Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses.

OBJECTIVES: To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses. METHODS: Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed. RESULTS: In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%. CONCLUSIONS: CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (15): clinical and ultrasound characteristics of uterine sarcoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of uterine sarcomas. METHODS: This was a retrospective multicenter study. From the databases of 13 ultrasound centers, we identified patients with a histological diagnosis of uterine sarcoma with available ultrasound reports and ultrasound images who had undergone preoperative ultrasound examination between 1996 and 2016. As the first step, each author collected information from the original ultrasound reports from his/her own center on predefined ultrasound features of the tumors and by reviewing the ultrasound images to identify information on variables not described in the original report. As the second step, 16 ultrasound examiners reviewed the images electronically in a consensus meeting and described them using predetermined terminology. RESULTS: We identified 116 patients with leiomyosarcoma, 48 with endometrial stromal sarcoma and 31 with undifferentiated endometrial sarcoma. Median age of the patients was 56 years (range, 26-86 years). Most patients were symptomatic at diagnosis (164/183 (89.6%)), the most frequent presenting symptom being abnormal vaginal bleeding (91/183 (49.7%)). Patients with endometrial stromal sarcoma were younger than those with leiomyosarcoma and undifferentiated endometrial sarcoma (median age, 46 years vs 57 and 60 years, respectively). According to the assessment by the original ultrasound examiners, the median diameter of the largest tumor was 91 mm (range, 7-321 mm). Visible normal myometrium was reported in 149/195 (76.4%) cases, and 80.0% (156/195) of lesions were solitary. Most sarcomas (155/195 (79.5%)) were solid masses (> 80% solid tissue), and most manifested inhomogeneous echogenicity of the solid tissue (151/195 (77.4%)); one sarcoma was multilocular without solid components. Cystic areas were described in 87/195 (44.6%) tumors and most cyst cavities had irregular walls (67/87 (77.0%)). Internal shadowing was observed in 42/192 (21.9%) sarcomas and fan-shaped shadowing in 4/192 (2.1%). Moderate or rich vascularization was found on color-Doppler examination in 127/187 (67.9%) cases. In 153/195 (78.5%) sarcomas, the original ultrasound examiner suspected malignancy. Though there were some differences, the results of the first and second steps of the analysis were broadly similar. CONCLUSIONS: Uterine sarcomas typically appear as solid masses with inhomogeneous echogenicity, sometimes with irregular cystic areas but only very occasionally with fan-shaped shadowing. Most are moderately or very well vascularized. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (14): clinical and ultrasound characteristics of ovarian clear cell carcinoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian pure clear cell carcinoma. METHODS: This was a retrospective study involving data from 11 ultrasound centers. From the International Ovarian Tumor Analysis (IOTA) database, 105 patients who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016 were identified with a histologically confirmed pure clear cell carcinoma of the ovary. An additional 47 patients diagnosed with pure clear cell carcinoma between 1999 and 2016 and with available complete preoperative ultrasound reports were identified retrospectively from the databases of the departments of gynecological oncology in the participating centers. The ultrasound images of all tumors were described using IOTA terminology. Clinical and ultrasound characteristics were analyzed for the whole group, and separately, for patients with and those without histologically confirmed endometriosis, and for patients with evidence of tumor developing from endometriosis. RESULTS: Median age of the 152 patients was 53.5 (range, 28-92) years and 92/152 (60.5%) tumors were FIGO Stage I. Most tumors (128/152, 84.2%) were unilateral. On ultrasound examination, all tumors contained solid components and 36/152 (23.7%) were completely solid masses. The median largest diameter of the lesion was 117 (range, 25-310) mm. Papillary projections were present in 58/152 (38.2%) masses and, in most of these (51/56, 91.1%), vascularized papillary projections were seen. Information regarding the presence, site and type of pelvic endometriosis at histology was available for 130/152 patients. Endometriosis was noted in 54 (41.5%) of these. In 24/130 (18.6%) patients, the tumor was judged to have developed from endometriosis. Patients with, compared to those without, evidence of tumor developing from endometriosis were younger (median 47.5 vs 55.0 years, respectively), and ground-glass echogenicity of cyst fluid was more common in pure clear cell cancers developing from endometriosis (10/20 vs 13/79 (50.0% vs 16.5%), respectively). CONCLUSIONS: Ovarian pure clear cell carcinoma is usually diagnosed at an early stage and typically appears as a large unilateral mass with solid components. Patients with clear cell carcinoma developing from endometriosis are younger than other patients with clear cell carcinoma, and clear cell cancers developing from endometriosis more often manifest ground-glass echogenicity of cyst fluid. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (13): clinical and ultrasound characteristics of endometrioid ovarian cancer.

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian pure endometrioid carcinomas. METHODS: This was a retrospective multicenter study of patients with a histological diagnosis of pure endometrioid carcinoma. We identified 161 patients from the International Ovarian Tumor Analysis (IOTA) database who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016, and another 78 patients from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. In addition, one author reviewed all available ultrasound images and described them using pattern recognition. RESULTS: Median age of the 239 patients was 55 years (range, 19-88 years). On ultrasound examination, two (0.8%) endometrioid carcinomas were described as unilocular cysts, three (1.3%) as multilocular cysts, 37 (15.5%) as unilocular-solid cysts, 115 (48.1%) as multilocular-solid cysts and 82 (34.3%) as solid masses. Median largest tumor diameter was 102.5 mm (range, 20-300 mm) and median largest diameter of the largest solid component was 63 mm (range, 9-300 mm). Papillary projections were present in 70 (29.3%) masses. Most cancers (188 (78.7%)) were unilateral. In 49 (20.5%) cases, the cancer was judged by the pathologist to develop from endometriosis. These cancers, compared with those without evidence of tumor developing from endometriosis, more often manifested papillary projections on ultrasound (46.9% (23/49) vs 24.7% (47/190)), were less often bilateral (8.2% (4/49) vs 24.7% (47/190)) and less often associated with ascites (6.1% (3/49) vs 28.4% (54/190)) and fluid in the pouch of Douglas (24.5% (12/49) vs 48.9% (93/190)). Retrospective analysis of available ultrasound images using pattern recognition revealed that many tumors without evidence of tumor developing from endometriosis (36.3% (41/113)) had a large central solid component entrapped within locules, giving the tumor a cockade-like appearance. CONCLUSIONS: Endometrioid cancers are usually large, unilateral, multilocular-solid or solid tumors. The ultrasound characteristics of endometrioid carcinomas developing from endometriosis differ from those without evidence of tumor developing from endometriosis, the former being more often unilateral cysts with papillary projections and no ascites. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Clinical and ultrasound characteristics of surgically removed adnexal lesions with largest diameter ≤ 2.5 cm: a pictorial essay.

OBJECTIVES: To describe the ultrasound characteristics, indications for surgery and histological diagnoses of surgically removed adnexal masses with a largest diameter of ≤ 2.5 cm (very small tumors), to estimate the sensitivity and specificity of diagnosis of malignancy by subjective assessment of ultrasound images of very small tumors and to present a collection of ultrasound images of surgically removed very small tumors, with emphasis on those causing diagnostic difficulty. METHODS: Information on surgically removed adnexal tumors with a largest diameter of ≤ 2.5 cm was retrieved from the ultrasound databases of seven participating centers. The ultrasound images were described using the International Ovarian Tumor Analysis terminology. The original diagnosis, based on subjective assessment of the ultrasound images by the ultrasound examiner, was used to calculate the sensitivity and specificity of diagnosis of malignancy. RESULTS: Of the 129 identified adnexal masses with largest diameter ≤ 2.5 cm, 104 (81%) were benign, 15 (12%) borderline malignant and 10 (8%) invasive tumors. The main indication for performing surgery was suspicion of malignancy in 22% (23/104) of the benign tumors and in all 25 malignant tumors. None of the malignant tumors was a unilocular cyst (vs 50% of the benign tumors), all malignancies contained solid components (vs 43% of the benign tumors), 80% of the borderline tumors had papillary projections (vs 21% of the benign tumors and 20% of the invasive malignancies) and all invasive tumors and 80% of the borderline tumors were vascularized on color/power Doppler examination (vs 44% of the benign tumors). The ovarian crescent sign was present in 85% of the benign tumors, 80% of the borderline tumors and 50% of the invasive malignancies. The sensitivity of diagnosis of malignancy by subjective assessment of ultrasound images was 100% (25/25) and the specificity was 86% (89/104). Excluding unilocular cysts, the specificity was 71% (37/52). Analysis of images illustrated the difficulty in distinguishing benign from borderline very small cysts with papillations and benign from malignant very small well vascularized (color score 3 or 4) solid adnexal tumors. CONCLUSIONS: Very small malignant tumors manifest generally accepted ultrasound signs of malignancy. Small unilocular cysts are usually benign, while small non-unilocular masses, particularly ones with solid components, incur a risk of malignancy and pose a clinical dilemma. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (5): clinical and ultrasound characteristics in fibroma and fibrothecoma of the ovary.

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%, 10/44) 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 > or =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.

Sonographic features of primary ovarian fibrosarcoma: a report of two cases.

Two cases of primary cellular fibroblastic tumor of the ovary are described, which presented a challenging clinical and histopathological differential diagnosis of primary ovarian fibrosarcoma and mitotically active cellular fibroma. On sonographic evaluation they both appeared as solid lesions with irregular margins, and on histological analysis both showed a count of 5-7 mitotic figures per 10 high-power fields. Histopathological examination of the first case was characterized by the presence of hemorrhage, necrosis and severe nuclear atypia, with a metastatic peritoneal lesion, and the eventual diagnosis was primary ovarian fibrosarcoma. The second case, however, was diagnosed as a 'mitotically active cellular fibroma' owing to the lack of substantial severe cellular atypia, hemorrhage or necrosis. We speculate that ovarian fibrosarcoma at the preoperative examination might be considered in the differential diagnosis whenever a unilateral, heterogeneous, largely round solid ovarian lesion is detected.

The 'lead vessel': a vascular ultrasound feature of metastasis in the ovaries.

OBJECTIVE: To investigate, in a series of metastatic and primary invasive ovarian lesions examined by color Doppler, the prevalence of a main peripheral vessel penetrating into the central part of the ovarian mass with a tree-shaped morphology, defined as the 'lead vessel'. METHODS: This was a retrospective study of 31 patients with histopathologically confirmed metastatic involvement of the ovary and 106 patients with confirmed primary invasive ovarian carcinoma, who had undergone standardized ultrasound examination, with established definitions of ultrasound characteristics. We retrieved sonographic images and videoclips, focusing on the detection of the lead vessel. RESULTS: The presence of the lead vessel was detected in 11/31 (35.4%) metastatic ovarian tumors, and in only two (0.01%) cases of primary ovarian carcinoma (P = 0.0001). At color Doppler analysis, metastatic ovarian lesions were characterized by significantly lower pulsatility index (P = 0.0001) and resistance index (P = 0.0001) values, and significantly higher peak systolic velocity (P = 0.0002) and time-averaged maximum velocity (P = 0.04) values, when compared with primary ovarian carcinomas. The lead vessel was detected in 11/21 (52%) solid metastatic lesions and in no cases of multilocular or multilocular-solid lesions (P = 0.008). CONCLUSION: The lead vessel is a novel sonographic feature of vascular morphology in solid ovarian metastases. The more frequent observation of this feature in metastatic ovarian tumors compared with primary invasive ovarian carcinomas warrants further investigation in order to explore its potential role in the diagnosis of metastatic ovarian masses.

VLA-2 and VLA-5 cell adhesion molecules expression in CD34+ cells from umbilical cord blood and from bone marrow.

BACKGROUND/AIMS: Umbilical cord blood contains a large number of early hematopoietic cells with high proliferating capacity, that has been used as an alternative to bone marrow transplantation. The aim of this study is to investigate the number of two cell adhesion molecules in cord blood and in bone marrow. METHODS: We investigated two integrins, named VLA-2 and VLA-5 (Very Late Appearing Antigen), expressed in the surface of CD34+ cells. The CD34+ cells, isolated with MACS CD34+ isolation kit, were labelled with the appropriate monoclonal antibodies. RESULTS: Cell adhesion molecules showed highly expressed in both cord blood and bone marrow CD34+ cells. CONCLUSION: There are no significant differences between the two sources of CD34+ populations.

Umbilical cord blood collection in Cesarean section: a comparison before and after placental delivery.

Fetal stem cells transplants depend on nucleated cells from fetal blood. This study was a prospective randomized trials to compare the collection of fetal blood by gravity into a bag containing anticoagulant, before and after delivery of the placenta. The obstetric and the newborn characteristics in the two group were not significantly different. The mean volume of fetal blood collected while the placental was still in utero was 74.93+/-7.1 ml as against 35.78+/-3.6 ml for collection of fetal blood after delivery of the placenta.

Early clamping of umbilical cord blood and foetal CD34 enrichment.

We describe the relation between clamping time and blood volume collected, and two enrichment systems of CD34+ stem cells from umbilical cord blood, in order to determine the criteria for an excellent recovery with high proliferative ability and bone marrow reconstitution. After an obstetrician-based cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies, negative selections, using the Stem Sep method, or with a positive cells selection owing to their surface CD34 antigens, using the Mini Macs system. An excellent recovery of haematopoietic progenitors--burst forming unit erythroid; colony-forming unit granulocyte and macrophage; and colony-forming unit granulocyte, erythroid, monocyte, and macrophage--inversely related to an increase in clamping time, was achieved using the Mini Macs system (54% of colonies with a 90% purity), while the recovery of haematopoietic progenitors was 35% (with a 80% purity) using the Stem Sep method. By clamping umbilical cord blood at an early stage, we obtained a greater number of CD34+ cells, and their clonogenic activity increased with enrichment. This is particularly useful considering that the number of CD34+ stem cells contained in a unit of placental blood is sufficient for transplanting into a child but not for an adult engraftment. Thus, using these methods, we obtain a larger number of CD34+ stem cells. This increases the possibility of reducing graft versus host disease in adult patients and produces survival rates similar to the ones we observed in transplantation of bone marrow from unrelated donors.

Placing the newborn on the maternal abdomen increases the volume of umbilical cord blood collected.

Haematopoietic stem cell transplantation is an important therapy for certain haematological and malignant disorders. Umbilical cord blood contains a high proportion of potentially transplantable haematopoietic progenitor cells. However, the use of cord blood stem cell transplantation is limited by the low number of stem cells obtainable from a single cord blood donor. The aim of our study was to investigate the possibility that procedures during delivery might influence the number of umbilical cord blood haematopoietic progenitor cells available for transplantation. We assessed the effects of upper and lower positions of the newborn infant on the yield of cord blood stem cells in 51 vaginal deliveries. Neonates in the upper position group were placed by the midwife on the maternal abdomen immediately after birth, while those in the lower position group were placed on the delivery table, below the maternal introitus. The total volume of cord blood and the total number of CD34+ cells collected from babies in the upper position group were significantly higher than those from babies in the lower position group. There were no significant differences in cord blood haemoglobin levels and white blood cell counts between the two groups, nor were there any adverse effects in the newborn infants. The simple manoeuvre of placing the newborn on the maternal abdomen after delivery may thus increase the yield of transplantable haematopoietic progenitor cells in cord blood.

Reasons to Eliminate Umbilical Cord Blood Units before Cryopreservation.

Hematopoietic stem cells collected from umbilical cord blood (UCB) are widely considered a potential alternative to bone marrow. Research on UCB has now developed with the establishment of cord blood banks throughout the world. The aim of our study is to improve the efficiency of our bank because of the high cost and the administrative effort involved in its organization, finding a correlation between the terms of UCB units discarding, such as the low volume and for the low cell counts, and the obstetrics causes. This process has been made to cut the cost of the research and to improve the final result of each bank. We obtained, in 15 months, 683 cord blood units by blood withdrawal from the placenta. The units were cryopreserved within 24 h of collection, in a volume of at least 60 ml with a nucleated cells total of more than 800 per 10(6). Specific analyses of the unit blood to exclude bacterial contamination were undertaken. Of the 683 bags collected, 340 (49.75%) were discarded, and 343 were banked. The main reasons for rejecting the UCB units were: low volume; low cell counts; clinical history; bacterial contamination; freezing problems; unit misidentification; and no informed consent. We suggest that regular monitoring of the reasons for the rejection of the UCB units could give a significant effort to the bank organization, and identifying those units that are suitable before the cryopreservation could save precious resources.