ENDOMETRIOSIS

Novel approaches to diagnosing and treating endometriosis

By Larry Demco, MD

Relieving the pain of endometriosis requires visualization of "invisible" lesions and complete elimination of all implants. Blue light, pain mapping, and laser therapy hold promise in increasing the likelihood of success.

Endometriosis has been studied for more than 90 years, and descriptions of the lesions associated with it have led to several theories on how endometrial tissue arrives at the affected organ or the peritoneum.^1-4 While the origin of endometriosis remains uncertain, there is no doubt that the basic problem is normal tissue in an abnormal location.

Endometriosis is analogous to a misplaced eyelash. Like the endometrium, an eyelash is a "normal" part of the eye quite separate from the surrounding organ, or eyeball. When a "normal" eyelash is placed on a "normal" eyeball, the eye becomes red, with dilated corkscrew vessels. The result is a painful eye that continues to function, but not optimally. Once the eyelash is removed, the eyeball returns to normal. Like the eyeball, a woman's body reacts in a similar manner when "normal" peritoneum is exposed to "normal endometrial tissue." The peritoneal lining develops red lesions with dilated corkscrew vessels and becomes painful. The woman's pelvic organs continue to function, but not optimally, which can lead to infertility. The way to cure the problem is to find and remove the "normal endometrial tissue." Although this analogy is not perfect, patients seem to grasp the concept, because they have all experienced an eyelash in the eye.

Unfortunately, it's not as easy to find and remove endometrial tissue that has migrated as it is to retrieve an eyelash. Early on in the treatment of endometriosis, laparotomy was the only approach to accessing the pelvis, and lesions seen with the naked eye were biopsied and removed. The result was marginal pain relief because lesions too small to be seen were left untreated.

With laparoscopy, we can now identify more endometriotic lesions, including red and white lesions, but unfortunately, the outcome for patients is not significantly better.^5-7 Patients often awake from surgery with no relief from pain, or abatement that lasts only 6 to 24 months. Some experts have recommended more radical therapy, including hysterectomy and bilateral salpingo-oophorectomy, in the belief that cramps originate in the uterus and estrogen production by the ovaries encourages development of endometrial tissue. While these procedures do improve the outcome for some women, many patients still have pelvic pain and cramps.⁸ The surgeons may then conclude that the symptoms don't originate in the uterus and send the patients off for extensive bowel work-up. Many women are thus left with a diagnosis of irritable bowel syndrome or told that their pain is psychosomatic.

Some researchers have persisted in exploring the cause of endometriosis-related pain. Redwine, for example, theorized that it originated in the peritoneum, and removal of that structure in its entirety would eliminate the pain.⁹ The procedure was a success but so extensive that it increased risk of adhesions and associated pain. Redwine's pathology specimens, however, showed microscopic endometriosis in "normal-appearing" peritoneum, a finding that has been confirmed by Martin and others.⁶ This, finally, explained recurrence of endometriosis symptoms. The microscopic implants in normal-looking peritoneum are not excised because they are not "seen" and later develop into larger lesions, which produce symptoms.⁹ This article reviews the roles of pain mapping and blue light in better identifying and treating microscopic endometriosis.

The era of pain mapping

Recently, interest in laparoscopy on patients who are awake has resurged. With smaller microlaparoscopes and microinstrumentation, coupled with video-laparoscopy, a patient can now participate in her own operation by interacting with the surgeon. This technique, known as Patient Assisted Laparoscopy (PAL), or laparoscopy under IV conscious sedation, may have particular benefits for treatment of endometriosis, as I will describe here based on my own case series.¹⁰

PAL makes sense for endometriosis because it enables a patient to help "map" the areas of pain associated with lesions so that a surgeon can better determine where disease starts and ends. Initial work with the technique in this setting resulted in some thought-provoking findings (Table 1).¹¹ Only 11% of patients reported that the classic black lesions of endometriosis were painful to the touch, whereas pain was associated with 20% of white lesions, 37% of red lesions, and 42% of clear lesions. Given these results, it is easy to see why previous therapies produced such poor outcomes. The lesions that surgeons can see tend to be the least painful, whereas those associated with the most pain cannot be visualized during laparotomy, and thus remain untreated.

TABLE 1
Prevalence of pain versus lesion type

From pain mapping, researchers also have learned that pain associated with endometriosis can extend as much as 28 mm beyond the visible border of a lesion into what looks like "normal" peritoneum (Figure 1).^11,12 Therefore, it is insufficient to confine excision to a lesion's borders. Rather, the surgeon should use the patient's pain as a guide to the location of microscopic disease.

Findings from pain mapping. PAL is helping clinicians gain new understanding of the mechanisms by which endometriosis produces symptoms. For example, in neither normal patients nor women with endometriosis did uterine palpation during the procedure elicit pain or cramps. In patients with endometriosis, cramping was produced by palpating their lesions. Postoperatively, the women said they were able to detect a difference between cramps associated with endometriosis and those from menstruation. Furthermore, lesion palpation also produced cramps in the patients who had undergone bilateral salpingo-oophorectomy with hysterectomy. This confirmed other researchers' findings that hysterectomy often does not eliminate the pain of endometriosis, since the lesions—and not a woman's uterus—are responsible for the cramping.

In most cases, lesion location and the site of pain are related. For example, palpation of lesions on the uterosacral ligament causes pain or cramps in the back. Palpation of lesions on the sidewall of the pelvis results in pain or cramps radiating down the leg. With pain mapping, a surgeon can better confirm that a particular lesion is causing a patient's pain before therapy is begun. Interestingly, however, some patients with endometriosis do not have right/left orientation of the pelvis.¹² That is to say, palpation of an endometriotic lesion on the left side of a woman's pelvis may produce pain that she perceives as being on the right side, and vice versa. This explains the not uncommon phenomenon of a patient who complains of right-sided pain only to be told by her surgeon that laparos-copy under general anesthesia showed a normal-looking pelvis on that side. It is no wonder that a survey of the Endometriosis Association's members revealed that the average length of time from onset of symptoms to treatment of their endometriosis was 9.2 years and it took an average of 2.3 operations.¹³

How PAL has evolved. Pelvic pain mapping initially involved mapping the areas of pain associated with endometriotic lesions and recording the patient's input during the operation using a twin video system with picture-in-picture. After the mapping was complete, the patient then was anesthetized and the lesions and areas of pain that had been mapped were treated. Postoperative follow-up was in the office.

The next evolution in this therapy was keeping the patient awake for both the mapping and the treatment.⁵ With this approach, the surgeon and the patient work as a team to diagnose, map, and treat the lesions. When treatment with the ERBE Argon Plasma Beam (APB) is complete, the area is remapped so the patient can confirm whether her pain is gone. (Settings of 1.5 L/min gas flow and 40 watts of power are used to create a 1- to 3-mm burn and to seal small veinules and ateriols.) While it would seem that "awake" treatment would be too painful, two thirds of patients undergoing the procedure have completed surgery without general anesthesia (Table 2).

TABLE 2
Patient tolerance to mapping and treatmentin awake laparoscopy

Visualization of lesions with blue light

Researchers also have experimented with different techniques for visualizing microscopic endometriosis—from invasive probes to use of dyes and lights.¹⁵

Thermocoagulation. Semm first reported on the thermocoagulation test, an invasive method for detecting endometriosis in normal-appearing peritoneum.¹⁶ He described use of a thermal probe at 100°C, which changed normal peritoneum from pink to white and endometrial tissue to brown (hemosiderin effect), clearly distinguishing the two types of tissue.

Paints, dyes, and light. Other attempts at visualization of microscopic disease have included peritoneal blood painting (Redwine) and painting the peritoneum with methylene blue dye (Menches). ¹⁷

Visualization of cervical tissue during colposcopy led to the finding that green light enhanced detection of abnormal vasculature and aided in the diagnosis of microinvasive disease of the cervix. That and experience with methylene blue dye in testing for endometriosis led investigators to speculate that blue light might help visualize microscopic endometriosis. A photodynamic diagnosis source that emits light at 440 Hz was chosen because the heme molecule—which is inherent in hemosiderin—reflects light at that wavelength.

Unlike dyes, blue light is noninvasive and easy to use and the light source can be switched from blue back to normal white light for therapy. A special camera that lets in low-intensity blue light allows the surgeon to see visible lesions of endometriosis more easily and also reveals microscopic endometriosis and neovascularization that would be invisible under white light (Figure 2).¹² The surgeon can use these markers to determine the extent of the disease (Figure 3).¹⁹ This should translate into better patient outcomes, since pain relief is dependent upon the surgeon's ability to identify and treat all of the endometriotic lesions. However, the findings do need to be verified in a multicenter clinical trial.

The one drawback of blue light is "disappearance" of lesions if treatment causes bleeding. Because blood contains heme, it reflects blue light, as does endometriosis. Thus, either the lesion margins seen under blue light must be marked prior to excision or ablation, or therapy that does not cause bleeding must be used. Needlepoint cautery is not an option because the marks are quickly lost as the tissue retracts, leaving the potential for disorientation and incomplete excision of the lesion. Lasers are effective for marking but expensive, not available to every surgeon, and require training and expertise.

The ERBE APB is an inexpensive device that can easily be used to mark a continuous line around an endometriotic lesion. This line allows for easier identification of a lesion's borders and reduces the chances that the surgeon will become disoriented while dissecting deep lesions. The APB has been shown to be effective for treatment of superficial endometriosis in the awake patient.¹⁸ And because it does not cause bleeding, the blue light can be left on during treatment to ensure complete lesion destruction.

What the future holds

Endometriosis is very difficult to diagnose and treat effectively, frustrating both physicians and patients. Pain mapping and blue light offer new directions in detection of visible and nonvisible endometriosis. More precise disease detection should result in a greater chance for successful treatment. Results with pain mapping and blue light also indicate that needlepoint cautery is no longer appropriate for endometriosis because the lesions are much larger than we had previously thought. We need to further study wider excision and/or treatment with a laser or the APB as ways to achieve greater success in treating endometriosis.

REFERENCES

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2. Cullen TS. The distribution of adenomyomata containing uterine mucosa. Am J Obstet Gynecol. 1919;80:130-138.

3. Sampson JA. Perforating hemorrhagic (chocolate) cysts of the ovary. Their importance and especially their relation to pelvic adenomas of the endometrial type. Arch Surg. 1921;3:245-323.

4. Sampson JA. The development of the implantation theory for the origin of peritoneal endometriosis. Am J Obstet Gynecol. 1940;40:549-557.

5. Evers JL, Dunselman GA, Land JA, et al. Is there a solution for recurrent endometriosis? Br J Clin Pract Suppl. 1991;72:45-50.

6. Martin DC, Hubert GD, Vander Zwaag R, et al. Laparoscopic appearances of peritoneal endometriosis. Fertil Steril. 1989;51:63-67.

7. Redwine DB. Conservative laparoscopic excision of endometriosis by sharp dissection: life table analysis of reoperation and persistent or recurrent disease. Hum Reprod. 1989;56:628-634.

8. Redwine DB. Endometriosis persisting after castration: clinical characteristics and results of surgical management. Obstet Gynecol. 1994;83:405-413.

9. Redwine DB. Laparoscopic en bloc resection for treatment of the obliterated cul-de-sac in endometriosis. J Reprod Med. 1992;37:695-698.

10. Demco LA. Mapping pelvic pain under local anesthesia: patient-assisted laparoscopy. In: Hulka JF, Reich H. Textbook of Laparoscopy. 3rd ed. Philadelphia, Pa: W.B. Saunders Company; 1998:391-397.

11. Demco L. Mapping the source and character of pain due to endometriosis by patient assisted laparoscopy. J Am Assoc Gynecol Laparosc. 1998;5:241-245.

12. Murphy AA, Guzick DS, Rock JA. Microscopic peritoneal endometriosis. Fertil Steril. 1989;51:1072-1074.

13. Demco LA. Pain referral patterns in the pelvis. J Am Assoc Gynecol Laparosc. 2000;7:181-183.

14. Baldwin M. Endometrial Association membership survey results presented at the World Endometriosis Congress Meeting, Quebec City, Canada, June 1998.

15. Redwine DB. Is "microscopic"peritoneal endometriosis invisible? Fertil Steril. 1989;50:665-666.

16. Semm K. Operative Manual for Endoscopic Abdominal Surgery: Operative Pelviscopy, Operative Laparoscopy. Chicago, IL: Yearbook Medical Publishers; 1987:286-287.

17. Redwine DB. Peritoneal blood painting: an aid in the diagnosis of endometriosis. Am J Obstet Gynecol. 1989;161:865-866.

18. Demco L. Mapping and treatment of endometriosis in the awake patient. Presented at the Annual Meeting of the Society of Laparoendoscopic Surgeons, December 1998.

19. Demco L. Laparoscopic spectral analysis of endometriosis. J Am Assoc Gynecol Laparosc. May 2004. In press.

DR. DEMCO is Assistant Clinical Professor, University of Calgary, Calgary, Alberta, Canada.

 

Larry Demco. Novel approaches to diagnosing and treating endometriosis. Contemporary Ob/Gyn Apr. 15, 2004;49:12-18.