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.