Total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) has become the gold standard procedure for patients with medically refractory ulcerative colitis. But a retrospective study conducted by Mount Sinai researcher Maia Kayal, MD, suggests that approximately 30 percent of patients who undergo the procedure are at risk of developing chronic pouchitis.
“It was alarming to see that, because the whole idea of a proctocolectomy is to remove the organ that is causing the problem,” says Dr. Kayal, Assistant Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai. “Instead, we found that patients were experiencing the same symptoms they had presurgery, such as urgency, nocturnal awakenings, and bleeding.”
These findings are among the first to emerge from a series of studies Dr. Kayal has conducted on pouchitis prevalence, associated risk factors, and treatment efficacy among patients who have undergone TPC with IPAA. Her interest in the condition began during her inflammatory bowel disease rounds as a first-year fellow at The Mount Sinai Hospital. “I was seeing patients who had undergone TPC with IPAA because they were told that surgery would resolve their symptoms, but they were now experiencing the same symptoms they had preprocedure,” Dr. Kayal explains. “As I investigated this phenomenon, I discovered that the available literature was limited and outdated. Mount Sinai performs 100 TPC with IPAA procedures every year, and I saw that as an opportunity to build a database and investigate patient trajectories from the date of their ulcerative colitis diagnosis to their postprocedure outcomes.”
Supported by Marla C. Dubinsky, MD, Professor of Pediatrics, and Medicine (Gastroenterology), at the Icahn School of Medicine, and Bruce E. Sands, MD, MS, Professor of Medicine (Gastroenterology) at the Icahn School of Medicine, Dr. Kayal spent a year developing the database, which now includes more than 700 Mount Sinai patients who have undergone the procedure since 2005. In her first study, “Inflammatory Pouch Conditions Are Common After Ileal Pouch Anal Anastomosis in Ulcerative Colitis Patients,” Dr. Kayal identified 386 patients who had available pouchoscopy data for a median follow-up of four years and found that 205 patients (53.1 percent) had acute pouchitis, 60 of whom (29.2 percent) had progressed to chronic pouchitis. Also notable, 119 patients (30.8 percent) and 46 patients (11.9 percent) experienced cuffitis and Crohn’s disease-like condition (CDLC), respectively. The findings were published in Inflammatory Bowel Diseases.
“The numbers we saw for acute and chronic pouchitis were higher than we had anticipated based on the available literature, but the CDLC numbers were essentially mid-range,” Dr. Kayal says. “The problem with the literature relative to CDLC is that no one had really defined this disease, so reports range from as low as 5 percent prevalence to as high as 25 percent. This study is novel in that we used predefined criteria for CDLC in reviewing patients—severe inflammation of the pouch and afferent limb unresponsive to antibiotics; strictures of the pouch, afferent limb, or proximal small bowel; and fistulae between the pouch and perineum or proximal small bowel. Thus, we believe our numbers are accurate.”
For her second study, Dr. Kayal assessed the prognostic potential of endoscopy to identify asymptomatic patients at risk for developing pouchitis. She reviewed 143 cases, grading index endoscopic pouch body activity as 0 (normal) in 86 patients (60.1 percent), 1 (mucosal inflammation) in 26 patients (18.2 percent), and 2 (mucosal breaks) in 31 patients (21.7 percent). She found that primary acute idiopathic pouchitis occurred in 44 patients (30.8 percent) and chronic idiopathic pouchitis in 12 patients (8.4 percent), most of whom were graded 2 based on the scope. Furthermore, grade 2 endoscopic pouch activity was associated with the development of acute pouchitis (hazard ratio (HR), 2.39; 95 percent confidence interval (CI), 1.23‐4.67), but not chronic pouchitis (HR, 1.76; 95 percent CI, 0.53‐5.87). The findings, “Endoscopic Activity in Asymptomatic Patients with an Ileal Pouch is Associated with an Increased Risk of Pouchitis,” were published October 3, 2019, in Alimentary Pharmacology and Therapeutics.
“These findings make a case for scoping one year after final surgical stage to facilitate stratifying patients according to their risk of acute pouchitis,” Dr. Kayal says. “They also suggest that mucosal healing and suppression of mucosal breaks is a reasonable therapeutic target for mitigating the risk of future pouchitis, even if patients are feeling fine. But the concern is that we do not have enough data as to the impact on the pouch when treating an asymptomatic patient.”
For her third study, “Clostridioides Difficile Infection is a Rare Cause of Infectious Pouchitis,” Dr. Kayal explored the phenomenon of Clostridioides difficile infection among patients who have undergone TPC with IPAA. Of the 154 patients in the database who had been tested for C. diff, Dr. Kayal noted that 11 patients (7.1 percent) had been diagnosed a median of 139 days after the final surgical stage. Ten of these patients (90.9 percent) received oral vancomycin for 10 days and the remaining patient received oral metronidazole for 2 weeks. Ten patients (90.9 percent) reported improvement in their symptoms following therapy, and nine (81.8 percent) were found to be negative for recurrent C. diff symptoms upon retesting. Dr. Kayal says no patient had C. diff recurrence. The results were published February 19, 2020, in Inflammatory Intestinal Diseases.
“The takeaway here is that clinicians should routinely check for C. diff in pouch patients who present with new symptoms and then treat them with vancomycin,” Dr. Kayal says. Dr. Kayal subsequently launched her first prospective study, which will look at patient trajectories from the point of their TPC with IPAA procedure to five years postsurgery. The goal is to enroll 150 patients and collect tissue, stool, and blood samples to study the evolution of the pouch transcriptome, microbiome, and proteome. This could potentially help identify risk factors associated with pouchitis and determine where CDLC lies on the spectrum of inflammatory bowel disease.
“The true transcriptome signature of CDLC, and how it relates to true Crohn’s disease, is not fully understood,” explains Dr. Kayal. “We are investigating whether there is a specific omic signature at baseline—before colon removal—that can predict which patients will develop CDLC. If we can find this baseline risk signature, we can better counsel patients before surgery and use targeted therapies postprocedure to decrease their risk of CDLC. That would be a real game changer for pouch surgery.”
Maia Kayal, MD
Assistant Professor of Medicine (Gastroenterology)