Guideline Summaries

Adapted from ACG guidelines. Please see full text - here

Listen to the AJG podcast summary with the author - here

• This updated guideline includes significant changes, including...

  • relaxed surveillance intervals for short segment BE 

  • broadening of acceptable screening modalities

  • volume criteria for endoscopic therapy

Important distinctions when reading these guidelines

• These guidelines are meant to help aid in making informed decisions, not dictate a standard of care

  • Strong Recommendation - denoted by "we recommend" 

    • Most individuals should receive this intervention 

  • Conditional Recommendation - denoted by "we suggest"

    • Different choices may be appropriate based on patient preference. Employ shared decision making and consider using decision aids

• Quality of evidence 

  • High - Significant confidence that the true effect lies close to that of the estimate of the effect

  • Moderate - Moderate confidence. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low - Limited confidence. The true effect may be substantially different from the estimate of the effect.

  • Very low - Very little confidence. The true effect is likely to be substantially different from the estimate of effect

Summary

Diagnosis

• Strong recommendation, low quality of evidence

  • (Strong, low) - ACG recommends that finding of dysplasia of any grade in biopsies for BE must be confirmed by a second pathologist with GI pathology expertise 

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests diagnosis of BE requires ≥ 1 cm of columnar mucosa 

    • Do not biopsy a normal appearing z-line

    • Segments < 1 cm without any visible lesions should not be biopsied 

    • An irregular z-line without any visible lesions should not be biopsied 

  • (Conditional, low) - ACG suggests taking at least 8 biopsies for screening with ≥ 1 cm of endoscopic BE mucosa

    • The author suggests taking 8 biopsies even in segments 1-2 cm

    • If 8 biopsies are not technically feasible, they suggest at least 6 biopsies

    • Seattle protocol (4 quadrant biopsies every 2 cm) should be followed for segments > 4 cm

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - ACG suggests diagnosis of BE requires finding of intestinal metaplasia (IM) in the esophagus

    • guidelines from British Society of Gastroenterology and the Asia Pacific region do not require this

Screening

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests agains repeat screening with an initial negative screening EGD

    • The author suggests that those with erosive esophagitis (LA grade B or worse) on initial EGD should undergo repeat EGD in 8–12 weeks after treatment with PPIs to ensure healing of esophagitis and to assess for BE

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - ACG suggests screening EGD in those with chronic GERD and ≥ 3 risk factors

    • male sex, age >50 y, White race, tobacco smoking, obesity, and family history of BE or EAC in a 1st-degree relative

  • (Conditional, very low) - ACG suggests screening with a swallowable, nonendoscopic capsule sponge device (Fig 3) combined with a biomarker is acceptable in those who meet criteria for screening 

    • ex. Cytosponge with immunohistochemical testing for a protein marker expressed in IM, trefoil factor 3 (TFF3)

Surveillance

• Strong recommendation, moderate quality of evidence

  • (Strong, moderate) - ACG recommends high definition white light endoscopy and chromoendoscopy (electronic acceptable)

    • The author suggests that careful and long examination for irregularities is key, not just use of chromoendoscopy 

    • The author suggests there is not yet enough data and/or evidence of increased value/cost-effectiveness to support the use of other advanced imaging techniques (ex. confocal laser endomicroscopy, volumetric laser endomicroscopy) for surveillance 

    • The author is unable to make a recommendation on the use of wide-area transepithelial sampling with computer-assisted 3-dimensional (WATS-3D) analysis

    • The author is unable to make a recommendation on the use of predictive tools (p53 staining and TissueCypher) in addition to standard histopathology for risk stratification due to low sensitivity and specificity

  • (Strong, moderate) - ACG recommends length of the non-dysplastic BE (NDBE) segment be considered when determining surveillance intervals such that...

    • NDBE segment ≥ 3 cm - survey q3y

    • NDBE segment <3 cm - survey q5y

  • (Strong, moderate) - ACG recommends surveillance following successful endoscopic eradication therapy (EET) 

    • surveillance intervals are based on pre-EET histology (Table 7)

    • See Fig 6 for suggested biopsy protocol 

      • biopsy from the GEJ and distal esophagus (2–5 cm) in separate jars

      • unclear significance of nondysplastic IM recurrence in the cardia

      • The author suggests cessation of surveillance after complete eradication of dysplasia (CED) and IM (CEIM) is not recommended unless precluded by overall medical status

• Strong recommendation, low quality of evidence

  • (Strong, low) - ACG recommends using the Seattle protocol for BE surveillance to minimize detection bias

    • 4 quadrant biopsies at intervals q2 cm from the lower esophageal sphincter to the squamocolumnar junction

    • biopsy visible lesions and islands separately 

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - ACG suggests surveillance intervals be dictated by degree of dysplasia on prior biopsy

    • though retrospective studies suggest a mortality benefit associated with surveillance, a case-control study in the Kaiser Permanente system demonstrated no difference within 3 years

    • Indefinite for dysplasia (IND)

      • pathologist is unable to determine whether the histology represents true dysplasia or just inflammatory changes

      • confirm finding with an expert GI pathologist

        • Confirmed cases - intensify antireflux therapy and repeat EGD in  6 mo

        • Persistent IND - the author suggests surveillance should proceed annually until the findings normalize 

        • Downgraded cases to non-dysplastic BE (NDBE) - follow NDBE surveillance interval (q3-5 y)

• Key concepts

  • The author suggests BE surveillance should be discontinued when..

    •  estimated survival of less than 5 years 

    • patients are no longer fit for repeated endoscopy

    • patients cannot tolerate endoscopic, surgical, or oncological intervention for esophageal neoplasia

      • the author suggests calculating the patient's comorbidity index

    • Discussion of surveillance cessation is suggested around the age of 75 y

Medical therapy

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests treating patients with BE with at least once daily PPI

    • The author us unable to make a recommendation on combination therapy with ASA and PPI for chemoprevention

      • improved all-cause mortality with ASA may be related more to cardioprotective effects

  • (Conditional, low) - ACG suggests against antireflux surgery as an antineoplastic measure

Endoscopic therapy

• Strong recommendation, moderate quality of evidence

  • (Strong, moderate) - ACG recommends endoscopic eradication therapy (EET)  over esophagectomy in BE with high-grade dysplasia (HGD) or intramucosal cancer (IMC)

    • T1b EAC with superficial submucosal invasion (sm1—invasion into the upper third of the submucosa to a depth ,500 mm) and low-risk features (deep margin negative, well-moderate differentiation and no lymphovascular invasion)

    • Risk of lymph node metastasis in T1b sm1 EAS is felt to be lower than mortality associated with esophagectomy

    • Those with high risk histology should be treated with esophagectomy

• Conditional recommendation, moderate quality of evidence

  • (Conditional, moderate) - ACG suggests either EET in BE with confirmed low-grade dysplasia (LGD) or endoscopic surveillance as an acceptable alternative

    • If proceeding with surveillance - q6 mo for the first year (due to increased risk of progression) then annually until there is no evidence of LGD, then revert to NDBE surveillance intervals q3 y

    • The author emphasizes the importance of share decision making for full understanding of risks/benefits

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - ACG suggests initial endoscopic resection (ER) fo visible lesions prior to ablative EET

    • ER of early-stage EAC provides accurate tumor (T) staging and prognostic information

    • T1a - low prevalence of lymph node metastasis

    • T1b invading the mid- to deep submucosa - significant prevalence of lymph node metastasis (20-30%)

      • EUS is not routinely recommended for evaluation of HGD/LGD or early EAC to differentiate between mucosal vs submucosally invasive disease (only modest accuracy)

    • Following ER of visible abnormalities, the author suggests ablation of residual BE segment with cryotherapy or radiofrequency ablation (RFA) regardless of histology to achieve complete eradication of dysplasia (CED) and IM (CEIM) and reduce the risk of recurrent dysplasia/EAC

  • (Conditional, very low) - ACG suggests EET be performed at high-volume centers

Adapted from AGA guidelines. Please see full text - here

• A prior technical review and guideline was published by the AGA in 2014

• This updated guideline incorporates new evidence and therapies 

Important distinctions when reading these guidelines

• These guidelines are meant to help aid in making informed decisions, not dictate a standard of care

  • Strong Recommendation - denoted by "we recommend" 

    • Most individuals should receive this intervention 

  • Conditional Recommendation - denoted by "we suggest"

    • Different choices may be appropriate based on patient preference. Employ shared decision making and consider using decision aids

• Certainty of evidence 

  • High - Significant confidence that the true effect lies close to that of the estimate of the effect

  • Moderate - Moderate confidence. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low - Limited confidence. The true effect may be substantially different from the estimate of the effect.

  • Very low - Very little confidence. The true effect is likely to be substantially different from the estimate of effect

Summary

• Strong recommendation, high certainty of evidence

  • Linaclotide - (Strong, high) AGA recommends use in IBS-C

    • a nonabsorbed 16-amino acid peptide structurally similar to uroguanylin

      • guanylate cyclase C (GC-C) receptor agonist

        • activates the cystic fibrosis transmembrane conductance regulator in enterocytes

      • similar mechanism to plecanatide but linaclotide is NOT pH-sensitive

    • ultimately increases fluid as well as chloride and bicarbonate secretion

    • has antinociceptive effects

    • FDA approved for IBS-C: 290 µg once daily

    • FDA approved for chronic idiopathic constipation (CIC): 72 µg and 145 µg once daily

    • Side Effects: diarrhea

• Conditional recommendation, moderate certainty of evidence

  • Plecanatide - (Conditional, moderate) AGA suggests use in IBS-C

    • a nonabsorbed 16-amino acid peptide structurally similar to uroguanylin

      • guanylate cyclase C (GC-C) receptor agonist

        • activates the cystic fibrosis transmembrane conductance regulator in enterocytes

      • similar mechanism to linaclotide but plecanatide is pH-sensitive

        • greater affinity for GC-C receptor in lower pH environments (ex. proximal duodenum)

    • ultimately increases fluid as well as chloride and bicarbonate secretion

    • has antinociceptive effects

    • FDA approved for IBS-C and chronic idiopathic constipation (CIC): 3 mg daily

    • Side Effects: diarrhea

  • Tenapanor - (Conditional, moderate) AGA suggests use in IBS-C

    • a small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3

      • this exchanger is on the apical surface of the small intestine and colon

      • the drug acts locally at the exchanger and is minimally absorbed

    • decreases absorption of sodium and phosphate, increasing water secretion

    • has antinociceptive effects

    • FDA approved for IBS-C: 50 mg BID

    • Side Effects: diarrhea

  • Tegaserod - (Conditional, moderate) AGA suggests use in IBS-C

    • partial agonist of the 5-HT4 receptor

    • increased fluid secretion and stimulates gastrointestinal motility

    • reduces abdominal pain

    • FDA approved for IBS-C in women <65 yo without a history of cardiovascular ischemic events: 6 mg BID

    • Side effects: diarrhea, headaches

      • increased cardiovascular risk in one retrospective study

      • possible increased risk in those with known cardiovascular risk factors 

  • Lubiprostone - (Conditional, moderate) AGA suggests use in IBS-C

    • a chloride channel type 2 activator

    • increased chloride secretion, accelerated intestinal transit

    • reduces abdominal pain

    • FDA approved for IBS-C in women: 8 µg BID

    • FDA approved for CIC in men and women: 24 µg BID

• Conditional recommendation, low certainty of evidence

  • Polyethylene Glycol Laxatives - (Conditional, low) AGA suggests use in IBS-C

    • a long-chain polymer of ethylene oxide

    • an osmotic laxative

    • no significant improvement in abdominal pain

Adapted from AGA guidelines. Please see full text - here

Adapted from ACG guidelines. Please see full text - here

Listen to the AJG podcast summary with the author - here

• This updated guideline addresses several clinical situations regarding anticoagulants and antiplatelets including...

  • temporary interruption 

  • reversal

  • periprocedure bridging

  • post procedure resumption

• Due to limited available data and the rapid evolution of endoscopic techniques, not all clinical situations have been addressed 

• Overall high quality studies on this topic are limited. Recommendations have been downgraded due to indirectness, risk of bias, and imprecision of evidence.

Important distinctions when reading these guidelines

• These guidelines are meant to help aid in making informed decisions, not dictate a standard of care

  • Strong Recommendation - denoted by "we recommend" 

    • Most individuals should receive this intervention 

  • Conditional Recommendation - denoted by "we suggest"

    • Different choices may be appropriate based on patient preference. Employ shared decision making and consider using decision aids

• Quality of evidence 

  • High - Significant confidence that the true effect lies close to that of the estimate of the effect

  • Moderate - Moderate confidence. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low - Limited confidence. The true effect may be substantially different from the estimate of the effect.

  • Very low - Very little confidence. The true effect is likely to be substantially different from the estimate of effect

Summary

Vitamin K antagonist (VKA) reversal

• Unable to reach a recommendations

  • Unable to recommend for or against use of PCC in warfarin treated patients with acute GI bleed due to insufficient evidence

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - In warfarin treated patients with acute GI bleed, recommend against FFP

  • (Conditional, very low) - In warfarin treated patients with acute GI bleed, recommend treating with PCC rather than FFP

    • evidence is limited, but more rapid correction of INR is seen with PCC

    • most patients will not require PCC, but this can be considered in life threatening bleed or in those in whom massive blood transfusion may lead to worsening coagulopathy and/or dilution of blood components

  • (Conditional, very low) - In warfarin treated patients with acute GI bleed, recommend against treating with vitamin K

    • no evidence to suggest vitamin K improves clinical outcomes in GI bleed

    • Vitamin K acts slowly, reversing coagulopathy over 24-48 hr and does not achieve rapid hemostasis. Endoscopic intervention may more directly yield hemostasis for limited bleeds

Direct thrombin inhibitor reversal

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - In dabigatran treated patients with acute GI bleed, recommend against treating with idarucizumab

    • Limited evidence of benefit with high cost

    • May consider in life threatening bleed with dabigatran taken in the last 24 hr

Direct oral anticoagulant reversal

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - In rivaroxaban or apixaban treated patients with acute GI bleed, recommend against treating with andexanet alfa

    • Limited evidence of benefit with high cost

    • May consider in life threatening bleed with rivaroxaban or apixaban taken in the last 24 hr

  • (Conditional, very low) - In DOAC treated patients with acute GI bleed, recommend against treating with PCC

    • Limited evidence of benefit with high cost

    • May consider in life threatening bleed with DOAC taken in the last 24 hr

Antiplatelet reversal, interruption, and resumption

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - In antiplatelet treated patients with acute GI bleed who are not thrombocytopenic, recommend against treating with platelet transfusion

    • Though evidence is limited, there appears to be a trend towards increased mortality without clinical benefit

    • ASA, clopidogrel, prasugrel - irreversibly inhibit plt function for 7-10 d

    • ticagrelor - inhibits plt function for 3-5 d reversal agent (cyclopentyltriazolopyrimidine)

  • (Conditional, very low) -  In ASA (for secondary cardiovascular prevention) treated patients with acute GI bleed, recommend against holding ASA

    • well documented cardiac benefit

    • reduced mortality seen in early resumption of ASA after endoscopic hemostasis in high-risk ulcer bleeding

    • recommendation does not apply to ASA for primary cardiovascular prevention where the literature suggests limited cardiovascular benefit with significant increase in risk of serious GI bleeding

  • (Conditional, very low) -  In ASA (for secondary cardiovascular prevention) treated patients with acute GI bleed where ASA therapy is interrupted, recommend restarting on the day (within 24 hr) of endoscopic hemostasis

    • There is some evidence of increased rate of rebleeding in those with high risk ulcers with early ASA resumption

    • recommendation does not apply to ASA for primary cardiovascular prevention where the literature suggests limited cardiovascular benefit with significant increase in risk of serious GI bleeding

Adapted from AGA guidelines. Please see full text - here

Important distinctions when reading these guidelines

• These guidelines are meant to help aid in making informed decisions, not dictate a standard of care

  • Strong Recommendation - denoted by "we recommend" 

    • Most individuals should receive this intervention 

  • Conditional Recommendation - denoted by "we suggest"

    • Different choices may be appropriate based on patient preference. Employ shared decision making and consider using decision aids

• Quality of evidence 

  • High - Significant confidence that the true effect lies close to that of the estimate of the effect

  • Moderate - Moderate confidence. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low - Limited confidence. The true effect may be substantially different from the estimate of the effect.

  • Very low - Very little confidence. The true effect is likely to be substantially different from the estimate of effect

Summary

Bleeding Related Questions

• Unable to reach a recommendations

  • Unable to recommend for or against the use of visco-elastic testing (VET) to predict bleeding risk prior to procedure in patient with stable cirrhosis due to limited evidence.

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - In patients with stable cirrhosis undergoing common gastrointestinal procedures (ex. paracentesis, thoracentesis, variceal banding, colonic polypectomy, ERCP, and liver biopsy), recommend against extensive preprocedure testing of PT/INR or PLT 

    • No direct evidence that PT/INR or PLT accurately predicts bleeding risk in cirrhosis

    • bleeding risk affected by multiple factors (AKI, advanced CTP cirrhosis, presence of acute on chronic liver failure) and PLT cutoff alone may not be sufficient to predict bleeding risk

  • (Conditional, very low) - In patients with stable cirrhosis undergoing common gastrointestinal procedures (ex. paracentesis, thoracentesis, variceal banding, colonic polypectomy, ERCP, and liver biopsy), recommend against routine use of blood products (FFP or PLT) for bleeding prophylaxis

    • low vs high risk procedures determined based on 1.5% threshold for procedure-related bleeding risk

    • unable to determine threshold for severe thrombocytopenia or coagulopathy. recommend use of clinical judgement

    • when considering transfusion of blood products must consider the cost, short half-life, and risk of alloimmunization along with other adverse reactions 

  • (Conditional, very low) - In patients with stable cirrhosis undergoing common gastrointestinal procedures, recommend against routine use of thrombopoietin receptor agonists (TPO-RA) for bleeding prophylaxis 

    • Must balance the risk of thrombosis with TPO-RA therapy (~1% for avatrombopag and lusutrombopag)

Thrombosis Related Questions

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - In hospitalized patients with cirrhosis who otherwise meet standard guidelines for the use of VTE prophylaxis, prophylaxis is recommended over no anticoagulation.

  • (Conditional, very low) - In patients with cirrhosis, routine screening for PVT is not recommended.

    • May consider screening in patients who place a lower value on the risks of anticoagulation therapy if PVT is found

    • The clinical relevance of nontumoral PVT is unclear though increased mortality and graft failure has been noted in patients with PVT who undergo liver transplant

    • Limited data on treatment outcomes for PVT, though there is evidence to suggest increased rates of recanalization in those treated with anticoagulation

  • (Conditional, very low) - In patients with cirrhosis and acute or subacute nontumoral PVT, treatment with anticoagulation is recommended over no anticoagulation

    • No anticoagulation may be considered in patients who place a higher value on avoiding the risks of anticoagulation therapy

    • There is limited evidence showing that anticoagulation may lead to increased rates of recanalization with decreased bleeding (perhaps due to reduced portal pressure and subsequent reduction in incidence of variceal bleeding)

    • There is no evidence to suggest benefit of one anticoagulant over another

  • (Conditional, very low) - In patients with cirrhosis and atrial fibrillation, treatment with anticoagulation is recommended over no anticoagulation

    • No anticoagulation may be considered in patients with advanced cirrhosis and low CHA2DS2-VASC who place a higher value on avoiding the risks of anticoagulation therapy and a lower value on reducing the risk of stroke

Adapted from ACG guidelines. Please see full text - here

• Recommendations regarding management of pain in gastroparesis (GP) were not provided in these guidelines. In general opioid, including tramadol (retards orocecal transit) and tapentadol (retards gastric emptying), should not be used as these can worsen gastroparesis

Important distinctions when reading these guidelines

• These guidelines are meant to help aid in making informed decisions, not dictate a standard of care

  • Strong Recommendation - denoted by "we recommend" 

    • Most individuals should receive this intervention 

  • Conditional Recommendation - denoted by "we suggest"

    • Different choices may be appropriate based on patient preference. Employ shared decision making and consider using decision aids

• Quality of evidence 

  • High - Significant confidence that the true effect lies close to that of the estimate of the effect

  • Moderate - Moderate confidence. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low - Limited confidence. The true effect may be substantially different from the estimate of the effect.

  • Very low - Very little confidence. The true effect is likely to be substantially different from the estimate of effect

Summary

Risk Factors

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests optimal glucose control in diabetic gastroparesis to reduce risk of gastroparesis aggravation

    • Hb A1C is associated with the 4 hr retention value on nuclear gastric emptying (GE) scan

Diagnostic Testing

• Strong recommendation, moderate quality of evidence

  • (Strong, moderate) - Scintigraphic gastric emptying (SGE) is the gold standard for documenting presence of delayed GE. ACG suggests  assessing emptying of a solid meal over 3 hours or more. 

    • The study should be continued for up to 4 hr unless more than 90% of the solid meal has emptied at 3 hr.

    • Delayed gastric emptying = 10% retention at 4 hr

    • Avoid medications that may affect study results for 48 hr prior (opioids, cannabinoids, prokinetics, antiemetics, neuromodulators)

    • Meta-analysis shows testing in this way results in a significant association of delayed GE with nausea

      • In those with DM, delayed GE is associated with early satiety and fullness but not with nausea and vomiting 

• Conditional recommendation, very low quality of evidence

  • (Conditional, very low) - Radioopaque markers (ROM) testing is not suggested for diagnostic evaluation in GP patients  with upper GI symptoms

    • There is evidence to show that scintigraphy testing correlates with GI symptom severity while ROM testing does not

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests wireless motility capsule (WMC) testing may be an alternative to SGE for the evaluation of GP patients with upper GI symptoms

    • In those without DM - higher proportion of delayed GE was detected with WMC compared to SGE

    • In those with DM - higher proportion of delayed GE was detected with SGE compared to WMC

    • WMC also provides a measure of gastric and small bowel contractile amplitude which can be assessed along with the timing of capsule emptying (pH change as capsule passes the gastric pylorus) to assess for other motility disorders

    • GP symptoms may not be correlated with WMC transit

  • (Conditional, low) - ACG suggests stable isotope (13C-spirulina) breath test is a reliable test for the evaluation of GP in patients with upper GI symptoms

    • Also approved for use in children

Dietary Interventions

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests management should include a small particle diet to increase the likelihood of symptoms relief and enhance gastric emptying

    • Stepwise progression from oral nutrition -> jejunal nutrition -> parenteral nutrition

    • Also monitor for eating disorders given common avoidant/restrictive patterns

Pharmacologic Interventions

• Conditional recommendation, low quality of evidence

  • (Conditional, low) - ACG suggests