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Women with type 2 diabetes (T2D) have a higher risk of being diagnosed with breast cancer and have worse survival than non-diabetic women if they do develop breast cancer. However, more research is needed to elucidate the biological underpinnings of these relationships. Here, we found that forkhead box A1 (FOXA1), a forkhead family transcription factor, and metformin (1,1-dimethylbiguanide hydrochloride), a medication used to treat T2D, may impact hormone-receptor-positive (HR+) breast cancer (BC) tumor cell growth and metastasis. Indeed, fourteen diabetes-associated genes are highly expressed in only three HR+ breast cancer cell lines but not the other subtypes utilizing a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Notably, elevated FOXA1 expression correlated with poorer overall survival in patients with estrogen-receptor-positive/progesterone-receptor-positive (ER+/PR+) breast cancer. Furthermore, experiments demonstrated that loss of the FOXA1 gene inhibited tumor proliferation and invasion in vitro using MCF-7 and T47D HR+ breast cancer cell lines. Metformin, an anti-diabetic medication, significantly suppressed tumor cell growth in MCF-7 cells. Additionally, either metformin treatment or FOXA1 gene deletion enhanced tamoxifen-induced tumor growth inhibition in HR+ breast cancer cell lines within an ex vivo three-dimensional (3D) organoid model. Therefore, the diabetes-related medicine metformin and FOXA1 gene inhibition might be a new treatment for patients with HR+ breast cancer when combined with tamoxifen, an endocrine therapy.
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Neoplasias da Mama , Proliferação de Células , Fator 3-alfa Nuclear de Hepatócito , Metformina , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Metformina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Invasividade Neoplásica , Células MCF-7 , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genéticaRESUMO
INTRODUCTION: Recent classification of neuroendocrine neoplasms has defined well-differentiated high-grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens. MATERIALS AND METHODS: This was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients' demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression-free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). RESULTS: Treatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki-67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum-etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96-16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months. CONCLUSION: Among patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short-lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy. IMPLICATIONS FOR PRACTICE: High-grade well-differentiated neuroendocrine tumors (NET G3) are considered a different entity from low-grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well-differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.
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Tumores Neuroendócrinos , Capecitabina , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The current diagnosis of infective endocarditis (IE) is based on the modified Duke criteria, which has approximately 80% sensitivity for the diagnosis of native valve endocarditis (NVE), with lower sensitivity for the diagnosis of prosthetic valve endocarditis (PVE) and culture-negative endocarditis. There is preliminary evidence that 18F-FDG PET/CT is an adjunctive diagnostic test with high accuracy reported in small studies to date. We therefore performed a meta-analysis of studies evaluating the use of PET/CT in the diagnosis of IE to establish a more precise estimate of accuracy. METHODS: PubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov were searched from January 1990 to April 2017 for studies evaluating the accuracy of PET/CT for the evaluation of possible IE. RESULTS: We identified 13 studies involving 537 patients that were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of IE was 76.8% (95% CI 71.8-81.4%; Q = 39.9, P < 0.01; I2 = 69.9%) and the pooled specificity was 77.9% (95% CI 71.9-83.2%; Q = 44.42, P < 0.01; I2 = 73.0%). Diagnostic accuracy was improved for PVE with sensitivity of 80.5% (95% CI 74.1-86.0%; Q = 25.5, P < 0.01; I2 = 72.5%) and specificity of 73.1% (95% CI 63.8-81.2%; Q = 32.1, P < 0.01; I2 = 78.2%). Additional extracardiac foci of infection were found on 17% of patients on whole body PET/CT. CONCLUSION: PET/CT is a useful adjunctive diagnostic tool in the evaluation of diagnostically challenging cases of IE, particularly in prosthetic valve endocarditis. It also has the potential to detect clinically relevant extracardiac foci of infection, malignancy, and other sources of inflammation leading to more appropriate treatment regimens and surgical intervention.
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Endocardite/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: We performed a meta-analysis evaluating the use of fluorine-18-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in the diagnosis of cardiovascular implantable electronic device (CIED) infections. BACKGROUND: PET/CT may be helpful in the diagnosis of CIED infection, particularly in patients with the absence of localizing signs or definitive echocardiographic findings. METHODS: PubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov from January 1990 to April 2017 were searched for studies evaluating the accuracy of PET/CT in the diagnosis of CIED infections. RESULTS: Overall, 14 studies involving 492 patients were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of CIED infection was 83% (95% CI 78%-86%) and the pooled specificity was 89% (95% CI 84%-94%). PET/CT demonstrated a higher sensitivity of 96% (95% CI 86%-99%) and specificity of 97% (95% CI 86%-99%) for diagnosis of pocket infections. Diagnostic accuracy for lead infections or CIED-IE was lower with pooled sensitivity of 76% (95% CI 65%-85%) and specificity of 83% (95% CI 72%-90%). CONCLUSION: Use of PET/CT in the evaluation of CIED infection has both a high sensitivity (83%) and specificity (89%) and deserves consideration in the management of selected patients with suspected CIED infections.
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Desfibriladores Implantáveis/efeitos adversos , Endocardite/diagnóstico por imagem , Fluordesoxiglucose F18 , Marca-Passo Artificial/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Infecções Relacionadas à Prótese/diagnóstico por imagem , Endocardite/etiologia , Humanos , Infecções Relacionadas à Prótese/etiologia , Compostos RadiofarmacêuticosRESUMO
OBJECTIVE: Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS: Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS: Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION: PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis from squamous cell carcinoma and nonsquamous cell carcinoma metastasis.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Parotídeas/metabolismo , Neoplasias Parotídeas/cirurgia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga TumoralRESUMO
Background: Many patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information. Purpose: To evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel 177Lu-PSMA-617 therapy for prostate cancer. Materials and methods: Two experts listed the 12 most commonly asked questions by patients on 177Lu-PSMA-617 therapy. These twelve questions were prompted to OpenAI ChatGPT-4 and Google Bard. AI-generated responses were distributed using an online survey platform (Qualtrics) and blindly rated by eight experts. The performances of the AI chatbots were evaluated and compared across three domains: accuracy, conciseness, and readability. Additionally, potential safety concerns associated with AI-generated answers were also examined. The Mann-Whitney U and chi-square tests were utilized to compare the performances of AI chatbots. Results: Eight experts participated in the survey, evaluating 12 AI-generated responses across the three domains of accuracy, conciseness, and readability, resulting in 96 assessments (12 responses x 8 experts) for each domain per chatbot. ChatGPT-4 provided more accurate answers than Bard (2.95 ± 0.671 vs 2.73 ± 0.732, p=0.027). Bard's responses had better readability than ChatGPT-4 (2.79 ± 0.408 vs 2.94 ± 0.243, p=0.003). Both ChatGPT-4 and Bard achieved comparable conciseness scores (3.14 ± 0.659 vs 3.11 ± 0.679, p=0.798). Experts categorized the AI-generated responses as incorrect or partially correct at a rate of 16.6% for ChatGPT-4 and 29.1% for Bard. Bard's answers contained significantly more misleading information than those of ChatGPT-4 (p = 0.039). Conclusion: AI chatbots have gained significant attention, and their performance is continuously improving. Nonetheless, these technologies still need further improvements to be considered reliable and credible sources for patients seeking medical information on 177Lu-PSMA-617 therapy.
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Treatment with 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after 177Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing 177Lu-PSMA-617 therapy. Methods: The clinical records and imaging data of patients who received their initial dose of 177Lu-PSMA-617 between March 2022 and November 2022 were retrospectively reviewed. All patients presenting for medical evaluation, regardless of specific specialty appointments, with new or worsening neurologic symptoms were included in the study. Results: A total of 185 patients underwent 177Lu-PSMA-617 therapy. The median age was 70 y (range, 58-90 y). The mean follow-up time was 12.04 ± 2.87 mo. Fifty-five new or worsening neurologic symptoms were observed in 50 patients (27%, 50/185). Of these, 27 (11.9%, 27/185) reported altered taste. Eleven patients (6%, 11/185) experienced dizziness with no other clear etiology; 2 of these patients were admitted to the emergency department (ED). Paresthesia symptoms were reported in 6 patients (3.2%, 6/185). Five patients (2.7%, 5/185) reported headaches, 3 of these patients were admitted to the ED because of the severity of the symptoms. Two patients (1.08%, 2/185) presented with extremity weakness. Two patients (1.08%, 2/185) had an ischemic stroke and were admitted to the ED. One patient (0.05%, 1/185) exhibited gait disturbances. In total, 7 patients (3.78%, 7/185) were admitted to the ED because of neurologic symptoms. None of the patients discontinued or failed to complete the 177Lu-PSMA-617 therapy because of neurologic symptoms. Conclusion: After 177Lu-PSMA-617 treatment, the most common neurologic symptoms were dysgeusia and dizziness. In this study, our follow-up period and population size might not have been sufficient to detect delayed or uncommon neurologic symptoms. In patients without neurologic symptoms or central nervous system metastases before treatment, we found the development of severe neurologic problems to be rare and unlikely to require discontinuation of treatment.
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The field of theranostics is rapidly advancing, driven by the goals of enhancing patient care. Recent breakthroughs in artificial intelligence (AI) and its innovative theranostic applications have marked a critical step forward in nuclear medicine, leading to a significant paradigm shift in precision oncology. For instance, AI-assisted tumor characterization, including automated image interpretation, tumor segmentation, feature identification, and prediction of high-risk lesions, improves diagnostic processes, offering a precise and detailed evaluation. With a comprehensive assessment tailored to an individual's unique clinical profile, AI algorithms promise to enhance patient risk classification, thereby benefiting the alignment of patient needs with the most appropriate treatment plans. By uncovering potential factors unseeable to the human eye, such as intrinsic variations in tumor radiosensitivity or molecular profile, AI software has the potential to revolutionize the prediction of response heterogeneity. For accurate and efficient dosimetry calculations, AI technology offers significant advantages by providing customized phantoms and streamlining complex mathematical algorithms, making personalized dosimetry feasible and accessible in busy clinical settings. AI tools have the potential to be leveraged to predict and mitigate treatment-related adverse events, allowing early interventions. Additionally, generative AI can be utilized to find new targets for developing novel radiopharmaceuticals and facilitate drug discovery. However, while there is immense potential and notable interest in the role of AI in theranostics, these technologies do not lack limitations and challenges. There remains still much to be explored and understood. In this study, we investigate the current applications of AI in theranostics and seek to broaden the horizons for future research and innovation.
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Inteligência Artificial , Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Neoplasias/diagnóstico , Neoplasias/terapia , Algoritmos , Nanomedicina Teranóstica/métodos , Nanomedicina Teranóstica/tendênciasRESUMO
BACKGROUND: The anti-estrogen tamoxifen is a highly effective hormonal therapy for hormonal-positive (HR+) breast cancer patients; however, the estrogen receptor-negative, progesterone receptor-positive (ER-/PR+) subtype does not give the benefits of tamoxifen. Therefore ER-/PR+ breast cancer has a poor clinical outcome, and novel drug therapy for ER-/PR+ breast cancer could benefit these patients. METHODS: 53,805 gene expressions were characterized into HR+ BC and triple-negative breast cancer (TNBC) and analyzed through Breast Cancer Gene Expression Miner in 4319 breast cancer patient samples. The clinical outcomes including overall survival, distant metastasis-free survival, and relapse-free survival were obtained from the PrognoScan database containing 1190 human breast cancer patient samples. To determine the function of ERα and inflammation-related genes such as USP1, CDC20, and CASP1, we used the CRISPR-Cas9 system or gene knockdown (KD) system. To check tumor cell proliferation and migration of ERα KO breast cancer cell line, we used tamoxifen and the inflammation inhibitor Ac-YVAD-CHO. For further confirmation, cancer growth was checked with the inflammation inhibitor in ERα KO breast cancer cell line using a three-dimensional (3D) organoid tissue culture system (ex vivo). RESULTS: We found that gene expression in ER-/PR+ hormonal-positive breast cancer is positively related to ER-/PR- very similar to TNBC, not other HR+ breast cancer using a 4319 breast cancer patient database. Especially, inflammation-related genes, USP1, CDC20, and CASP1, which are highly expressed in TNBC, are also upregulated in ER-/PR+ HR+ breast cancer. Suppression of USP1, CDC20, and CASP1 inhibited tumor cell growth and metastasis in ERα KO (ER-/PR +) cell lines. Interestingly, loss of ERα in HR+ cell lines is not responsive to tamoxifen, but highly sensitive to the inflammation inhibitor, Ac-YVAD-CHO. In in vitro and ex vivo (3D organoid) models, inflammation inhibitor-specific blocks ER-/PR+ tumor proliferation and migration. CONCLUSIONS: These findings suggest that an inflammation inhibitor might be a potential option for therapy for ER-/PR+ HR breast cancer patients.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Receptores de Estrogênio/metabolismo , Inflamação/tratamento farmacológico , Receptores de Progesterona/metabolismo , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêuticoRESUMO
Radioligand therapy (RLT) with [177Lu]Lu-DOTA-TATE is a standard of care for adult patients with somatostatin-receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Taking advantage of this precision nuclear medicine approach requires diligent monitoring and surveillance, from the use of diagnostic SSTR-targeted radioligand imaging for the selection of patients through treatment and assessments of response. Published evidence-based guidelines assist the multidisciplinary healthcare team by providing acceptable approaches to care; however, the sheer heterogeneity of GEP-NETs can make these frameworks difficult to apply in individual clinical circumstances. There are also contradictions in the literature regarding the utility of novel approaches in monitoring and surveilling patients with GEP-NETs receiving RLT. This article discusses the emerging evidence on imaging, clinical biochemistry, and tumor assessment criteria in the management of patients receiving RLT for GEP-NETs; additionally, it documents our own best practices. This allows us to offer practical guidance on how to effectively implement monitoring and surveillance measures to aid patient-tailored clinical decision-making.
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Diabetes mellitus (DM) is one of the most researched metabolic diseases worldwide. It leads to extensive complications such as cardiovascular disease, nephropathy, retinopathy, and peripheral and central nervous system through an inability to produce or respond to insulin. Although oxidative stress-mediated mitophagy has been reported to play an important role in the pathogenesis of DM, specific studies are still lacking as well as remain highly controversial. Here, we found that Parkin-mediated mitophagy in pancreatic ß cells under streptozotocin (STZ)-diabetic stress was induced by Polo-like kinase 3 (Plk3) and inhibited by the transcription factor Forkhead Box O3A (FOXO3A). STZ stress induces mitochondrial recruitment of Parkin through Plk3-mediated mitochondrial reactive oxygen species (ROS) generation, which causes pancreatic cell damage. Conversely, FOXO3A acts as negative feedback to prevent diabetic stress by inhibiting Plk3. Meanwhile, antioxidants including N-acetylcysteine (NAC) and natural COA water scientifically block these mitochondrial ROS and mitochondrial recruitment of Parkin by inhibiting Plk3. Through a 3D organoid ex vivo model, we confirmed that not only ROS inhibitors but also mitophagy inhibitory factors such as 3-MA or Parkin deletion can compensate for pancreatic cell growth and insulin secretion under STZ diabetic stress. These findings suggest that the Plk3-mtROS-PINK1-Parkin axis is a novel mitophagy process that inhibits pancreatic ß-cell growth and insulin secretion and FOXO3A and antioxidants may provide new alternatives for effective diabetes treatment strategies in the future.
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Diabetes Mellitus , Células Secretoras de Insulina , Humanos , Mitofagia , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/farmacologia , Células Secretoras de Insulina/metabolismo , Proteínas Quinases/metabolismo , Diabetes Mellitus/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
The aim of the current study was to describe the risk of hepatotoxicity for patients with gastroenteropancreatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy (PRRT) with a very high liver tumor burden, defined as tumor involving more than 75% of the liver. Methods: We conducted a retrospective analysis of 371 patients who received at least 1 cycle of 177Lu-DOTATATE at Mayo Clinic for advanced gastroenteropancreatic neuroendocrine tumors. We identified 15 total patients with more than 75% liver involvement on 68Ga-DOTATATE PET/CT and with either a contrast-enhanced abdominal MRI or dual-phase abdominal CT examination. Results: Of the 15 patients with more than 75% liver involvement, 1 experienced hepatotoxicity (i.e., worsening liver enzymes or bilirubin) as defined by the Common Terminology Criteria for Adverse Events, version 5.0. No patients had grade 3-5 hepatotoxicity (i.e., clinical signs of liver failure). Conclusion: When considering the risk of liver injury from PRRT due to burden of disease, our data suggest that PRRT may be a safe option in patients with more than 75% liver involvement. Future efforts should be made to determine the safety profile of PRRT in patients with varying degrees of liver involvement.
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Doença Hepática Induzida por Substâncias e Drogas , Neoplasias Hepáticas , Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Receptores de Peptídeos , Radioisótopos , Compostos Organometálicos/efeitos adversosRESUMO
We report a case of a 40-year-old woman with renal angiomyoadenomatous tumor, a rare neoplasm with only 6 previous cases reported in the literature. Unlike our case, most tumors have been identified in middle-aged males; they present as well-circumscribed, encapsulated tan-brown masses with variably prominent cystic areas. Microscopically, the tumors have a variably thick leiomyomatous capsule, which invaginates into the tumor and intermixes with tubules or solid nests of clear epithelial cells. The epithelial cells have low-grade basally oriented nuclei, and their basement membranes are intimately linked to a labyrinthine network of capillaries and pericytes. Microscopically, these tumors can be confused with clear cell carcinoma, papillary carcinoma, mixed epithelial and stromal tumors, and angiomyolipoma. This is also the first case report correlating the radiographic and morphological findings of this rare entity. The differentiating features of these neoplasms and a review of literature of are herein presented.
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Angiomiolipoma/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/patologia , Adulto , Angiomiolipoma/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma de Células Renais/diagnóstico por imagem , Diagnóstico Diferencial , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND/AIM: The functions of the specific genes involved in the three types of breast cancer (BC) are unclear. MATERIALS AND METHODS: A total of 53,805 genes were assessed from the RNA-sequencing database of BC cells and classified into those involved in hormonal positive (HR+) BC and triple-negative breast cancer (TNBC). Overall, distant metastasis-free, and relapse-free survival obtained from the Breast Cancer Gene-Expression Miner database containing 13,603 human breast cancer patient samples were assessed for gene associations using the RNA-sequencing database. To examine cell invasion and cytokine levels, inflammation-related genes were knocked down. The role of inflammation in cancer metastasis was confirmed using inflammatory inhibitors in a three-dimensional organoid ex vivo. RESULTS: Genes affecting inflammation and cancer metastasis were highly expressed in TNBC, unlike HR+ BC. The A20/TNFAIP3-CDC20-CASP1 axis, which includes inflammation-related genes found in TNBC, was associated with poor patient prognosis, cancer metastasis, and cytokine levels. Inflammation inhibitors prevented the metastasis of aggressive TNBC. CONCLUSION: The A20/TNFAIP3-CDC20-CASP1 axis is closely related to the metastatic potential of TNBC, and inflammation inhibitors might be a novel target therapy for TNBC.
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Caspase 1/genética , Proteínas Cdc20/genética , Neoplasias de Mama Triplo Negativas/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Citocinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação , Mediadores da Inflamação/metabolismo , Metástase Neoplásica , Prognóstico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Metastatic neuroendocrine tumour (NET) to brain has been reported in 1.5-5% of patients with NETs. Differentiation between intracranial NET metastasis and meningiomas can cause a diagnostic dilemma. We present a symptomatic case of a 66-year-old male with a history of left-sided skull base mass. The diagnosis of a meningioma was made based on the MRI findings and clinical presentation. The patient received radiation and the mass remained stable on serial MRI images at follow-up visits. Five years after his initial presentation, the patient's mass showed further growth. He also complained of worsening of his recent diagnosis of irritable bowel syndrome and fluctuations in his blood pressure. Surgical resection was performed, and histopathological features were consistent with moderately differentiated neuroendocrine tumour. Further evaluation with 68 Gallium-DOTATATE positron emission-computed tomography (Ga-68 PET/CT) showed metastatic disease involving the bones, lymph nodes, and liver without convincing evidence of the location of primary malignancy within the bowel loops or the pancreas. The patient was started on combination of capecitabine and temozolomide with partial response and significant improvement of his symptoms. This case highlights the clinical and radiological behaviour of intracranial NET that can mimic the diagnosis of meningioma.
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Angioedema is a self-limited, localized tissue swelling, resulting from fluid extravasation into interstitial spaces. It may occur in isolation or be accompanied by urticaria and/or anaphylaxis. The phenomenon has been linked to multiple medications, including non-steroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors (ACEIs). NSAID-induced angioedema is observed in < 0.3% of patients taking NSAIDs. While isolated visceral angioedema has been reported from ACEIs, it has not been documented from NSAID use, particularly aspirin usage. Here, we report a case of isolated visceral angioedema attributed to aspirin use.
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Angioedema , Hipersensibilidade a Drogas , Urticária , Angioedema/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Humanos , Urticária/induzido quimicamenteRESUMO
OBJECTIVE: Studies evaluating leptomeningeal disease on whole-body 18F-FDG PET are lacking. The purpose was to evaluate PET imaging of leptomeningeal disease and investigate the incremental utility of newer PET reconstructions in leptomeningeal disease. METHODS: PET imaging of 56 patients with leptomeningeal disease detected initially on MRI (n = 53) or cytopathology (n = 35) were retrospectively reviewed. Regular 3-dimensional iterative reconstruction (3D IR, n = 56) and advanced reconstruction (AdvRecon, n = 41) PET images were evaluated by readers blinded to clinical and MRI findings for uptake involving cauda equina, posterior fossa and spinal cord. Spinal cord uptake pattern was classified as normal (uptake < liver), uptake = liver, conus uptake > liver, conus and cervical cord uptake > liver and multifocal/diffuse uptake > liver. SUVmax ratios of conus/liver, conus/left atrium and conus/cervical cord were compared between 3D IR and AdvRecon datasets. RESULTS: Cauda equina uptake was seen in 64% and 78% on 3D IR and AdvRecon; posterior fossa uptake was seen in 52% and 54% on 3D IR and AdvRecon, respectively. Twelve percent had cauda equina or posterior fossa uptake visible only on AdvRecon. On 3D IR, normal spinal cord uptake was most common (27%); on AdvRecon, conus and cervical cord uptake > liver was most common (32%). Seven of 11 patients with normal spinal cord uptake on 3D IR were upgraded to increased uptake on AdvRecon. AdvRecon showed significantly higher conus/liver, conus/blood pool and conus/cervical cord SUVmax ratios (P < 0.0001). CONCLUSION: Abnormal uptake in cauda equina, posterior fossa and spinal cord uptake are visible on FDG PET in leptomeningeal disease with increased conspicuity advanced PET reconstructions.
Assuntos
Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Imagem Corporal Total , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The aim of this narrative review is to evaluate the current status of 177Lu-PSMA (prostate specific membrane antigen) therapy for metastatic castration-resistant prostate cancer (mCRPC) in the light of the current literature. We also addressed patient preparation, therapy administration and side effect profiles. 177Lu-PSMA therapy efficacy was assessed by using prospective trials, meta-analyses and major retrospective trials. Predictors of efficacy were also mentioned. Although there are some different approaches regarding the use of 177Lu-PSMA therapy in different countries, this type of therapy is generally safe, with a low toxicity profile. From the oncological point of view, a PSA (prostate specific antigen) decline of ≥50% was seen in 10.6-69% of patients with mCRPC; whereas progression-free survival (PFS) was reported to be 3-13.7 months in different studies. Consequently, 177Lu-PSMA therapy is a promising treatment in patients with mCRPC, with good clinical efficacy, even in heavily pretreated patients with multiple lines of systemic therapy. Currently, there are ongoing clinical trials in the United States, including a phase III multicenter FDA registration trial.
RESUMO
BACKGROUND: There is scant insight into the presence of nuclear medicine (NM) and nuclear radiology (NR) programs on social media. OBJECTIVE: Our purpose was to assess Twitter engagement by academic NM/NR programs in the United States. METHODS: We measured Twitter engagement by the academic NM/NR community, accounting for various NM/NR certification pathways. The Twitter presence of NM/NR programs at both the department and program director level was identified. Tweets by programs were cross-referenced against potential high-yield NM- or NR-related hashtags, and tabulated at a binary level. A brief survey was done to identify obstacles and benefits to Twitter use by academic NM/NR faculty. RESULTS: For 2019-2020, 88 unique programs in the United States offered NM/NR certification pathways. Of these, 52% (46/88) had Twitter accounts and 24% (21/88) had at least one post related to NM/NR. Only three radiology departments had unique Twitter accounts for the NM/molecular imaging division. Of the other 103 diagnostic radiology residency programs, only 16% (16/103) had a presence on Twitter and 5% (5/103) had tweets about NM/NR. Only 9% (8/88) of NM/NR program directors were on Twitter, and three program directors tweeted about NM/NR. The survey revealed a lack of clarity and resources around using Twitter, although respondents acknowledged the perceived value of Twitter engagement for attracting younger trainees. CONCLUSIONS: Currently, there is minimal Twitter engagement by the academic NM/NR community. The perceived value of Twitter engagement is counterbalanced by identifiable obstacles. Given radiologists' overall positive views of social media's usefulness, scant social media engagement by the NM community may represent a missed opportunity. More Twitter engagement and further research by trainees and colleagues should be encouraged, as well as the streamlined use of unique hashtags.
RESUMO
Celiac disease is an immune-mediated disorder triggered by hypersensitivity to gluten occurring in genetically susceptible individuals. A high-index of suspicion is needed for diagnosis as patients can be asymptomatic or present with atypical symptoms or extra-intestinal manifestations. Typical 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) gastrointestinal manifestations of celiac disease include increased multifocal or diffuse jejunal and ileal uptake; focal duodenal uptake is less common. Splenomegaly with increased splenic FDG uptake is also uncommon in celiac disease in the absence of portal hypertension; small-sized spleen and functional hyposplenism are more typical. We report a case of celiac disease diagnosed after PET/CT showed FDG uptake in the duodenum and enlarged spleen. Follow-up after gluten-free diet showed complete metabolic resolution and regression of splenomegaly. The combination of focal bowel and splenic uptake is unusual in celiac disease and may be mistaken for a lymphoproliferative disorder. Awareness of this entity may avoid misdiagnosis and guide appropriate management.