History In 1981, Chatman observed that unsuspected E. could be found in peritoneal pockets. In 1986 Jansen & Russel published their observations on non-pigmented E. They concluded that: •Visualization of pigment is not necessary to diagnose E. •E. in earlier stages of histogenesis may display only non-pigmented lesions. Definition (Subtle,atypical, non-pigmented) Endometriotic lesions that lack the typical black-blue, powder-burn appearance (Jansen & Russel,1986) Prevalence Diagnosis of SE increased from 15% in 1986 to 65% in 1988 (Nisole et al,1993). SE are more common than the classic lesions in the adolescents with pelvic pain (Davis et al,1993). The incidence decreases with age (Konincks et al,1991). The most common is white opacification of the peritoneum The next most common is a glandular-like excrescence. The least common, but nevertheless characteristic, is the red flame like (Jansen & Russel,1986). Classification & morphology Red lesions: 1.Red flame-like lesions or red vesicular excrescences: more commonly affecting the broad ligament & uterosacral ligaments. Histologically: active E surrounded by stroma 2. Glandular excrescences resemble the mucosal surface of the endometrium seen at hysteroscopy Histologically: numerous endometrial glands. 3. Areas of petechial peritoneum or areas with hypervascularization: resemble the peticheal lesions due to manipulation of the peritoneum or to hypervascularization of the peritoneum. They frequently affect the bladder & the broad ligam. Histologically: red blood cells are very rare. White lesions: 1. White opacification: appears as peritoneal scaring or as circumscribed patches often thickened & sometimes raised. Histologically: an occasional retroperitoneal glandular structure & scanty stroma surrounded by fibrotic tissue or connective tissue. 2. Subovarian adhesions. Histologically: connective tissue with sparse endometrial glands 3. Yellow-brown peritoneal patches resembling café au lait patches. Histologically:similar to those observed in white opacification, but haemosiderin among the stroma cells produces the café au lait colour. 4. Circular peritoneal defects: frequently occur in areas of the pelvis which overlie loose connective tissue. 80% of peritoneal defects are associated with E, either on the border of the defect or in the defect itself (Donnez et al,1992) NATURE E is a dynamic disease, especially in the early phase, with S lesions emerging & vanishing again(Evers et al,1998). In the end however the peritoneal defense system will prevail & the disease will be contained in the majority of patients. Koninckx et al (1994) considered SE a natural condition occurring intermittently in all women Biological activity SE are thought to be more biologically active than typical forms. Vernon et al (1986) demonstrated that red peticheal implants produce twice the amount of PGF than brown lesions, which in turn produce more PGF than typical powder-burn implants. On other hand Muzii et al (2000) found that the biologic activity of red & black implants was similar The sample size of their study was relatively small to draw firm conclusions Natural progression to classic lesions • Redwine (1986) showed that: 1. Clear & red lesions occur at a mean age 10 years earlier than the black lesions. 2.A progression of E: from clear to red to white to black, with increasing age. • Increasing age is associated with a decreasing incidence of SE & increased incidence of typical E, endometrioma & deeply infiltrating E (Koninckx et al,1991). • SE progress to pigmented E over time (Jansen & Russel,1986). Second look laparoscopy in untreated patients 6 to 24 months following the initial surgery, documented pigmented lesions in areas previously contained SE Prognosis 1. Vascularization is one of the most important factors of growth & invasion of endometrial glands in other tissue (Donnez et al,1989). When compared with typical black lesion, the vascularization was found to be significantly higher in red lesions & significantly lower in white lesions. This change was due to an increase (red) or decrease (white) in the volume occupied by the vessels, as proved by both mean capillary surface area & the ratio of capillaries/stroma surface area. So, 1. Red lesions are probably the first stage of early implantation of endometrial glands & stroma. 2. White lesions could be latent stages of E as suggested by the poor vascularization observed. They are probably non-active lesions which have been quiescent for a long time 2. Mitotic index: Mitotic processes permit the maintenance & the growth of peritoneal E. MI is significantly different in typical & subtle E . The absence of mitosis in white lesions proves their low activity (Nisolle et al,1993) American Society for Reproductive Medicine (ASRM) classification of E The only difference between the 1985 AFS classification & 1996 ASRM classification is that the latter includes information on the morphologic appearance of the disease. In the new ASRM classification, peritoneal & ovarian implants are categorized into 3 subgroups: 1. Red (red, red-pink & clear lesions) 2. White (white, yellow-brown & peritoneal defects) 3. Black (black & blue lesions). The percentage of surface involvement of each implant type (red, white, & black) must be recorded on the opposite form. The new ASRM classification of E is the gold standard to clearly document the extent & location of the disease (Muzii et al,2000)) Clinical features • SE has the same (possibly PG related) symptoms that characterize classic E (Jansen & Russel,1986) 1. IFERTILITY 2. PAIN: dysmenorhea, dysparunia, ch.pelvic pain 3. PREMENSTRUAL BLEEDING 1.INFERTILITY: SE is the most common single cause (70%) of unexplained infertility (Propst & Laufer,1999). SE can be etiologically important in infertility. 2. PAIN: • Acquired deep dysparunia was found in 18% of SE (Jansen & Russel,1986). On other hand Vercellini et al(1996) observed that deep dysparunia was associated only with typical lesions & not with atypical fresh clear implants. •Increasing dysmenorrhea suggestive of active E is present in 64% of SE (Tansen & Russel,1986). The number of typical or S implants did not correlate with the severity of dysmenorrhea (Muzii et al,1997). The S forms, however, were considered together & were not categorized into red & white subgroups , as in the new ASRM classification. Recently Muzi et al (2000) found no correlation between the ASRM classification of E & associated dysmenorrhea. White implants are associated with milder pain symptoms than the black or red lesions. . •Chronic pelvic pain: SE is the most common single cause of chronic pelvic pain not responding to medical treatment (Propst & Laufer,1999). 3.PREMENSTRUAL SPOTTING: In the absence of pigmented E at laparoscopy, premenstrual spotting was highly predictive of SE (Jansen & Russel,1986) . Diagnosis The ability to diagnose SE is directly related to the experience & skill of the surgeon(Cook & Rock,1993) 1. Laparoscopy: A. Standard laparoscopy: Negative laparoscopy results do not mean that the patient has no E (Martin,1999) B. lactated Ringer or normal saline introduced into the pelvis (Laufer,1997). Laparoscopic visualization of of clear vesicular lesions can be facilitated by the use of the three-dimensional effect of the fluid. The laparoscope is submerged so that the optical distension medium is now liquid as opposed to CO2. The magnification focal length of the laparoscope is adjusted for the new refractory index through the liquid. Vesicular lesions are no longer falsely interpreted as light reflection. C. Near-contact laparoscopy (Redwin,1987): Visualization at magnifications of 1- to 7-power D.Peritoneal blood painting (Redwin,1989): SE can be seen more easily by painting the peritoneal surface with bloody peritoneal fluid. The physical- chemical properties of blood cause it to interact with S. physical deformities of the peritoneal surface in such a way as to cause flowing erythrocytes to outline surface irregularities. E. Bubble test (Amer A & Omar M., 2002) During laparoscopy, the posterior cul de sac is irrigated with short bursts of saline under controlled pressure. Development of dense soap like bubbles staying for at least 5 seconds indicates a positive test. The positivity of the test is apparently related to increased level of triglycerides in peritoneal fluid in cases of E. 2. Transvaginal hydrolaparoscopy is superior to standard laparoscopy for detection of S endometriotic adhesions of the ovary (Brosen et al,2001) 3. Elevated serum levels of endometrial secretory protein (placenta protein 14). The highest levels in patients with E are found on days 1 to 4 of the cycle (Seppala et al,1989) 4. Histopathologic examination of biopsy taken from suspected lesions. Differential diagnosis Not all abnormalities of the peritoneum represent E (Cock & Rock,1993). Stripling et al (1988) confirmed E in 91% of white lesions, 75% of red lesions, 33% of haemosiderin lesions, & 85% of other lesions 1. White E should be differentiated from postoperative scaring & from fibrotic adhesions resulting from inflammatory disease (Cock & Rock,1993) 2.Other lesions which may mimic E include hemangiomas, old suture, residual carbon from laser surgery, reaction to oil-contrast medium, epithelial inclusions, secondary breast & ovarian cancer, inflammatory cystic inclusions,Walthard rests, adrenal rests(Cock & Rock,1993). Differentiation between SE & other lesions may be impossible visually but may be achieved histologically through excision or biopsy. An abnormality of the peritoneum, no matter what its size, shape, or appearance, should suggest the possibility of E. Treatment E, whether its lesions are pigmented or not, does not itself demand treatment unless it is causing, or it is likely to cause symptoms. SE should receive the same pathophysiological & therapeutic attention that classic lesions do. There is a substantial difference between the expectant management of the isolated lesions found incidentally in a woman towards the end of reproductive years & the active management for a widespread non-pigmented lesions in a teenager with many years of ovulation before her. The first question to be asked is whether treatment is appropriate at that time (Kim,1999). If it is, a comprehensive plan should be formulated that takes into account the woman’s primary complaint (infertility or pain) & reproductive desires. The guidelines of the Royal College of obstetricians & Gynaecologists in management of E.( july, 2000 1. Endometriosis & pain: a. Medical management: Several drugs are effective in temporarily relieving pain associated with E. Non-steroidal anti- inflammatory drugs may be effective in reducing the pain associated with E. The choice between the combined oral contraceptive, progestagens, danazol & GnRH agonists depends principally upon their side-effect profiles because they relieve pain associated with E. equally well. It seems sensible to prescribe the safest & cheapest therapy. b. Surgical management: Although there are limited data available from RCT assessing the effectiveness of surgery in relieving pain, it is clearly effective for many women. However, clinical experience shows that some women fail to respond to surgical treatment either because of incomplete excision or because of post-operative disease recurrence. 2. Endometriosis & infertility: a. Medical management: There is no role for medical therapy with hormonal drugs in the treatment of E associated infertility. Ovarian stimulation with intrauterine insemination (IUI) is more effective than either no treatment or IUI alone in infertile women with minimal or mild E. b. Surgical management: In infertile women with minimal or mild E. detected at laparoscopy, destruction or ablation of the endometriotic implants & lysis of adhesions at that time is recommended to improve the chance of pregnancy. 1. SE are more common than the classic dark blue- black lesions in adolescents 2. The most common type of SE is white opacification the next most common is glandular-like excrescence. 3. SE progress to pigmented E over time 4. Red lesions are probably the first stage of early implantation of endometrial glands & stroma & white lesions could be latent stages of E. 5. In the new ASRM classification, peritoneal & ovarian implants are categorized into red, white & black 6. SE has the same symptoms that characterize classic E. 7. Negative laparoscopy results do not mean that the patient has no E 8. E, whether its lesions are pigmented or not, does not itself demand treatment unless it is causing, or it is likely to cause symptoms.