Study of the Kono-S Anastomosis Versus the Side-to-side Functional End Anastomosis

Study Aim:

• The primary aim of this study is to compare the postoperative recurrence of CD using the modified Rutgeerts score at 3-6 months between the novel Kono-S anastomosis (Group1) and side-to-side functional end anastomosis (Group2) and surgical recurrence rate at 60 and 120 months between the groups. Evaluate histologic features in surgical specimen collected at the index surgery as predictors for endoscopic, clinical, and surgical recurrence after ileocecal resection for CD. To evaluate the histological mucosal healing at 60 months between the novel Kono-S anastomosis (Group1) and side-to-side functional end anastomosis (Group2) using Global Histology Activity Score and The Inflammatory Bowel Disease-Distribution, Chronicity, Activity [IBD-DCA] score.
• The secondary aim is to evaluate the postoperative endoscopic recurrence of CD using the modified Rutgeerts score at 12-18, 60 and 120 months between the groups; time to surgical recurrence between Group1 and Group2 measured in months from the index surgery; yearly Crohn's disease surgical therapy impact using the Work Productivity and Activity Impairment (WPAI) questionnaire; yearly Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire; to evaluate before surgery, and yearly after the surgery up 60 months the patient perception of illness measured by The Brief Illness Perception Questionnaire, (a 9-item questionnaire) score between the groups, to evaluate disease activity yearly using Harvey-Bradshaw Index, and monitor medication therapy, anastomotic strictures, readmission rates, and mortality rates through the 120 months follow-up, and utilize Focus Groups from national and international study sites to evaluate patient's perspectives on surgical treatment, patients' goals of surgical treatment, and surgical treatment's personal and social impacts, patient perspective on nutrition; and long-term psychosocial impact and nutrition challenges, and to evaluate the differences in the histological/mucosal healing between Kono-S and Side-to-Side anastomoses.

Methods

Design: This will be a multi-center randomized prospective trial with 500 subjects. Patients with Crohn's ileitis or Crohn's ileocolitis requiring initial resection will be randomized to undergo either the Kono-S anastomosis or the side-to-side functional end anastomosis.

Patients will be randomized into two Groups:

Group 1: Kono-S anastomosis vs. Group 2: side-to-side functional end anastomosis (control group).

The purpose of this study is to compare the postoperative recurrence of Crohn's disease between the Kono-S procedure and the side-to-side functional end anastomosis and to evaluate the surgical recurrence rate at 60 and 120 months between the groups.

In any intestine surgery, after the sick portion of the bowel is removed, the intestinal tract is restored by reconnecting the healthy ends together. The new connecting line is called anastomosis and could be created in a variety of ways by the surgeon. This study will compare two different intestinal connections called Kono-S anastomosis and the traditional side-to-side functional end anastomosis. Initial studies have demonstrated that the Kono-S anastomosis has prevented endoscopic evidence of the post-operative recurrence of Crohn's disease at greater rates than the traditional side-to-side functional end anastomosis.

Follow-up: Patients will be discharged on no prophylactic treatments, and they will be followed post-operatively at 3 to 6, 12 to 18, 60-, and 120 months with a colonoscopy to assess for endoscopic recurrence. The mucosa will be graded with the modified Rutgeerts score for postoperative recurrence. All colonoscopies are part of the standard treatment. All patients will have also standard 30 days, 3 to 6, 12 to 18, 24, 36-, 48-, 60-, 72-, 84-, 96-, 108-, and 120 months follow-ups by phone call, through medical records, or during the postoperative clinic visit.

Follow-up Care: Patients with a Rutgeerts score at 3-to-6 months of:

• All participating sites follow the same endoscopic evaluation protocol at 3-6, 12-18, 60, and 120 months, using the modified Rutgeerts score for grading the endoscopic recurrence
• 0, 1, or 2a will be followed prospectively with or without introducing medical treatment at the discretion of the gastroenterologist.
• above >2a will initiate medical therapy for Crohn's disease at the discretion of the gastroenterologist.
• Should the patient's symptoms warrant, medical treatment can be initiated at any time at the discretion of the gastroenterologist. This is a standard of care
• 3 Colonoscopic images (still color photos acceptable) are taken to ensure standardized evaluation of the anastomoses and will be shown to a gastroenterologist blinded to the goal of the study for determination of the Rutgeerts score in addition to the initial evaluation by the sites endoscopists, and for additional analyses.
• post-operative endoscopic recurrence of CD using the modified Rutgeerts score at 12-18-, 60-, and 120 months between the groups. An endoscopic Rutgeerts score of 2b or higher will be considered a recurrence.
• Time to surgical recurrence between Group1 and Group2 measured in months from the index surgery
• Work Productivity and Activity Impairment (WPAI) questionnaire (a 6-item questionnaire that measures the amount of absenteeism and presenteeism due to health problems) will be administered annually for up to 120 months.
• Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (a 10-item shortened version of the original IBDQ, measuring the quality of life in four domains: bowel symptoms, emotional health, systemic systems, and social function) will be administered annually for up to 120 months.
• The Brief Illness Perception Questionnaire, (a 9-item questionnaire) score measuring the patient perception of illness before surgery, at 24-, 36-, 48-, 60-, 72-, 84-, 96-, 108-, and 120-months post-procedure.
• Harvey Bradshaw Index as a marker of clinical disease activity will be used. This will be recorded before the procedure (baseline), at 3 to 6 and 12-18 months, 24-, 36-, 48-, 60-, 72-, 84-, 96-, 108-, and 120-months post-procedure.
• Other monitoring- monitor medication therapy, readmission rates, postoperative morbidity and mortality rates annually through the 120 months of follow-up between the groups
• Focus groups from national and international study sites to evaluate patients' perspectives on surgical treatment, patients' goals of surgical treatment, and surgical treatment's personal and social impacts, patient perspective on nutrition; and long-term psychosocial impact and nutrition challenges. This is a qualitative evaluation.
• surgical pathology margin evaluation will be used to assess for histologic predictors for endoscopic and clinical remission in Crohn's Disease after ileocecal resection
• The differences in the histological mucosal healing between Kono-S and Side- to Side anastomosis measured by the histological score between the groups using the modified Global Histology Activity Score (Modified) between the groups at 60 months.

Inclusion criteria

• Patients with Crohn's ileitis or ileocolitis requiring initial surgical resection.
• Age of 18 years and older, male and female
• All Phenotypes of Crohn's diisease will be included: nonpenetrating (B1), stricturing (B2), and penetrating (fistulating) (B3), according to the Vienna classification
• The patients can be on any medications coming into surgery, including prior anti- tumor necrosis factor(TNF) therapy.

Exclusion criteria

• Patients under 18 years of age
• Patients with recurrent Crohn's
• Pregnant patients
• Patients with more than one non-contiguous site of active disease, thus requiring multiple resections or additional bowel sparing procedures at the time of surgery.
• Patients with Crohn's disease extending to the cecum and ascending colon
• Patients who will need preventive postoperative medical treatment
• Patients that need change of surgical procedure as per the surgeon at the time of the intraoperative abdominal evaluation.