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Case Rep Oncol. 2022 Nov 8;15(3):950-959. doi: 10.1159/000526256. eCollection 2022 Sep-Dec.
ABSTRACT
Trabectedin is a chemotherapeutic used to treat advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Although it is associated with a low incidence of cardiotoxicity, when this occurs it can be fatal or significantly compromise the quality of life in patients with advanced cancer. Here, we present a series of 4 cases where trabectedin-treated sarcoma patients developed cardiovascular complications. Similar to previous literature describing this association, all patients had prior treatment with anthracyclines and presented at different time points following treatment initiation. Each patient presented with exertional breathlessness and was found to have severely impaired left ventricular systolic function (ejection fraction ≤35%), and 1 patient had concurrent atrial fibrillation with a fast ventricular rate. All of the patients were treated with neurohormonal blockade, and a multi-disciplinary decision was made to stop trabectedin in 3 patients and continue in 1 patient. Two of the 4 patients had an improvement in their left ventricular systolic function. It is unclear what effect preceeding anthracycline or tyrosine kinase inhibitor treatment has in priming patients to develop cardiotoxicity in this setting. Our case series adds to the evidence surrounding this association and highlights that trabectedin-associated cardiotoxicity can present in an insidious fashion.
PMID:36636681 | PMC:PMC9830299 | DOI:10.1159/000526256
Case Rep Oncol. 2022 Nov 8;15(3):927-935. doi: 10.1159/000525608. eCollection 2022 Sep-Dec.
ABSTRACT
As a rare entity, sarcomas of the head and neck are challenging cases. In this paper, we represent a unique case of Ewing sarcoma of mandible, serving as an example of multidisciplinary team importance in a developing country.
PMID:36636676 | PMC:PMC9830304 | DOI:10.1159/000525608
Cureus. 2022 Dec 11;14(12):e32394. doi: 10.7759/cureus.32394. eCollection 2022 Dec.
ABSTRACT
Kaposi sarcoma is a malignancy common in patients with acquired immune deficiency syndrome (AIDS). It is a proliferative soft-tissue tumor commonly manifesting as pigmented papules and nodules on the skin. Lesions can also appear on the mucosal lining of the oropharynx and other parts of the body such as the lymph nodes. Head and neck involvement in Kaposi sarcoma is not unusual; however, laryngeal involvement is not commonly seen. We report the case of a 31-year-old gentleman, a former smoker with AIDS, who developed a mass in the throat with progressive hoarseness of voice without stridor. An elective tracheostomy was done to protect his airway before performing a direct laryngoscopy with biopsy. Histopathology examination showed neoplastic spindle cells positive for CD31, erythroblast transformation specific-related gene, and human herpesvirus 8, consistent with Kaposi sarcoma. The diagnosis of laryngeal Kaposi sarcoma in immunodeficient patients requires a high index of suspicion, especially when it occurs without classical dermatological manifestation, an interesting feature in this report.
PMID:36636532 | PMC:PMC9830648 | DOI:10.7759/cureus.32394
Cureus. 2022 Dec 11;14(12):e32395. doi: 10.7759/cureus.32395. eCollection 2022 Dec.
ABSTRACT
Primary pulmonary Ewing sarcoma is an extremely rare tumor of neuroectodermal tissue. In this article, we report on the case of a 45-year-old female who presented in the emergency department with shortness of breath and night fever. Radiologic findings suggested a massive pulmonary mass and a metastatic liver lesion. The diagnosis of Ewing sarcoma was established through a percutaneous biopsy of the lung mass and liver lesion. We highlight the importance of considering a broad differential diagnosis for a large pulmonary mass in order to lead to a prompt diagnosis and treatment.
PMID:36636530 | PMC:PMC9830843 | DOI:10.7759/cureus.32395
Rare Tumors. 2023 Jan 6;15:20363613221150218. doi: 10.1177/20363613221150218. eCollection 2023.
ABSTRACT
The author describes a rare case of giant adenoid cystic carcinoma (ACC) mimicking large paraganglioma with lower cranial nerve palsy. A 60-year-old female presented with a progressive increase in postauricular swelling with unilateral hearing loss, facial deviation, difficulty in swallowing, and hoarseness of voice. MRI brain showed highly vascular infiltrating and osteolytic mass suggestive of large glomus jugulare versus sarcoma. It was completely engulfing the jugular foramen and lower cranial nerves with bony erosion of the jugular foramen and occipital condyle. The whole mastoid was filled with the tumor. On digital subtraction angiography the majority of blood supply was from the occipital branch of the external carotid artery and vertebral artery. The patient underwent percutaneous embolization followed by external carotid ligation and resection of the mass. The postoperative course was uneventful. Histopathology was suggestive of mixed ACCs. The patient received radiotherapy. After 1 year of follow up no recurrence or distant metastasis was noted.
PMID:36636105 | PMC:PMC9830093 | DOI:10.1177/20363613221150218
J Gastrointest Oncol. 2022 Dec;13(6):3329-3335. doi: 10.21037/jgo-21-700.
ABSTRACT
BACKGROUND: Epstein Barr virus-associated smooth muscle tumors (EBV-SMT) are rare neoplasms that can occur in immunocompromised individuals. The native or transplanted liver is the most commonly involved site in post transplant patients. Systemic therapies have been utilized in EBV-SMT with modest activity.
CASE DESCRIPTION: We describe a 23-year-old female kidney transplant recipient who presented with acute myeloid leukemia (AML) and hepatic myeloid sarcoma (MS). Although it was not recognized initially, her liver biopsy revealing MS at diagnosis was posthumously found to have synchronous EBV-SMT. She underwent anthracycline based induction and achieved a complete remission of her AML by bone marrow biopsy. Due to a persistent hepatic mass, she was given salvage chemotherapy including fludarabine, etoposide, cytarabine, decitabine, and venetoclax for presumed refractory MS. Re-biopsy of the liver revealed the absence of MS and presence of EBV-SMT, which subsequently grew rapidly and precluded her from a liver tumor resection. The patient underwent sirolimus mammalian target of rapamycin (mTOR) therapy with palliative intent, but the patient's EBV-SMT progressed shortly after. At time of autopsy, the patient remained in complete remission from AML/MS, but was found to have multifocal progressive metastatic EBV-SMT.
CONCLUSIONS: To our knowledge this is the first reported case of synchronous AML/MS and post transplant hepatic EBV-SMT that underwent treatment for AML/MS. Our report suggests that the chemotherapeutic agents utilized for AML/MS may have poor efficacy against EBV-SMT.
PMID:36636068 | PMC:PMC9830336 | DOI:10.21037/jgo-21-700
Cell Cycle. 2023 Jan 12:1-12. doi: 10.1080/15384101.2023.2166195. Online ahead of print.
ABSTRACT
Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and master transcription factor of adipogenesis-related genes, and has been reported as an antitumor target for chondrosarcomas. Herein, we show that the nonsteroidal anti-inflammatory drug, zaltoprofen, induces the expression of PPARγ at the mRNA and protein levels, following the induction of PPARγ-activating factors, such as Krox20, C/EBPβ, and C/EBPα, in human extraskeletal chondrosarcoma H-EMC-SS cells. Upregulation of the cell cycle checkpoint proteins, p21, p27, and p53, was observed upon treatment of H-EMC-SS cells with zaltoprofen, which probably resulted in the inhibition of proliferation of these cells observed in vitro. Zaltoprofen treatment inhibited tumor growth, induced tumor cell apoptosis, and was well tolerated in a mouse model of extraskeletal myxoid chondrosarcoma. Our results provide mechanistic insights into the therapeutic effect of zaltoprofen that should promote further studies on the rational use of this drug for the effective treatment of sarcomas.
PMID:36636023 | DOI:10.1080/15384101.2023.2166195
Int J Biol Sci. 2023 Jan 1;19(2):537-551. doi: 10.7150/ijbs.69541. eCollection 2023.
ABSTRACT
Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.
PMID:36632464 | PMC:PMC9830506 | DOI:10.7150/ijbs.69541
Int J Biol Sci. 2023 Jan 1;19(2):412-425. doi: 10.7150/ijbs.77688. eCollection 2023.
ABSTRACT
Osteosarcoma is a highly mortal bone tumor, with a high metastatic potential, promoted in part by the enzyme procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2). Increasing level of PLOD2 in osteosarcoma tissue correlates with lymphatic and distant metastasis. The adipokine apelin (APLN) is also found in different cancers and APLN upregulation promotes angiogenesis and metastasis, but its effects on osteosarcoma metastasis are uncertain. We explored APLN functioning in metastatic osteosarcoma. An analysis of records from the Gene Expression Omnibus (GEO) database showed higher levels of APLN expression in osteosarcoma tissue than in normal tissue. Similarly, levels of APLN and PLOD2 mRNA synthesis were upregulated in osteosarcoma tissue. Levels of APLN and PLOD2 protein correlated positively with osteosarcoma clinical stages. APLN increased PLOD2 expression in human osteosarcoma cell lines and cell migration via the mammalian Sterile 20-like kinase 1 (MST1), monopolar spindle-one-binder protein (MOB)1, and YAP cascades, and through hsa_circ_0000004 functioning as a sponge of miR-1303. We also found that knockdown of APLN antagonized lung metastasis in mice with osteosarcoma. APLN may be a therapeutic target in osteosarcoma metastasis.
PMID:36632453 | PMC:PMC9830518 | DOI:10.7150/ijbs.77688
J Med Case Rep. 2023 Jan 12;17(1):11. doi: 10.1186/s13256-022-03719-7.
ABSTRACT
BACKGROUND: Pulmonary vein thrombosis (PVT) is rarely associated with malignancies. Leiomyosarcoma, a malignant tumor originating from smooth muscles, has never been reported as the etiology of PVT.
CASE PRESENTATION: In this case report, we described a 43-year-old Kurdish woman with a known case of leiomyosarcoma who presented with hemoptysis, dyspnea, and pleuritic chest pain. Chest computed tomography (CT) angiography revealed a thrombus in the left infero-posterior pulmonary vein. She was successfully treated with unfractionated heparin administered intravenously followed by orally administered warfarin. At the end of the article, we describe and compare other reports of malignancy-related PVT.
CONCLUSIONS: While malignancies are not a common cause of PVT, both primary lung tumors and metastatic cancers could be associated with PVT. Delay in diagnosis may lead to serious complications and even death. Therefore, clinicians should be aware of the possibility of the development of PVT in different malignancies for appropriate diagnosis and treatment.
PMID:36631902 | PMC:PMC9835261 | DOI:10.1186/s13256-022-03719-7
J Chemother. 2023 Jan 12:1-8. doi: 10.1080/1120009X.2022.2164116. Online ahead of print.
ABSTRACT
Relative dose intensity (RDI) has been associated with improved survival in patients with advanced solid tumours. However, there is no evidence regarding RDI in patients under long-term treatment with trabectedin for adult advanced soft tissue sarcoma (STS). Pegfilgrastim use was associated with chemotherapy dose intensity maintenance in patients with various cancers. We retrospectively evaluated the RDI in patients with STS receiving trabectedin. The patients were grouped based on whether trabectedin administration was supported by pegfilgrastim. RDI was obtained for 114 of the 140 included patients. Chemotherapy cycles that included filgrastim were excluded. Patients treated with and without pegfilgrastim had similar RDI rates (77.1% ± 17.6% vs 78.8% ± 16.4%; P = 0.485). Moreover, we found no association between patients receiving ≥4 trabectedin cycles and the use of pegfilgrastim. These results suggested that trabectedin dose delays or reductions should be considered before administering prophylactic pegfilgrastim.
PMID:36633925 | DOI:10.1080/1120009X.2022.2164116
Oncol Ther. 2023 Jan 12. doi: 10.1007/s40487-022-00219-y. Online ahead of print.
ABSTRACT
INTRODUCTION: Pain and fatigue are commonly reported by patients with soft tissue sarcoma (STS) as distressing symptoms, yet no patient-reported outcome (PRO) measures have been validated or developed specifically for STS. This study aimed to develop novel PRO scales using existing item banks to measure pain and fatigue in STS.
METHODS: A three-stage mixed-methods approach was used. Stage 1: a literature review examined the development and validation of the European Organization for Research and Treatment of Cancer (EORTC) library, Patient-Reported Outcomes Measurement Information System (PROMIS) pain/fatigue item banks, Functional Assessment of Cancer Therapy-General, and FACIT-Fatigue. Conceptual models were developed for pain and fatigue. Stage 2: semi-structured interviews were conducted with clinical experts (n = 3) and STS patients (n = 28) to ensure conceptual coverage and cognitively debrief the selected PRO items. Stage 3: exploratory Rasch measurement theory (RMT) analyses were performed to examine the measurement properties of the proposed scales.
RESULTS: Stage 1: The conceptual model for fatigue was organized into two overarching domains: fatigability and fatigue, further split into two subdomains: symptoms and impact. The conceptual model for pain had one overarching domain split into two subdomains: descriptors and impact. Pain (n = 56) and fatigue (n = 40) items were selected from the EORTC item library. Stage 2: qualitative findings ensured conceptual coverage, provided insight into the relevance and comprehension of the items, and informed subsequent item reduction. Stage 3: The total item number was reduced to 43 (pain n = 18, fatigue n = 25). Exploratory RMT analyses supported the final scales' psychometric properties.
CONCLUSIONS: This mixed-methods research generated important information on the experience of pain and fatigue in specific subtypes of STS. Five novel PRO scales have been developed through careful item selection in consultation with experts and supported by qualitative and quantitative evidence. These scales may be of value to future clinical trials for STS.
PMID:36633810 | DOI:10.1007/s40487-022-00219-y
Disabil Rehabil. 2023 Jan 12:1-6. doi: 10.1080/09638288.2022.2164364. Online ahead of print.
ABSTRACT
PURPOSE: Standard post-operative care following sacrectomy requiring plastic surgical reconstruction limits hip flexion and avoids wound pressure. Extended bed rest adversely affects patient function, strength and range of movement. This feasibility study assessed whether early postoperative use of the tilt table was possible and promoted faster mobilisation.
METHODS: Data from 10 patients were collected; five from a "standard tilt table group" and five from an "early tilt table group". Number of days post-operatively patients stood, walked, and were discharged was recorded.
RESULTS: Patients had undergone partial or sub-total sacrectomy with wound closure using a variety of plastic surgical techniques. The "early tilt table" group started on the tilt table at 4.8 ± 2.8 days whereas the "standard tilt table" group started at 13 ± 5.1 days (p = 0.01*). Patients in the "early tilt table group" walked significantly earlier [10.6 ± 2.7*] than the standard group (28 ± 13) (p = 0.02*). LOS in the "early" group was 37.11 ± 11.9 days compared to 58.2 ± 21.8 days in the standard group (p = 0.10). No difference in complications between the groups.
CONCLUSIONS: Early tilt table use after sacrectomy was safe and enabled a faster achievement of functional goals, thereby reducing LOS. This highlights the need for further evaluation of rehabilitation practice for this group of patients.IMPLICATIONS FOR REHABILITATIONMultidisciplinary discussion between the plastic surgeon, the tissue viability nurse and the physiotherapist about post-operative precautions and their impact on rehabilitation is essential and may enable earlier use of the tilt table.Early use of the tilt table can enable quicker mobilisation leading to the faster achievement of functional milestones and potentially a reduced length of stay (LOS) without detriment to patient outcomes/complications.The early use of the tilt table can support the central goal of surgery of enabling independence, especially as with such extensive surgery there is a big risk of institutionalisation and prolonged disability.There are potential mental health benefits to earlier mobilisation; however, this needs further investigation.
PMID:36633487 | DOI:10.1080/09638288.2022.2164364
Gastroenterol Rep (Oxf). 2022 Dec 30;11:goac083. doi: 10.1093/gastro/goac083. eCollection 2023.
ABSTRACT
With the advent of Kirsten rat sarcoma viral oncogene homologue G12C (KRAS G12C) inhibitors, RAS is no longer considered undruggable. For the suppression of RAS, new therapeutic approaches have been suggested. However, current clinical studies have indicated therapeutic resistance after short-lived tumour suppression. According to preclinical studies, this might be associated with acquired genetic alterations, reactivation of downstream pathways, and stimulation for upstream signalling. In this review, we aimed to summarize current approaches for combination therapy to alleviate resistance to KRAS G12C inhibitors in colorectal cancer with a focus on the mechanisms of therapeutic resistance. We also analysed the relationship between various mechanisms and therapeutic resistance.
PMID:36632627 | PMC:PMC9825714 | DOI:10.1093/gastro/goac083
Cancer Diagn Progn. 2023 Jan 3;3(1):107-114. doi: 10.21873/cdp.10187. eCollection 2023 Jan-Feb.
ABSTRACT
BACKGROUND/AIM: The solitary fibrous tumor (SFT) is a mesenchymal neoplasm and belongs to the group of soft tissue sarcomas. The SFT is characterized by indolent, slowly progressive growth and manifests itself clinically by compression of neighboring structures. The treatment of choice is surgical removal of the tumor. In advanced stages, there is also the possibility of chemotherapy, systemic therapy, or immunotherapy, as well as radiotherapy. Depending on their location and severity, SFTs show different recurrence rates and survival functions.
CASE REPORT: The present case report shows an extremely rare localization of a low-risk SFT in the floor of the mouth. Despite complete surgical removal of the SFT, the patient showed a metastasis of the SFT in the mandible two years postoperatively. Therefore, this case report shows that even a low-risk SFT in the localized stage can metastasize despite of total surgical removal. Consequently, SFTs of the head and neck region require close clinical and imaging follow-up.
CONCLUSION: Although the localization of the SFT in the oral cavity is a rarity, this entity should be included in the differential diagnosis in the case of long-term space-occupying processes in the head and neck region. This report is the first regarding metastasis of a SFT to the mandible.
PMID:36632580 | PMC:PMC9801440 | DOI:10.21873/cdp.10187
Oncoimmunology. 2023 Jan 7;12(1):2163784. doi: 10.1080/2162402X.2022.2163784. eCollection 2023.
ABSTRACT
Primary effusion lymphoma (PEL), an aggressive non-Hodgkin lymphoma caused by Kaposi sarcoma-associated herpesvirus (KSHV), lacks standard therapy and has a median survival of 10-22 months with combination chemotherapy. PEL is a tumor of plasmablast-like B cells generally expressing CD38, the target of daratumumab (Dara). Initially, we assessed PEL cells from eight patients and established that each expressed high levels of CD38 by flow cytometry. PEL cell lines were also evaluated and most had high CD38 expression. We then assessed Dara's effects on complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of PEL cell lines as well as its clinical benefits on two patients with PEL. Despite high CD38 expression, Dara did not induce CDC of PEL cell lines, due in part to high levels of the complement-inhibitory proteins, CD55 and CD59. However, Dara induced significant and dose-dependent increases in ADCC, particularly in those lines with high CD38 levels. Two FDA-approved drugs, all trans-retinoic acid (ATRA) and pomalidomide (Pom), significantly increased surface CD38 levels in low-CD38 expressing PEL cell lines, resulting in increased Dara-induced ADCC. Two patients with refractory PEL were treated with Dara alone or in combination with Pom. One patient with leptomeningeal PEL had a complete response to Dara and Pom combination treatment. Others had improvement in performance status and resolution of malignant ascites with Dara alone. Together, these data support the use of Dara monotherapy or in combination with ATRA or Pom as a potential therapeutic option for PEL.
PMID:36632565 | PMC:PMC9828731 | DOI:10.1080/2162402X.2022.2163784
BJR Case Rep. 2022 Nov 1;8(6):20210218. doi: 10.1259/bjrcr.20210218. eCollection 2022 Nov 1.
ABSTRACT
We present a case of upper limb muscle metastasis in a female patient with a history of malignant melanoma. Although melanoma is the fifth most common cancer in the UK, muscle metastases are extremely rare, with only a few cases reported in the literature. We discuss the challenge of diagnosing muscle metastasis on radiological imaging and in particular of distinguishing metastatic lesions to muscle from sarcoma. We also review the imaging findings of other published cases in a literature review. We conclude that although certain characteristic features of melanoma metastases can be identified on imaging (e.g., hyperintensity on T 1-weighted MRI), the radiological appearances are highly variable and histopathological examination is necessary to confirm the diagnosis.
PMID:36632557 | PMC:PMC9809911 | DOI:10.1259/bjrcr.20210218
Medicine (Baltimore). 2022 Dec 9;101(49):e32258. doi: 10.1097/MD.0000000000032258.
ABSTRACT
BACKGROUND: Osteosarcoma (OS) is a heterogeneous malignant spindle cell tumor in children under the age of 20. This study aims to research the association between Solute Carrier Family 7 Member 8 (SLC7A8) as well as related genes and OS.
METHOD: OS and normal samples (GSE38698 and GSE85537) were downloaded from Gene Expression Omnibus dataset. The bioinformatics analysis was performed to distinguish 2 differentially expressed genes, prognostic candidate genes and functional enrichment pathway. Immunohistochemistry and quantitative real-time PCR were utilized for further study.
RESULTS: There were 5 DEMs and 10 differentially expressed genes in cancer tissues compared to normal tissues. According to the km-plot software, ARHGEF3, BSN, PQLC3, and SLC7A8 were significantly related to the overall survival of patients with OS. Furthermore, Multivariate analysis included that SLC7A8 was independent risk factors for OS patients. Furthermore, immunohistochemistry and quantitative real-time PCR outcomes indicated that the expression level of SLC7A8 and hsa-miR-506 was differentially expressed in lung metastasis OS tissues and non-metastasis tissues.
CONCLUSION: The prognostic model based on the miRNA-mRNA network could provide predictive significance for prognosis of OS patients, which would be worthy of clinical application. Our results concluded that SLC7A8 may play a key role in the development of OS.
PMID:36626488 | PMC:PMC9750666 | DOI:10.1097/MD.0000000000032258
Trends Mol Med. 2023 Jan 10:S1471-4914(22)00318-5. doi: 10.1016/j.molmed.2022.12.003. Online ahead of print.
ABSTRACT
Endothelial-to-mesenchymal transition has been described in tumors as a source of mesenchymal stroma, while the reverse process has been proposed in tumor vasculogenesis and angiogenesis. A human oncogenic virus, Kaposi's sarcoma herpes virus (KSHV), can regulate both processes in order to transit through this transition 'boulevard' when infecting KS oncogenic progenitor cells. Endothelial or mesenchymal circulating progenitor cells can serve as KS oncogenic progenitors recruited by inflammatory cytokines because KSHV can reprogram one into the other through endothelial-to-mesenchymal and mesenchymal-to-endothelial transitions. Through these novel insights, the identity of the potential oncogenic progenitor of KS is revealed while gaining knowledge of the biology of the mesenchymal-endothelial differentiation axis and pointing to this axis as a therapeutic target in KS.
PMID:36635149 | DOI:10.1016/j.molmed.2022.12.003
Can J Ophthalmol. 2023 Jan 9:S0008-4182(22)00378-7. doi: 10.1016/j.jcjo.2022.12.008. Online ahead of print.
NO ABSTRACT
PMID:36634907 | DOI:10.1016/j.jcjo.2022.12.008
J Am Acad Dermatol. 2023 Jan 9:S0190-9622(23)00058-0. doi: 10.1016/j.jaad.2022.12.036. Online ahead of print.
NO ABSTRACT
PMID:36634748 | DOI:10.1016/j.jaad.2022.12.036
Ear Nose Throat J. 2023 Jan 12:1455613221141612. doi: 10.1177/01455613221141612. Online ahead of print.
ABSTRACT
A tonsillar mass in a young patient with no medical issues routinely presents as an infectious process. Practitioners must maintain a broad differential if diagnostic testing does not support an infection. Neoplasm must be excluded. Otolaryngologists must consider malignancies other than squamous cell carcinoma, the most common oropharyngeal malignancy, and lymphoma. Rare tumors, such as sarcomas, must also be considered. Otolaryngologists must be familiar with the proper management of rare oropharyngeal malignancies.
PMID:36634208 | DOI:10.1177/01455613221141612
PLoS Pathog. 2023 Jan 12;19(1):e1011080. doi: 10.1371/journal.ppat.1011080. Online ahead of print.
ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) causes the inflammatory and angiogenic endothelial cell neoplasm, Kaposi's sarcoma (KS). We previously demonstrated that the KSHV Kaposin B (KapB) protein promotes inflammation via the disassembly of cytoplasmic ribonucleoprotein granules called processing bodies (PBs). PBs modify gene expression by silencing or degrading labile messenger RNAs (mRNAs), including many transcripts that encode inflammatory or angiogenic proteins associated with KS disease. Although our work implicated PB disassembly as one of the causes of inflammation during KSHV infection, the precise mechanism used by KapB to elicit PB disassembly was unclear. Here we reveal a new connection between the degradative process of autophagy and PB disassembly. We show that both latent KSHV infection and KapB expression enhanced autophagic flux via phosphorylation of the autophagy regulatory protein, Beclin. KapB was necessary for this effect, as infection with a recombinant virus that does not express the KapB protein did not induce Beclin phosphorylation or autophagic flux. Moreover, we showed that PB disassembly mediated by KSHV or KapB, depended on autophagy genes and the selective autophagy receptor NDP52/CALCOCO2 and that the PB scaffolding protein, Pat1b, co-immunoprecipitated with NDP52. These studies reveal a new role for autophagy and the selective autophagy receptor NDP52 in promoting PB turnover and the concomitant synthesis of inflammatory molecules during KSHV infection.
PMID:36634147 | DOI:10.1371/journal.ppat.1011080
Gen Thorac Cardiovasc Surg. 2023 Jan 12. doi: 10.1007/s11748-023-01905-y. Online ahead of print.
ABSTRACT
BACKGROUND: Metastatic sarcoma confers a grave prognosis to patients and poses a management dilemma for clinicians. Pulmonary metastasectomy is frequently performed for the recurrence of sarcomatous tumours in the lung, but the evidence-base is poor. No guidelines exist to inform clinicians on appropriate patient selection and surgical technique.
AIM: This review aims to establish and analyse the most important prognostic factors for survival post pulmonary metastasectomy for recurrent sarcoma. We summarise the key tumour, peri-operative and patient characteristics that should guide surgical management.
METHODS: A comprehensive search of the literature utilising OVID Medline and PubMed databases was conducted to identify all relevant research within the past 15 years. We evaluated all articles that specifically studied sarcoma patients (both bone and soft tissue).
CONCLUSION: Disease-free interval and tumour burden remain important prognostic factors, while tumour grade is likely not significant. VATS is a safe and viable alternative to thoracotomy without sacrificing survival outcomes. No single peri-operative characteristic provides useful prognostic information in isolation.
PMID:36631707 | DOI:10.1007/s11748-023-01905-y
Histopathology. 2023 Jan 11. doi: 10.1111/his.14862. Online ahead of print.
ABSTRACT
AIMS: Soft tissue tumours are rare and both accurate diagnosis and proper treatment represent a global challenge. Current treatment guidelines also recommend review by specialized pathologists. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of soft tissue sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of international pathology and cancer organizations.
METHODS AND RESULTS: According to the ICCR's guidelines for dataset development, an international expert panel consisting of pathologists, a surgical oncologist and a medical oncologist produced a set of core and non-core data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were subspecialized soft tissue sarcoma experts and affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the datasets, which include a synoptic reporting guide, were published on the ICCR website.
CONCLUSIONS: These first international datasets for soft tissue sarcomas are aimed to promote high quality, standardized pathology reporting. Their adoption will improve consistency of reporting, facilitate multidisciplinary communication and enhance comparability of data, all of which will help to improve patient's management.
PMID:36631406 | DOI:10.1111/his.14862
Int J Gynecol Cancer. 2023 Jan 11:ijgc-2022-003800. doi: 10.1136/ijgc-2022-003800. Online ahead of print.
ABSTRACT
OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease.
METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021.
RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy.
CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.
PMID:36631151 | DOI:10.1136/ijgc-2022-003800
Lung Cancer. 2023 Jan 7;176:98-102. doi: 10.1016/j.lungcan.2023.01.004. Online ahead of print.
ABSTRACT
BACKGROUND: We reported the efficacy and safety results of high-dose, continuous-infusion Ifosfamide,in patients with advanced thymoma (TM) and thymic carcinoma (TC).
METHODS: This was a multicentric, prospective study in patients with advanced TM or TC, who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis or anti-PD(L)1 was allowed. Patients received Ifosfamide (1 g/m2/day) and sodium-2-mercaptoethanesulfonate (1 g/m2/day), as continuous infusion, via a portable pumps for 14 consecutive days. Treatment was administered every 4 weeks until progression or unacceptable toxicity, up to a maximum of 6 cycles. The primary endpoint was the overall response rate (ORR) assessed by RECIST1.1. Secondary endpoints included disease control rate (DCR), Progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: Eighteen patients were enrolled from October 2020 to January 2022. Twelve patients had a TC, 5 a TM and 1 a mixed TM/TC. Sixty-one percent of patients (11/18) had stage IVB disease according to Masaoka-Koga, and 39% (7/18) had an ECOG-PS 2. The median number of previous lines of therapy was 2 (range:1-5), and 72% (13/18) and 61% (11/18) of patients were pretreated with an anti-angiogenesis drug and an anti-PD(L)1 drug respectively. The ORR and the disease control rate (DCR) were 28 % (95 %CI: 10 %-53 %) and 67 % (95 %CI: 41 %-86 %), respectively. The median follow-up for PFS was 17.3 months (95 %CI: 4.3-NA), and median PFS was 5.4 months (95 %CI: 2.9-6.4). The median duration of response and SD was respectively 19.6 months (95 %CI: 3.5-NA) and 6.0 months (95 % CI: 3.8-6.4). In patients with TC, the ORR and DCR were 15 % (95 % CI: 2 %-45 %) and 54 % (95 % CI: 25 %-81 %), respectively. In the subgroup of 5 patients with TM, 2 PR and 3 SD were observed. Most patients had only mild (grade 1-2) AEs, the most common being nausea and vomiting (39%; 7/18) and transaminases elevation (33%; 6/18). Twenty-two percent of patients (4/18) experienced an AEs of grade 3 and required ifosfamide dose reduction. No patients had severe AEs.
CONCLUSION: High-dose continuous-infusion Ifosfamide can be considered as a valuable treatment option in patients with advanced thymic epithelial tumors.
PMID:36630822 | DOI:10.1016/j.lungcan.2023.01.004
Oral Dis. 2023 Jan 11. doi: 10.1111/odi.14499. Online ahead of print.
ABSTRACT
OBJECTIVES: To explore the predictive value of inflammatory-nutritional score (INS) and a nomogram for survivals in head and neck soft tissue sarcoma (HNSTS) patients with negative resection margins (R0).
METHODS: Clinical characteristics and hematological features of 315 HNSTS patients underwent R0 surgery were analyzed.
RESULTS: The 5-year overall survival (OS) rate, 3-year recurrence-free survival rate and disease-free survival (DFS) rate were 77.3%, 61.0% and 55.4%, respectively. High INS was associated with a deep tumor location (p<0.001), high tumor grade (p<0.001), and advanced AJCC stage (p<0.001). The low-risk group (INS 0) exhibited a higher 5-year OS rate and 3-year DFS rate than others (87.6% vs. 81.3% vs. 53.3%, p<0.001; 62.2% vs. 56.9% vs. 37.9%, p=0.007). The INS (p=0.023), tumor depth (p<0.001), pT classification (p=0.022), pN classification (p<0.001) and tumor grade (p<0.001) were independent survival predictors. Moreover, a novel nomogram for predicting OS was generated and assessed by the concordance index, exhibiting a better performance than the p7TNMG classification alone (p<0.001).
CONCLUSIONS: For R0 resected HNSTS patients, the oncological outcomes can be predicted using the INS system and a specific nomogram.
PMID:36630573 | DOI:10.1111/odi.14499
Clin Exp Dermatol. 2022 Dec 10:llac111. doi: 10.1093/ced/llac111. Online ahead of print.
ABSTRACT
The clinical features, histological subtypes and management of dermatofibrosarcoma protuberans (DFSP) are reviewed in this article. DFSP is an uncommon cutaneous sarcoma first described in 1890. It has a high local recurrence rate, low metastatic rate and low mortality. The crude incidence rate in England in 2019 was reported as 3.0 per million person-years. A fusion of platelet-derived growth factor subunit B (PDGFB) and COL1A1, t(17;22)(q22;q13), has been found in over 90% of people with DFSP. This fusion is thought to upregulate PDGFB expression, stimulating cell growth by activation of Ras mitogen-activated protein kinases and PI3K-AKT-mTOR, potentiating oncogenesis. DFSP usually presents as an asymptomatic flesh-coloured, thickened, rubbery plaque or nodule with an uneven surface. The most common sites are the trunk followed by lower limbs, head and neck and upper limbs. Larger tumours can infiltrate underlying local structures and around 1% metastasize. Key histological features in DFSP are spindle cells arranged in a storiform pattern with intense CD34 staining. Histological subtypes include classical DFSP, Bednar, myxoid, giant cell fibroblastoma, atrophic and DFSP-fibrosarcomatous. The gold standard management for localized tumours is surgical: current recommendations favour Mohs micrographic surgery over wide local excision. Adjuvant radiotherapy may be offered after surgery. Imatinib can be used as neoadjuvant therapy and in patients with inoperable or metastatic tumours. Further research should be conducted to better understand pathogenesis of DFSP, identify associated risk factors and standardize management.
PMID:36630365 | DOI:10.1093/ced/llac111
Immunotherapy. 2023 Jan 11. doi: 10.2217/imt-2022-0157. Online ahead of print.
NO ABSTRACT
PMID:36628569 | DOI:10.2217/imt-2022-0157
Int J Clin Exp Pathol. 2022 Dec 15;15(12):476-479. eCollection 2022.
ABSTRACT
Soft tissue sarcomas are mesenchymal tumors that account for about 1% of all malignancies. We retrospectively analyzed a rare case of a painful intra-muscular extraskeletal myxoid chondrosarcoma in the thigh of a 35-year-old man, that had undergone excision. Histological and immunohistochemical analysis of the mass revealed extraskeletal myxoid chondrosarcoma. The patient proceeded to radiotherapy and chemotherapy after curative surgery and had a good outcome.
PMID:36628074 | PMC:PMC9827227
Cureus. 2022 Dec 9;14(12):e32338. doi: 10.7759/cureus.32338. eCollection 2022 Dec.
ABSTRACT
Of all primary renal neoplasms, 80-85% are renal cell carcinomas (RCCs), which develop in the renal cortex. There are more than 10 histological and molecular subtypes of the disease, the most frequent of which is clear cell RCC, which also causes most cancer-related deaths. Other renal neoplasms, including urothelial carcinoma, Wilms' tumor, and renal sarcoma, each affect a particular age group and have specific gross and histological features. Due to the genetic susceptibility of each of these malignancies, early mutation discovery is necessary for the early detection of a tumor. Furthermore, it is crucial to avoid environmental factors leading to each type. This study provides relatively detailed and essential information regarding each subtype of renal carcinoma.
PMID:36627997 | PMC:PMC9825816 | DOI:10.7759/cureus.32338
Am J Case Rep. 2023 Jan 11;24:e938311. doi: 10.12659/AJCR.938311.
ABSTRACT
BACKGROUND Reports of venous stenting for inferior vena cava (IVC) syndrome (IVCS) due to sarcoma are limited, and the treatment's efficacy and safety are not clear. CASE REPORT A 36-year-old woman with myxoid liposarcoma was admitted to the Department of Respiratory Medicine for treatment of bilateral lower-leg edema and to be evaluated for acute liver dysfunction. She was 13 years old when she was diagnosed with myxoid liposarcoma. Over the next 18 years, she had 4 tumor resections and 1 round of radiation therapy. She had been on chemotherapy for 4 years and then pazopanib at the age of 35. The edema did not improve after admission despite treatment with diuretics. Computed tomography revealed a huge liposarcoma occupying the right thoracic cavity and a compressed IVC, which caused the edema. Although doxorubicin was administered as fifth-line treatment, there was no response. Since there was no additional chemotherapy regimen, her prognosis was considered to be less than 6 months. She could not be discharged to her home since she was unable to walk due to the edema; therefore, IVC stenting was performed to improve her dysmotility. After IVC stenting, the lower-leg edema improved without any adverse events, enabling her to walk and eventually return home. CONCLUSIONS In patients with IVCS caused by rare malignancies such as myxoid liposarcoma, an IVC stent can be safely implanted and can help to alleviate symptoms. IVC stenting can improve symptoms and allow for home care, resulting in improved quality of life.
PMID:36627831 | DOI:10.12659/AJCR.938311
Elife. 2023 Jan 9;12:e79432. doi: 10.7554/eLife.79432.
ABSTRACT
Chondrosarcomas are primary cancers of cartilaginous tissue and capable of alteration to highly aggressive, metastatic, and treatment-refractory states, leading to a poor prognosis with a five-year survival rate at 11 months for dedifferentiated subtype. At present, the surgical resection of chondrosarcoma is the only effective treatment, and no other treatment options including targeted therapies, conventional chemotherapies, or immunotherapies are available for these patients. Here, we identify a signal pathway way involving EZH2/SULF1/cMET axis that contributes to malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. A non-biased chromatin immunoprecipitation sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1 (SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Overexpressed EZH2 resulted in downregulation of SULF1 in chondrosarcoma cell lines, which in turn activated cMET pathway. Pharmaceutical inhibition of cMET or genetically silenced cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.
PMID:36622753 | PMC:PMC9829410 | DOI:10.7554/eLife.79432
Front Immunol. 2022 Dec 23;13:1096009. doi: 10.3389/fimmu.2022.1096009. eCollection 2022.
ABSTRACT
BACKGROUND: Glycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis and cholesterol synthesis-related genes (GCSRGs) signature for effective prognostic assessments of osteosarcoma patients.
METHODS: Gene expression data and clinical information were obtained from GSE21257 and TARGET-OS datasets. Consistent clustering method was used to identify the GCSRGs-related subtypes. Univariate Cox regression and LASSO Cox regression analyses were used to construct the GCSRGs signature. The ssGSEA method was used to analyze the differences in immune cells infiltration. The pRRophetic R package was utilized to assess the drug sensitivity of different groups. Western blotting, cell viability assay, scratch assay and Transwell assay were used to perform cytological validation.
RESULTS: Through bioinformatics analysis, patients diagnosed with osteosarcoma were classified into one of 4 subtypes (quiescent, glycolysis, cholesterol, and mixed subtypes), which differed significantly in terms of prognosis and tumor microenvironment. Weighted gene co-expression network analysis revealed that the modules strongly correlated with glycolysis and cholesterol synthesis were the midnight blue and the yellow modules, respectively. Both univariate and LASSO Cox regression analyses were conducted on screened module genes to identify 5 GCSRGs (RPS28, MCAM, EN1, TRAM2, and VEGFA) constituting a prognostic signature for osteosarcoma patients. The signature was an effective prognostic predictor, independent of clinical characteristics, as verified further via Kaplan-Meier analysis, ROC curve analysis, univariate and multivariate Cox regression analysis. Additionally, GCSRGs signature had strong correlation with drug sensitivity, immune checkpoints and immune cells infiltration. In cytological experiments, we selected TRAM2 as a representative gene to validate the validity of GCSRGs signature, which found that TRAM2 promoted the progression of osteosarcoma cells. Finally, at the pan-cancer level, TRAM2 had been correlated with overall survival, progression free survival, disease specific survival, tumor mutational burden, microsatellite instability, immune checkpoints and immune cells infiltration.
CONCLUSION: Therefore, we constructed a GCSRGs signature that efficiently predicted osteosarcoma patient prognosis and guided therapy.
PMID:36618348 | PMC:PMC9822727 | DOI:10.3389/fimmu.2022.1096009
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):87-90. doi: 10.3760/cma.j.cn112151-20220531-00477.
ABSTRACT
原发性心脏血管肉瘤(primary cardiac angiosarcoma,PCAS)十分罕见,恶性程度高,患者常表现为非特异性症状,早期诊断困难,预后差。目前对于PCAS治疗主要以手术切除为主并辅以放化疗,但远期生存情况尚不理想。了解心脏血管肉瘤的分子病理研究进展,寻找靶向治疗的可能有效靶点,是目前延长PCAS患者生存期的希望。.
PMID:36617920 | DOI:10.3760/cma.j.cn112151-20220531-00477
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):76-78. doi: 10.3760/cma.j.cn112151-20220506-00374.
ABSTRACT
子宫腺肉瘤是女性生殖道罕见的恶性肿瘤,约占子宫肉瘤的5%,腺肉瘤通常具有较低的恶性潜能,约25%的病例表现为局部复发,不到5%的病例发生远处转移。伴性索样分化的子宫腺肉瘤更为罕见,本文报道1例低级别伴性索分化的子宫腺肉瘤肺转移病例,结合国内外文献,就子宫腺肉瘤伴性索样分化的临床病理学特征、免疫表型、诊断及鉴别诊断进行探讨。.
PMID:36617916 | DOI:10.3760/cma.j.cn112151-20220506-00374
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):67-69. doi: 10.3760/cma.j.cn112151-20221027-00887.
ABSTRACT
隆突性皮肤纤维肉瘤(dermatofibrosarcoma protuberans,DFSP)是一种发生于浅表部位的局部侵袭性的低级别肉瘤,复发率高,儿童罕见。本文报道1例少见的发生于手背部的儿童DFSP。患儿男,6岁。因发现右手背侧包块1年,进行性增大3个月入院,超声示右手背皮下可见一大小约2.7 cm×2.1 cm×0.7 cm的低回声区。术后镜下观察,真皮内见短梭形瘤细胞弥漫浸润性生长,核分裂象较多见,表达CD34和bcl-2。分子检测结果:荧光原位杂交检测示COL1A1-PDGFB融合基因伴基因拷贝数增多,逆转录-聚合酶链反应及基因测序结果示COL1A1第38号外显子和PDGFB第2号外显子融合。.
PMID:36617913 | DOI:10.3760/cma.j.cn112151-20221027-00887
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):46-48. doi: 10.3760/cma.j.cn112151-20221014-00854.
ABSTRACT
目的: 探讨间叶性软骨肉瘤(mesenchymal chondrosarcoma,MC)伴横纹肌标志物异常表达的临床病理学特征。 方法: 收集福建省立医院2006年9月至2021年9月2例异常表达横纹肌标志物的MC患者的临床资料、影像学检查、病理特征,荧光原位杂交(FISH)检测NCOA2基因及二代测序检测,并复习相关文献。 结果: 例1女,34岁。例2男,19岁。2例肿瘤发生部位分别为盆腔及前列腺。镜下观察:肿瘤由未分化的小细胞和透明软骨岛构成。小细胞呈圆形、卵圆形、短梭形,排列为片状、巢状,可见血管外皮瘤样结构,2例灶性可见细胞质嗜酸性横纹肌母细胞。免疫表型:SOX9小细胞与软骨阳性,软骨细胞S-100蛋白阳性。2例横纹肌母细胞均MyoD1、Myogenin、结蛋白阳性。FISH检测均未检测到NCOA2基因分离,二代测序检测例1有HEY1-NCOA2融合基因。 结论: MC伴异常表达横纹肌标志物罕见,易误诊,诊断时需综合临床影像、病理、免疫组织化学,必要时需借助分子甚至基因检测以明确诊断。.
PMID:36617906 | DOI:10.3760/cma.j.cn112151-20221014-00854
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):13-18. doi: 10.3760/cma.j.cn112151-20221006-00832.
ABSTRACT
Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.
PMID:36617900 | DOI:10.3760/cma.j.cn112151-20221006-00832
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):3-6. doi: 10.3760/cma.j.cn112151-20221110-00943.
ABSTRACT
组织学分级是骨和软组织肉瘤指导治疗和预测肿瘤预后的关键参数之一。目前WHO推荐的骨和软组织肉瘤组织学分级方法在临床实践工作中已经使用了几十年,有效地指导了临床进行相应治疗。随着分子遗传学技术的进步和对肿瘤精准治疗需求的提升,以肉瘤复杂指数(CINSARC)为代表的分子分级方法也被大家有所重视。本文详细介绍了骨和软组织肉瘤常用的分级方法及其局限性,并就CINSARC分子分级系统的构成、应用和进展进行了讨论,以期提升临床和病理医师对骨和软组织肉瘤分子分级的理解和认识。.
PMID:36617898 | DOI:10.3760/cma.j.cn112151-20221110-00943
Molecules. 2022 Dec 22;28(1):97. doi: 10.3390/molecules28010097.
ABSTRACT
Since natural substances are widely explored as epigenetic modulators of gene expression and epigenetic abnormalities are important causes of cancerogenesis, factors with pro-tumor activities subjected to epigenetic control, e.g., neutral endopeptidase (NEP, neprilysin), are promising anticancer targets for potential therapies acting via epigenetic regulation of gene expression. Alpha-ketoglutarate (AKG) is a naturally occurring co-substrate for enzymes involved in histone and DNA demethylation with suggested anti-cancer activity. Hence, we investigated a potential effect of AKG on the NEP expression in cells derived from various cancers (cervical, colon, osteosarcoma) and normal epithelial cells and osteoblasts. Moreover, the overall methylation status of histone H3 was explored to establish the molecular target of AKG activity. Additionally, it was investigated whether AKG in combination with thiorphan (NEP specific inhibitor) exhibited enhanced anticancer activity. The results revealed that AKG downregulated the expression of NEP at the protein level only in highly aggressive osteosarcoma HOS cells (flow cytometry and fluorometric assays), and this protease was found to be involved in AKG-induced growth inhibition in osteosarcoma cells (siRNA NEP silencing, BrdU assay, flow cytometry). Unexpectedly, AKG-induced hypermethylation of H3K27 in HOS cells, which was partially dependent on EZH2 activity. However, this effect was not implicated in the AKG-induced NEP downregulation (flow cytometry). Finally, the combined treatment with AKG and thiorphan was shown to significantly enhance the growth inhibitory potential of each one towards HOS cells (BrdU assay). These preliminary studies have shown for the first time that the downregulation of NEP expression is a promising target in therapies of NEP-implicating HOS cells. Moreover, this therapeutic goal can be achieved via AKG-induced downregulation of NEP and synergistic activity of AKG with thiorphan, i.e., a NEP specific inhibitor. Furthermore, this study has reported for the first time that exogenous AKG can influence the activity of histone methyltransferase, EZH2. However, this issue needs further investigation to elucidate the mechanisms of this phenomenon.
PMID:36615293 | PMC:PMC9821816 | DOI:10.3390/molecules28010097
Int J Mol Sci. 2023 Jan 3;24(1):856. doi: 10.3390/ijms24010856.
ABSTRACT
Rhabdomyosarcoma (RMS) in adults is a rare and aggressive disease, which lacks standard therapies for relapsed or advanced disease. This retrospective study aimed to describe the activity of BOMP-EPI (bleomycin, vincristine, methotrexate and cisplatin alternating with etoposide, cisplatin and ifosfamide), an alternative platinum-based regimen, in adult patients with relapsed/metastatic RMS. In the study, 10 patients with RMS with a median age at diagnosis of 20.8 years and a female/male distribution of 6/4 received a mean of 2.5 cycles of BOMP-EPI. The best RECIST response was a complete response in 1/10 (10%) patients, a partial response in 5/10 (50%), stable disease in 3/10 (30%) and progression in 1/10 (10%). With a median follow-up in the alive patients from the start of therapy of 30.5 months (15.7-258), all patients progressed with a median progression-free survival of 8.47 months (95% CI 8.1-8.8), and 7/10 patients died with a median overall survival of 24.7 months (95% CI 13.7-35.6). BOMP-EPI was an active chemotherapy regimen in adults with pediatric-type metastatic RMS, with outcomes in terms of survival that seem superior to what was expected for this poor-prognosis population. Low HMGB1 expression level was identified as a predictive factor of better response to this treatment.
PMID:36614297 | PMC:PMC9821763 | DOI:10.3390/ijms24010856
Int J Mol Sci. 2023 Jan 3;24(1):839. doi: 10.3390/ijms24010839.
ABSTRACT
Chondrosarcoma is the second most common type of bone cancer. Surgical resection is the best choice for clinical treatment. High-grade chondrosarcoma is destructive and is more possible to metastasis, which is difficult to remove using surgery. Doxorubicin (Dox) is the most commonly used chemotherapy drug in the clinical setting; however, drug resistance is a major obstacle to effective treatment. In the present study, we compared Dox-resistant SW1353 cells to their parental cells using RNA sequencing (RNA-Seq). We found that the apelin (APLN) pathway was highly activated in resistant cells. In addition, tissue array analysis also showed that APLN was higher in high-grade tissues compared to low-grade tissues. APLN is a member of the adipokine family, which is a novel secreted peptide with multifunctional and biological activities. Previously, studies have shown that inhibition of the APLN axis may have a therapeutic benefit in cancers. However, the role of APLN in chondrosarcoma is completely unclear, and no related studies have been reported. During in vitro experiments, APLN was also observed to be highly expressed and secreted in Dox-resistant cells. Once APLN was knocked down, it could effectively improve its sensitivity to Dox. We also explored possible upstream regulatory microRNAs (miRNAs) of APLN through bioinformatics tools and the results disclosed that miR-631 was the most likely regulator of APLN. Furthermore, the expression of miR-631 was lower in the resistant cells, but overexpression of miR-631 in the Dox-resistant cell lines significantly increased the Dox sensitivity. These results were also observed in another chondrosarcoma cell line, JJ012 cells. Taken together, these findings will provide rationale for the development of drug resistance biomarkers and therapeutic strategies for APLN pathway inhibitors to improve the survival of patients with chondrosarcoma.
PMID:36614283 | PMC:PMC9820978 | DOI:10.3390/ijms24010839
Nature. 2023 Jan 10. doi: 10.1038/s41586-022-05632-x. Online ahead of print.
NO ABSTRACT
PMID:36627494 | DOI:10.1038/s41586-022-05632-x
J Neurosci. 2023 Jan 6:JN-RM-2082-22. doi: 10.1523/JNEUROSCI.2082-22.2022. Online ahead of print.
ABSTRACT
Dysregulation of pain-associated genes in the dorsal root ganglion (DRG) is considered to be a molecular basis of neuropathic pain genesis. Fused in sarcoma (FUS), a DNA/RNA-binding protein, is a critical regulator of gene expression. However, whether it contributes to neuropathic pain is unknown. This study showed that peripheral nerve injury caused by the fourth lumbar (L4) spinal nerve ligation (SNL) or chronic constriction injury of the sciatic nerve produced a marked increase in the expression of FUS protein in injured DRG neurons. Blocking this increase through microinjection of the adeno-associated virus (AAV) 5 expressing Fus shRNA into the ipsilateral L4 DRG mitigated the SNL-induced nociceptive hypersensitivities in both male and female mice. This microinjection also alleviated the SNL-induced increases in the levels of phosphorylated extracellular signal-regulated kinase ½ (p-ERK1/2) and glial fibrillary acidic protein (GFAP) in the ipsilateral L4 dorsal horn. Furthermore, mimicking this increase through microinjection of AAV5 expressing full-length Fus mRNA into unilateral L3/4 DRGs produced the elevations in the levels of p-ERK1/2 and GFAP in the dorsal horn, enhanced responses to mechanical, heat and cold stimuli, and induced the spontaneous pain on the ipsilateral side of both male and female mice in the absence of SNL. Mechanistically, the increased FUS activated the NF-κB signaling pathway by promoting the translocation of p65 into the nucleus and phosphorylation of p65 in the nucleus from injured DRG neurons. Our results indicate that DRG FUS contributes to neuropathic pain likely through the activation of NF-κB in primary sensory neurons.SIGNIFICANT STATEMENT:In the present study, we reported that FUS, a DNA/RNA-binding protein, is upregulated in injured DRG following peripheral nerve injury. This upregulation is responsible for nerve injury-induced translocation of p65 into the nucleus and phosphorylation of p65 in the nucleus from injured DRG neurons. Because blocking this upregulation alleviates nerve injury-induced nociceptive hypersensitivity, DRG FUS participates in neuropathic pain likely through the activation of NF-κB in primary sensory neurons. FUS may be a potential target for neuropathic pain management.
PMID:36627209 | DOI:10.1523/JNEUROSCI.2082-22.2022
HIV Med. 2023 Jan 10. doi: 10.1111/hiv.13455. Online ahead of print.
ABSTRACT
OBJECTIVES: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach.
METHODS: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania.
RESULTS: Among 171 patients, the median age was 9.3 years, 37% (n = 63) were female, and 87% (n = 149) had HIV. Breakdown by stage was as follows: 18% (n = 31) stage 1, 33% (n = 56) stage 2, 19% (n = 33) stage 3, and 30% (n = 51) stage 4. Age (younger stage 2 and older stage 3), severe CD4 count suppression (lower CD4 for stages 1 and 4), and presence of severe anaemia and thrombocytopenia (worse for stages 2 and 4) differed across stages. Estimated 2-year event-free survival/progression-free survival/overall survival by stage was as follows: stage 1, 81%/81%/87%; stage 2, 50%/50%/63%; stage 3, 24%/49%/81%; and stage 4, 29%/34%/54%. Sub-analysis of stage 2 lymphadenopathic KS demonstrated superior long-term 6-year event-free survival of 70% (95% confidence interval [CI] 49-83) for younger children (aged <7 years) versus 27% (95% CI 8-51) for older children.
CONCLUSIONS: This paediatric-specific staging classification categorizes patients with distinct characteristics and patterns of treatment response. This platform may guide clinicians to provide risk-stratified treatment with the hope of improving survival among children with KS.
PMID:36627111 | DOI:10.1111/hiv.13455
Medicine (Baltimore). 2022 Dec 9;101(49):e32189. doi: 10.1097/MD.0000000000032189.
ABSTRACT
To present the clinical experience of primary renal Ewing's sarcoma/primitive neuroectodermal tumors (rEWs/PNET) admitted to our hospital and systematically review the published literature. A retrospective analysis was performed on patients with pathologically confirmed renal EWs/PNET (rEWs) in our hospital, and the literature on rEWs published in PubMed and Embase databases before March 1, 2022 was searched for analysis. A total of 337 rEWs were included in the statistical analysis, including 6 cases of our patients and 331 cases published in the literature. The common clinical symptoms of rEWs are abdominal pain, hematuria, abdominal mass and so on. computed tomography (CT) plays an important role in the diagnosis of rEWs, and the typical manifestation is a large heterogeneous soft tissue density mass, with a specific "septum-like" enhancement in contrast-enhanced scan. The 2-year overall survival rate of rEWs was 48%, with a median survival time of 18 months. "Septum-like" enhancement on CT can be used as a relatively specific sign for the differential diagnosis of rEWs from Wilms tumor and neuroblastoma. The maximum diameter of the rEWs was usually greater than 10 cm, the clinical symptoms of weight loss, metastasis at diagnosis, tumor thrombogenesis of renal vein or/and inferior vena cava tumor, and the failure to undergo radical nephrectomy were the factors of poor prognosis. The incidence of primary rEWs is low and the prognosis is poor. Early diagnosis and radical nephrectomy combined with chemotherapy is the key to improve the prognosis of patients, and CT plays an important role in early diagnosis.
PMID:36626543 | PMC:PMC9750559 | DOI:10.1097/MD.0000000000032189
Medicine (Baltimore). 2022 Dec 9;101(49):e32242. doi: 10.1097/MD.0000000000032242.
ABSTRACT
RATIONALE: Angiomatosis is a rare non-neoplastic proliferative vascular lesion that typically develops during childhood or adolescence with a female predominance. Management of angiomatosis is challenging because of the manifestation of a wide variety of lesions as well as their invasive and highly recurrent nature.
PATIENT CONCERNS: We report the case of a 74-year-old man who presented with a right lower back mass that persisted for a decade. The mass progressively enlarged and had been painful in the previous month.
DIAGNOSIS: Computed tomography (CT) revealed suspected lipomatous sarcoma with invasion of the ribs, pleurae, and lung parenchyma. The final pathological examination revealed angiomatosis.
INTERVENTIONS: The patient underwent wide composite excision of the tumor along with excision of the pleura and lung nodules in the right lower and middle lobes via video-assisted thoracoscopic surgery (VAST). Fasciocutaneous rotational flap reconstruction was performed immediately after the wide composite excision and video-assisted thoracoscopic surgery (VAST).
OUTCOMES: The patient recovered uneventfully, was discharged without complications, and tolerated the daily activities well.
LESSONS: Angiomatosis is a rare benign vascular tumor that frequently mimics malignancy. Even if the patient profile does not match the reported epidemiology of this disease, differential diagnosis should be considered. Complete resection is the mainstay of treatment for the prevention of recurrence.
PMID:36626528 | PMC:PMC9750596 | DOI:10.1097/MD.0000000000032242
Medicine (Baltimore). 2022 Dec 9;101(49):e32213. doi: 10.1097/MD.0000000000032213.
ABSTRACT
The prognosis of patients with Ewing's sarcoma family of tumors (ESFT) relapse is poor; the 5-year overall survival (OS) is 13%. We evaluated the effectivity of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in adult patients with ESFT relapse. Between January 2010 and January 2021, we retrospectively analyzed 20 patients with ESFT who received HDT upon relapse. A combination of busulfan with melphalan was used as a conditioning regimen before ASCT. The median follow-up from diagnosis and from first relapse was 46.08 months (range; 10.71-186.87) and 14.41 months (range; 4.34-104.11), respectively. The median of age patients was 21.2 years (range, 17.6-25.3), and 10 (50%) patients were female. The tumor originated from the bone in 13 patients and soft tissue in 7 patients. Twelve patients had early (<2 years) relapse, and 8 patients had late (>2 years) relapse. Before HDT, 13 (65%) and 7 (35%) patients had pulmonary and extrapulmonary metastasis, respectively. After induction chemotherapy, 14 patients achieved complete response. The median OS1 and OS2 were 51.6 months (95% confidence interval [CI], range: 16.2-87) and 15.7 months (95% CI, range: 10.2-21.2), respectively. The 1-, 2-, and 5-year OS rates were 50%, 30%, and 15%, respectively. One patient died (sepsis) 1 month after ASCT. In univariate analyses, a disease-free interval (DFI) of < 2 years (P = .008) and incomplete response (P = .021) before ASCT were poor prognostic factors for OS2.HDT with ASCT can result in long-term survival of patients with ESFT relapse. HDT should be considered an important treatment opt ion in patients with a DFI > 2 years and complete response before transplantation.
PMID:36626465 | PMC:PMC9750591 | DOI:10.1097/MD.0000000000032213
Medicine (Baltimore). 2022 Dec 9;101(49):e31422. doi: 10.1097/MD.0000000000031422.
ABSTRACT
BACKGROUND: Systematic pain management of children is insufficient in China, and there is no literature on pain in children with sarcoma.
METHODS: Clinical data of 188 patients with newly diagnosed sarcoma admitted to the Medical Oncology Department of Beijing Children's Hospital was collected from October 2018 to December 2020. Children experiencing pain received analgesic treatment and regular assessment.
RESULTS: Thirty-seven patients (19.7%) suffered from pain. Six cases (16.2%) had mild pain, 17 (46.0%) moderate, and 14 (37.8%) severe. Daily lives of 31 patients were affected by pain. Twenty-six cases had bone invasion. The analgesic rate was 54.1% before admission and 89.2% after admission. Nine cases were treated with oral morphine regularly, and their pain was relieved before chemotherapy; the dose of morphine was 0.14 ± 0.034 mg/kgQ4H when the target was reached. No serious adverse reactions were observed. The period of morphine application after chemotherapy was 5 to 9 days, and there was no withdrawal reaction.
CONCLUSION: Pain in children with newly diagnosed sarcoma was mainly moderate to severe, and the incidence of pain in sarcoma with bone invasion was higher, with greater intensity. Patients who received standardized pain assessment and regular analgesics reached pain relief quickly, and no serious adverse reactions were observed within the recommended dosage.
PMID:36626440 | PMC:PMC9750675 | DOI:10.1097/MD.0000000000031422
World J Surg Oncol. 2023 Jan 9;21(1):4. doi: 10.1186/s12957-022-02883-w.
ABSTRACT
BACKGROUND: It is known that specimen collection followed by histopathological workup is the core of evidence-based medical therapy of musculoskeletal tumors. There exist many controversies about how a biopsy should be performed. While some centers recommend minimal invasive biopsy procedures, mostly the core needle biopsy (CNB), others prefer the incisional biopsy.
PURPOSE OF THE STUDY: This study aimed to determine the accuracy of incisional biopsy for malignant tumors in the musculoskeletal system. Moreover, advantages and disadvantages to other biopsy methods are discussed.
METHODS: This retrospective, single-center study about 844 incisional biopsies (benign and malignant) analysis the diagnostic accuracy of 332 malignant tumors, concerning the final histopathological result. In addition, surgical complications are analyzed to find the best way to plan and treat patients timely and correct. Secondary endpoints are the patients age, the pure operation time, as well as the type of tumor, and the subsequent therapy.
RESULTS: In summary, incisional biopsy corresponded a sensitivity of 100% for malignancy in 844 incisional biopsies and a specificity of 97.6% in 332 malignant tumors, but it features greater operative expense (incision/suture 23.5 min) and the risk of general anesthesia.
CONCLUSION: The method of biopsy should be tailored to the individual patient and the experience of the center performing the procedure.
PMID:36624456 | PMC:PMC9827702 | DOI:10.1186/s12957-022-02883-w
BMC Womens Health. 2023 Jan 9;23(1):10. doi: 10.1186/s12905-023-02161-1.
ABSTRACT
BACKGROUND: To estimate the incidence, prevalence and incidence-based mortality in patients with gynecologic sarcoma (GS), and described the trends of survival and initial treatments in the US by using the Surveillance, Epidemiology, and End Results (SEER) database.
METHODS: GS cases aged 20 years or older between 1975 and 2015 were identified from SEER 9 registries. Incidence, prevalence, and incidence-based mortality were estimated, all rates were age adjusted to the 2000 US standard population and presented as per 100,000 persons. Annual percentage change (APC) and average APC (AAPC) were calculated to describe the trends. In addition, stage distribution, cancer-specific survival (CSS) and initial treatment pattern over time were also reported.
RESULTS: The overall age-adjusted incidence of GS increased from 2.38 to 3.41 per 100,000 persons from 1975 to 2015, with an AAPC of 1.0 (P < 0.05), and the AAPC increased to 1.3 (P < 0.05) in the last decade. The incidence of population aged ≥ 55 years was three or more times than that of population aged 20-54 year from 1975 to 2015. Corpus and uterus GS was the main subtype, and it increased significantly during last three decades (an APC of 1.5). In addition, the prevalence of corpus and uterus GS increased mostly among all GSs. The incidence of GS with regional and distant stages increased pronouncedly, but not for local stage. GS cases showed increasing 3-year and 5-year CSS rates except for other sites GS. Approximately 87.7% GS cases received surgery during the first-course treatment, but the proportion decreased over years. In contrast, the proportion of receiving multiple treatment modalities increased.
CONCLUSIONS: The incidence of GS increased significantly with improved survival, which might due to the strategy of combination of multiple treatment. However, no obvious improvement on the early detection of GS was found, which should be facilitated to further improve the prognosis of GS.
PMID:36624439 | PMC:PMC9830743 | DOI:10.1186/s12905-023-02161-1
Nat Med. 2023 Jan 9. doi: 10.1038/s41591-022-02128-z. Online ahead of print.
ABSTRACT
Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies.
PMID:36624315 | DOI:10.1038/s41591-022-02128-z
J Cancer Res Clin Oncol. 2023 Jan 10. doi: 10.1007/s00432-022-04556-3. Online ahead of print.
ABSTRACT
PURPOSE: We investigated predictors of limitations in work performance, odds of drop out of work, and odds of receiving disability pension in sarcoma patients.
METHODS: We measured clinical and sociodemographic data in adult sarcoma patients and recorded if the patients received a (1) disability pension at baseline or (2) had dropped out of work 1 year after initial assessment. (3) Work limitations were assessed using the Work-limitations questionnaire (WLQ©). We analyzed exploratively.
RESULTS: (1) Amongst 364 analyzed patients, odds to receive a disability pension were higher in patients with abdominal tumors, older patients, high grade patients and with increasing time since diagnosis. (2) Of 356 patients employed at baseline, 21% (n = 76) had dropped out of work after 1 year. The odds of dropping out of work were higher in bone sarcoma patients and in patients who received additive radiotherapy ± systemic therapy compared with patients who received surgery alone. Odds of dropping out of work were less amongst self-employed patients and dropped with increasing time since diagnosis. (3) Work limitations were higher in woman and increased with age. Patients with bone and fibrous sarcomas were more affected than liposarcoma patients. Patients with abdominal tumors reported highest restrictions. Sarcoma treatment in the last 6 months increased work limitations.
CONCLUSION: Work limitations, drop out of work and dependence on a disability pension occurs frequently in patients with sarcoma adding to the burden of this condition. We were able to identify vulnerable groups in both the socioeconomic and disease categories.
PMID:36624191 | DOI:10.1007/s00432-022-04556-3
Neurocirugia (Astur : Engl Ed). 2023 Jan-Feb;34(1):22-31. doi: 10.1016/j.neucie.2022.11.005.
ABSTRACT
INTRODUCTION: Resection of malignant tumors located in the anterior and middle fossae of the skull base requires thorough anatomical knowledge, as well as experience regarding the possible reconstructive options to resolve the resulting defects. The anatomical and functional relevance of the region, the complexity of the defects requiring reconstruction and the potential complications that can occur, represent a true challenge for the surgical team. The goal of this study is to describe the microsurgical reconstructive techniques available, their usefulness and postoperative complications, in patients with malignant tumors involving the skull base.
MATERIALS AND METHOD: This observational, retrospective study, included all patients who underwent surgery for malignant craniofacial tumors from January 1st, 2009 to January 1st, 2019 at a University Hospital in Argentina. Only patients who required reconstruction of the resulting defect with a free flap were included.
RESULTS: Twenty-four patients required reconstruction with FF; 14 were male (58.3%) and mean age was 54.9 years. Sarcoma was the most frequent tumor histology. Free flaps used were the following: anterolateral thigh, rectus abdominis, radial, latissimus dorsi, iliac crest and fibular. Complications occurred in 6 cases and no deaths were reported in the study group.
CONCLUSION: Free flaps are considered one of the preferable choices of treatment for large skull base defects. In spite of the complexity of the technique and the learning curve required, free flaps have shown to be safe, with a low rate of serious complications. For these patients, the surgical resolution should be performed by a multidisciplinary team.
PMID:36623890 | DOI:10.1016/j.neucie.2022.11.005
Clin Cancer Res. 2023 Jan 9:CCR-22-3546. doi: 10.1158/1078-0432.CCR-22-3546. Online ahead of print.
ABSTRACT
PURPOSE: The optimal dose schedule of vincristine, irinotecan and temozolomide (VIT) in relapsed or refractory Ewing sarcoma patients requires clarification.
PATIENTS AND METHODS: Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter dx5 schedule (irinotecan 50mg/m2/d D1-5, vincristine 1.4mg/m2 D1) or protracted dx5x2 schedule (irinotecan 20mg/m2/d D1-5,8-12, vincristine 1.4mg/m2 D1,8) together with temozolomide (100mg/m2/d D1-5). Patients were treated every 3 weeks for up to eight cycles until progression or unacceptable toxic effects occurred. The primary endpoint was objective response rate at 12 weeks (ORR12w). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety.
RESULTS: A total of 46 patients presenting with relapsed or refractory Ewing sarcoma were randomly assigned to the dx5 (n=24) or dx5x2(n=22) schedules. Median follow-up was 10.7 months in the dx5 group and 8.3 months in the dx5x2 group. ORR12w was lower for dx5 (5/24 [20.8%]) patients than for dx5x2 (12/22[54.5%]; p=0.019), but no significant difference was found in PFS ( median PFS: 2.3 months for dx5 vs 4.3 months for dx5x2) or OS (median OS: 14.8 months for dx5 and 12.8 months for dx5x2). Patients receiving the dx5 schedule reported more grade 3 and 4 adverse events (AEs) than those receiving dx5x2, including diarrhea/abdominal pain, vomiting/nausea.
CONCLUSIONS: The protracted dx5x2 VIT schedule showed superior efficacy and favorable tolerability compared with the shorter dx5 VIT schedule in patients with relapsed or refractory Ewing sarcoma.
PMID:36622702 | DOI:10.1158/1078-0432.CCR-22-3546
Clin Cancer Res. 2023 Jan 9:CCR-22-1564. doi: 10.1158/1078-0432.CCR-22-1564. Online ahead of print.
ABSTRACT
PURPOSE: Continuous intravenous infusion (CIV) of doxorubicin (DOX), versus bolus (BOL), may minimize dose-dependent DOX cardiomyopathy, but it is unclear whether this advantage is evident as employed in typical soft tissue sarcoma (STS) treatment. The impact of administration mode on adverse events (AEs) and efficacy were compared using data from a randomized trial of DOX-based therapy (SARC021/TH CR-406).
EXPERIMENTAL DESIGN: In this post hoc analysis, CIV vs. BOL was at discretion of the treating physician. Likelihood of AEs, and objective responses were assessed by adjusted logistic regression. Progression-free (PFS) and overall survival (OS) were compared using Kaplan-Meier, log-rank test, and adjusted Cox regression.
RESULTS: DOX was administered by BOL to 556 and by CIV to 84 patients. Proportions experiencing hematologic, non-hematologic or cardiac AEs did not differ by administration mode. Hematologic AEs were associated with age, performance status, and cumulative DOX. Non-hematologic AEs were associated with age, performance status, and cumulative evofosfamide. Cardiac AEs were only associated with cumulative DOX; there was no interaction between DOX dose and delivery mode. PFS and OS were similar (median 6.14 months BOL vs. 6.11 months CIV, p=0.47; mOS 18.4 months BOL vs. 21.4 months CIV, p=0.62). PFS, OS, and objective responses were not associated with delivery mode.
CONCLUSIONS: CIV was not associated with superior outcomes over BOL within DOX dosing limits of SARC021. Cardiac AEs were associated with increasing cumulative DOX dose. While not randomized with respect to DOX delivery mode, the results indicate that continued investigation of AE mitigation strategies is warranted.
PMID:36622694 | DOI:10.1158/1078-0432.CCR-22-1564
Orbit. 2023 Jan 9:1-12. doi: 10.1080/01676830.2022.2160766. Online ahead of print.
ABSTRACT
PURPOSE: To describe a series of eight adult patients with primary orbital sarcoma and to review the existing literature on orbital sarcoma and post-irradiation sarcoma.
METHODS: Report of eight cases and literature review.
RESULTS: We report eight cases of primary orbital sarcoma, three of which were radiation-induced. Only one patient had a history of retinoblastoma. The most common presentations were painful proptosis and reduced vision. Most tumours arose in the extraconal compartment. The overall median age at diagnosis was 50 years. The pathology comprised a diverse group of tumours. Treatment and outcome varied between patients and their clinical circumstances.
CONCLUSIONS: Adult primary orbital sarcomas are rare. They can comprise a variety of tumour types and are difficult to treat. Irradiation is a significant risk factor, and the incidence of post-irradiation sarcoma of the orbit may be increasing due to the widespread use of radiotherapy and improved survival of patients with cancer. Post-irradiation sarcoma should be considered in the differential diagnosis of an orbital space-occupying lesion in a patient with a history of radiotherapy.
PMID:36622318 | DOI:10.1080/01676830.2022.2160766
Ann R Coll Surg Engl. 2023 Jan 9. doi: 10.1308/rcsann.2021.0222. Online ahead of print.
ABSTRACT
Oesophageal carcinosarcoma (OCS) is a rare oesophageal cancer, expressing both carcinomatous and sarcomatous elements. Although believed to have a better prognosis, no standard guidelines exist for its diagnosis and management. We report a case of a 60-year male presenting with progressive dysphagia and weight loss. Endoscopy and contrast-enhanced computed tomography of the chest revealed a large polypoidal intraluminal growth at the mid-oesophagus. Endoscopic biopsy revealed a sarcoma of the oesophagus. The patient underwent McKeown minimally invasive oesophagectomy. Final histopathology was suggestive of OCS. Postoperatively, the patient received adjuvant chemoradiation. At 20-month follow-up, he was asymptomatic with no radiological evidence of recurrence.
PMID:36622226 | DOI:10.1308/rcsann.2021.0222
Nanomedicine (Lond). 2023 Jan 9. doi: 10.2217/nnm-2022-0070. Online ahead of print.
ABSTRACT
Background: Despite medicinal advances, cancer is still a big problem requiring better diagnostic and treatment tools. Magnetic nanoparticle (MNP)-based nanosystems for multiple-purpose applications were developed for these unmet needs. Methods: This study fabricated novel trifunctional MNPs of Fe3O4@PLA-PEG for drug release, MRI and magnetic fluid hyperthermia. Result: The MNPs provided a significant loading of curcumin (∼11%) with controllable release ability, a high specific absorption rate of 82.2 W/g and significantly increased transverse relaxivity (r2 = 364.75 mM-1 s-1). The in vivo study confirmed that the MNPs enhanced MRI contrast in tumor observation and low-field magnetic fluid hyperthermia could effectively reduce the tumor size in mice bearing sarcoma 180. Conclusion: The nanocarrier has potential for drug release, cancer treatment monitoring and therapy.
PMID:36621896 | DOI:10.2217/nnm-2022-0070
J Surg Oncol. 2023 Jan 9. doi: 10.1002/jso.27199. Online ahead of print.
ABSTRACT
BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors for which surgical resection is the principal treatment. There is no established model to predict perioperative risks for RPS. We evaluated the association between preoperative sarcopenia, frailty, and hypoalbuminemia with surgical and oncological outcomes.
METHODS: We performed a prospective cohort analysis of 65 RPS patients who underwent surgical resection. Sarcopenia was defined as Total Psoas Area Index ≤ 1st quintile by sex. Frailty was estimated using the modified frailty index (mFI). Logistic regression models were used to assess predictors of 30-day postoperative morbidity. The Kaplan-Meier method with log-rank test was utilized to assess factors associated with overall (OS) and recurrence-free survival (RFS).
RESULT: Sarcopenia was associated with worse OS with a median of 54 compared with 158 months (p = 0.04), but no differences in RFS (p > 0.05). Hypoalbuminemia was associated with worse OS with a median of 72 compared with 158 months (p < 0.01). MFI scores were not associated with OS or RFS (p > 0.05). Sarcopenia, mFI, and hypoalbuminemia were not associated with postoperative morbidity (p > 0.05).
CONCLUSION: This study suggests that sarcopenia may be utilized as a measure of overall fitness, rather than a cancer-specific risk, and the mFI is a poor predictive measure of outcomes in RPS.
PMID:36621854 | DOI:10.1002/jso.27199
Int J Surg Case Rep. 2022 Dec 31;102:107858. doi: 10.1016/j.ijscr.2022.107858. Online ahead of print.
ABSTRACT
INTRODUCTION AND IMPORTANCE: Rhabdomyosarcoma (RMS) is a malignant tumor that arises from embryonal skeletal muscle cells. It's responsible for 3 % of cancer cases among children aged from 0 to 14 and 1 % among adolescents and young adults aged from 15 to 19. Embryonal RMS (ERMS) is the most prevalent subtype of rhabdomyosarcoma in the female genital tract. Botryoid sarcomas are a polypoid variant of ERMS. Our objective is to describe the clinical, pathological features and the treatment of a patient diagnosed with RMS botryoid of the cervix.
CASE PRESENTATION: We report a case of a 19-year-old female patient diagnosed with botryoid RMS of the cervix. The histopathological evaluation of the cervix showed a polypoid tumor lined by squamous epithelium exhibiting a large hypocellular edematous area. It was classified as group II and stage 1, according to the IRSG multicenter studies. Cervical polypectomy was performed as an oncological surgical treatment and adjuvant chemotherapy consisting of Vincristine 1.5 mg/m2/day and Actinomycin D 0.045 mg/kg/day (VA) for 45 weeks. After 6 months of follow up, she had no evidence of recurrence.
CLINICAL DISCUSSION: Cervical ERMS is a rare tumor, especially in adolescence. It's usually presents as a cervical polyp or multiple polyps. Multimodal approaches have remarkably improved the prognosis and decreased the need for radical surgery with its associated morbidity.
CONCLUSION: There are a variety of treatment strategies for a rare disease such as cervical botryoid RMS. This case was approached through fertility-conserving surgery, followed by adjuvant chemotherapy and oncological clinical follow up.
PMID:36621217 | DOI:10.1016/j.ijscr.2022.107858
Cureus. 2022 Dec 5;14(12):e32219. doi: 10.7759/cureus.32219. eCollection 2022 Dec.
ABSTRACT
Castleman's disease is a rare disorder caused by a polyclonal proliferation of B lymphocytes and plasma cells. Half of all cases of multicentric Castleman's disease are associated with HIV or Kaposi's Sarcoma. Typically, unicentric Castleman's disease presents as an enlarged thoracic lymph node but can present in multiple other body areas, such as the head and neck. This case report presents a rare large extrathoracic mass causing back pain in a 71-year-old man.
PMID:36620841 | PMC:PMC9812280 | DOI:10.7759/cureus.32219
Front Oncol. 2022 Dec 23;12:1040833. doi: 10.3389/fonc.2022.1040833. eCollection 2022.
ABSTRACT
BACKGROUND: Retroperitoneal sarcomas (RPSs) located in the lower abdominal quadrants involving iliac vessels are difficult to manage. This study introduced a 5-step method for en bloc resection with graft interposition using the abdominoinguinal approach and evaluated its efficacy and safety.
METHODS: Data of 24 consecutive patients who met the inclusion criteria from 272 patients with RPS who underwent surgical treatment between April 2015 and April 2022 were retrospectively collected and analyzed.
RESULTS: The patients underwent left- or right-sided abdominoinguinal incision. In all patients, the abdominoinguinal approach provided good exposure, and complete resection was achieved. Iliac artery+vein, vein, and artery resection and replacement by graft were performed in 70.8%, 25.0%, and 4.2% of patients, respectively. Additional resected organs mainly included the colon, ureter, bladder, kidney, and abdominal wall. The median number of organs resected was 5. In 37.5% of patients, reconstruction of the lower abdominal wall and inguinal ligament was performed using a mesh. Venous graft thrombosis occurred in 21.7% of patients, while no patient had pulmonary embolism or arterial occlusion. Major complications occurred in 20.8% of patients, and no 30-day mortality was observed. The estimated 5-year local recurrence and distant metastasis rates were 54.4% and 22.1%, respectively, with a median recurrence-free survival of 27 months.
CONCLUSIONS: En bloc resection of RPS involving iliac vessels with graft interposition using the abdominoinguinal approach is feasible and advantageous. Good complete resection rate and safety can be achieved. The long-term survival benefit of this surgical approach should be verified by further large-scale prospective controlled studies.
PMID:36620578 | PMC:PMC9816569 | DOI:10.3389/fonc.2022.1040833
Clin Case Rep. 2023 Jan 3;11(1):e6779. doi: 10.1002/ccr3.6779. eCollection 2023 Jan.
ABSTRACT
Here we present a case of metastatic PNET which arose from an immature teratoma that was refractory to standard Ewing sarcoma chemotherapy. This PNET was determined to have elevated levels of ALK protein via IHC. The patient was treated with crizotinib on a palliative basis with a sustained response.
PMID:36619485 | PMC:PMC9810838 | DOI:10.1002/ccr3.6779
Biomed Res Int. 2022 Dec 28;2022:5297235. doi: 10.1155/2022/5297235. eCollection 2022.
ABSTRACT
Sarcoma, the second common type of solid tumor in children and adolescents, has a wide variety of subtypes that are often not properly diagnosed at an early stage, leading to late metastases and causing serious loss of life and property to patients and families. It exhibits a high degree of heterogeneity at the cellular, molecular, and epigenetic levels, where DNA methylation has been proposed to play a role in the diagnosis of sarcoma subtypes. Thus, this study is aimed at finding potential biomarkers at the DNA methylation level to distinguish different sarcoma subtypes. A machine learning process was designed to analyse sarcoma samples, each of which was represented by lots of methylation sites. Irrelevant sites were removed using the Boruta method, and remaining sites related to the target variables were kept for further analyses. Afterward, three feature ranking methods (LASSO, LightGBM, and MCFS) were adopted to rank these features, and six classification models were constructed by combining incremental feature selection and two classification algorithms (decision tree and random forest). Among these models, the performance of RF model was higher than that of DT model under all three ranking conditions. The specific expression of genes obtained from the annotation of highly correlated methylation site features, such as PRKAR1B, INPP5A, and GLI3, was proven to be associated with sarcoma by publications. Moreover, the quantitative rules obtained by decision tree algorithm helped us to understand the essential differences between various sarcoma types and classify sarcoma subtypes, providing a new means of clinical identification and determining new therapeutic targets.
PMID:36619306 | PMC:PMC9812612 | DOI:10.1155/2022/5297235
Biomed Res Int. 2022 Dec 30;2022:9426623. doi: 10.1155/2022/9426623. eCollection 2022.
ABSTRACT
BACKGROUND: Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment.
OBJECTIVE: To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress.
METHODS: In this study, we examined the effectiveness of ATO and D-VC on xenograft models-AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS.
RESULTS: The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.
PMID:36619305 | PMC:PMC9822755 | DOI:10.1155/2022/9426623
J Cardiol Cases. 2022 Oct 11;27(1):41-45. doi: 10.1016/j.jccase.2022.09.013. eCollection 2023 Jan.
ABSTRACT
Cardiac sarcoma is a very rare cause of primary cardiac tumor. We present a case of an undifferentiated, pleomorphic cardiac sarcoma, masquerading as a cardiac myxoma on multimodal imaging evaluation, which was definitively diagnosed on intra-operative histopathologic examination followed by surgical resection.
LEARNING OBJECTIVE: Evaluate and diagnose a rare primary cardiac tumor via multimodal imaging and a multidisciplinary approach.
PMID:36618849 | PMC:PMC9808479 | DOI:10.1016/j.jccase.2022.09.013
Cureus. 2023 Jan 5;15(1):e33398. doi: 10.7759/cureus.33398. eCollection 2023 Jan.
ABSTRACT
Leiomyosarcomas are the least frequent primary breast sarcomas, making it an extraordinarily rare malignancy. The clinical manifestation of this entity as a fungating breast wound is, on its own, highly unusual in developed nations, mainly due to the improvement of worldwide screening programs and easier access to health care. Management of this breast wound remains challenging, and an accurate histopathological diagnosis is essential for a proper treatment plan. Thus, we present this rare case of metastatic breast leiomyosarcoma to contribute to the scarce literature regarding this disease.
PMID:36618497 | PMC:PMC9815483 | DOI:10.7759/cureus.33398
J Family Med Prim Care. 2022 Oct;11(10):6593-6597. doi: 10.4103/jfmpc.jfmpc_688_22. Epub 2022 Oct 31.
ABSTRACT
Syringocystadenoma papilliferum (SCAP) is an uncommon, benign adnexal neoplasm that occurs de novo or in an organoid nevus. It usually presents as a skin-coloured to pink, solitary, smooth, hairless plaque, verruca or nodule frequently on the scalp and forehead. SCAP may be present at unusual sites including the arm, forearm, trunk and chest. Diagnosing SCAP arising on uncommon sites is difficult owing to its varied presentation. Mostly, they are wrongly diagnosed clinically and found to be SCAP only on histopathology. We present this study of cases of SCAP with unusual location and varied presentations, which were clinically misdiagnosed. The five cases included in this study were patients attending the dermatology outpatient department in a tertiary care centre in North India. The clinical presentation and the involved sites were noted by the dermatologist, and a clinical diagnosis was made. Biopsy of the lesions was sent for histopathological examination. There are five patients in the series - four are male and one female, with age ranging from 28 to 48 years. Locations included the forearm, arm, anterior chest wall and lateral abdominal wall. The lesions clinically appeared as warty papule or nodules and one lesion appeared within a plaque, with the average duration being 5.3 years. In all five patients, the lesions were clinically suspected to be either tuberculosis verruca cutis or nodular basal cell carcinoma or dermatofibroma sarcoma protuberans (DFSP) or verruca or fibroma or pyogenic granuloma. A confirmatory diagnosis of SCAP was made for all the patients on histopathology. We are presenting five cases which were misdiagnosed clinically due to the unusual location and varied presentation to emphasise the importance of histopathology in diagnosing SCAP arising de novo, which was clinically misdiagnosed. Also, we present this case series to alert the clinicians about the likelihood of SCAP on unusual locations with varied clinical presentation.
PMID:36618202 | PMC:PMC9810847 | DOI:10.4103/jfmpc.jfmpc_688_22
Radiol Case Rep. 2022 Dec 26;18(3):943-947. doi: 10.1016/j.radcr.2022.11.077. eCollection 2023 Mar.
ABSTRACT
The first case of synovial sarcoma was published in 1893. The disease is a type of primary malignancy of the soft tissues. It is a rare and aggressive neoplasm of unknown tissue origin, characterized by strong metastatic potential and poor prognosis. The present case of a 64-year-old male patient with pain and swelling in his right shoulder and progressive loss of movement demonstrates an uncommon location for the neoplasm. Magnetic resonance proton-density fat-suppressed turbo spin-echo sequences show a heterogeneous mass in the right shoulder. The lack of homogeneity in the signal has been described in medical literature as the "triple sign" and is represented by low, intermediate, and high signal intensity areas through the neoplasm. Visible serpentine vessels spread through the tumor. There was a visible metastatic disease in the regional lymph nodes and metastatic foci in the adjacent bones. Pathological analysis of the tumor confirmed the diagnosis of biphasic synovial sarcoma. An oncological committee advised chemotherapy and radiotherapy. More prominent magnetic resonance imaging findings in synovial sarcoma that may facilitate the diagnostic process are the inhomogeneity and "triple sign" in proton density and T2 sequences, multilobulated tumors, septa, irregular borders, serpentine vascular channels, engagement of the adjacent bones and bone marrow, and involvement of the joint synovia.
PMID:36618086 | PMC:PMC9813573 | DOI:10.1016/j.radcr.2022.11.077
Zhonghua Bing Li Xue Za Zhi. 2023 Jan 8;52(1):49-51. doi: 10.3760/cma.j.cn112151-20220925-00806.
ABSTRACT
目的: 探讨胰腺骨外尤因肉瘤(extraosseous Ewing sarcoma,EES)的临床病理学特征。 方法: 收集上海交通大学医学院附属瑞金医院2019年12月至2021年12月病理诊断为胰腺EES患者3例,总结临床病理资料并进行随访及预后分析。 结果: 3例患者均为女性,发病年龄分别为24、26、40岁,平均年龄30岁。影像检查发现2例位于胰腺头部,1例位于胰腺体部;大体检查肿物与周围胰腺组织界欠清,最大径4.0~8.0 cm,切面灰白灰红、质偏软,部分伴出血及坏死。镜下肿瘤由一致的小蓝圆细胞构成,部分肿瘤细胞呈巢片状、器官样排列,个别可见少量Homer-Wright菊形团结构;高倍镜下肿瘤细胞核圆形或卵圆形、核质比高、染色质细腻、部分细胞核呈空泡状,核仁不明显,病理性核分裂象可见。免疫表型:3例肿瘤细胞波形蛋白、CD99、NKX2.2、广谱细胞角蛋白及CD56均阳性,其中CD99为弥漫膜阳性,2例bcl-2阳性,1例Fli1弱阳性,Ki-67阳性指数40%~70%。3例病例行荧光原位杂交(FISH)检测均检测到EWSR1基因重排,2例行二代测序检测,均发现EWSR1-FLI-1融合基因。随访时间0.6~2年,3例均无复发。 结论: 尤因肉瘤是一种罕见的软组织恶性肿瘤,具有经典的免疫表型及分子遗传学特征,原发于胰腺的EES非常罕见,诊断需注意与其他小圆形细胞肿瘤进行鉴别,免疫组织化学标志物及分子检测可以帮助诊断。.
PMID:36617907 | DOI:10.3760/cma.j.cn112151-20220925-00806
Neurol Res. 2023 Jan 8:1-8. doi: 10.1080/01616412.2022.2164446. Online ahead of print.
ABSTRACT
INTRODUCTION: Synovial sarcomas occurring as primary nerve tumors (SSPN) are rare and only 69 cases of SSPNs are reported in literature. Despite the little data available, SSPNs differ from other SSs in some distinctive aspects such as epidemiology, location, and early onset of symptoms. SSPN are consequently underdiagnosed and easily mistaken for benign or malignant peripheral nerve sheath tumors (PNST). Therefore, cytogenetic or molecular testing becomes essential in order to make a correct diagnosis. This article deals with an extremely rare case of monophasic SSPN of the posterior cords of the right brachial plexus. To our knowledge, this is only the tenth case of intraneural synovial sarcoma involving the brachial plexus.
CASE PRESENTATION: We report the case of a 64-year-old man, who came to our attention due to a slow-growing painful right axillary neoformation, approximately 25 mm in size. The patient did not show any neurological impairments. Ultrasonography and constrast MRI showed a heterogeneous mass arising from the posterior cord of the right brachial plexus, resembling a schwannoma. The patient underwent total resection of tumor and capsule. Histologically, a diagnosis of monophasic synovial sarcoma was made based on histologic features and the immunohistochemical profile.
CONCLUSIONS: We report a rare primary synovial sarcoma of the brachial plexus. Given its rarity, the diagnosis may be challenging and requires a core biopsy or the surgical specimen to permit immune-molecular analysis. Margin-free surgery is the mainstay of curative treatment, while chemo- or radiotherapy may have a role in advanced or margin-positive neoplasms.
PMID:36617792 | DOI:10.1080/01616412.2022.2164446
Ear Nose Throat J. 2023 Jan 8:1455613231151466. doi: 10.1177/01455613231151466. Online ahead of print.
ABSTRACT
Synovial sarcoma is a soft tissue tumor originating from mesenchymal precursor stem cells. It is usually seen in young males and lower extremities. It is only seen in 10% of head and neck region and nasopharynx which is a very unexpected location. We report a rare case treated with radiotherapy and chemotherapy.
PMID:36617705 | DOI:10.1177/01455613231151466
Pediatr Transplant. 2023 Jan 8:e14469. doi: 10.1111/petr.14469. Online ahead of print.
ABSTRACT
BACKGROUND: Kaposi sarcoma (KS) is an endothelial cell tumor, rare in children. It is 200 times more frequent after solid organ transplantation than in the general population.
METHODS: We report three cases of pediatric patients who developed KS after liver transplantation (LT).
RESULTS: Case 1, a 4-year-old boy undergoing LT due to familial intrahepatic cholestasis. Five months after LT, he presented with fever, dyspnea, and cough with enlarged lymph nodes and splenomegaly, anemia, thrombocytopenia, elevated liver enzymes, and positive EBV viral load. Lymph node biopsy diagnosed KS with an elevated HHV8 viral load. Case 2, a 4-year-old boy who underwent LT due to secondary biliary cirrhosis resulting from extrahepatic biliary atresia. Two years later, graft dysfunction was noticed with positive EBV viral load, thrombocytopenia, massive cervical lymph node enlargement, and splenomegaly. Lymph node biopsy diagnosed KS, Castleman's disease, and plasmablastic lymphoma related to HHV8 infection. Case 3, a 15-month-old girl, who received two LT due to biliary cirrhosis. Six months later, she presented with diarrhea, abdominal distension, anemia, thrombocytopenia, enlarged lymph nodes, splenomegaly, and positive CMV viral load. Axillary lymph node biopsy diagnosed KS and HHV8 infection was confirmed. In all three cases, tacrolimus was discontinued and, after diagnosis, sirolimus was started. All recovered without relapse and have a good graft function.
CONCLUSIONS: Kaposi sarcoma is a rare disease post-LT in children. Recognizing keywords and early diagnosis is crucial for timely treatment and survival.
PMID:36617693 | DOI:10.1111/petr.14469
Int J Mol Sci. 2022 Dec 30;24(1):680. doi: 10.3390/ijms24010680.
ABSTRACT
Although the overall survival of advanced soft-tissue sarcoma (STS) patients has increased in recent years, the median progression-free survival is lower than 5 months, meaning that there is an unmet need in this population. Among second-line treatments for advanced STS, eribulin is an anti-microtubule agent that has been approved for liposarcoma. Here, we tested the combination of eribulin with gemcitabine in preclinical models of L-sarcoma. The effect in cell viability was measured by MTS and clonogenic assay. Cell cycle profiling was studied by flow cytometry, while apoptosis was measured by flow cytometry and Western blotting. The activity of eribulin plus gemcitabine was evaluated in in vivo patient-derived xenograft (PDX) models. In L-sarcoma cell lines, eribulin plus gemcitabine showed to be synergistic, increasing the number of hypodiploid events (increased subG1 population) and the accumulation of DNA damage. In in vivo PDX models of L-sarcomas, eribulin combined with gemcitabine was a viable scheme, delaying tumour growth after one cycle of treatment, being more effective in leiomyosarcoma. The combination of eribulin and gemcitabine was synergistic in L-sarcoma cultures and it showed to be active in in vivo studies. This combination deserves further exploration in the clinical context.
PMID:36614121 | PMC:PMC9820645 | DOI:10.3390/ijms24010680
Int J Mol Sci. 2022 Dec 30;24(1):669. doi: 10.3390/ijms24010669.
ABSTRACT
The Kirsten rat sarcoma viral G12C (KRASG12C) protein is one of the most common mutations in non-small-cell lung cancer (NSCLC). KRASG12C inhibitors are promising for NSCLC treatment, but their weaker activity in resistant tumors is their drawback. This study aims to identify new KRASG12C inhibitors from among the FDA-approved covalent drugs by taking advantage of artificial intelligence. The machine learning models were constructed using an extreme gradient boosting (XGBoost) algorithm. The models can predict KRASG12C inhibitors well, with an accuracy score of validation = 0.85 and Q2Ext = 0.76. From 67 FDA-covalent drugs, afatinib, dacomitinib, acalabrutinib, neratinib, zanubrutinib, dutasteride, and finasteride were predicted to be active inhibitors. Afatinib obtained the highest predictive log-inhibitory concentration at 50% (pIC50) value against KRASG12C protein close to the KRASG12C inhibitors. Only afatinib, neratinib, and zanubrutinib covalently bond at the active site like the KRASG12C inhibitors in the KRASG12C protein (PDB ID: 6OIM). Moreover, afatinib, neratinib, and zanubrutinib exhibited a distance deviation between the KRASG2C protein-ligand complex similar to the KRASG12C inhibitors. Therefore, afatinib, neratinib, and zanubrutinib could be used as drug candidates against the KRASG12C protein. This finding unfolds the benefit of artificial intelligence in drug repurposing against KRASG12C protein.
PMID:36614109 | PMC:PMC9821013 | DOI:10.3390/ijms24010669
Int J Mol Sci. 2022 Dec 30;24(1):632. doi: 10.3390/ijms24010632.
ABSTRACT
The histological diagnosis of sarcoma can be difficult as it sometimes requires the combination of morphological and immunophenotypic analyses with molecular tests. A total of 2705 tissue samples of sarcoma consecutively collected from 2006 until 2020 that had undergone molecular analysis were assessed to evaluate their diagnostic utility compared with histological assessments. A total of 3051 molecular analyses were performed, including 1484 gene fusions tested by c/qRT-PCR, 992 gene rearrangements analysed by FISH, 433 analyses of the gene status of MDM2, 126 mutational analyses and 16 NGS analysis. Of the samples analysed, 68% were from formalin-fixed, paraffin-embedded tissue and 32% were from frozen tissue. C/qRT-PCR and FISH analyses were conclusive on formalin-fixed, paraffin-embedded tissue in 74% and 76% of samples, respectively, but the combination of the two methods gave us conclusive results in 96% and 89% of frozen and formalin-fixed, paraffin-embedded tissues, respectively. We demonstrate the utility of c/qRT-PCR and FISH for sarcoma diagnosis and that each has advantages in specific contexts. We conclude that it is possible to accurately predict the sarcoma subtype using a panel of different subtype-specific FISH probes and c/qRT-PCR assays, thereby greatly facilitating the differential diagnosis of these tumours.
PMID:36614077 | DOI:10.3390/ijms24010632
Int J Mol Sci. 2022 Dec 29;24(1):559. doi: 10.3390/ijms24010559.
ABSTRACT
Asparagine Synthetase Deficiency (ASNSD) is a disease caused by mutations in asparagine synthetase (ASNS). Newborns exhibit microcephaly, intractable epileptic-like seizures, progressive brain atrophy, and axial hypotonia. ASNSD results in global developmental delays and premature death. The present report describes a 9-year-old child who is a compound heterozygote with ASNS mutations c.1439C > T and c.239A > G leading to variants p.S480F and p.N80S, respectively. When grown in a complete culture medium, primary fibroblasts from the child contained ASNS mRNA and protein levels similar to an unrelated wild-type fibroblast cell line. When the child's fibroblasts were cultured for up to 72 h in a medium lacking asparagine, proliferation was reduced by about 50%. Purification of ASNS proteins harboring either the S480F or the N80S substitution had reduced enzymatic activity by 80% and 50%, respectively. Ectopic expression of either variant in ASNS-null Jensen rat sarcoma (JRS) cells did not support proliferation in the absence of medium-supplied asparagine, whereas expression of wild-type enzyme completely restored growth. These studies add to the list of pathogenic ASNS variants and use enzyme activity and protein expression in ASNS-null cells to expand our knowledge of the biological impact of mutations in the ASNS gene.
PMID:36613999 | DOI:10.3390/ijms24010559
Int J Mol Sci. 2022 Dec 23;24(1):247. doi: 10.3390/ijms24010247.
ABSTRACT
Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt's lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized.
PMID:36613688 | DOI:10.3390/ijms24010247
Int J Environ Res Public Health. 2022 Dec 21;20(1):80. doi: 10.3390/ijerph20010080.
ABSTRACT
To establish the risk of the endocrine disrupting activity of polycyclic aromatic compounds, especially oxygenated and nitrated polycyclic aromatic hydrocarbons (oxy-PAHs and nitro-PAHs, respectively), antiandrogenic and estrogenic activities were determined using chemically activated luciferase expression (CALUX) assays with human osteoblast sarcoma cells. A total of 27 compounds including 9 oxy-PAHs (polycyclic aromatic ketones and quinones) and 8 nitro-PAHs was studied. The oxy-PAHs of 7H-benz[de]anthracen-7-one (BAO), 11H-benzo[a]fluoren-11-one (B[a]FO), 11H-benzo[b]fluoren-11-one (B[b]FO), and phenanthrenequinone (PhQ) exhibited significantly the potent inhibition of AR activation. All nitro-PAHs exhibited high antiandrogenic activities (especially high for 3-nitrofluoranthene (3-NFA) and 3-nitro-7H-benz[de]anthracen-7-one (3-NBAO)), and the AR inhibition was confirmed as noncompetitive for 3-NFA, 3-NBAO, and 1,3-dinitropyrene (1,3-DNPy). Antiandrogenic activity of 3-NFA demonstrated characteristically a U-shaped dose-response curve; however, the absence of fluorescence effect on the activity was confirmed. The prominent estrogenic activity dependent on dose-response curve was confirmed for 2 oxy-PAHs (i.e., B[a]FO and B[b]FO). Elucidating the role of AR and ER on the effects of polycyclic aromatic compounds (e.g., oxy- and nitro-PAHs) to endocrine dysfunctions in mammals and aquatic organisms remains a challenge.
PMID:36612408 | DOI:10.3390/ijerph20010080
Cancers (Basel). 2023 Jan 3;15(1):315. doi: 10.3390/cancers15010315.
ABSTRACT
Orthopedic surgery and soft-tissue sarcoma (STS) both independently increase the risk of developing symptomatic venous thromboembolic events (SVTE), but there are no established risk factors or guidelines for how to prophylactically treat patients with STS undergoing surgery. The objectives of this study were to (1) identify the prevalence of SVTE in patients undergoing STS surgery, (2) identify risk factors for SVTE, and (3) determine the risk of wound complications associated with VTE prophylaxis. This retrospective study was conducted in a tertiary level, academic hospital. A total of 642 patients were treated for soft-tissue sarcoma in the lower extremity with follow up for at least 90 days for the development of SVTE such as deep venous thrombosis and pulmonary embolism. Multivariate logistic regression was used to identify predictors for these events by controlling for patient characteristics, surgical characteristics, and treatment variables, with significance held at p < 0.05. Twenty eight patients (4.36%) were diagnosed with SVTE. Multivariate analysis found six significant predictors ordered based on standardized coefficients: pre-operative (PTT) partial thromboplastin time (p < 0.001), post-operative PTT (p = 0.010), post-op chemotherapy (p = 0.013), metastasis at diagnosis (p = 0.025), additional surgery for metastasis or local recurrence (p = 0.004), and tumor size larger than 10 cm (p < 0.001). The risk of wound complications (p = 0.04) and infection (p = 0.017) increased significantly in patients who received chemical prophylaxis. Our study identifies risk factors for patients at increased risk of developing VTE. Further prospective research is necessary to identify which protocols would be beneficial in preventing SVTE in high-risk patients with a low profile of wound complications.
PMID:36612310 | DOI:10.3390/cancers15010315
Cancers (Basel). 2023 Jan 2;15(1):305. doi: 10.3390/cancers15010305.
ABSTRACT
Basal cell carcinoma (BCC) is the most common form of skin cancer, contributing to nearly a third of new cancer cases in Western countries. Most BCCs are considered low risk "routine" lesions that can either be excised through surgery or treated with chemotherapeutic agents. However, around 1-2% of BCC cases are locally aggressive, present a high risk of metastasis, and often develop chemoresistance, termed advanced BCC. There currently exists no animal model or cell line that can recapitulate advanced BCC, let alone intermediate-risk and high-risk early BCC. We previously found that aggressive BCC tumours presented a Th2 cytokine inflammation profile, mesenchymal stem cell properties, and macrophage-induced tumoral inflammation. In this study, we aimed to identify potential BCC "relatives" among solid-organ malignancies who present similar immune cell proportions in their microenvironment compositions. Using immune cell type deconvolution by CIBERSORTx, and cell type enrichment by xCell, we determined three cancers with the most similar tumour microenvironments as compared to BCC. Specifically, chromophobe renal cell carcinoma, sarcoma, and skin cutaneous melanoma presented significance in multiple cell types, namely in CD4+ T lymphocytes, gammadelta T lymphocytes, and NK cell populations. Consequently, further literature analysis was conducted to understand similarities between BCC and its "relatives", as well as investigating novel treatment targets. By identifying cancers most like BCC, we hope to propose prospective druggable pathways, as well as to gain insight on developing a reliable animal or cell line model to represent advanced BCC.
PMID:36612301 | DOI:10.3390/cancers15010305
Cancers (Basel). 2022 Dec 30;15(1):272. doi: 10.3390/cancers15010272.
ABSTRACT
We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting.
PMID:36612267 | DOI:10.3390/cancers15010272
Cancers (Basel). 2022 Dec 30;15(1):259. doi: 10.3390/cancers15010259.
ABSTRACT
Establishment of clinically annotated, molecularly characterized, patient-derived xenografts (PDXs) from treatment-naïve and pretreated patients provides a platform to test precision genomics-guided therapies. An integrated multi-OMICS pipeline was developed to identify cancer-associated pathways and evaluate stability of molecular signatures in a panel of pediatric and AYA PDXs following serial passaging in mice. Original solid tumor samples and their corresponding PDXs were evaluated by whole-genome sequencing, RNA-seq, immunoblotting, pathway enrichment analyses, and the drug-gene interaction database to identify as well as cross-validate actionable targets in patients with sarcomas or Wilms tumors. While some divergence between original tumor and the respective PDX was evident, majority of alterations were not functionally impactful, and oncogenic pathway activation was maintained following serial passaging. CDK4/6 and BETs were prioritized as biomarkers of therapeutic response in osteosarcoma PDXs with pertinent molecular signatures. Inhibition of CDK4/6 or BETs decreased osteosarcoma PDX growth (two-way ANOVA, p < 0.05) confirming mechanistic involvement in growth. Linking patient treatment history with molecular and efficacy data in PDX will provide a strong rationale for targeted therapy and improve our understanding of which therapy is most beneficial in patients at diagnosis and in those already exposed to therapy.
PMID:36612255 | DOI:10.3390/cancers15010259
Cancers (Basel). 2022 Dec 29;15(1):216. doi: 10.3390/cancers15010216.
ABSTRACT
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST.
PMID:36612211 | DOI:10.3390/cancers15010216
Cancers (Basel). 2022 Dec 27;15(1):157. doi: 10.3390/cancers15010157.
ABSTRACT
Background: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4-6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression. Methods: We performed a retrospective review of patients with LMS who underwent treatment at Stanford Cancer Center between September 2019 and May 2022. ctDNA detection was performed using a personalized, tumor-informed ctDNA assay. Genomic analysis was conducted to characterize tumor mutation burden (TMB) and known driver mutations. Results: A total of 148 plasma samples were obtained from 34 patients with uterine (N = 21) and extrauterine (N = 13) LMS (median follow-up: 67.2 (19-346.3) weeks] and analyzed for ctDNA presence. Nineteen patients had metastatic disease. The most frequently mutated driver genes across sub-cohorts were TP53, RB1, and PTEN. Patients were stratified into four sub-cohorts (A-D) based on ctDNA kinetics. ctDNA levels tracked longitudinally with progression of disease and response to therapy. Conclusion: Our results indicate that while undetectable ctDNA may suggest a lower likelihood of relapse, ctDNA positivity may indicate progressive disease, enabling closer monitoring of patients for early clinical intervention.
PMID:36612153 | DOI:10.3390/cancers15010157
Cancers (Basel). 2022 Dec 22;15(1):66. doi: 10.3390/cancers15010066.
ABSTRACT
The foundations of evidence-based practice are the triad of patient values and preferences, healthcare professional experience, and best available evidence, used together to inform clinical decision-making. Within the field of rhabdomyosarcoma, collaborative groups such as the European Paediatric Soft Tissue Sarcoma Group (EpSSG) have worked to develop evidence to support this process. We have explored many of the key research developments within this review, including patient and public involvement, decision-making research, research into areas other than drug development, core outcome sets, reporting and dissemination of research, evidence synthesis, guideline development and clinical decision rules, research of research methodologies, and supporting research in RMS.
PMID:36612064 | DOI:10.3390/cancers15010066
Cancers (Basel). 2022 Dec 22;15(1):47. doi: 10.3390/cancers15010047.
ABSTRACT
Sarcomas represent a large group of rare to very rare diseases, requiring complex management with a transdisciplinary approach. Overall progress has been hampered because of discipline, institution and network fragmentation, and there is no global data harmonization or quality standards. To report on and improve quality, a common definition of quality indicators (QIs) of sarcoma care as well as the capacity to assess longitudinal real-time data is required. An international advisory board of world-renowned sarcoma experts defined six categories of QIs, totaling more than 80 quality indicators. An interoperable (web-based) digital platform was then created combining the management of the weekly sarcoma board meeting with the sarcoma registry and incorporating patient-reported outcome measures (PROMs) into the routine follow-up care to assess the entire care cycle of the patient. The QIs were then programmed into the digital platform for real-time analysis and visualization. The definition of standardized QIs covering all physician- (diagnostics and therapeutics), patient- (PROMS/PREMS), and cost-based aspects in combination with their real-time assessment over the entire sarcoma care cycle can be realized. Standardized QIs as well as their real-time assessment and data visualization are critical to improving the quality of sarcoma care. By enabling predictive modelling and introducing VBHC, precision health care for a complex disease is on the horizon.
PMID:36612043 | DOI:10.3390/cancers15010047
Animals (Basel). 2022 Dec 21;13(1):34. doi: 10.3390/ani13010034.
ABSTRACT
A 9-year-old, 4.7 kg, spayed female Chihuahua presented with a 3.5 cm soft tissue sarcoma on the dorsal right thoracic wall. The tumor was resected, including the 11-13th ribs, resulting in a caudal dorsal thoracic wall defect. The defect was reconstructed with direct traction of part of the diaphragm dorsally, preserving the diaphragmatic attachments to the body wall, and the diaphragm was sutured to the surrounding ribs and muscles. Possible respiratory complications, including paradoxical respiration and exercise intolerance, were not observed during the perioperative or postoperative observation periods. This novel procedure is expected to be an option for caudal thoracic wall reconstruction when the diaphragmatic attachments remain intact even after the resection of the last rib. In addition, this procedure can be performed in dogs weighing <5 kg, with small pleural cavities and without respiratory disorders.
PMID:36611644 | DOI:10.3390/ani13010034