Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.786
Filtrar
1.
Medicine (Baltimore) ; 99(10): e19304, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150065

RESUMO

BACKGROUND: Somatostatin analog therapies showed great potential for patients suffering advanced neuroendocrine tumors (NETs). This study was aimed to evaluate the therapeutic efficacy of Lu-DOTATATE/DOTATOC (Lu-octreotate/octreotide) peptide receptor radionuclide therapy (PRRT) in advanced or inoperable NETs patients. METHODS: Pubmed, Web of Science, Embase and Cochrane Library were searched from 1950 to April 2019. Eligible studies should include randomized or nonrandomized controlled trials (RCTs)-based investigations of Lu-octreotate/octreotide PRRT for NETs. All these studies were assessed with Response Evaluation Criteria in Solid Tumors (RECIST), RECIST 1.1, Southwest Oncology Group (SWOG) criteria or World Health Organization (WHO) criteria. Disease response rates (DRRs) and disease control rates (DCRs) were calculated according to each response criteria group. DRRs were defined as the percentages of patients with complete response (CR) + partial response (PR), while DCRs represented the percentages of patients with CR+ PR+ stable disease (SD). The pooled proportions were calculated with either a fixed-effects model or a random-effects model depending on the test for heterogeneity. RESULTS: A total of 22 studies (1758 patients) were included in this meta-analysis: 8 studies with 478 patients met RECIST criteria, 10 studies with 1127 patients met RECIST 1.1 criteria, 5 studies with 459 patients met SWOG criteria, and 1 study with 40 patients met WHO criteria, and among these articles 1 study met both RECIST and RECIST 1.1 criteria and 1 met both RECIST 1.1 and SWOG criteria. The pooled DRRs were 33.0% (95% CI: 25.0%-42.0%, I = 65%), 35.0% (95% CI: 26.0%-45.0%, I = 91%) and 25.0% (95% CI: 14.0%-36.0%, I = 84%) according to RECIST, RECIST 1.1 and SWOG criteria, respectively. The pooled DCRs were 79.0% (95% CI: 75.0%-83.0%, I = 97%), 83.0% (95% CI: 78.0%-88.0%, I = 0) and 82.0% (95% CI: 75.0%-89.0%, I = 91%), respectively. CONCLUSION: In advanced NETs patients, DRRs and DCRs were significantly elevated after initial treatment with Lu-DOTATATE PRRT, which shows that this treatment would be beneficial and promising for advanced or inoperable NETs patients.


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/análogos & derivados , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/uso terapêutico , Compostos Radiofarmacêuticos/administração & dosagem , Critérios de Avaliação de Resposta em Tumores Sólidos
2.
Zhonghua Nei Ke Za Zhi ; 59(4): 297-302, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32209196

RESUMO

Objective: To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC). Methods: A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN. Results: In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis (P=0.041, 0.025). Conclusions: Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.


Assuntos
Tumores Neuroendócrinos/patologia , Neoplasias Gástricas/patologia , China/epidemiologia , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Humanos , Tumores Neuroendócrinos/mortalidade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
3.
Z Gastroenterol ; 58(2): 137-145, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32050284

RESUMO

PURPOSE: Rectal neuroendocrine tumors are rare with good prognosis. Several endoscopic methods such as endoscopic polypectomy, endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and modified endoscopic mucosal resection (m-EMR) are used in the treatment of rectal neuroendocrine tumors. Although m-EMR is derived from traditional EMR, it has not been widely used in clinical practice. In this study, we compared the efficacy and safety of EMR and m-EMR in the treatment of rectal neuroendocrine tumors by performing a meta-analysis. MATERIALS AND METHODS: We searched PubMed, Web of Science, and EMBASE index up to the end of January 2017 for all published literature about EMR and m-EMR in the treatment of rectal neuroendocrine tumors. RESULTS: A total of 11 studies involving 811 patients were included. The pooled data suggested that there was a significantly higher rate of histologic complete resection and endoscopic complete resection among patients treated with m-EMR than those treated with EMR (histologic complete resection: OR = 0.23, 95 % CI = 0.10-0.51, p < 0.01; endoscopic complete resection: OR = 0.13, 95 % CI = 0.02-0.74, p = 0.02). The procedure time of EMR was longer than m-EMR (MD = 2.40, 95 % CI = 0.33-4.46, p = 0.02). There was a significantly higher rate of vertical margin involvement among patients treated with EMR than those treated with m-EMR; whereas, there was no significant difference of lateral margin involvement between the m-EMR and EMR groups (vertical margin involvement: OR = 5.00, 95 % CI = 2.67-9.33, p < 0.01; lateral margin involvement: OR = 1.44, 95 % CI = 0.48-4.37, p = 0.52). There was no significant difference in mean tumor size among patients treated with m-EMR versus those treated with EMR (MD = -0.30, 95 % CI = -0.75-0.14, p = 0.18); further, there was no significant difference in endoscopic mean sizes of the tumor and pathological mean sizes of the tumor between the m-EMR and EMR groups (endoscopic mean sizes of the tumor: MD = 0.20, 95 % CI = -0.44-0.84, p = 0.43; pathological mean sizes of the tumor: MD = 0.62, 95 % CI = -0.68-1.92, p = 0.05). No significant differences were detected among the treatment groups with regard to complications (bleeding: OR = 0.87, 95 % CI = 0.39-1.95, p = 0.73; complications (bleeding and perforation): OR = 0.87, 95 % CI = 0.40-1.88, p = 0.73). CONCLUSION: The efficacy of m-EMR are better than EMR among patients undergoing endoscopic treatment of rectal neuroendocrine tumors, and the safety of m-EMR is equivalent to EMR treatment.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Endoscopia Gastrointestinal/efeitos adversos , Tumores Neuroendócrinos/cirurgia , Neoplasias Retais/cirurgia , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Tumores Neuroendócrinos/patologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
4.
Nat Commun ; 11(1): 1009, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081882

RESUMO

The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1-/- driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.


Assuntos
Dano ao DNA/genética , Neoplasias Pulmonares/genética , Tumores Neuroendócrinos/genética , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Diferenciação Celular , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Knockout , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais
5.
Eur J Endocrinol ; 182(4): 439-446, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32061159

RESUMO

Introduction: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. Aim of the study: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. Materials and methods: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. Results: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. Conclusions: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.


Assuntos
Insulinoma/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Feminino , Humanos , Hipoglicemia/etiologia , Hipoglicemia/mortalidade , Hipoglicemia/patologia , Insulinoma/patologia , Insulinoma/terapia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
Medicine (Baltimore) ; 99(3): e18736, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011453

RESUMO

Recently, the American Joint Committee on Cancer (AJCC) 8th staging manual stipulated the World Health Organization (WHO) G3 pancreatic neuroendocrine carcinomas (p-NECs) should all be classified by the system for pancreatic exocrine adenocarcinomas, which had ignored the heterogeneity of G3 p-NECs. We focused on demonstrating whether the heterogeneous subgroups of G3 p-NECs would influence the accurate application of AJCC 8th staging systems.G3 p-NECs were divided into well-differentiated and poorly-differentiated subgroups, whose clinical features and overall survival (OS) were compared. Survival analysis by applying 2 new AJCC 8th staging systems to well-differentiated G3 p-NECs were performed to validate whether these subgroup patients should also be staged by the system proposed for all G3 p-NECs.We enrolled 172 patients who were histopathologically diagnosed as G3 p-NECs, including 64 well-differentiated G3 p-NECs and 108 poorly-differentiated ones, whose patient demographics and tumor characteristics present no notably differences (P > .05), except their Ki-67 index and mitotic rate (P = .031, P = .025; respectively). The estimated OS of well-differentiated G3 p-NECs was significantly better than those of poorly-differentiated tumors (P < .001). When applying the new AJCC system for all G3 p-NECs to well-differentiated G3 tumors, 18, 22, 12, and 12 patients were respectively distributed in the new AJCC Stage I, Stage II, Stage III, and Stage IV. Using the AJCC 8th staging system for WHO G1/G2 pancreatic neuroendocrine tumors (p-NETs) to well-differentiated G3 p-NECs, there were 5, 25, 22, and 12 patients classified from the new AJCC Stage I to Stage IV, respectively. The system for G1/G2 p-NETs could significantly differentiate the survival differences between each new stage of well-differentiated G3 p-NECs (P < .05), while comparisons of survivals between Stage II with Stage III or Stage III with Stage IV by the system for G3 p-NECs were not statistically different (P = .334, P = .073; respectively).G3 p-NECs were heterogeneous with well-differentiated and poorly-differentiated subgroups. Both AJCC 8th staging systems proposed for all G3 p-NECs and G1/G2 p-NETs were practical for well-differentiated G3 p-NECs, while the one originally applied to G1/G2 p-NETs appeared to be superior in performance due to its better prognostic stratification and more accurate predicting ability.


Assuntos
Metástase Linfática , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Análise de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estados Unidos , Organização Mundial da Saúde
7.
Br J Radiol ; 93(1106): 20190735, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31922897

RESUMO

OBJECTIVE: To assess the usefulness of a single-phase contrast-enhanced CT to differentiate subtypes of neuroendocrine tumour (NET) liver metastases and to evaluate the correlation between CT features and Ga-68 DOTATATE positron emission tomography/CT (PET/CT) findings. METHODS: Between December 2017 and April 2019 patients with liver metastases of neuroendocrine tumours who underwent CT and Ga-68 DOTATATE PET/CT were enrolled in the study. All patients involved in the study had undergone a standardised single-phase contrast-enhanced CT. Whole body PET/CT images were obtained with a combined PET/CT scanner. All CT images were retrospectively analysed by two radiologists. Enhancement patterns of lesions were assessed. For quantitative examination; CT attenuation values of metastatic lesions, liver parenchyma and aorta were measured using a freehand ROI and tumour-to-liver ratio [T-L = (Tumour-Liver) / Liver] and tumour-to-aorta ratio [T-A = (Tumour-Aorta) / Aorta] were calculated. The lesion with the highest Ga-68 DOTATATE uptake in the liver was used for calculations. The metabolic tumour volume (MTV), maximum standardised uptake value (SUV max) and SUV mean were calculated for the target liver lesion. RESULTS: A total of 137 NET liver metastases divided into in three groups: 49 (35.7%) pancreatic, 60 (44.5%) gastroenteric and 26 (18.9%) lung NET liver metastases were analysed. Gastroenteric NET metastases often showed heterogeneous enhancement which was significantly higher than in the pancreas and lung NET liver metastases (p < 0.001). 96.72% (n = 59) of the gastroenteric NET liver metastases were hypoattenuating whereas the most frequent presentation for the pancreatic group was hyperattenuation (63.26%,n = 31). The difference in enhancement patterns of the liver metastases was statistically significant (p < 0.001) with respect to the location of the primary tumour. For quantitative analysis; tumour CT values were significantly different between the groups (p < 0.001). The T-L ratio was statistically different between gastroenteric and pancreatic NET liver metastases and pancreatic and lung NET groups (p < 0.001). The T-A ratio was significantly higher in the pancreatic NET metastases (p < 0.001). SUVmax, SUVmean and MTV values, however, were not significantly different between the subgroups. There was a weak positive correlation between T-L ratio and SUV meanvalues. CONCLUSION: We noticed statistically significant differences in both qualitative and quantitative CT features between histologic subgroups of neuroendocrine tumour liver metastases at a single phase contrast-enhanced CT. ADVANCES IN KNOWLEDGE: Our study will be the first in the literature which extensively focus on assessing the CT features of liver metastases of NETs at a single phase CT and Ga-68DOTATATE PET/CT. As the different histological subtypes of NET liver metastases exhibit different clinical outcomes, these features might help to identify the primary tumour to provide optimal treatment.


Assuntos
Neoplasias Gastrointestinais , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Variações Dependentes do Observador , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Imagem Corporal Total
8.
Z Gastroenterol ; 58(2): 133-136, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31896137

RESUMO

High-grade neuroendocrine neoplasms (NEN) comprise a rare entity. Due to the lack of randomized controlled trials, therapy recommendations were mainly extrapolated from its pulmonary analogue, small cell lung cancer and mostly validated in small retrospective case series. The multicentric Nordic NEC Study of gastro-entero-pancreatic (GEP) and cancer of unknown primary (CUP) high-grade neuroendocrine neoplasms showed a significant disease control upon treatment with etoposide and platinum-based chemotherapies 1. Such a combination with etoposide and a platinum (CE) compound is currently considered standard first-line treatment for high-grade GEP/CUP NEN. High-grade mixed-neuroendocrine-non-neuroendocrine neoplasms (MiNEN) formerly termed mixed adeno-neuroendocrine carcinomas (MANEC) also have a poor prognosis and are generally treated like other high-grade NEN. The CE protocol has significant activity in high-grade NEN and MiNEN, but the response is short-lived in most cases with response rates around 50-60 %. Second-line treatment alternatives are not established so far. The need for additional treatment options is evident.Combination chemotherapy with doxorubicin, cyclophosphamide and vincristine (CAV) showed efficacy in small cell lung carcinoma (SCLC) and was considered standard first-line therapy before the era of etoposide and platinum combinations. Due to a better toxicity profile, doxorubicin was replaced by epirubicin, resulting in the combination of epirubicin, cyclophosphamide and vincristine (abbreviated as EpiCO or CEV).In analogy to SCLC, selected patients with high-grade NEN were treated with the EpiCO regimen in second line (or in one patient first line) at our center. In this report we present the retrospective series of 5 cases with metastatic high-grade GEP/CUP NEN/MiNEN who received chemotherapy according to this protocol.


Assuntos
Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Vincristina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Pulmonares/patologia , Tumores Neuroendócrinos/patologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
9.
Crit Rev Oncol Hematol ; 146: 102840, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918344

RESUMO

Neuroendocrine neoplasms (NENs) are a group of tumors originating from the neuroendocrine system. They mainly occur in the digestive system and the respiratory tract. It is well-know a strict interaction between neuroendocrine system and inflammation, which can play an important role in NEN carcinogenesis. Inflammatory mediators, which are produced by the tumor microenvironment, can favor cancer induction and progression, and can promote immune editing. On the other hand, a balanced immune system represents a relevant step in cancer prevention through the elimination of dysplastic and cancer cells. Therefore, an inflammatory response may be both pro- and anti-tumorigenic. In this review, we provide an overview concerning the complex interplay between inflammation and gastroenteropancreatic NENs, focusing on the tumorigenesis and clinical implications in these tumors.


Assuntos
Neoplasias Gastrointestinais/imunologia , Mediadores da Inflamação/imunologia , Inflamação/imunologia , Neoplasias Intestinais/imunologia , Tumores Neuroendócrinos/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Gástricas/imunologia , Citocinas/metabolismo , Neoplasias Gastrointestinais/patologia , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/patologia , Microambiente Tumoral
10.
Nat Commun ; 11(1): 384, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959826

RESUMO

Emergence of an aggressive androgen receptor (AR)-independent neuroendocrine prostate cancer (NEPC) after androgen-deprivation therapy (ADT) is well-known. Nevertheless, the majority of advanced-stage prostate cancer patients, including those with SPINK1-positive subtype, are treated with AR-antagonists. Here, we show AR and its corepressor, REST, function as transcriptional-repressors of SPINK1, and AR-antagonists alleviate this repression leading to SPINK1 upregulation. Increased SOX2 expression during NE-transdifferentiation transactivates SPINK1, a critical-player for maintenance of NE-phenotype. SPINK1 elicits epithelial-mesenchymal-transition, stemness and cellular-plasticity. Conversely, pharmacological Casein Kinase-1 inhibition stabilizes REST, which in cooperation with AR causes SPINK1 transcriptional-repression and impedes SPINK1-mediated oncogenesis. Elevated levels of SPINK1 and NEPC markers are observed in the tumors of AR-antagonists treated mice, and in a subset of NEPC patients, implicating a plausible role of SPINK1 in treatment-related NEPC. Collectively, our findings provide an explanation for the paradoxical clinical-outcomes after ADT, possibly due to SPINK1 upregulation, and offers a strategy for adjuvant therapies.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumores Neuroendócrinos/genética , Neoplasias da Próstata/genética , Inibidor da Tripsina Pancreática de Kazal/metabolismo , Antagonistas de Receptores de Andrógenos/uso terapêutico , Animais , Caseína Quinase I/antagonistas & inibidores , Caseína Quinase I/metabolismo , Linhagem Celular Tumoral , Proteínas Correpressoras/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Transcrição Genética/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Am J Pathol ; 190(3): 689-701, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31953039

RESUMO

The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and an unfavorable survival rate. A better understanding of the drivers of PNET tumorigenesis is urgently needed. Distinct miRNA signatures have been identified for different stages of tumorigenesis in both human and mouse PNETs. The functions of these miRNAs are poorly understood. miR-431 is the most up-regulated miRNA in the metastatic signature. However, it is unknown whether miR-431 contributes to metastasis of PNETs. Herein, we show that miR-431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes epithelial-mesenchymal transition, migration/invasion in vitro, and metastasis in both xenograft and spontaneous mouse models of PNET. Treatment of PNET cells with Erk inhibitor or locked nucleic acids sequestering miR-431 inhibits invasion. Four target prediction modules and dual-luciferase reporter assays were used to identify potential mRNA targets of miR-431. A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 target. Overexpression of DAB2IP's rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR-431's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. Taken together, miR-431 silences DAB2IP to active Ras/Erk and promote metastasis of PNETs. miR-431 may be targeted to manage metastatic PNETs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Carcinogênese , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Metástase Neoplásica , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Ratos , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo
12.
Clin Nucl Med ; 45(3): 241-243, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977472

RESUMO

We present here a case with ß-radiation-refractory metastatic neuroendocrine tumors, who demonstrated an excellent therapy response after 1 cycle of Ac-DOTATOC, without any significant adverse effects even after 10 cycles of ß-emitter peptide receptor radionuclide therapy followed by α-peptide receptor radionuclide therapy.


Assuntos
Actínio/uso terapêutico , Progressão da Doença , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Receptores de Peptídeos/metabolismo , Idoso , Partículas beta/uso terapêutico , Feminino , Humanos , Tumores Neuroendócrinos/metabolismo , Octreotida/uso terapêutico , Resultado do Tratamento
13.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 10-14, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958924

RESUMO

Gastric carcinoma, gastrointestinal stromal tumor and gastric neuroendocrine tumor are the most common gastric neoplasms. A series of researches in 2019 showed that the safety and efficacy of laparoscopic gastrectomy in the treatment of both early and advanced gastric cancer patients are similar to open surgeries, providing a high-level evidence-based medical basis for the promotion of laparoscopic surgery in the treatment for gastric cancer. In multidisciplinary treatment and perioperative chemoradiotherapy, major research results have also been published, and clinical researches in China are gradually gaining international recognition and attention. Although the application of targeted therapy and immunotherapy has made progress, the first-line therapy after gastric cancer surgery has not been established. In the field of gastrointestinal stromal tumors, laparoscopic surgery has gradually been recognized, and surgical treatment of patients with advanced drug resistance still has its value. In terms of gastric neuroendocrine tumors, the latest researches showed that surgical methods should be selected according to tumor characteristics, and gastric adenocarcinoma with neuroendocrine components may have a worse prognosis.


Assuntos
Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , China , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Laparoscopia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Gástricas/patologia , Resultado do Tratamento
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 38-43, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958929

RESUMO

Objective: To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN). Methods: Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test. Results: In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012). Conclusions: Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.


Assuntos
Tumores Neuroendócrinos/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
16.
Am J Forensic Med Pathol ; 41(1): 75-77, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31714290

RESUMO

Ruptured esophageal varices can present as sudden death from gastrointestinal hemorrhage. The most common underlying pathology causing esophageal varices is cirrhosis leading to portal hypertension. However, not all esophageal varices arise from portal hypertension, and not all portal hypertensions are caused by cirrhosis. We present a rare case of ruptured esophageal varices casing death in an individual with metastatic tumor (high-grade) neuroendocrine tumor in the liver causing portal hypertension. This is, to the best of our knowledge, the first case report in the literature reporting a neuroendocrine tumor causing esophageal varices. This case report aims to document this rather rare entity, highlight another mechanism on how metastatic disease can result in sudden death, and give a brief review of literature on metastatic tumor in the liver causing esophageal varices.


Assuntos
Varizes Esofágicas e Gástricas/patologia , Hemorragia Gastrointestinal/patologia , Hipertensão Portal/complicações , Neoplasias Hepáticas/patologia , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Hipertensão Portal/etiologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Ruptura Espontânea/etiologia , Ruptura Espontânea/patologia
17.
Am J Clin Pathol ; 153(1): 74-81, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415691

RESUMO

OBJECTIVES: This study aimed to determine whether Ki-67 index evaluated on cytologic material could reliably grade pancreatic neuroendocrine tumors (PanNETs). METHODS: Cases with adequate cell block and available surgical specimens were included. Ki-67 index was calculated using "eyeballing," "hot spot," and "complete" counting methods. RESULTS: The overall concordance rates between cytology and surgical specimens were 71%, 73%, and 59%, respectively, by using eyeballing, hot spot, and complete counting approaches. All grade 1 tumors were correctly graded on cytology, but in grade 2 tumors concordance rates were only 36%, 41%, and 9%, respectively. All grade 2 tumors were undergraded when cell blocks contained fewer than 1,000 cells, while concordance rate increased to 57%, 64%, and 14%, respectively, in cases with 1,000 cells or more. CONCLUSIONS: Grade 2 PanNETs can be significantly undergraded when Ki-67 index is evaluated on cell block material. In cases with 1,000 or more cells, the hot spot counting method has better correlation with surgical specimens.


Assuntos
Antígeno Ki-67/análise , Tumores Neuroendócrinos/classificação , Neoplasias Pancreáticas/classificação , Adulto , Biópsia por Agulha Fina , Biologia Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Manejo de Espécimes
18.
Am J Clin Pathol ; 153(1): 99-104, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31587038

RESUMO

OBJECTIVES: We investigated the ability of routine flow cytometry (FC) to detect nonhematologic neoplasms (non-HN) using antibody panels routinely used for the diagnosis of hematologic neoplasms. METHODS: FC analyses of 4,000 various diagnostic samples were retrospectively reviewed to identify cases in which an aberrant, viable CD45-negative, nonhematologic neoplastic population was detected by FC panels designed to evaluate hematologic neoplasms. RESULTS: A total of 57 (1.4%) diverse non-HNs were identified, representing neuroendocrine tumors (33/57) and carcinomas (9/57), as well as other malignancies (15/57) such as sarcoma and melanoma. The majority of neoplasms were positive for at least one antibody, typically CD56 (43/51, 84.3%), followed by CD117 (15/34, 44.1%) and CD138 (6/33, 18.2%). CONCLUSIONS: Our findings highlight the importance of carefully inspecting CD45-negative events to identify non-HNs by routine FC analysis. This can help expedite further downstream immunophenotypic analysis of specimens and triage samples for appropriate genetic and molecular studies.


Assuntos
Citometria de Fluxo , Neoplasias Hematológicas/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Medula Óssea/patologia , Neoplasias Hematológicas/patologia , Humanos , Imunofenotipagem , Antígenos Comuns de Leucócito/metabolismo , Tumores Neuroendócrinos/patologia
19.
Surgery ; 167(1): 180-186, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31537303

RESUMO

BACKGROUND: Many current guidelines recommend nonoperative management for pancreatic neuroendocrine tumors <2 cm. The objective of this study was to evaluate the utilization and outcomes of resection for these pancreatic neuroendocrine tumors in the United States. METHODS: Using the National Cancer Database (2004-2014), 3,243 cases of T1 (≤2.0 cm) pancreatic neuroendocrine tumors were identified. Additional patient and tumor characteristics were examined. Multivariate models were used to identify factors that predicted resection and to assess patient survival after resection. RESULTS: 75% of pancreatic neuroendocrine tumors measuring 0 to 1.0 cm and 80% of pancreatic neuroendocrine tumors measuring >1.0 and ≤2.0 cm were resected. Eighty-four pancreatic neuroendocrine tumors were functional, of which 82% were resected. Variables influencing resection included positive lymph nodes, tumor in body or tail of pancreas, well or moderately differentiated tumors, and resection at academic medical centers (odds ratio 1.5-4.9). When controlling for other variables, patients with pancreatic neuroendocrine tumors 1 to 2 cm who underwent resection had a prolonged 5-year survival rate (hazard ratio 0.51, confidence interval 0.34-0.75) when compared with those who did not undergo resection. This survival benefit of resection was not found for pancreatic neuroendocrine tumors 0 to 1 cm (hazard ratio = 0.63, confidence interval 0.36-1.11). CONCLUSIONS: Contrary to many current recommendations, most patients with pancreatic neuroendocrine tumors ≤2.0 cm undergo surgical resection in the United States. A survival benefit was found for resection of pancreatic neuroendocrine tumors 1 to 2 cm, suggesting that current recommendations should perhaps be revised.


Assuntos
Tumores Neuroendócrinos/cirurgia , Pâncreas/patologia , Pancreatectomia/normas , Neoplasias Pancreáticas/cirurgia , Padrões de Prática Médica/normas , Idoso , Tomada de Decisão Clínica/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Pâncreas/cirurgia , Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral , Estados Unidos/epidemiologia
20.
Surgery ; 167(1): 189-196, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629542

RESUMO

BACKGROUND: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2. METHODS: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography. RESULTS: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration. CONCLUSION: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.


Assuntos
Inibidores de Histona Desacetilases/administração & dosagem , Imagem Molecular/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Receptores de Somatostatina/metabolismo , Animais , Linhagem Celular Tumoral , Separação Celular , Depsipeptídeos/administração & dosagem , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Tumores Neuroendócrinos/patologia , Compostos Organometálicos/administração & dosagem , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Análise Serial de Tecidos , Transcrição Genética/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA