Good News from the Bad News Department: Outcomes of Intestinal Transplantation in Patients with Crohn’s Disease

Briefly noted:  A recent retrospective study (BN Limketkai et al. Clin Gastroenterol Hepatol 2016; 14: 1574-81) examined outcomes of 142 patients with Crohn’s disease (CD) out of a total of 1115 cases of intestinal transplantation.  The authors examined the Scientific Registry of Transplant Recipients. Since intestinal transplantation would be a very undesirable outcome in patients with CD, I titled this post as coming from the “Bad News Department.”  The good news is that in the last 15 years, patients with CD disease do not appear to have worsened outcomes compared to patients without CD.  Overall, during the period 1990-2014, the risk of graft failure was higher, mainly due to the initial 10 years.  Graft failure was 18.6% at 1 year, 38.7% at 5 years, and 49.2% at 10 years in patients with CD compared with 14.1%, 32.1% and 41.0% in non-CD patients.  The cumulative risk of death at 10 years for CD patients was 59.7%.

My take: It is good that intestinal transplantation outcomes for CD patients are now similar to all patients.  In addition, intestinal transplantation outcomes are improving. Nevertheless, there is still a high death rate over 10 years.

High Endoscopy Complication Rate After Intestinal Transplantation

A recent study (J Yeh et al. JPGN 2015; 61: 636-40) indicated a high rate of endoscopy complications in pediatric patients who have undergone intestinal transplantation.

Key points:

  • Complications: In this single-center study with 1770 endoscopies (1014 sessions), the serious GI complication rate was 1.8% (32/1770).  The complications included 11 GI perforations, 13 GI bleeds, 6 GI hematomas, 1 gastric mucosa avulsion, and 1 distention from retained air. The authors’ database was not designed to capture cardiopulmonary complications.
  • In comparison, the authors note that adults without intestinal transplantation have an estimated a perforation rate of 0.09% and serious complication rates (GI and non-GI complications) of 0.15% for upper endoscopy and of 0.2% for colonoscopy. In addition, a large pediatric study of non-transplant patient endoscopies, found a perforation rate of 0.014% for EGDs and 0.028% for colonoscopies. Thus, the authors are reporting a perforation rate (11 of 1770) that is more than 20-fold higher than this pediatric study’s colonoscopy perforation rate.
  • Their techniques are well-described. For example, “for ileoscopies, 2 to 3 sites each consisting of 2 to 3 biopsies were also taken every 5 to 10 cm from the distal graft…typically surveyed up to 50 to 60 cm from the ostomy or ileocolonic anastomosis.”
  • The reasons for endoscopy were most frequently related to diarrhea/stool output in 35% and for surveillance in 32%.
  • The other interesting finding was that “of histology-proven rejections, 45% had normal-appearing endoscopies.”

The authors recommend that patients with intestinal transplantation should have endoscopy at a specialized center with teams who are intimately familiar with these children.

My take: I worry that the high complication rates reported at this center may indicate that individuals (perhaps in training) who are less familiar with the patient’s anatomy are performing many of these endoscopies.  I think individuals very familiar with the patient’s anatomy are best-suited to perform these endoscopies; this may limit some individuals at these specialized centers and may include some skilled endoscopists outside of intestinal transplant centers.

Related blog postSomething Bad is Going to Happen | gutsandgrowth

Galapagos

Galapagos

 

Stick with the (intestinal) rehab program?

More data on the progress of treatment of short bowel syndrome (SBS) programs:

  • Avitzur J, et al. JPGN 2015; 61: 18-23

In this study, the researchers from Toronto and the Group for Improvement of Intestinal Function and Treatment (GIFT) retrospectively examine 84 patients over 3 time periods: 1999-2002, 2003-2005, and 2006-2009.

Key points:

  • Across those time periods, the authors find fewer SBS patients that needed to be listed for transplantation despite similar baseline characteristics.  In addition, many more patients in the late period were removed from the transplant waiting list due to clinical improvement.
  • Another important finding was a drop in mortality (15% vs >60%) and a shift from previous causes like liver failure and sepsis to death from other comorbid conditions.
  • “Since 2009, we have performed only 1 IT [intestinal transplant].”  They note this is a worldwide trend with ~50% reduction in pediatric IT since 2008.
  • Even with ultrashort bowel (small bowel length <30 cm), there are reports that “50% of these patients achieved PN independence within 2 years.”  As such, this is a declining indication for IT listing. In this study, ultrashort bowel was the reason for listing in 11% in the last period compared 21% in the first time period.

Why is this happening?

The authors credit the intestinal rehab program (IRP) for this impact along with specific management changes including new lipid emulsions/lipid minimization to reduce IFALD, use of ethanol locks to reduce bloodstream infections, and bowel reconstructive procedures (e.g. STEP).

Briefly noted: Merras-Salmio L, Pakarinen MP. JPGN 2015; 61: 24-9. This second retrospective study (n=48) from Finland reinforces the view of improvements in cholestasis  and prognosis from 1988-2014.  Similar strategies, as noted above, were implemented in SBS management protocols.

Bottomline: The outlook has improved for SBS.  While this is good news, at the same time, there will be less pediatric gastroenterologists with extensive intestinal transplantation experience.

In Wyoming often there are stretches of nearly deserted highways

In Wyoming often there are stretches of nearly deserted highways

Related blog posts:

Race Associated with Outcomes in Intestinal Failure

The best preparation for tomorrow is to do today’s work superbly well”  –William Osler (quote cited in NEJM 2014; 371: 1565-66).

The quote above is not directly related to today’s post but I liked it a lot.

While race “encompasses social, economic, and cultural issues,” it is a marker for health outcomes including in children with intestinal failure (JPGN 2014; 59: 537-43). This Pediatric Intestinal Failure Consortium study retrospectively analyzed 272 subjects, though 22 did not have adequate data regarding race.  In this cohort, there were 204 white and 46 nonwhite children.

Key findings:

  • Nonwhite children were more likely to die without an intestinal transplant (P<0.001). At 48 months after entry criteria were met, cumulative probability of death without an intestinal transplant was 0.40 for nonwhite children compared with 0.16 for white children.
  • Nonwhite children were less likely to receive an intestinal transplant (P=0.003). At 48 months after entry criteria were met, cumulative probability of receiving an intestinal transplant was 0.07 for nonwhite children compared with 0.31 for white children.

These findings held up when examined for biological factors like low birth rate and reason for intestinal transplantation; other factors that were accounted for included evidence of liver disease, residual bowel length, and whether child had received care at an intestinal transplantation center.  Even factors like receiving breast milk in the nursery were similar between the two groups.

Bottomline: Nonwhite race appears to be a marker for poor outcomes in children with intestinal failure.  Based on this retrospective data which examined multiple factors, the reasons do not have a biological basis.  As such, issues like barriers to treatment/access to care, social support, parental education, and cultural differences need to be considered.

 

Omega-3 Fatty Acids, Lipid Emulsions, and Hepatic Pathology

Many have advocated for the use of parenteral fish oil lipids like Omegaven which are rich in omega-3 polyunsaturated fatty acids (O3FAs), though the data in support of them are limited (New lipid emulsions — lacking data to support usage ).

A recent study (J Pediatr 2014; 165: 59-64) identified seven liver-inclusive intestinal transplants who had received O3FAs.   This retrospective review study took place between 2003-2012.  These seven patients had received O3FAs for a mean of 62% of their total life span before transplant.  While these patients almost all had resolution of cholestasis (mean total bilirubin 0.7 mg/dL at time of transplant), advanced fibrosis (stage 3 or 4) was noted on explant pathology.  The histologic inflammatory scores were lower (P=.056) in comparison to O6FA group.

The authors make several important points:

  • The “results provide additional evidence that the improvement in hyperbilirubinemia following O3FA substitution therapy does not consistently produce histologic recovery of the liver.”
  • This study does not address whether comparable improvements could have been obtained from lipid restriction among the O6FA group.
  • Only 1 of 20 studies of O3FA lipid emulsion in PNALD includes hepatic histopathology as an outcome measure.

This is not the first study that indicates that liver fibrosis may persist and progress on O3FA therapy (J Pediatr 2010; 156: 327-31, J Pediatr Surg 2010; 45: 95-9, JPGN 2013; 56: 364-9).

Bottomline: Continued investigation of O3FA emulsions in PNALD is needed and assessing liver histology may be needed prior to intestinal transplantation.

Related blog posts:

 

NASPGHAN Preview

I had a few free minutes so I decided to take a look at a bunch of upcoming lectures from the 2013 NASPGHAN upcoming meeting.  With electronic media, it is easy to take a quick glance.  Here’s the master link to all of the following talks:

Annual Meeting page.

Some of the power point lectures that I’ve seen so far:

  • Is my PPI dangerous for me? Eric Hassall MBChB, University of British Columbia One point in his slides that I had not seen much about was a hypothesis that PPI use may predispose to the development of eosinophilic esophagitis by allowing food proteins to be more intact ( attributed to Merwat, Spechler. Am J Gastro ’09).  He explains that “acid reflux” is a clever marketing term and has a slide with Madmen actors.  If there is “acid,” one must need acid suppression.
  • My child doesn’t go to school Lynne Walker MD, Vanderbilt University.  Lynne shows an interesting fax from a parent that asks if the problem is physical, how will she help? And, if it is psychological, how can this be remedied?  She outlines a lot of pain theory and indicates that parents need to become health coaches, avoid catastrophizing (?spelling), and encourages mental health evaluation.  Use the parents words ‘I’m going to refer xxx for relaxation and stress management.’
  • My child’s H. pylori will not go away – (the resistant bug) Benjamin Gold MD, Children’s Center for Digestive Healthcare. Ben manages to stuff so much information into his talk.  His talk is like one of those clown cars where more and more people keep coming out.  He has slides with worldwide resistance maps, slides with treatment regimens and algorithms, and the reasons for treatment failure. Perhaps I can convince him to give a live preview.
  • Administrative/executive functioning Richard Colletti MD, Fletcher Allen Healthcare. Offers personal and pragmatic advice for career advancement.  His slides indicate that he started his GI fellowship at age 40.  One of his quotes, “80% of success is showing up” (Woody Allen) is definitely true.  It’s pretty much akin to what I learned about success in medical school.  You need the three As: availability, affability, and ability.  My mentor said the first was what people needed most.
  • The changing face of intestinal transplantation
    Simon Horslen MD, Seattle Children’s Hospital.  Lecture notes that number of intestinal transplants have decreased dramatically, particularly in children. In 2012, only about 100 intestinal transplants were performed whereas it had peaked at nearly 200.  Much of the credit is due to intestinal rehabilitation work and adjustments in parenteral nutrition (eg. lipid minimization, line care).  Two most common reasons for intestinal transplantation at this time are gastroschisis and volvulus.
  •  Gluten sensitivity: Fact or fiction Alessio Fasano MD, MassGeneral Hospital for Children. This blog has covered a lot of the same material, but Alessio’s slides are pretty impressive.  Also, I was not aware that Lady Gaga consumes a gluten-free diet
  • Controversies in parenteral nutrition Christopher Duggan MD, Boston Children’s Hospital.  This lecture provides a timely update on nutrient deficiencies due to component shortages and discusses lipid minimization compared with fish oil-based lipid emulsions.
  • Vitamin D and immunity James Heubi MD, Cincinnati Children’s Hospital and Medical Center.  In the beginning of the slides, Jim provides a very user-friendly definition of an expert and a suitable picture.  He indicates that in 2011 there were 3746 vitamin D publications but inexplicably only chooses to review a tiny fraction.

At the time of this posting, I haven’t had a chance to look through these talks: