A venetoclax and azacitidine bridge-to-transplant strategy for NPM1-mutated acute myeloid leukaemia in molecular failure.

NPM1-mutated acute myeloid leukaemia (NPM1mut AML) represents a mostly favourable/intermediate risk disease that benefits from allogeneic haematopoietic stem cell transplantation (HSCT) in case of measurable residual disease (MRD) relapse or persistence after induction chemotherapy. Although the negative prognostic role of pre-HSCT MRD is established, no recommendations are available for the management of peri-transplant molecular failure (MF). Based on the efficacy data of venetoclax (VEN)-based treatment in NPM1mut AML older patients, we retrospectively analysed the off-label combination of VEN plus azacitidine (AZA) as bridge-to-transplant strategy in 11 NPM1mut MRD-positive fit AML patients. Patients were in MRD-positive complete remission (CRMRDpos ) at the time of treatment: nine in molecular relapse and two in molecular persistence. After a median number of two cycles (range 1-4) of VEN-AZA, 9/11 (81.8%) achieved CRMRD -negative (CRMRDneg ). All 11 patients proceeded to HSCT. With a median follow-up from treatment start of 26 months, and a median post-HSCT follow-up of 19 months, 10/11 patients are alive (1 died from non-relapse mortality), and 9/10 patients are in MRDneg status. This patient series highlights the efficacy and safety of VEN-AZA to prevent overt relapse, achieve deep responses and preserve patient fitness before HSCT, in patients with NPM1mut AML in MF.

International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.

OBJECTIVE: To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. RESULTS: Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. CONCLUSIONS: Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Pelvic myeloid sarcoma: a multidisciplinary approach.

Myeloid sarcoma (MS) is a rare tumor mass derived from the extramedullary proliferation of blasts of one or more of myeloid lineages. It usually occurs at an anatomical site other than the bone marrow (BM). Among the anatomical site which may be involved, female genital tract is a rare localization. When MS follows a previous history of myeloid pathology it is usually associated to a poor prognosis. To date this disease was managed with exploratory laparotomy or with surgical debulking. The authors report a case of laparosc6pic diagnosis of a pelvic myeloid sarcoma in a patient previously affected by acute mycloid leukemia, evidencing the importance of minimally invasive diagnosis and subsequent multidisciplinary management.

Pelvic floor muscle dysfunction on 3D/4D transperineal ultrasound in patients with deep infiltrating endometriosis: a pilot study.

OBJECTIVE: Pelvic floor muscle (PFM) dysfunction seems to play an important role in the pathophysiology of pelvic pain, including that associated with deep infiltrating endometriosis (DIE). The aim of this study was to evaluate the static and dynamic morphometry of the PFM using three-dimensional (3D) and four-dimensional (4D) transperineal ultrasound in women with DIE compared with asymptomatic healthy women. METHODS: This was a pilot, prospective study conducted at our tertiary center between March and November 2015. Fifty nulliparous women with DIE (study group) and 35 nulliparous asymptomatic healthy women (control group) were included. 3D/4D transperineal ultrasound examination of the PFM was performed in both groups. Levator hiatal area (LHA) and anteroposterior and left-right transverse diameters were evaluated at rest, on maximum PFM contraction and on maximum Valsalva maneuver. Persistent levator ani muscle (LAM) coactivation during Valsalva maneuver was investigated. RESULTS: Compared with the control group, women with DIE had a smaller LHA at rest (P = 0.03) and during Valsalva maneuver (P < 0.01). Furthermore, reduction in LHA during PFM contraction (P < 0.001) and enlargement in LHA during Valsalva maneuver (P = 0.01) were significantly less marked. In comparison with controls, women with DIE presented a higher frequency of LAM coactivation during Valsalva maneuver, although this difference did not reach statistical significance (P = 0.05). CONCLUSIONS: 3D and 4D transperineal ultrasound is an objective and non-invasive method for PFM morphometry and may have a role in detecting PFM dysfunction in women with DIE. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Histological evaluation of ureteral involvement in women with deep infiltrating endometriosis: analysis of a large series.

STUDY QUESTION: In women with deeply infiltrating endometriosis (DIE) what is the prevalence of involvement of endometriotic tissue and fibrosis in ureteral endometriosis (UE), as assessed by histological staining? SUMMARY ANSWER: In women with DIE, ureteral involvement is more often due to endometriotic tissue rather than fibrosis. WHAT IS KNOWN ALREADY: In the current literature, histological evaluation of ureteral endometriosis is mainly based on the degree of wall infiltration by endometriosis instead of the tissue composition. A few studies reported ill-defined and contradictory histological data on the tissue composition of UE. STUDY DESIGN, SIZE, DURATION: Retrospective observational study based on clinical records of women affected by DIE, laparoscopically treated for UE at a tertiary referral center, between January 2010 and March 2013. All cases of ureteral nodule excision or ureterectomy with histological examination of the specimens were included. Exclusion criteria were other identified causes of hydroureteronephrosis, medical therapy for a period of at least 3 months before surgery and previous surgery for DIE. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 77 patients were included in the study and among them seven (9%) presented with bilateral ureteral involvement, giving a total of 84 cases of UE available for analysis. All patients had stage IV endometriosis. According, respectively, to the presence of endometrial glands and/or stroma cells or of fibrotic tissue only, the endometriotic UE and fibrotic UE groups were compared with regard to hydroureteronephrosis at pre-operative urinary tract computerized tomography scan, type of surgical procedure performed to treat UE (nodule removal or ureterectomy), association with other locations of the disease and post-operative complications (ureteral fistula or stenosis). MAIN RESULTS AND THE ROLE OF CHANCE: For the 84 cases of UE, 65 (77%) and 19 (23%), respectively, showed endometriotic tissue and fibrotic tissue only. Presence of hydroureteronephrosis and endometriotic pattern of UE showed a significant association [endometriotic UE 44/65 (68%) versus fibrotic UE 8/19 (42%); P = 0.04]. Fibrotic pattern of UE and presence of concomitant recto-vaginal endometriosis showed a significant association [endometriotic group: 29/65 (45%) versus fibrotic group 18/19 (95%); P < 0.001]. LIMITATIONS, REASONS FOR CAUTION: The retrospective and monocentric (tertiary referral center) study design. WIDER IMPLICATIONS OF THE FINDINGS: Besides the distinction between extrinsic and intrinsic UE based on the degree of wall infiltration by endometriosis, a new classification according to the histological pattern of UE could be useful for clinicians, both in the diagnostic and therapeutic fields. STUDY FUNDING/COMPETING INTERESTS: None.

Urodynamic evaluation and anorectal manometry pre- and post-operative bowel shaving surgical procedure for posterior deep infiltrating endometriosis: a pilot study.

STUDY OBJECTIVE: To analyze bowel and urinary function in patients with posterior deep infiltrating endometriosis (DIE) >30 mm in largest diameter at transvaginal ultrasound before and after surgical nerve-sparing excision. DESIGN: Prospective observational study (Canadian Task Force classification III). SETTING: Tertiary care university hospital in Bologna, Italy. PATIENTS: Twenty-five patients with posterior DIE were included in the study between June 2011 and December 2012. Patients did not receive hormone therapy for at least 3 months before and 6 months after surgery. INTERVENTIONS: Patients underwent urodynamic studies and anorectal manometry before and after nerve-sparing laparoscopic excision of the posterior DIE nodule. MEASUREMENTS AND MAIN RESULTS: Intestinal and urinary function was evaluated in patients with bulky posterior DIE using urodynamic and anorectal manometry. Results of urodynamic studies and anorectal manometry were similar before and after nerve-sparing surgical excision of the posterior DIE nodule. Urodynamic studies demonstrated a high prevalence of voiding dysfunction, whereas anorectal manometry showed no reduction in rectoanal inhibitory reflex and hypertone of the internal anal sphincter. CONCLUSIONS: Patients with posterior DIE >30 mm in greatest diameter demonstrate preoperative dysfunction at urodynamic study and anorectal manometry, probably due to DIE per se. The nerve-sparing surgical approach seems not to influence the motility or sensory capacity of the bladder and the rectosigmoid colon.

Intra- and interobserver agreement with regard to describing adnexal masses using International Ovarian Tumor Analysis terminology: reproducibility study involving seven observers.

OBJECTIVES: To estimate intraobserver repeatability and interobserver agreement in assessing the presence of papillary projections in adnexal masses and in classifying adnexal masses using the International Ovarian Tumor Analysis terminology for ultrasound examiners with different levels of experience. We also aimed to identify ultrasound findings that cause confusion and might be interpreted differently by different observers, and to determine if repeatability and agreement change after consensus has been reached on how to interpret 'problematic' ultrasound images. METHODS: Digital clips (two to eight clips per adnexal mass) with gray-scale and color/power Doppler information of 83 adnexal masses in 80 patients were evaluated independently four times, twice before and twice after a consensus meeting, by four experienced and three less experienced ultrasound observers. The variables analyzed were tumor type (unilocular, unilocular solid, multilocular, multilocular solid, solid) and presence of papillary projections. Intraobserver repeatability was evaluated for each observer (percentage agreement, Cohen's kappa). Interobserver agreement was estimated for all seven observers (percentage agreement, Fleiss kappa, Cohen's kappa). RESULTS: There was uncertainty about how to define a solid component and a papillary projection, but consensus was reached at the consensus meeting. Interobserver agreement for tumor type was good both before and after the consensus meeting, with no clear improvement after the meeting, mean percentage agreement being 76.0% (Fleiss kappa, 0.695) before the meeting and 75.4% (Fleiss kappa, 0.682) after the meeting. Interobserver agreement with regard to papillary projections was moderate both before and after the consensus meeting, with no clear improvement after the meeting, mean percentage agreement being 86.6% (Fleiss kappa, 0.536) before the meeting and 82.7% (Fleiss kappa, 0.487) after it. There was substantial variability in pairwise agreement for papillary projections (Cohen's kappa, 0.148-0.787). Intraobserver repeatability with regard to tumor type was very good and similar before and after the consensus meeting (agreement 87-95%, kappa, 0.83-0.94). With regard to papillary projections intraobserver repeatability was good or very good both before and after the consensus meeting (agreement 88-100%, kappa, 0.64-1.0). CONCLUSIONS: Despite uncertainty about how to define solid components, interobserver agreement was good for tumor type. The interobserver agreement for papillary projection was moderate but very variable between observer pairs. The term 'papillary projection' might need a more precise definition. The consensus meeting did not change inter- or intraobserver agreement.

B-flow ultrasound facilitates visualization of contrast medium during hysterosalpingo-contrast sonography.

OBJECTIVE: To assess if B-flow ultrasound improves visualization of flow of contrast medium in the Fallopian tubes during hysterosalpingo-contrast sonography (HyCoSy) compared with grayscale ultrasound. METHODS: This prospective observational study included 160 women referred for HyCoSy as part of infertility work-up between January 2011 and September 2012. In each woman, at the same session, HyCoSy was performed first using saline with air and then using Sonovue®, and for each contrast medium, grayscale ultrasound was first used and then B-flow ultrasound was used. Flow of contrast was observed in three parts of each tube: intramural, middle and distal. RESULTS: In 129 (81%) women, flow of Sonovue was observed in the intramural part of both tubes and in the pouch of Douglas when using grayscale ultrasound. In these women, flow of Sonovue was seen in the middle part of 70% of the 258 tubes when using grayscale ultrasound and in 93% when using B-flow ultrasound; and in the distal part in 81% when using grayscale ultrasound and in 98% when using B-flow ultrasound. When using air and saline, flow was seen in the intramural part of 90% and 93% of the tubes, in the middle part in 54% and 72%, and in the distal part in 66% and 90%, using grayscale ultrasound and B-flow ultrasound, respectively. CONCLUSION: B-flow ultrasound facilitates detection of flow of contrast in the middle and distal parts of the tubes at HyCoSy, especially when a mixture of saline and air is used as contrast medium.

Intra- and interobserver reproducibility of assessment of Doppler ultrasound findings in adnexal masses.

OBJECTIVES: To estimate intra- and interobserver reproducibility and reliability of assessment of the color content in adnexal masses at color/power Doppler ultrasound examination for observers with different levels of experience, and to determine if they change after a consensus meeting. METHODS: Digital clips with color/power Doppler information on 103 adnexal masses were evaluated independently four times, twice before and twice after a consensus meeting, by four experienced and three less experienced ultrasound examiners. The color content of the adnexal mass was estimated using the International Ovarian Tumor Analysis color score and a 100-mm visual analog scale (VAS score). Intraobserver repeatability was estimated for each observer. Interobserver agreement was estimated for the four most experienced observers (six pairs), for the three less experienced observers (three pairs), and for four other pairs of observers, each pair consisting of one of the experienced and one of the less-experienced observers. RESULTS: Intra- and interobserver agreement for the color score was moderate to very good, percentage agreement ranging from 48 to 82.5% (kappa, 0.52-0.82) before and from 59 to 90% (kappa, 0.60-0.88) after the consensus meeting. For seven of 13 pairs of observers, interobserver agreement improved after the consensus meeting. Intraobserver intraclass correlation coefficient (ICC) values for the VAS score ranged from 0.80 to 0.92 before and from 0.75 to 0.94 after the consensus meeting, but limits of agreement were wide (± 20-35 mm). For six of the seven observers the ICC values were higher after the consensus meeting than before. Interobserver ICC values for the VAS score ranged from 0.77 to 0.88 before and from 0.77 to 0.91 after the consensus meeting, but limits of agreement were wide (± 30-40 mm). For 10 of 13 pairs of observers the ICC values improved after the consensus meeting. CONCLUSIONS: Intra- and interobserver agreement for the color score was good, especially after the consensus meeting, but there is room for improvement. VAS score results varied substantially within and between observers both before and after the consensus meeting. General consensus needs to be reached about how to interpret color/power Doppler ultrasound findings in adnexal masses.