Ovarian endometrioma: severe pelvic pain is associated with deeply infiltrating endometriosis.

BACKGROUND: The objective of this study was to evaluate the significance of severe preoperative pain for patients presenting with ovarian endometrioma (OMA). METHODS: Three hundred consecutive patients with histologically proven OMA were enrolled at a single university tertiary referral centre between January 2004 and May 2010. Complete surgical excision of all recognizable endometriotic lesions was performed for each patient. Pain intensity was assessed with a 10-cm visual analogue scale (VAS). Pain was considered as severe when VAS was ≥ 7. Prospective preoperative assessment of type and severity of pain symptoms (VAS) was compared with the peroperative findings (surgical removal and histological analysis) of endometriomas and associated deeply infiltrating endometriosis. Correlations were sought with univariate analysis and a multiple regression logistic model. RESULTS: After multiple logistic regression analysis, uterosacral ligaments involvement was related with a high severity of chronic pelvic pain [odds ratios (OR) = 2.1; 95% confidence interval (CI): 1.1-4.3] and deep dyspareunia (OR = 2.0; 95% CI: 1.1-3.5); vaginal involvement was related with a higher intensity of lower urinary symptoms (OR = 13.4; 95% CI: 3.2-55.8); intestinal involvement was related with an increased severity of dysmenorrhoea (OR = 5.2; 95% CI: 2.7-10.3) and gastro-intestinal symptoms (OR = 7.1; 95% CI: 3.3-15.3). CONCLUSIONS: In case of OMA, severe pelvic pain is significantly associated with deeply infiltrating lesions. In this situation, the practitioner should perform an appropriate preoperative imaging work-up in order to evaluate the existence of associated deep nodules and inform the patient in order to plan the surgical intervention strategy.

Report of 7 uterine rupture cases after laparoscopic myomectomy: update of the literature.

The objective of this article is to report 7 previously unpublished uterine rupture cases in pregnancy after laparoscopic myomectomy and to update the medical literature. All cases were reported to the Board of Endoscopic Gynecologic Surgery (Athens, Greece) from 1998 to 2011. Myomas were single in 85.7% of patients, subserosal or pedunculated in 85.7%, and ≤5 cm in 71.4%. Bipolar diathermy was the sole method used for hemostasis in 28.6%, and could be characterized as excessive in 85.7%. A 2-layer closure with stitches of the myometrium was performed in just 14.3% of cases. Mean (SD) time between surgery and pregnancy was 1.4 (0.5) years. Uterine rupture occurred at 34 weeks of gestation or later in 85.7%, and during labor in 14.3% of cases. All women survived. Fetal demise was reported in 1 twin pregnancy (both fetuses) with rupture at 24 weeks of gestation. Laparoscopic myomectomy should be performed by adequately trained and experienced surgeons. Excessive use of diathermy for hemostasis should be avoided, and multiple-layer suturing should always be used for repairing the myometrial defect in cases of intramural and subserosal myomas with deep intrusion.

Endometriosis: contribution of 3.0-T pelvic MR imaging in preoperative assessment--initial results.

PURPOSE: To determine the accuracy of 3.0-T pelvic magnetic resonance (MR) imaging in the preoperative assessment of endometriosis and to evaluate colon wall involvement after intrarectal gel administration. MATERIALS AND METHODS: Institutional review board approval for this study was obtained, and each patient gave written informed consent. Forty-one consecutive patients with clinical suspicion of endometriosis underwent pelvic MR imaging at 3.0 T before surgery. Single-shot and high-spatial-resolution axial T2-weighted, sagittal fat-suppressed T2-weighted, and axial fat-suppressed T1-weighted sequences were performed. T2-weighted sequences were repeated after the rectum was filled with ultrasonographic (US) gel. Two blinded readers interpreted images independently. Image quality was scored by using a four-point scale. Detailed mapping of deep endometriosis was performed. Colon wall infiltration was graded (none, serosa, muscularis, submucosa, mucosa). MR imaging results were compared with surgical and pathologic findings. Interobserver agreement was assessed by using kappa statistics. Nonparametric tests were performed to compare colon wall infiltration scores without and those with US gel and between observers. RESULTS: Twenty-seven of 41 patients had deep endometriosis at surgery and histopathologic examination. Sensitivity, specificity, positive and negative predictive values, and accuracy for the diagnosis of deep endometriosis at MR imaging were 96.3% (26 of 27), 100% (14 of 14), 100% (26 of 26), 93.3% (14 of 15), and 97.6% (40 of 41), respectively. kappa Values ranged from 0.65 to 1.0, depending on the location of deep endometriosis. Colon wall infiltration assessment by both readers correlated well with pathologic findings (Spearman coefficient, >0.93), although median wall involvement scores were lower at pathologic examination than for both readers both before (P = .042 and P = .011) and after (P = .079 and P = .011) intrarectal gel filling. CONCLUSION: MR imaging of the pelvis at 3.0 T is accurate in the diagnosis and staging of deep endometriosis for the preoperative assessment of patients clinically suspected of having endometriosis.

Lymph node involvement in multicystic peritoneal mesothelioma.

Multicystic peritoneal mesothelioma is an uncommon lesion most frequently encountered in women of reproductive age. Although the pathologic characteristics have been documented, the lymph node status associated with this pathology, the etiopathogenesis and prognosis of which remain unclear, is unknown. We report here the case of a 35-year-old woman with a 5.5 cm multicystic mesothelioma affecting the pelvic peritoneum of the rectum. Involvement by multicystic mesothelioma was observed within two lymph nodes simultaneously resected with the tumor. To the best of our knowledge, lymph node involvement has not been described in previous studies.

Does infusion of colloid influence the occurrence of postoperative nausea and vomiting after elective surgery in women?

BACKGROUND: The impact of the type of fluid on postoperative nausea and vomiting (PONV) is not well defined. In this study we investigated the effects of colloids or crystalloids on PONV when given in addition to a background minimal crystalloid infusion in a female population of surgical patients. METHODS: This prospective, randomized, double-blind study included 115 women undergoing gynecological or breast surgery who were randomly allocated to receive hydroxyethyl starch (HES) 130/0.4 or normal saline in addition to a fixed background infusion of 5% dextrose in 0.45% saline at a flow rate of 0.5 mL x kg(-1) x h(-1). A bolus of 500 mL of the study fluid (HES or normal saline) was infused before the induction of anesthesia, followed by a continuous infusion of 1 mL x kg(-1) x h(-1) adjustable according to hemodynamic needs. The primary outcome variable was the incidence of PONV during the 24 h postoperative period. Secondary end points were the need for antiemetic rescue therapy, incidence of hypotensive episodes, pain scores, and need for additional analgesia. RESULTS: Nausea occurred in 11 of 56 patients who received HES and in 11 of 58 patients who received saline (P > 0.05). There were no differences between groups in the incidence of vomiting. There were no differences between the groups regarding antiemetic rescue therapy, hypotensive episodes, pain scores, or need for opioids. CONCLUSIONS: In surgical procedures with minimal blood loss and minimal fluid shifts, the type of fluid replacement administered (colloid vs 0.9% normal saline) has minimal effect on the incidence of PONV.

Omental trophoblastic implants after surgical management of ectopic pregnancy.

Peritoneal implants secondary to a tubal ectopic pregnancy or extratubal omental secondary trophoblastic implants (ESTI) are a rare entity often underestimated or unknown. It can be responsible of rising in the ss-hCG titer after salpingectomy for ectopic tubal pregnancy. Moreover, implants on the omentum are exceptional. This particular localization is exceptional and its physiopathology, diagnosis, surgical management and follow-up are discussed in this paper.

Androgen receptor expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix.

If in vitro studies have demonstrated a potential interaction between human papillomavirus (HPV) and androgen receptor (AR), their expression in vivo during cervical carcinogenesis remains unknown. To clarify the issue, we have tested by immunohistochemistry the expression status of AR in low-grade cervical intraepithelial neoplasia (LSIL-CIN1) (n=30), high-grade cervical intraepithelial neoplasia (HSIL-CIN2/3) (n=30), and invasive squamous cell carcinoma (ISCC) (n=13). All the patients with these lesions have got a corresponding liquid-based cytology and were proved to be HPV positive by using hybrid capture II methodology with probes against high-risk oncogenic HPVs (HR-HPVs). Thirty cases of normal exocervix epithelium served as controls. The evaluation of AR expression was performed by using H-score system, and an H-score >50 was considered positive. Androgen receptor expression was observed in 100% of normal epithelium (30/30) and LSIL (30/30), but only in 63% of HSIL (19/30) and 23% of ISCC (3/13). A statistically significant difference (P<0.05) concerning this expression was found between normal epithelium and HSIL or ISCC, between LSIL and HSIL or ISCC, and between HSIL and ISCC. To the best of our knowledge, this is the first study describing that the loss of AR expression is a frequent and common event in HSIL and ISCC resulting probably from complex interactions between HR-HPVs and these receptors. These data provide new insights concerning a potential role of androgen and AR in cervical carcinogenesis, which should be confirmed in furthers studies.

Adenolipoleiomyoma Polyp of the Uterus: A Case Report and Review of the Literature.

Adenolipoleiomyoma is a very rare lesion of the uterus. Only four cases were reported. We describe one case of adenolipoleiomyoma presenting as a polyp in a postmenopausal woman with menorrhagia. Adenolipoleiomyoma is a very rare lesion and the histogenesis remains unclear. We discuss the origin and the differential diagnosis of this lesion.

Hormonal therapy deregulates prostaglandin-endoperoxidase synthase 2 (PTGS2) expression in endometriotic tissues.

CONTEXT: Endometriosis is a common gynecologic condition characterized by an important inflammatory process mediated by the prostaglandin pathway. Oral contraceptives are the treatment of choice for symptomatic endometriotic women. However the effects of oral contraceptives use and prostaglandin pathway in endometriotic women are actually still unknown. OBJECTIVE: To investigate the expression of prostaglandin pathway key genes in endometriotic tissue, affected or not by hormonal therapy, as compared with healthy endometrial tissue. DESIGN: This was a comparative laboratory study. SETTING: This study was conducted in a tertiary-care university hospital. PATIENTS: Seventy-six women, with (n = 46) and without (n = 30) histologically proven endometriosis. MAIN OUTCOME MEASURES: Prostaglandin-endoperoxidase synthase (PTGS)1, PTGS2, prostaglandin E receptor (PTGER)1, PTGER2, PTGER3, and PTGER4 mRNA levels in endometrium of disease-free women and in eutopic and ectopic endometrium of endometriosis-affected women. PTGS2 expression was further investigated by immunohistochemistry, using specific monoclonal antibodies. PTGS2 expression was analyzed at mRNA and protein levels and correlated with taking hormonal treatment. RESULTS: PTGS2 expression was significantly increased in eutopic and ectopic endometrium as compared with healthy tissue (induction of 9.6- and 6.3-fold, respectively; P = .001). PTGS2 immunoreactivity increased gradually from normal endometrium to eutopic and ectopic endometrium (h-score of 96.7 ± 55.0, 128.3 ± 66.1, and 226.7 ± 62.6, respectively, P < .001). PTGER2, PTGER3, and PTGER4 expression increased significantly and gradually from normal to eutopic and ectopic endometrium, whereas PTGER1 remained unchanged. Patients under hormonal treatment had a higher PTGS2 expression at transcriptional and protein levels as compared with those without treatment (P = .002 and P = .025, respectively). CONCLUSIONS: Prostaglandin pathway is strongly deregulated in eutopic and ectopic endometrium of women suffering from endometriosis for the benefit of an increased PTGS2 expression. We show for the first time that hormonal treatment appears to enhance even more PTGS2 expression. These results contribute to explain why medical treatment could fail to control endometriosis progression.

Galectin-3 is overexpressed in various forms of endometriosis.

Endometriosis is an enigmatic disease of unknown etiology and pathogenesis, which is defined as the presence of endometrial glands and stroma outside the uterus. The most widely accepted theory to explain endometriosis is probably the transplantation of an endometrial fragment during menstruation to ectopic sites, but the development of endometriosis is extremely complex and includes the adherence to the peritoneal surface and secondary invasion of the underlying tissues. In this study, we have investigated the potential role of galectin-3 (gal-3), a member of a group of carbohydrate-binding proteins, which plays a major role in cell adhesion, migration, angiogenesis, and invasion. The expression of gal-3 has been carried out by immunohistochemistry, according to the different phases of cycle in 50 cases of endometriosis (peritoneal endometriosis: n=10; ovarian endometriosis: n=10; deeply infiltrating endometriosis: n=30) and in 34 cases of eutopic endometrium (10 without endometriosis and 24 with endometriosis). In the proliferative and secretory phases of the cycle, the nuclear and membranous gal-3 expression was higher, first in each variant of the endometriosis than in the eutopic endometrium (P<0.05), and second in the eutopic endometrium of women with endometriosis than in eutopic endometrium of women without endometriosis. Our data suggest that gal-3 may have a potential role in the development of endometriosis.

The steroidogenic factor-1 protein is not expressed in various forms of endometriosis but is strongly present in ovarian cortical or medullary mesenchymatous cells adjacent to endometriotic foci.

Steroidogenic factor-1 (SF-1) protein expression was not observed in any form of endometriosis (peritoneal, ovarian, or deep infiltrating endometriosis), which suggests that SF-1 locally produced by endometrial or stromal cells may not play a major role in the development of endometriosis. However, the strong expression of SF-1 in cortical and medullary ovarian mesenchymatous cells may be capable of creating a favorable steroidogenic environment and the development of the disease.

Steroidogenic factor-1 expression in ovarian endometriosis.

Steroidogenic factor-1 (SF-1), a major protein regulating the complex cascade of steroidogenis, has been postulated to play a role in ovarian endometriosis. However, the expression in situ of SF-1 in ovarian endometriosis is unknown. To shed light on its presence, the expression of SF-1 was studied by immunohistochemistry in 30 cases of ovarian endometriosis (proliferative, n=15; secretory phase, n=15) and in 10 cases of normal eutopic endometrium coming from the same patients. No SF-1 immunoreactivity was observed in glands or endometrial stroma from ovarian endometriosis or eutopic endometrium. In contrast, a strong immunoreactivity was observed in the adjacent ovarian cortical or medullary mesenchymatous cells in all the cases examined independently of the cycle's phases. Contrary to the earlier reported hypothesis, our data showed for the first time the absence of SF-1 expression in glands and endometrial stroma from ovarian endometriosis and eutopic endometrium. However, the strong expression of SF-1 observed in cortical and medullary ovarian mesenchymatous cells adjacent to endometriosis, suggests a potential role for these cells in locally induced steroidogenesis.

Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis.

OBJECTIVE: To analyze the expression of estrogen (ER) and progesterone (PR) receptors in the smooth muscle component (SMC) of deep infiltrating endometriosis (DIE). DESIGN: A prospective clinical and pathologic study of 60 cases of DIE. SETTING: University Hospital Department of Gynacology. PATIENT(S): Sixty patients with symptomatic DIE (uterosacral endometriosis n = 14; bladder endometriosis n = 10; colonic endometriosis n = 16; rectovaginal endometriosis n = 20). INTERVENTION(S): Laparoscopic surgery. MAIN OUTCOME MEASURE(S): The expression of ER and PR was studied by immunohistochemistry in the SMC directly around endometriotic foci and at distance (at least >1.5 cm) from them in correlation with proliferative and secretory phases of cycle. RESULTS: The ER and PR were present in the SMC of DEI in each location excepting colonic endometriosis where ER were absent. Independently of cycle's phases the PR were more abundant than ER. With the exception of rectovaginal endometriosis, where the ER and PR were more abundant in the proliferative than in the secretory phase, in other locations the ER and PR did not differ significantly with cycle's phases. Last, if ER and PR were more abundant in SMC around endometriotic foci than at a distance from them. However, the difference was not significant. CONCLUSIONS: Our data substantially confirm for the first time that in various forms of DIE, ER and PR are present not only in glands and stroma but also in the smooth muscle major histologic component of this disease.

Recurrence of mitotically active cellular fibroma of the ovary.

Background. 10% of ovarian fibromatous tumours typically exhibit increased cellularity, mitotic activity, and less frequently nuclear atypia. Therefore, the classification within the group of fibromatous tumours may represent some difficulties, thus, one or several of these features should appear. Case. We introduce the clinical and pathologic features based on one case of recurrence of a mitotically active cellular ovarian fibroma (MACF) in the pararectal fossa. This recurrence took place six years after primary surgery. Macroscopically, the tumour was firm, fibrous, well delimited, yellow-white without gross necrosis. On microscopic examination, it was composed of a densely cellular proliferation of fibrolastic-like cells with bland nuclear features and arranged in a fascicular pattern. There was no sign of significant atypia or necrosis. Conclusion. Recently, this case is the first report of a recurrence of MACF, following primary surgery with no tumoral rupture or surgical difficulty. The clinical outcome of ovarian cellular fibromas (CFs) and MACFs is typically uneventful. This case, however, strongly suggests maintaining a long-term clinical follow-up even though the principal tumour was surgically treated without tumour rupture or in the absence of adherence or any surgical difficulty.

Anatomic significance of a positive barium enema in deep infiltrating endometriosis of the large bowel.

PURPOSE: The anatomopathological significance of a positive double-contrast barium enema (DCBE) for suspicion of deep infiltrating endometriosis of the large bowel was studied. This is a retrospective study of a prospective database. METHODS: A large-bowel resection was proposed for patients who were suspicious for large-bowel endometriosis and had a positive DCBE. In a series of 73 patients, 71 large-bowel resections were performed. Histology and immunohistochemistry with the monoclonal antibody CD-10 were performed on the resection specimen. Outcome measures were the length of the resected specimen, the largest diameter of the lesion, the positivity of the resection margins, and the degree of infiltration of the large bowel. We also compared the mean largest diameters of the lesions with the degree of infiltration of the large bowel. RESULTS: Between December 1997 and October 2005, 80 patients were suspicious for large-bowel endometriosis: 73 (91%) had positive DCBEs, and 7 (9%) had negative DCBEs. Of the 73 with positive DCBEs, 4 (5%) refused digestive resection and 1 (1.4%) was excluded. Three patients underwent two large-bowel resections because of the presence of bifocal lesions (left and right colon). A total of 71 resections were performed. In case of positive DCBE, the perivisceral fat and the whole muscularis were infiltrated in 100% of cases. The infiltration reached the submucosa and the mucosa respectively in 82% and 18% of cases. A total of 9.9% of resection margins were positive at histology but only focally. The mean largest diameter of the lesions infiltrating the whole thickness of the large bowel was not statistically different from the mean largest diameter of more superficial lesions. CONCLUSIONS: Findings of mass effect with indentations and ridging of the mucosa on DCBE in a setting suspicious for large-bowel endometriosis correspond well with pathologic findings of deep infiltration of the large-bowel wall. Clinicians dealing with deep infiltrating endometriosis should be aware of these findings, which could influence their choice of surgical treatment.

Lymph node involvement and lymphovascular invasion in deep infiltrating rectosigmoid endometriosis.

OBJECTIVE: To analyze the lymph node involvement by endometriotic foci in rectosigmoid endometriosis and to correlate it with clinical and histological parameters including the presence of lymphovascular invasions, which could explain this lymph node involvement. DESIGN: A prospective study of 26 consecutive cases of rectosigmoid endometriosis between January 2005 and January 2007. SETTING: A multidisciplinary study including clinical and pathological data. PATIENT(S): Twenty-six patients with symptomatic rectosigmoid endometriosis. INTERVENTION(S): Laparoscopic surgery with pathological analysis of each specimen. MAIN OUTCOME MEASURE(S): Involvement of lymph nodes by endometriotic foci was correlated with the size and the wall layers affected by endometriotic lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions demonstrated by D2-40, a specific antibody to lymphatic vessels. RESULT(S): Lymph node involvement by endometriosis was observed in 11 of the 26 patients (42.3%) and correlated with the size of the lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions, which were observed in 36.3% of cases. CONCLUSION(S): Our data confirm that lymph node involvement by endometriotic foci is a frequent event in rectosigmoid endometriosis and may result at least partially from a lymphatic spread of the disease.

Ureteral mullerian carcinosarcoma (mixed mullerian tumor) associated with endometriosis occurring in a patient with a concentrated soy isoflavones supplementation.

Malignant transformation and particularly malignant mixed mullerian tumor arising in extragenital endometriosis is extremely rare and occurs in the majority of cases after estrogen replacement therapy. We present a case of a 75-year-old woman who developed a ureteral malignant mullerian carcinosarcoma in a context of florid endometriosis. The patient had a history of total hysterectomy with bilateral salpingo-oophorectomy 30 years earlier for extensive endometriosis. Since 5 years, the patient has been on phytoestrogen supplementation consisting of 72 mg/day of superconcentrated soy isoflavones. This is the first case of ureteral mullerian carcinosarcoma arising in endometriosis foci after extensive phytoestrogen supplementation. Our data suggest that phytoestrogens at least in concentrated form may play a role not only in maintenance of endometriosis but also in its malignant transformation. Given the extraordinary popularity and availability of these dietary supplements, several studies are indispensable regarding their safety particularly in women with extensive endometriosis.

Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis.

OBJECTIVE: To detect and quantify mast cells in peritoneal, ovarian, and deep infiltrating endometriosis and to study the relationship between mast cells and nerves in endometriosis. DESIGN: Prospective histological and immunohistochemical study. SETTING: University of Brussels, Belgium. PATIENT(S): Sixty-nine women undergoing laparoscopic excision of endometriosis for pain. Thirty-seven biopsies of normal tissue were obtained from women without endometriosis. INTERVENTION(S): Excision of endometriosis from different anatomical locations. MAIN OUTCOME MEASURE(S): Immunohistochemistry with chymase and tryptase to confirm the presence of mast cells and activated mast cells, respectively, in endometriotic lesions. Quantification of mast cells, activated mast cells, and degranulating mast cells in the different locations of endometriosis. Study of the relationship between mast cells and nerves by quantifying mast cells located less than 25 mum from nerves immunohistochemically stained with S-100 protein. Preoperative pain score evaluation by visual analogue scales. RESULT(S): Patients with deeply infiltrating lesions had significantly higher preoperative pain scores than patients with peritoneal or ovarian endometriosis. Mast cells and degranulating mast cells are significantly more abundant in endometriotic lesions than in nonaffected tissues. Deep infiltrating lesions show a significantly higher number of mast cells, activated mast cells, and mast cells located <25 microm from nerves than peritoneal and ovarian lesions. We found significantly more degranulating mast cells in deep infiltrating lesions than in peritoneal lesions. CONCLUSION(S): The presence of increased activated and degranulating mast cells in deeply infiltrating endometriosis, which are the most painful lesions, and the close histological relationship between mast cells and nerves strongly suggest that mast cells could contribute to the development of pain and hyperalgesia in endometriosis, possibly by a direct effect on nerve structures.

Laparoscopical insertion of intraperitoneal catheters for intraperitoneal chemotherapy.

BACKGROUND AND METHODS: Eight patients (seven clinically negative stage Ill ovarian cancer and one peritoneal mesothelioma) respectively underwent second-look laparoscopy for staging, adhesiolysis and insertion of an intraperitoneal catheter and fixation of a portal. All patients had received six courses of cisplatin-paclitaxel-based chemotherapy intravenously. At the end of the laparoscopic staging, a 5-mm catheter was inserted under direct vision through a 5-mm trocar in the abdomen. A preaponevrotic forceps was used to grasp the catheter and bring it to the portal, which is located on the intercostal aponevrosis 2 or 3 cm above the laparoscope entry. RESULTS: Although previously operated, laparoscopy was possible in all patients and the catheters were easily inserted. All patients received intraperitoneal chemotherapy on the second postoperative day. We did not observe any complication after a mean follow-up of 12 months. CONCLUSIONS: Laparoscopic insertion of intraperitoneal catheters is a feasible and safe procedure but requires experience in laparoscopic surgery. In many cases it might preclude from performing non-useful laparotomies. It might help to reduce the hospital stay and the morbidity in relation to second-look laparotomies. Compared with the blind surgical technique of insertion of intraperitoneal catheters, this technique also allows intraabdominal staging. Nevertheless, further studies are necessary to confirm our results.

Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis.

BACKGROUND: The aim of this study was to investigate a possible role for nerve growth factor (NGF) in the mechanism of pain and hyperalgesia induced by deep adenomyotic nodules and other forms of endometriosis and to clarify the relationship between endometriotic lesions and the surrounding nerves. METHODS: Endometriotic lesions (deep adenomyotic nodules, peritoneal endometriosis, ovarian endometriosis) and eutopic endometrium were obtained from 51 patients presenting with pain. Patients were allocated to two groups (group 1: patients with a deep adenomyotic nodule (n = 23); group 2: patients with peritoneal and/or ovarian endometriosis but without deep adenomyotic nodule (n = 28). Immunohistochemistry with antibodies against NGF, NGF specific tyrosine-kinase receptor (Trk-A) and S-100 protein was performed. Results were expressed as mean H-scores +/- SD, and correlated with the presence of hyperalgesia. RESULTS: The percentage of patients presenting hyperalgesia at physical examination was significantly higher in group 1 (96%) than in group 2 (11%) (P < 0.001). NGF expression was significantly stronger in deep adenomyotic nodules (DAN) than in ovarian (OE) and peritoneal endometriosis (PE), both in the proliferative phase in the glands [DAN: 226 +/- 18; OE: 140 +/- 9 (P < 0.001); PE: 110 +/- 7 (P < 0.001)] and in the stroma [(DAN: 204 +/- 21; OE: 125 +/- 15 (P < 0.001); PE: 100 +/- 9 (P < 0.01)]. NGF expression in DAN is also significantly stronger than in OE and PE in the secretory phase in the glands [DAN:181 +/- 32; OE: 85 +/- 3.3 (P < 0.001); PE: 65 +/- 9 (P < 0.001)] and in the stroma [DAN: 173 +/- 28; OE: 85 +/- 3.7 (P < 0.001); PE: 35 +/- 13 (P < 0.001)]. Perineurial and intraneurial invasion by endometriotic lesions were found only in deep adenomyotic nodules and not in the other forms of endometriosis. The specific receptor for NGF (Trk-A) is expressed in all the nerves that were included in the biopsies. CONCLUSIONS: These results suggest a role of NGF in endometriotic pain and hyperalgesia in deep adenomyotic nodules. The strong expression of the NGF-TrkA pathway in deep adenomyotic nodules could explain why this type of lesion infiltrates in richly innervated anatomical sites.