Pathophysiology of cyclic hemorrhagic ascites and endometriosis

Pathophysiology of Cyclic Hemorrhagic Ascites and Endometriosis Anastasia Ussia, MD, George Betsas, MD, Roberta Corona, MD, Carlo De Cicco, MD,and Philippe R. Koninckx, MD*From the Department of Obstetrics and Gynecology, Villa Giose, Crotone, Italy (Dr. Ussia); Department of Obstetrics and Gynecology, UZ Gasthuisberg,Katholieke Universiteit Leuven, Belgium (Drs. Betsas, Corona, De Cicco, and Koninckx); University of Thessaloniki, Greece (Dr. Betsas); University ofCagliari, Italy (Dr. Corona); and University Cattolica, Rome, Italy (Drs. De Cicco and Koninckx).
Massive hemorrhagic ascites (4470 mL, range 1–10 L) in women with endometriosis is a rare condition occurring predomi-nantly in black women. Of the 43 case reports published, 42 are compatible with the hypothesis that the hemorrhagic ascitesis predominantly a consequence of excessive ovarian transudation similar to a Meigs syndrome. Indeed, bilateral ovariectomycures the condition without recurrences, whereas after unilateral ovariectomy or cystectomy recurrence rate is more than 50%;during ovarian suppression by luteinizing hormone-releasing hormone agonist ascites disappears, but reappears after treatment.
Superficial pelvic endometriosis also contributes to the ascites because after superficial endometriosis destruction the recur-rence rate is only 4 in 14. Based on these data, it is suggested, to scrutinize the ovaries for tumors given the analogy with Meigssyndrome. In women desiring fertility, conservative treatment with destruction of endometriosis only can be attempted giventhe cure rate of some 20%. It is unknown what the effect of ovulation induction would be. Journal of Minimally Invasive Gy-necology (2008) 15, 677–681 Ó 2008 AAGL. All rights reserved.
Endometriosis; Ascites; Meigs syndrome; Cystic ovarian endometriosis Peritoneal fluid during the normal menstrual cycle was de- tions of blood proteins are lower in peritoneal fluid. For scribed to be predominantly formed as an ovarian exudate.
example, albumin concentration being some 70% of the Women without ovarian activity have less than 5 mL of plasma concentration whereas the concentration of larger peritoneal fluid whereas in cyclic women the volume of molecules such as gammaglobulins and fibrinogen is even peritoneal fluid increases progressively up to a few hundred lower This also is the reason that locally secreted large milliliters during ovulation The increased vascular per- molecular–weight proteins, such as CA 125 and PP14, accu- meability around the developing follicle was postulated as mulate and their concentrations can be very high in peritoneal the underlying mechanism, explaining the high steroid hor- mone concentrations in peritoneal fluid mediated by local Inflammation, either locally after a mechanical trauma factors such as the extremely high estrogen concentrations, such as surgery or more generalized during peritonitis, also and other factors such as angiogenic factors, prostaglandins, increases the volume of peritoneal fluid by a mechanism of histamine, and cytokines. The massive ascites in women with exudation. This fluid typically contains similar protein con- ovarian hyperstimulation syndrome have been explained by centrations as in blood, with high fibrinogen content and similar mechanisms . The mesothelial cells of the perito- neum actively regulate the exchange between peritoneal fluid The Meigs syndrome is well known as the association of an and the bloodstream, and the transport rate is much slower for ovarian fibroma, massive ascites, and hydrothorax . The larger molecules. This explains the fact that the concentra- mechanism of the increased ovarian exudation is, to our knowl-edge, not yet identified. After the excision of the ovarian tumoror after adnexectomy, the ascites disappears. By analogy, a ma- The authors have no commercial, proprietary, or financial interest in the lignant ovarian tumor, or a metastasis in the ovary together products or companies described in this article.
with ascites and hydrothorax is called a pseudo-Meigs syn- Corresponding author: Philippe R. Koninckx, MD, Department of Obstetricsand Gynecology, UZ Gasthuisberg, Katholieke Universiteit Leuven, B3000- drome. Other rare causes of pseudo-Meigs syndrome are the struma ovarii and rare cases of uterine fibroma .
Pelvic endometriosis is known to constitute a low-grade pelvic inflammation and the peritoneal fluid volume Submitted July 15, 2008. Accepted for publication August 20, 2008.
Available at and is only slightly higher than in women without endometriosis 1553-4650/$ - see front matter Ó 2008 AAGL. All rights reserved.
doi:10.1016/j.jmig.2008.08.012 Journal of Minimally Invasive Gynecology, Vol 15, No 6, November/December 2008 . In addition, in women with severe bilateral cystic She is symptom free without ascites, dysmenorrhea, or pelvic ovarian endometriosis and with extensive superficial endo- pain and with an excellent quality of life. Because the patient metriosis, the volume of peritoneal fluid is hardly increased.
wants to continue this treatment we do not know whether stop- Occasionally, some women with endometriosis have an im- ping the treatment would cause a recurrence. In vitro portant hemorrhagic ascites as described in 43 case reports.
fertilization will be considered in the near future.
The pathophysiology of this hemorrhagic ascites is unknown,but the widely held belief that the ascites is a consequence of the superficial endometriosis, similar to peritoneal metasta-ses, remains speculative.
A 26-year-old, Caucasian, nulliparous woman had an Two cases of massive hemorrhagic ascites together with emergency laparoscopy and more than 1 L of hemorrhagic endometriosis in women with mechanical fertility prompted ascites was evacuated. One year later a second laparoscopy us to review the literature in detail, to evaluate whether the was performed for acute pain. Again, more than 1 L of hem- pathophysiology could be similar to Meigs syndrome, and orrhagic ascites was drained. Severe superficial endometri- to decide whether ovulation induction for in vitro fertilization osis involving the bowel, peritoneum, and omentum was excised. Two years later an ultrasound-guided evacuationof 2 L of hemorrhagic ascites was performed for recurringpain. Two months later a third laparoscopy was performed because of severe pain, massive ascites, and increased con- centrations of white blood cell count, increased concentrationof C-reactive protein, and slight fever. Ascites was drained, A 23-year-old nulligravida woman had severe dysmenor- and an adhesiolysis together with the excision of an endo- rhea and menstrual right shoulder pain. A hydrothorax was metriotic rectovaginal nodule was performed. Less than 1 drained twice, confirming the diagnosis of endometriosis.
year later the patient again had acute pain, important ascites, During treatment with luteinizing hormone-releasing hor- and signs of an inflammatory reaction. Another paracentesis mone agonists symptoms disappeared, but 3 months later was performed and 1.5 L of hemorrhagic fluid evacuated.
symptoms recurred. A pleurectomy was performed with re- Some 2 months later, the ascites had returned and pain was moval of many small endometriotic lesions on the pleura, intolerable. Because at magnetic resonance imaging a 2-cm a 2-cm nodule in the right diaphragm, a 4-cm nodule in the up- ovarian cyst was found, a laparotomy was performed. Mas- per part, and a 3.5-cm nodule in the middle part of the right sive adhesions were lysed, and an appendicectomy, an omen- lung. Four months later, she was readmitted with severe pelvic tectomy, and a unilateral adnexectomy were performed. One pain and ascites. At laparoscopy, massive hemorrhagic ascites year later symptoms and ascites had returned, and after another was found together with a frozen pelvis, bowel adhesions, and paracentesis to evacuate hemorrhagic fluid, gonadotropin- multiple spots of endometriosis on the peritoneum and the releasing hormone therapy was started. With this therapy, patient is still symptom free after 3 years.
releasing hormone agonists the patient was free of symptomsbut 1 year after stopping the treatment, she was readmitted with symptoms of subocclusion, ascites, and pain. A large sig-moid nodule was diagnosed on contrast enema. At laparos- All original case reports (n 5 44) written since 1980 were copy, 1.5 L of hemorrhagic ascites was found together with reviewed in detail except 2 articles we could not retrieve severe adhesions and 2 big nodules of deep endometriosis.
We looked specifically for pathophysiology, volume A low rectovaginal nodule of 5-cm diameter attached to the of peritoneal fluid, presence of hematothorax, CA 125 con- right spine was excised with a carbon-dioxide laser, together centrations, age, parity, race, whether a tumor or mass was with ureterolysis over a double J because of hydronephrosis detected in the ovaries before or during surgery, and the of the left ureter. For a sigmoid nodule of some 4-cm diameter outcome of ovarian suppression therapy, adnexectomy, and with more than 50% occlusion of the bowel, a resection anas- other therapies. For volume we recorded the original volumes tomosis was performed. A liver lesion was biopsied but re- vealed fibrosis only. Thorough inspection of the ovariesduring surgery and by ultrasound failed to identify any tumor.
After surgery she received 6 months of gonadotropin-releasinghormone agonists, followed by intermittent administration of Statistics were performed with the SAS system (SAS corticosteroids (Fiorenzo De Cicco) for unclear reasons.
Institute, Inc., Cary, NC), using Spearman correlation.
With this treatment she remained symptom free. Because ofpersisting primary infertility, a second-look laparoscopy was performed 1 year later showing few adhesions, no residualendometriosis, and no ascites. Two years later, the patient is The age of the women reported in the literature ranged without medical treatment except intermittent corticosteroids.
from 20 to 50 years with a mean age of 31.9 6 8.8 years Table 1Literature review of hemorrhagic ascites in endometriosis A 5 Asian; B 5 black; BSO 5 bilateral salpingo-oophorectomy; DB 5 dark brown; GnRH 5 gonadotropin-releasing hormone; H 5 hemorrhagic; TAH 5 total abdominal hysterectomy; USO 5 unilateral salpingo-oophorectomy; W 5 white.
(Surprisingly, during this 27-year period, the age of dark brown in 17 and as hemorrhagic in 15 (9 missing). Peri- the women published increased significantly (p 5 .001). The toneal fluid was liquid without clots in all cases.
volume of the ascites was high at 4470 6 2625 L. CA 125, if Race distribution was 21 black, 5 Asian, 1 Hispanic, 3 reported, was elevated. Color of the fluid was described as white, and 13 not reported (p 5 .001 for black).
Journal of Minimally Invasive Gynecology, Vol 15, No 6, November/December 2008 An endometrioma was described in 25 women with 2 rup- leaking from the ovary is associated with active endometri- turing. All other ovaries were reported as normal at inspec- otic lesions or an open cystic ovarian endometriosis, some tion. In none of the reports nor in our 2 cases was an blood staining will occur, resulting by accumulation of red ovarian tumor or mass identified by preoperative computer blood cells in dark brown ascites fluid, with some red blood aided tomography scan (n 5 17) magnetic resonance imag- cells in all cases when reported. The 50% recurrence rate after ing (n 5 1), ultrasound (n 5 16), during surgery or by pathol- unilateral ovariectomy or cystectomy also is compatible with the concept that the ovary is the source of the fluid.
Surgical treatment consisted of bilateral salpingo- The pathology clearly is acquired and not congenital.
oophorectomy (with or without hysterectomy) in 14 women Symptoms start many years after menarche, and are unrelated followed by ovarian suppression in 2. Unilateral oophorec- to a pregnancy. No explanation exists as to why the preva- tomy was performed in 6 followed by medical treatment in lence is higher in black women than in white, as observed 3; cystectomy in 5 with medical treatment in all 5; and de- before, nor for the observation that the age of the women in struction of peritoneal endometriosis and adhesiolysis in 10 the case reports increases over time.
followed by ovarian suppression in 8. In all 14 women treated In conclusion, the pathophysiology of the hemorrhagic as- by bilateral salpingo-oophorectomy, ascites disappeared cites is suggested to be similar to Meigs syndrome (i.e., a local without recurrence. In all 26 patients receiving ovarian sup- intraovarian factor). Whether this is related to the endometri- pression, the ascites disappeared during treatment of up to osis is unknown, although the deep brown color of the ascites 5 years. After unilateral oophorectomy, ascites redeveloped suggests a causal relationship. Unfortunately we do not yet in 2 of 6. After excision of ovarian endometriosis only, the have any conclusive evidence for this, as we do not know recurrence rate was 2 of 3 and after destruction of superficial the pathophysiology of Meigs syndrome. Superficial pelvic endometriosis is suggested to be a cofactor, contributing tothe ascites and to the dark brown color. Ovulation inductionor in vitro fertilization was not reported yet.
Hemorrhagic ascites together with endometriosis belongs to the rare but seemingly well-known pathologies, with mas-sive ascites, either dark brown or hemorrhagic, but without Fiorenzo De Cicco, Universita` Cattolica del Sacro Cuore clots. The pathophysiology repetitively was suggested to be Roma, Italy, and G. Melis and A. Angioni, University of caused by rupture of an endometrioma or by exudation Cagliari, Italy, are thanked for reviewing the manuscripts.
from widespread pelvic endometriosis. The available evi- We thank the University of Leuven, Belgium, and the Uni- dence suggests, however, that both suggestions are either er- versita` Cattolica, Rome, Italy, for supporting the collabora- roneous or insufficient. An endometrioma was found in only tion between both universities in deep endometriosis surgery.
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