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Author(s):  
Mohamed Tantawi ◽  
Susan Shamimi-Noori ◽  
Colette M. Shaw ◽  
John R. Eisenbrey

AbstractLocoregional therapies (LRTs) are an essential management tool in the treatment of primary liver cancers or metastatic liver disease. LRTs include curative and palliative modalities. Monitoring treatment response of LRTs is crucial for maximizing benefit and improving clinical outcomes. Clinical use of contrast-enhanced ultrasound (CEUS) was introduced more than two decades ago. Its portability, cost effectiveness, lack of contraindications and safety make it an ideal tool for treatment monitoring in numerous situations. Two-dimensional dynamic CEUS has been proved to be equivalent to the current imaging standard in the guidance of LRTs, assessment of their adequacy, and detection of early tumor recurrence. Recent technical advances in ultrasound transducers and image processing have made 3D CEUS scanning widely available on most commercial ultrasound systems. 3D scanning offers a broad multiplanar view of anatomic structures, overcoming many limitations of two-dimensional scanning. Furthermore, many ultrasound systems provide real-time dynamic 3D CEUS, also known as 4D CEUS. Volumetric CEUS has shown to perform better than 2D CEUS in the assessment and monitoring of some LRTs. CEUS presents a valid alternative to the current imaging standards with reduced cost and decreased risk of complications. Future efforts will be directed toward refining the utility of 4D CEUS through approaches such as multi-parametric quantitative analysis and machine learning algorithms.


Author(s):  
Paul J Newey ◽  
John Newell-Price

Abstract Clinical Practice Guidelines for patients with Multiple Endocrine Neoplasia type 1 (MEN1) recommend a variety of surveillance options. Given progress over the past decade in this area, it is timely to evaluate their ongoing utility. MEN1 is characterized by the development of synchronous or asynchronous tumors affecting a multitude of endocrine and non-endocrine tissues, resulting in premature morbidity and mortality, such that the rationale for undertaking surveillance screening in at-risk individuals appears robust. Current guidelines recommend an intensive regimen of clinical, biochemical and radiological surveillance commencing in early childhood for those with a clinical or genetic diagnosis of MEN1, with the aim of early tumor detection and treatment. Although it is tempting to assume that such screening results in patient benefits and improved outcomes, the lack of a strong evidence base for several aspects of MEN1 care, and the potential for iatrogenic harms related to screening tests or interventions of unproven benefit, make such assumptions potentially unsound. Furthermore, the psychological, as well as economic burdens of intensive screening remain largely unstudied. Although screening undoubtedly constitutes an important component of MEN1 patient care, this perspective aims to highlight some of the current uncertainties and challenges related to existing MEN1 guidelines with a particular focus on the role of screening for pre-symptomatic tumors. Looking forward, a screening approach that acknowledges these limitations and uncertainties and places the patient at the heart of the decision-making process, is advocated.


2022 ◽  
Vol 11 ◽  
Author(s):  
Federica Recine ◽  
Alessandro De Vita ◽  
Valentina Fausti ◽  
Federica Pieri ◽  
Alberto Bongiovanni ◽  
...  

BackgroundNTRK (neurotrophic tyrosine receptor kinase)-rearranged spindle cell neoplasms are a new group of tumors included in the new 5th edition of the World Health Organization (WHO) classification of soft Tissue and Bone Sarcomas. These tumors are characterized by NTRK gene fusions and show a wide spectrum of histologies and clinical behavior. Several targeted therapies have recently been approved for tumors harboring NTRK fusions, including STS.Case PresentationA 26-year-old male with advanced, pretreated NTRK rearranged spindle cell neoplasm and liver, lung and bone metastases was treated with larotrectinib on a continuous 28-day schedule, at a dose of 100 mg twice daily. An 18FDG-PET/CT scan performed after 7 days of treatment showed tumor shrinkage in both visceral and bone lesions. There was no drug-related toxicity. Subsequent evaluations confirmed continued tumor regression in disease sites. The patient is well and continues treatment.ConclusionThe clinical and radiological response of our patient with an uncommon TPM4 (exon 7)-NTRK1 (exon 12) gene fusion tumor treated with a first-generation TRK inhibitor could contribute to a better understanding of the biology of this new STS entity and help to improve patient management.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Osman Öcal ◽  
Regina Schinner ◽  
Kerstin Schütte ◽  
Enrico N. de Toni ◽  
Christian Loewe ◽  
...  

Abstract Background The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. Methods Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. Results The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22–0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. Conclusion OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.


2022 ◽  
Vol 10 ◽  
pp. 2050313X2110679
Author(s):  
Shunsuke Yahiro ◽  
Takuya Fujimoto ◽  
Ikuo Fujita ◽  
Toshihiro Takai ◽  
Toshiko Sakuma ◽  
...  

Proximal-type epithelioid sarcoma is an aggressive malignant soft-tissue neoplasm, a “proximal” variant of epithelioid sarcoma, resistant to multimodal therapy and involved in early tumor-related death. Pertinent treatments are, therefore, continually being explored. A 24-year-old woman with nonmetastatic proximal-type epithelioid sarcoma, originating subcutaneously on the right side of the vulva, underwent surgical resection; the lesion recurred, however, leading to death 3 months after the second surgery. Here described is a case of proximal-type epithelioid sarcoma expressing L-type amino acid transporter 1 (LAT1) that transports essential amino acids and p-borono-L-phenylalanine (BPA)—the chemical compound used in boron neutron capture therapy (BNCT)—and is highly expressed in many malignant tumors. Recently, LAT1 has drawn attention, and relevant treatments have been studied—LAT1 inhibitor and BNCT. LAT1 expression in proximal-type epithelioid sarcoma may lead to cogent treatments for the disease.


2021 ◽  
Vol 23 (1) ◽  
pp. 164
Author(s):  
Guang-Yu Lian ◽  
Thomas Shiu-Kwong Mak ◽  
Xue-Qing Yu ◽  
Hui-Yao Lan

Natural killer (NK) cell is a powerful malignant cells killer, providing rapid immune responses via direct cytotoxicity without the need of antigen processing and presentation. It plays an essential role in preventing early tumor, metastasis and minimal residual disease. Although adoptive NK therapies achieved great success in clinical trials against hematologic malignancies, their accumulation, activation, cytotoxic and immunoregulatory functions are severely impaired in the immunosuppressive microenvironment of solid tumors. Now with better understandings of the tumor evasive mechanisms from NK-mediated immunosurveillance, immunotherapies targeting the key molecules for NK cell dysfunction and exhaustion have been developed and tested in both preclinical and clinical studies. In this review, we introduce the challenges that NK cells encountered in solid tumor microenvironment (TME) and the therapeutic approaches to overcome these limitations, followed by an outline of the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies, as well as promising strategies to optimize current NK-targeted immunotherapies for solid tumors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hermine Mohr ◽  
Alessia Foscarini ◽  
Katja Steiger ◽  
Simone Ballke ◽  
Christoph Rischpler ◽  
...  

AbstractPheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.


Author(s):  
Chen Xue ◽  
Xinyu Gu ◽  
Ganglei Li ◽  
Zhengyi Bao ◽  
Lanjuan Li

The dysregulation of mRNA translation is common in malignancies and may lead to tumorigenesis and progression. Eukaryotic initiation factor 4A (eIF4A) proteins are essential for translation, exhibit bidirectional RNA helicase function, and act as RNA-dependent ATPases. In this review, we explored the predicted structures of the three eIF4A isoforms (eIF4A1, eIF4A2, and eIF4A3), and discussed possible explanations for which function during different translation stages (initiation, mRNA localization, export, and mRNA splicing). These proteins also frequently served as targets of microRNAs (miRNAs) or long noncoding RNAs (lncRNAs) to mediate epithelial-mesenchymal transition (EMT), which was associated with tumor cell invasion and metastasis. To define the differential expression of eIF4A family members, we applied the Tumor Immune Estimation Resource website. We figured out that the eIF4A family genes were differently expressed in specific cancer types. We also found that the level of the eIF4A family genes were associated with abundant immune cells infiltration and tumor purity. The associations between eIF4A proteins and cancer patient clinicopathological features suggested that eIF4A proteins might serve as biomarkers for early tumor diagnosis, histological classification, and clinical grading/staging, providing new tools for precise and individualized cancer treatment.


2021 ◽  
Vol 32 (01) ◽  
pp. 03-08
Author(s):  
Adeel Niaz ◽  
Muhammad Iqbal ◽  
Muhammad Ilyas ◽  
Ghulam Dastgir Khan ◽  
Riaz Ahmed Shahid ◽  
...  

ABSTRACT Introduction: Juvenile nasopharyngeal angiofibroma is a benign vasculartumor.It is commonly found in teen age males. Its site of origin is sphenopalatine foramen. Exact pathogenesis of angiofibroma is not known. It has predictable natural history and growth pattern. This tumor most often involves nasopharynx, nasal cavity, paranasal sinuses, pterygopalatine fossa and infratemporal fossa. It can also involve orbit and can spread intracranially. Its very important to diagnose this tumor very early on the basis of clinical examination and imaging. As early tumor confined to nose and sinuses can be removed exclusively with endoscope. It is very helpful to do angiography before surgery to ascertain itsblood supply and then embolization can be done to reduce intraoperative bleeding. Objective: To describe our experience of Juvenile Nasopharyngeal Angiofibroma cases in ENT Unit-I of Lahore General Hospital. Study Design: Descriptive Study with retrospective analysis after approval from Institutional Review Board (IRB) of LGH/PGMI/AMC Lahore. Methods: We studied 20 patients who underwent surgery in our department from October 2019 to October 2020. We analyzed following factors: age, gender, symptoms, staging, mode of surgery and need for intraoperative blood transfusion, hospital stay, complications and recurrences. Results: Range of patient’s age was 12 to 25 years. Eight patients underwent surgery with endoscope. Mean blood loss was about 400 ml and mean operating time was 140 minutes. All the cases were embolized preoperatively. Conclusion: Endoscopic surgery is a safe and effective method in early stage JNA patients. While patients with advance stage tumors should be managed with combined endoscopic and conventional open approaches. KEYWORDS: juvenile nasopharyngeal angiofibroma, JNA, endoscopic surgery  


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