NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #215

Medicare Coverage for Home Parenteral Nutrition: Policy Change After Almost Four Decades

October 2021 • Volume XLV, Issue 10
Penny Allen

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In November 2020, the Durable Medical Equipment Medicare Advisory Contractors retired the policies known as Local Coverage Determinations (LCDs) for home parenteral and enteral nutrition. On September 5, 2021, new LCDs take effect after almost four decades of no change or updates to home nutrition support coverage criteria for Medicare beneficiaries. This article briefly reviews the historical challenges of the retired parenteral nutrition (PN) policy and highlights what the new policy means, specifically for patients requiring PN support at home and the providers that care for them.

INTRODUCTION

I am sorry, your patient does not meet the Medicare criteria for home parenteral nutrition”, was a common refrain whenever physicians and case managers were trying to set up home parenteral nutrition for a Medicare beneficiary.

A number of publications, abstracts, and reports from national home parenteral nutrition (HPN) providers have documented that qualifying patients for HPN coverage under Medicare historically showed a success rate of < 15%, due to an outdated, now retired, parenteral nutrition (PN) policy or Local Coverage Determination (LCD).1-4

One of the first abstracts published in 2007 reported that only 16% of 133 Medicare HPN referrals received by a national infusion provider (with a large geographically and medically diverse sample) met the government’s HPN policy requirements for coverage.1 Almost 10 years later, a different national infusion provider with similar referral statistics demonstrated that even fewer Medicare beneficiaries (10.5% of 95) referred for HPN met the restrictive policy requirements, leaving few options for beneficiaries unless they had a secondary major medical insurance policy.2 A third national infusion provider reported in 2019, that out of an estimated 400 Medicare PN referrals only 13% met criteria for HPN coverage,3 with many unable to receive care due to lack of documentation and/or required testing, the same reasons reported by a separate PN provider in 2016.4

This article provides the clinician with an update of recent changes to Medicare HPN policy and a review of what is required for coverage as of September 5, 2021, when the new LCDs for PN and enteral nutrition (EN) were implemented by the Durable Medical Equipment Medicare Advisory Contractors (DME MACs).5,6 After the former policies were retired in November 2020 and until the new LCDs were implemented September 5th, coverage was based on the longstanding 1984 National Coverage Determination (NCD) focused on permanence and “reasonable and necessary” criteria, not the long list of tests and studies previously required. Atleast one national provider reports improved access to HPN for beneficiaries since the original LCDs retired (63% of 238 Medicare HPN referrals qualified for coverage November 12, 2020 through June 2021).7 The new PN LCD is based on the premise of the original NCD language and the provisions of the Prosthetic Device Benefit, bringing hope for somewhat better access to HPN moving forward.

Whether a patient has Medicare or any other insurance provider, the recommendation stands that if there is a possibility that a patient may require HPN post discharge, the planning process should start immediately. The healthcare team and patient/ beneficiary must be made aware of what is required to secure coverage and assure a safe transition to the home setting.

Background

Medicare, the federal healthcare program enacted by Congress as part of Title 18 of the Social Security Act of 1965, is the largest health insurance program in the United States.

For more than 35 years PN and EN therapies have been covered under the Prosthetic Device Benefit within the Part B Durable Medical Equipment and Prosthetics/Orthotics and Supplies

(DMEPOS) benefit.8

“Parenteral Nutrition is covered under the Prosthetic Device benefit (Social Security Act § 1861(s) (8)). Parenteral nutrition is covered for a beneficiary with permanent, severe pathology of the alimentary tract which does not allow absorption of sufficient nutrients to maintain weight and strength commensurate with the beneficiary’s general condition.” The analogy utilized by the Centers for Medicare and Medicaid Services or CMS, is that PN and EN via a tube and/or the devices to administer these therapies replace an organ or function of an organ that is permanently impaired, serving as a prosthesis. If an impairment of the gastrointestinal or “alimentary” tract as CMS

refers to it, “permanently” (previously defined in the retired LCD as > 3 months) prevents the patient from receiving nutrients into the GI tract (enteral) or absorbing nutrients from the GI tract (parenteral) to maintain weight and strength commensurate with health status; and this is documented and supported with objective data in the medical record, then Medicare may cover home PN or EN along with related accessories and/or supplies. 

Highlights and History of Advocacy Efforts

Medicare PN policies have not kept up with clinical paradigms, best practices, and nationally accepted standards for the appropriate utilization of HPN.9- 11 Organizations including the American Society for Parenteral and Enteral Nutrition (ASPEN), the National Home Infusion Association (NHIA), and the Oley Foundation have lobbied CMS and the DME MACs for decades in an attempt to update and/or change the law in support of meaningful home infusion therapy benefits for Medicare beneficiaries.

CMS created the first and only National Coverage Determination (NCD) for PN and EN in 1984, the same year ASPEN organized a key group of members into a Public Policy/Advocacy Committee under the direction of the late Executive Director, Barney Sellers.12

In 2008 ASPEN regrouped and reorganized the mission of this Public Policy and Advocacy Committee, with the charge to set a new agenda and develop initiatives related to public policy and advocacy surrounding nutrition support. Efforts regarding HPN reimbursement and access to care at that time were focused on the Medicare Home Infusion Act in its various iterations, by appealing to Congress to pass legislation which would allow Medicare beneficiaries access to home infusion therapy, similar to all other payers.

This was done in partnership with NHIA and the Digestive Disease National Coalition (DDNC). Advocacy efforts to update HPN and HEN policies focusing on the “permanence” aspect of the Prosthetic Device Benefit were unsuccessful. Current research backed by the European Society for Clinical Nutrition and Metabolism had been published with common indicators for HPN.13 The consensus in the recommendations included the need for expert care, but not the need

for HPN permanence. The “permanence” issue alone has created significant access challenges for decades for those patients who may require shorter courses of home therapy resulting in either lack of coverage for home PN or EN, or longer hospital stays to complete therapy at a much higher cost; with beneficiaries assuming they had home coverage through the Medicare system.12 In 2014 ASPEN surveyed physicians, healthcare providers, home infusion vendors and patients about how healthcare reform was affecting their ability to provide or access nutrition care. One major finding was that 72% of home care company respondents reported that they had to discharge patients from service because of insurance issues.14 As a result of the survey, ASPEN partnered with NHIA to file a “Reconsideration to Policy” with the DME MACs to communicate updated clinical research related to restrictive aspects of the HPN criteria, and to

provide recommendations for modifying the PN LCDs. Ongoing challenges for HPN coverage included:

  • requiring a fecal fat test to prove malabsorption
  • use of an albumin level as a marker of protein status, and
  • mandating a tube feeding trial for “moderate abnormalities” including partial small bowel obstruction
  • radiologic reports to prove “complete mechanical small bowel obstruction”

The reply from the DME MACs was that they saw no reason to change the coverage criteria in the previous PN LCD.

Five years later, the LCD Reconsideration Process – Medical Policy Article changed, allowing for greater transparency when Reconsiderations are filed.15 This, together with a change in medical leadership within the DME MACs, prompted a renewed collaboration between NHIA and ASPEN to once again revisit an attempt to update the PN LCD, which has historically prevented 85-90% of Medicare beneficiaries from receiving “reasonable and necessary” HPN. A subcommittee of ASPEN subject matter experts convened, researched current literature to support changes to the PN LCD and a pre-Reconsideration hearing was scheduled for July 2020. A representative from both NHIA and ASPEN met with DME MAC medical directors and presented their recommendations.

As a result of that meeting, on October 8, 2020, the DME MACs released a statement that the existing LCDs for PN and EN were being retired effective November 12, 2020, “due to the evolution of clinical paradigms”.16

We Have New Policies for Coverage, but What Really HAS NOT Changed?

When the former PN and EN LCDs were retired in November, the DME MACs issued new Billing and Coding documents for each therapy 17,18 during the interim period of November 2020 through September 2021. These documents provided some of the same information previously included in the retired LCDs (billing codes, guidance for calories, protein, units of fat allowed, etc.). Early in 2021, the DME MACs drafted and posted new proposed PN and EN LCDs19 and invited live and written commentary from providers. Many groups including ASPEN, NHIA, the Healthcare Nutrition Council, the Oley Foundation, and individual home PN and EN providers submitted comments in April 2021 which contributed to the final version of the new nutrition LCDs. The original 1984 NCD remains the overarching general policy regarding coverage for HPN and HEN8 at this time even with the new LCDs rolled

out; however, there is current discussion regarding updating or retiring the 1984 NCD which contains some outdated information and language.

Criteria for HPN coverage moving forward remains based on the following two premises:

  1. “Test of Permanence”: PN and EN LCDs remain under the Prosthetic Device Benefit, so the “permanent impairment” of the gastrointestinal or “alimentary” tract criteria prevails i.e., permanence defined as “long and indefinite”. In the new LCD, there is no defined timeframe as there was in the retired LCD where it stated, “ordinarily 3 months or longer”. The treating practitioner must document an estimated length of need for PN or EN therapy in the medical record prior to discharge; if the medical judgment and medical record supports that PN therapy

is for temporary or short-term utilization, then PN or EN therapy will not be covered. The prescriber should be as clear as possible documenting the estimated length of need, for example: 2 weeks, 2 months, 4 months, a year, lifetime etc. The length of need must be truthful and in the best judgment of the practitioner – even if it means there will be no coverage. The chart needs to support a prosthesis/ permanent impairment of the GI tract, so if the patient only needs PN for 2 more weeks, 4-6 more weeks etc.? This is not a permanent impairment and would not be covered. With the new LCD, there is no specific timeframe stated to meet coverage—only that the chart needs to support the “long and indefinite” language and the permanent impairment.

  1. The medical record must provide evidence that PN is “reasonable and

necessary” as defined by CMS below:

“Parenteral nutrition is covered for a beneficiary with permanent, severe pathology of the alimentary tract which does not allow absorption of sufficient nutrients to maintain weight and strength commensurate with the beneficiary’s general condition”.20 There are no specifics for testing or evidence required in the new LCD other than documentation in the medical record must support the above policy statements. Clinicians need to fully document the patient diagnosis, indication and rationale for PN. In other words, clearly tell the story of what the disease process or diagnosis is, how it is affecting nutrient absorption, why does the patient require PN and how long will they need it at home (estimate as accurately as possible) – so that any non-clinician can understand. Medicare requires that therapy be “reasonable and necessary”, and the record must reflect that there is a permanent impairment of the intestinal tract that is not allowing absorption of nutrients, this is the CMS definition of reasonable and necessary. For example, there would likely be no coverage of HPN for clinical situations where enteral therapy would be indicated such as upper GI cancers, neurological impairments, esophageal or gastric outlet obstructions. In these scenarios if there is functioning small bowel capable of absorbing nutrients, PN would probably not be covered.

What Has Changed?

  1. More (not all) Medicare beneficiaries will have access to HPN (Table 1).

The new PN LCD opens with the premise that “When nutritional support other than the oral route is necessary, enteral nutrition (EN) is usually initially preferable to parenteral nutrition…” leading to a new documentation requirement from the treating practitioner stating that enteral nutrition has been considered and is not possible.

“For parenteral nutrition to be considered reasonable and necessary, the treating practitioner must document that enteral nutrition has been considered and ruled out, tried and been found ineffective, or that EN exacerbates gastrointestinal tract dysfunction”.”20

From the author: if a tube feeding failed or cannot be used because it is unsafe or inappropriate then documentation in the record should reflect that, so the prescriber should document in detail why enteral is not able to be used vs. just stating that it cannot be tried with no explanation. Two case examples:

  1. “Patient has ovarian cancer with a partial bowel obstruction due to carcinomatosis tumor burden. Enteral tube feeding is not possible at this time due to tumor involvement; it is estimated she will need PN for at least 4 more months.”
  2. “Patient has been trialed on an enteral formula, but the rate cannot be advanced beyond 30mL/hour without exacerbating nausea and vomiting.  The patient will require PN for the next 3 months at least, and most probably, the rest of his/her life.
  1. The treating practitioner (prescriber who made decision to initiate PN i.e., MD/NP/ PA) is required to evaluate the beneficiary within 30 days of initiation of parenteral nutrition vs. prior to the initial certification or required recertification. (This was the language in the retired PN LCD).  If the treating practitioner does not see the beneficiary within this timeframe, they must document the reason why and describe what other monitoring methods were used to evaluate the beneficiary’s PN needs. There must be documentation in the medical record supporting the clinical diagnosis.20
  2. The elimination of former Situations A-H in the retired LCD which mandated certain studies that were either outdated or not possible, such as:
    • Use of albumin as marker of nutritional status (previously needed to be less than 3.4gm/dL)
    • 72-hour fecal fat testing to prove malabsorption (most institutions do not prescribe 50-100gm fat diets and 72-hour quantitative stool collections to diagnose fat malabsorption)
    • Mandatory trial of enteral feeding without an allowance for appropriateness or safety if the patient had a moderate abnormality.

Under the “Nutrient” section of the LCD, the protein and lipid ranges increased, which will decrease the amount of documentation required by the prescriber. The treating practitioner must document the medical necessity for protein orders outside the range of 0.8-2.0 gm/kg/day (formerly 0.8-1.5 gm/kg/day); dextrose concentration less than 10%; or lipid use per month in excess of the product-specific FDA-approved dosing recommendations (formerly a maximum of 1500 gm/month).20 For example, if the dosing recommendation in the prescribing information (PI) for a lipid product says 1.0 gm/kg/day for adults, then a 70 kg patient could be prescribed up to 70 gm* lipid/day, or an 85 kg patient could receive 85 gm* lipid/day—without the prescriber having to document why the monthly total grams exceeds 1500.

 *Serieseditor: = 350mL and 425mL 20% IV lipids respectively.

When Planning a PN Discharge, What Should Providers be Aware Of?

The selection of HPN infusion providers who are knowledgeable and compliant with Medicare policies and federal laws can protect beneficiaries from financial hardship down the road. Some companies will accept Medicare HPN referrals quickly and without a thorough assessment, then later discontinue care when they learn there is no reimbursement because they do not have necessary documentation to meet coverage criteria, such as a length of need for home PN for a long

and indefinite timeframe in the medical record or a permanent impairment of the GI tract that is not allowing nutrient absorption. If an infusion provider quickly accepts a Medicare HPN case without a complete review of documentation prior to discharge, it should be a red flag to the prescriber/referral source. Qualified reputable HPN providers should offer consultative guidance in the way of a “records review” or checklist of qualifying questions (Table 2) at the time of referral to help physicians navigate the complexity and changes to policy with the ultimate goal of protecting the patient. 

During open enrollment time periods, physicians and HPN providers should guide patients to investigate all insurance options including Medicare Advantage or Replacement plans which may offer more meaningful benefits if a patient requires HPN or other home infusion therapies. Although not ideal, Medicare beneficiaries still have full coverage for PN in a skilled nursing facility (SNF), so if they do not have coverage because of a shorter length of need, the patient will have coverage for PN in the SNF setting. 

CONCLUSION

After 35+ years, the restrictive, obsolete, and thankfully retired Medicare nutrition support policies have been somewhat updated. There is collective optimism for the receptiveness of the DME MACs to consider updated nutritional research, evidence-based science, current consensus papers, and clinical paradigms when making policy decisions.

With the NCD still serving as the overarching policy, advocacy efforts to either eliminate or update its language will continue, allowing more beneficiaries who need HPN to qualify for home coverage. Inherent restrictions of the Prosthetic Device Benefit will continue to restrict coverage for Medicare beneficiaries without a “permanent” impairment and until this requirement changes, some beneficiaries will require treatment in a much higher cost care setting or pay for therapy out of pocket.

All providers involved in the care of patients requiring home infusion, particularly HPN, should fully understand Medicare reimbursement regulations to advocate for better access to life sustaining home nutrition support without significant patient financial risk. For additional resources and information, see Table 3 and Table 4.

References

  1. Allen P. Medicare TPN coverage criteria: How many patients actually meet criteria? Nutr Clin Pract. 2007;22(1):106. [Abstract].
  2. Allen P. Medicare parenteral nutrition policy 20 years later: need for change when 9 out of 10 do not qualify for benefits. Clinical Nutrition Week 2016, American Society for Parenteral and Enteral Nutrition (ASPEN), Austin, TX. Abstract S21:25.
  3. Weihl H. A Retrospective Analysis of Medicare Referrals Requiring Home Parenteral Nutrition. P20, p.571, 2021. https://aspenjournals. onlinelibrary.wiley.com/doi/full/10.1002/jpen.2095. Accessed 9/14/21.
  4. Kinder LM. Medicare Part B and Home Parenteral Nutrition Coverage: How Often Is Objective Evidence Available? Clinical Nutrition Week 2016, American Society for Parenteral and Enteral Nutrition (ASPEN), Austin, TX. Abstract S10:14. (Available through ASPEN website.)
  5. CGS Administrators, LLC and Noridian Healthcare Solutions, LLC, Local Coverage Determination (LCD) Enteral Nutrition
    (L33783) Effective: 10/1/2015 Revision: 1/1/2020, Retirement Date: ANTICIPATED 11/12/2020.
  6. CGS Administrators, LLC and Noridian Healthcare Solutions, LLC, Local Coverage Determination (LCD) Parenteral Nutrition (L33798) Effective: 10/1/2015, Revision: 1/1/2020, Retirement Date: ANTICIPATED 11/12/2020.
  7. Optum Infusion Pharmacy. National Referral Database and Medicare PN Referral Tracking. Nov.12 2020-July 31, 2021. (Optum Internal Data)
  8. https://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?NCDId=242&ver=1. Accessed 9/14/21.
  9. Worthington P, Balint J, Bechtold M, et al. When Is Parenteral Nutrition Appropriate? JPEN J Parenter Enteral Nutr. 2017;41(3):324377.
  10. Durfee SM, Adams SC, Arthur E, et al. ASPEN Standards for Nutrition Support: Home and Alternate Site Care. Nutr Clin Pract. 2014;29(4):542-555.
  11. American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors. Clinical Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients. JPEN J Parenter Enteral Nutr. 2009;33(3):255-259.
  12. Murphy L, Allen P, Bond B, et al. Home Parenteral Nutrition Reimbursement and American Society for Parenteral and Enteral Nutrition Public Policy Efforts. Nutr Clin Pract. 2018;33(3):316-324.
  13. Staun M, Pironi L, Bozzetti F, et al. ESPEN Guidelines on Parenteral Nutrition: home parenteral nutrition (HPN) in adult patients. Clin Nutr. 2009;28(4):467-79.
  14. ASPEN Public Policy Committee. Results of provider and consumer survey on nutrition therapy insurance coverage. Nutr Clin Pract. 2015;30(4):577–5.
  15. https://www.cms.gov/medicare-coverage-database/view/article.aspx? articleId=52842&ver=13&Cntrctr=272. Accessed 9/14/21.
  16. https://cgsmedicare.com/jb/pubs/news/2020/10/cope19136.html. Accessed 9/14/21.
  17. https://med.noridianmedicare.com/web/jadme/policies/ dmdarticles/2020/parenteral-nutrition-correct-coding-and-billing. Accessed 9/14/21.
  18. https://med.noridianmedicare.com/web/jadme/policies/dmdarticles/2020/enteral-nutrition-correct-coding-and-billing. Accessed 9/14/21.
  19. https://www.cms.gov/medicare-coverage-database/details/lcddetails.aspx?LCDId=38952&ver=9. Accessed 9/14/21.
  20. Local Coverage Determination (LCD): Parenteral Nutrition
    (L38953). 2021. CMS National Coverage Policy. CMS Pub. 10003 (National Coverage Determinations Manual), Chapter 1, Section 180.2. https://www.cms.gov/medicare-coverage-database/view/lcd. aspx?lcdid=38953. Accessed 9/14/21.

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FRONTIERS IN ENDOSCOPY, SERIES #75

Double Balloon Enteroscopy: Current Status and Indications

October 2021 • Volume XLV, Issue 10
Daniel L. Raines,Douglas G. Adler

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INTRODUCTION

The double balloon enteroscopy (DBE) system (Fujinon Inc., Saitama, Japan) has been available for use in the United States since 2004 following initial development by Yamamoto el al.1 This system combines an enteroscope and overtube, both equipped with latex balloons which are insufflated/deflated in alternating cycles to pleat the bowel onto the overtube. DBE technique allows for intubation in the deep small bowel with therapeutic capability and access to the entire gastrointestinal tract lumen in many cases. Evolution of Device Assisted Enteroscopy (DAE)

Following the introduction of DBE, additional technologies were developed for intubation of the deep small bowel applying the same principle of small bowel pleating. Single balloon enteroscopy (SBE) (Olympus Optical Co, Tokyo, Japan) was introduced in 2007 followed by spiral enteroscopy (SE) in 2008 (Spirus Medical LLC,

West Bridgewater, MA, USA).2,3 More recently, the NaviAid device (SMART Medical Systems Ltd., Ra’anana Israel) was approved as a throughthe-scope balloon catheter which facilitates advancement of a standard colonoscope into the deep small bowel for “balloon-guided endoscopy (BGE)”.4  An enteroscope with a motorized, spiral tip is currently in development which may decrease procedure time and increase total enteroscopy rates.5 These techniques are all collectively known as device assisted enteroscopy (DAE) procedures. Double Balloon Enteroscopy Equipment DBE requires a base Fujinon endoscopy processor and light source combined with a balloon pump controller and DBE enteroscope (Figures 1a,1b,1c). The utilization of DBE in the U.S. has been somewhat limited by the prevalence of Olympus endoscopy equipment compared to that of Fujinon. In facilities in which an Olympus or other non-Fujinon system is already in use, it may be challenging to justify the capital expense of a second endoscopy system for this specialized procedure.

available in a standard, 200cm length with 3.2mm (therapeutic) accessory channel (EN-580T) as well as a shorter, 155cm length with a 3.2mm accessory channel for altered anatomy ERCP procedures (EI580BT). The 3.2mm channel, as well as the 2.8mm channel found in older models (EN-450T5), allows for passage of nearly all standard instruments.6 A slim-version 200cm enteroscope (EN-580XP) is also currently available for pediatric procedures. This model has a reduced diameter but a smaller accessory channel.

• Additional Equipment

A pressure-regulated air pump controls the exchange of air to and from the balloons for insufflation/deflation. This pump system includes tubes and diaphragms which are multiuse. Carbon dioxide insufflation of the small bowel lumen has been found to increase insertion depth while decreasing symptoms of abdominal distension postprocedure compared to examinations using air.7,8 Therefore, a CO2 controller should be employed. Complementary equipment for DBE includes a Fujinon ST-10 balloon setting tool (Figure 2a), Zutron stiffening device (Figure 2b) and instrument cap with irrigation port (Figure 2c).

Other Considerations

The choice of sedation is dependent on the length of the procedure, patient characteristics and individual preference. Endotracheal intubation is often appropriate for long anterograde DBE procedures while moderate sedation is safe for retrograde exams and shorter anterograde exams. Fluoroscopy is no longer commonly used as a complement to DBE but may be beneficial in select cases.

Standard Performance of DBE

Double balloon enteroscopy may be performed via anterograde or retrograde route. Total enteroscopy rates (TER) for DBE range from 16-86% with a pooled rate of 44% reported in a recent, large meta-analysis.9,10 Although total enteroscopy is achievable through anterograde DBE alone, it is most commonly accomplished using a combination of anterograde and retrograde approaches with a submucosal ink tattoo placed at the maximal insertion site of the initial approach. Total enteroscopy rates with DBE are impacted by Figures 1a, 1b, & 1c. Fujinon endoscopy processor & light source (1a), balloon pump controller (1b) and enteroscope (1c) *with permission from Fujinon*

small bowel pathology as well as access to the diverted stomach and ampulla in patients with surgically altered anatomy. It has also been shown to be effective in completing difficult colonoscopy examinations such that the adoption of DBE for this indication has expanded over time. A list of DBE indications is included in Table 2.

There are several conditions in which DBE has little or no demonstrated utility but is often contemplated. DBE is not routinely indicated in the evaluation of patients with disorders of gutbrain interaction (DGBIs), formerly functional gastrointestinal disorders (FGIDs).17 Small bowel obstruction due to adhesions or intestinal carcinomatosis is not managed with DBE, although one series of 4 cases has been published describing

the benefit of push enteroscopy in treating early post-operative bowel obstruction.18 DBE is not indicated to exclude a diagnosis of small bowel Crohn’s disease after negative video capsule endoscopy (VCE) as VCE has a high negative

predictive value for this indication.19

  • Small Bowel Bleeding

DBE has a diagnostic yield of up to 60-80% in cases of suspected small bowel bleeding. VCE produces a similar diagnostic yield for this indication but is less invasive.9 Therefore, DBE is generally recommended after abnormal VCE as a therapeutic procedure to treat identified bleeding sources. DBE is indicated after normal VCE in patients under the age of 50 as small bowel tumors may be missed by VCE in 18% of cases.20,21 (Figures 3a & 3b)

DBE is also indicated after normal VCE in patients older than age 50 who experience continued blood loss as evidence by a drop in hemoglobin by > 4gm/dl or overt bleeding.9,22 Finally, DBE may be required to evaluate the pancreatobiliary intestinal limb and diverted stomach for bleeding sources in patients with altered anatomy such as long Rouxen-y gastric bypass.23 (Figures 4a & 4b)

  • Abnormal Small Bowel Imaging

In patients with small bowel ulceration observed on VCE, DBE is often required to obtain tissue samples to confirm a diagnosis of Crohn’s disease, NSAID enteropathy or small bowel lymphoma. (Figures 5a, 5b, 5c) DBE may be performed as an alternative to VCE in patients with suspected small bowel Crohn’s disease who are at high risk for capsule retention. Abnormal small bowel imaging of the small bowel is also an indication for DBE when suggestive of a new diagnosis of small bowel tumor or other pathology. (Figures 6a & 6b)

  • Altered Anatomy ERCP

Altered anatomy ERCP is an indication for DBE which requires a specialized skillset and equipment. The reported success rates of DBE-assisted ERCP in surgically altered anatomy varies by type of post-surgical anatomy. Success rates of up to 100% have been reported with DBE-ERCP in cases of Billroth II, Whipple pancreaticoduodenectomy and short-limb Roux-en-y anatomy. In patients with long-limb Roux-en-y anatomy, success rates for cannulation are much lower at 60-84%. (Figure 7) When considering DBE-ERCP, it is important to appreciate that the risk of post-ERCP pancreatitis is higher in altered anatomy ERCP due to challenging cannulation which often requires pre-cut sphincterotomy.24,25,26

The utility of DBE and other DAE methods in facilitating biliary access in long-limb Rouxen-y gastric bypass (RYGP) anatomy, has recently been studied head-to-head with alternative methods such as laparoscopic-assisted ERCP (LA-ERCP) and EUS-assisted transgastric ERCP (EDGE). In a recent cohort study comparing DAE-ERCP, LAERCP and EDGE in 130 patients, DAE-ERCP was successful in only 59% of patients in comparison with success rates of 98% for LA-ERCP and 100% for EDGE. EDGE was also associated with shorter

hospitalization and fewer adverse events.27 Many therapeutic endoscopists have adopted EDGE as their method of choice for biliary access in patients with long-limb RYGP as a result of this and similar studies.28

• Foreign Body Removal

Foreign bodies may be removed from the deep small bowel using DBE, including retained video capsules, motility capsules, self-expandable metal stents, intragastric bariatric balloon, dentures and other objects.29 A pooled success rate of 86.5% was reported in one large review of video capsule retrieval by DBE. Anterograde approach and jejunal location were predictors of success compared to retrograde approach and ileal location. The performance of DBE for video capsule retrieval also reduced the need for surgery for benign strictures and helped define strictures due to malignancy.30 Video capsule retention may be considered as a positive event in cases in which retention aids in localization of pathology. (Figure 8) Finally, DBE has a limited role in dilation of strictures of the small bowel related to Crohn’s disease, NSAID enteropathy or other benign etiologies.31 (Figures 9a, 9b & 9c) Intestinal Polyposis

Surveillance of intestinal polyposis syndromes including Peutz-Jeghers Syndrome (PJS) and Familial Polyposis (FAP) is an infrequent indication for DBE due to the rarity of these conditions. In patients with PJS, prophylactic resection of hamartomatous small bowel polyps >10mm in size may decrease the risk of repeated laparotomy require to treat intussusception, obstruction or bleeding.32,33,34 (Figures 10a & 10b) Each laparotomy increases the risk of future surgeries as well as risk of complications such as short bowel and intestinal obstruction due to adhesions.35 DBE may be useful in the surveillance of adenomatous polyps of the proximal small bowel in FAP.36 Balloon-Assisted Colonoscopy Double-balloon enteroscopy equipment has proven to be valuable in the completion of colonoscopy after failure of colonoscopy with standard equipment. A 2017 meta-analysis of 18 studies, including a total of 667 patients, described a successful completion

rate of >97% with DBE.37 A more recent study of 122 cases produced similar results with a 92% completion rate.38

Comparison of DAE Techniques

DBE, SBE, SE and BGE may all be considered for the above indications with advantages, disadvantages and limitations with each technique. Comparison trials have been performed for several of these indications which are useful for reference. However, the primary deciding factors in selection of DAE technique are: availability of the required equipment in the endoscopy unit and experience of the endoscopist. A summary of important comparisons are listed in Table 3.

  • Total Enteroscopy Rate (TER) Total enteroscopy with DBE using a combination of anterograde and retrograde exams was reported as achievable in 86% of patient in the initial study.1 Although TERs have been lower in subsequent studies, DBE has been demonstrated to outperform SBE, SE and BGE in this regard. The average TER with DBE is 34% compared to 12% with SBE and 3% with SE, considering data from across multiple studies.39,40,41,42,43
  • Procedure Time

Average procedure time with anterograde DBE is significantly longer at 76 +/- 6min compared to 60 +/- 10min for anterograde SBE and 41 +/- 4min for anterograde SE. Procedure times for retrograde DBE are also longer than SBE and SE.44

  • Diagnostic Yield

The diagnostic yield of device-assisted enteroscopy is similar across all techniques at ~40 – 60% despite differences in TER.45,46,47 Lack of correlation between diagnostic yield and TER may be related to inclusion of upper GI tract abnormalities when calculating diagnostic yield for anterograde enteroscopy. The overall diagnostic yield of push enteroscopy ranges from 20-80% but half of abnormalities are found within reach of a standard gastroscope. Distribution of pathology within the small bowel may also explain similar diagnostic yield across techniques.48 Angioectasias, the most common pathology found on DAE, are most frequently observed in the proximal 1/3

of the small bowel which is within reach of all anterograde enteroscopy techniques.49 (Figure 11a & 11b). The diagnostic yield of anterograde DAE is comparatively higher than that of retrograde DAE likely for these same reasons.50

  • Altered Anatomy ERCP

Successful completion of DAE-ERCP appears to be equal between DBE, SBE and SE techniques when studied in all types of surgically altered anatomy.28 There is a practical advantage to using a short (155cm) model enteroscope, now available for DBE and SBE, as it allows for the use of all accessories of standard length. For the challenging indication of DAE-ERCP in long limb surgical bypass, DBE, SBE and SE were compared within a cohort of 129 patients. Cannulation by DAE-ERCP was successful in 63% of cases overall with similar success rates between all three methods.51 These results are consistent with previous studies of DBE, SBE and SE in the performance of DAE-ERCP.

  • Device-Assisted Colonoscopy

The success rate of colonoscopy with DAE equipment approaches 100% in individual as well as comparison studies regardless of DAE technique. The largest comparison study of double balloon and single balloon technique for colonoscopy in patients with previous incomplete exams using standard equipment demonstrated success rates of 93% & 100%, respectively with each method.52

Spiral enteroscopy and through-the-scope balloon catheters have also been utilized with success in completion of difficult colonoscopy cases.

CONCLUSION

The advent of double balloon enteroscopy in Japan (2001) then in the U.S. (2004) was an important milestone in gastrointestinal endoscopy as this technology allows for access to the entire small bowel for therapeutic intervention. This procedure is well tolerated and low risk, especially when compared to intraoperative enteroscopy. DBE equipment is currently utilized for a variety of endoscopic indications in addition to the common indication of small bowel bleeding. Although additional technologies for DAE have been subsequently developed, DBE has an advantage over other DAE techniques in regard to rate of total enteroscopy. The performance of DBE in the U.S. may be inhibited by availability of Fujinon endoscopy systems. However, the DBE system should be considered as an essential tool for centers which manage a significant volume of patients with small bowel bleeding or other small bowel pathology.

References

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  2. Hartmann D, Eickhoff A, Tamm R, Riemann JF. Balloon-assisted enteroscopy using a single-balloon technique. Endoscopy 2007;39 Suppl 1:E276.
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  4. Ali R, Wild D, Shieh F, et al. Deep enteroscopy with a conventional colonoscope: initial multicenter study by using a through-the-scope balloon catheter system. Gastrointest Endosc 2015 Nov; 82(5):855-860.
  5. Beyna T, Arvanitakis M, Schneider M et al. Total motorized spiral enteroscopy: first prospective clinical feasibility trial. Gastrointest Endosc 2021 Jun;93(6):1362-1370.
  6. Lo SK, Medhizadeh S. Therapeutic uses of double-balloon enteroscopy. Gastrointest Endosco Clin N Am 2006;16:363-376.
  7. Domagk D, Bretthauer M, Lenz P et al. Carbon dioxide insufflation improves intubation depth in double-balloon enteroscopy: a randomized, controlled, double-blind trial. Endoscopy 2007:39:1064-1067.
  8. Dellon ES, Hawk JS, Grimm IS et al. The use of carbon dioxide for insufflation during GI endoscopy: a systematic review. Gastrointest Endosc 2009;69:843-849.
  9. Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding. Am J Gastroenterol 2015;110(9):1265-1287.
  10. Xin L, Liao Z, Jiang Y, Li ZS. Indications, detectability, positive findings, total enteroscopy, and complications of diagnostic double-balloon endoscopy: a systematic review of data over the first decade of use. Gastrointest Endosc 2011;74(3):563-570.
  11. Gross S, Stark M. Initial experience with double-baloon enteroscopy at a US center. Gastrointest Endosc 2008;67(6):890-897.
  12. Raines DL, Arbour A, et al. Variation in small bowel length: a factor in achieving total enteroscopy? Digestive Endoscopy 2015;27(1):67-72.
  13. Acosta R, Abraham NS, Chandrasekhara V et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc 2016;83(1):3-16.
  14. Raines DL, Spera M, Bollinger E. The safety and efficacy of deviceassisted enteroscopy in the setting of thienopyridine antiplatelet therapy. J Clin Gastroenterol 2017;51(1):e1-e4.
  15. Heine GD, Madithi M, Groenen MJ et al. Double-balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease. Endoscopy 2006; 38(1):42-48.
  16. Gralnek IM. Complications of diagnostic colonoscopy, upper endoscopy, and enteroscopy. Best Pract Res Clin Gastroenterol 2016; 30: 705–718.
  17. Lacy BE, Mearin F, Chang L et al. Bowel Disorders (Rome IV). Gastroenterology 2016;150:1393–1407.
  18. Gersin KS, Ponsky LJ, Fanelli RD. Enteroscopic treatment of early postoperative small bowel obstruction. Surg Endosc 2002;16:115–116.
  19. Jensen MD, Nathan T, Rafaelsen SR, Kjeldsen J. Diagnostic accuracy of capsule endoscopy for small bowel crohn’s disease is superior to that of MR enterography or CT enterography. Clinical Gastroenterology and Hepatology 2011;9:124-129.
  20. Huprich JE, Fletcher JG, Alexander JA et al. Obscure gastrointestinal bleeding: evaluation with 64-section multiphase CT enterography-initial experience. Radiology 2008; 246: 562-571.
  21. Raines DL, Hutchings JJ. Evaluation of obscure gastrointestinal bleeding after a negative capsule endoscopy. In Capsule Endoscopy by Case Study. Ed. Daniel Raines. Ambris Publishing. 2012
  22. Gurudu SR, Bruining DH, Acosta RD. The role of endoscopy in management of suspected small bowel bleeding. Gastrointestinal Endoscopy 2017;85(1):22-32.
  23. Skinner M, Peter S, Wilcox CM, Mönkemüller K. Diagnostic and therapeutic utility of double-balloon enteroscopy for obscure GI bleeding in patients with surgically altered upper GI anatomy. Gastrointest Endosc 2014; 80:181-186.
  24. Emmett DS, Mallat DB. Double-balloon ERCP in patients who have undergone Roux-en-Y surgery: a case series. Gastrointest Endosc 2007;66: 1038-1041.
  25. Schreiner MA, Chang L, Gluck M, et al. Laparoscopy-assisted versus balloon enteroscopy-assisted ERCP in bariatric post-Roux-en-Y gastric bypass patients. Gastrointest Endosc 2012;75:748-756.
  26. Siddiqui AA, Chaaya A, Shelton C, et al. Utility of the short double balloon enteroscope to perform pancreaticobiliary interventions in patients with surgically altered anatomy in a US multicenter study. Dig Dis Sci 2013; 58: 858-64
  27. Wang TJ, Cortes P, Jirapinyo P, et al. A comparison of clinical outcomes and cost utility among laparoscopy, enteroscopy, and temporary gastric access-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Surgical Endoscopy 2020; Sept 4.
  28. Barakat M, Adler DG. Endoscopy in patients with surgically altered anatomy. Am J Gastroenterol 2021;116(4):657-665.
  29. Kim J, Lee BJ, Ham NS et al. Balloon-assisted enteroscopy for retrieval of small intestinal foreign bodies: a KASID multicenter study. Gastroenterol Res Pract 2020:3814267.
  30. Gao Y, Xin L, Wang YX et al. Double-balloon enteroscopy for retrieving retained small-bowel video capsule endoscopes: a systematic review. Scandinavian Journal of Gastroenterology 2020;55(1):105-113.
  31. Despott EJ, Gupta A, Burling D et a. Effective dilation of small-bowel strictures by double-balloon enteroscopy in patients with symptomatic Crohn’s disease. Gastrointest Endosc 2009:70(5):1030-1060.
  32. Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lip and digits: a syndrome of diagnostic significance. N Engl J Med 1949;241:1031-1036.
  33. Gao H, Van Lier MG, Poley JW et al. Endoscopic therapy of small-bowel polyps by double-balloon enteroscopy in patients with Peutz-Jeghers syndrome. Gastrointest Endosc. 2010 Apr;71(4):768-773.
  34. Wang YX, Dian DJ, Zhu HY et al. The role of double-balloon enteroscopy in reducing the maximum size of polyps in patients with Peutz-Jeghers syndrome: 12-year experience. J Dig Dis 2019;20(8):415-420.
  35. Cunningham JD, Vine AJ, Karch L, et al. The role of laparoscopy in the management of intussusception in the Puetz-Jeghers syndrome: case report and review of the literature. Surg laparosc Endosc 1998;8:17-20.
  36. Mönkemüller K, Fry LC, Ebert M, et al. Feasibility of double-balloon enteroscopy-assisted chromoendoscopy of the small bowel in patients with familial adenomatous polyposis. Endoscopy 2007;39(1):52-57.
  37. Tan M, Lahiff C, Bassett P et al. Efficacy of balloon overtube-assisted colonoscopy in patients with incomplete or previous difficult colonoscopies: A meta-analysis. Clin Gastroenterol Hepatol 2017; 15:1628-1630.
  38. Robertson A, Koulaouzidis A, Yung D, et al. Balloon-assisted colonoscopy after incomplete conventional colonoscopy. Journal of Clinical Medicine 2020;9:2979-2981.
  39. May A, Farber M, Aschmoneit I et al. Prospective multicenter trial comparing push-and-pull enteroscopy with single- and double- balloon techniques in patients with small-bowel disorders. Am J Gastroenterol 2010;105:575581.
  40. Wadhwa V, Sethi S, Tewani S et al. A meta-analysis on efficacy and safety: single-balloon vs. double-balloon enteroscopy. Gastroenterol Rep 2015;3:148-155.
  41. Lipka S, Rabbanifard R, Kumar A et al. Single vs. double balloon enteroscopy for small bowel diagnostics: a systematic review and meta-analysis. J Clin Gastroenterol 2015;49:177-184.
  42. May A, Manner H, Aschmoneit I et al. Prospective, cross-over, single center trial comparing oral double-balloon enteroscopy and oral spiral enteroscopy in patients with suspected small bowel vascular malformations. Endoscopy 2011;43:477-483.
  43. Despott EJ, Murino A, Bourikas L et al. A prospective comparison of performance during back-to-back, anterograde manual spiral enteroscopy and double-balloon enteroscopy. Dig Liver Dis 2015; 47: 395-400.
  44. Lenz P, Domagk D. Double- vs. single-balloon vs. spiral enteroscopy. Best Pract Res Clin Gastroenterol 2012;26:303-313.
  45. Rondonotti E, Spada C, Adler S, May A, Despott EJ, Koulaouzidis A, Panter S, Domagk D, FernandezUrien I, Rahmi G, Riccioni ME, van Hooft JE, Hassan C, Pennazio M. Small-bowel capsule endoscopy and deviceassisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy 2018;50:423-446.
  46. Moschler O, May A, Muller MK et al. Complications in and performance of double-balloon enteroscopy (DBE). Results from a large prospective DBE database in Germany. Endoscopy 2011;43:484-489.
  47. Noujaim MG, Parish A, Raines DL et al. Use, Yield, and Risk of Device-assisted Enteroscopy in the United States: Results From a Large Retrospective Multicenter Cohort. J Clin Gastroenterol 2020;Sept 17.
  48. Chauhan SS, Manfredi MA, Dayyeh BKA et al. Enteroscopy.
  49. Gastrointestinal Endoscopy 2015;82(6): 975-990.
  50. Bollinger EA, Saitta P, Raines DL. Distribution of bleeding intestinal angioectasias. World of Journal of Gastroenterology 2012;18(43):62356239.
  51. Sanaka MR, Udayakumar N, Kosuru B, et al. Antegrade is more effective than retrograde enteroscopy for evaluation and management of suspected small bowel disease. Clinical Gastroenterology and Hepatology 2012;10:910-916.
  52. Shah RJ, Smolkin M, Yen R. A multicenter, U.S. experience of singleballoon, double-balloon, and rotational overtube-assisted enteroscopy ERCP in patients with surgically altered pancreaticobiliary anatomy. Gastrointestinal Endoscopy 2013;77(4):593-600.
  53. Dzeletovic I, Harrison ME, Pasha SF, et al. Comparison of single- versus double-balloon assisted-colonoscopy for colon examination after previous incomplete standard colonoscopy. Dig Dis Sci 2012;57:2680–2686.

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DISPATCHES FROM THE GUILD CONFERENCE, SERIES #41

Update on Colon Polyp Surveillance

September 2021 • Volume XLV, Issue 9
David Lieberman

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The benefits of surveillance colonoscopy after removal of adenomas have been uncertain. Recommendations for surveillance intervals have previously relied on studies which determined the risk of advanced adenomas after colonoscopy, as a surrogate of colorectal cancer (CRC). Over the past few years, new studies with CRC endpoints have emerged. The evidence that high-risk adenomas (defined as adenomas >10mm, or with villous histology or high-grade dysplasia) are associated with a high risk of CRC during surveillance is strong. These are individuals most likely to benefit from surveillance colonoscopy at relatively short intervals. Low-risk adenomas (defined as 1-2 tubular adenomas <10mm) are associated with a low risk of CRC, which is similar to the risk in patients with no adenomas. These patients may not need surveillance. New recommendations highlight the importance of a high-quality baseline exam as the cornerstone of surveillance interval recommendations.

INTRODUCTION

Colon polyp surveillance is part of the colorectal low-risk adenomas (LRA) defined as 1-2 tubular cancer (CRC) screening continuum. As more adenomas <10mm, and there is growing evidence patients are screened, more adenomas are that the risk of CRC in such patients is low. detected and surveillance is recommended. This Therefore, many patients undergoing surveillance information informs 2020 recommendations from the US Multi-Society Task Force (USMSTF) on CRC.2 In addition to understanding how the biology of polyps detected at the initial baseline colonoscopy impacts subsequent CRC risk, there is also increased awareness of the impact of the colonoscopy quality on the risk of CRC after colonoscopy. This review will focus on this new data. 

Why Should Surveillance be Considered?

It would be wonderful if a single colonoscopy eliminated the risk of CRC, but that is not the case. The true risk of post-colonoscopy CRC is uncertain. Cancer registry studies look back at a cohort with CRC and ask: how many of these patients had a colonoscopy within three years in which cancer was not diagnosed? The answer is 2-9%, with the most recent study from a Danish registry with over 10,000 CRCs finding that 7% had prior colonoscopy.3 This does not prove that surveillance will necessarily confer benefit, but it establishes that CRC does develop after colonoscopy – either related to biology, quality of the baseline exam or both.

Biology:

Risk of CRC After Removal of LRA and HRA There is new evidence establishing the risk of CRC after polypectomy depending on the baseline findings (Table 1). Combined, these studies reveal that individuals with baseline HRA have

a 2 to 4 fold increased risk of CRC during follow-up, compared to individuals with LRA or no adenomas.4-6 This finding confirms the relevance of HRA, and justifies an intensive regimen of surveillance for individuals with HRA. For individuals with LRA, the risk is similar to those with no adenomas, and therefore, the benefits of surveillance are less clear. These patients account for more than 65% of adenoma-bearing patients, representing a substantial colonoscopy burden. The lower risk is reflected in the USMSTF recommendations for less intensive surveillance (7-10 year interval). It is entirely possible that such patients could be reentered into routine screening after 10 years and enjoy a similar benefit as surveillance.7

In addition to standard adenomas, there is growing evidence of the importance of the sessile serrated polyp (SSP) pathway in the development of CRC. This pathway may account for 10 to 15% of CRCs. In the spectrum of post-colonoscopy CRC, features of the SSP pathway are twice as common compared to CRCs discovered at baseline exam. Li et al.8 found that SSPs >10mm were associated with a significantly higher risk of CRC within 3-5 years, compared to individuals with small proximal or distal SSPs. Therefore these lesions should be managed like classical HRA with a three year interval for surveillance.2 Table 2 provides summary of the USMSTF recommendations.

What about continued surveillance after the first surveillance exam? Five relevant studies were reviewed by USMSTF,2 and the consistent conclusion was that the presence of a HRA either at baseline or during the surveillance period identified a high-risk individual. The data do not include studies with CRC endpoints, so this “high” risk refers to the risk of developing more HRA.

Update on Colon Polyp Surveillance

Nevertheless, when combined with the new data about HRA noted above, intensive follow-up is likely to be beneficial if patients have HRA at some point in the surveillance continuum. These recommendations are summarized in Table 3. Impact of Quality on Surveillance

Over the past few years, there has been growing evidence that quality of the baseline colonoscopy impacts post-colonoscopy outcomes. Corley et al.9 demonstrated an inverse correlation between adenoma detection rate (ADR) and risk of postcolonoscopy CRC. Kaminski et al.10 found a similar inverse relationship, and also showed that if ADR was improved, rates of post-colonoscopy CRC declined. Lam et al.11 confirm this inverse relationship between ADR and post-colonoscopy CRC incidence occurring within 36 months and also 60 months of the baseline exam.

What about CRC mortality? A new study12 found a strong relationship of overall quality (defined by cecal intubation, bowel prep and ADR) on both CRC incidence and mortality of post-colonoscopy patients. Both CRC incidence and mortality were two-fold higher in patients receiving low quality colonoscopy compared to high-quality colonoscopy. 

In addition to polyp detection, complete polyp resection is another element of quality. A new metaanalysis13 found that there was residual neoplastic tissue detected after 16-21% of polypectomies, and it is likely that this may underestimate the true rate of incomplete resection in clinical practice.

These studies confirm that quality matters, and impacts post-colonoscopy outcomes. The USMSTF recommendations acknowledge this effect by placing quality as the cornerstone of the recommendations (Table 2). High quality is defined as a complete exam to the cecum, with an adequate bowel prep (to detect lesions >5mm), complete polyp resection, performed by an endoscopist with demonstrated adequate ADR of 20% in women, 30% in men.2

HRA* defined as tubular adenoma(s) >10mm, or with villous histology or high-grade dysplasia

Legend: Follow-up of patients after the first colonoscopy surveillance, adapted from Gupta et al.2

greatest benefit of colonoscopy is derived from the baseline exam, when polyps are detected and removed. The demonstration that surveillance impacts key outcomes such as CRC incidence and mortality is uncertain. These studies would require large cohorts with very long-term followup. Decision models often fill in gaps where data is lacking. A new model7 suggests that intensive surveillance for HRA at a three-year interval results in significant CRC incidence reduction. The PLCO study14 analyzed a subset of their cohort, concluding that surveillance resulted in a 30% reduction in CRC incidence, particularly in individuals with HRA. While these studies do not prove benefit, they provide some additional evidence which supports intensive surveillance for individuals with HRA.

CONCLUSIONS New studies provide an evidence-based approach to colon polyp surveillance. There is now strong evidence that individuals with HRA at baseline colonoscopy have a risk of CRC after

baseline colonoscopy which is 2 to 4 fold higher than individuals with LRA or no adenomas at a baseline screening exam. This supports the notion that biology is important – namely, that these individuals have whatever it takes in terms of genetic predisposition and lifestyle to develop CRC, and are most likely to benefit from PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2021 surveillance. Current recommendations for a

3-year surveillance interval, would precede the development of CRC in most cases, and result in cancer prevention. Individuals with LRA have a risk of CRC similar to individuals with no adenomas. Surveillance benefit is uncertain, meaning that there is no evidence that surveillance will reduce CRC incidence or mortality in these individuals. New recommendations suggest a 7 to 10 year interval for surveillance, providing flexibility based on the quality of the baseline exam. Finally, there is new evidence that individuals with high-risk SSPs (>1cm) do have a high risk of CRC and should have more intensive surveillance, similar to those individuals with HRA. Colonoscopy quality impacts surveillance outcomes. The evidence that colonoscopy performed by endoscopists with low ADR is associated with higher risk of post-colonoscopy CRC highlights the importance of quality.  The 2020 recommendations place quality as a cornerstone of the surveillance recommendations.2

References

  1. Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;
    143: 844-857
  2. Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, Robertson DJ, Shaukat A, Syngal S, Rex DK. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020; 158: 436-440Gupta S, Lieberman D et al. Gastroenterol. 2020;115:415-434
  3. Stoffel EM, Erichsen R, Froslev T et al; Clinical and molecular charactersitcis of post-colonoscopy colorectal cancer: A population-based Study. Gastroenterol 2016; 151: 870-8
  4. He X, Hang D, Wu K et al. Long-term risk of colorectal cancer after removal of conventional adenomas and serrated polyps. Gastroenterol 2020; 158: 852-61
  5. Wieszcsy P, Kaminski MF, Franczyk R et al. Colorectal cancer incidence and mortality after removal of adenomas during screening colonoscopies. Gastroenterol 2020; 158: 875-83
  6. Lee JK, Jensen CD, Levin TR et al. Long-term risk of colorectal cancer and related death after adenoma removal in a large, community-based population. Gastroenterol 2020; 158: 884-94
  7. Meester RGS, Landsorp-Vogelaar I, Winawer SJ, et al. High-intensity versus low-intensity surveillance for patients with colorectal adenoma. A cost-effectiveness study. Ann Intern Med 2019; 171:612-22.
  8. Li D, Liu L, Fevrier HB et al. Increased risk of colorectal cancer in individuals with a history of serrated polyps. Gastroenterol 2020; 159:502-11
  9. Corley DA, Jensen CD, Marks AR et al. Adenoma detection rate and risk of colorectal cancer and death. NEJM 2014;370:1298-306
  10. Kaminski MF, Wieszczy P, Rupinski M et al. Increaed rate of adenoma detection associates with reduced risk of colorectal cancer and death. Gastroenterol 2017; 153:98-105
  11. Lam AY, Li Y, Gregory DL et al. Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program. Gastrointest Endosc 2020; 92: 355-64
  12. Pilonis ND, Bugajski M, Wieszczy P et al. Longterm colorectal cancer incidence and mortality after a single negative scrfeening colonoscopy. Ann
    Intern Med 2020; 173: 81-91 doi:10.7326/M19-2477
  13. Djinbachian R, Iratni R, Durand M et al. Rates of incomplete resection of 1-to 20-mm colorectal polyps: A systematic review and meta-analysis. Gastroenterol 2020; 159: 904-14
  14. Pinsky PF, Schoen RE. Contribution of surveillance colonoscopy to colorectal cancer prevention. Clin
    Gastroenterol Hepatol 2020; 18: 2937-44

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Medical Bulletin Board

Aspen Malnutrition Awareness Week: Helping Gi Clinicians Intervene And Treat Malnutrition

September 2021 • Volume XLV, Issue 9

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On October 4-8, 2021, the American Society for Parenteral and Enteral Nutrition (ASPEN) will launch its annual campaign to educate healthcare professionals on detecting, intervening, and treating malnutrition. The 2021 program includes live CME webinars, special interactive Zoom discussions, and a wide array of complimentary videos, podcasts, tools, and resources addressing malnutrition.

The offerings will be of keen interest to gastroenterologists, as malnourished patients have longer hospital stays, higher readmission rates, and increased hospital costs and inpatient death rates.

The American Society for Gastrointestinal Endoscopy and the Society of Gastroenterology Nurses and Associates are among the growing number of more than 110 organizations that support Malnutrition Awareness WeekTM.

Five of the live webinars, which are free to ASPEN members and supporting organizations, provide continuing medical education credits. They will be offered on the following dates:

October 4: Malnutrition Diagnosis and Documentation: Strategies for Success

October 5: Addressing Malnutrition in COVID-19 Patients: From Hospital to Home

October 6:Collaborating with NonNutrition Clinicians on Malnutrition Strategies

October 7: Ramifications of Nutrient Shortages in the Neonatal Population

October 8: Applying Latest Findings from Notable Malnutrition Publications to Your Practice

Webinar capacity is limited so early registration is strongly recommended.

All other Malnutrition Awareness Week educational materials are available free of charge, including short, on-demand videos that will cover a range of topics including performing nutrition assessment via telehealth in inpatient and outpatient settings.

The videos, podcasts, resources, and other tools, ranging from clinician guides to patient handouts, will be released throughout September and October.

To register for the webinars and to access the complimentary resources, visit: nutritioncare.org/PG-MAW

About ASPEN

The American Society for Parenteral and Enteral Nutrition (ASPEN) is dedicated to improving patient care by advancing the science and practice of nutrition support therapy and

metabolism. It is an interdisciplinary organization whose members are involved in the provision of clinical nutrition therapies, including parenteral and enteral nutrition. With members from around the world, ASPEN is a community of dietitians, nurses, nurse practitioners, pharmacists, physicians, scientists, students, and other health professionals from every facet of nutrition support clinical practice, research, and education.

For more information about ASPEN, please visit:

nutritioncare.org

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Medical Bulletin Board

Fujifilm Unveils Advanced Image Enhancement Technology Upgrade For Eluxeo Endoscopic Imaging System At Sages 2021

September 2021 • Volume XLV, Issue 9

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This technology is the first in-market solution to enable visualization of hemoglobin oxygen saturation (StO2) levels in tissue during laparoscopic and endoluminal procedures

Lexington, Mass. – FUJIFILM Medical Systems U.S.A., Inc., a leading provider of endoscopic and endosurgical imaging technology, announces the commercial launch of the ELUXEO® 7000X System, a new video imaging technology developed to enable real-time visualization of hemoglobin oxygen saturation (StO2) levels in tissue using laparoscopic and/or endoluminal imaging.

The ELUXEO 7000X is an upgrade to the company’s ELUXEO® Endoscopic Imaging System, and was unveiled at the annual Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) conference, held August 31 – September 3 at Sands Expo Convention Center in Las Vegas Nevada. The ELUXEO Endoscopic Imaging System revolutionized endoscopic visualization when it was introduced to the U.S. market in 2018 with its proprietary 4-LED Multi-light technology. The ELUXEO 7000X System employs 5-LED technology to enable this enhanced imaging capability.

Enabling the visualization and analysis of StO2 levels helps surgeons more accurately identify potentially ischemic tissue, better positioning surgeons to address and prevent tissue necrosis.

Today’s standard for visualizing tissue perfusion is to leverage fluorescent imaging using indocyanine green (ICG) dye – a method in which an injectable dye circulates through the bloodstream and is excited using nearinfrared light. Physicians then use that excited dye to identify blood flow. Fujifilm’s innovation was developed to address potential limitations resulting from ICG:

  • Intravenous dye injections are not required prior to imaging.
  • GI tract observation time frame can be extended as liver filtration of ICG dye is no longer a factor.

In addition, ICG does not allow physicians to detect potential ischemic tissue during endoluminal procedures, making the ELUXEO 7000X the only product on the market to enable this visualization via StO2 measurements.

The technology was granted “breakthrough device” designation by the U.S. Food and Drug Administration (FDA) in September, 2020, and received 510(k) clearance from the FDA on June 30, 2021.

The endosurgical research team at Fujifilm has been working closely on clinical usage of the technology with key opinion leaders from top medical centers in the United States and Japan.

“I find the ELUXEO 7000X System to be a game changing technology in the fields of MIS and endosurgery,” says Paul Curcillo, MD, FACS, Department of Surgical Oncology, Division of Minimally Invasive Surgery, Fox Chase Cancer Center. “The ability for real-time assessment of StO2 allows me to identify tissue necrosis

  • Intravenous dye injections are not required prior to imaging.
  • GI tract observation time frame can be extended as liver filtration of ICG dye is no longer a factor.

In addition, ICG does not allow physicians to detect potential ischemic tissue during endoluminal procedures, making the ELUXEO 7000X the only product on the market to enable this visualization via StO2 measurements.

The technology was granted “breakthrough device” designation by the U.S. Food and Drug Administration (FDA) in September, 2020, and received 510(k) clearance from the FDA on June 30, 2021.

The endosurgical research team at Fujifilm has been working closely on clinical usage of the technology with key opinion leaders from top medical centers in the United States and Japan.

“I find the ELUXEO 7000X System to be a game changing technology in the fields of MIS and endosurgery,” says Paul Curcillo, MD, FACS, Department of Surgical Oncology, Division of Minimally Invasive Surgery, Fox Chase Cancer Center. “The ability for real-time assessment of StO2 allows me to identify tissue necrosis

without factoring in time restrictions and the need for consumables. In addition, we can use it in any laparoscopic case we are doing with our existing ELUXEO endoscopic imaging system.”

“Our ELUXEO product portfolio is engineered to revolutionize conventional minimally-invasive and endoluminal procedures and to raise the standard of patient care,” said Taisuke Fujita, vice president, Endoscopy Division, FUJIFILM Medical Systems U.S.A. “Fujifilm continues to draw on our traditional medical imaging and optical expertise to meet today’s needs of surgeons across the entire clinical spectrum.”

Same suite, single cart

The Fujifilm ELUXEO System allows minimally invasive and endoluminal procedures to be performed in the same suite using a single tower, reducing the amount of valuable space needed in the OR. 

“The American Board of Surgery now requires surgeons to be trained in flexible endoscopy, powering the rise in surgeons’ use of less invasive endoluminal techniques,” added Fujita. “The ELUXEO Endoscopic Imaging System is a surgical device disruptor, empowering enhanced procedural workflow, and optimizing space in surgical suites.” The ELUXEO Endoscopic Imaging System is uniquely engineered with 4-LED Multi-light technology, combining brilliantly clear white light imaging with Linked Color Imaging

(LCI®) and Blue Light Imaging (BLI) modes. The result is unparalleled image clarity and visualization in full high definition to enhance observation, improve detection, and enable full characterization. Surgeons using LCI can clearly see and distinguish anatomical structures of tissue, fat, and vessels to more accurately and precisely determine incision placement.

About Fujifilm

FUJIFILM Medical Systems U.S.A., Inc. is a leading provider of unrivaled diagnostic imaging products and medical informatics solutions that meet the evolving needs of healthcare facilities today and into the future.

Medical imaging solutions span digital radiography (DR), detectors, portables and suites, mammography systems with digital breast tomosynthesis, computed tomography solutions for oncology and radiology applications, as well as technologically advanced flexible and surgical endoscopy solutions. Fujifilm enables interoperability through its Systems Integration offering as well as its comprehensive, AI-supported Synapse® Enterprise Imaging portfolio, which includes the TeraMedica Division of Fujifilm. FUJIFILM Medical Systems U.S.A., Inc. is headquartered in Lexington, Massachusetts. For more information please visit healthcaresolutionsus.fujifilm.com.   FUJIFILM Holdings Corporation, Tokyo, Japan, brings cutting edge solutions to a broad range of global industries by leveraging its depth of knowledge and fundamental technologies developed in its relentless pursuit of innovation. Its proprietary core technologies contribute to

the various fields including healthcare, highly functional materials, document solutions and imaging products. These products and services are based on its extensive portfolio of chemical, mechanical, optical, electronic and imaging technologies. For the year ended March 31, 2021, the company had global revenues of $21 billion, at an exchange rate of 106 yen to the dollar. Fujifilm is committed to responsible environmental stewardship and good corporate citizenship.

For more information, please visit: fujifilmholdings.com

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Medical Bulletin Board

Phathom Pharmaceuticals Submits Two Ndas to U.S. Fda for Vonoprazan-based Treatment Regimens for the Treatment of H. Pylori Infection

September 2021 • Volume XLV, Issue 9

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Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a late clinical-stage biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal diseases, announced that it has submitted two new drug applications (NDAs) to the U.S. Food and Drug Administration (FDA) for the use of vonoprazan in combination with amoxicillin and clarithromycin (vonoprazan triple therapy) and vonoprazan in combination with amoxicillin (vonoprazan dual therapy) as a treatment for Helicobacter pylori (H. pylori) infection in adults. With current standard of care therapies, H. pylori eradication rates have declined in the U.S. If approved, vonoprazan-based treatments offer two new therapeutic options that have demonstrated superior eradication rates as compared to standard of care lansoprazole-based triple therapy.  “The submission of these NDAs is the first step towards addressing the declining H. pylori eradication rates in the U.S. and providing new potential treatment options for the millions of H. pylori sufferers in need of more efficacious treatments,” said Azmi Nabulsi, M.D., Chief Operating Officer at Phathom. “Today’s announcement underscores Phathom’s commitment to changing the treatment landscape for acid-related diseases. If approved, patients and healthcare providers would have two novel options to combat this highly prevalent bacterial infection. We look forward to working with the FDA to advance these vonoprazan-based treatment regimens toward approval. If approved, we anticipate launch in the U.S. in the second half of 2022.”

These NDAs are based on the positive data previously announced from Phathom’s pivotal Phase 3 PHALCON-HP trial, the largest U.S. registrational trial ever conducted for H. pylori. The study evaluated eradication rates of H. pylori infection using vonoprazan triple therapy and vonoprazan dual therapy compared to lansoprazolebased triple therapy. Vonoprazan triple therapy and vonoprazan dual therapy successfully met the study’s primary non-inferiority endpoints and all secondary endpoints, demonstrating superior eradication rates versus lansoprazole-based triple therapy among all patients including in patients with clarithromycin resistant strains of H. pylori.

The FDA has previously designated vonoprazan triple therapy and vonoprazan dual therapy as qualified infectious disease products (QIDP) and awarded them Fast Track designation, in each case, for the treatment of H. pylori infection. In connection with the NDA submissions, Phathom requested Priority Review, which, if granted, will shorten the review period from 10 months to 6 months following FDA acceptance of the submissions for filing.

About Helicobacter pylori (H. pylori) infection

H. pylori is a bacterial pathogen that is estimated to infect over 200 million individuals in the United States and Europe. Approximately 50% of the world and 36% of the US population are infected with the bacterium.1 In many cases, H. pylori is acquired in childhood and through intrafamilial transmission.2 As a result of the chronic inflammation induced by H. pylori infection, infected patients develop a range of pathologies including dyspepsia, peptic ulcer disease, gastric cancer, and mucosaassociated lymphoid tissue (MALT) lymphoma.3 Studies have found that roughly 1 in 5 patients treated for H. pylori will fail first line therapy when using standard clarithromycin triple therapy.2,4

About PHALCON-HP

PHALCON-HP was a randomized, multicenter,

Phase 3 trial that enrolled 1046 patients of which 992 patients with a confirmed H. pylori infection were randomized to one of three arms: vonoprazan 20 mg administered twice a day (BID) and amoxicillin 1g administered three times a day (TID) (n=324); vonoprazan 20 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID (n=338); and lansoprazole 30 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID (n=330). Each treatment regimen was administered for 14 days. Diagnoses of infection and test of cure were confirmed by 13C-urea breath test. Additional efficacy analyses were

conducted using the prespecified per protocol population (n=822), a subset of the mITT population comprised of patients who were protocol compliant.

About Vonoprazan

Vonoprazan is an investigational, oral small molecule potassium-competitive acid blocker (P-CAB). P-CABs are a novel class of medicines that block acid secretion in the stomach. Vonoprazan has shown the potential to have rapid, potent, and durable anti-secretory effects as a single agent in the treatment of gastroesophageal reflux disease (GERD) and in combination with antibiotics for the treatment of Helicobacter pylori (H. pylori) infection. The FDA has awarded qualified infection disease product (QIDP) status and granted Fast Track designation to vonoprazan in combination with both amoxicillin and clarithromycin and with amoxicillin alone for the treatment of H. pylori infection. Phathom in-licensed the U.S., European, and Canadian rights to vonoprazan from Takeda, which completed 19 Phase 3 trials for vonoprazan and received marketing approval in Japan and numerous other countries in Asia and Latin America.

About Phathom

Phathom Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel treatments for gastrointestinal diseases and disorders. Phathom has in-licensed the exclusive rights in the United

States, Europe, and Canada to vonoprazan, a novel potassium competitive acid blocker (P-CAB) in late-stage development for the treatment of acidrelated disorders.

For more information about Phathom, visit the Company’s website at:

phathompharma.com or follow the Company on social media: LinkedIn at:

linkedin.com/company/phathompharma and Twitter @PhathomPharma

Forward Looking Statements

Phathom cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company’s current beliefs and expectations. Such forwardlooking statements include, but are not limited to, statements regarding: the potential acceptance and approval by the FDA of our NDAs for vonoprazan; the ability of vonoprazan-based treatments to address declining H. pylori eradication rates; and our plans to commercially launch vonoprazan in the second half of 2022. The inclusion of forwardlooking statements should not be regarded as a representation by Phathom that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Phathom’s business, including, without limitation: the FDA may disagree that the existing safety and efficacy data is sufficient to accept or approve the NDAs; the inherent risks of clinical development of vonoprazan; Phathom’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of vonoprazan that may limit its development, regulatory approval and/ or commercialization, or may result in recalls or product liability claims; Phathom’s ability to obtain and maintain intellectual property protection for vonoprazan; Phathom’s ability to comply with its license agreement with Takeda; Phathom’s ability to maintain undisrupted business operations due to the COVID-19 coronavirus, including delaying or otherwise disrupting its clinical trials, manufacturing and supply chain; and other risks described in the Company’s prior press releases and the Company’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Phathom undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

  1. Hooi et al. Gastroenterology. 2017;153:420.
  2. Chey et al. Am J Gastroenterol.2017;112:212.
  3. Malfertheiner et al. Gut. 2017;66:6.
  4. Alsamman et al. Dig Dis Sci. 2019;64:2893.

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NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #214

Ileostomy and C. difficile Infection

September 2021 • Volume XLV, Issue 9
Gabriella C. Squeo,Sook C. Hoang

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Clostridioides difficile is a common cause of infectious colitis, and a less recognized cause of enteritis. There have been several reported cases of C. difficile enteritis in patients who have an end ileostomy after a total colectomy. Like colitis caused by C. difficile, C. difficile enteritis can have a wide range of clinical manifestations, ranging from diarrhea to septic shock, although the most common presenting symptom is increased ileostomy output. Risk factors include recent antibiotic use, proton pump inhibitor use, inflammatory bowel disease, and immunosuppression. Diagnosis and treatment are the same as for C. difficile colitis, as diagnosis is confirmed with stool toxin assays and first line treatment is oral vancomycin. C. difficile enteritis is a rare disease that can have a fatal outcome, and thus providers must have a high index of suspicion to reduce morbidity and mortality.

INTRODUCTION

Clostridioides difficile (CD) is a Gram-positive, end-organ failure and death. Less appreciated is its spore-forming, toxin-producing bacillus, that role as a cause of small bowel enteritis in patients is the most common etiology of nosocomial who have undergone a total colectomy with an infectious diarrhea, and antibiotic-associated end ileostomy or ileal pouch-anal anastomosis.
diarrhea.1 The incidence of C. difficile has been increasing rapidly since the early 2000s, in part due to the highly virulent NAP1/BI/027 strain.2 Lower clinical cure rates, increased recurrence rates, more severe disease, and higher 14-day mortality rates have been seen in patients infected with this strain.3

C. difficile infection (CDI) is well known to affect the colon, resulting in a large range of clinical outcomes, ranging from relatively asymptomatic diarrhea, to toxic megacolon and fulminant colitis which can result in hemodynamic instability,

As CDI enteritis is rare, much of our knowledge of the disease comes from case reports, with approximately 60 cases reported in the literature to date.2,4-22

CDI enteritis is associated with increased hospital length of stay (LOS) and health care costs, poor patient quality of life, and high mortality rate approaching 30%.2,4 This high mortality rate is likely due to delay in diagnosis given the rarity of the illness. Unfortunately, many patients are diagnosed only at the time of autopsy where pseudomembranes are identified within the small intestine.10 Luckily, with increased recognition of the disease and early diagnosis, prognosis is improving. Here, we aim to summarize the current evidence regarding CDI enteritis, specifically in the

subset of patients who have had a total colectomy and an end ileostomy, and increase awareness of this underdiagnosed, yet potentially fatal disease. Risk Factors and Pathogenesis

Risk factors for CDI enteritis include recent antibiotic and proton pump inhibitor (PPI) use, ICU or prolonged hospital stay, increasing age, immunosuppression, history of gastrointestinal surgery of the colon, and inflammatory bowel disease (IBD).4,14 Approximately 70% of patients have been found to have antibiotic usage in the 4 weeks prior to presentation, and approximately 35% have been found to have a medical condition that might lead to an immunocompromised state.2,9 Similar to colonic CDI, patients with a history of IBD are also at an increased risk of developing CDI enteritis. Approximately 40-50% of patients with CDI enteritis have a history of IBD.2,9 The abnormal gut mucosal immune response in IBD patients may play a role in increasing susceptibility to gastrointestinal infection amongst these patients.14

The pathogenesis of CDI enteritis in patients with an end ileostomy is unclear; however, several hypotheses have been suggested. There appears to be an increase in susceptibility to disease as a result of the histologic and microbiologic similarity between the small bowel and colon that may develop after a total colectomy. A competent ileocecal valve has been suggested to inhibit small bowel colonization with colonic bacterial flora. With removal of the colon and ileocecal valve, the small bowel flora changes such that the neoterminal ileum is characterized by colonic-type fecal flora, thereby making it more susceptible to overgrowth with CD.4,14 Patients with a history of CDI colitis are more susceptible to developing CDI enteritis, especially in the early postoperative phase, as a result of bacterial migration from the colon to the small bowel.14 Patients also develop colonic-type metaplasia and partial villous atrophy of the terminal end of the ileostomy as a result of alterations in fecal flow, thereby increasing its similarity to the colonic environment.2,4,8

Symptoms and Diagnosis

Patients with CDI enteritis may present with nonspecific symptoms. The most common presenting symptom amongst case reports is increased ileostomy output, which may lead to dehydration or acute kidney injury.14 Diagnosis is often missed in those with an ileostomy, as watery diarrhea is expected, especially in the immediate postoperative period. Additionally, increased ileostomy output could have several other causes, including infection and partial obstruction, etc. Other symptoms include ileus, fever, abdominal or pelvic pain, and abdominal cramping. Depending on the severity of disease and degree of dehydration, some patients may present with hemodynamic instability, including tachycardia and hypotension.4,6,10 However, many patients are non-toxic with normal vital signs, and may or may not be febrile.5,8 Physical exam findings can include diffuse tenderness without signs of peritonitis.2,4,6 Laboratory and imaging studies may aid in the diagnosis of CDI enteritis. Patients will often have leukocytosis. In severe cases, patients may have evidence of acute kidney injury and electrolyte derangements as a result of dehydration.12,18 A computed tomography (CT) scan can show findings of distended, fluid-filled small bowel in the presence of mesenteric fat stranding and free intraabdominal fluid suggestive of enteritis.19 Although this is also nonspecific, the combination of laboratory derangements, CT scan findings and patient’s symptoms should raise one’s clinical index of suspicion and aid in the diagnosis of CDI enteritis.

CDI enteritis should be considered in any patient with an ileostomy presenting with the aforementioned symptoms, especially if they have a history of recent antibiotic use, IBD, or immunosuppression. Diagnosis is confirmed by the presence of CD toxin in a stool sample by polymerase chain reaction (PCR) or enzyme immunoassay.1

Management

Management of CDI enteritis parallels that of CDI colitis, and is dictated by disease severity. The first line treatment for mild/moderate disease is a 10day course of oral vancomycin or fidaxomicin. Metronidazole is a second-line agent but should be avoided in patients with associated IBD due to poor absorption. Recurrence may be treated with For a second recurrence, one should consider fidaxomicin, pulse tapered regimen of vancomycin, or rifaximin regimen following PO vancomycin.4 Additional recurrences may necessitate consideration of a fecal microbiota transplant administered via upper endoscopy or ileoscopy through the stoma itself.4,24 As with CDI colitis, severe cases should be treated with antibiotics, supportive care and early consideration for surgical intervention.4

C. Difficile in Patients with

Ileal Pouch-Anal Anastomosis

Total colectomy with ileal pouch-anal anastomosis (IPAA), commonly referred to as a “J-pouch,” is the operation of choice for many patients with treatment-refractory ulcerative colitis, as it may cure the patient’s disease without necessitating a permanent ileostomy. Pouchitis, or inflammation of the ileal pouch, is the most common complication after IPAA, with cumulative incidence approaching 45% at 5 years.23 It can be caused by infection, recurrence of IBD, and irritation to the pouch mucosa. CDI of the ileal pouch has been recognized as a possible cause of pouchitis. Approximately 10% of symptomatic patients seen at a tertiary referral center for pouch dysfunction are diagnosed with CDI of the pouch.24

Unlike CDI enteritis, postoperative antibiotic exposure and use of immunosuppressive agents or PPIs do not appear to be associated with CDI pouchitis.24 Rather, risk factors include male gender, recent hospitalization, and pre-surgery antibiotic usage.24-26 Patients with an ileal pouch are susceptible to CDI due to similarities of the pouch with the colon at both physiological and structural levels.24 Fecal stasis within the pouch promotes gut microbial dysbiosis and colonic metaplasia of the ileal mucosa, which may predispose to CDI infection and colonization.23

Patients commonly present with abdominal

or pelvic pain and increased stool frequency.23,27,28 Diagnosis is confirmed with stool toxin assays, and endoscopic visualization by pouchoscopy may be of value.24 CDI should be considered in ileal pouch patients particularly if there is a change to their usual symptomology and if the episode of pouchitis appears to be refractory to antibiotic management.24

Testing for CDI should be considered in pouch patients presenting with fever, urgency, increased stool frequency, hematochezia, incontinence, and abdominal or pelvic pain.23

Treatment for CDI pouchitis is the same as treatment for CDI colitis and enteritis, with oral vancomycin being the first line agent. Although exploratory, fecal microbiota transplantation may be useful in severe or antibiotic-refractory cases.24 Overall, the prognosis is relatively good, and most patients are successfully treated with antibiotics; however more severe cases of CDI pouchitis have also been reported. There is one case reported in the literature that required pouch excision with conversion to ileostomy,29 and one case of fulminant CDI resulting pseudomonas aeruginosa septicemia, intravascular coagulopathy, acute renal failure, hemorrhagic ascites, respiratory failure, and eventual death.30

SUMMARY AND RECOMMENDATIONS

Although better known for causing colitis,

Clostridioides difficile is a rare cause of enteritis, particularly in patients who have undergone a total colectomy. Physicians treating patients with end ileostomies and ileal pouch-anal anastomoses should have a high index of suspicion for C. difficile infection in any patient presenting with increased stool output, abdominal cramping, and/or fever, especially if they have a history of recent antibiotic use, PPI use, inflammatory bowel disease, or an immunosuppressed state. CDI enteritis can be a highly morbid and even fatal disease, and thus prompt recognition and initiation of treatment is imperative to improve outcomes. See Table 1 for a summary of identification and management of CDI enteritis.

References

  1. Dupont HL. Diagnosis and management of Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11(10):1216-23.
  2. Dineen SP, Bailey SH, Pham TH, et al. Clostridium difficile enteritis: A report of two cases and systematic literature review. World J Gastrointest Surg. 2013;5(3):37-42.
  3. Marsh JW, Arora R, Schlackman JL, et al. Association of relapse of Clostridium difficile disease with BI/NAP1/027. J Clin Microbiol. 2012;50(12):4078-82.
  4. Aujla AK, Averbukh LD, Potashinsky A, et al. A Rare Case of Clostridium difficile Enteritis: A Common Bug in an Uncommon Place. Cureus. 2019;11(4):e4519.
  5. Causey MW, Spencer MP, Steele SR. Clostridium difficile enteritis after colectomy. Am Surg. 2009;75(12):1203-6.
  6. Freiler, JF, Durning SJ, Ender PT. Clostridium difficile small bowel enteritis occurring after total colectomy. Clin Infect Dis. 2001;33(8):1429-32.
  7. Gagandeep D, Ira S. Clostridium difficile enteritis 9 years after total proctocolectomy: a rare case report. Am J Gastroenterol. 2010;105(4):962-3.
  8. Khan MS, Levy D, Mann S. Clostridium difficile infection in the absence of a colon. BMJ Case Rep. 2010 Oct 21;2010:bcr0220102728.
  9. Kim JH, Muder RR. Clostridium difficile enteritis: a review and pooled analysis of the cases. Anaerobe. 2011;17(2):52-5.
  10. Kim KA, Wry P, Hughes E, et al. Clostridium difficile small-bowel enteritis after total proctocolectomy: a rare but fatal, easily missed diagnosis. Report of a case. Dis Colon Rectum. 2007;50(6):920-3.
  11. Kurtz LE, Yang SS, Bank S. Clostridium difficile-associated small bowel enteritis after total proctocolectomy in a Crohn’s disease patient. J Clin Gastroenterol. 2010;44(1):76-7.
  12. Lundeen SJ, Otterson MF, Binion DG, et al. Clostridium difficile enteritis: an early postoperative complication in inflammatory bowel disease patients after colectomy. J Gastrointest Surg. 2007;11(2):138-42.
  13. Nasser H, Munie S, Shakaroun D, et al. Clostridium difficile Enteritis after Total Abdominal Colectomy for Ulcerative Colitis. Case Rep Crit Care. 2019;2987682.
  14. Navaneethan U, Giannella RA. Thinking beyond the colon-small bowel involvement in clostridium difficile infection. Gut Pathog. 2009;1(1):7.
  15. Peacock O, Speake W, Shaw A, et al. Clostridium difficile enteritis in a patient after total proctocolectomy. BMJ Case Rep. 2009;2009:bcr10.2008.1165.
  16. Seril DN, Shen B. Clostridium difficile infection in the postcolectomy patient. Inflamm Bowel Dis. 2014;20(12):2450-69.
  17. Tarasiuk-Rusek A, Shah KJ. Clostridium difficile ileitis in a patient, after total colectomy. BMJ Case Rep. 2016 Feb 22;2016:bcr2015214319.
  18. Vesoulis Z, Williams G, Matthews B. Pseudomembranous enteritis after proctocolectomy: report of a case. Dis Colon Rectum. 2000;43(4):551-4.
  19. Wee B, Poels JA, McCafferty IJ, et al. A description of CT features of Clostridium difficile infection of the small bowel in four patients and a review of literature. Br J Radiol. 2009;82(983):890-5.
  20. Williams RN, Hemingway D, Miller AS. Enteral Clostridium difficile, an emerging cause for high-output ileostomy. J Clin Pathol. 2009;62(10):951-3.
  21. Yafi FA, Selvasekar CR, Cima RR. Clostridium difficile enteritis following total colectomy. Tech Coloproctol. 2008;12(1):73-4.
  22. El Muhtaseb MS, Apollos JK, Dreyer JS. Clostridium difficile enteritis: a cause for high ileostomy output. ANZ J Surg. 2008 May;78(5):416.
  23. Kayal M, Tixier E, Plietz M, et al. Clostridioides Difficile Infection Is a Rare Cause of Infectious Pouchitis. Inflamm Intest Dis. 2020;5(2):59-64.
  24. Seril DN, Shen B. Clostridium difficile infection in patients with ileal pouches. Am J Gastroenterol. 2014;109(7):941-7.
  25. Li Y, Qian J, Queener E, et al. Risk factors and outcome of PCRdetected Clostridium difficile infection in ileal pouch patients. Inflamm Bowel Dis. 2013;19(2):397-403.
  26. Shen BO, Jiang ZD, Fazio VW, et al. Clostridium difficile infection in patients with ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol. 2008;6(7):782-8.
  27. Shen B, Goldblum JR, Hull TL, et al. Clostridium difficileassociated pouchitis. Dig Dis Sci. 2006;51(12):2361-4.
  28. Mann SD, Pitt J, Springall RG, et al. Clostridium difficile infection-an unusual cause of refractory pouchitis: report of a case. Dis Colon Rectum. 2003;46(2):267-70.
  29. Martinez Ugarte ML, Lightner AL, Colibaseanu D, et al. Clostridium difficile infection after restorative proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis. Colorectal Dis. 2016;18(5):O154-7.
  30. Shen B, Remzi FH, Fazio VW. Fulminant Clostridium difficileassociated pouchitis with a fatal outcome. Nat Rev Gastroenterol Hepatol. 2009;6(8):492-5.

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RE-INTRODUCTION: LIVER DISORDERS SERIES

Re-Introduction: Liver Disorders Series

September 2021 • Volume XLV, Issue 9
Michael Babich

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In 2014, Practical Gastroenterology first introduced a series of review articles with the goal of providing a detailed review of many aspects of the management of liver and biliary diseases, intended for professionals to use as reference points in their clinical practices. Today, we re-introduce a new series of liver-related articles, to continue and expand upon this purpose.

Fostering a foundation of knowledge related to liver disease management remains a highly relevant practice for all clinicians. The CDC estimates that 4.5 million adults in the United States, nearly 2% of the population, carry a diagnosis of liver disease, which is responsible for over 44,000 deaths per year.1 The economic burden of chronic liver disease to the United States remains substantial. Considering just inpatient costs, the national hospitalization costs in patients with chronic liver disease exceeds $81 billion, while, on the ambulatory side, in considering only nonalcoholic fatty liver disease, or NAFLD, which affects roughly 100 million Americans, costs accrued by the United States healthcare system in 2018 reached $32 billion annually.2,3 While liver diseases such as chronic hepatitis B and C and hemochromatosis are now relatively easy to control and prevent progression, or cure, current management options for alcohol use disorder and NAFLD remain suboptimal, despite the high prevalence of these diseases. Consequently, the prevalence of advanced liver disease and cirrhosis remains high, with over 600,000 patients estimated to have cirrhosis in the United States.4 For many patients with decompensated cirrhosis, liver transplantation remains the only option to significantly improve mortality. The total cost billed for a liver transplant from 30 days prior to transplant to 6 months after transplant was estimated to average $577,000.5

For a practicing clinician, having a solid understanding of the diagnosis and management of liver-related conditions is essential to optimizing the care and prognoses of their patients. In most cases, early diagnosis is optimal. The goal of this series is to provide timely and relevant reviews on a variety of liver diseases, highlighting the most recent advances and management strategies published in the medical literature. We aim to provide information, and will focus our selections of topics, so as to be relevant to general gastroenterologists and primary care providers, who are on the front lines of patient care. Our first review, appearing in this issue, will detail the diagnosis and management of autoimmune liver disease variants. Future articles in this series will address topics including acute liver failure, hepatic encephalopathy, drug-induced liver injury, intrahepatic cholestasis, dietary approaches to the management of NAFLD, evaluation of solid liver lesions, and a review of newer concepts in pre- and post-liver transplant care directed towards the primary care provider.

References

  1. Summary Health Statistics Tables for U.S. Adults: National Health Interview Survey, 2018, Table A-4b, A-4c.
  2. JAMA Netw Open. 2020;3(4):e201997. doi:10.100 /jamanetworkopen.2020.1997
  3. Intermountain Medical Center. “Economic burden of fatty liver disease in US is $32 billion annually, new study finds.” ScienceDaily. www.sciencedaily.com/ releases/2018/07/180703105956.htm
  4. Journal of Clinical Gastroenterology: September 2015 – Volume 49 – Issue 8 – p
    690-696
  5. Google

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FROM THE PEDIATRIC LITERATURE

Underreporting of Nonalcoholic Fatty Liver Disease

September 2021 • Volume XLV, Issue 9

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Nonalcoholic fatty liver disease (NAFLD) is not uncommon in children and can be associated with hepatic fibrosis with the risk of long-term associated mortality. Thus, early detection is important in order to monitor disease activity and to provide resources to improve health outcomes. Children often undergo computed tomography (CT) of the abdomen for various reasons, and the authors of this study evaluated for incidental hepatic steatosis findings in a group of children undergoing CT for nephrolithiasis.

This retrospective, single-center study included patients younger than 18 years of age who underwent abdominal CT imaging for concern of nephrolithiasis over a 5-year period. Patients with known medical conditions that could cause steatosis such as metabolic/storage diseases, Wilson disease, autoimmune hepatitis, and viral hepatitis were excluded. Patients with asplenia also were excluded. Patient parameters including height, weight, age, and standard laboratory data were obtained from the electronic medical record. Liver and spleen parenchymal attenuation were measured with moderate-to-severe steatosis defined as a histologic fat concentration greater than 30%. This value (defined as “original criteria”) was obtained by using specific parameters of liver and spleen attenuation differences calculated as Hounsfield Units on CT. Mild steatosis was defined as histologic fat concentrations ≥ 5% and was determined using mDIXON-Quant magnetic resonance imaging to calculate Hounsfield Units (defined as “secondary criteria”). These two criteria categories were compared to patients who underwent CT for nephrolithiasis who did not have hepatic steatosis. Kappa statistics were used to determine degree of agreement of imaging findings between 2 radiologists. A total of 584 patients with appropriate inclusion criteria underwent abdominal CT for a diagnosis of nephrolithiasis during this period. Most patients were non-Hispanic females, and the median age of the patients was 14.8 years. The median body mass index (BMI) was at the 73rd percentile with 41% of patients being defined as overweight or obese. It was noted that 541 patients had no steatosis on imaging while 42 patients did have steatosis. The two CT criterium (“original” for moderate to severe; “secondary” for mild) used to determine steatosis demonstrated a prevalence rate of steatosis between 3%-35%. Kappa statistics between radiologists showed excellent correlation of findings. No significant difference in ethnicity was found between patients with or without steatosis. However, BMI percentiles and median serum alanine aminotransferase (ALT) levels were significantly higher in patients with any degree of steatosis compared to patients with no steatosis. Steatosis ranged between 6%-47% in those patients who were overweight or obese compared to 0.3%24% of patients with a normal BMI percentile. Additionally, steatosis was present in 11%-43% of patients with elevated ALT levels while steatosis was present in 0.7%-27% of patients with normal ALT levels. Finally, using a non-contrast CT liver attenuation value of less than 48 Hounsfield Units, only 12 of 42 patients (29%) had steatosis reported in the original radiology reports, and only 2 of these 12 patients had a known history of NAFLD.

This study suggests that steatosis can be found during CT imaging of the abdomen ordered for non-hepatic reasons. If steatosis is found, it is essential to have such patients be referred to pediatric gastroenterology to assist with diagnosis and treatment options to prevent the long-term complications of NAFLD.

Okura H, Yodoshi T, Thapaliya S, Trout A, Mouzaki M. Under-reporting of hepatic steatosis in children: a missed opportunity for early detection. Journal of Pediatrics 2021; 234: 92-98.

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FROM THE PEDIATRIC LITERATURE

Could Glucocorticoids Improve Enteral Feeding?

September 2021 • Volume XLV, Issue 9

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Short bowel syndrome (SBS) in children is a rare disease with extremely high health care costs due to long-term parenteral nutrition (PN) requirements and the potential for frequent hospitalizations. Many patients can have PN requirements reduced or can wean from PN completely if enteral nutrition can be advanced successfully. However, risk factors such as production of inflammatory mediators and bacterial overgrowth can lead to intestinal inflammation in pediatric patients with SBS, and the authors of this study looked at the potential benefit of glucocorticoids in this specific population.

This retrospective study from a medical center with expertise in pediatric intestinal rehabilitation looked at all pediatric patients with SBS at their institution who had undergone glucocorticoid therapy for intestinal inflammation diagnosed by endoscopy with biopsy. Patients on glucocorticoids for organ transplantation or food allergy therapy were excluded. Those patients with SBS and who received glucocorticoid therapy received either prednisone or budesonide. Specifically, patients with high parenteral nutrition needs initially were placed on prednisone and then tapered to budesonide with sulfasalazine. Sulfasalazine was added if colonic inflammation was present. Patients with lower parenteral nutrition needs were initially placed on budesonide and sulfasalazine, and budesonide was eventually weaned off. All patients had linear growth monitored, and bone age and bone density were checked annually. Standard laboratory data was reviewed as well.

A total of 15 patients (9 girls) were included in this study. Gastroschisis was the leading cause of SBS occurring in 10 of the patients, and the median small bowel length for this patient group was 46 centimeters with most patients having at least half of their colon length conserved. Significant bowel inflammation with associated eosinophilia was present in the biopsies of 6 patients. The median age of starting glucocorticoid therapy and the median length of time these patients were on parenteral nutrition was 3.3 years. The median time of glucocorticoid therapy was 18 months (range 1-64 months). The ability to wean parenteral nutrition occurred in 11 patients once glucocorticoid therapy was initiated, and 7 patients were able to stop parenteral nutrition. The authors noted that linear growth was not affected, and no metabolic bone disease occurred in the study group.

Although the results are encouraging, it is still unknown if glucocorticoid therapy has the potential to reduce or remove parenteral nutrition needs in pediatric patients with SBS. The exact mechanisms for improvement in such patients are unknown (including the potential of intestinal microbiome changes), and a randomized controlled trial for this type of therapy is needed.

Wang F, Gerhardt B, Iwansky S, Hobson B, Logan S, Mercer D, Quiros-Tejeira R. Glucocorticoids improve enteral feeding tolerance in pediatric short bowel syndrome with chronic intestinal inflammation. Journal of Pediatric Gastroenterologists and Nutrition 2021; 73: 17-22.

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