Esophageal Disorders: POEM in Kids, Mitomycin C for Refractory Strictures

At our recent national meeting, Dr. Peter Kahrilas indicated that POEM (Per-oral Endoscopic Myotomy) was now the treatment of choice for most adults with achalasia (#NASPGAN19 Postgraduate Course -Part 3).

A Chone et al (JPGN 2019; 69: 523-7) provide recent multicenter retrospective data on POEM in the pediatric age group (mean age 14 years), n=117.

Key findings:

  • Clinical success, defined as Eckardt score ≤3 during followup, was achieved in 90.6% of cases. The Eckardt score was >3 in 5 (4.3%) and data was missing in 6 (5.1%)
  • Adverse events included 1 case with significant bleeding, 2 cases of aspiration pneumonia (related to anesthesia), 1 esopleural fistula (managed endoscopically), and 6 mild AEs (4 mucosomtomies, 2 subcutaneous emphysema)

Additional related blog posts:

D Ley et al (JPGN 2019; 69: 528-32) provide retrospective data on 39 patients, median age 19 months, with refractory esophageal strictures which were treated with mitomycin C.  The authors considered mitomycin C after a minimum of two previous dilatations.

Key findings:

  • Etiology: The majority had strictures/stenosis associated with esophageal atresia (n=25) followed by caustic ingestion in 9.
  • Number of stenosis: The majority (n=35) had a single stenosis.
  • In 26 patients (67%), topical application of mitomycin C was considered a success based on a reduction in the number of dilatations.  In this group, the number of dilatations dropped from 102 to 17 over a comparable period.
  • 16 (41%) never required further dilatation following mitomycin C application

My take: This study provides some of the best evidence that mitomycin C may be helpful.  Long-term followup and more studies are needed.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Lincoln Park, Chicago

Endoscopic Incisional Therapy for Esophageal Strictures

MA Manfredi et al. JPGN 2018; 464-8. This retrospective chart review describes the use of endoscopic electrocautery incisional therapy as a treatment for refractory benign esophageal anastomotic strictures (n=57) from 2011-2017.

The authors define refractory as inability to achieve an adequate esophageal lumen diameter after 5 dilatations to the following:

  • Age <9 months: at least 8 mm
  • 9-23 months: at least 10 mm
  • 24 months to 5 years: at least 12 mm
  • 6 years or older: at least 14 mm

Key findings:

  • The median number of dilatations prior to EIT was 8 in the refractory group (n=36) and 3 in the nonrefractory group
  • In the 2 years following EIT the median number of dilatations was 2 in the refractory group and 1 in the nonrefractory group
  • Major complications were reported in 3 (2.3%) —>”non-contained” leak. All healed without surgical intervention. There were an additonal 4 cases of contained fluid leaks (total of 5.3% of esophageal leaks)
  • The authors had a 61% treatment success in children with refractory anastomotic strictures.  Their definition of success “no stricture resection, appropriate diameter for age, and fewer than 7 dilatations in the 2 years following the first EIT session.”
  • The authors note that patients were generally referred for stricture resection in the refractory group after the first or second EIT session IF there was not improvement in esophageal diameter.

Role of this therapy/technical aspects:

  • The authors note that this technique is particularly suited to an asymmetric stricture rather than a completely circular stricture.  With a circular stricture, typical balloon or bougie dilatations exert force equally in all directions and “will more likely tear less dense tissue adjacent to the thicker shelf.”
  • Fluoroscopy during a conventional dilatation may facillitate identification of stricture asymmmetry.
  • In the associated editorial (J Mack, MR Narkewicz) note that the technique should be limited to short (<1 cm) refractory strictures
  • In the technique for EIT, the authors note that combining EIT with balloon dilatation frequently allows a more shallow incision and likely lowers the risk of perforation.

My take: This is a promising treatment for a stubborn problem though its use will require advanced therapeutic experience. As an aside, I think their definition of success is at odds with common sense.

Related blog posts:

The first bear I saw in Banff

Work on Both Ends

Two articles provide some insight into endoscopic interventions on both ends of the gastrointestinal tract.

In the first article (JPGN 2014; 59: 608-11), the authors retrospectively studied 11 children who received mitomycin-C concurrently with endoscopic dilatation for the treatment of anastomotic strictures after esophageal atresia repair.  Key finding: 8 of 11 achieved resolution of their strictures, 2 remained with stenosis, and 1 needed surgical correction. However, the authors found no benefit of mitomycin C in the resolution of the strictures compared with endoscopic dilatation alone in historical controls (n=10). In fact, in this small study, the control group patients had fewer endoscopic dilatations (3.7 vs. 5.4 dilatations per patient) and 9 of 10 achieved stricture resolution.

In the second article (JPGN 2014; 59: 604-08), the authors retrospectively reviewed the outcome of children (n=33) with surgically-treated Hirschsprung’s disease (HD) who were treated with intrasphincteric Botox injections for obstructive symptoms. In these children with median age of first Botox injection was 3.6 years; a median of 2 injections were given.  26 (79%) had had a transanal endorectal pull-through.  Key finding: initial improvement was noted in 76% and “good/excellent” long-term response was evident in 52% (Table 2).

Bottomline: Botox therapy appears helpful for non-relaxing sphincters in HD whereas mitomycin-C remains an unproven therapy for esophageal strictures.

Also briefly noted: JPGN 2014; 59: 674-78.  “Use of cyproheptadine in young children with feeding difficulties and poor growth in a pediatric feeding program.” n=127.  Of the 82 who took cyproheptadine regularly, 96% reported a positive change in feeding behaviors and there was a significant improvement in weight gain.

Also, with regard to stooling problems, Sana Syed (Emory GI fellow) pointed out a useful website that emphasizes proper positioning for functional constipation: squattypotty.com.  While the website promotes their product to provide proper foot support (with elevation), there are other ways to get a similar result.  As noted previously (“Poo in You” Video | gutsandgrowth) proper positioning can help a lot.

Related posts:

 

Endoscopy Module -Postgraduate Course Notes

Advances in Hemostasis for Upper GI Bleeding Brad Barth, MD, MPH  (page 77)

Upper GI Bleeding

Effect of IV PPI on patients with UGI bleeding PRIOR to EGD

  • 6 trials including 2223 patients
  • No significant difference in mortality, rebleeding or need for surgery compared to controls
  • DID significantly reduce rates of high risk stigmata identified on EGD
  • DID significantly decrease the need for endoscopic therapy
  • Reference: Sreedharan A, Martin J, Leontiadis G, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010

 

Upper GI Bleeding – Proton Pump Inhibitors/Prokinetics

  • Omeprazole 1 mg/kg q 12 hours  (Solana, et al. J Pediatr 2013:162:776-82)
  • Proposed PPI drip dose: 1 mg/kg bolus followed by 0.1 mg/kg/hour infusion
  • IV erythromycin or metoclopramide; infuse 20-120 minutes prior to endoscopy in patients with acute UGIB; decreased need for repeat endoscopy to determine cause and site of bleeding. Prokinetic did NOT affect transfusion requirements, duration of stay, need for surgery. Reference: Barkun et al. Prokinetics in acute upper GI bleeding:a metaanalysis. GIE 2010;17:126-132

Upper GI Bleeding —Other points:

  • Epinephrine alone is RARELY enough
  • Non bleeding adherent clot has 8-35% chance of rebleeding in adults. Consider removing it CAREFULLY!
  • A conservative transfusion strategy is usually appropriate

Useful References

Surveillance Endoscopies: The established, the debated, and the unknown –Mitchell Shub, M.D. (page 85)

“Beware of false knowledge; it is more dangerous than ignorance.” —George Bernard Shaw

Familial Adenomatous Polyposis

Surveillance protocol: Age of initial evaluation/Type of procedure/Frequency

  • Colon 10 – 12 y of age (Sooner: family h/o aggressive disease) -Flex sig or Colonoscopy, 1 – 2 y
  • Upper GI tract 20 – 25 y or at initial colonoscopy
  • EGD and side viewing scope, 1 – 3 y
  • Post-colectomy (pouch) 6 – 12 mo. after surgery, Flex sig 1 y (6 mo. If retained rectum)
  • Small bowel: capsule or MRI, frequency unknown

Peutz-Jeghers Syndrome: begin screening at age 8 years or when symptomatic with colonoscopy, EGD, and small bowel imaging (?capsule vs alternatives); then every 2-3 years

Juvenile Polyposis Syndrome: begin screening at age 10-15 years or when symptomatic with colonoscopy, EGD, and  possibly small bowel imaging (?capsule vs alternatives); then every 1-3 years

Discussed guidelines for IBD cancer surveillance and for Barrett’s esophagus

  • For UC, start surveillance 8-10 years after diagnosis.
  • For Crohn’s with ~1/2 colon (or more) involvement, follow same guidelines
  • For coexisting PSC, annual surveillance
  • Barrett’s esophagus in children: adenocarcinoma very rare, evidence lacking to develop surveillance schedule

Expanding the view: Update on Upper GI StricturesMark A. Gilger, M.D. (page 95)

Why balloons for kids (for dilatation)?

You can see what you’re doing

  • Blind pouches
  • Abnormal mucosa
  • Caustic injury
  • Epidermolysis bullosa
  • Already requires general anesthesia
  • Ability to wire through narrow strictures
  • Ability to use radiographic assistance

Tip: Can use vegetable spray (eg. Pam) to make advancement of balloon catheter easy

How to do balloon dilation

  • Inflate balloon to ½ desired initial atmospheres & re‐check placement
  • Begin dilation at to 1‐2 mm more than initial estimated stricture diameter
  • Hold for 1 minute/dilation
  • •ove balloon catheter in and out during dilation;  if balloon moves freely, increase diameter by 1mm.  If stricture moves with the balloon, hold x 1 minute, then done
  • Oh, oh, there’s blood! Good! No blood, no dilation.
  • After dilation, carefully advance endoscope through the stricture; if resistance stop, can try cork‐screw maneuver
  • Document everything; especially stricture location (CM from incisors), dilation diameters (to help you next time)

Adjunct therapy for recalcitrant strictures  –adjunct therapy to sustain dilation needs further study

  • Oral & intravenous corticosteriods
  • Injectable corticosteroids – Thins the mucosa, OK 1‐2 times, but not repeated
  • Mitomycin C
  • Acid reduction
  • Stents

Endoscopy in the high‐risk patient: Keeping your patient safeJenifer R. Lightdale, MD, MPH (page 63)

Safety of Pediatric GI Procedures

  • Peds‐CORI data from >10,000 procedures
  • Overall rate of complications 2.3%: risk of hypoxia 1.5%; risk of bleeding 0.3%

Examples of pediatric populations at increased risk for perforation

  • History of caustic ingestion
  • Esophageal atresia/tracheo‐esophageal fistula
  • Severe duodenitis
  • Severe ulcerative colitis
  • Patients with multiple co‐morbidities (i.e. Type I diabetes, cerbrovascular disease, peripheral vascular disease, renal insufficiency, liver disease)
  • Ehlers‐Danlos Syndrome (Vascular Type)

Pre‐procedure Assessment –lends itself to a checklist 

Thrombocytopenia -Current recommendations

  • EGD ok if platelets >20,000/mL
  • Biopsies ok if platelets >50,000/mL

Bleeding –discussed high risk conditions

Decreasing Risk of Perforation:

  • Avoiding excessive pressure
  • Avoiding premature cutting of a polyp – Coagulate before cutting
  • Avoiding blind intubation of the lumen

Decreasing Risks of Infection

  • SBE Prophylaxis– generally NOT indicated in diagnostic procedures. Congenital heart disease is complex & may be needed on a case‐by‐case basis
  • Single‐dose cephalexin has been shown to decrease peristomal infection during PEG placement
  • Prophylactic antibiotics recommended for cirrhotic patients admitted with GI hemorrhage

Postgraduate Course Syllabus (posted with permission) with complete slides of above lectures: PG Syllabus

Related blog references:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

Injecting steroids for esophageal strictures -does it work?

A recent report indicates that steroid injections are not effective in patients with cervical anastomotic strictures (Clin Gastroenterol Hepatol 2013; 11: 795-801).

While this double-blind randomized control multicenter study of 60 patients (mean age 63) dealt with a specific subtype of strictures, the implications may be broader.  In this study, all patients had undergone esophectomy with gastric tube reconstruction.  The treatment group had 4 quadrant injections of 0.5 mL (20 mg) of triamcinolone and the control group had saline injections.  After injections, patients had Savary dilation to 16 mm.  Patients were followed for 6 months subsequently.

Results: In the treatment group 45% remained dysphagia-free for 6 months compared with 36% of controls (RR=12.6, p=0.46).  Median number of dilatations was 2 in treatment group compared with 3 in the controls.  One corticosteroid-treated patient developed a probable perforation and was excluded from final analysis. Four patients in the treatment group, and none in controls, developed Candida esophagitis.

No statistically significant decrease in dilatations or symptoms was demonstrated.

In their discussion, the authors review the effects of intraesophageal corticosteroid therapy and previous studies.  “Thus far, RCTs supporting this…are limited and, if available, are only small-sized and not focused on anastomotic strictures.”  According to the discussion, the evidence for steroid injection may be strongest for peptic strictures, primarily based on a small, sham-controlled RCT (Am J Gastroenterol 2005; 100: 2419) which demonstrated lower redilatation rates in this setting.

To prove that steroids would be effective if there was only a 10-20% improvement would take at least 200-750 patients

Take-home message (from authors): the routine use of corticosteroid injections in patients with benign anastomotic strictures cannot be recommended.

Related references:

  • -Refractory strictures (NASPGHAN 2011): =if not >14 mm after 5 sessions.   Complex strictures: >2 cm long, tortuous, or if scope cannot be passed predilatation. Consider Fluoro for complex strictures. Described technique of endoknife if only one-sided stricture which are hard to dilate.
  • -Am J Gastroenterol 2005; 100: 2419.  Double-blind, randomized trial showed benefit of steroid injection for Rx of recalcitrant peptic strictures. Consider triamcinolone along length of stricture; max ~10mg (2-4 mg/injection)
  • -JPGN 2007; 44: 336. n=16 pts. Mitomycin 0.1mg/mL; apply for 2-3min c pledget.
    -JPGN 2006; 42: 437.  Case report of using indwelling balloon for daily dilatation in refractory patients.
  • -Endoscopy. 2006; 38(4):404-7).  Mitomycin C: an alternative conservative treatment for refractory esophageal stricture in children?
  • -JPGN 2005; 41: 35A (pg503).  Use of stents for refractory benign strictures, n=10.
  • -Gastroenterol 1999; 117: 229 & 233. AGA position statement and technical review.

**Dosing regarding triamcinolone or mitomycin C has not been clearly established for esophageal strictures.  Doses listed above are based on my reading of the references but no specific dose is advocated on this posting.