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1.
Int Urogynecol J ; 34(10): 2373-2380, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37129627

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The use of synthetic mesh for prolapse and incontinence surgery is discussed controversially and in several countries is either no longer used or permissible. Previous approaches with autologous tissue did not show from a patient´s perspective convincing long-term results. As there have been repeatedly significant complications with synthetic mesh, a new approach is urgently needed. During orthopedics and trauma surgeries, tendons from the thigh have been used for decades to replace cruciate ligament. The procedure of tendon removal from the thigh is fast, easy to learn and morbidity is low. In addition, a long-term durability of the transplant ought to be expected. The objective of this investigation was to show our experience with a semitendinosus tendon instead of a mesh for genital prolapse repair. METHOD: After the first successful attempts using such tendons in cervicosacropexy and pectopexy in patients with genital prolapse, we initiated a national multicenter study in 2020. Five German hospitals participated in order to determine the feasibility of cervicosacropexy with tendon tissue instead of mesh. RESULT: Up until now, we have operated and observed 113 patients for at least 6 months and have seen stable results in terms of fixation of the apical compartment. The expected low morbidity at the donor site was also confirmed through subjective assessment of the patients (Knee and Osteoarthritis Outcome Score). Improvement of quality of life was confirmed after the procedure with the Short Form Health Survey 12, Version 2.0. The results of this multicenter study showed that the desired elevation of the apical compartment with tendon tissue can be achieved with low morbidity and without a synthetic mesh. CONCLUSION: Women with uterine prolapse can be treated minimally invasively and with very low morbidity by using the semitendinosus tendon. The involvement of multiple (five) medical centers confirms that the technique is easy to learn and be transferred to other clinical centers.

2.
Clin Genitourin Cancer ; 19(6): 501-509, 2021 12.
Article in English | MEDLINE | ID: mdl-34629300

ABSTRACT

BACKGROUND: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC. PATIENTS AND METHODS: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg. BID) with either MET 850 mg BID (D+M) or placebo (D+P) up to 10 cycles. Prostate-Specific Antigen (PSA) response ≥50% from baseline was the primary end point. Secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL). RESULTS: Out of 99 patients were randomized (D+M = 50; D+P = 49) in 10 French centers. The median follow-up was 86 (IQR 73-88) months. The PSA-response rate reached 66% in the D+M arm, but was not different from that observed in the D+P arm (63%, P = 0,94). In the D+M and D+P arms, the ORR was 28% and 24%, the median PFS was 7.8 and 6.0 months and the median OS was 27 and 20 months (ns), respectively. Diarrhea grade I to II was more frequent in the MET arm (66% vs. 43%). No impairment of QoL was observed. CONCLUSION: MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed.


Subject(s)
Metformin , Prostatic Neoplasms, Castration-Resistant , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Docetaxel/therapeutic use , Humans , Male , Metformin/therapeutic use , Prednisone/therapeutic use , Prospective Studies , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/drug therapy , Quality of Life , Retrospective Studies , Treatment Outcome
4.
Mod Pathol ; 34(1): 13-19, 2021 01.
Article in English | MEDLINE | ID: mdl-32661296

ABSTRACT

Fibroma of tendon sheath (FTS) is an uncommon benign fibroblastic/myofibroblastic neoplasm that typically arises in the tenosynovial tissue of the distal extremities. Histologically, it is a well-circumscribed proliferation of spindle cells within collagenous stroma with peripheral slit-like vessels. Most examples are relatively hypocellular and more densely collagenous than nodular fasciitis; however, a cellular variant has been described, which has considerable morphologic overlap with nodular fasciitis and has been shown to harbor USP6 translocations in a subset of cases. The incidence of these rearrangements and the identity of the USP6 fusion partners have not been described in detail. In this study we evaluate 13 cases of cellular fibroma of tendon sheath by anchored multiplex PCR/next generation sequencing in order to detect potential gene fusions. Nucleic acids of adequate quality were obtained in 11 cases, demonstrating gene fusions in 7/11 (64%), all of which involve USP6 with a variety of partners, including PKM, RCC1, ASPN, COL1A1, COL3A1, and MYH9. Some unusual histomorphologic findings were present in a subset of cases including palisading growth pattern, epithelioid cells, and osteoclast-like multinucleated giant cells, particularly in the tumors with PKM and ASPN gene partners. Overall, the findings support a biologic relationship between cellular fibroma of tendon sheath and other lesions within the spectrum of USP6-rearranged neoplasms, particularly nodular fasciitis.


Subject(s)
Fibroma/genetics , Oncogene Proteins, Fusion/genetics , Soft Tissue Neoplasms/genetics , Tendons/pathology , Ubiquitin Thiolesterase/genetics , Adult , Female , Gene Rearrangement , Humans , Male , Middle Aged
5.
Genes Chromosomes Cancer ; 60(4): 282-286, 2021 04.
Article in English | MEDLINE | ID: mdl-33170538

ABSTRACT

In this article, we describe a spindle cell neoplasm harboring an EML4-ALK gene fusion presenting as an intraosseous vertebral mass with extension into the adjacent soft tissue in a 65-year-old man. Histologically, the lesion was characterized by the presence of monotonous, cytologically bland spindle cells with loose myxoedematous stroma and interspersed areas of amianthoid-like collagen fiber deposition. Immunohistochemistry demonstrated strong diffuse staining for CD34 and S100, with absent immunoreactivity for SOX10. At 1 year of follow-up after resection, there is no evidence of local recurrence or metastatic disease. This case adds to the clinical and pathologic spectrum of the recently described group of kinase fusion-positive spindle cell neoplasms and represents the first reported intra-osseous example. The presence of ALK rearrangement in this lesion represents a potential therapeutic target, if clinically indicated.


Subject(s)
Neoplasms, Connective Tissue/diagnosis , Oncogene Proteins, Fusion/genetics , Spine/pathology , Aged , Antigens, CD34/metabolism , Bone Neoplasms/diagnosis , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/pathology , Diagnosis, Differential , Humans , Male , Neoplasms, Connective Tissue/diagnostic imaging , Neoplasms, Connective Tissue/genetics , Neoplasms, Connective Tissue/pathology , SOXE Transcription Factors/metabolism , Spine/diagnostic imaging , Tomography, X-Ray Computed
6.
Urol Case Rep ; 32: 101257, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32477879

ABSTRACT

In a 40-year-old caucasian patient with stress incontinence was a TVT operation performed with an autologous semitendinosus tendon transplant. The operation was done with spinal anesthesia. The tendon of the right musculus semitendinosus was stripped from the popliteal fossa and used instead of a synthetic tape as midurethral sling, as it is done in a classical retropubic TVT procedure. The operation was performed successfully. On the first day after the operation the transurethral catheter was removed, continence was reached, and no urinary retention was seen. Mobility and power of the affected leg did not change.

7.
Eur J Obstet Gynecol Reprod Biol ; 249: 37-41, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32344247

ABSTRACT

OBJECTIVE: To show the feasibility of tendon transplantation for minimally invasive pectopexy in pelvic organ prolapse repair. STUDY DESIGN: Patients with uterine or vaginal vault prolapse (POP-Q point C Stage 2-4) were offered laparoscopic pectopexy by means of autologous semitendinosus tendon transplantation. This paper presents a case series and describes the technique regarding the first 10 patients who underwent surgery. After preparing the vagina or cervix for laparoscopic pectopexy a tendon of the patient's semitendinosus muscle was stripped and brought intraabdominally through the 10 mm trocar. The tendon was fixed between the cervix or vagina and to the pectineal ligaments on both sides of the pelvis. RESULTS: All operations were performed successfully without complications. Vaginal examination demonstrated the intended elevation of the middle compartment. Mobility and power of the affected leg did not change. Recovery was fast, and discharge was possible between the second and third postoperative day. CONCLUSION: Our approach demonstrates the feasibility and safety of a laparoscopic pectopexy with a semitendinosus autograft instead of a synthetic mesh. The experience from orthopedic surgery shows that a semitendinosus tendon autograft is long-lasting and stable. In addition, the morbidity on the operated leg is low.


Subject(s)
Cervix Uteri/surgery , Laparoscopy/methods , Pelvic Organ Prolapse/surgery , Tendons/transplantation , Vagina/surgery , Adult , Aged , Feasibility Studies , Female , Humans , Middle Aged , Prospective Studies , Treatment Outcome
8.
Urol Oncol ; 38(1): 2.e1-2.e9, 2020 01.
Article in English | MEDLINE | ID: mdl-31447087

ABSTRACT

OBJECTIVES: The role of 18F-fluorocholine positron emission tomography/computed tomography (18F-Choline PET/CT) in different clinical situations remains controversial and current practices are very heterogeneous. The aim of this study was to evaluate the "real-world" practice of 18F-Choline PET/CT in patients with prostate cancer and its potential impacts on therapeutic strategy. METHODS AND MATERIALS: This is a retrospective multicenter observational study including 265 consecutive men who underwent 18F-Choline PET/CT for prostate cancer between November 2014 and November 2015. Primary outcome was impact on therapeutic strategy. Secondary outcomes were sensitivity of the 18F-Choline PET/CT and predictive factors associated with positive scans. Statistical analyses comprised Student's t test for continuous variables or chi-squared test for qualitative variables. RESULTS: Median PSA level at the time of PET/CT was 4.19 ng/ml. The decision to perform PET/CT was made after multidisciplinary discussion in 29.8% of cases; most were prescribed by urologists (50.2% of cases). Three main indications were concerned: biochemical recurrence after local treatment (61.1%), initial staging (26.0%), or at the time of progression to castration-resistance (12.9%). Upon biochemical recurrence, 18F-Choline PET/CT allowed identification of ≥1 site(s) with a sensitivity of 80.9%. In multivariate analysis, predictive factors associated with 18F-Choline PET/CT sensitivity were serum PSA level and local treatment type in cases of biochemical recurrence, and PSA doubling time and Gleason score in case of initial staging. 18F-Choline PET/CT results allowed restaging and change in therapeutic strategy in 58.1% of all combined indications. CONCLUSIONS: Indications of 18F-Choline PET/CT were varied. The detection rate of metastatic lesions was suitable, especially when PSA rate was >1 ng/mL. In most cases, 18F-Choline PET/CT led to a change in therapeutic strategy, particularly in the setting of biochemical recurrence.


Subject(s)
Choline/analogs & derivatives , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Choline/therapeutic use , Humans , Male
10.
Am J Surg Pathol ; 43(6): 766-772, 2019 06.
Article in English | MEDLINE | ID: mdl-30950843

ABSTRACT

Congestive hepatopathy is a complication of right heart failure and chronically elevated right heart pressure. Histologic findings include sinusoidal dilatation, centrilobular hepatocellular plate atrophy, and fibrosis. We performed a validation study of a recently proposed scoring system (0 to 4 scale) for congestive hepatic fibrosis on 38 liver biopsies. Glutamine synthetase immunohistochemistry was also performed, and loss of centrizonal immunoreactivity correlated with increasing fibrosis score (P<0.01). Interobserver concordance for congestive hepatic fibrosis score based on Masson trichrome stain was initially fair (Fleiss κ=0.28, weighted concordance coefficient=0.60) and significantly improved (κ=0.40, weighted concordance coefficient=0.66) following a multiheaded microscope training session and inclusion of glutamine synthetase immunohistochemistry. Average congestive hepatic fibrosis score correlated with significantly higher right atrial pressure, severity of right atrial dilation, presence of right ventricular dilation, elevated serum alanine aminotransferase, platelet counts, prothrombin time, and model for end-stage liver disease score. In conclusion, the congestive hepatic fibrosis scoring system is reproducible among pathologists and correlates with clinical and laboratory markers of congestive hepatopathy.


Subject(s)
Glutamate-Ammonia Ligase/analysis , Immunohistochemistry , Liver Cirrhosis/diagnosis , Liver/enzymology , Liver/pathology , Adult , Biomarkers/analysis , Biopsy , Female , Humans , Liver Cirrhosis/enzymology , Liver Cirrhosis/pathology , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Reproducibility of Results , Severity of Illness Index
11.
Genes Chromosomes Cancer ; 58(10): 713-722, 2019 10.
Article in English | MEDLINE | ID: mdl-31033080

ABSTRACT

Detection of disease-defining gene fusions in sarcoma has led to refining their classification, as well as to discover several new entities. The advent of anchored multiplex PCR/targeted RNA next-generation sequencing (AMP/RNA-seq) has allowed for the development of scalable platforms that can simultaneously examine multiple fusion transcripts without prior knowledge of specific fusion partners.In this study, we assess the utility of a FusionPlex sarcoma panel analysis by AMP/RNA-seq to detect disease-defining gene fusions in 16 cases of undifferentiated round cell sarcoma in which prior diagnostic work-up could not establish a definitive diagnosis. The clinical and pathologic features of these cases were correlated with the molecular findings. Validation of the method using 41 cases with known diagnoses showed analytic sensitivity and specificity of 98% and 100%, respectively. Of the 16 cases of undifferentiated round cell sarcoma, gene fusions were found in 9 (56%). These included three cases with CIC-DUX4 fusion, two cases with BCOR-CCNB3, and four single cases with CIC-NUTM2A, HEY1-NCOA2, EWSR1-NFATC2, and NUT-MGA1 fusions. Overall, despite some degree of morphologic overlap, all fusion-positive cases had distinct morphologic features, which can be helpful for their histologic classification. We also describe the first adult case of MGA-NUTM1 fusion sarcoma, as well as cartilaginous differentiation in a BCOR-CCNB3 fusion sarcoma, which has not been previously reported. Our study demonstrated that FusionPlex sarcoma panel analysis, in the appropriate morphologic context, is a sensitive and precise ancillary method for the detection of disease-defining gene fusions in undifferentiated round cell sarcomas, aiding in their definitive classification.


Subject(s)
Genetic Testing/methods , High-Throughput Nucleotide Sequencing/methods , Multiplex Polymerase Chain Reaction/methods , Oncogene Fusion , Sarcoma/genetics , Sequence Analysis, RNA/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Sarcoma/pathology
12.
Mod Pathol ; 32(4): 585-592, 2019 04.
Article in English | MEDLINE | ID: mdl-30420727

ABSTRACT

Dedifferentiated liposarcoma is defined as progression of atypical lipomatous tumor/well-differentiated liposarcoma to a higher grade usually non-lipogenic sarcoma, with amplification of 12q13-15. This region contains several genes involved in liposarcoma pathogenesis, including MDM2, CDK4, and DDIT3. While the former two are thought of as the main drivers in dedifferentiated liposarcoma, DDIT3 is typically rearranged in myxoid liposarcoma. Overexpression of DDIT3, along with MDM2 and CDK4, may contribute to the pathogenesis of dedifferentiated liposarcoma by interfering with adipocytic differentiation. Dedifferentiated liposarcoma with DDIT3 amplification has not been well characterized. In this study we evaluate the presence of DDIT3 amplification in 48 cases of dedifferentiated liposarcoma by cytogenomic microarray analysis and its correlation with demographic, clinical, and morphologic characteristics. Data from The Cancer Genome Atlas were also evaluated to determine a relationship between DDIT3 amplification and prognostic outcomes. Of the 48 cases, 16 (33%) had amplification of DDIT3; these patients were on average 11 years younger than patients without DDIT3 amplification (P < 0.05). Myxoid liposarcoma-like morphologic features were identified in 12/16 (75%) cases with DDIT3 amplification and in 7/32 (22%) cases without amplification (P < 0.05). Homologous lipoblastic differentiation was seen in 6/16 (38%) cases with DDIT3 amplification and 2/32 (6%) cases without it (P < 0.05). There was no significant correlation between DDIT3 amplification and tumor location, disease-specific or recurrence-free survival, and distant metastasis. DDIT3 amplification appears to interfere with the adipogenic molecular program and plays a role in inducing or maintaining a lipogenic phenotype in dedifferentiated liposarcoma. From a diagnostic standpoint, it is important to consider DDIT3-amplified dedifferentiated liposarcoma in the differential diagnosis of myxoid liposarcoma, particularly in small biopsies. Further studies evaluating the significance of DDIT3 amplification in the pathogenesis of dedifferentiated liposarcoma, as well as a potential predictor of tumor behavior in well-differentiated liposarcoma, are needed.


Subject(s)
Liposarcoma/genetics , Liposarcoma/pathology , Transcription Factor CHOP/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Female , Gene Amplification , Humans , Liposarcoma, Myxoid/pathology , Male , Middle Aged
13.
Case Rep Orthop ; 2018: 4549836, 2018.
Article in English | MEDLINE | ID: mdl-30151289

ABSTRACT

Fibroma of the tendon sheath most often presents around small joints and involves the tendon and tendon sheaths of the fingers, hands, and wrist. In rare instances, it presents as an intra-articular mass. It has never been described in the hip joint. In the current case presentation, this benign tumor was found to be the source of a patient's atypical severe hip pain. Arthroscopic resection of this tumor alleviated the patient's pain.

14.
J Pathol ; 244(1): 97-106, 2018 01.
Article in English | MEDLINE | ID: mdl-28991373

ABSTRACT

Superficial malignant peripheral nerve sheath tumour (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle/desmoplastic melanoma (SDM). Herein, we sought to identify molecular targets for therapy by using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin-fixed paraffin-embedded tissue were extracted and processed. Massive high-throughput deep parallel sequencing was performed with the Oncomine comprehensive panel, enabling detection of relevant single-nucleotide variants, copy number variations, gene fusions and indels for 143 unique genes on the Ion torrent sequencer for clinical trial research programmes. Gene expression analysis was carried out with a customized 770-gene expression panel combining markers for 24 different immune cell types and 30 common cancer antigens, including key checkpoint blockade genes analysed with the Ncounter system. Fifty-one patients (SDM, 16/11; MPNST, 24; male, n = 37; female, n = 16) had sufficient DNA and RNA for testing. NF1 deleterious mutations and/or deep/homozygous deletions were identified in 73% of MPNSTs and 67% of SDMs, with 50% of the mutations involving the RAS-binding domain. Inactivating/deleterious mutations of TSC1/TSC2 were identified in 40% and 41% of MPNSTs and SDMs, respectively. Activating mutations affecting the EGFR-like and the negative regulatory domains of NOTCH1 and KDR (VEGFR2) were identified in 45% and 40% of SDMs and in 30% and 8% of MPNSTs, respectively. Differential gene expression and gene clustering analysis showed significantly perturbed immune pathway components, including nuclear factor-κB (NF-κB), JAK-STAT, and CXCL12-CXCR4, and differentially expressed CD274 and CTLA4, in both SDM and MPNST. Angiogenesis (KDR and NOTCH1) and mammalian target of rapamycin complex (mTORC) pathways offer a rationale for anti-angiogenic and selective mTORC inhibition as treatment strategies for MPNST and SDM. Cytokines and the JAK-STAT, TNF and NF-κB axes were perturbed in both SDM and MPNST. These pathways have been targeted in haematological malignancies and present promising targets for these tumours. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Subject(s)
Melanoma/pathology , Neurilemmoma/pathology , Adult , Aged , Aged, 80 and over , DNA Copy Number Variations , Female , Gene Expression Profiling , Gene Library , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation , Sequence Analysis, DNA , Sequence Analysis, RNA , Tumor Microenvironment
15.
Cancer Genet ; 218-219: 69-80, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29153098

ABSTRACT

Dedifferentiated liposarcoma (DDLS) is characterized at the molecular level by amplification of genes within 12q13-15 including MDM2 and CDK4. However, other than FNCLCC grade, prognostic markers are limited. We aim to identify molecular prognostic markers for DDLS to help risk stratify patients. To this end, we studied 49 cases of DDLS in our institutional archives and performed cytogenomic microarray analysis on 47 cases. Gene copy numbers for 12 loci were evaluated and correlated with outcome data retrieved from our institutional electronic medical records. Using cut point analysis and comparison of Kaplan-Meier survival curves by log rank tests, high amplification levels of MDM2 (>38 copies) and CDK4 (>30 copies) correlated with decreased disease free survival (DFS) (P = .0168 and 0.0169 respectively) and disease specific survival (DSS) (P = .0082 and 0.0140 respectively). Additionally, MDM2 and CDK4 showed evidence of a synergistic effect so that each additional copy of one enhances the effect on prognosis of each additional copy of the other for decreased DFS (P = .0227, 0.1% hazard). High amplification of JUN (>16 copies) also correlated with decreased DFS (P = .0217), but not DSS. The presence of copy number alteration at 3q29 correlated with decreased DSS (P = .0192). The presence of >10 mitoses per 10 high power fields and FNCLCC grade 3 also correlated with decreased DFS (P = .0310 and 0.0254 respectively). MDM2 and CDK4 gene amplification levels, along with JUN amplification and copy alterations at 3q29, can be utilized for predicting outcome in patients with DDLS.


Subject(s)
Biomarkers, Tumor/genetics , Cell Differentiation , Cyclin-Dependent Kinase 4/genetics , Gene Amplification , Liposarcoma/pathology , Proto-Oncogene Proteins c-mdm2/genetics , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Gene Dosage , Humans , In Situ Hybridization, Fluorescence , Liposarcoma/genetics , Male , Microarray Analysis , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies
16.
Cancer ; 123(17): 3291-3304, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28463396

ABSTRACT

BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vß gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.


Subject(s)
Programmed Cell Death 1 Receptor/genetics , Sarcoma/genetics , Sarcoma/mortality , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/mortality , T-Lymphocytes/cytology , Adult , Aged , Aged, 80 and over , Analysis of Variance , Biopsy, Needle , Clone Cells , Cluster Analysis , Cohort Studies , Combined Modality Therapy , Databases, Factual , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Sarcoma/pathology , Sarcoma/therapy , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/therapy , Survival Analysis , T-Lymphocytes/immunology , Young Adult
17.
Arch Gynecol Obstet ; 295(1): 39-43, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27581586

ABSTRACT

PURPOSE: To assess the effects of mechanical dilatation of the cervix during cesarean section on postoperative morbidity. METHODS: A total of 447 women with elective cesarean section were included in the Dondi trial (Dilatation or no dilatation of the cervix during cesarean section). The primary outcome measure of this randomized controlled trial was postpartum hemorrhage (PPH) within 6 weeks. Infectious morbidity (puerperal fever, endometritis, wound infection, and urinary tract infection), blood loss (need for blood transfusion or change in hemoglobin levels), and operating time were also evaluated. RESULTS: The rate of PPH within 6 weeks was not different between the two groups [dilatation group: 5 (2.4 %), no dilatation group: 3 (1.2 %), p = 0.479]. Infectious morbidity, blood loss, and operating time were not diverse as well. The only significant difference between the two groups was the rate of retained products of conception with fewer cases after cervical dilatation (0 versus 6.2 %, p < 0.001). CONCLUSIONS: Dilatation of the cervix during cesarean section compared with no dilatation of the cervix did not influence the risk of postpartum hemorrhage. However, there were fewer cases with retained products of conception after dilatation.


Subject(s)
Cesarean Section/methods , Dilatation/adverse effects , Adult , Cesarean Section/adverse effects , Female , Humans , Postpartum Hemorrhage/etiology , Pregnancy , Prospective Studies , Puerperal Disorders/etiology , Single-Blind Method
18.
J Oral Maxillofac Surg ; 74(1): 95-103, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26212094

ABSTRACT

This report outlines the workup and management of a 55-year-old woman with a synovial sarcoma of the lateral border of the tongue that was initially diagnosed as a glomus tumor. A review was performed of the literature on synovial sarcomas of the oral cavity and current National Comprehensive Cancer Network guidelines. Synovial sarcomas of the tongue are rare neoplasms, with variable morphologic microscopic types and immunohistochemical profiles. Fluorescence in situ hybridization analysis of the known gene translocation also can be used in diagnosis. According to the literature, resection of the tumor is the current treatment of choice; however, owing to the rarity of this entity, diagnosis and management prove challenging for the oral and maxillofacial surgeon.


Subject(s)
Sarcoma, Synovial/diagnosis , Tongue Neoplasms/diagnosis , Actins/analysis , Angiography/methods , Diagnosis, Differential , Embolization, Therapeutic/methods , Female , Follow-Up Studies , Glomus Tumor/diagnosis , Glossectomy/methods , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Laser Therapy/methods , Magnetic Resonance Angiography/methods , Middle Aged , Radiotherapy, Adjuvant/methods , Plastic Surgery Procedures/methods , Tomography, X-Ray Computed/methods , Tongue/blood supply
19.
Hum Pathol ; 46(9): 1398-404, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26198745

ABSTRACT

Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma.


Subject(s)
Biomarkers, Tumor/genetics , Cell Dedifferentiation , Chondrosarcoma/genetics , Chondrosarcoma/pathology , Femoral Neoplasms/genetics , Femoral Neoplasms/pathology , Isocitrate Dehydrogenase/genetics , Biopsy , Chondrosarcoma/enzymology , Chondrosarcoma/surgery , DNA Mutational Analysis , Exons , Femoral Neoplasms/enzymology , Femoral Neoplasms/surgery , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Neoplasm Recurrence, Local , Osteotomy , Time Factors , Treatment Outcome
20.
Mod Pathol ; 28(1): 37-47, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25059573

ABSTRACT

Dedifferentiated liposarcoma represents a form of liposarcoma composed of a non-lipogenic sarcoma associated with well-differentiated liposarcoma. The prognostic significance of histological grading of the dedifferentiated component remains to be elucidated due to vague grading criteria employed in previous studies. Molecular markers of tumor behavior, including amplification levels of murine double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) genes, have been explored in a limited number of cases. Here we investigate whether 'Fédération Nationale des Centres de Lutte Contre le Cancer' (FNCLCC) grade and MDM2 gene amplification levels have prognostic value in dedifferentiated liposarcoma in terms of local recurrence and disease-specific survival. Fifty cases were retrieved, reviewed and FNCLCC grade was scored for the dedifferentiated component. Testing for MDM2 gene amplification was performed by fluorescence in situ hybridization. Amplification was categorized as high level (≥20 copies) and as low level (<20 copies). Follow-up data was obtained through chart review. Log-rank test and Cox proportional hazard models were used to determine the effect of grade and level of MDM2 amplification on outcomes. Our series includes 50 patients (male n=28, female n=22) with an average age of 63 years (range, 28-88) and a median follow-up of 28 months (range, 2-120). Tumors were graded as grade 1 (6%), grade 2 (58%), and grade 3 (36%). When adjusted for age, sex, site, tumor size, and margin status, grade 3 patients had a higher recurrence rate than grades 1 and 2 (HR=2.07, 95% CI: 1.24, 7.62; P=0.015). Patients with high-level MDM2 amplification had higher recurrence rate on univariate analysis (P=0.028), but not on multivariate analysis (HR=1.69, 95% CI: 0.73, 3.94; P=0.221). FNCLCC grade 3 dedifferentiation confers a worse prognosis in dedifferentiated liposarcoma in terms of local recurrence. MDM2 amplification level remains a useful diagnostic tool in dedifferentiated liposarcoma, but has no prognostic value in terms of local recurrence.


Subject(s)
Liposarcoma/genetics , Liposarcoma/pathology , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Proto-Oncogene Proteins c-mdm2/genetics , Adult , Aged , Aged, 80 and over , Female , Gene Amplification , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Liposarcoma/mortality , Male , Middle Aged , Neoplasm Grading , Prognosis , Proportional Hazards Models , Retrospective Studies
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