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1.
Support Care Cancer ; 29(1): 49-66, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32734392

RESUMO

PURPOSE: Taste and smell disturbances in patients affected by cancer are very common, but often under-recognized symptoms. If not addressed properly, they may impact nutritional status, food enjoyment, and quality of life. Treatment tools available for clinicians to manage chemosensory alterations are limited and are often based on personal clinical experiences. The aim of this study was to assess current oncological and palliative care literature through a scoping review, in order to identify available treatments for taste and smell alterations in cancer patients. METHODS: Medline, Embase, CINAHL, ProQuest Dissertations and Theses, and Google Scholar were searched from inception until January 2020, with subject headings relevant to the domains of chemosensory alterations, palliative, and cancer care. A total of 10,718 English and French language publications were reviewed, yielding 43 articles on the researched topic. RESULTS: The heterogeneity of selected articles led to difficulties in interpretation and analysis of the available evidence. Included publications differed in study design, population sample, anticancer treatments, and measures of assessment for taste and smell disturbances. A broad variety of treatment options were described including zinc and polaprezinc, radio-protectors, vitamins and supplements, anti-xerostomia agents, active swallowing exercises, nutritional interventions, delta-9-tetrahydrocannabinol, and photobiomodulation. CONCLUSION: This scoping review identifies the current state of knowledge regarding chemosensory alterations within supportive cancer care. Despite not reaching firm conclusions, this article offers therapeutic venues to further explore in larger and more methodologically sound studies.


Assuntos
Transtornos do Olfato/tratamento farmacológico , Olfato/fisiologia , Distúrbios do Paladar/tratamento farmacológico , Paladar/fisiologia , Adulto , Amifostina/uso terapêutico , Carnosina/análogos & derivados , Carnosina/uso terapêutico , Dronabinol/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Estado Nutricional/fisiologia , Transtornos do Olfato/patologia , Compostos Organometálicos/uso terapêutico , Cuidados Paliativos/métodos , Qualidade de Vida/psicologia , Selênio/uso terapêutico , Distúrbios do Paladar/patologia , Compostos de Zinco/uso terapêutico
2.
Br J Radiol ; 94(1117): 20201041, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095671

RESUMO

OBJECTIVES: Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting. METHODS: A total of 468 metastatic/advanced NET patients (wide range of primary sites including CUP-NETs), who underwent at least two cycles of 177Lu-DOTATATE PRRT with available follow-up information, were included and analysed retrospectively in this study. In-house labelling of DOTATATE with 177Lu (direct route produced) was carried out in the hospital radiopharmacy and treatment administered in cycles (dose: 5.55 to 7.4 GBq per patient), at 10-12 weeks interval. The assessment of long-term outcome was undertaken under three broad headings: (a) Therapeutic response, (b) Survival outcome and (c) Toxicity assessment. The median point estimate with 95% CI for progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic covariates for association with PFS and OS was investigated by Cox proportional hazards model (univariate and multivariate Hazard Ratios) and with disease control rate (DCR) by Chi-square test, with significant P value defined as <0.05. RESULTS: Long-term outcome (follow-up ranging from 4 to 97.6 months; median period:46 months following first 177Lu-DOTATATE PRRT) results showed, (i) on symptomatic response evaluation scale, complete response (CR) in 214 patients (45.7%), partial response (PR) in 108 (23.1%), stable disease (SD) in 118 (25.2%), progressive disease (PD) in 28 (6%). (ii) Biochemical response evaluation showed CR in 52 (12%), PR in 172 (40%), SD in 161 (38%), and PD in 42 patients (10%). (iii) Molecular imaging response (by PERCIST criteria) showed CR in 29 (6%), PR in 116 (25%), SD in 267 (57%) and PD in 56 (12%) patients. (iv) On RECIST 1.1 criteria, CR was observed in 14 patients (3%), PR in 126 patients (27%), SD in 282 patients (60%) and PD in 46 patients (10%). The median PFS and OS were not reached at a median follow-up of 46 months. Observed PFS and OS at 7 years were 71.1% 95% CI (62.4-79.7%) and 79.4% 95% CI (71.4-86.9%) respectively. PFS was dependent on previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake, site of primary tumour, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake and number of PRRT cycles. The OS was dependent on baseline 68Ga-DOTATATE uptake, site of primary tumour, presence of bony metastatic disease, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for bony metastatic disease and number of PRRT cycles. Transient haematological toxicity of Grade 1, Grade 2, and Grade 3 was found in 8 (1.7%), 1 (0.2%) and one patient (0.2%), respectively. Nephrotoxicity of Grade 1, Grade 2, Grade 3, and Grade 4 were seen in 16 (3.5%), 3 (0.6%), 2 (0.4%) and one patient (0.2%), respectively. On a separate sub-analysis of 322 NET patients with progressive disease at the initiation point of PRRT, overall response rates (CR + PR + SD) were 93.5%, 88.5%, 89.1 and 87.9% on symptomatic, biochemical, RECIST 1.1 and PERCIST criteria and PFS and OS at 7 years 68.3% and 79.2%, respectively. CONCLUSIONS: The present results demonstrate that 177Lu-DOTATATE PRRT improved symptoms and biochemical markers substantially in most of the NET patients, with disease stabilisation on both anatomical and molecular imaging in majority and response in a sizeable fraction. Additionally, the therapeutic protocol with lesser dose per cycle (mean 5.92 GBq/cycle) and prolonged duration (over 5 cycles and 1.5 years) in a metastatic NET setting proved equally efficacious (with superior PFS and OS rates) and relatively better tolerated with minimal toxicity. ADVANCES IN KNOWLEDGE: The present work critically examines the long-term results, survival outcome and toxicity profile of the indigenous 177Lu-DOTATATE (produced through direct neutron activation of enriched 176Lu) in metastatic progressive NETs across a wide range of primary sites and malignancies. Such long-term outcome data establishes the favourable impact of PRRT in a wide patient base and also the therapeutic efficacy of the product.


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/secundário , Octreotida/análogos & derivados , Octreotida/análise , Compostos Organometálicos/uso terapêutico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos Retrospectivos , Análise de Sobrevida , Atenção Terciária à Saúde , Resultado do Tratamento , Adulto Jovem
3.
Antivir Chem Chemother ; 28: 2040206620983780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33353394

RESUMO

BACKGROUND: Gallium has demonstrated strong anti-inflammatory activity in numerous animal studies, and has also demonstrated direct antiviral activity against the influenza A H1N1 virus and the human immunodeficiency virus (HIV). Gallium maltolate (GaM), a small metal-organic coordination complex, has been tested in several Phase 1 clinical trials, in which no dose-limiting or other serious toxicity was reported, even at high daily oral doses for several months at a time. For these reasons, GaM may be considered a potential candidate to treat coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus and can result in severe, sometimes lethal, inflammatory reactions. In this study, we assessed the ability of GaM to inhibit the replication of SARS-CoV-2 in a culture of Vero E6 cells. METHODS: The efficacy of GaM in inhibiting the replication of SARS-CoV-2 was determined in a screening assay using cultured Vero E6 cells. The cytotoxicity of GaM in uninfected cells was determined using the Cell Counting Kit-8 (CCK-8) colorimetric assay. RESULTS: The results showed that GaM inhibits viral replication in a dose-dependent manner, with the concentration that inhibits replication by 50% (EC50) being about 14 µM. No cytotoxicity was observed at concentrations up to at least 200 µM. CONCLUSION: The in vitro activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Compostos Organometálicos/farmacologia , Pironas/farmacologia , /efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antivirais/uso terapêutico , Antivirais/toxicidade , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ferro/metabolismo , Compostos Organometálicos/uso terapêutico , Compostos Organometálicos/toxicidade , Pironas/uso terapêutico , Pironas/toxicidade , Células Vero , Replicação Viral/efeitos dos fármacos
4.
Dalton Trans ; 49(45): 16004-16033, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33030464

RESUMO

In light of the Covid-19 outbreak, this review brings together historical and current literature efforts towards the development of antiviral metallodrugs. Classical compounds such as CTC-96 and auranofin are discussed in depth, as pillars for future metallodrug development. From the recent literature, both cell-based results and biophysical assays against potential viral biomolecule targets are summarized here. The comprehension of the biomolecular targets and their interactions with coordination compounds are emphasized as fundamental strategies that will foment further development of metal-based antivirals. We also discuss other possible and unexplored methods for unveiling metallodrug interactions with biomolecules related to viral replication and highlight the specific challenges involved in the development of antiviral metallodrugs.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Complexos de Coordenação/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/farmacologia , Complexos de Coordenação/farmacologia , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Humanos , Compostos Organometálicos/farmacologia , Pandemias , Pneumonia Viral/epidemiologia
5.
PLoS One ; 15(10): e0237270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33001974

RESUMO

OBJECTIVES: We aimed to elucidate the prognostic factors of the patients with taste disorders who were treated with popular and common medication in Japan. MATERIALS AND METHODS: A retrospective study on the medical charts of a total of 255 patients with taste disorders who were treated primarily with oral medication including a zinc agent. RESULTS: The factors below were significantly linked with poor prognosis: 1) male gender, 2) taste disorders that began 3 months before starting treatment and 3) a severe taste disorder grade at the initial visit. CONCLUSIONS: We have concluded that the prognosis for the patients with taste disorders who were treated by popular and standard medication therapy in Japan recently was significantly linked to gender, the period of 3 months before starting the treatment and the severity of the disorder at the time of diagnosis. In addition, we recognized some limitations we should resolve in further research including a method of measuring "umami" and so on. CLINICAL RELEVANCE: Better awareness of these factors should be clinically useful when we manage patients with taste disorders. Earlier treatment should be started to cure the symptoms.


Assuntos
Carnosina/análogos & derivados , Compostos Organometálicos/uso terapêutico , Distúrbios do Paladar/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carnosina/administração & dosagem , Carnosina/uso terapêutico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Paladar/efeitos dos fármacos , Paladar/fisiologia , Distúrbios do Paladar/fisiopatologia , Limiar Gustativo/efeitos dos fármacos , Limiar Gustativo/fisiologia , Resultado do Tratamento , Adulto Jovem , Compostos de Zinco/administração & dosagem , Compostos de Zinco/uso terapêutico
6.
Nucleic Acids Res ; 48(17): 9986-9994, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32853337

RESUMO

Telomeric DNA, whose length homeostasis is closely correlated with immortality of cancer cells, is regarded as a molecular clock for cellular lifespan. Regarding the capacity in forming G-quadruplex, G-rich 3'-overhang (G-overhang) has been considered as an attractive anticancer target. However, it is still challenging to precisely target telomeric G-overhang with current ligands because of the polymorphism of G-quadruplexes in cells. Herein, we construct a telomeric G-overhang-specific near-infrared-traceable DNA nano-hydrolase, which is composed of four parts: (i) dexamethasone for targeting cell nuclei; (ii) complementary DNA for hybridizing with G-overhang; (iii) multinuclear Ce(IV) complexes for hydrolyzing G-overhang; and (iv) upconversion nanoparticles for real-time tracking. The multivalent targeted DNA nano-hydrolase can be traced to precisely digest telomeric G-overhang, which contributes to telomeric DNA shortening and thereby causes cell aging and apoptosis. The anticancer treatment is further proved by in vivo studies. In this way, this design provides a telomeric G-overhang-specific eradication strategy based on a non-G-quadruplex targeting manner.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Compostos Organometálicos/farmacologia , Telômero/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Cério/química , Dexametasona/química , Quadruplex G , Humanos , Hidrólise , Células MCF-7 , Camundongos , Nanopartículas/metabolismo , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/uso terapêutico , Telômero/química
7.
Clin Nucl Med ; 45(9): 714-715, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32657872

RESUMO

The efficacy of Lu-DOTATATE in large neuroendocrine tumors (NETs) is reduced because of the lower energy (Eßmax 0.497 MeV) and shorter range of Lu. The pure ß-emitter Y with its longer ß range is more effective in larger tumors. This should be balanced with the greater risk of Y-DOTATATE-related nephrotoxicity. Sequential duo-peptide receptor radionuclide therapy may result in a better response with minimal adverse effects in large-volume heterogeneous NETs. A 56-year-old man with large rectal NET liver metastases, treated with Y-DOTATATE and Lu-DOTATATE and sequential duo-peptide receptor radionuclide therapy, presented with post-Y-DOTATATE bremsstrahlung and PET/CT in comparison with Ga-DOTATATE PET/CT and Lu-DOTATATE scans.


Assuntos
Complexos de Coordenação/uso terapêutico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Receptores de Peptídeos/metabolismo , Carga Tumoral , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Octreotida/uso terapêutico , Carga Tumoral/efeitos da radiação
8.
Clin Nucl Med ; 45(9): e393-e399, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32604121

RESUMO

PURPOSE: Advanced inoperable/metastatic neuroendocrine tumors (NETs) pose a therapeutic challenge with limited treatment options. Peptide receptor radionuclide therapy (PRRT), being specific in targeting the somatostatin receptors, is a promising and viable option in this setting. In this study, we intended to evaluate the role of PRRT as the first-line systemic therapy in advanced inoperable/metastatic NETs. METHODS: Data of consecutive patients of advanced inoperable/metastatic NETs treated with first-line Lu-DOTATATE at our center, from September 2012 to August 2019, were collected and analyzed. RESULTS: Forty-five patients (median age, 50 years; range, 14-72 years) with treatment-naive advanced NETs received a median cumulative dose of 27 GBq (range, 13.3-41.3 GBq; over 2-7 cycles) Lu-DOTATATE and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Three patients were lost to follow-up, 2 had nonmeasurable lesions on CT, and hence, radiological response using Response Evaluation Criteria in Solid Tumors version 1.1 could be assessed in 40 patients. Twelve of 40 patients (30%) showed a partial response, whereas stable disease was observed in 22 of 40 patients (55%). Disease progression was limited to 6 of 40 patients (15%). Treatment-related adverse effects were minimal with grade 3/4 anemia, leukopenia, neutropenia, and hepatotoxicity observed in 2%, 2%, 4%, and 4% of the patients, respectively. Median progression-free survival was 48 months (95% confidence interval, 34.7-61.3 months). CONCLUSIONS: Our results indicate the efficacy and safety of first-line PRRT in advanced NETs. Future randomized trials, comparing PRRT and somatostatin analogs in treatment-naive patients, are required to identify the definite sequence of treatment options for these patients.


Assuntos
Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Receptores de Peptídeos/metabolismo , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/cirurgia , Octreotida/uso terapêutico , Intervalo Livre de Progressão , Adulto Jovem
9.
Clin Nucl Med ; 45(11): e493-e494, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32604119

RESUMO

The whole-body absolute quantification of Lu-DOTATATE therapy was achieved using a high-speed 360° CZT SPECT/CT system. Twelve high-resolution swelling detectors may be positioned close to patients, providing a high-count sensitivity that is particularly advantageous for the low-count rate conditions of Lu imaging. After initially validating Lu quantification on phantom, serial whole-body SPECT/CT acquisitions of only 20 minutes were obtained for a 70-year-old woman treated by Lu-DOTATATE injections for a metastatic recurrence of a pancreatic neuroendocrine tumor. The progressive decrease in tumor uptake between the consecutive Lu-DOTATATE injections could be quantified, and thereby the corresponding dosimetry changes could be estimated.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Imagem Corporal Total/instrumentação , Idoso , Estudos de Viabilidade , Feminino , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Imagens de Fantasmas , Radiometria
12.
PLoS One ; 15(6): e0235006, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559258

RESUMO

Distal limb wounds are common injuries sustained by horses and their healing is fraught with complications due to equine anatomy, prevalence of infection, and challenges associated with wound management. Gallium is a semi-metallic element that has been shown to possess antimicrobial properties and aid in wound healing in various preclinical models. The effects of Gallium have not been studied in equine wound healing. Therefore, the objective of this study was to compare healing rates between gallium-treated and untreated wounds of equine distal limbs and to demonstrate the antimicrobial effects of gallium on wounds inoculated with S. aureus. Using an established model of equine wound healing we demonstrated beneficial effects of 0.5% topical gallium maltolate on equine wound healing. Specifically we documented reduced healing times, reduced bioburden, and reduced formation of exuberant granulation tissue in wounds treated with gallium maltolate as compared with untreated wounds. Gallium appeared to exert its beneficial effects via its well-described antimicrobial actions as well as by altering the expression of specific genes known to be involved in wound healing of horses and other animals. Specifically, gallium maltolate appeared to increase expression of transforming growth factor-ß in both infected and un-infected wounds. Further work is needed to document the effects of gallium on naturally occurring equine wounds and to compare the effects of gallium with other wound treatment options. These data, however, suggest that gallium may be an attractive and novel means of improving equine distal limb wound healing.


Assuntos
Antibacterianos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Traumatismos da Perna/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Pironas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Carga Bacteriana , Citocinas/genética , Citocinas/metabolismo , Doenças dos Cavalos/metabolismo , Cavalos , Traumatismos da Perna/metabolismo , Traumatismos da Perna/veterinária , Compostos Organometálicos/administração & dosagem , Pironas/administração & dosagem , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/veterinária , Cicatrização
13.
Tumori ; 106(4): 325-332, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32567505

RESUMO

INTRODUCTION: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. METHODS: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: 18F-FDG, 18F-choline (FCH), and 68Ga-PSMA. RESULTS: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue 18F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). CONCLUSIONS: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2-positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.


Assuntos
Infecções por Coronavirus/diagnóstico , Neoplasias/diagnóstico , Pneumonia Viral/diagnóstico , Pneumonia/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Betacoronavirus/patogenicidade , Meios de Contraste/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Surtos de Doenças , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Itália/epidemiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Glicoproteínas de Membrana/uso terapêutico , Neoplasias/complicações , Neoplasias/terapia , Neoplasias/virologia , Compostos Organometálicos/uso terapêutico , Pandemias , Pneumonia/complicações , Pneumonia/terapia , Pneumonia/virologia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Compostos Radiofarmacêuticos/uso terapêutico
16.
J Cancer Res Clin Oncol ; 146(6): 1533-1543, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32281025

RESUMO

PURPOSE: To evaluate the efficacy of 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) radionuclide therapy in patients with inoperable or metastatic neuroendocrine tumours (NETs), (PROSPERO ID CRD42019130755). METHODS: All published clinical studies of NETs treated with 177Lu-DOTATATE were identified based on systematic searches in the PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov databases up to January 2019. Among these studies, only the reports evaluated with the "Response Evaluation Criteria in Solid Tumours (RECIST)" or "Southwest Oncology Group (SWOG)" criteria or both were included. We analysed the disease response rate (DRR) and disease control rate (DCR) of each group to evaluate the efficacy of 177Lu-DOTATATE. RESULTS: Fifteen studies were selected from 715 references. The pooled effect in the RECIST group (13 studies) was 27.58% (95% confidence interval (CI) 21.03-35.27%) for the DRR and 79.14% (95% CI 75.83-82.1%) for the DCR. In the SWOG criteria group (7 studies), the pooled effect was 20.59% (95% CI 10.89-35.51%) for the DRR and 78.28% (95% CI 74.39-81.72%) for the DCR. Therefore, the RECIST and SWOG groups showed similar DRRs and DCRs after177Lu-DOTATATE treatment, indicating that 177Lu-DOTATATE treatment has excellent efficacy with a control rate of approximately 78-79%. Moreover, adverse effects of 177Lu-DOTATATE were minimal, including fatigue, nausea, vomiting and hormonal disorders. CONCLUSIONS: For patients with inoperable or metastatic NETs, 177Lu-DOTATATE is an effective treatment with minimal side effects.


Assuntos
Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Metástase Neoplásica , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico
17.
BJU Int ; 125(6): 876-883, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32181951

RESUMO

OBJECTIVES: To examine the anatomical distribution of prostate cancer (PCa) recurrence on gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron-emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after undergoing radical prostatectomy (RP) with pathological lymph node metastasis (pN1) in their extended pelvic lymph node dissection (ePLND), and to compare the location of PCa recurrence with the location of the initial lymph node metastasis at ePLND. MATERIALS AND METHODS: We retrospectively reviewed 100 patients with BCR (PSA 0.05-5.00 ng/mL) after RP with pN1 ePLND who underwent 68 Ga-PSMA PET/CT to guide salvage therapy. Clinical and pathological features and anatomical locations of PCa recurrence on 68 Ga-PSMA PET/CT were obtained, and management impact was recorded. RESULTS: In all, 68 patients (68%) had a positive and 32 patients (32%) had a negative 68 Ga-PSMA PET/CT result. Of the 68 patients with a positive 68 Ga-PSMA PET/CT, 44 (65%) showed abnormal uptake only in the pelvic area, seven (10%) only outside the pelvic area, and 17 (25%) both within and outside the pelvic area. 68 Ga-PSMA PET/CT-positive pelvic lymph nodes were often (84%) detected on the same side as the lymph node metastasis diagnosed at ePLND. Based on the outcomes of the 68 Ga-PSMA PET/CT, change of management was noted in 68% of the patients. CONCLUSION: Recurrence of PCa on 68 Ga-PSMA PET/CT was limited to the pelvis in the majority of patients with BCR after RP with pN1 ePLND. Moreover, recurrence was often detected on the same side as the lymph node metastasis at ePLND. The results confirm the diagnostic value of 68 Ga-PSMA PET/CT in patients with BCR after RP with pN1 ePLND. Prospective studies are needed to support the long-term benefit of 68 Ga-PSMA PET/CT-dictated management changes.


Assuntos
Metástase Linfática , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata , Idoso , Humanos , Excisão de Linfonodo , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Glicoproteínas de Membrana/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos Organometálicos/uso terapêutico , Próstata/diagnóstico por imagem , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos
18.
Dig Dis Sci ; 65(7): 1917-1931, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32170476

RESUMO

As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.


Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Amoxicilina/uso terapêutico , Antígenos de Bactérias/análise , Biópsia , Bismuto/uso terapêutico , Testes Respiratórios , Claritromicina/uso terapêutico , Técnicas de Cultura , Doxiciclina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Dispepsia/etiologia , Fezes/química , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Levofloxacino/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/etiologia , Metronidazol/uso terapêutico , Compostos Organometálicos/uso terapêutico , Úlcera Péptica/etiologia , Reação em Cadeia da Polimerase , Rifabutina/uso terapêutico , Salicilatos/uso terapêutico , Terapia de Salvação , Testes Sorológicos , Neoplasias Gástricas/etiologia , Tetraciclina/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Ureia/metabolismo
19.
Lancet Oncol ; 21(4): 561-570, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112737

RESUMO

BACKGROUND: In patients with metastatic neuroendocrine neoplasms, the liver is the most commonly affected organ and a crucial factor for prognosis and survival. Peptide receptor radionuclide therapy can prolong progression-free survival in these patients. Additional treatment of liver disease might further improve outcomes. We aimed to investigate the safety and efficacy of additional holmium-166 (166Ho) radioembolisation after peptide receptor radionuclide therapy in patients with metastatic liver neuroendocrine neoplasms. METHODS: The Holmium Embolization Particles for Arterial Radiotherapy Plus 177Lu-Dotatate in Salvage Neuroendocrine Tumour Patients (HEPAR PLuS) study was a single-centre, phase 2 study done at the University Medical Center Utrecht (Utrecht, Netherlands). Patients, aged at least 18 years, with histologically proven grade 1 or 2 neuroendocrine neoplasms of all origins, an Eastern Cooperative Oncology Group performance status of 0-2, and three or more measurable liver metastases according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria received 166Ho-radioembolisation within 20 weeks after four cycles of peptide receptor radionuclide therapy (lutetium-177-dotatate [177Lu-dotatate]). The primary endpoint was objective liver tumour response in the treated liver volume, defined as complete response (disappearance of all lesions) or partial response (≥30% decrease in the sum of the longest diameters of the target lesions, compared with baseline measurements), according to RECIST 1.1, analysed per protocol at 3 months. Safety was assessed in all patients who received treatment. This study is registered with ClinicalTrials.gov, NCT02067988. Recruitment is completed and long-term follow-up is ongoing. FINDINGS: From Oct 15, 2014, to Sept 12, 2018, 34 patients were assessed for eligibility. 31 patients received treatment and 30 (97%) patients were available for primary endpoint assessment and completed 6 months of follow-up. Three (9%) patients were excluded at screening and one (3%) patient was treated and died before the primary endpoint and was replaced. According to the per-protocol analysis 13 (43%; 95% CI 26-63) of 30 patients achieved an objective response in the treated volume. The most frequently reported Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 clinical and laboratory toxicities within 6 months included abdominal pain (three [10%] of 31 patients), increased γ-glutamyl transpeptidase (16 [54%]), and lymphocytopenia (seven [23%]). One (3%) fatal treatment-related serious adverse event occurred (radioembolisation-induced liver disease). Two (6%) patients had serious adverse events deemed to be unrelated to treatment (gastric ulcer and perforated cholecystitis). INTERPRETATION: 166Ho-radioembolisation, as an adjunct to peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm liver metastases, is safe and efficacious. Radioembolisation can be considered in patients with bulky liver disease, including after peptide receptor radionuclide therapy. A future randomised, controlled study should investigate the added benefit of this treatment on progression-free survival. FUNDING: None.


Assuntos
Embolização Terapêutica/métodos , Hólmio/uso terapêutico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Radioisótopos/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
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