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2.
Front Endocrinol (Lausanne) ; 15: 1383814, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952387

RESUMO

Objectives: To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs). Methods: A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed. Results: A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts. Conclusion: A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.


Assuntos
Endossonografia , Insulinoma , Aprendizado de Máquina , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Endossonografia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Insulinoma/diagnóstico por imagem , Insulinoma/patologia , Adulto , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Diagnóstico Diferencial , Idoso , Nomogramas , Radiômica
3.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 655-659, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-38955694

RESUMO

The 5th edition of the WHO Endocrine and Neuroendocrine Oncology Blue Book, released in 2022, contained some changes in the classification of neuroendocrine tumors. A brief summary of the main changes has been provided in this section. Mainly summarized as changes in naming, differentiation and classification of neuroendocrine tumors, and tumor grading systems related to anatomical locations, morphological characteristics of neuroendocrine tumors in different locations, auxiliary diagnostic and prognostic/therapeutic markers, differential diagnosis and diagnostic difficulties of neuroendocrine tumors.


Assuntos
Tumores Neuroendócrinos , Organização Mundial da Saúde , Humanos , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/classificação , Diagnóstico Diferencial , Gradação de Tumores , Biomarcadores Tumorais/metabolismo , Prognóstico
4.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 722-727, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-38955705

RESUMO

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.


Assuntos
Hormônio Adrenocorticotrópico , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/diagnóstico , Adulto , Idoso , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico , Hormônio Adrenocorticotrópico/metabolismo , Proteínas com Domínio T/metabolismo , Imageamento por Ressonância Magnética , Hidrocortisona/metabolismo , Proteínas de Homeodomínio
5.
Pancreas ; 53(7): e560-e565, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38986077

RESUMO

OBJECTIVE: We investigated metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on pre-treatment FDG-PET as prognostic markers for survival in patients with metastatic neuroendocrine neoplasms (NENs) receiving peptide receptor radionuclide therapy (PRRT). METHODS: A retrospective review of patients with metastatic NENs receiving PRRT was undertaken. Pre-treatment FDG-PET images were analyzed and variables collected included MTV and TLG (dichotomized by median into high vs low). Main Outcomes were overall survival (OS) and progression-free survival (PFS) by MTV and TLG (high vs low). RESULTS: One hundred five patients were included. Median age was 64 years (50% male). Main primary NEN sites were small bowel (43.8%) and pancreas (40.0%). Median MTV was 3.8 mL and median TLG was 19.9. Dichotomization formed identical cohorts regardless of whether MTV or TLG were used. Median OS was 72 months; OS did not differ based on MTV/TLG high versus low (47.4 months vs not reached; hazard ratio, 0.43; 95% confidence interval [CI], 0.18-1.04; P = 0.0594). Median PFS was 30.4 months; PFS differed based on MTV/TLG high versus low (21.6 months vs 45.7 months; hazard ratio, 0.35; 95% CI, 0.19-0.64; P = 0.007). CONCLUSIONS: Low MTV/TLG on pre-treatment FDG-PET was associated with longer PFS in metastatic NEN patients receiving PRRT.


Assuntos
Fluordesoxiglucose F18 , Tumores Neuroendócrinos , Octreotida , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Carga Tumoral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Estudos Retrospectivos , Idoso , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Organometálicos/uso terapêutico , Adulto , Receptores de Peptídeos/metabolismo , Glicólise , Idoso de 80 Anos ou mais , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Intervalo Livre de Progressão , Resultado do Tratamento
6.
Sci Rep ; 14(1): 15782, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982134

RESUMO

This study aims to assess the predictive capability of cylindrical Tumor Growth Rate (cTGR) in the prediction of early progression of well-differentiated gastro-entero-pancreatic tumours after Radio Ligand Therapy (RLT), compared to the conventional TGR. Fifty-eight patients were included and three CT scans per patient were collected at baseline, during RLT, and follow-up. RLT response, evaluated at follow-up according to RECIST 1.1, was calculated as a percentage variation of lesion diameters over time (continuous values) and as four different RECIST classes. TGR between baseline and interim CT was computed using both conventional (approximating lesion volume to a sphere) and cylindrical (called cTGR, approximating lesion volume to an elliptical cylinder) formulations. Receiver Operating Characteristic (ROC) curves were employed for Progressive Disease class prediction, revealing that cTGR outperformed conventional TGR (area under the ROC equal to 1.00 and 0.92, respectively). Multivariate analysis confirmed the superiority of cTGR in predicting continuous RLT response, with a higher coefficient for cTGR (1.56) compared to the conventional one (1.45). This study serves as a proof of concept, paving the way for future clinical trials to incorporate cTGR as a valuable tool for assessing RLT response.


Assuntos
Progressão da Doença , Neoplasias Pancreáticas , Neoplasias Gástricas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Idoso , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Curva ROC , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/patologia , Estudo de Prova de Conceito , Carga Tumoral
8.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000088

RESUMO

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.


Assuntos
Neoplasias Colorretais , Dopamina , Epinefrina , Estadiamento de Neoplasias , Tumores Neuroendócrinos , Norepinefrina , Serotonina , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/diagnóstico , Serotonina/sangue , Epinefrina/sangue , Prognóstico , Norepinefrina/sangue , Idoso , Dopamina/sangue , Dopamina/metabolismo , Adulto , Biomarcadores Tumorais/sangue , Avaliação Nutricional , Neurotransmissores/sangue , Neurotransmissores/metabolismo , Inflamação/sangue , Inflamação/patologia
9.
Oncology (Williston Park) ; 38(7): 264-268, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39024198

RESUMO

Neoadjuvant and adjuvant treatment in lung neuroendocrine tumors (NETs) is a field that has not been explored in-depth, with little information on the impact on disease-free survival. This case study highlights the effectiveness of neoadjuvant treatment with capecitabine plus temozolomide (CAPTEM) in a woman with well-differentiated atypical carcinoid. The patient was asymptomatic at diagnosis and was referred to the outpatient NET clinic at Sotiria Hospital in Athens, following an incidental finding on a chest x-ray. 18F-fluorodeoxyglucose (FDG) PET/CT and 68Ga-Dotatoc PET/CT revealed another mass in the pancreas, with avidity in both imaging studies. The patient underwent treatment for 6 months with CAPTEM with a response in the lung NET and mediastinal lymph nodes. However, the mass in the pancreas slightly increased and was removed with a central pancreatectomy. The patient continued treatment with CAPTEM for 6 more months. There was further response according to RECIST 1.1 criteria (partial response in the mediastinal lymph nodes and a 21% regression in the primary tumor size). Pathology report after lobectomy with lymph node dissection showed a pathologic complete response in the mediastinal lymph nodes. Twenty-four months after surgery, the patient remains disease-free and has a good quality of life. Although large clinical trials are needed, this case study underlines the value of preoperative chemotherapy in atypical carcinoids.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Neoplasias Pulmonares , Terapia Neoadjuvante , Temozolomida , Humanos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Feminino , Temozolomida/uso terapêutico , Temozolomida/administração & dosagem , Terapia Neoadjuvante/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
10.
Turk J Pediatr ; 66(3): 332-339, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39024601

RESUMO

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare in children and adolescents. Standard management of these tumors has not been well established due to their rarity in this age group. We aimed to report the clinical and pathological characteristics of patients with this rare disease followed and treated between the years 1993-2022. MATERIALS AND METHODS: The medical records of patients with GEP-NETs were reviewed. RESULTS: Fourteen patients (11 girls, 3 boys) were diagnosed with GEP-NET. The median age was 13 (9-18) years. Tumor localization was the appendix in 12, stomach in one and pancreas in one patient. Mesoappendix invasion was detected in four patients two of whom underwent right hemicolectomy (RHC) and lymph node dissection (LND). Of those, one patient had lymph node involvement. The other two had not further operations. Somatostatin was used in one with pancreatic metastatic disease and the other with gastric disease after surgery. No additional treatment was given in other patients. All patients are under follow-up without evidence of disease at a median follow-up of 85 months (7-226 months). CONCLUSION: GEP-NETs should be considered in the differential diagnosis of acute appendicitis and in cases with persistent abdominal pain. In children, there is invariably a favorable prognosis, and additional surgical interventions other than simple appendectomies generally do not provide benefits. Mesoappendix invasion may not necessitate RHC and LND.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Adolescente , Masculino , Feminino , Criança , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Intestinais/cirurgia , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/patologia , Estudos Retrospectivos
11.
J Pak Med Assoc ; 74(7): 1382-1383, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39028080

RESUMO

68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We present the case of a 59-year-old male with well differentiated gastric neuroendocrine tumour (grade II) treated with surgery. 68Ga-DOTA NOC PET/CT was performed to rule out metastasis. 68Ga-DOTA NOC showed physiological uptake in the bilateral adrenal and horseshoe kidney appearing as the famous character Super Mario. There is no evidence of any abnormal somatostatin avid lesion.


Assuntos
Tumores Neuroendócrinos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Somatostatina , Neoplasias Gástricas , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Receptores de Somatostatina/metabolismo , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Compostos Radiofarmacêuticos , Compostos Organometálicos , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia
12.
Adv Cancer Res ; 161: 403-429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39032955

RESUMO

Worldwide, prostate cancer (PCa) remains a leading cause of death in men. Histologically, the majority of PCa cases are classified as adenocarcinomas, which are mainly composed of androgen receptor-positive luminal cells. PCa is initially driven by the androgen receptor axis, where androgen-mediated activation of the receptor is one of the primary culprits for disease progression. Therefore, in advanced stage PCa, patients are generally treated with androgen deprivation therapies alone or in combination with androgen receptor pathway inhibitors. However, after an initial decrease, the cancer recurs for majority patients. At this stage, cancer is known as castration-resistant prostate cancer (CRPC). Majority of CRPC tumors still depend on androgen receptor axis for its progression to metastasis. However, in around 20-30% of cases, CRPC progresses via an androgen receptor-independent pathway and is often presented as neuroendocrine cancer (NE). This NE phenotype is highly aggressive with poor overall survival as compared to CRPC adenocarcinoma. NE cancers are resistant to standard taxane chemotherapies, which are often used to treat metastatic disease. Pathologically and morphologically, NE cancers are highly diverse and often co-exist with adenocarcinoma. Due to the lack of proper biomarkers, it is often difficult to make an early diagnosis of this lethal disease. Moreover, increased tumor heterogeneity and admixtures of adeno and NE subtypes in the same tumor make early detection of NE tumors very difficult. With the advancement of our knowledge and sequencing technology, we are now able to better understand the molecular mediators of this transformation pathway. This current study will give an update on how various molecular regulators are involved in these lineage transformation processes and what challenges we are still facing to detect and treat this cancer.


Assuntos
Tumores Neuroendócrinos , Humanos , Masculino , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/genética , Receptores Androgênicos/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Animais , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Regulação Neoplásica da Expressão Gênica
13.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(7): 734-739, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39004990

RESUMO

The cancer staging system of the American Joint Committee on Cancer (AJCC) is the most widely used clinical basis for tumor staging. In October 2023, AJCC released the staging system (ninth version) for the neuroendocrine tumors of stomach (NET), which has been implemented in January 2024. The ninth version of NET staging system mainly updated the histopathologic classification, diagnosis and staging methods, clinical and pathological staging, prognosis grade, tumor and non-tumor prognostic features. The update and implementation of the staging system provide a more detailed reference for the accurate diagnosis, staging and precise treatment of gastric neuroendocrine tumors. Moreover, it is convenient for clinicians to carry out clinical practice. The purpose of our article is to provide a high-level overview of the major changes in AJCC staging system (version 9) for gastric NET based on the latest evidence-based medical research.


Assuntos
Estadiamento de Neoplasias , Tumores Neuroendócrinos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico , Estadiamento de Neoplasias/métodos , Prognóstico
14.
Dtsch Med Wochenschr ; 149(15): 871-878, 2024 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-39013407

RESUMO

Despite, or perhaps because of the rarity of neuroendocrine neoplasms, the diagnosis and treatment of these malignancies is of particular importance. Nuclear medicine can make an important contribution to this challenge. It offers the most sensitive and specific imaging of these tumor entities and can be helpful in treatment due to the radiotherapeutic drugs that have recently been approved. This theragnostic (fusion of therapeutic and diagnostic) concept is based on the frequent overexpression of somatostatin receptors on neuroendocrine tumor cells.Using diagnostic and therapeutic pharmaceuticals based on analogues from somatostatin, most applications from the nuclear medicine are successful, an additional therapeutic method is SIRT, also known as TARE, in which the hypervascularization of NEN-metastases is used as a therapeutic target.


Assuntos
Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/terapia , Medicina Nuclear/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Receptores de Somatostatina , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
16.
Dtsch Med Wochenschr ; 149(15): 887-893, 2024 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-39013409

RESUMO

Neuroendocrine neoplasms are classified according to the WHO classification based on morphological criteria into neuroendocrine tumors, neuroendocrine carcinomas, and mixed neuroendocrine-non-neuroendocrine neoplasms. Neuroendocrine tumors are well differentiated neoplasms and show characteristic site-specific histological and molecular features, which is important for their clinical management. In cases dealing with metastasis, pathology often can help to identify the primary tumors using a small immunohistochemical marker panel. Neuroendocrine carcinomas are poorly differentiated neoplasms. They are subdivided into neuroendocrine carcinomas of small cell and large cell type. The molecular profile of neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms shows a close relationship to conventional adenocarcinomas with site-specific features. Molecular analysis of neuroendocrine carcinomas and neuroendocrine-non-neuroendocrine neoplasms are not yet fully integrated in daily diagnostics and are mainly performed in the context of precision oncology.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Biomarcadores Tumorais/genética , Neoplasias Intestinais/patologia , Neoplasias Intestinais/genética , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
17.
J Cancer Res Ther ; 20(3): 811-816, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-39023587

RESUMO

AIM: Neuroendocrine tumors are heterogenous group of neoplasms that includes benign and malignant tumors that originate from neuroendocrine or nonneuroendocrine organs. Insulinoma-associated protein 1 (INSM1) is a zinc finger transcription factor originally isolated from subtraction library of human insulinoma. The main aim was to study the INSM1 expression in a spectrum of neuroendocrine tumors and a limited spectrum of nonneuroendocrine tumors. MATERIALS AND METHODS: A total of 100 cases of which 57 neuroendocrine neoplasms and 43 nonneuroendocrine neoplasms were included in the study. Immunohistochemistry (IHC) was done and expression patterns of INSM1 were analyzed. Pituitary adenoma, medullary carcinoma of thyroid, pheochromocytoma lung, gastrointestinal, and pancreatic neuroendocrine tumors were the neuroendocrine tumors that were included in the study. Papillary carcinoma of thyroid, gastrointestinal adenocarcinoma, lung adenocarcinoma, and squamous cell carcinoma were the nonneuroendocrine tumors that were included in the study. Depending upon the tissue availability, comparison of INSM1 with synaptophysin and chromogranin was also done in few neuroendocrine tumors. RESULTS: All the 57 neuroendocrine tumors showed positive expression for INSM1 and all the nonneuroendocrine tumors were negative for INSM1. This study is statistically significant. CONCLUSION: Our study suggests that INSM1 is a diagnostic marker for neuroendocrine tumors with high degree of sensitivity and specificity. The study is significant and suggests that INSM1- IHC shows nuclear positivity in a spectrum of neuroendocrine tumors. Being a nuclear marker, interpretation is easy and more reliable than the cytoplasmic markers. INSM1 has a stronger positivity than synaptophysin and chromogranin in the present study especially for small cell carcinoma lung. Hence, INSM1 may be included in the routine panel for neuroendocrine tumors along with synaptophysin and chromogranin.


Assuntos
Biomarcadores Tumorais , Imuno-Histoquímica , Tumores Neuroendócrinos , Proteínas Repressoras , Humanos , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/diagnóstico , Proteínas Repressoras/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Centros de Atenção Terciária , Idoso , Sinaptofisina/metabolismo , Adulto Jovem
18.
JCO Precis Oncol ; 8: e2400143, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38976813

RESUMO

PURPOSE: Thrombocytopenia is a relatively common dose-limiting toxicity during peptide receptor radionuclide therapy (PRRT) in patients with NET. Although uncommon, some patients develop persistent cytopenia and eventually therapy-related myeloid neoplasm (t-MN), which has a dismal prognosis. As the indications for PRRT are expanding, it is important to investigate factors that may predict cytopenias during/after PRRT. We prospectively evaluated the prevalence of clonal hematopoiesis (CH) and cytopenia in patients with NET undergoing PRRT. MATERIALS AND METHODS: Patients with metastatic NET with plan to receive four cycles of lutetium-177 were enrolled. CH was evaluated before PRRT using a panel of 220 genes with a targeted depth of ≥1,000×. Patients were followed during PRRT and every 3 months thereafter. RESULTS: Of 37 patients enrolled, the median age was 68 years and 51.4% were male. Previous treatment exposures included alkylating agents in 30%, platinum agents in 8%, and external radiation in 13%. CH was detected in 35.1% using a variant allele frequency (VAF) cutoff of ≥2% and 45.9% with a VAF of ≥1%. The most common mutations were in age-related genes (DNMT3A, TET2). CH was not associated with anemia or neutropenia; however, it was associated with lower platelet count at baseline and more time spent in a thrombocytopenic state during/after PRRT. Five patients had bone marrow biopsies (BMBs) because of sustained hematologic dysfunction post-PRRT, and of those, diagnoses included clonal cytopenia of undetermined significance (CCUS) in three and idiopathic cytopenia of undetermined significance (ICUS) in two. CONCLUSION: CH is present in 35.1% of patients with NET and is associated with thrombocytopenia risk during PRRT. Future studies with long-term follow-up will delineate whether CH might be a predictor for higher risk of t-MN after PRRT.


Assuntos
Hematopoiese Clonal , Lutécio , Tumores Neuroendócrinos , Trombocitopenia , Humanos , Masculino , Feminino , Idoso , Trombocitopenia/genética , Trombocitopenia/etiologia , Tumores Neuroendócrinos/genética , Estudos Prospectivos , Pessoa de Meia-Idade , Lutécio/uso terapêutico , Lutécio/efeitos adversos , Hematopoiese Clonal/genética , Idoso de 80 Anos ou mais , Adulto , Radioisótopos/uso terapêutico , Radioisótopos/efeitos adversos
19.
Recenti Prog Med ; 115(7): 361-365, 2024.
Artigo em Italiano | MEDLINE | ID: mdl-39011919

RESUMO

Well-differentiated neuroendocrine tumors of the appendix (NETs) are rare in pediatric and adolescent age groups. However, they are the most common gastrointestinal epithelial tumor in this age group and the most common malignancy of the appendix in the general population. The classification of these tumors considers factors such as the proliferation index, size of the neoplasm, and the presence of perineural and/or lymphovascular invasion, which can contribute to distant metastases. Preoperative diagnosis is challenging, except in cases where patients exhibit symptoms of carcinoid syndrome or signs of metastatic disease, which are uncommon in pediatric and adolescent patients. For tumors smaller than 1 cm, appendectomy is usually curative, while larger tumors or those at risk of spreading may require right hemicolectomy with lymphadenectomy. We present a case of an adolescent with NET and provide a literature review on the diagnostic and therapeutic approaches that should be considered for this relatively rare condition.Key words. Adolescent age, appendix, neuroendocrine tumors, pediatric age.


Assuntos
Apendicectomia , Neoplasias do Apêndice , Apendicite , Tumores Neuroendócrinos , Adolescente , Humanos , Apendicectomia/métodos , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/cirurgia , Apendicite/cirurgia , Apendicite/diagnóstico , Apendicite/patologia , Colectomia/métodos , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/cirurgia
20.
Dtsch Med Wochenschr ; 149(15): 879-886, 2024 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-39013408

RESUMO

Due to the complexity and heterogeneity of metastatic NEN an interdisciplinary expert team should be involved in an individualized treatment strategy. SSA is the mainstay of antisecretory treatment in most functioning tumors. In antiproliferative intention SSA are first line treatment in receptor positive low proliferative NET. In intestinal metastatic disease PRRT is best established second line treatment. Further options are Everolimus (labeled) and tyrosine kinase inhibitors (off-label). Everolimus is the only approved drug for antiproliferative treatment in patients with metastatic lung NET, whereas in pancreatic NET more therapeutic options are available (SSA, chemotherapy, PRRT, Sunitinib, Everolimus) without a standard of best sequence. In patients with metastatic NEC standard first line treatment (platinum + etoposide) has not changed for decades and new treatment options for this fatal disease are urgently needed. Benefit of immunotherapy is limited to a small subset of patients - new combinations are under investigation. This review summarizes the standard of care, criteria of treatment selection and new developments for systemic therapy in patients with metastatic NEN.


Assuntos
Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/patologia , Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Metástase Neoplásica
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