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RATIONALE AND OBJECTIVES: The role of lactate dehydrogenase A (LDHA) expression in differentiated thyroid cancer (DTC), especially in radioiodine-refractory DTC, remains unclear. The aim of this study was to analyse the relationships and the prognostic value of LDHA, glycolysis, and radioactive iodine (RAI) avidity in DTC. METHODS: DTC patients who underwent 18F-FDG PET/CT and subsequent total thyroidectomy or metastasectomy were enroled. The expression levels of LDHA, glucose transporters (Glut) and Ki67 proteins in tumour tissue were measured using immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT were measured. A radioiodine whole body scan was used to determine lesion radioiodine avidity. RESULTS: 69 patients with DTC were enroled in this study, including 37 women (53.6%) and 32 men (46.4%), with a median age of 52 years (11 to 77 years). Regarding the pathological category, papillary thyroid cancer was documented in 50 patients (72.5%), while follicular and poorly differentiated thyroid cancer were found in 12 patients (17.4%) and seven patients (10.1%), respectively. Distant metastases were observed in 27 (39.1%) patients; 34 (49.3%) were classified as stage I, 16 (23.2%) as stage II, and 3 (4.3%) and 16 (23.2%) patients in stages III and IV, respectively. LDHA expression levels were correlated with Glut3 expression levels (r = 0.395, P = 0.003) and SUVmax (r = 0.408, P = 0.002). The median LDHA expression and lesion SUVmax of the RAI avidity group were lower than those of the non-RAI avidity group (200 vs. 285, P = 0.036; 3.06 vs. 8.38, P = 0.038, respectively). Elevated SUVmax (P = 0.004), MTV (P = 0.014), TLG (P = 0.001) and LDHA expression (P = 0.048) led to shorter time to progression (TTP); Cox regression analysis revealed that TLG (HR: 4.773, P = 0.047) was an independent prognostic factor of TTP. CONCLUSION: Elevated LDHA is correlated with increased glucose metabolism, decreased radioiodine avidity, and accelerated disease progression. Moreover, 18F-FDG PET/CT acting as "in vivo pathology" is an excellent predictor of DTC prognosis.
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INTRODUCTION: It is important to explore strategies reducing the number of SB cores taken to minimize biopsy-related morbidity and patient's discomfort during biopsy. This study aims to optimize prostate biopsy procedures by reducing the number of systematic biopsy (SB) cores while preserving cancer detection rates in the era of combined biopsy. PATIENTS AND METHODS: We prospectively recruited patients with ≥1 magnetic resonance imaging (MRI) lesions and they underwent transperineal combined 12-core SB+3-core targeted prostate biopsy (TB, reference standard). New strategy was defined as a laterally 6-core SB+3-core TB. Patients were served as their own control. Detection rates for overall prostate cancer (PCa) and clinically significant PCa (csPCa) were compared among the standard SB, MRI-TB, 6-core SB +3-core TB, and reference standard. Pathology consistency was assessed using the Kappa test. RESULTS: A total of 204 men were included, of which 111 (54.41%) and 92 (45.10%) harbored overall PCa and csPCa. Referenced combined biopsy detected significantly 6.86% (P = .0005) or 4.90% (P = .0044) more csPCa than performing only SB or 3-core TB, but was comparable to the new biopsy strategy. (45.10% vs. 43.14%, P = .1336) Similar results persisted when limiting patients in biopsy-naïve men or stratified by Prostate Imaging Reporting and Data System scores, PSAD, and index lesion parameters. Additionally, performing 6-core SB+3-core TB demonstrated high consistency with reference standard in grade group distribution (Kappa coefficient: 0.952 for all, 0.961 for biopsy-naïve men) and achieved superior sensitivity of 95.7% (All: 95% CI: 89.2%-99.8%) and 96.9% (Biopsy-naïve: 95% CI: 91.1%-99.7%), respectively. CONCLUSIONS: The 6-core SB+3-core TB approach maintains expected detection rates while reducing the total core count, offering a promising alternative to the reference standard, which may help to tailor transperineal combined biopsy procedures.
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Biopsia Guiada por Imagen , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Persona de Mediana Edad , Biopsia Guiada por Imagen/métodos , Estudios Prospectivos , Biopsia con Aguja Gruesa/métodos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Próstata/patología , Próstata/diagnóstico por imagen , Ultrasonografía Intervencional/métodosRESUMEN
Variations in the tumor genome can result in allelic changes compared to the reference profile of its homogenous body source on genetic markers. This brings a challenge to source identification of tumor samples, such as clinically collected pathological paraffin-embedded tissue and sections. In this study, a probabilistic model was developed for calculating likelihood ratio (LR) to tackle this issue, which utilizes short tandem repeat (STR) genotyping data. The core of the model is to consider tumor tissue as a mixture of normal and tumor cells and introduce the incidence of STR variants (φ) and the percentage of normal cells (Mxn) as a priori parameters when performing calculations. The relationship between LR values and φ or Mxn was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had Log 10(LR) values greater than 1014. In the non-contributor test, 99.9% of the quartiles had Log 10(LR) values less than 0. When the defense's hypothesis took into account the possibility that the tumor samples came from the patient's relatives, LR greater than 0 was still obtained. Furthermore, this study revealed that LR values increased with decreasing φ and increasing Mxn. Finally, LR interval value was provided for each tumor sample by considering the confidence interval of Mxn. The probabilistic model proposed in this paper could deal with the possibility of tumor allele variability and offers an evaluation of the strength of evidence for determining tumor origin in clinical practice and forensic identification.
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[This corrects the article DOI: 10.3389/fonc.2022.934291.].
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Prostatic malakoplakia (PMP) is a rare inflammatory disease, and misdiagnosis on imaging is a major reason for unnecessary punctures; however, information on imaging is even rarer. Five patients with PMP between May 2022 and February 2023 were enrolled in this study to summarize the imaging manifestations. All patients underwent ultrasound (US)-guided prostate biopsy and were confirmed by pathology, and the presence of prostate cancer was also excluded by pathology. The five patients, with a median age of 71 years (range = 58-74 years), had a median total prostate-specific antigen (T-PSA) of 10.40 ng/mL (range = 1.74-63.42 ng/mL). In two patients, chest computed tomography showed pulmonary infections. All patients underwent magnetic resonance imaging (MRI). Of these patients, four had a Prostate Imaging-Reporting and Data System (PIRADS) score of 5, while one had a score of 4. The lesions were mostly distributed in the peripheral zone of the prostate and appeared as a high signal on T1-weighted imaging (T1WI) and a low signal on T2-weighted imaging (T2WI). In the US examination, four patients had abnormal prostate morphology, with an unsmooth envelope and non-uniform parenchymal echogenicity. Four patients had increased prostate volume. US showed a hypoechoic nodule with non-uniform internal echogenicity, and an abundant internal blood flow signal was detected by color Doppler US. PSA, MRI, and US were not specific for PMP in our study, but we found that a history of co-infection may be helpful in an accurate diagnosis and to avoid unnecessary biopsy.
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As a new diagnosis and treatment decision-making model, shared decision making (SDM) can effectively solve the problem of patient compliance in the diagnosis and treatment of thoracic tumors, balance the status of both doctors and patients, and gradually get attention and application in the clinical practice of thoracic surgery. The application of SDM in the diagnosis and treatment of thoracic tumors is conducive to improve doctors' diagnosis and treatment level and alleviating the pressure of responsibility, reduce patients' psychological pressure and improve patients' compliance and also improve medical trust and reduce doctor-patient conflict. Due to the limited medical literacy and autonomy of patients, the time for diagnosis and treatment is short due to the imbalance of doctor-patient ratio. Meanwhile, due to the limited sample size of existing studies, SDM model cannot be proved to have a clear gain for the treatment of thoracic tumors, and the implementation of SDM model still faces resistance. In the future, the development of auxiliary decision-making system and the improvement of doctors' humanistic care ability will be conducive to promote the practical application of SDM model in thoracic surgery.â©.
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Neoplasias Pulmonares , Médicos , Humanos , Toma de Decisiones Conjunta , Toma de Decisiones , Relaciones Médico-PacienteRESUMEN
PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. RESULTS: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.
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Carcinoma de Células Renales , Fumarato Hidratasa , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Fumarato Hidratasa/deficiencia , Fumarato Hidratasa/genética , Masculino , Femenino , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Persona de Mediana Edad , Anciano , Adulto , Activación de Linfocitos/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Memoria Inmunológica , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inmunoterapia/métodos , Células T de Memoria/inmunología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.