Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Surgical outcomes of diaphragmatic resection during cytoreductive surgery for advanced gynecological ovarian neoplasia: A randomized single center clinical trial - DRAGON.

INTRODUCTION: Ovarian cancer (OC) represent nearly 4% of gynecologic malignancies and it is often diagnosed at advanced stage. Diaphragmatic surgery, a fundamental step of advanced stage ovarian cancer (ASOC) debulking surgery, is associated with a high post-operative complication incidence, which is supposedly reduced with thoracostomy tube placement. We assessed the role of intra-operative thoracostomy tube placement, as a prevention measure for post-operative complications, after diaphragmatic resection. METHODS: This was a single center prospective randomized trial. Ovarian cancer patients, who underwent mono-lateral diaphragmatic resection, were randomized 1:1 into two arms. Arm A included patients receiving intra-operative thoracostomy tube placement (TP); Arm B patients did not receive thoracostomy tube placement (NTP). After surgery, all patients underwent seriate chest x-ray and ultrasound to record thoracic complications. Statistical analysis included uni- and multivariable logistic regression model (proportional odds model). RESULTS: Three hundred seventy-one patients were screened and 88 patients were enrolled: 44 in arm A and B, respectively. No statistically significant differences for intra-operative (p = 0.291) and any grade of post-operative complication (p = 0.072) were detected, while 6.8% of patients in arm A and 22.7% in arm B experienced severe respiratory symptoms (p = 0.035); 18.2% of patients in arm A had a moderate/large pleural effusion versus 65.9% in arm B (p < 0.0001). At multivariable analysis, results confirmed that the NTP-group had a higher risk to receive post-operative thoracostomy tube placement due to pleural effusion than the TP-group (odds ratio [95% Confidence Interval] = 14.5 [3.7-57.4]). CONCLUSIONS: Thoracostomy intra-operative tube placement after diaphragmatic resection is effective to prevent post-operative thoracic complications. The extension of resection does not influence outcomes and the risk of post-operative thoracentesis or TP remain elevated.

Imaging in gynecological disease (20): clinical and ultrasound characteristics of adnexal torsion.

OBJECTIVES: To describe the clinical and ultrasound characteristics of adnexal torsion. METHODS: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. RESULTS: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1-88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30-349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. CONCLUSION: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Minimal residual disease at primary debulking surgery versus complete tumor resection at interval debulking surgery in advanced epithelial ovarian cancer: A survival analysis.

OBJECTIVES: To compare survival outcomes and peri-operative complications in patients with advanced ovarian cancer with 1-10 mm residual disease (RD) at primary debulking surgery (PDS) versus those achieving no gross residual disease (NGR) at interval debulking surgery (IDS). METHODS: Patients operated with the intent of complete cytoreduction for epithelial ovarian/fallopian tube/primary peritoneal cancer, FIGO stage IIIC-IV, RD 1-10 mm at PDS and NGR at IDS, between 01/2010 and 12/2016, were retrospectively included. All patients had at least 2-years of follow-up completed. RESULTS: 207 patients were included (59 PDS and 148 IDS). Patients in PDS group were younger and had a higher surgical complexity score. There was a higher rate of intra- and major early post-operative complications in the group of PDS vs IDS (16.9% vs 1.3% and 28.8% vs 2.0%, p < 0.0001 respectively). After a median follow up of 56.4 months (range 59.2-65.4), 117 (56.5%) patients died of disease in the whole population. Forty-eight (81.4%) patients had progression/recurrent disease in the PDS group and 120 (81.1%) in the IDS group. Median PFS was 16.2 months and 18.9 months for PDS and IDS group, respectively (p = 0.111). Median OS was 41.4 months and 52.4 months for PDS and IDS group, respectively (p = 0.022). CONCLUSIONS: IDS should be considered the preferred treatment in case millimetric residual disease is expected at PDS in view of the superimposable PFS and the reduced number of perioperative complications.

Ultrasound morphometric and cytologic preoperative assessment of inguinal lymph-node status in women with vulvar cancer: MorphoNode study.

OBJECTIVE: To assess the accuracy of preoperative ultrasound examination for predicting lymph-node (LN) status in patients with vulvar cancer. METHODS: This was a single-institution retrospective observational study of all women with a histological diagnosis of vulvar cancer triaged to inguinal surgery within 30 days following ultrasound evaluation between December 2010 and January 2016. For each groin examined, 15 morphological and dimensional sonographic parameters associated with suspicion for LN involvement were examined. A morphometric ultrasound pattern (MUP) was expressed for each groin, classifying the inguinal LN status into five groups (normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive) according to subjective judgment, followed by stratification as positive or negative for metastasis according to morphometric binomial assessment (MBA). In cases of positive MBA, fine-needle aspiration cytology was performed. Combining the information obtained from MUP and cytologic results, a binomial final overall assessment (FOA) was assigned for each groin. The final histology was considered as the reference standard. Comparison was performed between patients with negative and those with positive LNs on histology, and receiver-operating-characteristics curves were generated for statistically significant variables on univariate analysis, to evaluate their diagnostic ability to predict negative LN status. RESULTS: Of 144 patients included in the analysis, 87 had negative inguinal LNs and 57 had positive LNs on histology. A total of 256 groins were analyzed, of which 171 were negative and 85 showed at least one metastatic LN on histology. The following parameters showed the greatest accuracy, with the best balance between specificity and sensitivity, in predicting negative LN status: cortical (C) thickness of the dominant LN (cut-off, 2.5 mm; sensitivity, 90.0%; specificity, 77.9%); short-axis (S) length of the dominant LN (cut-off, 8.4 mm; sensitivity, 63.9%; specificity, 90.6%); C/medulla (M) thickness ratio of the dominant LN (cut-off, 1.2 mm; sensitivity, 70.4%; specificity, 91.5%), the combination of S length and C/M thickness ratio (sensitivity, 88.9%; specificity, 82.4%); and the FOA analysis (sensitivity, 85.9%; specificity, 84.2%). CONCLUSIONS: Preoperative ultrasound assessment, with or without the addition of cytology, has a high accuracy in assessing inguinal LN status in patients with vulvar cancer. In particular, the combination of two ultrasound parameters (S length and C/M thickness ratio) provided the greatest accuracy in discriminating between negative and positive LNs. Copyright © 2019 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.

Synchronous primary cancers of endometrium and ovary vs endometrial cancer with ovarian metastasis: an observational study.

OBJECTIVE: To compare the ultrasound characteristics of patients with synchronous primary cancers of the endometrium and ovary vs those of patients with endometrial cancer with ovarian metastasis. METHODS: This was a single-institution retrospective observational study of patients with a histological diagnosis of endometrial cancer and an ovarian malignant mass, who had undergone preoperative ultrasound examination at our unit. Based on the histological diagnosis, patients were classified into two groups: those with synchronous primary cancers of the endometrium and ovary (synchronous group) and patients with endometrial cancer with ovarian metastasis (metastasis group). We compared the ultrasound features of ovarian malignant masses and of endometrial cancers between the two groups. Student's t-test, Mann-Whitney U-test, χ2 test or Fisher's exact test were used for comparisons of variables between the two histological groups, as appropriate. RESULTS: We identified 131 patients, of whom 51 had synchronous primary cancers of the endometrium and ovary (synchronous group) and 80 had endometrial cancer with ovarian metastasis (metastasis group). On ultrasound examination, ovarian masses in the synchronous group were more often multilocular-solid and less often bilateral than those in the metastasis group. With respect to the ultrasound features of the endometrial lesions, the median largest diameter was 29 (range, 11-118) mm in the synchronous group in comparison with 51.5 (range, 6-150) mm in the metastasis group (P < 0.0001). Endometrial lesions in the synchronous group presented more often with no myometrial infiltration and less often with a multiple-vessel pattern on color Doppler compared with the endometrial lesions in the metastasis group. CONCLUSIONS: Synchronous primary cancers of the endometrium and ovary have significantly different sonomorphological patterns compared with endometrial cancer with ovarian metastasis. Ovarian masses in women with synchronous primary cancers of the endometrium and ovary appeared as unilateral multilocular-solid or solid masses, whereas ovarian masses in women with endometrial cancer with ovarian metastasis were mostly bilateral solid masses. The different sonomorphology of these two cancers may facilitate their preoperative identification, helping the surgeon to determine optimum management for the patient. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The INTERNATIONAL MISSION study: minimally invasive surgery in ovarian neoplasms after neoadjuvant chemotherapy.

OBJECTIVES: The aim of this retrospective multicenter study was to investigate the extent, feasibility, and outcomes of minimally invasive surgery at the time of interval debulking surgery in different gynecological cancer centers. METHODS/MATERIALS: In December 2016, 20 gynecological cancer centers were contacted by e-mail, to participate in the INTERNATIONAL MISSION study. Seven centers confirmed and five were included, with a total of 127 patients diagnosed with advanced epithelial ovarian cancer after neoadjuvant chemotherapy and minimally invasive interval surgery. Only women with a minimum follow-up time of 6 months from interval surgery or any cancer-related event before 6 months were included in the survival analysis. Baseline characteristics, chemotherapy, and operative data were evaluated. Survival analysis was evaluated using the Kaplan-Meier method. RESULTS : All patients had optimal cytoreduction at the time of interval surgery: among them, 122 (96.1%) patients had no residual tumor. Median operative time was 225 min (range 60 - 600) and median estimated blood loss was 100 mL (range 70 - 1320). Median time to discharge was 2 days (1-33) and estimated median time to start chemotherapy was 20 days (range 15 - 60). Six (4.7%) patients experienced intraoperative complications, with one patient experiencing two serious complications (bowel and bladder injury at the same time). There were six (4.7%) patients with postoperative short-term complications: among them, three patients had severe complications. The conversion rate to laparotomy was 3.9 %. Median follow-up time was 37 months (range 7 - 86): 74 of 127 patients recurred (58.3%) and 31 (24.4%) patients died from disease. Median progression-free survival was 23 months and survival at 5 years was 52 % (95% CI: 35 to 67). CONCLUSIONS: Minimally invasive surgery may be considered for the management of patients with advanced ovarian cancer who have undergone neoadjuvant chemotherapy, when surgery is limited to low-complexity standard cytoreductive procedures.

Prospective multimodal imaging assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery-the "PRICE" study 2: role of conventional and DW-MRI.

OBJECTIVES: To assess the diagnostic performance of conventional and DW-MRI parameters in the detection of residual tumor in locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and radical surgery METHODS: Between October 2010 and June 2014, 88 patients with histologically documented cervical cancer (FIGO stage IB2-IVA) were prospectively included in the study. Maximum tumor diameters (maxTD), tumor volume (TV), DWI signal intensity (SI), and ADCmean were evaluated at MRI after nCRT. Histology was the reference standard. Treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, χ2, and Fisher's exact tests. ROC curves were generated for variables to evaluate diagnostic ability to predict PR and to determine the best cutoff value to predict PR. For each diagnostic test, sensitivity, specificity, and accuracy were calculated. RESULTS: TV and maxTD were significantly smaller in the CR than in the PR group (p < 0.001; p = 0.001) and showed, respectively, sensitivity of 68.8%, specificity of 72.5%, and accuracy of 70.5% and of 47.9, 87.5, and 65.9% in predicting PR. High DWI SI was more frequent in the PR (81.8%) than in the CR group (55.3%) (p < 0.009). ADCmean was higher in the CR (1.3 × 10-3 mm2/s, range 0.8-1.6 × 10-3 mm2/s) than in the PR group (1.1 × 10-3 mm2/s; range 0.7-1.8 × 10-3 mm2/s) (p < 0.018). High DWI SI showed sensitivity, specificity, and accuracy of 81.8, 44.7, and 64.6% in predicting PR. The ADCmean measurement increased sensitivity, specificity, and accuracy to 75.0, 76.2, and 75.4%. CONCLUSIONS: Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. The ADCmean value ≤ 1.1 × 10-3 mm2/s was the best cutoff to predict PR. KEY POINTS: • Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. • The combination of T2 sequences, DW-MRI, and the quantitative measurement of ADC mean showed the best results in predicting pathological PR. • The best cutoff for predicting pathological PR was ADCmeanvalue ≤ 1.1 × 10-3 mm2/s.

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 (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.

The PRICE study: The role of conventional and diffusion-weighted magnetic resonance imaging in assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery.

OBJECTIVES: To analyse the role of DW-MRI in early prediction of pathologically-assessed residual disease in locally-advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by radical surgery. METHODS: Between October 2010-June 2014, 108 women with histologically-proven cervical cancer were screened; 88 were included in this study. Tumour volume (TV) and ADCmean were measured before (baseline-MRI) and after 2 weeks of chemoradiotherapy (early-MRI). According to histopathology, treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, Wilcoxon and χ2 tests. ROC curves were generated for statistically significant parameters on univariate analysis. RESULTS: CR and PR were documented in 40 and 48 patients. At baseline-MRI, TV did not differ between groups. At early-MRI, TV was higher in PR than in CR (p=0.001). ΔTV reduction after treatment was lower in PR than in CR (63.6% vs. 81.1%; p=0.001). At baseline-MRI and early-MRI, ADCmean did not differ between PR and CR. ROC curve showed best cut-off for predicting pathological PR was ΔTV reduction of 73% with sensitivity, specificity, accuracy, NPV, PPV of 73%, 72.5%, 72.7%, 76%, 69%. CONCLUSIONS: TV evaluated before and early after treatment could predict pathological response in LACC. ADCmean did not correlate with treatment outcome. KEY POINTS: • Early-MRI tumour volume assessment could predict pathological response to nCRT in LACC. • Best cut-off for predicting pathological PR was ΔTV reduction of 73 %. • Early-MRI ADC mean measurements did not correlate with treatment outcome.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

OBJECTIVE: Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. METHODS: Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response. RESULTS: There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%). CONCLUSIONS: Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to assess residual tumor in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

OBJECTIVE: To determine the diagnostic performance of two-dimensional (2D) ultrasound parameters, three-dimensional (3D) power Doppler and contrast-enhanced indices in detecting residual disease in locally advanced cervical cancer patients triaged to neoadjuvant treatment followed by radical surgery. METHODS: Between October 2010 and June 2014, we screened 108 women with histologically documented locally advanced cervical cancer Stage IB2-IVA, of whom 88 were included in the final analysis. 2D ultrasound parameters, 3D power Doppler and contrast-ultrasound parameters were assessed 5 weeks after the end of neoadjuvant chemoradiation therapy. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (including microscopic and/or macroscopic residual tumor at pathology examination). The two response groups were compared and receiver-operating characteristics (ROC) curves generated to determine the best cut-off value of sonographic tumor diameter to predict residual disease. Histology was considered as reference. RESULTS: Complete pathological response to chemoradiation was observed in 40 (45.5%) patients and partial response in 48 (54.5%). The presence of residual disease, as confirmed at pathology examination, was detected by 2D grayscale ultrasound with a sensitivity of 64.6% and specificity of 65%. Color Doppler examination in the cases with lesions visualized on grayscale imaging detected the presence of residual disease, confirmed at pathology, with a sensitivity of 87.1% and specificity of 21.4%. The best area under the ROC curve (0.817) was for the detection of pathological residual disease of at least 6 mm in diameter, using a cut-off value of 12 mm for the largest tumor diameter assessed using 2D grayscale ultrasound (sensitivity, 95%; specificity, 70.6%). Neither 3D vascular indices nor contrast-ultrasound parameters obtained for lesions suspected at ultrasound following chemoradiation differed significantly between patients with histological complete and those with partial response. CONCLUSIONS: Our results show that grayscale and color Doppler ultrasound have a low level of diagnostic performance in detecting residual disease after neoadjuvant chemoradiation in patients with locally advanced cervical cancer. The best performance was achieved in detection of macroscopic (≥ 6 mm) residual disease. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (11): clinical and ultrasound features of mucinous ovarian tumors.

OBJECTIVE: To describe the clinical and ultrasound findings in patients with mucinous ovarian tumors. METHODS: In this retrospective study, women with a histological diagnosis of mucinous ovarian tumor who had undergone preoperative ultrasound examination were identified from the database of a single ultrasound center. The histological examination was performed by the same pathologist in all cases, and the ultrasound appearance of the tumors was described using the terms and definitions of the International Ovarian Tumor Analysis group. RESULTS: We identified 123 women with a histological diagnosis of mucinous ovarian tumor, of whom 57 (46%) had benign cystadenoma, 34 (28%) had gastrointestinal (GI)-type borderline tumor, 10 (8%) had endocervical-type borderline tumor and 22 (18%) had GI-type invasive carcinoma. On ultrasound examination, 65% (37/57) of cystadenomas were multilocular, of which 59% had ≤ 10 locules, and 79% (27/34) of GI-type borderline tumors were multilocular, of which 89% had > 10 locules. Conversely, 60% (6/10) of endocervical-type borderline tumors had papillations. Eighty-two percent (18/22) of invasive masses contained solid components and 55% (12/22) were multilocular-solid cysts. Bilateral mucinous cystadenomas were found in two women (4% of women with benign tumors) and bilateral borderline tumors of endocervical type in two women (20% of women with borderline tumors of endocervical type). No woman had a bilateral GI-type borderline tumor or a bilateral invasive tumor. CONCLUSIONS: A multilocular cyst with 2-10 locules is representative of a benign cystadenoma, whereas a multilocular cyst with > 10 locules is indicative of a GI-type borderline tumor. Most invasive tumors of mucinous GI-type contain solid components, the most typical ultrasound appearance being that of a multilocular-solid tumor. Papillary projections are typical features of endocervical-type borderline tumors. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (12): clinical and ultrasound features of invasive and non-invasive malignant serous ovarian tumors.

OBJECTIVES: To describe clinical and ultrasound features of different subclasses of malignant serous ovarian tumors according to the World Health Organization 2014 classification. METHODS: Patients with a histological diagnosis of borderline tumor (BOT), non-invasive and invasive low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), who had undergone preoperative ultrasound examination, were retrospectively identified from two ultrasound centers. The masses were described using the terms of the International Ovarian Tumor Analysis Group. RESULTS: Sixty-four (15.8%) women had a serous BOT, 11 (2.7%) a non-invasive LGSC, 31 (7.6%) an invasive LGSC and 300 (73.9%) had a HGSC. The vast majority of BOTs (82.3%) and non-invasive LGSCs (90.9%) were Stage I according to the International Federation of Gynecology and Obstetrics (FIGO) classification scheme, whereas most invasive LGSCs (74.2%) and HGSCs (74.0%) were FIGO Stage III. On ultrasound examination, most borderline lesions were described as unilocular-solid (54.7%) or as multilocular-solid (29.7%) cysts. Papillary projections were present in 52 (81.3%) BOTs. Most non-invasive LGSCs (63.6%) were multilocular-solid cysts and 81.8% had papillary projections. Invasive LGSCs were multilocular-solid cysts in 54.8% of cases, and papillary projections were present in 32.3% of lesions. HGSCs were multilocular-solid (32.7%) or solid (64.0%) masses, with papillary projections in only 7% of cases. CONCLUSIONS: Papillary projections were the most typical ultrasound feature of non-invasive (borderline and low-grade) malignant serous tumors, while the presence of solid components but few, if any, papillations was the most representative feature of invasive (low-grade and high-grade) serous tumors. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Ovarian masses with papillary projections diagnosed and removed during pregnancy: ultrasound features and histological diagnosis.

OBJECTIVE: To elucidate the ultrasound features that can discriminate between benign and malignant ovarian cysts with papillary projections but no other solid component in pregnant women. METHODS: Thirty-four women with an ultrasound diagnosis of an ovarian cyst with papillary projections but no other solid component that had been removed surgically during pregnancy were identified from the databases of four ultrasound units. Some clinical and ultrasound information was collected prospectively. Missing information was obtained retrospectively from ultrasound images, ultrasound reports and patient records. Using prospectively and retrospectively collected data, the ultrasound appearance of the tumors was described using the terms and definitions of the International Ovarian Tumor Analysis group. The ultrasound characteristics were compared with the histological diagnosis. RESULTS: Of the 34 cases included, 19 (56%) lesions were benign (16 decidualized endometriomas, one cystadenofibroma, one simple cyst, one struma ovarii), 12 (35%) were borderline tumors and three (9%) were primary invasive tumors (two immature teratomas, one endometrioid cystadenocarcinoma). The contour of the cyst papillations was smooth in 79% (15/19) of benign tumors vs 27% (4/15) of malignant tumors (P = 0.002). The cystic content showed ground-glass echogenicity in 74% (14/19) of benign tumors vs 13% (2/15) of malignant tumors (P = 0.0006). All ovarian masses with smooth papillations and ground-glass content (n = 12) were decidualized endometriomas. The papillary projections were vascularized and the color score was 3 or 4 in 88% (14/16) of decidualized endometriomas vs 42% (5/12) of borderline tumors (P = 0.013). CONCLUSIONS: In pregnant women, ovarian cysts with ground-glass echogenicity and papillations with a smooth contour on ultrasound are most likely to be decidualized endometriomas. Cysts with anechoic or low-level echogenicity and papillations with an irregular contour suggest borderline malignancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.