Intracorporeal Vs Extracorporeal Anastomosis in Patients Undergoing Laparoscopic Right Hemicolectomy: a Multicenter Randomized Clinical Trial (The IVEA-study)
Phase: NA
Conditions: Colorectal Surgery, Anastomotic Leak, Colectomy, Laparoscopy
Sponsor: Hospital Universitario Torrecárdenas

INTRACORPOREAL VS. EXTRACORPOREAL  ANASTOMOSIS 
IN PATIENTS UNDERGOING LAPAROSCOPIC RIGHT 
HEMICOLECTOMY: A MULTICENTER RANDOMIZED CLINICAL 
TRIAL (THE IVEA-STUDY) 
INTRODUCTION AND JUSTIFICATION OF THE WORK: 
BACKGROUND AND CURRENT STATUS OF THE SUBJECT 
Colon cancer is the third most frequent malignant tumor currently constituting a major health 
problem in Western countries. In Spain, it represents approximately 15% of the incidence of all 
tumors, registering more than 25,000 new cases per year, and is the second cause of cancer 
death (more than 13,000 deaths / year). 
The average survival in our country is 48% at 5 years after the diagnosis of colon cancer1, 
possibly because it is performed late in most cases and because of the little introduction of 
screening programs for this neoplasm. 
The objective of the surgical treatment of colon cancer is the block resection of the tumor with 
correct margins of safety, as well as the exeresis of all the corresponding lymph node territory 
with the ligation of the vessels at their origin. Usually, a proximal and distal margin of at least 5 cm 
is considered correct, although this is further determined by the vascularization of the colonic 
segment. When the colon has invaded the surrounding structures locally, a block resection should 
be scheduled2,3. 
Tumors located in the cecum or ascending colon require 5-10 cm of terminal ileum with ligation of 
the ileocolic pedicle and right branch of the middle colic vessels, with resection at the level of the 
middle transverse colon (right hemicolectomy). A tumor located at the hepatic angle or in the 
proximal transverse colon requires an enlarged right hemicolectomy, with ligature of the ileocolic 
artery, right colic and middle colic, and resection of the distal transverse or descending colon2. 
Intestinal reconstruction is performed by a manual or mechanical ileocolic anastomosis. For years, 
multiple investigations have been realized to determine the best technique for ileocolic 
anastomosis (suture in one or two planes, simple or continuous suture, resorbable or non-
absorbable material, mechanical sutures, etc.), but until now there have been no diﬀerences 
regarding the rate of suture dehiscence. 
Lymphadenectomy has diﬀerent objectives: staging the tumor in the surgical act and trying to 
perform a complete resection to improve oncological results, this way evaluating the quality of the 
surgical procedure. There is a direct correlation between the number of lymph nodes excised, and 
therefore evaluated, with survival. For a long time is known that the existence of ganglia in the 
surgical piece depends on the surgical technique and the methodology used. The Clinical 
Guidelines recommend a minimum of 12 lymph nodes studied for a correct tumor stage3-4. 
For years, minimally invasive surgery is performed in a large number of interventions in a safe way. 
Jacobs et al5 described the ﬁrst laparoscopic resection in sigma cancer in 1991. Since then the 
experience has grown rapidly, and diﬀerent clinical trials6,7,8 showed improvements in the 
postoperative period of the patient without oncological diﬀerences. Only the Lacy study showed 
greater lymph node excision with the laparoscopic technique9. 
At present laparoscopic surgery has show to be a safe technique, which a better recovery of the 
patient (decreasing postoperative ileus, early oral diet, more controlled pain, fewer days of 
hospital stay ...) and also reduces the rates of complications if performed by experienced surgical 
teams10. The most recent randomized studies have shown no oncological diﬀerences with respect 
to open surgery. The percentage of conversion in the literature varies from 2 to 46% depending 
mainly on the experience of the team. 
Among surgical techniques by means of minimally invasive surgery, right colectomy can be 
considered a particular case in which the technical diﬃculty added by the frequent anatomical 
variations, especially vascular ones, have meant a more gradual acceptance of the laparoscopic 
approach11. Unlike the technique used in rectal-sigmoid neoplasms, ileocolic anastomoses after 
right hemicolectomy can be performed in two ways: extracorporeal or intracorporeal.  

The extracorporeal anastomosis is performed by externalizing the ileum and colon through the 
incision through which the surgical specimen is extracted. The intracorporeal anastomosis is 
performed completely laparoscopically, and the incision made is only to remove the surgical 
specimen. 
JUSTIFICATION: 
Right hemicolectomy using a minimally invasive technique allows for an earlier recovery, with less 
postoperative pain and less hospital stay. After right hemicolectomy, the ileocolic anastomosis is 
not performed "naturally" as is habitually done in low anterior resections or sigmoidectomies. 
There is, therefore, no standardization in the reconstruction technique, with two possibilities: 
intracorporeal and extracorporeal anastomosis14. 
The intracorporeal anastomosis allows proper visualization of it, ensuring adequate conformation 
(absence of rotation or traction), in addition allowing the closure of the mesos and avoiding the 
possible appearance of internal hernia, also allowing to choose the location and length of the 
incision necessary for the extraction of the piece. On the other hand, it is a diﬃcult technique that 
requires high training in advanced laparoscopy. 
The extracorporeal anastomosis is performed by extracting both ends (terminal ileum and 
transverse colon) through the incision through which the piece is obtained, and the anastomosis 
is performed. It does not require, therefore, an important training in intracorporeal sutures. On the 
contrary, it forces to make the abdominal incision in the area that allows the extraction of said 
ends. In obese patients it can be diﬃcult since the mesos are short and do not allow their 
extraction easilywith ,so sometimes, it forces excessive traction. In addition, intestinal rotations 
during the anastomosis may go unnoticed. 
Although there are currently defenders of both techniques, the extracorporeal anastomosis is 
currently the most performed in our environment and will be used as a reference treatment in the 
present study. 
Numerous studies have been published comparing both techniques11-20. A very recent meta-
analysis21, including 12 non-randomized comparative studies with 1492 patients, concluded that 
intracorporeal anastomosis is associated with less morbidity and a reduction in hospital stay, 
suggesting a faster recovery. To date, no well-designed, prospective, randomized and randomized 
study exists in the literature. We believe it is necessary, therefore, to carry out a project that 
compares both surgical techniques in the treatment of right colon cancer and assess which is 
associated with a lower postoperative morbidity. 
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Lacy AM, García-Valdecasas JC, Delgado S, Castells A, Taurá P, Piqué JM, et al.Laparoscopy-
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OBJECTIVES: 
The objectives of our study are: 
GENERAL: 
- To compare perioperative morbidity between laparoscopic right hemicolectomy with 
intracorporeal anastomosis versus extracorporeal anastomosis within 30 days after surgery. 

SPECIFIC: 
- Quantify, by means of the Visual-Analogue Scale (VAS), postoperative pain 24 hours after 
surgery and the day of hospital discharge, and determine which of the two laparoscopic right 
hemicolectomy techniques produces less pain. 
- To evaluate and compare the rate of anastomotic dehiscence in both groups of anastomoses 
up to 30 days after surgery. 
- To evaluate the diﬀerence in surgical time between right hemicolectomy with intracorporeal 
versus extracorporeal anastomosis. 
- To evaluate the infection rate of the surgical site in both groups up to 30 days after surgery. 
- To compare the diﬀerence of days of hospital stay in both groups of anastomoses. 
WORK HYPOTHESIS: 
In patients with right colon cancer, laparoscopic right hemicolectomy with intracorporeal 
anastomosis presents less perioperative morbidity than extracorporeal anastomosis. 
MATERIALS AND METHODS: 
Patients treated in 4 Spanish South-east hospitals with preoperative diagnosis of right colon 
neoplasm were included. All participating hospitals have vast experience in minimally invasive 
approach.  
Study Design 
The IVEA-study is a prospective multicenter randomized trial with two parallel groups being done 
IA or EA in laparoscopic right hemicolectomy for right colon neoplasia. The patients were 
randomized using http://www.randomization.com. 
Inclusion and Exclusion Criteria 
• Inclusion criteria. All patients had to be 18 years of age or over, to be programmed for 
laparoscopic surgery for right colon neoplasm and provide a signed written consent form. 
• Exclusion criteria. All patients who do not meet all the inclusion criteria were excluded. The 
other exclusion criteria included the need for emergency surgery, renal failure deﬁned by 
haemodialysis, Crohn's disease, ulcerative colitis, T4 tumor invading adjacent organs, 
synchronous colorectal neoplasm, metastasis or carcinomatosis at diagnosis, bowel 
obstruction, psychiatric disorders or contraindication for laparoscopic approach. 
Outcome Measures 
Patient baseline characteristics at the time of surgery; age, gender, ASA score, major 
comorbidities and operative variables were obtained from each patient. The 30-day postoperative 
complications were recorded. Complications were deﬁned as any deviation from the normal 
postoperative course and graded using Clavien-Dindo classiﬁcation. The term anastomotic 
leakage (AL) deﬁnes all conditions with clinical or radiologic anastomotic dehiscence, with or 
without the need of surgical revision. Wound infection was deﬁned as spontaneous drainage of 
purulent material from the wound or from the surgeon´s deliberate revision and a positive culture 
of drained serous ﬂuid. The length of hospital stay (LOS), reinterventions, postoperative pain 
according to the visual analogical scale were also documented. For the subsequent analysis of 
the patient, the conversion to an extracorporeal anastomosis among the totally laparoscopic 
procedures or conversion to open surgery has not been included. 
Surgical technique 
Perioperative care was identical for both groups. Bowel preparation was not used, and 
intravenous antibiotics were administered preoperatively. Under general anesthesia, the patients 
were placed supine on the operating table, with open legs. Urinary catheter was inserted. 
Pneumoperitoneum was induced using carbon dioxide insuﬄated to an average pressure of 12 
mmHg by placement of a  infraumbilical trocar. Three additional ports were inserted: 12 mm in the 
left lower quadrant and two 5-mm trocars in the right lower quadrant and upper left quadrant. 
Laparoscopic right colectomy was performed with a medial-to-lateral approach, starting with 
ligation of the blood vessels at their origin followed by mobilization of the bowel and lateral 

dissection of the terminal ileum and colon attachments. The colon and ileum were transected with 
a 60-mm laparoscopic stapler in that order, followed by an ileo-transverse anastomosis. 
• Intracorporeal anastomosis:  
The specimen was preferentially extracted via a small Pfannenstiel-type incision with the 
protection of an Alexis Wound Protector (Applied Medical, Rancho Santa Margarita, California, 
USA).  The incision for the extraction of the right colon is sutured in two layers by absorbable 
suture. The ileum was held by the assistant to prevent rotation of its mesentery. A stay suture was 
applied 10 cm proximal and distal to the stapled ends of the terminal ileum and colon, 
respectively, and then held by the assistant. An enterotomy and colotomy were made sharply at 
the antimesenteric corner of the staple lines. An isoperistaltic side-to-side anastomosis was 
fashioned with a 60-mm laparoscopic stapler. A 2-0 double-barbed suture was used to close the 
enterocolotomy, in two planes (the ﬁrst submucosal, and the second sero-serous).  The 
mesenteric defect and the mesocolon after the construction of either type of anastomosis were 
not closed. Drains were not used routinely.  
• Extracorporeal anastomosis 
The mobilized colon was externalized preferentially via a transverse or midline incisión with the 
protection of an Alexis Wound Protector (Applied Medical, Rancho Santa Margarita, California, 
USA). A stay suture was applied 10 cm proximal and distal to the stapled ends of the terminal 
ileum and colon. An enterotomy and colotomy were made sharply at the antimesenteric corner of 
the staple lines. An isoperistaltic side-to-side anastomosis was fashioned with a 60-mm 
laparoscopic stapler. A 2-0 double-barbed suture was used to close the enterocolotomy, in two 
planes (the ﬁrst submucosal, and the second sero-serous). The mesenteric defect and the 
mesocolon after the construction of either type of anastomosis were not closed. The incision for 
the extraction of the right colon and the realization of the anastomosis is sutured in two layers by 
absorbable suture. Drains were not used routinely.  
Postoperative Management 
After surgery, nasogastric tubes were not used, the urinary catheters were removed on 
postoperative day 1. Early mobilisation was practised and oral ﬂuids administered early, switched 
to a diet after ﬁrst passage of ﬂatus.  and endovenous hydrations were suspended. Criteria for 
discharge included pain control, absence of nausea and tolerance of a soft diet without 
restrictions and passage of gas and stool. All patients were followed-up for at 30 days. 
Ethics 
The study was presented to the Hospital Ethical Board and accepted as a multicenter randomized 
trail. The research was conducted conformed to the Helsinki Declaration and to local legislation. 
Patients gave informed consent to participate in the study. This study has been registered in 
XXXXX register with the number XXXXX. 
Sample Size Calculation 
The hypothesis of this trial is that IRA will reduce overall postoperative 30-day morbidity rate. The 
sample size calculation is based on the detection of signiﬁcant diﬀerence in the primary endpoint 
parameter of the trial. We assumed a postoperative complication rate of 30% in ERA according 
with several complication rates after colorectal surgery. With an expected complication rate of 
11% in IRA, the sample size necessary for the trial with a power of 80% and one-sided 
signiﬁcance level of 0.05 was calculated to be 75 patients per group. An assumed 10% drop-out 
rate in this trial will raise the sample size to 84 patients per group. Therefore, at least a total of 168 
patients have to be included to the trial. 
Statistical Analyses 
Statistical analyses of any diﬀerences between the 2 groups were performed using SPSS version 
22 (SPSS Inc. Chicago, IL). Data were presented as means ± standard deviations or as medians 
and interquartile ranges where appropriate. For dichotomous outcomes, treatment groups were 
compared by means of the χ2 test. The Mann–Whitney U test and Kruskal–Wallis tests were used 
for continuous, not normally distributed outcomes. For continuous normally distributed data, the 
ANOVA test was used.  

Insurance policy 
An insurance policy will not be subscribed given that it is not a clinical trial with medications, and 
that the following conditions are met:  
1. The surgical treatments that are applied in the trial are authorized in Spain and their use is 
adjusted to the conditions authorized and of usual practice. 2. The interventions to which the 
subjects will be submitted for their participation in the trial suppose a risk equivalent or inferior to 
the one that would correspond to their attention in the usual clinical practice; complying with the 
criteria of clinical trial of low level of intervention as speciﬁed by Royal Decree 1090/2015, of 
December 4 that regulates clinical trials with drugs, the Research Ethics Committees with 
medicines and the Spanish Registry of Clinical Studies. 
CHRONOGRAM-PHASES OF WORK:  
• SURGICAL INTERVENTION: We will perform surgical interventions throughout the ﬁrst 18 
months of the study. Patients will be randomized and, depending on the group, the technique 
will be performed by intra-or extracorporeal anastomosis. During the ﬁrst eighteen months. 
• FOLLOW UP: Patients will be assessed daily during their hospital stay, and subsequently in 
consultation according to the protocol that is attached in methodology. 
• DATA COLLECTION: All data will be included in the data collection notebook, and will be added 
in a Microsoft Access XP database, throughout the entire study. 
• STATISTICAL STUDY: Once all the data have been collected, a statistical study will be carried 
out using the SPSS program as described in the data analysis (methodology). One month 
• REDACTION OF RESULTS. The results will be written when the deﬁnitive statistical study is 
carried out according to: introduction, objectives, hypothesis, patients and methods, results, 
discussion, conclusions and bibliography. Five months. 
AVAILABLE MEDIA: MATERIAL (PROVIDED BY THE OWN CENTER): 
There is adequate surgical space with all the necessary material for the realization of both 
interventions: Operating room; two laparoscopic towers (camera source, light source, CO2 
insuﬄator, monitors), laparoscopic optics of 0º and 30º; optics and last generation laparoscopy 
tower; laparoscopy box for colorectal surgery (complete equipment of laparoscopic instruments); 
hemostasis and cutting device (Ligasure®, Ultracision®) ... 
In addition, a computer system is available in an intrahospital network so that the database of the 
coloproctology unit can be consulted from diﬀerent teams. 
AVAILABLE MEDIA: RESEARCH TEAM: 
Dr. Manuel Ferrer Márquez. Unidad de Coloproctología. Especialista en laparoscopia avanzada 
Dr. Ángel Reina Duarte. Jefe de la Unidad de Coloproctología. Jefe de Sección. 
Francisco Rubio Gil. Unidad de coloproctología. Especialista en laparoscopia avanzada 
Dra. Elisabet Vidaña Márquez. Unidad de Coloproctología. Especialista en laparoscopia avanzada 
Dr. Juan Manuel García Torrecillas. Unidad de investigación, hospital Torrecárdenas 
Rocío Torres Fernández. Residente de Cirugía General y Digestiva.  
Almudena Moreno Serrano. Servicio de Cirugía General y Digestiva. Especialista en laparoscopia 
avanzada 
Paolo Fabiano. Servicio de Cirugía General y Digestiva. Especialista en laparoscopia avanzada 
Pedro Moya Forcén. Servicio de Cirugía General y Digestiva. Especialista en laparoscopia 
avanzada. 
Enrique Manuel Pellicer Franco. Unidad de Coloproctología. Especialista en laparoscopia 
avanzada. 
Jorge Alejandro Benavides Bueleje. Unidad de Coloproctología. Especialista en laparoscopia 
avanzada.