Accuracy of ultrasound signs on two-dimensional transvaginal ultrasound in prediction of adenomyosis: prospective multicenter study.

OBJECTIVE: Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D-TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis. METHODS: This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D-TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D-TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed. RESULTS: A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D-TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7-62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2-81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs. CONCLUSIONS: Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false-positive and false-negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis: Long Version - AWMF Registry No. 015-045.

In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic.

Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma.

Adult stem cells are thought to be responsible for the high regenerative capacity of the human endometrium, and have been implicated in the pathology of endometriosis and endometrial carcinoma. The RNA-binding protein Musashi-1 is associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. We investigated expression and localization of Musashi-1 in endometrial, endometriotic and endometrial carcinoma tissue specimens of 46 patients. qPCR revealed significantly increased Musashi-1 mRNA expression in the endometrium compared to the myometrium. Musashi-1 protein expression presented as nuclear or cytoplasmic immunohistochemical staining of single cells in endometrial glands, and of single cells and cell groups in the endometrial stroma. Immunofluorescence microscopy revealed colocalization of Musashi-1 with its molecular target Notch-1 and telomerase. In proliferative endometrium, the proportion of Musashi-1-positive cells in the basalis layer was significantly increased 1.5-fold in the stroma, and three-fold in endometrial glands compared to the functionalis. The number of Musashi-1 expressing cell groups was significantly increased (four-fold) in proliferative compared to secretory endometrium. Musashi-1 expressing stromal cell and cell group numbers were significantly increased (five-fold) in both endometriotic and endometrial carcinoma tissue compared to secretory endometrium. A weak to moderate, diffuse cytoplasmic glandular staining was observed in 50% of the endometriosis cases and in 75% of the endometrioid carcinomas compared to complete absence in normal endometrial samples. Our results emphasize the role of Musashi-1-expressing endometrial progenitor cells in proliferating endometrium, endometriosis and endometrioid uterine carcinoma, and support the concept of a stem cell origin of endometriosis and endometrial carcinoma.

[ENZIAN-score, a classification of deep infiltrating endometriosis]. / ENZIAN-Score, eine Klassifikation der tief infiltrierenden Endometriose.

The ENZIAN-Score is presented as a new instrument to classify the deep infiltrating endometriosis. Especially the retroperitoneal part of the severe endometriosis is focussed on. In analogy to an oncological staging four different stages are pronounced. The localisation and the expansion of the endometriosis nodule was indicated to different subgroups. The still used rAFS-score is of no clinical evidence, as we pointed out in a retrospective study of our patients with severe intestinal endometriosis.

A prospective randomized trial of closing laparoscopic trocar wounds by transcutaneous versus subcuticular suture or adhesive papertape.

BACKGROUND: Several methods for closure of trocar wounds are known in laparoscopic surgery. The choice of technique (mostly transcutaneous or subcuticular suture or adhesive papertape) is often based on the surgeon's personal experience. Thus, the objective of this trial was to assess the impact of these closure methods on potential complications of wound healing, cosmetic outcome, and patient satisfaction. METHODS: Sixty patients undergoing operative laparoscopic surgery for gynecologic indications were enrolled in this prospective randomized trial. Five-millimeter port-site incisions were closed either with subcuticular or transcutaneous absorbable sutures (4-0 polyglactin 910) or with adhesive papertape. Postoperative complications, pain, and patient satisfaction with scars were evaluated at 3-month follow-up after operation using a questionnaire. RESULTS: Data from 52 patients who returned the questionnaire were analyzed. Dissatisfying cosmetic results were reported significantly more frequently after subcuticular sutures (p < 0.05). Assessment of patient satisfaction with cosmetic outcome on a visual-analogue scale revealed significantly better results after transcutaneous skin closure than with other approaches (p < 0.05). Adverse wound healing (e.g., infections and dehiscence) was observed most frequently in the subcuticular suture group. Also, the rate of painful scars was highest with this technique. CONCLUSIONS: Transcutaneous closure with absorbable suture material seems to be the most suitable technique for closure of laparoscopic port-site incisions.

Genomic imbalance and onco-protein expression of ovarian endometrioid adenocarcinoma arisen in an endometriotic cyst.

BACKGROUND: Malignant transformation in endometriosis is a rare but well known complication. However, detailed mechanisms of malignant transition and tumourigenesis in endometriosis remain unknown. We here describe the case of an endometrioid carcinoma arisen in endometriotic ovarian cyst fulfilling Sampson's criteria for malignant transformation of endometriosis. We compared genetic alterations and oncoprotein expression in the endometriotic ovarian cyst and the associated endometrioid adenocarcinoma. MATERIALS AND METHODS: Genomic instability was evaluated by comparative genomic hybridization (CGH). Onco-protein expression was analysed by immunohistochemistry with antibodies against bcl-2, c-MYC, cyclin D1, p53, HER-2 and KIT protein. RESULTS: CGH revealed a gain of 8q, including the locus of the oncogene c-MYC at 8q24. Immunohistochemistry disclosed a differing protein expression profile between the epithelia of the pre-existing cyst and adenocarcinoma. Apart from HER-2, all onco-proteins were more strongly expressed in epithelial cells of the adenocarcinoma than of the endometriotic cyst. CONCLUSION: The solitary genomic imbalance of chromosome 8 possibly reflects the importance for initiation and/or progression of endometrioid carcinoma. Overexpression of onco-proteins then may occur subsequently in the malignant transformation of ovarian endometriosis. However, the exact mechanisms of malignant transition in ovarian endometriosis remain to be elucidated in future studies with a higher number of cases.

The diagnostic dilemma of minimal and mild endometriosis under routine conditions.

STUDY OBJECTIVE: To evaluate the reliability of diagnosing minimal and mild endometriosis under routine conditions, and to determine to what extent disease activity is taken into account. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University teaching hospital. INTERVENTION: Laparoscopy. PATIENTS: One hundred eighteen consecutive women with minimal and mild endometriosis undergoing routine surgery between 1994 and 1999. MEASUREMENTS AND MAIN RESULTS: Analytic parameters were the total number of endometriotic lesions; intraoperative description of pigmented, nonpigmented, and nondefined lesions; and number of extirpated lesions and histologic detection rate. In 118 patients, 311 suspected endometriotic lesions were documented. Nonpigmented lesions were reported in only 27% of women. In 51% of surgical reports no importance was attached to disease morphology or activity. Only 1.2 biopsies/patient were taken. The histologic detection rate was 56%. In 49 patients the assumed intraoperative diagnosis was confirmed by histologic examination. CONCLUSIONS: Intraoperative description of endometriotic lesions is inadequate. Little attention is paid to the activity of the illness. There is room for improvement in the number of excisions and histologic detection, and an attempt should be made to find a way out of this diagnostic dilemma.

Vascular endothelial growth factor mRNA in eutopic and ectopic endometrium.

OBJECTIVE: To evaluate changes in expression levels of vascular endothelial growth factor (VEGF) mRNA in human endometrial explants in a chicken chorioallantoic membrane model of endometriosis. DESIGN: Experimental prospective study. SETTING: University hospital. PATIENT(S): Endometrial biopsy samples were obtained from healthy, ovulating women undergoing elective surgery. INTERVENTION(S): Endometrial fragments were placed on the chicken chorioallantoic membrane and removed for analysis after 0, 24, 48, and 72 hours. MAIN OUTCOME MEASURE(S): Expression of different VEGF mRNA splice variants was tested. Expression of VEGF(165) mRNA was assessed by using competitive polymerase chain reaction and normalized to expression of the housekeeping gene human glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. RESULT(S): After 0, 24, 48, and 72 hours of incubation, all grafts expressed VEGF(121), VEGF(145), VEGF(165), and VEGF(189) mRNA. Expression of VEGF(165) mRNA increased up to 10-fold at 24 to 72 hours compared with precultivation values. CONCLUSION(S): Levels of VEGF(165) mRNA in endometrial grafts increase after implantation on chicken chorioallantoic membrane. Hypoxic induction of VEGF mRNA expression in endometrial cell cultures has been reported previously. Induction of VEGF expression might indicate relative hypoxia of the specimen due to insufficient vascularization. Expression of VEGF may assist in vascularization of endometrial explants after retrograde menstruation.

Prospective evaluation of the systemic immune response following abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy.

BACKGROUND: Alterations in serum levels of cytokine interleukin-6 (IL-6) and acute-phase protein C-reactive protein (CRP) correlate directly with extent of tissue damage and inflammatory reaction. We therefore prospectively compared the postoperative levels of IL-6 and CRP following abdominal (AH), vaginal (VH), and laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: A total of 29 patients were included in the study (10 VH, 10 LAVH, 9 AH). Nine blood samples were taken from each patient at various time points before, during, and after surgery. CRP and IL-6 were measured under standardized conditions using ELISA and turbidometry. RESULTS: Preoperative levels of IL-6 and CRP were low in all three patient groups. There was a significant increase in the IL-6 level in patients undergoing AH at the time of peritoneal closure that reached a maximum 2 h postoperatively and remained significantly elevated for 12 h postoperatively when compared to the IL-6 levels of patients undergoing VH or LAVH (p < 0.05). The levels of the IL-6 time courses differed significantly among the three operative procedures (p = 0.013). In contrast, the levels of the CRP time courses did not differ significantly (p = 0.066); however, CRP expression was elevated 36 h postoperatively in patients undergoing AH, as compared with those undergoing VH. CONCLUSION: Elevated IL-6 levels subsequent to AH may reflect significantly greater tissue damage in these patients than in patients who undergo VH or LAVH. LAVH should therefore be considered in cases that cannot be managed by the vaginal route alone.

Laparoscopic management of tubo-ovarian abscesses: retrospective analysis of 60 cases.

BACKGROUND: The laparoscopic management of tubo-ovarian abscesses (TOA) was evaluated. The study sought to answer the following question: Does operative laparoscopy with only incision of the abscess cavity and lavage (organ-preserving treatment) improve intraoperative and postoperative safety and long-term prospects of fertility as compared with laparoscopic salpingectomy or salpingo-oophorectomy (ablative treatment)? METHODS: A retrospective chart review of 60 patients with TOA undergoing laparoscopic treatment in combination with broad-spectrum antibiotics from 1994 to 1998 was performed. Patients not wishing to have children underwent salpingectomy or salpingo-oophorectomy, whereas patients wishing to remain fertile were treated by means of an organ-preserving procedure. To investigate the operative and reproductive outcome, patients were interviewed by telephone. RESULTS: Of 60 women with TOA, 25 were treated laparoscopically, preserving the internal genital organs, and 35 underwent ablative treatment. Apart from one postoperative readmission because of lower pelvic pain in the organ-preserving group, there were no operative complications or serious systemic sequelae. In contrast, there was a significantly higher incidence of intraoperative and postoperative complications when ablative treatment was performed: one intestinal perforation requiring subsequent laparotomy, four serosal lesions, two lesions of the greater omentum, two lacerated collaterals of the internal iliac artery, one postoperative fever higher than 38 degrees C for 2 days, two bowel obstructions, one thrombosis of the upper leg, and one thrombosis of the lower leg. There were no significant differences between the two patient groups in body mass index, duration of pelvic pain, laboratory findings at admission, ultrasonic assessment of abscess size, and the extent of the abscess at laparoscopy. CONCLUSIONS: When laparoscopic treatment of TOA is performed, organ-preserving treatment should be chosen irrespective of the patient's age or desire to have children because of the risk of complications.

Fluorescence diagnosis of endometriosis using 5-aminolevulinic acid.

BACKGROUND: The diagnosis of nonpigmented endometrial lesions by simple laparoscopic visualization is difficult and often inaccurate. We therefore sought to establish a new and more accurate method to visualize these nonpigmented peritoneal changes caused by endometriosis. METHODS: A total of 37 patients received 30 mg 5-aminolevulinic acid/kg body weight 10 to 14 hs prior to surgery. Laparoscopy was then performed using a D-light system (Storz, Tuttlingen, Germany). The findings were evaluated first in the white-light mode; the D-light system was then activated, and all areas of fluorescence were documented. Multiple specimens were obtained by biopsy. RESULTS: The sensitivity of the fluorescence diagnosis in detecting endometriosis in nonpigmented areas and normal-looking peritoneum is 100%, with a specificity of 75%. Diagnosis by simple visualization under white illumination has a sensitivity of only 69% and a specificity of 70%. Occult areas of endometriosis were discovered using fluorescence diagnosis. CONCLUSIONS: Our findings suggest that fluorescence diagnosis using 5-aminolevulinic acid is feasible and can improve the diagnosis of endometriosis in nonpigmented and occult endometrial lesions. Fluorescence diagnosis is a promising new tool in the diagnosis of endometriosis.

Myocardial magnesium transport: effect of gramicidin S and epinephrine.

Initial magnesium transport in low magnesium Ringer in the frog myocardium consists of at least two systems, a fast system with high capacity with a time constant of 30 seconds and a slow transport system that operates with a time constant of 165 seconds. Both transport systems appear to be electroneutral and can operate either against an electrochemical gradient or with an electrochemical gradient. The fast transport system can transport Mg2+ in an outward direction at 1.84 p mol cm-2 sec-1; the slow system causes Mg2+ to be transported outward at 0.05 p mol cm-2 sec-1. Gramicidin S (5 microM) decreases the slow outward transport system to 0.01 p mol cm-2 sec-1 and at concentrations greater than 1 microM inhibits not only slow magnesium outflux in low calcium Ringer but also inhibits magnesium influx during recovery of Mg2+ in Ringer. Gramicidin S at 5 microM decreases Mg2+ influx from .04 p mol cm-2 sec-1 to 0.01 p mol cm2 sec-1 indicating that influx and efflux may take place on the same transport system. In the presence of 10 mM Mg2+ Gramicidin S increases magnesium content. Epinephrine increases magnesium efflux and overcomes the inhibition of Mg2+ efflux by Gramicidin S.