Both conservative surgery with disk resection, and nerve- and vessel-sparing segmental resection reduce pain symptoms with equal morbidity. Fertility is improved with surgery with both techniques.
Objectives To evaluate interobserver agreement and accuracy of transvaginal sonography (TVS) in diagnosing deep infiltrating endometriosis (DIE) and endometriomas.
Methods (Gwet's AC1, 0.933; 62%/94% and 82%/94%), bladder (Gwet's AC1, 1.00; 67%/97% and 67%/97%), uterosacral ligaments (Gwet's AC1, 0.84; 73%/83% and 53%/90%), adnexa (Gwet's AC1, 0.95; 71%/93% and 71%/93%), rectovaginal septum (Gwet's AC1, 0.95; 40%/90% and 33%/87%) and rectosigmoid (Gwet's AC1, 0.98; 93%/96% and 94%/98%)
DDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.
Myelofibrosis (MF) is a clonal stem cell neoplasm characterized by abnormal JAK-STAT signaling, chronic inflammation, cytopenias and risk of transformation to acute leukemia. Despite improvements in the therapeutic options for MF patients, allogeneic hematopoietic stem cell transplantation remains the only curative treatment. We previously demonstrated multiple immunosuppressive mechanisms in MF patients, including elevated PD1 expression on T cells compared to healthy controls. Therefore, we conducted a multicenter, open-label, phase 2, single-arm study of pembrolizumab in patients with DIPSS intermediate 2 or greater primary, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with ruxolitinib (NCT03065400). The study followed a Simon two-stage design, and enrolled a total of 10 patients, 5 of which had JAK2V617 mutation, 2 had CALR mutation and 6 patients had additional mutations. Most patients were previously treated with ruxolitinib. Pembrolizumab treatment was well tolerated but there were no objective clinical responses and thus, the study closed after completion of the first stage. However, immune profiling by flow cytometry, TCR sequencing and plasma proteomics demonstrated changes in the immune milieu of patients suggesting improved T cell responses, which can potentially favor antitumor immunity. The fact that these changes were not reflected in a clinical response strongly suggest that combination immunotherapeutic approaches rather than monotherapy may be necessary to reverse the multifactorial mechanisms of immune suppression in MPN. The study is registered at http://www.clinicaltrials.gov as NCT03065400.
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