Inflammatory Bowel Disease Treatment | Publications

Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD.  Shouval DS et. al. Inflamm Bowel Dis. 2017 Nov;23(11):1950-1961.
Some children who develop Crohn's disease in infancy have a mutation in a gene called interleukin-10 receptor. If the function of this gene and protein are altered, patients will develop inflammation (pain, redness, and swelling) in the intestine. This paper outlined a possible mechanism by which patients with this mutation may develop inflammation.

Postoperative complications in children with Crohn’s disease treated with Infliximab.   Zimmerman LA, et. al. J Pediatr Gastroenterol Nutr 2016;63:352-6.
Infliximab is an immunosuppressive agent used to control Crohn’s disease. In this study the postoperative course was reviewed of 123 patients with Crohn’s disease requiring surgery and joining of two pieces of bowel together. The overall complication rate for these children and adolescents was 13%. In the 24 patients who received infliximab and the 99 who did not, there was no difference in the frequency of postoperative complications. Although there were only a small number of patients in this study, it suggests that prior use of this medication should not prevent surgery if required. This paper demonstrated that children receiving infliximab (Remicade) who require surgery are probably not at increased risk of surgical complications.

Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency.  Shouval DS, et. al. Gastroenterology. 2016 Dec;151(6):1100-1104
This study determined that mice with IBD and the interleukin 10 receptor mutation (a mutation found in humans) had an increase in IL-1, a protein made by white blood cells that causes inflammation. By using Anakinra (a medication that reduces the activity of IL-1), colon inflammation in both mice and a human patient improved.

Antibodies to infliximab are associated with lower infliximab levels and increased likelihood of surgery in pediatric IBD.  Zitomersky NL, et. al. Inflamm Bowel Dis. 2015;21:307-14.
Infliximab (Remicade) is a medicine commonly used to treat Crohn's and colitis. However, some patients on infliximab lose response (aka the drug stops working over time. In this study, we wanted to figure out if antibodies to infliximab were causing the drug to stop working. We determined that approximately 20% of our patients currently receiving infliximab have antibodies to this drug, and this results in a significant decrease in drug levels and drug effectiveness. This important pediatric paper has led to increased utilization of therapeutic drug monitoring in children receiving anti-TNF therapies (Remicade and Humira).

Predictive value of the pediatric ulcerative colitis activity index in the surgical management of ulcerative colitis.  Gray FL, et. al. J Pediatr Surg 2013;48:1540-5.
In this study of 60 patients with ulcerative colitis, the correlation between the “pediatric ulcerative colitis activity index” (PUCAI), a method of grading the severity of ulcerative colitis, and the ability to perform the colectomy and pullthrough in two or three stages was assessed. A clear correlation was found between a higher score (more active disease) and the need to perform an initial colectomy prior to the pullthrough. It was also demonstrated that the use of tacrolimus, an immunosuppressive agent, was effective at lowering the PUCAI score and in many cases allowing the colectomy and pullthrough to be performed in the same procedure. Minor and reversible side effects occurred in 46% of the patients receiving tacrolimus, but there was no increase in the frequency of surgical complications.

Comparison of laparoscopic-assisted and open total proctocolectomy and ileoanal pouch anal anastomosis in children and adolescents. Linden BC, et. al. J Pediatr Surg 2013;48:1546-50.
We reported and compared our experience in a large series of children and adolescents between those who had a traditional “open” approach (39 cases) using a long midline abdominal incision to those managed using a laparoscopic approach (68 cases). Out comes were quite comparable between the two groups although the laparoscopic approach did take longer than the open approach to perform. The most important finding in this study was a significantly lower incidence of intestinal obstruction occurring as a complication in the patients who had the laparoscopic approach for their surgery. The predicted risk of having intestinal obstruction in the first year after surgery was 1% in the patients having a laparoscopic procedure and 24% for those following an open procedure. This finding favors use of the laparoscopic-assisted approach in children and adolescents to avoid this post-operative complication.

Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease.  Papa E, et. al. PLoS One. 2012;7(6):e39242.
This study, a collaboration between Boston Children's and MIT scientists, used new "DNA fingerprinting" techniques to see if the intestinal bacteria differ between children with IBD and children without IBD. We determined that children with active IBD have different bacteria in their intestine (fewer Firmicutes, and more proteobacteria). We hope this finding will lead to treatments that may reduce inflammation by changing the bacteria in the intestine.

Technique of laparoscopic-assisted total proctocolectomy and ileal pouch anal anastomosis in children and adolescents: A single center’s 8-year experience.  Linden BC, et. al. J Pediatr Surg 2012;47:2345-8.
The method for removal of the colon and an ileoanal pullthrough using a laparoscopic approach which we began to use in 2003 was described. This method avoided a large midline abdominal incision in favor of several five millimeter incisions and a “bikini” incision in the lower abdomen which is easily hidden just above the pubic bone. We found that this approach was safe and effective in treating children with ulcerative colitis.

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations.  Rufo PA, et. al. J Pediatr Gastroenterol Nutr. 2012 Jul;55(1):93-108.
This paper established national recommendations for gastroenterologists and pediatricians caring for patients with IBD. Among other topics, this paper covered how often to see patienst, how often to get lab work, how to screen and treat for vitamin D deficiency, what immunizations should be given, and how to screen for depression and anxiety.

Prospective study of health-related quality of life and restorative proctocolectomy in children.  Lillehei CW, et.al. Dis Colon Rectum 2010;53:1388-1392.
This is the first prospective health-related quality-of-life study performed on pediatric patients following restorative proctocolectomy. The 44 patients and their parents completed validated quality-of-life questionnaires within one month after their colectomy and ileoanal pullthrough and also one year after their final surgery for ulcerative colitis or familial adenomatous polyposis. In this study the patients were compared with themselves. Prior to surgery patients with ulcerative colitis had substantially lower health-related quality-of-life scores which were mirrored in the parental surveys. Following surgery these patients had significant improvement in 7 of 8 subscales and all corresponding subscales in the parental questionnaire demonstrating that the quality of life was markedly improved after surgery.

Immune response to influenza vaccine in children with inflammatory bowel disease.  Lu Y, et. al. Am J Gastroenterol. 2009;104(2):444-53.
At the time we performed this study, and increasing proportion of our inflammatory bowel disease patients were being treated with drugs that reduce the activity of the immune system (such as Imuran and Remicade. Therefore, we did not know if routine vaccines such as the flu shot were effective in children with IBD. We therefore gave children the flu shot, and studied them to see if the flu shot was effective. We showed in this study that the flu shot was safe, effective, and did not increase the risk of IBD flares.

Restorative proctocolectomy and ileal pouch-anal anastomosis in children.  Lillehei CW, et. al. Dis Colon Rectum 2009;52:1645-9
The authors report a series of 100 children and adolescents in whom a total abdominal colectomy and ileoanal pullthrough were performed for ulcerative colitis and familial adenomatous polyposis. The patients did well from a functional perspective and had a limited risk of complications, most frequently a narrowing where the pouch was sewn to the anus in 18 patients requiring dilation. Almost half of the patients with ulcerative colitis had symptoms consistent with pouchitis postoperatively, but only 10 required prolonged treatments. Small bowel obstruction requiring surgery occurred in 18 patients. The average frequency of bowel movements was 5.4 times per day.

Pouch outcomes among children with ulcerative colitis treated with calcineurin inhibitors before ileal pouch anal anastomosis surgery.  Hait EJ, et. al. J Pediatr Surg 2007;42:31-35.
Fourteen patients in this study received intravenous immunosuppressive agents (cyclosporine or tacrolimus) prior to an ileoanal pullthrough. Follow-up of these patients demonstrated that chronic pouchitis was an infrequent sequelae to surgery and there was not an increased risk of postoperative complications.

Use of a gracilis muscle flap to facilitate delayed ileal pouch-anal anastomosis. Shamberger RC, et. al. Dis Colon Rectum 2000;43:1628-1631.
This is a case report of a patient who was referred from an outside institution after an ileal pouch failed due to lack of adequate blood supply and the pouch had to be removed. The authors described a procedure in which the area dissected for the pullthrough was preserved by rotating a muscle from the thigh to maintain this tract through the rectal muscular tunnel. The patient subsequently had a successful new ileoanal pullthrough through this area with excellent postoperative function and fecal continence.

Quality of life assessment following ileoanal pullthrough for ulcerative colitis and familial adenomatous polyposis.   Shamberger RC, et. al. J Pediatr Surg 1999;34:163-166.
Thirty-two patients and their parents completed validated quality of life questionnaires at least 6 months after having a total abdominal colectomy and ileoanal pullthrough for ulcerative colitis or familial adenomatous polyposis. In this study, the patients and their parents rated their quality of life as equivalent to “normal controls”. A supplemental set of questions demonstrated little adverse effect of the surgery with limited use of medications to control bowel frequency and little restriction of activity because of the frequency of bowel movements or fear of incontinence.

Anorectal function in children after ileoanal pull-through.  Shamberger RC, et. al. J Pediatr Surg 1994; 29:329-333.
Prospective evaluation of anorectal pressures was performed in this cohort of pediatric patients. It demonstrated that following an ileoanal pullthrough the resting rectal sphincter pressures and the maximum squeeze pressures were decreased, but following a “pouch training program” these pressures returned to normal and all patients were continent during the day and night.