Improving accuracy of intraoperative diagnosis of endometriosis: Role of firefly in minimal access robotic surgery.

Endometriosis continues to be a major primary gynecologic etiology of chronic pelvic pain. The symptom profile, which includes cyclic pelvic pain, dysmenorrhea, and dyspareunia or dyschezia, is nonspecific and does not correlate with the extent or severity of disease. Trans-vaginal or trans-rectal ultrasound, as well as magnetic resonance imaging, can help visualize endometriomas and deeply infiltrating endometriosis. Additionally, there have been no serum marker tests available so far. However, even intraoperatively, the diagnosis may be missed, leading to under diagnosis and delayed or noninitiation of treatment. There are thought to be three distinct endometriotic lesions of the pelvis that are seen laparoscopically. The first is that which is visible on the pelvic peritoneal surface or the surface of the ovary, which is commonly termed peritoneal endometriosis. Second, endometriotic lesions that occur within the ovary and form cysts that are often lined with endometrioid mucosa are termed endometriomas. Lastly, rectovaginal endometriomas are endometriotic lesions that contain a mixture of adipose and fibrous tissue located between the rectum and vagina. All of these lesions can be singular or multiple and the pelvis may contain one or all three types of lesions. The shared histologic feature with all three lesions is the presence of endometrial epithelial cells or endometrial stroma. During a diagnostic procedure, the da-Vinci robot and its firefly mode allow for three dimensional visualization and seven degrees of instrument articulation for meticulous dissection of fibrotic areas of peritoneum that may contain deep infiltrating lesions of endometriosis. This case report describes a relatively new and innovative technique for effectively diagnosing and successfully treating endometriosis when other less invasive methods have failed.

INTRODUCTION

Endometriosis is found in the pelvis at multiple sites including the ovaries, uterus, fallopian tubes, uterosacral ligaments, broad ligaments, round ligaments, cul-de-sac and ovarian fossa. It can also occur on the appendix, large bowel, ureters, bladder, or rectovaginal septum. Although rare, extra-pelvic locations of endometriosis can also include the upper abdomen, diaphragm, abdominal wall, or abdominal scar tissue. Up to 20% of women with endometriosis have concurrent chronic pain conditions, including irritable bowel syndrome, interstitial cystitis/painful bladder syndrome, fibromyalgia, and migraines.[1] Endometriosis has been estimated to be the third leading cause of gynecologic hospitalization in the United States.[2] An accurate diagnosis and treatment of endometriosis can greatly impact the long-term outcome of patient care. In a retrospective study done by Camagna et al., 50 consecutive patients were operated on for a clinical presumption of endometriosis nodules in the recto-vaginal septum. Forty-three patients had nodules excised. Forty-one nodules were endometriosis nodules while the remaining two were fibrotic nodules. Thirty-three patients were interviewed about the evolution of their pains over a mean history of 20 months. About 90% of the patients were satisfied with the management results.[3] In the case below, we describe one of the new ways of improving accuracy of intraoperative diagnosis of endometriosis, especially in the posterior cul-de-sac.

CASE REPORT

A 27-year-old G1 P0010 presented for consultation with a history of chronic pelvic pain. She was diagnosed in Korea in 2010 with endometriosis via laparoscopy; however, no tissue biopsy was performed. She had an intrauterine device placed, which was removed in 2011 due to no resolution of symptoms, and subsequently was given Depo Lupron. She reported that the pain persisted, and she received Lupron for a total of 12 months until June of 2012. She was then started on oral contraceptive pills but continued to have chronic pelvic pain. In August of 2013, she underwent a diagnostic laparoscopy and was told that she had endometriosis once again. However, no biopsy was completed during this surgical procedure. The patient reported debilitating pain with associated rectal pain during her menses. Additionally, she had pain on intercourse with deep penetration. An ultrasound showed no evidence of an endometrioma, and magnetic resonance imaging was negative for the recto-vaginal endometriosis.

After a thorough review of the signs and symptoms of endometriosis, as well as evaluation of pathophysiology and current management options, the patient opted to undergo a third diagnostic laparoscopy. The patient desired removal of endometriotic lesions if any were present. The patient underwent a robotic laparoscopy using the da-Vinci Si robot firefly mode, an integrated fluorescence imaging capability providing real-time image-guided identification of key anatomical landmarks using near-infrared technology, for identifying endometriotic lesions. The ureters were first identified bilaterally to avoid injury. In normal three-dimensional mode on the da-Vinci Si, the pelvis appears endometriosis free [Figure 1]. However, when correlating the patient's complaints with the Firefly mode on the da-Vinci Si, the endometriotic lesions appear as green vascular structures [Figure 2]. Additionally, in firefly mode there is a clear area surrounding the dark vascular lesion, which represents fibrosis [Figure 2]. This was subsequently confirmed by tissue diagnosis. The pathology specimen obtained by peritoneal stripping of the involved area revealed fibrous tissue with foci of endometriosis [Figures 3 and 4]. Once lesions were identified, they were removed using blunt and sharp dissection. The deep recto-vaginal lesion was removed by placing an EEA sizer in the rectum for identification and full dissection of fibrous implant tissue. Endometriosis was initially diagnosed by sending the deep fibrous implant tissue for frozen section [Figure 5]. Hemostasis was assured, and cystoscopy was performed at the end of the case to ensure urologic integrity. The patient was given intramuscular Lupron 11.75 mg postoperatively and subsequently has had no further pelvic or recto-vaginal pain or dyspareunia within a 3 months follow-up.

Figure 1

Normal three-dimensional mode on the da-Vinci Si, the posterior culdisac appears endometriosis free

Figure 2

Posterior cul-de-sac lesion using firefly mode, there is clear area surrounding the dark vascular lesion, which represents fibrovascular tissue around islands of endometrial tissue

Figure 3

Peritoneal stripping of the involved area revealed fibrous tissue with foci of endometriosis

Figure 4

A low-power view of pelvic sidewall tissue showing endometriosis. There is fibrous tissue and smooth muscle with a focus of endometriosis near the surface. A small amount of hemorrhage is present (×40)

Figure 5

A minute focus of endometriosis on the surface of the tissue, present in a small fold. The cilia of the endometrial cells showing tubal metaplasia are focally prominent. Note the flat mesothelium lining the surface of the tissue directly opposite the endometrial epithelium (×400)

DISCUSSION

Management of endometriosis remains a challenge even with technological and chemotherapeutic advances. Although the pathophysiology of endometriosis is better understood, there is still no clear definitive treatment. The chemotactic factors released by peritoneal epithelial cell membrane injury in response to endometriotic cell invasion, including PGA2, PGI2 and TXA2, can influence the extent of the endometriosis. When the mesothelial cells on the serous membrane of the peritoneal surfaces become injured, fibroblasts invade the area and deposit extracellular matrix material, including collagen, which contributes to the adhesion development.[4] Adhesions that are associated with endometriosis can attach to nearby pelvic structures or cause deep tissue scarring. Subsequently, these lesions often cause immobilization of pelvic structures and manifest as pain when external forces are applied to the adherent structures. Deep infiltrating endometriosis (DIE) has been defined as a nodular blend of fibro-muscular tissue and adenomyosis.[5] These lesions are primarily found in the utero-sacral ligaments or cul-de-sac, but may also involve the recto-vaginal septum. Patients with DIE may present with deep dyspareunia and various bowel symptoms ranging from diarrhea to dyschezia during menses, depending on the location of the deep lesions.

The firefly mode on the da-Vinci Si can often identify these lesions using infrared technology to identify the vascular islands surrounded by fibro-vascular tissue. Firefly imaging has been available since 2011 as an optional feature of the da-Vinci Si system; however, it was just recently Food and Drug Administration approved for florescence imaging use on August 21, 2014. The system uses near-infrared imaging to detect an injected tracer dye of indocyanine green (ICG) in the blood. ICG is a tracer dye that binds tightly to plasma proteins, has a peak spectral absorption at about 800 nm and becomes confined to the vascular system. It is administered intravenously (IV), eliminated from circulation by the liver and has a half-life of approximately 3-4 min. Five milligrams ICG is injected into the IV by the anesthesiologist and gives a detailed picture of the peritoneal blood supply to the pelvis.[6] The technology has been used for several years to remove kidney tumors while sparing portions of the kidney that are not involved in the cancer. The endometriotic lesion will fluoresce as a green island in a lighter area of fibrosis surrounding it [Figure 2]. These lighter areas mixed with dark green areas represent “islands” of endometriosis in a sea of fibro-vascular scarring [Figure 4].

The rationale for “peritonectomy procedures,” also known as peritoneal stripping, stems from one of the managements of peritoneal surface malignancies. Peritonectomy procedures have been known to successfully treat peritoneal surface malignancies with curative intent. Peritonectomy procedures are used in the areas of visible cancer progression in an attempt to leave the patient with only microscopic residual disease.[7] In a similar fashion, identifying the endometrial lesions with the firefly and removing as many lesions as possible, including those that are deep and fibrosed, may provide an improved opportunity for both diagnostic and therapeutic interventions as in this patient. Somigliana et al. reviewed the clinical and surgical records of 93 womens who were diagnosed with deep peritoneal pelvic endometriosis at the time of surgery between January 1995 and June 2002 at the Department of Obstetrics and Gynecology, Clinica “L. Mangiagalli.” The concomitant presence of superficial endometriotic implants, endometriomas, and pelvic adhesions was evaluated. The presence of superficial endometriotic implants, endometriomas, and pelvic adhesions was documented in 61.3% (95% confidence intervals [CI] 51.4-71.2%), 50.5% (95% CI 40.3-60.7%) and 74.2% (95% CI 65.3-83.1%) of patients with deep endometriotic nodules, respectively.[8]

The current clinical approach to diagnosing endometriosis has been drifting toward visual inspection with symptomatology; however, tissue pathologic biopsy diagnosis remains the gold standard. It is apparent that when lesions are present in the posterior cul-de-sac or adjacent to large vessels or ureters, there is a tendency to avoid biopsy to prevent injury to these vital structures. The patient who is experiencing the painful symptoms of endometriosis clearly requires a definitive diagnosis with tissue biopsies so that management can be implemented, and the maximal amount of endometriotic tissue can be removed. Subsequently, dissection of the lesions and underlying DIE may significantly improve the surgical outcome for patients who have exhausted medical management methods.