New Cross Linked Hyaluronan Gel After Deep Infiltrating Endometriosis Surgery
Condition: Endometriosis; Adhesion; Quality of Life; Surgery
MeSH terms: Endometriosis
Study type: Interventional

Summary: 
      Hyaluronan, a glycosaminoglycan found in connective tissues and extracellular matrix, has
      been postulated to reduce postoperative adhesions, because of its unconditioned biological
      functions at tissue repair but unfortunately it has a fluid nature that causes rapid
      degradation, and it cannot effect long enough to work as an adhesion barrier.(10,11) For this
      reason a New cross-linked hyaluronan (NCH) gel, that has higher viscosity compared to natural
      hyaluronan has been developed by BioRegen Biomedical (Changzhou, Jiangsu, China). It has the
      ability for gradually absorption within 1 to 2 weeks in vivo, which are the acquired repair
      period and the critical time for adhesion formation. Although it seems evident that
      endometriosis has a serious impact on the daily Quality of Life of women; comparable data for
      the effect of adhesion barriers to patients who have had laparoscopic (Deep infiltrating
      endometriosis) DIE surgery is missing.

      Therefore a pilot randomised controlled study was conducted to evaluate the effect of NCH gel
      on short term quality of life in patients who had undergone laparoscopic surgery due to DIE.
    

Detailed description: 
      A prospective 1:1 randomised placebo-controlled study was conducted in our department during
      the study period January 2017-January 2019. All patients were included after obtaining
      written, signed informed consent before participating. All of the procedures were performed
      by the same surgery team who are experienced in minimally invasive (Deep infiltrating
      endometriosis) DIE surgery. The study protocol was approved by the local Ethics Committee of
      hospital (Approval number: 2017/04/35) 60 patients who were underwent for laparoscopic
      surgery for the treatment of deep infiltrating endometriosis without bowel involvement were
      recruited.

      The inclusion criteria for this study were as follows, aged 18 to 45 years, and undergoing
      laparoscopic surgery for suspicious of DIE and persistent pain irrespective to any medical
      treatment. Patients were booked for follow-up visits at the 3rd and 6th month postoperative
      months and wanted to fill the questionnaires.

      The exclusion criteria for the study were as; acute or severe infection, autoimmune disease,
      known/suspected intolerance or hypersensitivity to Hyaluronan or its derivatives, concurrent
      use of a systemic anti-inflammatory or hormonal drug at least 3 months prior to the surgery,
      clinical evidence of cancer; use of anticoagulant, fibrin glue, other thromboembolic agents,
      or any other anti-adhesion agent during the procedure ,patients with surgically diagnosed
      bowel involvement or need bowel resection, and who want to receive any postoperative hormonal
      treatment.

      Participants were allowed to voluntarily withdraw from the trial for any reason at any time,
      and could be terminated by investigators owing to safety concerns, violations of
      inclusion/exclusion criteria, or pregnancy.

      Surgical procedure The patients were laid low lithotomy position under general anesthesia.
      Patients were assigned at random to either the NCH gel or control group in a 1:1 ratio
      through a computer based program. A standardised technic with 4 abdominal incision
      laparoscopic approach with 10 mm umbilical trocar for the optic camera and three 5 mm
      axillary ports for the surgical instruments were used. All of the surgeries initiated from
      exploring the pelvic cavity, identification of the ureters and dissection transection of the
      pelvic adhesion by 5 mm bipolar cautery used at 25 kw for coagulation mode and scissors. The
      incision was begun on the left pelvic sidewall just cephalad to the last deposit. The
      incision was then extended towards the uterus, lateral and parallel to the left uterosacral
      ligament. The uterosacral ligament was pushed medially and down and the healthy tissues
      including the ureter were pushed upwards and laterally away from the dissection. It then
      transected the right utero-sacral ligament and was continued along the right pelvic sidewall
      just lateral and above the right uterosacral ligament until it extends beyond all obvious
      deposits. All of the endometriotic foci was grasped and pulled then undercut and freed so
      that the whole lesion and a surrounding margin of healthy tissue was removed. After an
      extensive bleeding control the Patients in the intervention group had 40 mL of HyaRegen NCH
      gel instilled into the peritoneal cavity through a large-bore cannula following standard
      laparoscopic procedures. The patients in the control group had 40 cc sterile saline solution
      compatible with the body temperature. Operators could not be blinded to treatment allocation,
      but the questionnaire assessors and the patients were blinded to treatment allocation.

      Pre and Postoperative assessment of pain and quality of life A dedicated research assisted in
      this study was asked the validated (visual analogue scale) VAS (dysmenorrhea, dyschezia,
      dyspareunia, dysuria, and pelvic pain), (endometriosis health profile-5) EHP-5 and (short
      form 12) SF-12 questionnaires before the day of the surgery. (12-14) A validated form of VAS
      score was used and scored from 0: No pain to 10: the worst pain all in their lives in a
      likert fashion. The VAS and (quality of life ) QoL questions were asked then in the 3rd and
      6th month of during their follow up visits. A validated form of SF-12 that includes physical
      functioning, role limitation due to physical health problems, bodily pain, general health,
      vitality (energy/fatigue) social functioning, role limitations due to emotional problems and
      mental health (psychological distress or wellbeing) were asked. The questions are scored and
      analysed using a statistical algorithm to give two scores: the physical component summary and
      the mental component summary.

      A validated form of EHP-5 questionnaire was used to determine endometriosis related QoL of
      the patients. EHP-5 consists of two parts: the first has a central questionnaire that
      evaluate five dimensions - pain, control and powerlessness, emotional well-being, social
      support, and self-image; and the second part measuring the areas of sexual intercourse, work,
      relationship with children, feelings about medical professional, treatment and infertility.

      Statistical analysis Data analysis was performed by using SPSS (IBM SPSS Statistics for
      Windows, Version 20.0. Armonk, NY: IBM Corp.). A one-sample Kolmogorov-Smirnov test was
      performed to analyse the distribution of clinical variables. The frequency and percentage of
      the categorical variables and the mean, standard deviation, median and range values of the
      continuous and ordinal variables were presented. The study groups were compared using Student
      t test for parametric variables and Mann Whitney U test for the non-parametric variables. A
      post-hoc sample size calculation was performed via a two-sided Z test (α=0.05, β=0.20) for
      each study groups in order to obtain VAS scores as the primary outcome A p-value of < 0.05
      was considered statistically significant for all calculations
    

Intervention name(s): 40 cc HyaRegen NCH gel; 40 cc sterile saline solution
Intervention type(s): Drug; Drug
Intervention description(s): After an extensive bleeding control the patients in the intervention group had 40 mL of HyaRegen NCH gel instilled into the peritoneal cavity.; After an extensive bleeding control the patients in the control group had 40 cc sterile saline solution compatible with the body temperature.
Other intervention name(s): bleeding control; bleeding control
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Supportive Care