This study aims to investigate the relationship between the neurovascular density and the
amount of pain mediators present in the excised endometriotic nodule and peritoneal
surface during laparoscopic douglasectomy surgery routinely performed in cases of
endometriosis unresponsive to medical treatment, and their correlation with pain scores.
Together with the findings obtained, the goal is to determine the excision boundaries and
surgical safe margins in endometriosis surgery.
Since endometriosis primarily affects the pelvic region, women often encounter various
types of chronic pelvic pain, dyspareunia, dysmenorrhea, and dyschezia in daily life
depending on the size and location of the nodule, which do not pass frequently. These
pains often do not respond to analgesic drugs, and patients experience severe pain
attacks. As it is a disease dependent on estrogen in treatment, treatments containing
anti-estrogenic and progesterone are primarily applied to suppress the development of
endometriosis, while the surgical removal of endometriotic nodules in cases unresponsive
to medical treatment provides benefit in terms of pain palliation. In this context,
although surgery ideally performed as laparoscopic surgery, peritoneal nodules in the
pelvic region are excised together, a procedure called douglasectomy. In many animal
experiments, endometriosis nodules have been histopathologically examined, and it has
been shown that there is a rich structure in terms of nerve fibers, vascular structure,
and pain mediators within the nodule. However, this surgery is a highly specific surgical
method and is performed by experienced centers and surgeons. Consequently, the number of
patients undergoing ideal surgery is limited. In this limited population, the vascular
and neurogenic structure in the peritoneum and nodule surgically removed after
douglasectomy, as well as the amount of pain mediators synthesis, remains an unexplored
virgin subject. Although increased nerve density within the nodule has been shown in
limited studies, the clinical relationship of this density, and its effects on pain
scores, has not been investigated in any study on the pathology material removed after
douglasectomy operation.
Through the data obtained from this research, the investigators will conclude the
histological boundaries of neuro-angiogenic changes occurring in endometriosis disease,
the extent of involvement in the pelvic peritoneum, and thus the minimum amount of tissue
to be excised during surgery. This result will shed light on a topic that has not been
studied in the literature so far and will be a milestone in terms of excision boundaries
and surgical safe margins in endometriosis surgery.
This clinical study, approved by the Bursa Uludağ University Faculty of Medicine Clinical
Research Ethics Committee with decision number 2023-13/37 on 13.06.2023, will be
conducted in the Department of Obstetrics and Gynecology at Bursa Uludağ University
Faculty of Medicine. Women of reproductive age who apply to the endometriosis clinic,
cannot respond to medical treatment, and are planned for surgery will be included in the
study. An average of approximately 150 endometriosis surgeries are performed in our
clinic annually. The number of patients to be included in the study was calculated as at
least 15 in the power analysis conducted, and the patient recruitment for the study will
be completed in a short time in our center, where approximately 150 endometriosis
surgeries are performed annually. All demographic data of the patients, preoperative
laboratory, and clinical findings will be recorded through files. From the patients who
agree to participate in the study, peritoneal tissue samples of 1 cm in size (Figure-1)
taken from the pathology specimen removed after the routine surgical procedure will be
histopathologically examined, and nerve fibers and vascular structures per square
millimeter will be counted after appropriate staining (hematoxylin & eosin and toluidine
blue). In addition, tissue samples preserved under appropriate conditions will be
examined for pain mediators (bradykinin, substance P, nerve growth factor, PGP9.5) using
the ELISA (Enzyme-Linked ImmunoSorbent Assay) method with kits to be obtained. An average
of 10 peritoneal tissue samples will be taken from each patient, and a total of 150
samples will be examined. Each sample will be analyzed twice using the ELISA method, and
at least 4 sets of 96 kits will be required for the examination of mediators in 150
separate tissue samples. Results will be analyzed following the commercial ELISA kit
protocol. Through the obtained data, the correlation between preoperative pain scores
(VAS score - visual pain score) and the neurovascular density within the nodule will be
evaluated, and the effects of laparoscopic surgery with nodule excision on pain will be
histopathologically demonstrated.
