Department of Obsterics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
OBJECTIVE: To investigate the relationship between the distribution of nerve fibers in multiple endometriosis lesions and pelvic pain. METHODS: From Sept. 2007 to Sept. 2008, 120 endometriosis patients treated in Peking Union Hospital were enrolled in this study, which including 19 cases with stage I, 29 cases with stage II, 44 cases with stage III and 28 cases with stage IV. The pain symptom was evaluated by visual analogue scales (VAS) score and nerve fibers in multiple endometriosis lesions were detected by immunohistochemical staining. RESULTS: The number of nerve fibers in multiple endometriosis lesions were (29.74 +/- 17.33)/mm(2) in uterosacral ligament, (24.53 +/- 13.34)/mm(2) in vaginal septum, (17.09 +/- 10.09)/mm(2) in uterus rectum crux, (6.77 +/- 4.21)/mm(2) in peritoneal endometriosis lesions, (0.07 +/- 0.25)/mm(2) in endometriosis ovarian cyst wall. The number of nerve fibers in uterosacral ligament was mostly correlated with the degree of pain (r = 0.56). The nerve fibers of uterus rectum crux and vaginalseptum were correlated with defecation pain (r = 0.58 and 0.41) and dyspareunia (r = 0.82 and 0.67), which were significantly higher than those in endometriosis leision in peritoneum and ovary. There was no significant different number of nerve fibers among different stage disease (P > 0.05). CONCLUSION: There was significantly different distribution of nerve fibers in multiple endometriosis lesions, which was correlated with dysmenorrhea, anus pain, dyspareunia and chronic pelvic pain, not with clinical staging.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):256-9.
Protein gene product 9.5-immunoactive nerve fibers and its clinical significance in endometriotic peritoneal lesions.[Article in Chinese]
Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
OBJECTIVE: To investigate the association between distribution of protein gene product (PGP) 9.5-immunoactive nerve fibers in peritoneal endometriotic lesions and disease-associated pain symptoms. METHODS: Thirty two peritoneal endometriotic lesions from patients with endometriosis (16 cases with pain and 16 cases without pain) and matched with 20 peritoneal tissues from patients with uterine leiomyoma without endometriosis were stained immunohistochemically for PGP9.5-immunoactive nerve fibers. RESULTS: The positive rate and density of PGP9.5-immunoreactive nerve fibers in peritoneal endometriotic leision were 62% (10/16) and (3.8 +/- 1.7)/mm(2) in endometriosis patients with pain, which were significantly higher than 19% (3/16) and (1.7 +/- 0.5)/mm(2) in endometriosis patients without pain (P < 0.05) and 25% (5/20) and (1.3 +/- 0.6)/mm(2) in peritoneal tissues in women without endometriosis (P < 0.05). However, no differences were found between endometriosis patients without pain and women without endometriosis (P > 0.05). Moreover, the density of PGP9.5-immunoreactive nerve fibers in peritoneal lesions in endometriosis patients with pain was positively correlated with the severity of pain (r = 0.855, P < 0.05). In addition, the density of PGP9.5-immunoreactive nerve fibers in peritoneal lesions was statistically higher in endometriosis patients with chronic pelvic pain and(or) dysmenorrhea than those in endometriosis patients with other type of pain (P < 0.05), which was not associated with active lesion, site and staging (P > 0.05). CONCLUSION: It suggested that PGP9.5-immunoreactive nerve fibers might confer the mechanism of pelvic pain with endometriosis.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):252-5.
Relationship between cofilin-1 expression and implantation capacity in eutopic endometrium of patient with endometriosis.[Article in Chinese]
Department of Obstetrics and Gynecology, ShengJing Hospital, China Medical University, Shenyang 110004, China.
OBJECTIVE: To investigate the relationship between expression of cofilin-1 and in vivo implantation capacity of eutopic endometrium of endometriosis. METHODS: Eutopic endometrium of 20 cases with stage III or IV endometriosis were obtained by laparoscopic or laparotomy surgery (endometriosis group) matched with 20 cases of eutopic endometrium from patients with cervical cancer in situ (control group) in Department of Obstetrics and Gynecology, ShengJing Hospital. All cases’ eutopic endometrium were collected and injected into abdominal cavity of nude mice to establish endometriosis animal model, then the successful rate of animal model and volume of endometriosis lesion were calculated. The expression and positive rate of cofilin-1 protein were measured by western blot and immunohistochemistry staining. RESULTS: The mean volume of endometriosis lesions (2.38 +/- 0.22) mm(3) in endometriosis group was significantly bigger than (0.36 +/- 0.08) mm(3) in control group (P < 0.05). The successful rate of establishing endometriosis model was 95% (19/20) in endometriosis group and 5% (1/20) in control group, which reached statistical difference (P < 0.05). The expression and positive rate of cofilin-1 protein in eutopic endometrium and the expression of cofilin-1 protein in endometriosis lesion of animal model were 0.82 +/- 0.06, 90% (18/20), 0.85 +/- 0.03 and 0.21 +/- 0.03, 20% (4/20), 0.22 +/- 0.02 in control group, which reached statistical difference (P < 0.05). The successful rate of establishing endometriosis model with positive cofilin-1 in endometrium 86% (19/22) was significantly higher than 6% (1/16) of model’s endometrium with negative cofilin-1 expression(P < 0.05). CONCLUSIONS: Implanting capacity and cofilin-1 expression level of eutopic endometrium of endometriosis were more intensive than that of normal endometrium. High cofilin-1 expression was probably related with implanting capacity of eutopic endometrium of endometriosis.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):247-51.
Clinical efficacy and safety of gonadotropin releasing hormone agonist combined with estrogen-dydrogesteronea in treatment of endometriosis.[Article in Chinese]
Department of Gynecology, Obstetris and Gynecology Hospital, Fudan University, Shanghai 200011, China.
OBJECTIVE: To compare clinical effect of gonadotropin releasing hormone agonist (GnRH-a) alone and GnRH-a combined with low-dose dydrogesteronea and estradiol valerate on sex hormone, hypoestrogenic symptoms, quality of life and bone mineral density (BMD) in treatment of endometriosis. METHODS: Seventy patients with moderate or severe endometriosis, who were diagnosed by laparotomy or laparoscopic surgery within two months, were randomly assigned into two groups. 35 patients in GnRH-a group were treated by goserelin (3.6 mg) for three months, and 35 patients in add-back group were treated by goserelin (3.6 mg) combined with estradiol valerate 0.5 mg and dydrogesteronea 5 mg daily. Before and after the treatment, clinical parameters were recorded and analyzed, including visual analog scale (VAS), medical outcomes survey short form 36 (SF-36), Kupperman menopausal index (KMI), BMD, the serum level of follicle stimulating hormone (FSH), estradiol (E(2)) and bone gla-protein (BGP). The first menstruation and VAS were also followed up after treatment. RESULTS: Every 3 cases in two groups lost follow-up. (1) Reproductive hormone: the level of E(2) in add-back group [(94 +/- 71) pmol/L] was significantly higher than (54 +/- 52) pmol/L in GnRH-a group (P < 0.01). The level of FSH in add-back group [(3.0 +/- 1.9) U/L] was significantly lower than (5.7 +/- 2.9) U/L in GnRH-a group (P < 0.05). (2) VAS: after treatment, VAS in both group decreased significantly when compared with that before treatment (P < 0.05), and remained until menstruated. (3) KMI: KMI in add back-group (10 +/- 8)was significantly lower than (14 +/- 6) in GnRH-a group (P < 0.05). (4) BMD: compared with that before treatment, BMD decreased significantly after treatment in GnRH-a group (P < 0.05), no remarkable difference of BMD was observed before and after treatment in add-back group. Before treatment, serum BGP in both groups did not show statistical difference. After treatment, the level of BGP in GnRH-a group [(7932 +/- 5206) ng/L] was significantly higher than (5419 +/- 2917) ng/L in add-back group (P < 0.05). CONCLUSIONS: GnRH-a combined with estrogen-progesterone regimen could relieve pain from endometriosis as effectively as GnRH-a alone and reduce hypoestrogenic symptoms and bone loss. Therefore, it is a safe and effective treatment.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):243-6.
Zhonghua Fu Chan Ke Za Zhi. 2010 Apr;45(4):241-2.
Zhonghua Fu Chan Ke Za Zhi. 2010 May;45(5):363-6.
Measurement of serum human epididymis secretory protein 4 combined with CA(125) assay in differential diagnosis of endometriosis cyst and ovarian benign and malignant tumors.[Article in Chinese]
Gynecologic Oncology Center, Peking University People’s Hospital, Beijing 100044, China.
OBJECTIVE: To investigate the value of human epididymis secretory protein 4(HE4) combined with CA(125) assay in differential diagnosis of endometriosis cyst and ovarian malignant tumor. METHODS: The level of HE4 and CA(125) were measured by enzyme-linked immunosorbent assay (ELISA) in the serum specimens of 46 cases in endometriosis cyst group, 36 cases in malignant ovarian tumor group, 60 cases in benign ovarian diseases and 50 women in healthy women group. Those results were shown with median level. The normal range were 0 – 150 pmol/L in HE4 and 0 – 35 kU/L, which either one was more than the threshold value defined as positive index. The sensitivity of assay was evaluated by receiver operating characteristic (ROC) curve, the relation and value of HE4 or CA(125) alone and combination assay in diagnosis of endometriosis was analyzed by Mann-Whitney U test and correlation analysis. RESULTS: (1) HE4: the median levels of HE4 were 52.4, 51.0, 50.0 pmol/L in group of endometriosis, normal control and benign ovarian tumor, which didn’t show statistical difference. However, HE4 was 507.5 pmol/L in ovarian cancer group, which was significantly higher than those of 3 groups (P < 0.05). (2) CA(125): there were significant different in median level of CA(125) was observed as 743.0 kU/L in ovarian cancer, 84.9 kU/L in endoemtriosis, 15.4 kU/L in benign ovarian disease, and 11.5 kU/L in healthy women (P < 0.05). (3) The single assay: when compared with that in endometriosis group, receiver operating characteristic area under the curve (ROC-AUC) were 0.933 in HE4 alone and 0.821 in CA(125) alone assay in ovarian cancer group. The specificity was 95% and the sensitivity was 79.6% and 49.0%. (4) The combination assay: when compared with those in endometriosis group, the ROC-AUC was 0.936, the specificity was 95% and the sensitivity was 81.0% in ovarian cancer. CONCLUSIONS: Measurement of HE4 could be used in differential diagnosis of endometriosis cyst. And the combination of HE4 and CA(125) assay could discriminate ovarian endometriosis cysts from ovarian malignant tumors effectively.
In: Molecular Imaging and Contrast Agent Database [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2010.
2007 Aug 27 [updated 2007 Sep 24].
A favorable prognosis of estrogen therapy for breast cancer can often be predicted on the basis of response to the hormone because the estrogen receptor (ER) is a valuable marker to determine treatment outcome (1). The ER status of the tumors determines the likelihood of a favorable response to the treatment, and patients with ER-positive tumors have a better chance of recovery compared to those with ER-negative tumors. The presence of ER in the tissue is measured in a biopsy sample or after resection of a tumor. The random biopsy or tumor sampling may yield a false negative result because primary tumors usually have a heterogeneous ER distribution (2). In this regard a radioscintigraphic procedure could be more useful to determine the ER status of tumors because agents used for scintigraphy have a binding specificity for their targets. Tamoxifen is a selective ER modulator that blocks estrogen binding to the receptor and is often used to treat breast cancer. Using radioactive halogen ([18F] fluorine and [131I] iodine) derivatives of tamoxifen in conjunction with positron emission tomography (PET), some investigators have investigated and monitored the effects of this drug at the cellular and clinical levels for the treatment of cancer (3-6). Although the results obtained from these studies are encouraging, the expenses, availability, and water solubility of these derivatives are limiting factors for clinical use. As an alternative, Takahashi et al. decided to develop a meta-stable, technetium (99mTc)-labeled derivative of estradiol (EDL) to possibly investigate and monitor ER status in cancer patients because the isotope is inexpensive and easily available, and the derivative is water-soluble (7); this estradiol was conjugated to a poly-glutamate peptide (GAP) that could chelate the 99mTc isotope to obtain 99mTc-GAP-EDL for imaging and radiotherapeutic purposes. The investigators also explored the possibility of using 99mTc-GAP-EDL to detect endometriosis, an ER-associated condition, using a rabbit model (7-9).
In: Molecular Imaging and Contrast Agent Database [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2010.
2007 Aug 23 [updated 2009 Jun 18].
Approximately 10% of women of reproductive age are affected by endometriosis, a gynecological disorder (1). Painful periods, pelvic pain, and infertility are often associated with endometriosis. Although a variety of mechanisms, including the roles of different cytokines, growth factors, and hormones, have been proposed in the development of endometriosis, the exact etiology and epidemiology of this condition is unclear (1-3). Menstruation in the opposite direction with spillage of viable endometrial cells into the peritoneum is often observed in cycling women (4). Adhesion, proliferation, and spread of the shed endometrial cells to the peritoneum are believed to support the development of endometriosis (5-7). Endometriosis is usually detected by a surgical technique such as a laparoscopy. Performing such a procedure on patients with infertility is often complex, and it provides information only about the morphological and anatomical changes in the tissue (8). Moreover, endometriosis usually progresses or recurs after surgery, and any relief to the patient is temporary (9). Because the prevalence and progression of endometriosis cannot be studied in humans without a laparoscopy, non-primate and primate animal models, including rabbits, have been used to investigate this disease (10-12). It has also been shown that estrogen receptors (ER) are overexpressed in the uterine endometrium and endometriotic lesions in endometriosis (4). In an effort to develop a non-invasive method to detect endometriosis, Takahashi et al. explored the use of estrogen, an ER ligand, to image endometriosis induced in rabbits (8). For this, estradiol (EDL) was conjugated to a glutamate peptide (GAP), which contained 5–10 glutamic acid residues, to facilitate the chelation of radioactive gallium (68Ga) to obtain 68Ga-GAP-
In: Molecular Imaging and Contrast Agent Database [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2010.
2009 May 08 [updated 2009 Jul 01].
Aromatase is an enzyme complex of the cytochrome P450 superfamily (1). It is composed of P450 and a flavoprotein called NADPH-P450 reductase. Its main function is to aromatize androgens to estrogens. Aromatase is present in many tissues, including granulosa cells of the ovary, brain, fat, placenta, blood vessels, skin, bone, and endometrium. Aromatase is overexpressed in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer (2-6). (S)-6-[(4-Chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole (vorozole) is an aromatase inhibitor with a inhibition constant (K i) value of 1 nM. Lidstrom et al. (7) prepared [11C]vorozole by N-methylation of (S)-6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1H-benzotriazole (nor-vorozole) to use as a positron emission tomography (PET) radioligand to study aromatase activity.
Dtsch Arztebl Int. 2010 Jun;107(25):446-55; quiz 456. Epub 2010 Jun 25.
Deutsches Endometriosezentrum Berlin, Klinik für Gynäkologie und Geburtsmedizin, Berlin, Germany.
BACKGROUND: Endometriosis and adenomyosis uteri are the most common benign disorders affecting girls and women after uterine myomas (fibroids), with a prevalence of roughly 5% to 15%. There have been many advances in diagnostic assessment and in our understanding of the disease over the past decade. Steady improvements in treatment have been accompanied by heightened consciousness of the diagnosis among the affected women and the doctors who care for them. METHODS: A selective literature search was carried out in the Cochrane and PubMed databases using the key words “endometriosis,” “deep infiltrating endometriosis,” “endometriosis AND diagnostics,” “endometriosis AND surgical therapy,” “endometriosis AND endocrine treatment,” and others. The AWMF and ESHRE guidelines were also taken in account. RESULTS AND CONCLUSION: The main manifestations are primary or secondary dysmenorrhea, bleeding disturbances, infertility, dysuria, pain on defecation (dyschezia), cycle-dependent or (later) cycle-independent pelvic pain, nonspecific cycle-associated gastrointestinal or urogenital symptoms. Cycle-associated problems of urination and/or defecation that are due to endometriosis are most common in young, premenopausal women. Whenever such manifestations are present, endometriosis should be considered in the differential diagnosis, and evidence for it should be sought in the clinical history, physical examination, and ultrasound findings. If endometriosis is histologically confirmed and is of the deeply infiltrating kind, the recommended management today is to refer the patient to an endometriosis center.
Pain. 2010 Jul 15. [Epub ahead of print]
Department of Medicine and Science of Aging, G. D’Annunzio University of Chieti, Italy.
Co-existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms (viscero-visceral hyperalgesia). The present study assessed this phenomenon in different models of visceral interaction. In a prospective evaluation, patients with: (a) coronary artery disease (CAD)+gallstone (Gs) (common sensory projection: T5); (b) irritable bowel syndrome (IBS)+dysmenorrhea (Dys) (T10-L1); (c) dysmenorrhea/endometriosis+urinary calculosis (Cal)(T10-L1); and (d) gallstone+left urinary calculosis (Gs+LCal) (unknown common projection) were compared with patients with CAD, Gs, IBS, Dys or Cal only, for spontaneous symptoms (number/intensity of pain episodes) over comparable time periods and for referred symptoms (muscle hyperalgesia; pressure/electrical pain thresholds) from each visceral location. In patients’ subgroups, symptoms were also re-assessed after treatment of each condition or after no treatment. (a) CAD+Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms, respectively (0.001<p<0.05). (b) IBS+Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys; hormonal dysmenorrhea treatment also reduced IBS symptoms; IBS dietary treatment also improved dysmenorrhea (0.001<p<0.05) while no treatment of either conditions resulted in no improvement in time of symptoms from both. (c) Cal+Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms; lithotripsy for urinary stone also reduced menstrual symptoms (0.001<p<0.05). (d) In Gs+LCal, cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms, respectively. Mechanisms of viscero-visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero-viscero-somatic convergent neurons. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Eur J Neurol. 2010 Jul 15. [Epub ahead of print]
Increased headache prevalence in female adolescents and adult women with early menarche. The Head-HUNT Studies.
Norwegian National Headache Centre, St. Olav’s University Hospital, Trondheim, and Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Background: Age at menarche is associated with cardiovascular events and lifestyle factors such as body mass index (BMI), certain women’s diseases like breast cancer and endometriosis and with occurrence of certain physical symptoms during puberty. It is unclear whether age at menarche is an independent determinant of headache. Objectives: The aim of the study was to explore age of menarche in relation to headache prevalence in a large population-based study of both adolescents and adult women (HUNT). Methods: In the Nord-Trøndelag Health Study in Norway 1995-97 (HUNT 2), a total of 26 636 (57%) of 46 506 invited women responded to questions regarding menarche and headache (Head-HUNT). In the youth part of HUNT 2, 3196 female students were interviewed about their headache complaints and 2766 (87%) responded to questions regarding menarche. All the final analyses were adjusted for age, use of oral contraceptives and BMI, and for adults also for educational level. Results: Headache was more prevalent amongst females with menarche </= 12 years, both amongst adolescents (OR = 1.3, 95% CI = 1.1-1.5) and adults (OR = 1.1, 95% CI = 1.1-1.2), evident for migraine and non-migrainous headache. Conclusion: Headache, both migraine and non-migrainous headache, was more prevalent amongst both adolescents and adult females with early menarche. Early menarche may increase headache susceptibility, or be a consequence of a common pathogenetic factor, e.g., sensitivity to estrogens.
Gynecol Endocrinol. 2010 Jul 19. [Epub ahead of print]
Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.
Background. Aromatase inhibitors have recently been proposed for the treatment of endometriosis; however, no previous study examined the effects of these agents on pain and urinary symptoms of premenopausal women with bladder endometriosis. Case. Two premenopausal patients with bladder endometriosis were treated with letrozole (2.5 mg/day), norethisterone acetate (2.5 mg/day), elemental calcium and vitamin D3 for 6 months. The double-drug regimen quickly improved pain and urinary symptoms in both patients. One patient had no significant adverse effect and continued the therapy for 14 months. The other patient developed myalgia and severe arthralgia; pain and urinary symptoms recurred few months after the interruption of the 6-month treatment and the patient underwent laparoscopic partial cystectomy. Conclusion. Aromatase inhibitors improve pain and urinary symptoms in patients with bladder endometriosis; however, severe side effects of treatment may occur. These agents should be administered only to patients who refuse surgery and fail to respond to other therapies.
Bratisl Lek Listy. 2010;111(6):345-8.
Abdominal rectus muscle endometriosis after Cesarean section extrapelvic localization of endometriosis.
Obstetric/Gynecologic Clinic, Clinical Centre Kragujevac, Serbia. [email protected]
INTRODUCTION: Endometriosis is defined by the presence of functional endometrial tissue outside the uterus, where it is normally located. Endometriosis could has intra and extra pelvic localization. Abdominal endometriosis is the most common localization of extrapelvic endometriosis and is usually developed in the connective tissue surrounding the operation. Very rarely this could be found in the muscle tissue. The mechanical transplantation theory is responsible for the development of scar endometriosis. CASE REPORT: The patient, 35 years old, three years after caesarian section had an operation because of the assumption for the presence of front abdominal hernia, located at the place of previous section. The egg-sized tumor was removed from the abdominal rectus muscle and sent for PH and immunohistochemical analyses. The results showed endometriosis of the muscle with positive estrogen and progesterone receptors. One year after the operation, due to the repeated pains in the scar area, the treatment continued by GNRH analogues and control was performed by serial ultrasound and biochemical markers CA 125. CONCLUSION: Clinical diagnoses of scar endometriosis could be provided by an accurate anamnesis and physical, ultrasound and biochemical examinations. Scar endometriosis should always be considered when the symptoms are present in cyclic manner, hormone depending, mostly after gynecological operations and worsening during menstruation. The problem was diagnosed by pathohistological analyses (Fig. 4, Ref. 20).
Am J Obstet Gynecol. 2010 Jul 13. [Epub ahead of print]
Fertility in women with minimal endometriosis compared with normal women was assessed by means of a donor insemination program in unstimulated cycles.
Human Reproduction Unit, Department of Obstetrics and Gynecology, Hospital from Cruces, Basque Country University, Baracaldo, Spain; IVI-Bilbao, Leioa, Vizcaya, Spain.
OBJECTIVE: The purpose of this study was to compare the pregnancy rate in an artificial insemination donor program in women with minimal endometriosis and in women without endometriosis. STUDY DESIGN: A prospective double-blinded study was conducted in women with azoospermic partners. RESULTS: The per-cycle pregnancy rate was 8.6% (9/104 women) in the minimal endometriosis group vs 13.3% (26/196 women) in the control group. The per-woman pregnancy rate was 37.5% (9/24 women) in the minimal endometriosis group and 51.0% (26/51 women) in the control group. CONCLUSION: Pregnancy rates were statistically similar in normal women and in women with minimal endometriosis. Copyright © 2010 Mosby, Inc. All rights reserved.
Hiroshima J Med Sci. 2010 Jun;59(2):39-42.
Department of Surgery, Hiroshima City Funairi Hospital, 14-11 Funairisaiwai-cho, Naka-ku, Hiroshima 730-0844, Japan. [email protected]
Endometriosis is prevalent among women of reproductive age, and is most commonly found in the gynecologic organs themselves and the surrounding pelvic peritoneum. Endometriosis of the appendix, however, is rare. Preoperative diagnosis is difficult and a definitive diagnosis is usually established following histopathological examination of the appendix. We report a case of endometriosis of the appendix in a 29-year-old woman who presented with right lower quadrant abdominal pain. Rebound tenderness was localized to McBurney’s point. Her WBC count was 12,300/mm3 and her CRP was 6.497 mg/dl. Ultrasound and computed tomography detected a calcified region inside the cecum and slight thickening of the wall of the appendix. Based on these findings, the patient was diagnosed with acute appendicitis and underwent an appendectomy. The appendix appeared mildly congested, but the mucosa of the appendix was nearly normal and without macroscopic inflammation. Histopathological examination demonstrated ectopic endometrial glands and stroma in the muscularis. These stroma cells were positive for CD10 on immunohistochemical staining, establishing a diagnosis of endometriosis of the appendix. The patient had a good clinical course and no residual pain postoperatively.
Am J Surg Pathol. 2010 Aug;34(8):1211-6.
Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. [email protected]
The occurrence of benign epithelial inclusions in lymph nodes is well documented and can sometimes mimic metastatic carcinoma. Benign müllerian inclusions, such as endometriosis and endosalpingiosis, are common in pelvic and para-aortic lymph nodes, but their presence in supradiaphragmatic lymph nodes is a rare event. We report our experience with 3 patients found to have endosalpingiosis in axillary sentinel lymph nodes obtained for staging of breast carcinoma. All patients were postmenopausal women, with age ranging between 65 and 75 years. Endosalpingiosis involved a single lymph node in 1 patient, and 2 nodes in each of the other 2; it was present in the lymph node capsule in all the 3 cases, with few glands scattered within the lymph node parenchyma in 2 of the patients. The glands contained ciliated and intercalated peg cells, had no periglandular endometrial-type stroma, and showed no atypia or mitotic activity. The epithelium demonstrated positive nuclear immunoreactivity for WT1 and PAX8, and was devoid of myoepithelium or basement membrane. Endosalpingiosis had been misinterpreted as metastatic carcinoma at another hospital in 1 of the 3 patients, with subsequent dissection of 19 additional benign axillary lymph nodes. We conclude that endosalpingiosis can involve axillary lymph nodes and closely simulate metastatic mammary carcinoma. Morphologic identification of ciliated cells and “peg” cells is most helpful to recognize this benign inclusion, and positive immunoreactivity for WT1 and/or PAX8 can be used to support the diagnosis.
Reproduction. 2010 Jul 13. [Epub ahead of print]
K Meehan, Prince Henrys Institute, Melbourne, Australia.
Over the past decade, high-throughput proteomics technologies have evolved considerably and have become increasingly more commonly applied to the investigation of female reproductive diseases. Proteomic approaches facilitate the identification of new disease biomarkers by comparing the abundance of hundreds of proteins simultaneously, to find those specific to a particular clinical condition. Some of the most well studied areas of female reproductive biology applying proteomics include gynaecological cancers, endometriosis, and endometrial infertility. This review will discuss the progress that has been made in these areas and will highlight some of the emerging technologies that promise to contribute to better understanding of female reproductive disease.
Mol Hum Reprod. 2010 Jul 13. [Epub ahead of print]
Monash University Department of Obstetrics and Gynaecology and The Ritchie Centre, Monash Institute of Medical Research , 27-31 Wright Street, Clayton, Victoria, 3168 Australia.
Rare cells with adult stem cell activity were recently discovered in human endometrium. Endometrial stem/progenitor cell candidates include epithelial, mesenchymal and endothelial cells, and all may contribute to the rapid endometrial regeneration following menstruation, rather than a single candidate. Endometrial mesenchymal stem-like cells (eMSC) are prospectively isolated as CD146(+)PDGFRbeta(+) cells and are found in both basalis and functionalis as perivascular cells. Epithelial progenitor cells are detected in colony forming unit (CFU) assays but their identity awaits elucidation. They are postulated to reside in the basalis in gland bases. Endometrial stem/progenitor cells may be derived from endogenous stem cells, but emerging evidence suggests a bone marrow contribution. Endometrial endothelial progenitor cells are detected as Side Population (SP) cells, which express several endothelial cell markers and differentiate into endometrial glandular epithelial, stromal and endothelial cells. Investigating endometrial stem cell biology is crucial for understanding normal endometrial physiology and to determine their roles in endometrial proliferative diseases. The nature of endometriosis suggests that initiation of ectopic endometrial lesions involves endometrial stem/progenitor cells, a notion compatible with Sampson’s retrograde menstruation theory and supported by the demonstration of eMSC in menstrual blood. Evidence of cancer stem cells (CSC) in endometrial cancer indicates that new avenues for developing therapeutic options targeting CSC may become available. We provide an overview of the accumulating evidence for endometrial stem/progenitor cells, their possible roles in endometrial proliferative disorders and discuss the unresolved issues.
Reprod Biomed Online. 2010 Jul;21(1):4-5. Epub 2010 Apr 18.
Department of Pathology, Duke University Medical Center, DUMC 3712, Durham, NC 27710, USA.
Many theories have been proffered to explain the histogenesis of endometriosis (Robboy et al., 2009). Generally, they divide into those that favour transplantation of endometrial fragments to ectopic sites, metaplasia of the multipotential celomic peritoneum and induction of undifferentiated mesenchyme in ectopic sites to form endometriotic tissues after exposure to substances released from shed endometrium. Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Maturitas. 2010 Jun 3. [Epub ahead of print]
Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, Norwegian university of Science and Technology, Trondheim, Norway; Department of Obstetrics and Gynecology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
INTRODUCTION: Endometriosis is a common disease in women of reproductive age. The symptoms usually disappear after a natural or a surgical menopause. Estrogen-based hormone therapy is required in women with premature or early menopause until the average age of the natural menopause and should be considered in older women with severe climacteric symptoms. However use of hormone therapy raises concerns about disease recurrence with pain symptoms, need for surgery and possibly malignant transformation of residual endometriosis. AIM: To formulate a position statement on the management of the menopause in women with a past history of endometriosis. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: The data regarding hormone therapy regimens are limited. However it may be safer to give either continuous combined estrogen-progestogen therapies or tibolone in both hysterectomised and nonhysterectomised women as the risk of recurrence may be reduced. The risk of recurrence with hormone therapy is probably increased in women with residual disease after surgery. Management of potential recurrence is best monitored by responding to recurrence of symptoms. Women not wanting estrogen or those who are advised against should be offered alternative pharmacological treatment for climacteric symptoms or skeletal protection if indicated. Herbal preparations should be avoided as their efficacy is uncertain and some may contain estrogenic compounds. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Fertil Steril. 2010 Jun 3. [Epub ahead of print]
Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis.
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
To test the hypothesis that bacterial contamination of menstrual blood could be a local biologic event in the development of endometriosis, menstrual blood was cultured and bacterial endotoxin was measured in menstrual blood and peritoneal fluid. Our results suggest that compared with control women, higher colony formation of Escherichia coli in menstrual blood and endotoxin levels in menstrual fluid and peritoneal fluid in women with endometriosis may promote Toll-like receptor 4-mediated growth of endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Fertil Steril. 2010 Jun 3. [Epub ahead of print]
Detection of mitochondrial biomarkers in eutopic endometria of endometriosis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.
Department of Gynecology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
OBJECTIVES: To detect specific mitochondrial proteins in eutopic endometrial samples from women with and without endometriosis and to build diagnostic models. DESIGN: Eutopic endometrial samples from women with endometriosis (excluding adenomyosis) and women with benign indications as control were studied by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein-chip technology. After finding the biomarkers, the diagnostic model was evaluated and validated by leave-one cross-validation. SETTING: Collaborative investigation in an academic research environment. PATIENT(S): Twenty-four patients with endometriosis (excluding adenomyosis) and 29 patients with benign indications as control. INTERVENTION(S): Surgical excision of eutopic endometrial biopsy of patients with endometriosis and controls. MAIN OUTCOME MEASURE(S): Mitochondrial protein expression. RESULT(S): Seventy-eight qualified mitochondrial protein peaks were detected, ten of them had a significant difference. Three combined potential biomarkers, with mass-to-charge ratios (m/z) of 15,334, 15,128, and 16,069, were found, and the diagnostic system distinguished endometriosis from control samples with a specificity of 86.2% and a sensitivity of 87.5%. CONCLUSION(S): We discovered potential mitochondrial biomarkers of eutopic endometrium in endometriosis and set up a diagnostic model. Further identification of the proteins we found will help to explain pathology, new diagnoses, and therapeutic approaches for endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Zhonghua Yi Xue Za Zhi. 2010 Mar 23;90(11):768-71.
Role of a latent soluble TNF receptor type I (hsTNFRI) fusion protein in targeted treatment of endometriosis.[Article in Chinese]
Department of Obstetrics & Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
OBJECTIVE: To construct a latent human soluble tumor necrosis factor receptor I (hsTNFRI) using the latency associated protein (LAP) of transforming growth factor-beta1 (TGF-beta1) fused via a matrix metalloproteinase (MMP) cleavage site to hsTNFRI so as to detect the latent biological activity of LAP-MMP-hsTNFRI fusion protein. METHODS: A double-stranded deoxyoligonucleotide coding for MMP cleavage site was cloned into plasmid pcDNA3.1. LAP and hsTNFRI cDNA were then inserted into both two sides of MMP cleavage site. After being transferred by LAP-MMP-hsTNFRI fusion gene with liposome, the expression of fusion protein in COS-7 cells was detected by RT-PCR and Western blot. The inhibitory effect of fusion protein upon cytotoxicity of TNF-alpha was detected by methyl thiazolyl tetrazolium (MTT) assay before and after the fusion protein incubated in MMP or peritoneal fluid from endometriosis patients. RESULTS: The recombinant plasmid LAP-MMP-hsTNFRI-pcDNA3.1 was constructed successfully and was expressed effectively in COS-7 cells. The MTT assay showed that there was no difference in the mortality rate of L929 cells between LAP-MMP-hsTNFRI-pcDNA3.1 and empty vector transfection groups (P > 0.05). The mortality rates of L929 cells with 800 ng/L TNF-alpha in LAP-MMP-hsTNFRI-pcDNA3.1 transfection group after incubation with MMP or peritoneal fluid from endometriosis patients were (44.5 +/- 2.4)% and (33.8 +/- 1.9)% respectively. And it was lower than the pre-incubation period (58.1 +/- 2.4)% (P < 0.05). CONCLUSION: The biological activity of LAP-MMP-hsTNFRI fusion protein can be made latent by LAP and activated by peritoneal fluid from endometriosis. Thus a new method has been provided for a targeted therapy of endometriosis.
Haemophilia. 2010 Jul;16 Suppl 5:160-7.
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. [email protected]
SUMMARY: While women are rarely affected by haemophilia, they are equally as likely as men to have other bleeding disorders. Menorrhagia, or heavy menstrual bleeding, is the most common symptom that they experience. Not only is menorrhagia more prevalent among women with bleeding disorders, but bleeding disorders are more prevalent among women with menorrhagia. Although menorrhagia is the most common reproductive tract manifestation of a bleeding disorder, it is not the only manifestation. Women with bleeding disorders appear to be at an increased risk of developing haemorrhagic ovarian cysts and possibly endometriosis. Women suspected of having a bleeding disorder or being a carrier of haemophilia should be offered diagnostic testing before getting pregnant to allow for appropriate preconception counselling and pregnancy management. During pregnancy, women with bleeding disorders may be at an increased risk of bleeding complications. At the time of childbirth, women with bleeding disorders appear to be more likely to experience postpartum haemorrhage, particularly delayed or secondary postpartum haemorrhage. As women with bleeding disorders grow older, they may be more likely to manifest gynaecological conditions which present with bleeding. Women with bleeding disorders are more likely to undergo a hysterectomy and are more likely to have the operation at a younger age. While women with bleeding disorders are at risk for the same obstetrical and gynaecological problems that affect all women, women with bleeding disorders are disproportionately affected by conditions that manifest with bleeding. Optimal management involves the combined expertise of haemostasis experts and obstetrician-gynaecologists.
J Minim Invasive Gynecol. 2010 Jul;17(4):508-512.
Atlanta Center for Special Minimally Invasive Surgery and Reproductive Medicine, Atlanta, Georgia.
STUDY OBJECTIVES: To report the feasibility and description of robot-assisted presacral neurectomy (RPSN) and to compare outcomes with laparoscopic presacral neurectomy (LPSN). DESIGN: Prospective case series (Canadian Task Force classification III). SETTING: Tertiary care center. PATIENTS: Eighteen patients with central pelvic pain who underwent RPSN and 12 patients with central pelvic pain who underwent conventional LPSN in a metropolitan hospital between July 1, 2006, and April 30, 2008. INTERVENTIONS: The da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) was used for the robotic portion of the procedure. Availability of the robot was the sole determining factor for the procedure chosen. Bipolar, monopolar, and ultrasonic instruments were used for conventional laparoscopy. All patients underwent several additional procedures performed laparoscopically including adhesiolysis, treatment of endometriosis, appendectomy, enterolysis, and salpingo-ovariolysis. MEASUREMENTS AND MAIN RESULTS: All presacral neurectomies in both groups were successfully completed by excising the hypogastric nervous plexus within the interiliac triangle. Presence of nerve ganglion and fibers was confirmed at pathologic analysis in all cases. Mean duration of presacral neurectomy, from incision of the posterior peritoneum at the sacral promontory to complete excision of the superior hypogastric nerve plexus at the interiliac triangle (Cotte triangle) was less than 10 minutes in both groups. Mean estimated blood loss was less than 30 mL for the entire surgical procedure (29.4 mL for RPSN, and 28.8 mL for LPSN). Median (range) patient age was 25 (19-44) years in the RPSN group, and 26 (18-36) years in the LPSN group; gravidity was 0, and parity was 0. All patients had central pelvic pain, the primary indication for presacral neurectomy. Concomitant indications for surgery included ovarian cysts, endometriosis, and adhesions. There were no intraoperative or postoperative complications. At analysis, follow-up ranged from 13 to 36 months. No short- or long-term complications related to the surgical procedure were reported. All patients reported subjective improvement of pelvic pain. CONCLUSION: Robot-assisted laparoscopic presacral neurectomy is feasible and safe, without added risk of short- or long-term complications. It compares favorably to the conventional laparoscopic approach of presacral neurectomy. The surgical robot provides a better angle and 3-dimensional visualization of the operating field, similar to laparotomy, and supplemented with magnification. This combined with elimination of hand tremor enables better surgeon control. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.
J Minim Invasive Gynecol. 2010 Jul 7. [Epub ahead of print]
Laparoscopy and Body Mass Index: Feasibility and Outcome in Obese Patients Treated for Gynecologic Diseases.
GINTEAM, Unit of Minimally Invasive Gynaecology (Drs. Camanni, Bonino, Delpiano, and Deltetto) and the Department of Public Health and Microbiology, University of Turin (Drs. Migliaretti and Berchialla), Turin, Italy.
STUDY OBJECTIVE: To compare feasibility and surgical outcome of laparoscopic gynecologic surgery between obese, overweight, normal-weight, and underweight women. DESIGN: Retrospective case control study (Canadian Task Force classification II-3). SETTING: Surgery Unit of Minimally Invasive Gynaecology. PATIENTS: A total of 503 women who underwent laparoscopic procedures for both benign disease and malignancies. INTERVENTIONS: Four main categories of gynecologic disease were identified: uterine fibroids, benign adnexal masses, endometriosis, and endometrial cancer (stage I). For each category patients were divided into 4 groups: underweight (BMI <18.5 kg/m(2)), normal-weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >/=30 kg/m(2)). MEASUREMENTS AND MAIN RESULTS: Selected outcomes were duration of surgery, rate of laparotomy conversion, intraoperative and postoperative complications, and duration of hospital stay. No statistical difference regarding demographic data, surgical and medical history, and intraoperative findings was present between groups. No laparotomy conversion occurred. Regarding duration of surgery, we found no statistical difference among the BMI groups with regard to benign diseases, whereas pelvic lymphadenectomy in obese patients with endometrial cancer had a statistically significant longer duration than in the control group (122 +/- 47min vs 65 +/- 21 min, p <.001). The postoperative complication rate was 0.01%: 3 cases of blood transfusion and 1 case of hemoperitoneum among myomectomies; 1 ureteral fistula in surgery for pelvic endometriosis; and 1 case of postoperative lymphocele in endometrial cancer group. No statistically significant difference was found in duration of hospital stay among the BMI groups in any of the categories of disease. For each category we conducted an analysis to identify any possible risk factors other than BMI in the surgical outcomes. CONCLUSION: Laparoscopic approach in the various applications of gynecologic surgery does not appear to be significantly influenced by BMI in terms of surgical outcomes, laparotomy conversion rate, intraoperative and postoperative complications rate, and duration of hospital stay. The technical difficulties can be solved if skilled surgeons and anesthetists are available. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.
Reprod Biol Endocrinol. 2010 Jul 11;8:85.
Family incidence of endometriosis in first-, second-, and third-degree relatives: case-control study.
Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria. [email protected]
BACKGROUND: Initial publications examining the hereditary aspects of endometriosis appeared in the early seventies and demonstrated an up to seven-fold risk for endometriosis in first-degree relatives of endometriosis patients. The aim was to evaluate the influence of hereditary aspects on the endometriosis risk in our patient collective. METHODS: In a retrospective cohort study we evaluated the incidence of endometriosis among first-, second-, and third-degree relatives of endometriosis patients and compare it with its incidence among first-, second-, and third-degree relatives of patients without endometriosis. RESULT(S): Eighty patients in whom endometriosis had been confirmed laparoscopically and histologically by biopsy and 60 patients in whom no endometriosis had been found during laparoscopy were given a questionnaire about the presence of symptoms associated with endometriosis and its family incidence. Patients of both the endometriosis and the control group were 37.7 +/- 6.2 and 45.9 +/- 12.0 years of age at the time of the interview, respectively (p < 0.05). Information about the presence of endometriosis was more readily available for relatives of those in the endometriosis group than for those in the control group (325/749 [43.4%] vs. 239/425 [56.2%], p < 0.05). In 5/136 (3.7%) and 8/134 (6.0%) first-degree relatives of endometriosis patients and the control group, respectively, information about the presence of endometriosis was not available (p = 0.554). Endometriosis was found in 8/136 (5.9%) first-degree relatives of patients and in 4/134 (3.0%) first-degree relatives of controls in the real-case analysis (p = 0.248). When comparing endometriosis characteristics between endometriosis patients with and without a history of familial endometriosis, no significant differences were found. CONCLUSION(S): There is a trend toward an increased familial incidence of endometriosis. In contrast to the literature, we found a less dramatic increase in familial risk for the development of endometriosis.
Aust N Z J Obstet Gynaecol. 2010 Jun;50(3):306.
Aust N Z J Obstet Gynaecol. 2010 Jun;50(3):273-9.
Levonorgestrel-releasing intrauterine system (Mirena) and Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: a randomised controlled trial.
Department of Obstetrics & Gynaecology, Kwong Wah Hospital, Hong Kong, China. [email protected]
BACKGROUND: Progestogen therapy has been found to be useful in controlling endometriosis. For patients after conservative surgery, long-term medical maintenance therapy should be sought to prevent recurrence and control symptoms. Levonorgestrel-releasing intrauterine system (LNG-IUS) may be a useful form of prolonged progestogen therapy for endometriosis. AIMS: To evaluate and compare the efficacy and safety of LNG-IUS to depot medroxyprogesterone acetate (MPA) for patients with moderate or severe endometriosis following conservative surgery, in terms of symptoms control, recurrence prevention and patients’ acceptance. METHODS: A total of 30 patients after conservative surgery for endometriosis underwent randomisation. Of these patients, 15 received LNG-IUS and 15 had three-monthly depot MPA for three years. Their symptom control, recurrence, compliance and change in bone mineral density (BMD) were compared. The data were analysed using student’s t-test and chi-square test. RESULTS: Symptoms and recurrence were controlled by both therapies. The compliance was better in LNG-IUS Group with 13 patients staying on their therapy versus seven patients in Depot MPA Group. LNG-IUS users had a significantly better change in BMD (+0.023, +0.071 g/cm(2)) than Depot MPA users (-0.030, -0.017 g/cm(2)) in both hip and lumbar regions. CONCLUSIONS: Levonorgestrel-releasing intrauterine system was effective in symptom control and prevention of recurrence. LNG-IUS users showed a better compliance. After three years, bone gain was noted with LNG-IUS, but bone loss with depot MPA.