Carlos Rotman

Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis

OBJECTIVE To evaluate basal (constitutive) and stimulated synthesis of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-8, IL-10 by peritoneal macrophages (PM) in women with endometriosis. DESIGN Peritoneal macrophages were cultured in the presence or absence of lipopolysaccharide (LPS) for 24 hours. Peritoneal fluids (PF) and PM supernatants were assayed for cytokines using ELISA. SETTING Institute for the Study and Treatment of Endometriosis and university-based research laboratories. SUBJECTS Fertile controls undergoing tubal ligation (n = 8) and women with endometriosis (n = 17). INTERVENTION Peritoneal fluid samples were obtained at the time of diagnostic laparoscopy (endometriosis group) or laparoscopy for tubal ligation; both were performed in the midluteal phase of the cycle. RESULTS Both basal and LPS stimulated production of TNF alpha, IL-8, and IL-10 by the PM were elevated significantly in women with endometriosis as compared with the fertile controls. CONCLUSIONS This study demonstrated that cytokines TNF alpha, IL-8, and IL-10 are synthesized at greater than normal levels by basal and stimulated PM from women with endometriosis. The levels of TNF alpha and IL-8 correlated with the levels in the PF, suggesting that PM are the principal source of these cytokines in the PF.

The development of cytotoxicity in peritoneal macrophages from women with endometriosis

OBJECTIVE To assess the activation status of peritoneal macrophages from women with endometriosis. DESIGN Peritoneal macrophages from patients undergoing laparoscopy were tested for cytotoxic activity against a cultured hepatoma cell line. SETTING Patients were tested at initial laparoscopy or at the completion of therapy. PATIENTS AND PARTICIPANTS Fertile controls (n = 27), infertile controls (n = 20), untreated endometriosis (n = 43), danazol-treated endometriosis (n = 22), and gonadotropin-releasing hormone agonist (GnRH-a)-treated endometriosis (n = 13) were tested. INTERVENTIONS Danazol (800 mg/d) or GnRH-a therapy for 6 months. RESULTS Cytotoxicity was elevated in stage I and II endometriosis (P less than 0.02) and in infertile controls (P less than 0.05) compared with fertile controls. Cytotoxicity in stage III and IV endometriosis was lower (P less than 0.02) than in stage I and II endometriosis. Indomethacin in vitro increased cytotoxicity (P less than 0.05) in stage III and IV endometriosis but not in the other groups tested. Cytotoxicity in danazol or GnRH-a-treated patients was increased (P less than 0.05 or greater) compared with untreated patients with comparable stage of disease. CONCLUSIONS Peritoneal macrophage cytotoxicity in women with endometriosis is affected by (1) the extent of endometriosis, (2) prostaglandin metabolism, and (3) treatment with danazol or GnRH-a.

Monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis * †

OBJECTIVE To investigate the capacity of monocytes from women with endometriosis to influence endometrial cell proliferation. DESIGN Uterine endometrial cells were cultured in the presence and absence of autologous blood monocytes for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING Patients were tested at initial presentation for evaluation of infertility and/or endometriosis. PATIENTS, PARTICIPANTS Fertile controls, n = 17; infertile controls, n = 9; untreated endometriosis, n = 29. INTERVENTIONS None. RESULTS Endometrial cell proliferation was enhanced significantly by blood monocytes in patients with endometriosis but was suppressed significantly by blood monocytes in fertile controls. Endometrial cell proliferation was not affected significantly by blood monocytes in infertile controls analyzed as a group, but a subset of infertile patients also showed enhancement of endometrial cell proliferation by blood monocytes. CONCLUSIONS Blood monocytes from patients with endometriosis and a subset of patients with unexplained infertility enhance autologous endometrial cell proliferation, whereas blood monocytes from fertile patients suppress endometrial cell proliferation. The capacity of monocytes to enhance endometrial cell proliferation appears to require both monocyte-derived factors that stimulate endometrial cell proliferation and endometrial cells capable of responding to those stimulatory factors. If either of these factors is absent, monocytes either suppress or have no effect on endometrial cell proliferation.

Experience with laparoscopic hysterectomy

We conducted laparoscopic hysterectomy on 62 consecutive patients; 12 had laparoscopically assisted vaginal hysterectomy (LAVH), 16 had total laparoscopic hysterectomy (TLH), and 34 had supracervical laparoscopic hysterectomy (SLH). The groups were comparable with regard to age, weight, history of abdominal surgery, number of additional procedures performed, and weight of specimens; 74% had previous abdominal surgery, and 69% had additional procedures at hysterectomy. The mean estimated blood loss associated with LAVH was 2.5 times greater than that with TLH and 3 times greater than with SLH. The length of surgery was influenced by patient selection, surgeons experience, and equipment malfunction, with a mean of 213 minutes for LAVH, 244 for TLH, and 212 for SLH. The mean hospital stay for LAVH was 1.9 days and less than 1 day for TLH and SLH. There were nine total complications in the series (15%). Twelve (19%) of the specimens showed no abnormalities on pathologic examination. Total and supracervical laparoscopic hysterectomy and LAVH are appropriate operations for selected patients and compare favorably with standard abdominal or vaginal hysterectomy. The procedures demand sophisticated instrumentation and a dedicated endoscopy team to ensure safe and efficient performance.

Ovarian remnant syndrome after laparoscopic hysterectomy and bilateral salpingo-oophorectomy for severe pelvic endometriosis

Ovarian remnant syndrome is a rare complication of total abdominal hysterectomy and bilateral salpingo-oophorectomy (BSO). Ovarian enlargement and dense periovarian adhesions are the predisposing factors. Recurrent ovarian remnant syndrome was associated with recurrence of symptomatic endometriosis in a woman who underwent laparoscopic supracervical hysterectomy and BSO for severe endometriosis and extensive pelvic adhesions. After primary surgery she required five additional procedures for complete resection of all ovarian remnants. Definitive surgery for advanced endometriosis with extensive periovarian adhesions may be complicated by ovarian remnant syndrome and reactivation of the disease. Careful retroperitoneal resection of all ovarian tissue is of paramount importance in preventing the syndrome. This, however, may be a limitation of laparoscopic surgery. The choice between laparoscopy and laparotomy in such cases should be individualized and based on the degree of surgical difficulty and the surgeons level of experience.

Mitogen induced production of polyclonal IgG is decreased in women with severe endometriosis

PROBLEM: The etiology and/or pathogenesis of endometriosis may involve aspects of both humoral and cellular immunity.