The Impact of NOSE-colectomy on Fertility and Quality of Life Among Patients With Colorectal Endometriosis

Study Overview
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Brief Summary
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Deep infiltrating endometriosis (DIE) represents the most severe form of endometriosis and is present in 20-35% of all women suffering from the disease. Intestinal nodules are observed in 3% to 37% of endometriosis patients. In cases of colorectal DIE, adequate therapy depends on the depth of infiltration and the size of the lesion as well as the woman's quality of life. Removal of the specimen after segmental bowel resection can be performed by either mini-laparotomy or by the natural orifice specimen extraction (NOSE) technique . The assessment of the quality of life and fertility outcome of the patients was done by using electronic questionnaires before and after surgery.

Detailed Description
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Endometriosis is an enigmatic disease affecting 6-10% of women of reproductive age or 176 millions of women worldwide (1). Endometriosis is defined as the presence of endometrial-like tissue outside the uterus and it induces a chronic inflammatory reaction (2). Deep infiltrating endometriosis (DIE) represents the most severe form of endometriosis (described by the invasion of anatomical structures and organs deeper than 5 mm beyond the peritoneum) and is present in 20-35% of all women suffering from the disease (3). Intestinal deep infiltrating endometriosis is known as lesions infiltrating at least the muscular layer of the bowel wall and most commonly affects the rectum, sigmoid colon and the rectovaginal septum. (4). Even if bowel endometriosis may be totally asymptomatic, in many patients intestinal wall DIE alters significantly quality of life by provoking constipation, diarrhea, hematochezia, intestinal cramping, abdominal bloating, intestinal stenosis or obstruction and pain of defecation (5, 6). Rectal fixation to adjacent structures results in angulation of the rectum and subsequent defecatory pain and constipation. Fibrosis of nodules can lead to rectal constriction and stenosis, cyclical inflammation of the rectal wall may lead to changes in bowel habit (usually diarrhoea) with or without rectal bleeding (7). Although the surgical laparoscopic management of endometriosis is widely accepted, the optimal type of resection, whether conservative approach (shaving, disc resection) or radical technique (involves limited resection of the bowel wall with preservation of all adjacent structures-autonomic pelvic plexus, rectal vascular supply- known as nerve-vessel sparing limited segmental resection), is under discussion for treatment of deep endometriosis infiltrating the rectum. In cases of colorectal DIE, adequate therapy depends on the precise location, extent of the nodule and depth of invasion, as well as the woman's quality of life (3). Removal of the specimen after segmental bowel resection can be performed by either mini-laparotomy (conventional method) or by the natural orifice specimen extraction (NOSE) technique. (8). The conventional method raises concerns because this could disrupt the integrity of the abdominal wall. Moreover, extraction site laparotomy is associated with higher postoperative pain scores. The occurrence of particular complications such as incisional hernias and wound infections is also higher than after conventional laparoscopic procedures (8). In order to avoid these complications, NOSE technique has been introduced. During NOSE colectomy the specimen is extracted through a natural orifice and an intracorporeal anastomosis is performed (8). Several studies have demonstrated a significant drop in pain scores and amelioration of impaired sexual functioning and improved pregnancy rates in women following surgical resection of colorectal endometriosis (9). The aim of this study is to report the short, medium and long-term bowel functional outcomes and improvement of infertility, quality of life in women undergoing conventional and NOSE segmental bowel resection for endometriosis at our institution using validated questionnaires. Functional and psychological outcomes will be assessed using different questionnaires at baseline and postoperative follow-up moments. Endometriosis Health Profile, EHP 30 (10) Gastrointestinal Quality of Life Index, GIQLI (11) Low Anterior Resection Syndrome score, LARS (12) Assessment of endometriosis related pain: Visual Analog Scale (13) Psychological questionnaires: Pain catastrophizing Scale (14), Self-Efficacy for Managing Chronic Disease 6-item Scale (15).

Official Title
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The Impact of NOSE-colectomy on Fertility and Quality of Life Among Patients With Colorectal Endometriosis

Conditions
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Endometriosis, Quality of Life

Intervention / Treatment
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* Procedure: Surgical procedures( conventional laparoscopic and NOSE technique) for the treatment of colorectal DIE


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age: 18 - 45 years (both inclusive) Complaining of infertility and/or pain Deep endometriosis infiltrating the rectum on at least one imaging technique or confirmed by previous surgery up to 15 cm from the anus Involving at least the muscularis layer in depth Exclusion criteria A potential subject who meets any of the following criteria will be excluded from participation in this study: Suspected pelvic malignancy Pregnancy Patients without bowel resection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Our study was designed as a two-arm prospective randomized trial where all cases will be executed unblindly. As an experimental clinical trial the cases have been managed independently where the applied measures were computer based randomization. In addition clustering effect has been examined within the two groups. The statistical power will be calculated for a sample size. Randomization: Blinding in our study is not feasible. Assignment of a patient to conventional or NOSE-colorectal resection is based on a randomization list using the simple randomization method. In order to determine the allocation sequence a computer based (www.random.org) coin flipping is carried out by a staff member with no clinical involvement in the study. The randomization will start after the patient had completed all baseline assessments and had given written consent to be enrolled in the trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients operated with conventional laparoscopic technique<br>Patients operated with conventional laparoscopic technique for colorectal DIE | Procedure: Surgical procedures( conventional laparoscopic and NOSE technique) for the treatment of colorectal DIE<br>* For conventional laparoscopic and NOSE techniques a 4-port approach is used. The rectum is skeletonized. The distal rectum is closed using an endoscopic linear stapler. The mobilized rectum with the specimen is retrieved through a small suprapubic incision. The anvil of a conventional circular stapler is introduced in the proximal colon after placement of a purse string suture. A circular stapled colorectal anastomosis is fired. In case of NOSE, both the proximal sigmoid colon and the proximal rectum are tied off laparoscopically with a nonabsorbable suture. A transverse colotomy is performed in healthy tissue using a harmonic scalpel to deliver the anvil from a circular stapler introduced through the anus. The specimen is extracted transrectally in a specimen retrieval bag. Proximal part of the anastomosis is completed by suturing the anvil in place with a laparoscopic suture. The distal rectum is closed using a linear stapler. End-to-end anastomosis is made using the circular stapler<br>|
| Active Comparator: Patients operated with NOSE laparoscopic technique<br>Patients operated with NOSE technique for colorectal DIE | Procedure: Surgical procedures( conventional laparoscopic and NOSE technique) for the treatment of colorectal DIE<br>* For conventional laparoscopic and NOSE techniques a 4-port approach is used. The rectum is skeletonized. The distal rectum is closed using an endoscopic linear stapler. The mobilized rectum with the specimen is retrieved through a small suprapubic incision. The anvil of a conventional circular stapler is introduced in the proximal colon after placement of a purse string suture. A circular stapled colorectal anastomosis is fired. In case of NOSE, both the proximal sigmoid colon and the proximal rectum are tied off laparoscopically with a nonabsorbable suture. A transverse colotomy is performed in healthy tissue using a harmonic scalpel to deliver the anvil from a circular stapler introduced through the anus. The specimen is extracted transrectally in a specimen retrieval bag. Proximal part of the anastomosis is completed by suturing the anvil in place with a laparoscopic suture. The distal rectum is closed using a linear stapler. End-to-end anastomosis is made using the circular stapler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometriosis Health Profile, EHP 30 | To describe the difference in patient reported outcomes after conventional segmental bowel resection treatment in comparison to NOSE colectomy in patients with deep endometriosis infiltrating the rectum. The patients are asked to fill the questionnaires preoperatively, at 30 days, 6 months, 1 year and 2 years after the surgery. During the present study investigators are planning an average follow-up of 24 months. Impact of surgical technique on the quality of life. The outcome will be assessed using validated electronic questionnaires containing questions from Endometriosis Health Profile 30. This is a core questionnaire which consists of five scales (pain, control and powerlessness, emotional well-being, social support, and self-image) contains a total of 30 items. (10) | 24 months | 
| Gastrointestinal Quality of Life Index, GIQLI | To describe the difference in patient reported outcomes after conventional segmental bowel resection treatment in comparison to NOSE colectomy in patients with deep endometriosis infiltrating the rectum. The patients are asked to fill the questionnaires preoperatively, at 30 days, 6 months, 1 year and 2 years after the surgery. During the present study investigators are planning an average follow-up of 24 months. GIQLI is a 36-item patient reported outcomes instrument designed to assess GI-specific health-related quality of life in clinical practice of patients with gastrointestinal disorders. It has five domains (GI symptoms, emotion, physical function, social function and medical treatment) and subscores range from 0-4 while the total score range from 0-144. Higher scores mean better GI health-related quality of life. (11) | 24 months | 
| LARS score before and after colorectal resection for DIE | To describe the difference in patient reported outcomes after conventional segmental bowel resection treatment in comparison to NOSE colectomy in patients with deep endometriosis infiltrating the rectum. The patients are asked to fill the questionnaires preoperatively, at 30 days, 6 months, 1 year and 2 years after the surgery. During the present study investigators are planning an average follow-up of 24 months. The Low Anterior Resection Syndrome (LARS) is a common complication that occures after colorectal surgery. The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal surgery. Contains questions regarding incontinence, emptying difﬁculties, urgency, and frequency. The calculated score ranges from 0 to 42, with a score of 0-20 representing no LARS, a score of 21-29 representing minor LARS and a score of 30-42 representing major LARS. (12) | 24 months | 
| Endometriosis related pain before and after colorectal resection for DIE | To describe the difference in patient reported outcomes after conventional segmental bowel resection treatment in comparison to NOSE colectomy in patients with deep endometriosis infiltrating the rectum. The patients are asked to fill the questionnaires preoperatively, at 30 days, 6 months, 1 year and 2 years after the surgery. During the present study investigators are planning an average follow-up of 24 months. For the assessment of pre- and postoperative pain a Visual Analogue Scale is used (from 1-10, where 1 is the lowest and 10 is the maximum score) to assess the pre- and postoperative quality of life (dysmenorrhoea, dyspareunia, dyschezia, dysuria, CPP) (13). | 24 months | 
| Infertility outcomes after colorectal resection for bowel endometriosis | Number of pregnancies, cumulative pregnancy rate and take home baby rate after laparoscopic bowel resection. | 24 months | 
| Psychological questionnaires: | To describe the difference in patient reported outcomes after conventional segmental bowel resection treatment in comparison to NOSE colectomy in patients with deep endometriosis infiltrating the rectum. The patients are asked to fill the questionnaires preoperatively, at 30 days, 6 months, 1 year and 2 years after the surgery. During the present study investigators are planning an average follow-up of 24 months. Pain catastrophizing Scale, Self-Efficacy for Managing Chronic Disease 6-item Scale to investigate the psychological aspect of the disease (14,15). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complication rates after conventional and NOSE-colectomy performed for colorectal endometriosis | To measure the complication rates after conventional and NOSE-colectomy performed for colorectal endometriosis. The complication rates between the NOSE vs conventional specimen extraction technique will be examined. The difference between the complication rates will be presented according to Clavien-Dindo Classification System (16). As follows: Grade I Any deviation from the normal postoperative course without treatment by invasive interventions Grade II Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Grade III Requiring surgical, endoscopic or radiological intervention IIIa Intervention not under general anesthesia IIIb Intervention under general anesthesia Grade IV Life-threatening complication requiring IC/ICU-management IVa single organ dysfunction (including dialysis) IVb multiorgan dysfunction Grade V Death of a patient | 24 months | 
| Hospital stay after colorectal resection perfomed for the treatment of bowel endometriosis | To measure the hospital stay after colorectal resection perfomed for the treatment of bowel endometriosis | 24 months | 
| Lenght of recovery after colorectal resection performed for the treatment of bowel endometriosis | To measure the lenght of recovery after bowel resection will be assessed by the comparison of the hospital stay (mean +/- SD days) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fertility, Colorectal endometriosis, Surgery