Visualization of endometriosis with laparoscopy and near-infrared optics with indocyanine green.

INTRODUCTION: Endometriosis is a common health problem, affecting 10% of women of reproductive age. Laparoscopic surgery is proven to relieve pain and to improve fertility in women with endometriosis. However, identifying peritoneal endometriosis lesions may be difficult due to their polymorphic aspects. Endometriosis lesions harbor a high degree of neovascularization. The visualization of tissue perfusion by the additional use of near infrared fluorescence imaging with indocyanine green (ICG) may improve the detection of endometriosis lesions. MATERIAL AND METHODS: In a single-center, prospective, single-arm pilot study, patients undergoing laparoscopic surgery for suspected endometriosis and/or infertility were recruited. All patients first had white light imaging with systematical documentation of all suspicious areas. ICG was then administered intravenously at .3 mg/kg bodyweight and the near infrared imaging was activated and an identical documentation of suspected lesions was performed again. After removal, the specimen were sent to pathology. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT03850158. RESULTS: In total, 173 suspected lesions were identified and excised, of which 150 had histologically proven endometriosis. Of the total number, 166 suspected lesions were detected using white-light and 32 with ICG. Among the 32 suspected lesions found with ICG, 22 were confirmed to be endometriosis. Seven additional lesions were identified with ICG alone, of which only one was histologically proven endometriosis. Positive predictive values were 89.8%, 68.8% and 86.7% for white-light laparoscopy alone, near-infrared (NIR)-ICG visualization alone, and the combination of white-light and NIR-ICG, respectively. ICG exposure time, previous abdominal surgery and rARSM stage showed a statistically significant impact on the ICG detection rate. In seven patients, ICG was used for the resection of deep infiltrating nodules from the rectum. In these cases, NIR fluorescence imaging with ICG was useful to define the borders between an endometriotic nodule and healthy tissue. CONCLUSIONS: The diagnostic value of NIR-ICG imaging in identifying endometriosis appears to be minimal. ICG exposure time over 20 minutes, no previous abdominal surgery and low rASRM stages have a significant positive effect on the ICG detection rate. NIR fluorescence imaging with ICG was helpful in the resection of deep infiltrating nodules in providing a better visualization of endometriosis.

Near-Infrared Imaging with Indocyanine Green for Detection of Endometriosis Lesions (Gre-Endo Trial): A Pilot Study.

STUDY OBJECTIVE: To evaluate near-infrared radiation imaging with intravenous indocyanine green (NIR-ICG) during laparoscopic intervention to identify endometriosis lesions. DESIGN: A single-center, prospective, single-arm pilot study (Canadian Task Force classification II-2). SETTING: An academic tertiary care and research center. PATIENTS: Twenty-seven patients with symptomatic endometriosis were enrolled. INTERVENTIONS: Patients underwent laparoscopic surgery using a laparoscopic system prototype with NIR-ICG. MEASUREMENTS AND MAIN RESULTS: A total of 116 suspected endometriosis lesions were removed from 27 patients. One hundred lesions had already been visualized in white light imaging by an expert surgeon; the remaining 16 were detected and removed using NIR-ICG. A total of 111 specimens were positive for endometriosis pathology. Positive predictive value of 95% and 97.8% and negative predictive value of 86.2% and 82.3% were found by white light imaging and NIR-ICG, respectively, with sensitivity of 85.6% and 82% and specificity of 95.2% and 97.9%, respectively. CONCLUSION: NIR-ICG may be a tool for intraoperative diagnosis, confirmation of visible endometriosis lesions, and a marker for identifying occult endometriosis. Further prospective studies with a larger population sample are warranted to validate these encouraging preliminary results.

Occult microscopic endometriosis: undetectable by laparoscopy in normal peritoneum.

STUDY QUESTION: Is there any occurrence of hidden (occult) endometriotic lesions in normal peritoneum of women with and without visible endometriosis? SUMMARY ANSWER: We detected a slightly higher occurrence of occult microscopic endometriosis (OME) in normal peritoneum of women with visible endometriosis than in control women. WHAT IS KNOWN ALREADY: Based on a small number of cases, the concept of invisible microscopic endometriosis in visually normal peritoneum has been reported for more than a decade but there is controversy regarding their tissue activity and clinical significance. STUDY DESIGN, SIZE, DURATION: This case-controlled research study was conducted with prospectively collected normal peritoneal samples from 151 women with and 62 women without visible endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Normal peritoneal biopsy specimens from different pelvic sites of were collected during laparoscopy. A histological search of all peritoneal biopsy specimens for the detection of invisible endometriosis was done by immunoreaction to Ber-EP4 (epithelial cell marker), CD10 (stromal cell marker) and Calretinin (mesothelial cell marker). Tissue expression of estrogen/progesterone receptors (ER/PR) and cell proliferation marker, Ki-67, was performed by immunohistochemistry to identify tissue activity. MAIN RESULTS AND THE ROLE OF CHANCE: Three different patterns of OME were detected based on (I) the presence of typical gland/stroma, (II) reactive hyperplastic change of endometrioid epithelial cells with surrounding stroma and (III) single-layered epithelium-lined cystic lesions with surrounding stroma. A higher tendency toward the occurrence of OME was found in women with visible endometriosis (15.2%, 23/151) compared with control women (6.4%, 4/62) (P = 0.06, χ(2) test). The epithelial cells and/or stromal cells of OME lesions were immunoreactive to Ber-EP4 and CD10 but not reactive to Calretinin. ER and PR expression was observed in all patterns of OME lesions. Ki-67 index was significantly higher in pattern I/II OME lesions than in pattern III OME lesions (P< 0.05 for each). LIMITATIONS, REASONS FOR CAUTION: Bias in the incidence rate of OME lesions in this study cannot be ignored, because we could not analyze biopsy specimens from the Pouch of Douglas of women with revised classification of the American Society of Reproductive Medicine Stage III-IV endometriosis due to the presence of adhesions in the pelvis. WIDER IMPLICATIONS OF THE FINDINGS: We re-confirmed a decade long old concept of invisible (occult) endometriosis in visually normal peritoneum of women with visible endometriosis. The existence of a variable amount of tissue activity in these occult lesions may contribute to the recurrence/occurrence of endometriosis or persistence/recurrence of pain manifestation in women even after successful ablation or excision of visible lesions by laparoscopy. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science. There is no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: Not applicable.

Prevalence of occult microscopic endometriosis in clinically negative peritoneum during laparoscopy for chronic pelvic pain.

OBJECTIVE:  To determine the prevalence of occult microscopic endometriosis in patients with chronic pelvic pain and negative laparoscopy. METHODS: A retrospective cross-sectional study included women who underwent laparoscopic evaluation for chronic pelvic pain by three fellowship-trained gynecologic surgeons at a community hospital from January 2011 to December 2016. The aim was to evaluate the prevalence of microscopic endometriosis in this population. RESULTS:  In 142 patients with clinically negative peritoneum on laparoscopy, 39% had occult microscopic endometriosis. Cramping pain score during menses was found to be lower in the positive biopsy group (6.9 vs 8.0, P=0.046). No differences were appreciated in age of menarche, pain during various parts of the menstrual cycle, or duration of symptoms. The biopsy-positive group had a younger age at time of evaluation, although not statistically significant (P=0.179). Current use of hormones affected neither biopsy results nor menstrual or pain characteristics. Detection was similar between robotic and laparoscopic cases and operative morbidity was minimal. CONCLUSION: Occult microscopic endometriosis may be present in approximately 39% of patients with clinically negative appearing peritoneum undergoing laparoscopy for chronic pelvic pain. Given this, biopsies should be performed in patients undergoing laparoscopy who do not have visible lesions.