the positive predictive value for the RFS was 29% whereas with MII as the gold standard, the positive predictive value for the RFS was 40%.

My take: ENT doctors are unable to tell if a patient has reflux.  The finding of a red or swollen airway has poor predictive value in determining the presence of reflux –a coin toss is more reliable.  Based on this study and others, starting a PPI because of an abnormal airway exam does not make sense.

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Monet, Musee de l’Orangerie