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1.
  • Timmerman, D., et al. (author)
  • Simple ultrasound-based rules for the diagnosis of ovarian cancer
  • 2008
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 31:6, s. 681-690
  • Journal article (peer-reviewed)abstract
    • Objective To derive simple and clinically useful ultrasound-based rules for discriminating between benign and malignant adnexal masses. Methods In a multicenter study involving nine centers consecutive patients with persistent adnexal tumors underwent transvaginal gray-scale and Doppler ultrasound examination using a standardized examination technique and standardized terms and definitions. Information on 42 gray-scale ultrasound variables and six Doppler variables was collected and entered into a research protocol. When developing simple ultrasound-based rules to predict malignancy (M-rules) we chose the ultrasound variable or the combination of ultrasound variables that bad the highest positive predictive value (PPV) with regard to malignancy; when developing simple rules to predict a benign tumor (B-rules) we chose the ultrasound variable or the combination of ultrasound variables that had the lowest PPV with regard to malignancy. We selected ten rules that were in agreement with our clinical experience and were applicable to at least 30 tumors and then tested them prospectively on 507 tumors examined in three of the nine centers. Results 1066 patients with 1233 adnexal tumors were included. There were 903 benign tumors (73%) and 330 malignant tumors (27%). In 167 patients the tumors were bilateral. We selected five simple rules to predict malignancy (M-rules): (1) irregular solid tumor; (2) ascites; (3) at least four papillary structures; (4) irregular multilocular-solid tumor with a largest diameter of at least 100 mm; and (5) very high color content on color Doppler examination. We chose five simple rules to suggest a benign tumor (B-rules): (1) unilocular cyst; (2) presence of solid components where the largest solid component is < 7 mm in largest diameter; (3) acoustic shadows; (4) smooth multilocular tumor less than 100 mm in largest diameter; and (S) no detectable blood flow on Doppler examination. These ten rules were applicable to 76% of all tumors, where they resulted in a sensitivity of 93%, specificity of 90%, positive likelihood ratio (LR+) of 9.45 and negative likelihood ratio (LR-) of 0.08. When prospectively tested the rules were applicable in 76% (386/507) of the tumors, where they had a sensitivity of 95% (106/112), a specificity of 91% (249/274), LR+ of 10.37, and LR- of 0.06. Conclusion Most adnexal tumors in an ordinary tumor population can be correctly classified as benign or malignant using simple ultrasound-based rules. For tumors that cannot be classified using simple rules, ultrasound examination by an expert examiner might be useful. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Paladini, D., et al. (author)
  • Imaging in gynecological disease (5): clinical and ultrasound characteristics in fibroma and fibrothecoma of the ovary
  • 2009
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 34:2, s. 188-195
  • Journal article (peer-reviewed)abstract
    • Objectives To describe the clinical and ultrasound features of fibroma and fibrothecoma of the ovary. Methods Sixty-eight women with a histological diagnosis of fibroma or fibrothecoma of the ovary who had undergone a preoperative ultrasound examination between 1999 and 2007 were identified from the databases of four ultrasound centers. The tumors were characterized on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In 51 patients, ultrasound information had been collected prospectively; in the remaining 17 cases it was retrieved retrospectively from ultrasound reports and images. In 44 cases, electronic ultrasound images of good quality were available. These were reviewed by two observers, who described them using pattern recognition. Results Of the 68 patients identified, 53 had fibroma and 15 had fibrothecoma. The mean patient age was 54 (range, 17-80) years. Sixty-three percent (41/65) were postmenopausal and 60% (39/65) had no symptoms. Most (75%; 51/68) fibromas/fibrothecomas were solid tumors and most (75%; 51/68) manifested minimal or moderate blood flow on color Doppler examination. Using pattern recognition, all solid fibromas/fibrothecomas were described as round, oval or slightly lobulated tumors. Most (66%; 29/44) were solid tumors, with regular or slightly irregular internal echogenicity with stripy shadows, and some contained cystic spaces. Others (23%, 10144) were solid tumors with regular or slightly irregular internal echogenicity without stripy shadows and with or without cystic spaces. Two were solid tumors that were so dense it was difficult to assess their internal echogenicity, two were multilocular solid tumors with large cystic spaces and one was described as being mainly cystic. Half of the women with fibroma/fibrothecoma had fluid in the pouch of Douglas and 16% (11/68) had ascites; CA 125 titers >= 35 U/mL were found in 34% (17/50) of the cases in which CA,125 results were available. Conclusions Most fibromas and fibrothecomas are round, oval or lobulated solid tumors that cast stripy shadows and are associated with fluid in the pouch of Douglas, and most manifest minimal to moderate vascularization. A fibroma/fibrothecoma with atypical ultrasound appearance may be mistaken for a malignancy, in particular if associated with fluid in the pouch of Douglas or ascites, high color content and raised CA 125 levels. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Savelli, L., et al. (author)
  • Imaging of gynecological disease (4): clinical and ultrasound characteristics of struma ovarii
  • 2008
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 32:2, s. 210-219
  • Journal article (peer-reviewed)abstract
    • Objectives To describe the clinical history and ultrasound findings in women with struma ovarii. Methods Women with a histological diagnosis of struma ovarii who bad undergone preoperative ultrasound examination were identified front the databases of five ultrasound centers. The tumors were characterized on the basis of ultrasound images,, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, four authors reviewed all ultrasound images and described them using pattern recognition. Results Of 31 patients identified, 16 bad pure struma ovarii (one malignant), whereas in 15 patients the struma ovarii were 'impure', constituting the major part of a dermoid cyst (all benign, bilateral in one case). Median age was 40 (range, 18-80) years and 22 (71%) patients were of fertile age. Thirteen patients (42%) were asymptomatic, nine (29%) presented with pain, six (19%) with bloating, two (6%) with irregular bleeding and one (3%) with thyreotoxicosis. Most pure struma ovarii (11/16 cases, 69%) contained solid components, but cystic components were always present. The color content at Doppler examination varied front none to abundant. Four patients had ascites. Using pattern recognition the most specific feature of pure struma ovarii was the 'struma pearl', i.e. a smooth roundish solid area, similar, but not identical, to the 'round white ball' seen in dermoid cysts. 'Struma pearls' were present in six cases of Pure struma ovarii. Most (10116, 63%) cases of impure struma ovarii manifested ultrasound features compatible with a dermoid cyst, but six manifested ultrasound features similar to those of pure struma ovarii, 'struma pearls' being seen in three of these. Conclusions The sonographic features of struma ovarii vary. Struma ovarii may be suspected when a 'struma pearl' is seen. Whether 'struma pearls' are indeed a specific ultrasonographic feature of struma ovarii needs to be determined in a prospective study. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Sokalska, A., et al. (author)
  • Diagnostic accuracy of transvaginal ultrasound examination for assigning a specific diagnosis to adnexal masses
  • 2009
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 34:4, s. 462-470
  • Journal article (peer-reviewed)abstract
    • Objectives To determine the sensitivity and specificity of subjective evaluation of gray-scale and Doppler ultrasound findings (here called pattern recognition) when used by experienced ultrasound examiners with regard to making a specific diagnosis of adnexal masses. Methods Within the framework of a European multi-center study, the International Ovarian Tumor Analysis study, comprising nine ultrasound centers, women with at least one adnexal mass were examined with gray-scale and color Doppler ultrasonography by experienced ultrasound examiners. A standardized examination technique, and standardized terms and definitions were used. Using pattern recognition the examiners classified each mass as benign or malignant and suggested a specific diagnosis (e.g. dermoid cyst or endometrioma). The reference standard was the histology of the surgically removed adnexal tumors. Results A total of 1066 women were included, of whom 800 bad a benign mass and 266 a malignant mass. A specific diagnosis based on ultrasound findings was suggested in 899 (84%) tumors. The specificity was high for all diagnoses (range, 94-100%). The sensitivity was highest for benign teratoma/dermoid cysts (86%, 100/116), hydrosalpinges (86%, 18/21), peritoneal pseudocysts (80%, 4/5) and endometriomas (77%, 1531199), and lowest for functional cysts (17%, 4124), paraovarian/parasalpingeal cysts (14%, 3121), benign rare tumors (11%, 119), adenofibromas (8%, 3/39), simple cysts (6%, 1/18) and struma ovarii (0%, 0/5). The positive and negative likelihood ratios of pattern recognition with regard to dermoid cysts, hydrosalpinges and endometriomas were 68.2 and 0.14, 38.9 and 0.15, and 33.3 and 0.24, respectively. Dermoid cysts, hydrosalpinges, functional cysts, paraovarian cysts, peritoneal pseudocysts, fibromas/fibrothecomas and simple cysts were never misdiagnosed as malignancies by the ultrasound examiner, whereas more than 10% of inflammatory processes, adenofibromas and rare benign tumors including struma ovarii were misdiagnosed as malignancies. Conclusions Using subjective evaluation of gray-scale and Doppler ultrasound findings it is possible to make an almost conclusive diagnosis of a dermoid cyst, endometrioma and hydrosalpinx. Many other adnexal pathologies can be recognized but not confidently confirmed or excluded. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Testa, A. C., et al. (author)
  • Intravenous contrast ultrasound examination using contrast-tuned imaging (CnTI (TM)) and the contrast medium SonoVue (R) for discrimination between benign and malignant adnexal masses with solid components
  • 2009
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 34:6, s. 699-710
  • Journal article (peer-reviewed)abstract
    • Objective To determine whether intravenous contrast ultrasound examination is superior to gray-scale or power Doppler ultrasound for discrimination between benign and malignant adnexal masses with complex ultrasound morphology. Methods In an international multicenter study, 134 patients with an ovarian mass with solid components or a multilocular cyst with more than 10 cyst locules, underwent a standardized transvaginal ultrasound examination followed by contrast examination using the contrast-tuned imaging technique and intravenous injection of the contrast medium SonoVue (R). Time intensity curves were constructed, and peak intensity, area under the intensity curve, time to peak, sharpness and half wash-out time were calculated. The sensitivity and specificity with regard to malignancy were calculated and receiver-operating characteristics (ROC) curves were drawn for gray-scale, power Doppler and contrast variables and for pattern recognition (subjective assignment of a certainly benign, probably benign, uncertain or malignant diagnosis, using gray-scale and power Doppler ultrasound findings). The gold standard was the histological diagnosis of the surgically removed tumors. Results After exclusions (surgical removal of the mass > 3 months after the ultrasound examination, technical problems), 72 adnexal masses with solid components were used in our statistical analyses. The values for peak contrast signal intensity and area under the contrast signal intensity curve in malignant tumors were significantly higher than those in borderline tumors and benign tumors, while those for the benign and borderline tumors were similar. The area under the ROC curve of the best contrast variable with regard to diagnosing borderline or invasive malignancy (0.84) was larger than that of the best gray-scale (0.75) and power Doppler ultrasound variable (0.79) but smaller than that of pattern recognition (0.93). Conclusion Findings on ultrasound contrast examination differed between benign and malignant tumors but there was a substantial overlap in contrast findings between benign and borderline tumors. It appears that ultrasound contrast examination is not superior to conventional ultrasound techniques, which also have difficulty in distinguishing between benign and borderline tumors, but can easily differentiate invasive malignancies from other tumors. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Valentin, Lil, et al. (author)
  • Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses.
  • 2009
  • In: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 34, s. 345-354
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To determine whether CA 125 measurement is superior to ultrasound imaging performed by an experienced examiner for discriminating between benign and malignant adnexal lesions, and to determine whether adding CA 125 to ultrasound examination improves diagnostic performance. METHODS: This is a prospective multicenter study (International Ovarian Tumor Analysis (IOTA) study) conducted in nine European ultrasound centers in university hospitals. Of 1149 patients with an adnexal mass examined in the IOTA study, 83 were excluded. Of the remaining 1066 patients, 809 had CA 125 results available and were included. The patients underwent preoperative serum CA 125 measurements and transvaginal ultrasound examination by an experienced ultrasound examiner blinded to CA 125 values. The examiner classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant. The outcome measure was the sensitivity and specificity with regard to malignancy of CA 125, ultrasound imaging and their combined use, the 'gold standard' being the histological diagnosis of the adnexal mass removed surgically within 120 days after the ultrasound examination. RESULTS: There were 242 (30%) malignancies. For 534 tumors judged to be certainly benign or certainly malignant by the ultrasound examiner the sensitivity and specificity of ultrasound examination and CA 125 (>/=35 U/mL indicating malignancy) were 97% vs. 86% (95% CI of difference, 4.7-17.2) and 99% vs. 79% (95% CI of difference, 15.7-24.2); for 209 tumors judged probably benign or probably malignant, sensitivity and specificity were 81% vs. 57% (95% CI of difference, 12.3-36.0) and 91% vs. 74% (95% CI of difference, 8.5-25.7); for 66 tumors that were difficult to classify, sensitivity and specificity were 57% vs. 39% (95% CI of difference, -9.7 to 41.1) and 74% vs. 67% (95% CI of difference, -14.6 to 27.7). Diagnostic performance deteriorated when CA 125 was used as a second-stage test after ultrasound examination. CONCLUSIONS: Specialist ultrasound examination is superior to CA 125 for preoperative discrimination between benign and malignant adnexal masses, irrespective of the diagnostic confidence of the ultrasound examiner; adding CA 125 to ultrasound does not improve diagnostic performance. Our results indicate that greater investment in education and training in gynecological ultrasound imaging would be of value. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Van Holsbeke, C, et al. (author)
  • Imaging of gynecological disease (3): clinical and ultrasound characteristics of granulosa cell tumors of the ovary
  • 2008
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 31:4, s. 450-456
  • Journal article (peer-reviewed)abstract
    • Objectives To describe the clinical and ultrasound characteristics of granulosa cell tumors (GCTs) of the ovary, and to define the ultrasound appearance of GCTs based on pattern recognition. Methods Databases of four gynecological ultrasound centers were searched to identify patients with histologically proven GCTs who had undergone a standard preoperative ultrasound examination. Results A total of 23 women with confirmed GCT were identified. Twelve (52%) women were postmenopausal, nine (39%) were of fertile age and two (9%) were prepubertal. Clinical symptoms were abdominal distension (7/23, 30%), pain (5/23, 22%) and irregular vaginal bleeding (6/23, 26%). Seven patients (30%) were asymptomatic. Endometrial pathology was found in 54% (7/13) of the patients from whom endometrial biopsies were taken. On ultrasound scan 12/23 (52%) masses were multilocular-solid, 9/23 (39%) were purely solid, one mass (4%) was unilocular-solid and one mass was multilocular (4%). Multilocular and multilocular-solid cysts typically contained large numbers of small locules (> 10). The echogenicity of the cyst content was most often mixed (6/16, 38%) or low level (7/16, 44%). Papillary projections were found in only four women (17%). The GCTs were large tumors with a median largest diameter of 102 (range, 37-242) mm and manifested moderate or high color content at color Doppler examination (color score 3 in 13/23 tumors (57%); color score 4 in 8/23 tumors (35%)). Conclusions At ultrasound examination, most GCTs are large multilocular-solid masses with a large number of locules, or solid tumors with heterogeneous echogenicity of the solid tissue. Hemorrhagic components are common and increased vascularity is demonstrated at color/power Doppler ultrasound examination. The hyperestrogenic state that is created by the tumor often causes endometrial pathology with bleeding problems as a typical associated symptom.
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  • Van Holsbeke, C., et al. (author)
  • Real-time ultrasound vs. evaluation of static images in the preoperative assessment of adnexal masses
  • 2008
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 32:6, s. 828-831
  • Journal article (peer-reviewed)abstract
    • Objective To determine if the prediction of the Malignancy of all adnexal mass using pattern recognition, i.e. subjective evaluation of gray-scale and Doppler ultrasound findings, is as accurate when based on static images as it is when based on a real-time ultrasound examination. Methods The static images of 166 non-consecutive patients with 'difficult' adnexal masses, who all underwent surgery and for whom a histopathological diagnosis was available, were evaluated by three experts in gynecological ultrasound (image experts'). All ultrasound examinations bad been performed and the static images saved by a fourth expert sonologist ('real-time' sonologist). All four sonologists classified the adnexal masses as benign or malignant based on their subjective impression and stated with what degree of confidence their diagnosis was made. The diagnostic performance of the real-time sonologist was compared with that of each of The three image experts and with that of the 'consensus opinion' of the image experts (i.e. the diagnosis suggested by at least two of the latter). Results The real-time sonologist correctly predicted the diagnosis with an accuracy of 89% (148/166) vs. 85% (141/166) for the consensus opinion of static images (P = 0.0707). Equivalent values for sensitivity and specificity were 80% (56/170) vs. 83%, (58/70) (P = 0.4142) and 96%) (92/96) us. 86%, (83/96) (P = 0.0027), respectively. Conclusions The preoperative diagnosis of all adnexal mass made on the basis of a real-time ultrasound examination is more precise than a diagnosis made on the basis of saved static ultrasound images. Evaluation of static images is associated with lower diagnostic specificity. Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Van Holsbeke, C., et al. (author)
  • Ultrasound methods to distinguish between malignant and benign adnexal masses in the hands of examiners with different levels of experience
  • 2009
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 34:4, s. 454-461
  • Journal article (peer-reviewed)abstract
    • Objectives To determine the effect of an ultrasound training course on the performance of pattern recognition when used by less experienced examiners and to compare the performance of pattern recognition, a logistic regression model and a scoring system to estimate the risk of malignancy between examiners with different levels of experience. Methods Using ultrasound images of selected adnexal masses, two trainees classified the masses as benign or malignant by using pattern recognition both before and after they bad attended a theoretical gynecological ultrasound course. They also classified the masses by using a logistic regression model and a scoring system, but only after they bad attended the course. The performance of these three methods when they were used by the trainees was then compared with that when they were used by experts. Results One hundred and sixty-five adnexal masses were included, of which 42% were malignant (21% invasive tumors and 21% borderline tumors). The area under the receiver- operating characteristics curve of pattern recognition when used by the trainees was similar before and after they had attended the course. Training decreased sensitivity (84% vs. 70% for Trainee 1, P = 0.004; 70% vs. 61% for Trainee2, P = 0.08) and increased specificity (77% vs. 92% for Trainee 1, P = 0.001; 89% vs. 95% for Trainee 2, P = 0.058). The performance of pattern recognition was poorer in the hands of the trainees than in the bands of the experts. The sensitivities of the logistic regression model were 70% and 54% for the trainees vs. 83% for an expert (P = 0.020 and < 0.001, respectively) and the specificities were 84% and 94% vs. 89% (P = 0.25 and 0.59, respectively). The sensitivities of the scoring system were 59% and 54% for the trainees vs. 75% for the expert (P = 0.002 and < 0.001, respectively), and the specificities were 90% and 93% vs. 85% (P = 0.103 and 0.008, respectively). Conclusion Theoretical ultrasound teaching did not seem to improve the performance of pattern recognition in the bands of trainees. A logistic regression model and a scoring system to classify adnexal masses as benign or malignant perform less well when they were used by inexperienced examiners than when used by an expert. Before using a model or a scoring system, experience and/or proper training are likely to be of paramount importance if diagnostic performance is to be optimized. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Ameye, L., et al. (author)
  • A scoring system to differentiate malignant from benign masses in specific ultrasound-based subgroups of adnexal tumors
  • 2009
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 33:1, s. 92-101
  • Journal article (peer-reviewed)abstract
    • Objective To investigate if the prediction of malignant adnexal masses can be improved by considering different ultrasound-based subgroups of tumors and constructing a scoring system for each subgroup instead of using a risk estimation model applicable to all tumors. Methods We used a multicenter database of 1573 patients with at least one persistent adnexal mass. The masses were categorized into four subgroups based on their ultrasound appearance: ( 1) unilocular cyst; ( 2) multilocular cyst; ( 3) presence of a solid component but no papillation; and ( 4) presence of papillation. For each of the four subgroups a scoring system to predict malignancy was developed in a development set consisting of 754 patients in total ( respective numbers of patients: ( 1) 228; ( 2) 143; ( 3) 183; and ( 4) 200). The subgroup scoring system was then tested in 312 patients and prospectively validated in 507 patients. The sensitivity and specificity, with regard to the prediction of malignancy, of the scoring system were compared with that of the subjective evaluation of ultrasound images by an experienced examiner ( pattern recognition) and with that of a published logistic regression (LR) model for the calculation of risk of malignancy in adnexal masses. The gold standard was the pathological classification of the mass as benign or malignant ( borderline, primary invasive, or metastatic). Results In the prospective validation set, the sensitivity of pattern recognition, the LR model and the subgroup scoring system was 90% (129/143), 95% (136/143) and 88% (126/143), respectively, and the specificity was 93% (338/364), 74% (270/364) and 90% (329/364), respectively. Conclusions In the hands of experienced ultrasound examiners, the subgroup scoring system for diagnosing malignancy has a performance that is similar to that of pattern recognition, the latter method being the best diagnostic method currently available. The scoring system is less sensitive but more specific than the LR model. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
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  • Demidow, V N, et al. (author)
  • Imaging of gynecological disease (2): clinical and ultrasound characteristics of Sertoli cell tumors, Sertoli-Leydig cell tumors and Leydig cell tumors
  • 2008
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 31:1, s. 85-91
  • Journal article (peer-reviewed)abstract
    • Objective To describe the clinical history and ultrasound findings in women with ovarian Sertoli cell, Sertoli-Leydig cell and Leydig cell tumors. Methods Women with a histological diagnosis of Sertoli cell tumor, Sertoli-Leydig cell tumor or Leydig cell tumor who bad undergone preoperative ultrasound examination were identified from the databases of each of three participating ultrasound centers. The tumors were characterized on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions published by the International Ovarian Tumor Analysis (IOTA) group. In addition, all images were reviewed and described using pattern recognition. Results Of 22 patients identified, 15 bad Sertoli-Leydig cell tumors, two bad Sertoli cell tumors and five bad Leydig cell tumors. Four patients were postmenopausal, one 48-year-old woman bad undergone hysterectomy, 16 were of fertile age and one was a 4-year-old girl. Most patients (82%, 18122) bad endocrine symptoms, the most common being bleeding disturbance (64%, 14122) and hirsutism (32%, 7/22). Twenty-two (96%) of 23 tumors (one woman bad bilateral tumors) contained a solid component; 16 (70%) were purely solid. Pattern recognition showed that the Leydig cell tumors were small solid tumors (four of five had a largest diameter of 1-3 cm) and the two Sertoli cell tumors were somewhat larger solid tumors (4 cm and 7 cm); the Sertoli-Leydig cell tumors were either small (3-4 cm) or medium-sized (6- 7 cm) solid tumors, or multilocular solid tumors of any size (3-18 cm) with purely solid areas mixed with areas of innumerable closely packed small cyst locules. Conclusions On the basis of endocrine symptoms, the woman's age and ultrasound findings, it should be possible to suggest a correct preoperative diagnosis of Sertoli cell, Sertoli-Leydig cell or Leydig cell tumors in many cases.
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  • Lutgendorff, Femke, 1981-, et al. (author)
  • Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis
  • 2008
  • In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 295:5
  • Journal article (peer-reviewed)abstract
    • Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5 μg·kg-1·h-1, for 6 h). Daily probiotics or placebo were administered intragastrically, starting 5 days prior to AP. After cerulein infusion, pancreas samples were collected for analysis including lipid peroxidation, glutathione, glutamate-cysteine-ligase activity, histological grading of pancreatic injury, and NF-κB activation. The severity of pancreatic injury correlated to oxidative damage (r = 0.9) and was ameliorated by probiotics (1.5 vs. placebo 5.5, P = 0.014). AP-induced NF-κB activation was reduced by probiotics (0.20 vs. placebo 0.53 OD 450nm/mg nuclear protein, P < 0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo 0.51 pmol malondialdehyde/mg protein, P < 0.001). Not only was AP-induced glutathione depletion prevented (8.81 vs. placebo 4.1 μmol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 μmol/mg protein, P < 0.001). Biosynthesis of glutathione (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated animals. Probiotics enhanced the biosynthesis of glutathione, which may have reduced activation of inflammation and acinar cell injury and ameliorated experimental AP, via a reduction in oxidative stress. Copyright © 2008 the American Physiological Society.
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  • Lutgendorff, Femke, et al. (author)
  • Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis.
  • 2009
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2, s. e4512-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and (51)Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4+/-33.5 vs. placebo 223.7+/-93.7 a.u.; P<0.001), (51)Cr-EDTA flux (16.7+/-10.1 vs. 32.1+/-10.0 cm/s10(-6); P<0.005), apoptosis, lipid peroxidation (0.42+/-0.13 vs. 1.62+/-0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33+/-1.47 vs. 8.82+/-1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33+/-1.47 vs. 10.70+/-1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88+/-1.21 vs. placebo 1.94+/-0.55 nmol/min/mg protein; P<0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. CONCLUSIONS: Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis.
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  • Testa, A. C., et al. (author)
  • Imaging in gynecological disease (1): ultrasound features of metastases in the ovaries differ depending on the origin of the primary tumor
  • 2007
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 505-511
  • Journal article (peer-reviewed)abstract
    • Objective To describe the gray-scale and color Doppler ultrasound findings of metastatic tumors in the ovary according to the origin of the primary tumor. Methods Information was retrieved retrospectively from 67 patients who had undergone preoperative transvaginal gray-scale and color Doppler ultrasound examination and who were found subsequently to have metastatic tumors in their ovaries. In all women the ultrasound information had been collected prospectively using a standardized examination technique and predefined definitions of ultrasound characteristics. Stored ultrasound images were used only to describe retrospectively the external surface of the metastatic tumors. Information on presenting symptoms and on whether the patient had been treated for a malignancy in the past was retrieved retrospectively from patient records. Results Most (95%) ovarian metastases were solid, multilocular-solid or multilocular. Almost all (38/41, 93%) metastases that derived from the stomach, breast, lymphoma or uterus were solid, while most (16/22, 73%) metastases deriving from the colon, rectum, appendix or biliary tract were multilocular or multilocular-solid (P < 0.0001). Metastases that derived from the colon, rectum, appendix or biliary tract were larger compared with those from the stomach, breast, lymphoma or uterus (median maximum diameter, 122 (range, 16-200) mm vs. 71 (range, 27-170) mm, P = 0.02). In addition, irregular external borders were more common (19/22 (86%) vs. 19/41 (46%), P = 0.002), as were papillary projections (6/22 (27%) vs. 2/41 (5%), P = 0.011). They also appeared to be less vascularized, with 64% (14/22) manifesting moderate-to-abundant vascularization at color Doppler examination in comparison to 88% (36/41) of the ovarian metastases from stomach, breast, lymphoma or uterus (P = 0.024). Conclusion Ovarian metastases derived from lymphoma or from tumors in the stomach, breast and uterus are solid in almost all cases, whereas those derived from the colon, rectum or biliary tract manifest more heterogeneous morphological patterns, most being multicystic with irregular borders. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.
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29.
  • Timmerman, D, et al. (author)
  • Imaging in gynecological disease
  • 2007
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 483-484
  • Journal article (other academic/artistic)
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30.
  • Timmerman, D, et al. (author)
  • Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: A multicenter study by the International Ovarian Tumor Analysis Group
  • 2005
  • In: Journal of Clinical Oncology. - 1527-7755. ; 23:34, s. 8794-8801
  • Journal article (peer-reviewed)abstract
    • Purpose To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery. Patients and Methods Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign. Results Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%. Conclusion Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.
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31.
  • Van Calster, B, et al. (author)
  • Classifying ovarian tumors using Bayesian Multi-Layer Perceptrons and Automatic Relevance Determination: A multi-center study
  • 2006
  • In: Engineering in Medicine and Biology Society, 2006. EMBS '06. 28th Annual International Conference of the IEEE. - 1557-170X. ; 1, s. 5342-5345
  • Conference paper (peer-reviewed)abstract
    • Ovarian masses are common and a good pre-surgical assessment of their nature is important for adequate treatment. Bayesian Multi-Layer Perceptrons (MLPs) using the evidence procedure were used to predict whether tumors are malignant or not. Automatic Relevance Determination (ARD) is used to select the most relevant of the 40+ available variables. Cross-validation is used to select an optimal combination of input set and number of hidden neurons. The data set consists of 1066 tumors collected at nine centers across Europe. Results indicate good performance of the models with AUC values of 0.93-0.94 on independent data. A comparison with a Bayesian perceptron model shows that the present problem is to a large extent linearly separable. The analyses further show that the number of hidden neurons specified in the ARD analyses for input selection may influence model performance.
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32.
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33.
  • Van Calster, B., et al. (author)
  • Preoperative diagnosis of ovarian tumors using Bayesian kernel-based methods
  • 2007
  • In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 496-504
  • Journal article (peer-reviewed)abstract
    • Objectives To develop flexible classifiers that predict malignancy in adnexal masses using a large database from nine centers. Methods The database consisted of 1066 patients with at least one persistent adnexal mass for which a large amount of clinical and ultrasound data were recorded. The outcome of interest was the histological classification of the adnexal mass as benign or malignant. The outcome was predicted using Bayesian least squares support vector machines in comparison with relevance vector machines. The models were developed on a training set (n = 754) and tested on a test set (n = 312). Results Twenty-five percent of the patients (n = 266) bad a malignant tumor. Variable selection resulted in a set of 12 variables for the models: age, maximal diameter of the ovary, maximal diameter of the solid component, personal history of ovarian cancer, hormonal therapy, very strong intratumoral blood flow (i.e. color score 4), ascites, presumed ovarian origin of tumor, multilocular-solid tumor, blood flow within papillary projections, irregular internal cyst wall and acoustic shadows. Test set area under the receiver-operating characteristics curve (AUC) for all models exceeded 0.940, with a sensitivity above 90% and a specificity above 80% for all models. The least squares support vector machine model with linear kernel performed very well, with an AUC of 0.946, 91% sensitivity and 84% specificity. The models performed well in the test sets of all the centers. Conclusions Bayesian kernel-based methods can accurately separate malignant from benign masses. The robustness of the models will be investigated in future studies. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.
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