Resection of the Mesentery With Functional End-to-end Anastomosis vs Kono Anastomosis in Preventing Relapse After Ileocolic Resection for Primary Crohn Disease: a Prospective, Randomized, Controlled Trial Remeasure CD TRial
Phase: NA
Conditions: Ileocolic Crohn Disease, Kono S Anastomosis, Resection of the Mesentery
Sponsor: Azienda Ospedaliera Ordine Mauriziano di Torino

DATE: 09/09/2025
Michela Mineccia, MD
Chirurgia Generale ed Oncologica 
Ospedale Mauriziano “Umberto I”, Torino, 
Office: + 39 (0)11 5082590
Fax: +39115082592
e-mail: mmineccia@mauriziano.it
Torino, September 9, 2025
“Resection of the mesentery vs Kono-S anastomosis in preventing surgical recurrence for 
primary Crohn Disease: the REMEASURE prospective, randomized, controlled trial” 
Clinical Trial. Gov number NCT07164209
Remeasure study protocol + statistic
Sincerely
Michela Mineccia, MD

1
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
REsection of the MEsentery vs Anastomotic configuration and SUrgical Recurrence.
REMEASURE Trial in Crohn’s Disease V2.1
Resection of the mesentery with functional end-to-end anastomosis vs Kono-S anastomosis in 
preventing relapse after ileocolic resection for primary Crohn’s Disease.
A prospective, monocentric, randomized trial.
Michela Mineccia*
* Consultant Surgeon, Division of General and Oncologic Surgery. Department of Surgery. 
Ospedale Mauriziano “Umberto I”, Torino, Italia.
Office: + 39 (0)11 5082590. facsimile: +39115082592. E-mail: mmineccia@mauriziano.it

2
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
Background
Crohn’s disease (CD) is an Inflammatory Bowel Disease (IBD), with a relapsing and remitting 
course, and with an annual incidence of 3–25 per 100000 inhabitants. Over 80% of patients with CD 
will require a surgical procedure due to abdominal complications within 15 years from diagnosis, 
and 50% of them will require reoperation for recurrent intestinal disease in the next 15 years1,2.
The gold standard surgical treatment of CD patients, as reported by latest ECCO, ECCO-ESCP, and 
SICCR guidelines, is based on laparoscopic approach, bowel resection without microscopically 
disease-free margins, and stapled side-to-side anastomosis3-5. However, two novelties have recently 
appeared in the field of CD surgery, both aimed to improve long-term surgical recurrence: the 
inclusion of the mesentery in the resection of a diseased bowel loop, and a new anastomotic 
configuration to leave the mesentery far from the anastomotic margins6,7.
At present, the incidence and prevalence, clinical significance, surgical implications, and role in 
surgical recurrence of mesentery thickening and enlarged lymph nodes are completely unknown. 
Crohn’s disease has been thought to originate in the gut lumen, and thus the medical treatment tends 
to focus on mucosal inflammation. Surgical treatment is based on the resection of the diseased 
bowel but, unlike cancer surgery, the removal of the mesentery and associated lymph nodes is not 
considered essential for adequate treatment8. Since a thickened mesentery often bleeds heavily when 
divided, a common approach among surgeons has been to disconnect it flush with the intestine and 
to leave it retained. Furthermore, no long-term benefits in terms of recurrence have been reported 
after mesentery removal. However, recent data suggest that margin positivity and reoperation rates 
can be substantially reduced if resection is guided by mesenteric based strategies9,10. The mesenteric 
organ is a single structural entity spanning the gut from duodenojejunal flexure to mesorectum; it is 
now recognized that this histological overlap is the true intestinal hilum, where blood vessels enter 
or leave. At the intersection between the intestine and the mesentery, the mesenteric mesothelium 
continues onto the intestine and contributes to the cellular component of the outer layer, the serosa. 
From the serosa, connective tissue separations extend into underlying muscle and submucosa, 
meaning that the mesenteric and intestinal connective tissue are contiguous9,10. Crohn himself was 
the first to document mesenteric abnormalities, noting that mesenteric fat often advances over the 
intestinal surface11. Nowadays, the mesentery has been proposed as a separate organ, with a role in 
systemic inflammation. Visceral tissue plays an important role in immunoregulation and may

3
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
function as a pro-inflammatory agent; adipocytes release molecules like adiponectin and leptin are 
implicated in the production of pro and anti-inflammatory cytokines. Fibrocytes also play a central 
role in the development of systemic inflammation. In pathological states involving mesenteric 
inflammation (including CD) circulating fibrocytes levels are elevated, secreting cytokines, favoring 
antigen presentation and enhancing the production of metalloproteinases12. The most evident link 
between the mesentery and Crohn’s disease is the macroscopic phenomenon of “fat wrapping” or 
“creeping  fat,”  where  mesenteric  fat  is  inflamed  and  extends  beyond  its  normal  anatomical 
distribution over the surface of the contiguous intestine. Fat wrapping is a typical and constant 
finding in Crohn's disease, and is absent in all other forms of intestinal inflammation. The degree of 
fat wrapping seems to correlate with the severity of intestinal inflammation in the contiguous 
intestine. Furthermore, some patient presents with extensive lymph nodes enlargement throughout 
the mesentery tributary of a diseased segment. The reason of this phenomenon and its pathological 
rule are nowadays completely unknown. In consideration of the above-mentioned evidences, we 
could target the CD therapy also on the mesentery. At present there are no drugs specifically 
designed to act on the mesentery, so that the only target-therapy is surgical removal. Mesenteric 
division in CD is challenging because of bleeding that may be difficult to contro7,9,13. Excision of the 
mesentery  is  associated  with  an  increased  lymphatic  tissue  removal;  this  may  reduce  the 
immunological stimulation, resulting in improved post-operative outcomes. It may also reduce the 
recruitment of fibroblasts which subsequently migrate to the intestinal surface8. Coffey et al. 
reported the first retrospective study demonstrating the clinical relevance of including the mesentery 
in ileocolic resection for CD. The authors analyzed the rate of surgical recurrence after inclusion of 
the mesentery during ileocolic resection for CD, by comparing two cohorts of patients: cohort A (30 
patients who underwent classical ileocolic resection close to the bowel) and cohort B (34 patients in 
which the affected mesentery was fully dissected and partially excised). As a result, cumulative 
reoperation rate for CD recurrence were 40% and 2,9% in cohort A and B respectively. In addition, 
intestinal length and margin positivity rates were both reduced, while nodal yield was increased, 
following mesenteric resection7.
With the same intent of reducing surgical recurrence rate after ileocolic resection of CD, Kono et al. 
published in 2011 a paper concerning a new technique of an anti-mesenteric, functional end-to-end 
anastomosis (EEA), called Kono-S anastomosis6. After the bowel and the corresponding mesentery 
have been mobilized, ileal and colonic edges are transected with a linear cutter, with the mesentery

4
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
located at the center of the stump; the intervening mesentery is divided close to the bowel, to avoid 
any devascularization or denervation. The 2 staple lines are approximated to create a kind of 
supporting column to maintain the anastomosis caliber. Two longitudinal enterotomies, 7 cm long, 
are made at the antimesenteric side of the 2 bowel stumps, starting from 1 cm from the staple line. A 
hand-sewn,  side-to-side,  antimesenteric  anastomosis  is  then  performed,  approximating  the 
anastomotic ends in a transverse fashion. The endoscopic recurrence rate has been reported to be 
lower with Kono anastomosis than with conventional EEA, and two studies showed a 5-year 
surgical anastomotic recurrence rate was 1.8%, during a median follow-up of 65 months (range, 43– 
138 months)14,15. Shimada et al. published in 2019 a retrospective trial showing that the Kono 
anastomosis was associated with a low risk of recurrence after 1 year. Kono anastomosis was 
reported to be superior in terms of anastomotic recurrence at 5 years, using Kaplan–Meyer analysis, 
as well as having a lower anastomotic leakage rate16. The first RCT comparing Kono-S anastomosis 
and standard anastomosis in CD has been recently published. The authors found a significant 
reduction in postoperative endoscopic recurrence rate, and also a decrease in the severity of 
endoscopic recurrence score, in favor of the Kono-S technique comparing to a conventional side-to-
side anastomosis, performed with a double fire of a linear stapler, and with the transverse staple line 
buried in a running suture15. Despite some peculiarities in terms of suturing, the Kono anastomosis is 
a functional, end- to-end anastomosis which keeps the mesentery distant from the mucosal sutures 
but leaving in situ the mesentery regardless of its characteristics. In the study by Luglio et al., it was 
compared with a standard side-to-side anastomosis, but without mesentery removal15.
In conclusion, since the two surgical techniques are similar, and share the same pathophysiological 
rational in terms of relapse, the aim of this Troial is to verify if the manual Kono-S anastomosis, 
with mesentery preservation but exclusion form the anastomosis, has the same efficacy as a stapled, 
antimesenteric, functional end-to-end anastomosis performed after mesentery removal.

5
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
Aim of the study
Aim of the present study is to compare an antimesenteric, stapled, functional end-to-end, ileo-colic 
anastomosis with removal of the mesentery versus the manual, functional end-to-end, ileo-colic 
Kono-S anastomosis with mesentery preservation, in terms of peri-operative safety and efficacy in 
preventing endoscopic recurrence after ileocolic resection for Crohn Disease
Type of the study
Experimental
Design of the study
Prospective, randomized, controlled clinical trial
Target population and setting
Patients presenting with ileocolic primary Crohn disease either not suitable for medical treatment or 
with contraindications for therapy i.e: occlusion, abscess, contraindications to the use of biologics.

Patients > 18 years

Informed consent

Older than 70
Enrollment: 
Inclusion Criteria
Exclusion Criteria

Recurrent disease, previous surgery for CD

Clinicians or patients not willing to maintain a drug washout for six months

Emergency surgery

6
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
Endpoints
Primary endpoint: endoscopic recurrence (ER) (Rutgeerts score i2 or greater) after 6 months (see 
table Rutgeerts score). All patients will maintain a drug washout for six months.
Secondary endpoints: postoperative complications, clinical recurrence* (CR) after 12 months, ER 
after 18 months, surgical recurrence (SR) after 24 months.
(*) Clinical recurrence: recurrence of disease with bio-humoral alterations (PCR, Calproctectin) or 
symptoms that require hospitalization or resumption of medical therapy according the Harvey 
Bradshaw Index and according to the treating physician assessment.
Rutgeerts’ score
score
Endoscopic findings
Rutgeerts i0
Absence of any lesion at the site of anastomosis and in 
the neo-terminal ileum
Rutgeerts i1
>= 5 aphthous ulcers (< 5 mm)
> 5 aphthous ulcers with normal mucosa
Rutgeerts i2
Between the lesions, or skip lesions, or lesions confined 
to the ileocolic anastomosis
Rutgeerts i3
Diffuse neo-terminal ileitis with diffusely inflamed mucosa
Rutgeerts i4
Diffuse neo-terminal ileitis with large ulcers (<= 5 mm), 
nodules and/or narrowing

7
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
Methods
Patients who meet inclusion criteria will be randomized between two surgical procedures:
The excision of the mesentery and ileocolic anastomosis (group A) and the Kono-S anastomosis 
(group B) after ileocolic or ileo-cecal resection. The operation could be performed with open or 
laparoscopic approach. Two videos will be provided showing the anastomotic techniques in order to 
improve standardization among the contributing Centers.
1)
      Excision of the mesentery
 
 : the mesentery is fully dissected and excised to the limit of 
macroscopic “fat wrapping”, where mesenteric fat is inflamed and extends beyond its 
normal anatomical distribution over the surface of the contiguous intestine. A functional, 
end-to-end, stapled anastomosis between colon and ileum is than performed (the functional 
end-to-end  is  a  latero-lateral,  antiperistaltic,  antimesenteric  anastomosis,  which  has  a 
similar, final configuration of the Kono-S).
2)
      Kono-S anastomosis:
 
  the mesentery is not removed but cutted close to the bowel. The bowel 
is then divided transversely by placing a linear stapler perpendicular to the intestinal lumen 
and the mesentery. The corners of the two staple lines are reinforced and the two stumps are 
approximated using 5–7 sutures to create the column. If the caliber of the two intestinal 
segments differs significantly, the sutures should be spaced to evenly distribute the surplus 
tissue of the larger segment, in order to achieve good approximation and stable support for 
the anastomosis. To create the anastomosis, an antimesenteric longitudinal enterotomy (or 
colostomy) is performed on each stump to allow a transverse lumen of 7 cm in diameter for 
the small bowel or closer to 8 cm for the colon. In this way the supporting column is located 
immediately behind the posterior wall of the anastomosis providing a rigid and stable 
support to prevent mechanical deformation and functional constriction of the lumen of the 
anastomosis.

8
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
Study Design for a Randomized Trial
The aim of the study is to determine wheather the two therapies have the same efficacy; therefore, we 
are in the framework of No Difference Testing. 17 18
Based on previous literature the expected reduction rate of 6 months for endoscopic recurrence after 
Kono anastomosis was 25% in order to be more conservative (45% after resection of the mesentery 
group and 20% in the Kono group), and a value of 0.05 (1-sided) and 75% power was estimated a 
sample size of 70 patients.
After enrollment, patients will be randomly assigned in a 1 : 1 ratio between Kono anastomosis and 
resection of the mesentery, by controlling for age, sex, smoking habits, and other health related 
quantities, including the origin from different centers will be taken into account.
The  two  Groups  will  be  compared  for  safety  in  terms  of  perioperative  characteristics  and 
postoperative complications. Continuous variables will be analysed using a two-tailed, unpaired, 
Student’s t-test, and proportions will be compared using two-tailed, Fisher’s exact or chi-square test, 
where appropriate. Since multiple tests will be performed, a suitable p–value correction will be 
used, such as Bonferroni correction. A model-based approach for the multivariate analysis, setting 
the presence of postoperative complications as dependent variable will be performed, a binary 
logistic regression will be used, with all the variables significant at the univariate level as predictors. 
The greatest emphasis will be on the dummy variable encoding the different treatments (for 
example  1 =  ”Kono  anastomosis”,  0  =  ”Resection  of  the  mesentery”).  In  this  context,  the 
equivalence may be evaluated in two ways: 1 • the associated coefficient of the regression is not 
significant from a statistical point view. • the Odds Ratio (OR) associated to the corresponding 
coefficient is close to 1 (and in particular the 95% confidence interval contains 1), meaning that 
changing the type of treatment does not affect the probability postoperative complications.
Endoscopic, clinical, and surgical recurrences will be analyzed using the time-to-event estimates of 
the Kaplan-Meier function, and compared for univariate analysis with the Log-rank test. Cox 
proportional hazard regression analysis will be used to set up a predictive model simultaneously 
exploring the effects of the independent variables on recurrences in relation to time. Significance 
will be considered for p-value inferior to 0.05.

9
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
Data collection
Data will prospectively be collected using a web-based, dedicated, REDCup database. A local study 
manager will be identified for each participating center, and a dedicated REDCup username and 
password will be assigned. The completeness and congruity of the data will be checked periodically 
by the study's Scientific Committee. The Scientific Committee will refer to the local managers for 
any request for clarification.
Duration of the study 
24 months
Ethical consideration
The study will be performed according to the institutional guidelines and to the ethical standards of 
the Helsinki Declaration and the formal approval by the ethical Committee of each participant.
Funding
No funds needed
Data collections:
REDCup for REMEASURE trial database and CRF

10
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
REFERENCES
1.
Lewis RT, Maron DJ. Efficacy and complications of surgery for Crohn's 
disease. Gastroenterol Hepatol (N Y) 2010;6:587-96.
2.
Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence 
in Crohn's disease. Annals of surgery 2000;231:38-45.
3.
Adamina M, Bonovas S, Raine T, et al. ECCO Guidelines on Therapeutics in 
Crohn’s Disease: Surgical Treatment. Journal of Crohn's and Colitis 2019;14:155-68.
4.
Pellino G, Keller DS, Sampietro GM, et al. Inflammatory bowel disease position 
statement of the Italian Society of Colorectal Surgery (SICCR): Crohn’s disease. Techniques in 
Coloproctology 2020.
5.
Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCO-ESCP Consensus on 
Surgery for Crohn's Disease. Journal of Crohn's & colitis 2018;12:1-16.
6.
Kono T, Ashida T, Ebisawa Y, et al. A new antimesenteric functional end-to-end 
handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn's disease. Diseases 
of the Colon & Rectum 2011;54:586-92.
7.
Coffey CJ, Kiernan MG, Sahebally SM, et al. Inclusion of the Mesentery in Ileocolic 
Resection for Crohn's Disease is Associated With Reduced Surgical Recurrence. Journal of 
Crohn's & colitis 2018;12:1139-50.
8.
Wickramasinghe D, Warusavitarne J. The role of the mesentery in reducing recurrence 
after surgery in Crohn's disease. Updates Surg 2019;71:11-2.
9.
Coffey JC, O'Leary DP. The mesentery: structure, function, and role in disease. The 
Lancet Gastroenterology & Hepatology 2016;1:238-47.
10.
Coffey JC, O'Leary DP, Kiernan MG, Faul P. The mesentery in Crohn's disease: friend 
or foe? Current Opinion in Gastroenterology 2016;32:267-73.
11.
Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathological and 
clinical entity. JAMA 1932;99:1323-9.
12.
Rivera ED, Coffey JC, Walsh D, Ehrenpreis ED. The Mesentery, Systemic 
Inflammation, and Crohn's Disease. Inflammatory bowel diseases 2019
;25:226-34.
13.
Coffey JC, O'Leary DP, Kiernan MG, Faul P. The mesentery in Crohn's disease: friend 
or foe? Curr Opin Gastroenterol 2016;32:267-73.
14.
Kono T, Fichera A, Maeda K, et al. Kono-S Anastomosis for Surgical Prophylaxis 
of Anastomotic Recurrence in Crohn's Disease: an International Multicenter Study. Journal 
of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary 
Tract 2016;20:783-90.
15.
Luglio G, Rispo A, Imperatore N, et al. Surgical Prevention of Anastomotic Recurrence by 
Excluding Mesentery in Crohn's Disease: The SuPREMe-CD Study - A Randomized Clinical 
Trial. Annals of surgery 2020.
16.
Shimada N, Ohge H, Kono T, et al. Surgical Recurrence at Anastomotic Site After 
Bowel Resection in Crohn's Disease: Comparison of Kono-S and End-to-end Anastomosis. 
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary 
Tract 2019;23:312-9.

11
REsection of the MEsentery vs Anastomotic configuration and SUrgical 
REcurrence REMEASURE – a monocentric, Randomized trial
17.
Walker E, Nowacki AS. Understanding equivalence and noninferiority testing. J Gen 
Intern Med 2011;26:192-6.
18.
Hwang IK, Morikawa T. Design Issues in Noninferiority/Equivalence Trials. 
Drug information journal : DIJ / Drug Information Association 1999;33:1205-18.