Expert opinion on the use of transvaginal sonography for presurgical staging and classification of endometriosis.

Gynecological ultrasonography plays a central role in the management of endometriosis. The rapid technical development as well as the currently increasing evidence for non-invasive diagnostic methods require an updated compilation of recommendations for the use of ultrasound in the management of endometriosis. The present work aims to highlight the accuracy of sonography for diagnosing and classifying endometriosis and will formulate the present list of key messages and recommendations. This paper aims to demonstrate the accuracy of TVS in the diagnosis and classification of endometriosis and to discuss the clinical applications and consequences of TVS findings for indication, surgical planning and assessment of associated risk factors. (1) Sophisticated ultrasound is the primary imaging modality recommended for suspected endometriosis. The examination procedure should be performed according to the IDEA Consensus. (2) Surgical intervention to confirm the diagnosis alone is not recommended. A preoperative imaging procedure with TVS and/or MRI is strongly recommended. (3) Ultrasound examination does not allow the definitive exclusion of endometriosis. (4) The examination is primarily transvaginal and should always be combined with a speculum and a bimanual examination. (5) Additional transabdominal ultrasonography may enhance the accuracy of the examination in case of extra pelvic disease, extensive findings or limited transvaginal access. (6) Sonographic assessment of both kidneys is mandatory when deep endometriosis (DE) and endometrioma are suspected. (7) Endometriomas are well defined by sonographic criteria. When evaluating the ovaries, the use of IOTA criteria is recommended. (8) The description of sonographic findings of deep endometriosis should be systematically recorded and performed using IDEA terminology. (9) Adenomyosis uteri has sonographically well-defined criteria (MUSA) that allow for detection with high sensitivity and specificity. MRI is not superior to differentiated skilled ultrasonography. (10) Classification of the extent of findings should be done according to the #Enzian classification. The current data situation proves the best possible prediction of the intraoperative situs of endometriosis (exclusive peritoneum) for the non-invasive application of the #Enzian classification. (11) Transvaginal sonographic examination by an experienced examiner is not inferior to MRI diagnostics regarding sensitivity and specificity in the prediction of the extent of deep endometriosis. (12) The major advantage of non-invasive imaging and classification of endometriosis is the differentiated planning or possible avoidance of surgical interventions. The recommendations represent the opinion of experts in the field of non-invasive and invasive diagnostics as well as therapy of endometriosis. They were developed with the participation of the following national and international societies: DEGUM, ÖGUM, SGUM, SEF, AGEM/DGGG, and EEL.

Lymph node dissection in endometrial cancer and clinical outcome: A population-based study in 5546 patients.

BACKGROUND: According to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. MATERIALS AND METHODS: Data were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. RESULTS: Of 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. CONCLUSIONS: The application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.

Cancer of the ovary, fallopian tube, and peritoneum: a population-based comparison of the prognostic factors and outcomes.

PURPOSE: The objective was to compare the prognostic factors and outcomes among primary ovarian cancer (OC), fallopian tube cancer (FC), and peritoneal cancer (PC) patients in a population-based setting. METHODS: We analysed 5399 OC, 327 FC, and 416 PC patients diagnosed between 1998 and 2014 in the catchment area of the Munich Cancer Registry (meanwhile 4.8 million inhabitants). Tumour site differences were examined by comparing prognostic factors, treatments, the time to progression, and survival. The effect of the tumour site was additionally analysed by a Cox regression model. RESULTS: The median age at diagnosis, histology, and FIGO stage significantly differed among the tumour sites (p < 0.001); PC patients were older, more often diagnosed with a serous subtype, and in FIGO stage III or IV. The time to progression and survival significantly differed among the tumour sites. When stratified by FIGO stage, the differences in time to progression disappeared, and the differences in survival considerably weakened. The differences in the multivariate survival analysis showed an almost identical outcome in PC patients (HR 1.07 [0.91-1.25]) and an improved survival of FC patients (HR 0.63 [0.49-0.81]) compared to that of OC patients. CONCLUSION: The comparison of OC, FC, and PC patients in this large-scale population-based study showed differences in the prognostic factors. These differences primarily account for the inferior outcome of PC patients, and for the improved survival of FC compared to OC patients.

Pericardial teratoma: prenatal diagnosis and course.

We report on a case of primary pericardial teratoma detected in a 29-week-old fetus. Due to cardiac decompensation, pericardiocentesis was performed at 33 weeks of gestation, and surgical excision of the tumor was indicated shortly after birth. The present report draws attention to the impact of fetal echocardiography on perinatal management.

Lactoferrin-binding proteins of Tritrichomonas foetus.

Tritrichomonas foetus is a common, sexually transmitted, protozoan parasite of cattle. It has an essential requirement for iron, which it obtains from host lactoferrin. However, specific lactoferrin-binding protein receptors have not yet been identified in T. foetus. To differentiate specific and nonspecific binding of lactoferrin, lactoferrin affinity chromatography and Western blotting was used to identify metabolically or surface-labeled T. foetus lactoferrin-binding proteins. Bovine lactoferrin was shown to bind more efficiently than human lactoferrin, and each of these bound much better than bovine transferrin. This is relevant because T. foetus is both species-specific and only infects the mucosal surface of the reproductive tract, which has little transferrin. Whereas the majority of lactoferrin binding was specific, competitive inhibition studies showed that nonspecific, charge-related binding of lactoferrin to T. foetus may also be involved. In the presence of bovine cervical mucus, binding of lactoferrin to T. foetus was diminished, suggesting that mucus has an effect on lactoferrin binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surface biotinylated proteins affinity-purified on lactoferrin-Sepharose showed biotinylated bands at Mr values of 22, 49, 55, 72, and 155 kDa. Because lactoferrin-binding proteins may be susceptible to digestion by T. foetus extracellular cysteine proteinases, it is suspected that the 155-kDa protein is the specific lactoferrin-binding protein and that the lower-Mr lactoferrin-binding molecules may be fragmentation products that contain the lactoferrin-binding site; however, other interpretations are clearly feasible. It is possible that there may be multiple proteins or multimers of the same protein. In summary, the data showed that binding of lactoferrin to T. foetus may be regulated by an interplay of specific receptor interactions as well as by hydrophobic and charge-related interactions.

Preoperative diagnosis of ovarian tumors with MR imaging: comparison with transvaginal sonography, positron emission tomography, and histologic findings.

OBJECTIVE: Our study evaluated the diagnostic performance of MR imaging compared with that of transvaginal sonography and positron emission tomography (PET) in patients with clinically asymptomatic adnexal findings. An additional goal was to determine whether the combination of the three methods enhanced their diagnostic accuracy. SUBJECTS AND METHODS: Included in the study were 103 women with suspicious adnexal findings on sonography. Patients underwent transvaginal sonography, MR imaging, and PET within 3 weeks of the initial sonography. For MR imaging, axial and sagittal T1-weighted gradient-echo sequences (unenhanced and enhanced) and T2-weighted turbo-spin-echo sequences were acquired. Transvaginal sonography was performed with a 7.5-MHz transducer head. For PET, a modern full-ring scanner was used. The results of diagnostic imaging techniques were first evaluated separately, and reviewers were blinded to the results of other methods. Finally, a second session resulted in a consensus diagnosis based on the findings of all three methods. Results of histology were considered the gold standard. RESULTS: Histology revealed 12 malignant and 91 benign ovarian tumors. The following data were calculated for MR imaging, transvaginal sonography, PET, and consensus diagnosis: sensitivities, 83%, 92%, 58%, 92%; specificities, 84%, 59%, 78%, 84%; diagnostic accuracies, 83%, 63%, 76%, 85%, respectively. MR imaging, particularly with contrast-enhanced fat-saturated T1-weighted sequences, was found to correctly reveal dermoid and endometrial cysts. All three methods had false-negative findings with borderline tumors. CONCLUSION: Transvaginal sonography is the diagnostic method of choice as a screening technique for ovarian processes. Suspicious findings on transvaginal sonography should be confirmed on MR imaging. If MR imaging confirms a dermoid or endometrial cyst, further diagnostic procedures may be unnecessary. In all other cases, a surgical evaluation must be considered.

Endoscopic axillary surgery in breast cancer.

BACKGROUND: The aim was to provide an assessment of the current status of endoscopic axillary surgery in patients with breast cancer. METHODS: Fifty-three patients underwent endoscopic lymphadenectomy. The surgical efficiency (operating time, number of resected nodes, intraoperative and postoperative complications), short-term morbidity (duration of drainage, total lymph flow, seroma rate) and long-term outcome (pain, numbness, mobility, strength, oedema) were assessed. The incidence and severity of different arm symptoms were compared with the results of 396 patients treated with a conventional axillary procedure. Finally, all available data relating to endoscopic axillary surgery were reviewed. RESULTS: The operating time ranged from 60 to 150 min. A mean 17 (range 10-28) lymph nodes was resected. The extent of postoperative lymphorrhoea (mean 372 ml) and the seroma rate (eight of 34 patients) were not significantly reduced in comparison with conventional surgery. The assessment of long-term morbidity revealed fewer disturbances of sensitivity and a decreased rate of severe symptom intensity for pain, oedema and complaints related to mobility. CONCLUSION: Despite excellent visualization of anatomical landmarks and improved long-term morbidity, endoscopic lymph node dissection cannot be regarded as a suitable technique for routine axillary management in breast cancer because of long operating times.

An accessory role for the diacylglycerol moiety of variable surface glycoprotein of African trypanosomes in the stimulation of bovine monocytes.

The membrane-associated form of the variable surface glycoprotein (mfVSG) from African trypanosomes is a potent macrophage activator capable of inducing production of tumor necrosis factor alpha (TNFalpha) in both bovine and murine models. Using a bovine model, we have re-investigated the hypothesis that the diacylglycerol moiety of the glycosylphosphatodylinositol (GPI) anchor is involved in macrophage activation and might be the actual parasite toxin. The anchor of the variable surface glycoprotein (VSG) was labeled with (3)H-myristic acid and VSG purified in its membrane-associated form. The dimyristylglycerol moiety of the anchor was released by phospholipase C cleavage. Integrity of the anchor and efficiency of cleavage was verified by autoradiography and methanol:hexane extraction. For analysis of biological function, bovine monocytes were used which had been incubated with bovine interferon gamma (primed) or with culture medium (unprimed). The VSG purified in its membrane-associated form was found to stimulate both primed and unprimed cells to secrete TNFalpha. The same preparation from which the dimyristylglycerol moiety had been cleaved was no longer able to stimulate unprimed cells but could still stimulate primed cells. Our data indicate that the presence of the dimyristylglycerol is not an absolute requirement for induction of TNFalpha production but can substitute for the interferon gamma priming. Therefore, we favor the hypothesis that stimulation of macrophages to secrete TNFalpha by the mfVSG is mediated by an as yet unknown trigger moiety and is facilitated by the dimyristylglycerol anchor.

New service in a community hospital: the role of nursing staff development.

The purpose of this article is to describe strategies to assist nurses in staff development with planning and implementing a successful education program directed at preparing staff to provide a new patient service in a community hospital. The staff development instructor can play a crucial role in the successful implementation of a new service in a community hospital. This article focuses on the implementation of a cardiac surgery program in a community hospital.

Classification of asymptomatic adnexal masses by ultrasound, magnetic resonance imaging, and positron emission tomography.

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of sonography versus magnetic resonance imaging (MRI) and positron emission tomography (PET) in the characterization of adnexal masses. METHODS: One hundred and one patients with asymptomatic adnexal masses, which were scheduled for laparoscopy, underwent preoperative transvaginal ultrasound, MRI, and 2-[(18)F]fluoro-2-deoxy-d-glucose PET. Two different sonomorphological scoring systems were used to distinguish malignant from benign lesions. In addition, transvaginal Doppler flow velocimetry was performed and the resistance index (RI) of ovarian blood vessels was calculated. RI values below 0.45 were considered to indicate malignancy. MRI was evaluated on the basis of signal intensity and morphologic features such as wall thickness, septations, fluid or solid components, and vascularity. PET imaging was used to determine 2-[(18)F]fluoro-2-deoxy-D-glucose uptake. Malignancy was suspected if radiotracer uptake equaled or exceeded that of the liver. Based on histologic findings, sensitivity, specificity, positive and negative predictive values, and accuracy were first calculated independently for each imaging technique. Finally, a second session resulted in a consensus diagnosis being made based on the findings of all three modalities. RESULTS: Sonographic evaluation of adnexal masses resulted in correct classification of 11 of 12 ovarian malignancies (sensitivity 92%) but with a specificity of only 60%. With MRI and PET, specificities improved to 84 and 80% respectively, but sensitivities decreased. When all imaging modalities were combined, sensitivity and specificity were 92 and 85%, respectively, and accuracy was 86%. CONCLUSION: Combination of ultrasound with MRI and PET may improve accuracy in differentiation of benign from malignant ovarian lesions. However, negative MRI or PET results do not rule out early-stage ovarian cancer or borderline malignancies.

Predicting the histologic dating of an endometrial biopsy specimen with the use of Doppler ultrasonography and hormone measurements in patients undergoing spontaneous ovulatory cycles.

OBJECTIVE: To examine the relation between uterine blood flow and endometrial thickness on transvaginal Doppler ultrasonography, serum E2 and progesterone levels, and the histologic dating of an endometrial biopsy specimen obtained in the midluteal phase of a spontaneous cycle. DESIGN: Prospective clinical study. SETTING: A tertiary care infertility center. PATIENT(S): One hundred fifty-nine patients with normal menstrual cycles. INTERVENTION(S): Transvaginal Doppler ultrasonographic evaluation of uterine blood flow and endometrial thickness, determination of serum concentrations of E2 and progesterone, and endometrial biopsy. MAIN OUTCOME MEASURE(S): Resistance index, pulsatility index, serum E2 and progesterone levels, endometrial thickness, and histologic dating of the endometrium. RESULT(S): One hundred thirteen (71%) of the endometrial biopsy specimens showed complete secretory transformation and thus were classified as "in phase," and 46 (29%) of the specimens lacked some or all of the criteria for secretory transformation and thus were classified as "out of phase." There was no statistically significant difference between the in phase and out of phase groups with regard to patient age, endometrial thickness, serum hormone levels, or resistance index. The pulsatility index was significantly higher in the in phase group. The overall predictive value of the studied parameters was only 64% (sensitivity, 57%; specificity, 66%). CONCLUSION(S): Doppler ultrasonographic evaluation of uterine blood flow and measurement of hormone concentrations cannot be used to predict the histologic dating of an endometrial biopsy specimen obtained in the midluteal phase of a spontaneous cycle.

[Laparoscopic intraoperative differential diagnosis of adnexal tumors. A pilot study of 20 premenopausal patients]. / Laparoskopische Sonographie zur intraoperativen Differenzialdiagnostik von Adnextumoren. Eine Pilotstudie an 20 prämenopausalen Patientinnen.

AIM: The purpose of the study was to determine the feasibility and potential clinical value of laparoscopic intraoperative sonography in the female genital tract. PATIENTS AND METHOD: Intraoperative ultrasound was performed in 20 consecutive premenopausal patients with adnexal masses during laparoscopy using a 7.5 MHz semiflexible transducer. RESULTS: Laparoscopic ultrasound of the female genital tract improves image resolution. Furthermore, this new method allows accurate localisation of early tubal pregnancy and may be helpful if laparoscopic evaluation of the inner genital tract is impaired by severe adhesions. In 7 out of 20 patients, the therapeutical procedure was clearly influenced by the laparoscopic ultrasound findings, resulting in a benefit for the patients in all seven cases. CONCLUSION: Intraoperative laparoscopic ultrasound may improve minimal invasive management of adnexal masses.

[Preoperative assessment of asymptomatic adnexal tumors by positron emission tomography and F 18 fluorodeoxyglucose]. / Präoperative Dignitätsbeurteilung asymptomatischer Adnextumoren mittels Positronen-Emissions-Tomographie und F-18-Fluordeoxyglukose.

AIM: To evaluate use of F-18-FDG-PET in assessment of dignity of asymptomatic adnexal masses. METHODS: 85 asymptomatic patients with suspicious, asymptomatic adnexal masses were evaluated. Static FDG-PET (Exact HR+ or ECAT 931) imaging of the abdomen was performed following application of 222-555 MBq F-18-FDG. Iterative reconstruction was applied. PET data were analysed visually, at first without and second together with MRT images. Final diagnosis was made by histopathology. RESULTS: FDG-PET allowed correct identification of 4 of 8 malignant adnexal tumors. False negative results were obtained in 2 adenocarcinomas stage pT1a and 2 borderline-tumors. In 60 out of 77 benign adnexal masses malignancy could be excluded. False positive FDG-uptake, partly because of misinterpretation of gastrointestinal activity, was found in 3 inflammatory processes, 1 teratoma, 1 benign schwannoma, 1 dermoid cyst, 1 benign thecoma, 1 serous cyst, 1 serous cystadenoma, 2 mucinous cystadenomas, 2 corpus luteum cysts, 3 endometriosic cysts and 1 sactosalpinx. The overall sensitivity and specificity of FDG-PET alone were 50% and 78%. Evaluation together with MRT images showed a sensitivity of 50% and a specificity of 86%. CONCLUSION: Sensitivity of FDG-PET in detection of borderline-tumors and early stage ovarian cancer seems to be limited. Low incidence of malignant ovarian tumors requires for assessment of dignity a procedure of high specificity, that is not reached by FDG-PET neither without nor together with MRT images for topographic orientation. Therefore use of FDG-PET for assessment of dignity in suspicious, asymptomatic ovarian tumors is limited.

A cryptic protease activity from Trypanosoma cruzi revealed by preincubation with kininogen at low temperatures.

Cysteine proteases have been identified in parasitic protozoa including the causative agent of Chagas' disease Trypanosoma cruzi. T. cruzi lysates subjected to substrate-containing SDS-polyacrylamide gel electrophoresis exhibit major bands of proteolytic activity in the 45-55 kDa molecular mass range (cruzipain activity). Paradoxically, addition of kininogen (a cystatin-like protease inhibitor) to the lysates before electrophoresis results in the appearance of additional bands of proteolytic activity in the 160-190 kDa molecular mass range. This inhibitor-activated protease activity depends upon the reaction conditions and exhibits novel properties. For example, a 24-48 hour preincubation at low temperature (-20 degrees C optimum) greatly enhances the proteolytic activity. The results suggest that a metastable complex forms between kininogen and a cryptic 30 kDa cysteine protease from T. cruzi and that this complex participates in the activation of proteolytic activity.

Lack of correlation between ultrasonography and histologic staging of the endometrium in in vitro fertilization (IVF) patients.

In 53 patients of an in vitro fertilization (IVF) program with unsuccessful fertilization of oocytes, an endometrial biopsy was carried out on the day of the intended embryo transfer. The results were compared with the thickness (assessed on the very same day by means of ultrasonography) and the echo pattern of the endometrium, which was classified into four grades (A to D). We found grade A in 16 cases (30%), grade B in 22 cases (41.5%) and grade C in 15 cases (28.5%); no endometrium was assessed as grade D. The distribution of histologic findings was not significantly skewed within the respective grading categories (only 37.5% of grade A endometria, 63.5% of grade B endometria and 66.5% of grade C endometria were in phase with the menses). The in-phase and out-of-phase endometria did not display significant differences in endometrial thickness (8.8 +/- 0.29 mm vs. 9.13 +/- 0.4mm). Neither the sonographically measured endometrial thickness nor the echo pattern correlated with the histologic findings, suggesting that ultrasonography is inadequate for drawing reliable conclusions about endometrial receptivity in an IVF program.

Trypanosomatid cysteine protease activity may be enhanced by a kininogen-like moiety from host serum.

African trypanosomes contain cysteine proteases (trypanopains) the activity of which can be measured by in vitro digestion of fibrinogen, after electrophoresis in fibrinogen-containing SDS/polyacrylamide gels. When assessed by this procedure, trypanopain from Trypanosoma brucei (trypanopain-Tb) is estimated to have a molecular mass of 28 kDa. However, two additional bands of trypanopain activity (87 kDa and 105 kDa) are observed if serum is added to the trypanopain before electrophoresis. Formation of the 87 and 105 kDa bands is frequently accompanied by a reduction in the intensity of the 28 kDa activity which suggests that the extra bands are complexes of the 28 kDa trypanopain-Tb and a molecule from rat serum called rat trypanopain moledulator (rTM). The rTM-induced activation of cysteine proteases is not restricted to T. brucei as it is also observed with proteases from other protozoan parasites such as bloodstream forms of Trypanosoma congolense and the mammalian-infective in vitro-derived promastigote forms of Leishmania donovani and Leishmania major. The physical properties of rTM resemble those of the kininogen family of cysteine protease inhibitors. rTM is an acidic (pI 4.7) heat-stable 68 kDa glycoprotein with 15 kDa protease-susceptible domains. This resemblance between rTM and kininogens was confirmed by the positive, albeit weak, immunoreactivity between anti-(human low-molecular-mass kininogen) antibody and rTM as well as anti-rTM antibody and human low-molecular-mass kininogen. Furthermore, commercial preparations of human-low-molecular-mass kininogen and chicken egg white cystatin mimicked rTM by forming extra bands of proteolytic activity in the presence of trypanopain-Tb. In some instances, low-molecular-mass kininogen was also observed to increase the rate of hydrolysis of 7-(benzyloxycarbonyl-phenylalanyl-arginyl-amido)-4- methylcoumarin by live T. brucei. Although this effect was rather erratic, in no instance was significant inhibition observed when this putative cysteine protease inhibitor was used under these conditions. The activation of parasite cysteine proteases by commonly accepted cysteine protease inhibitors is unexpected and may have important pathological repercussions.

Laparoscopic Myomectomy: Sonographic Follow-Up and Second-Look Laparoscopy for the Evaluation of a New Technique

Between 1988 and 1993, 100 women underwent laparoscopic myomectomy in the Department of Obstetrics and Gynecology of the University of Ulm. Indications varied, although most myomectomies were done for fertility enhancement or preservation. Closure of the incision, especially with an open uterine cavity, was done in two or three layers. Several technical limitations specific to laparoscopic surgery impair complete and satisfactory closure of the myomectomy incision. In this study we evaluate the new technique by sonographic control and second-look laparoscopy. In 22 cases second-look laparoscopy was undertaken to assess post-operative adhesion formation and to effect adhesiolysis. The rate of adhesion formation was 28%, depending on site, size, and number of myomas. Adhesion formation was significantly higher (p<0:005) in myomas located on the posterior wall. The density of adhesions did not vary significantly. In 22 cases sonography was done preoperatively, one day after the operation and 6 weeks postoperatively to compare wound healing, depending on myoma site and size. In 74% of cases an intramural hematoma of varying size was observed. By the third control, 6 weeks later, an irregular hypodense area was seen in only 8%. This study demonstrates that laparoscopic myomectomy entails the risks of postoperative adhesion formation and impaired wound healing, including intramural hematoma. So far no data are available showing a correlation between these risks and post-operative infertility or higher incidence of uterine rupture.