Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.477
Filtrar
1.
Am Surg ; 86(5): 429-436, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684027

RESUMO

BACKGROUND: A randomized controlled trial (RCT) of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting. METHODS: Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed. RESULTS: Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts (P ≤.001) and softer glands (P = .04). For all pancreatectomies, there was no difference in POPF rates (OR 0.84; 95% CI 0.60-1.16, P = .29). Patients undergoing distal pancreatectomy (OR 0.70; 95% CI 0.30-1.63, P = .41) had similar rates of POPF versus pancreaticoduodenectomy (PD) patients that experienced a lower incidence of POPF (OR 0.60; 95% CI 0.42-0.86, P = .006). Mortality rates and LOS were similar. Readmission rates were decreased with pasireotide (OR 0.61; 95% CI 0.44-0.85). CONCLUSIONS: Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD and decreased readmission rates. Further prospective, randomized studies are warranted.


Assuntos
Pancreatectomia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia , Complicações Pós-Operatórias/prevenção & controle , Somatostatina/análogos & derivados , Humanos , Somatostatina/uso terapêutico
2.
J Surg Oncol ; 122(2): 195-203, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474957

RESUMO

BACKGROUND AND OBJECTIVES: Pasireotide was shown in a randomized trial to decrease the rate of postoperative pancreatic fistula (POPF). However, retrospective series from other centers have failed to confirm these results. METHODS: Patients who underwent pancreatoduodenectomy or distal pancreatectomy between January 2014 and February 2019 were included. Patients treated after November 2016 routinely received pasireotide and were compared to a retrospective cohort. Multivariate analysis was performed for the outcome of clinically relevant POPF (CR-POPF), with stratification by fistula risk score (FRS). RESULTS: Ninety-nine of 300 patients received pasireotide. The distribution of high, intermediate, low, and negligible risk patients by FRS was comparable (P = .487). There were similar rates of CR-POPF (19.2% pasireotide vs 14.9% control, P = .347) and percutaneous drainage (12.1% vs 10.0%, P = .567), with greater median number of drain days in the pasireotide group (6 vs 4 days, P < .001). Multivariate modeling for CR-POPF showed no correlation with operation or pasireotide use. Adjustment with propensity weighted models for high (OR, 1.02, 95% CI, 0.45-2.29) and intermediate (OR, 1.02, CI, 0.57-1.81) risk groups showed no correlation of pasireotide with reduction in CR-POPF. CONCLUSIONS: Pasireotide administration after pancreatectomy was not associated with a decrease in CR-POPF, even when patients were stratified by FRS.


Assuntos
Pancreatectomia/métodos , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/métodos , Somatostatina/análogos & derivados , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreatectomia/efeitos adversos , Pancreatectomia/estatística & dados numéricos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Lesões Pré-Cancerosas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Risco , Somatostatina/administração & dosagem
4.
Health Qual Life Outcomes ; 18(1): 188, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546236

RESUMO

BACKGROUND: Patients with metastatic small-intestinal neuroendocrine tumours (NET) have been shown to have a reduced quality of life compared to the general population and many have disabling symptoms during somatostatin analogue (SSA) treatment. The aim of this prospective study was to document the patient-reported symptoms, coping and quality of life during SSA treatment and to measure patients' fat-soluble vitamin levels. METHODS: Patients with metastatic small-intestinal NET on treatment with long-acting SSA were included. Data on patient characteristics, blood samples, questionnaires (EORTC-QLQ-C30 and GI.NET-21) and structured patient interviews were collected at inclusion and after 1 year. RESULTS: Eighty-eight patients were included, 77 (88%) attended 1 year follow-up. Approximately 50% of patients reported symptoms, the most common symptoms at baseline and after 1 year follow-up were diarrhoea, flatulence, fatigue, abdominal discomfort and sore injection lumps. Diarrhoea and fatigue were reported as their main complaint, 23% had > 5 daily episodes of diarrhoea and 59% reported fatigue. However, patients reported a high perceived quality of life, high daily activity, coped with their symptoms and managed their daily life well. Deficiency of vitamin D (27%) and A (13%) were observed. CONCLUSIONS: Patients with metastatic small-intestinal NET on SSA treatment reported a high frequency of symptoms. Minor improvements were seen after 1-year of follow-up, illustrating that many symptoms might be difficult to improve, or may not be recognised by the health service. Patients, however, generally reported a high quality of life. Care for NET patients on SSA treatment should include a regular systematic symptom registration and vitamin measurements.


Assuntos
Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Somatostatina/efeitos adversos , Adaptação Psicológica , Adulto , Idoso , Feminino , Humanos , Neoplasias Intestinais/psicologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/psicologia , Estudos Prospectivos , Somatostatina/análogos & derivados , Inquéritos e Questionários
5.
Eur J Endocrinol ; 183(1): G17-G23, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-205229

RESUMO

Patients with pituitary tumours, ensuing hormonal abnormalities and mass effects are usually followed in multidisciplinary pituitary clinics and can represent a management challenge even during the times of non-pandemic. The COVID-19 pandemic has put on hold routine medical care for hundreds of millions of patients around the globe, while many pituitary patients' evaluations cannot be delayed for too long. Furthermore, the majority of patients with pituitary tumours have co-morbidities potentially impacting the course and management of COVID-19 (e.g. hypopituitarism, diabetes mellitus, hypertension, obesity and cardiovascular disease). Here, we summarize some of the diagnostic and management dilemmas encountered, and provide guidance on safe and as effective as possible delivery of care in the COVID-19 era. We also attempt to address how pituitary services should be remodelled in the event of similar crises, while maintaining or even improving patient outcomes. Regular review of these recommendations and further adjustments are needed, depending on the evolution of the COVID-19 pandemic status. We consider that the utilization of successful models of pituitary multidisciplinary care implemented during the COVID-19 pandemic should continue after the crisis is over by using the valuable and exceptional experience gained during these challenging times.


Assuntos
Adenoma/terapia , Antineoplásicos Hormonais/uso terapêutico , Infecções por Coronavirus , Agonistas de Dopamina/uso terapêutico , Procedimentos Neurocirúrgicos , Pandemias , Apoplexia Hipofisária/terapia , Neoplasias Hipofisárias/terapia , Pneumonia Viral , Adenoma/diagnóstico , Cabergolina/uso terapêutico , Gerenciamento Clínico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Apoplexia Hipofisária/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Guias de Prática Clínica como Assunto , Radioterapia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Telemedicina , Fatores de Tempo , Testes de Campo Visual
6.
Eur J Endocrinol ; 183(1): G17-G23, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32369770

RESUMO

Patients with pituitary tumours, ensuing hormonal abnormalities and mass effects are usually followed in multidisciplinary pituitary clinics and can represent a management challenge even during the times of non-pandemic. The COVID-19 pandemic has put on hold routine medical care for hundreds of millions of patients around the globe, while many pituitary patients' evaluations cannot be delayed for too long. Furthermore, the majority of patients with pituitary tumours have co-morbidities potentially impacting the course and management of COVID-19 (e.g. hypopituitarism, diabetes mellitus, hypertension, obesity and cardiovascular disease). Here, we summarize some of the diagnostic and management dilemmas encountered, and provide guidance on safe and as effective as possible delivery of care in the COVID-19 era. We also attempt to address how pituitary services should be remodelled in the event of similar crises, while maintaining or even improving patient outcomes. Regular review of these recommendations and further adjustments are needed, depending on the evolution of the COVID-19 pandemic status. We consider that the utilization of successful models of pituitary multidisciplinary care implemented during the COVID-19 pandemic should continue after the crisis is over by using the valuable and exceptional experience gained during these challenging times.


Assuntos
Adenoma/terapia , Antineoplásicos Hormonais/uso terapêutico , Infecções por Coronavirus , Agonistas de Dopamina/uso terapêutico , Procedimentos Neurocirúrgicos , Pandemias , Apoplexia Hipofisária/terapia , Neoplasias Hipofisárias/terapia , Pneumonia Viral , Adenoma/diagnóstico , Cabergolina/uso terapêutico , Gerenciamento Clínico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Apoplexia Hipofisária/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Guias de Prática Clínica como Assunto , Radioterapia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Telemedicina , Fatores de Tempo , Testes de Campo Visual
7.
Eur J Endocrinol ; 182(6): 595-605, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32375119

RESUMO

Objective: T2-signal intensity and somatostatin (SST) receptor expression are recognized predictors of therapy response in acromegaly. We investigated the relationship between these predictors and the hormonal and tumoral responses to long-acting pasireotide (PAS-LAR) therapy, which were also compared with responsiveness to first-generation somatostatin receptor ligands (SRLs). Design: The PAPE study is a cohort study. Methods: We included 45 acromegaly patients initially receiving SRLs, followed by combination therapy with pegvisomant, and finally PAS-LAR. We assessed tumor volume reduction (≥25% from baseline), IGF-1 levels (expressed as the upper limit of normal), and T2-weighted MRI signal and SST receptor expression of the adenoma. Results: Patients with significant tumor shrinkage during PAS-LAR showed higher IGF-1 levels during PAS-LAR (mean (S.D.): 1.36 (0.53) vs 0.93 (0.43), P = 0.020), less IGF-1 reduction after first-generation SRLs (mean (S.D.): 0.55 (0.71) vs 1.25 (1.07), P = 0.028), and lower SST2 receptor expression (median (IQR): 2.0 (1.0-6.0) vs 12.0 (7.5-12.0), P = 0.040). Overall, T2-signal intensity ratio was increased compared with baseline (mean (S.D.): 1.39 (0.56) vs 1.25 (0.52), P = 0.017) and a higher T2-signal was associated with lower IGF-1 levels during PAS-LAR (ß: -0.29, 95% CI: -0.56 to -0.01, P = 0.045). A subset of PAS-LAR treated patients with increased T2-signal intensity achieved greater reduction of IGF-1 (mean (S.D.): 0.80 (0.60) vs 0.45 (0.39), P = 0.016). Conclusions: Patients unresponsive to SRLs with a lower SST2 receptor expression are more prone to achieve tumor shrinkage during PAS-LAR. Surprisingly, tumor shrinkage is not accompanied by a biochemical response, which is accompanied with a higher T2-signal intensity.


Assuntos
Acromegalia/tratamento farmacológico , Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Hormônios/uso terapêutico , Somatostatina/análogos & derivados , Acromegalia/sangue , Acromegalia/etiologia , Adenoma/sangue , Adenoma/complicações , Adulto , Estudos de Coortes , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Ligantes , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Receptores de Somatostatina/sangue , Somatostatina/uso terapêutico , Resultado do Tratamento , Carga Tumoral
8.
PLoS One ; 15(4): e0231240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287299

RESUMO

OBJECTIVE: REG-O3 is a 24-aminoacid chimeric peptide combining a sequence derived from growth hormone (GH) and an analog of somatostatin (SST), molecules displaying cartilage repair and anti-inflammatory properties, respectively. This study aimed to investigate the disease-modifying osteoarthritis drug (DMOAD) potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint. DESIGN: Osteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx). Treatments were administered intra-articularly from fourteen days after surgery through three consecutive injections one week apart. The effect of REG-O3, solubilized in a liposomal solution and injected at either 5, 25 or 50 µg/50 µL, was compared to liposomal (LIP), dexamethasone and hyaluronic acid (HA) solutions. The study endpoints were the pain/function measured once a week throughout the entire study, and the joint structure evaluated eight weeks after surgery using OARSI score. RESULTS: ACLT/pMMx surgery induced a significant modification of weight bearing in all groups. When compared to liposomal solution, REG-O3 was able to significantly improve weight bearing as efficiently as dexamethasone and HA. REG-O3 (25 µg) was also able to significantly decrease OARSI histological global score as well as degeneration of both cartilage and matrix while the other treatments did not. CONCLUSION: This study provides evidence of a remarkable protecting effect of REG-O3 on pain/knee joint function and cartilage/matrix degradation in ACLT/pMMx model of rat osteoarthritis. REG-O3 thus displays an interesting profile as a DMOAD.


Assuntos
Lesões do Ligamento Cruzado Anterior/complicações , Anti-Inflamatórios não Esteroides/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Hormônio do Crescimento/uso terapêutico , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Somatostatina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cartilagem Articular/patologia , Modelos Animais de Doenças , Hormônio do Crescimento/farmacologia , Articulação do Joelho/patologia , Masculino , Osteoartrite do Joelho/etiologia , Ratos , Ratos Endogâmicos Lew , Proteínas Recombinantes de Fusão/farmacologia , Somatostatina/análogos & derivados , Somatostatina/farmacologia
9.
J Surg Oncol ; 121(7): 1067-1073, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32153032

RESUMO

BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P < .01). CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.


Assuntos
Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/cirurgia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
10.
Eur J Endocrinol ; 182(6): 583, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217809

RESUMO

Objective: In the Phase III PAOLA study (clinicaltrials.gov: NCT01137682), enrolled patients had uncontrolled acromegaly despite ≥6 months of octreotide/lanreotide treatment before study start. More patients achieved biochemical control with long-acting pasireotide versus continued treatment with octreotide/lanreotide (active control) at month 6. The current work assessed the extent of comorbidities at baseline and outcomes during a long-term extension. Design/methods: Patients receiving pasireotide 40 or 60 mg at core study end could continue on the same dose in an extension phase if biochemically controlled or receive pasireotide 60 mg if uncontrolled. Uncontrolled patients on active control were switched to pasireotide 40 mg, with the dose increased at week 16 of the extension if still uncontrolled (crossover group). Efficacy and safety are reported to 304 weeks (~5.8 years) for patients randomized to pasireotide (core + extension), and 268 weeks for patients in the crossover group (extension only). Results: Almost half (49.5%; 98/198) of patients had ≥3 comorbidities at core baseline. During the extension, 173 patients received pasireotide. Pasireotide effectively and consistently reduced GH and IGF-I levels for up to 5.8 years' treatment; 37.0% of patients achieved GH <1.0 µg/L and normal IGF-I at some point during the core or extension. Improvements were observed in key symptoms. The long-term safety profile was similar to that in the core study; 23/173 patients discontinued treatment because of adverse events. Conclusions: In this patient population with a high burden of comorbid illness, pasireotide was well tolerated and efficacious, providing prolonged maintenance of biochemical control and improving symptoms.


Assuntos
Acromegalia/tratamento farmacológico , Hormônios/administração & dosagem , Somatostatina/análogos & derivados , Fatores de Tempo , Acromegalia/sangue , Adulto , Estudos Cross-Over , Esquema de Medicação , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Prospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Resultado do Tratamento
11.
Radiol Med ; 125(8): 715-729, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32189174

RESUMO

AIMS: This study analyses the capability of contrast-enhanced multi-detector computed tomography (MDCT) and spectrum of molecular imaging to characterize typical carcinoids (TCs) of lung and their relationship with Ki-67 index. MATERIALS AND METHODS: We analysed 68 patients with histological diagnosis of pulmonary TC, which underwent both MDCT and nuclear molecular imaging (somatostatin receptor scintigraphy/SPECT with 111In-pentetreotide and 18F-FDG-PET/CT) at staging evaluation before surgery. The MDCT scan was reviewed for the following features: size, margins, contrast enhancement, presence of calcifications, bronchial obstruction, lymph nodes and metastases. In 111In-pentetreotide SPECT, tumour/non-tumour ratio was measured at 4- and 24-h post-injection and the per cent difference was calculated (T/NT%). FDG uptake was measured as the ratio between lesion SUVmax and liver SUVmean (SUV ratio). All imaging features were correlated between them and with Ki-67 index. RESULTS: Forty-four of the 68 lesions (65%) were in the right lung. In MDCT, scan lesions appeared as a well-defined nodule in 44 patients (65%) and irregular mass in 24 patients (35%). Contrast intense enhancement was present in 53 patients (78%), calcifications in 20 patients (29%) and bronchial obstruction in 24 patients (35%). Lymph nodes and metastasis were present in 13 (19%) and 15 (22%) patients. Ki-67 index was negatively correlated with T/NT% and positively with SUV ratio; T/NT% and SUV ratio were inversely correlated. The presence of irregular margins and metastases was negatively related to T/NT%. The presence of a mass, irregular margins, bronchial obstruction, lymph nodes and metastasis was positively related to higher SUV ratio. The presence of irregular margins, bronchial obstruction, lymph nodes and metastases was significantly correlated with a higher grade of Ki-67 index. CONCLUSIONS: MDCT and nuclear molecular imaging are important to characterize lung TCs. The majority of TCs appear as a well-defined nodule generally not associated with extra-thorax signs. We found a significant correlation between some MDCT aspects, nuclear medicine features and Ki-67 index. The association of MDCT and nuclear medicine imaging may be useful in predicting proliferative activity and prognosis of lung TCs.


Assuntos
Tumor Carcinoide/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Tumor Carcinoide/patologia , Meios de Contraste , Feminino , Fluordesoxiglucose F18 , Humanos , Iohexol/análogos & derivados , Antígeno Ki-67/análise , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Somatostatina/análogos & derivados
13.
Expert Opin Pharmacother ; 21(2): 183-191, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760823

RESUMO

Introduction: Well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with a wide range of clinical behavior. Multiple treatment modalities exist, including novel and emerging systemic options, and an understanding of the advantages and disadvantages of each is imperative for optimizing the outcomes of patients with GEP-NETs.Areas covered: While surgical resection remains the preferred treatment for localized well-differentiated GEP-NETs, treatment of unresectable disease depends on its extent, location, and distribution as well as underlying aspects of tumor biology. Isolated hepatic metastases can be successfully treated with liver-directed therapies such as hepatic arterial based therapies or ablation. Diffuse metastatic disease often requires systemic treatments such as molecular-targeted therapeutics, peptide receptor radionuclide therapy (PRRT), or traditional chemotherapy. Somatostatin analogs are often the primary treatment option capable of simultaneously inhibiting hormone production and slowing tumor growth.Expert opinion: Recent advances in systemic treatment options for advanced well-differentiated GEP-NETs have emerged due to an improved understanding of the molecular mechanisms responsible for tumor development and progression. Future research is needed to determine the optimal indications for and sequencing of these novel therapies.


Assuntos
Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/terapia , Progressão da Doença , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Somatostatina/análogos & derivados
14.
Eur J Endocrinol ; 182(2): 207-217, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31804965

RESUMO

Objective: Monitoring of patients with Cushing's disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing's disease. Design: Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing's disease (clinicaltrials.gov: NCT01374906). Methods: Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time. Results: At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 (n = 92), 17.4% had both mLNSC ≤ULN and mUFC ≤ULN; 22.8% had mLNSC ≤ULN, and 45.7% had mUFC ≤ULN. There was high variability in LNSC (intra-patient coefficient of variation (CV): 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman's correlation: ρ = 0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ≤ULN and mUFC ≤ULN. Conclusion: mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing's disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.


Assuntos
Ritmo Circadiano , Hidrocortisona/metabolismo , Hipersecreção Hipofisária de ACTH/metabolismo , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/cirurgia , Adulto , Feminino , Hormônios/uso terapêutico , Humanos , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/etiologia , Hipersecreção Hipofisária de ACTH/urina , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Saliva/química , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Resultado do Tratamento
15.
Eur J Endocrinol ; 182(1): R1-R13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705792

RESUMO

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease. In view of the development of additional treatment concepts for the treatment of pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of an anti-angiogenic therapy. Moreover, the role of BMP-4 which stimulates prolactinoma development through the Smad signalling cascade is described and its role as putative drug target for the treatment of prolactinomas is discussed. Regarding the well-known resistance of a part of somatotropinomas to somatostatin analogue treatment, recently identified mechanisms responsible for the drug resistance are summarized and ways to overcome them in future treatment concepts are presented. Concerning novel therapeutic options for patients with Cushing's disease the impact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeutic impact of silibinin to resolve glucocorticoid resistance in these patients is critically discussed.


Assuntos
Neoplasias Hipofisárias/tratamento farmacológico , Pesquisa Médica Translacional/métodos , Animais , Humanos , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neoplasias Hipofisárias/fisiopatologia , Prolactinoma/tratamento farmacológico , Prolactinoma/fisiopatologia , Qualidade de Vida , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
16.
Eur J Endocrinol ; 182(1): 123-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705796

RESUMO

Objective: Primary SMSa treatment can be associated with hormonal control and tumor shrinkage in patients with GH-secreting pituitary adenomas. The aim of this study was to evaluate whether regular MRI follow-up was necessary in patients with acromegaly-treated and responsive to first-generation long-acting SMSa. Patients and methods: In this retrospective monocentric study we included patients with GH/IGF-1 hypersecretion and pituitary adenomas with normal visual field, primarily treated with first-generation long-acting SMSa between 1995 and 2015 and regularly monitored (clinical evaluation, GH/IGF-1 levels and pituitary MRI) for at least 3 years. Results: We included 83 patients (32 men and 51 women, mean age at diagnosis 50 ± 12 years) with mean GH = 19.3 ± 25.6 ng/mL, IGF-1 = 284 ± 110% ULN and pituitary adenoma height = 12.9 ± 4.7 mm. Mean follow-up was 8.9 ± 4.9 years in 36 controlled patients and 2.0 ± 1.6 years in 47 partial responders to SMSa alone. No significant increase in pituitary adenoma height was observed. Pituitary adenoma height decreased significantly in controlled patients (diagnosis: 11.9 ± 4.8 mm, SMSa: 9.6 ± 3.3 mm, P < 0.001), and in partially responders (diagnosis: 13.6 ± 4.5 mm, SMSa: 11.5 ± 4.5 mm, P < 0.001). Conclusion: During SMSa treatment, no significant increase in GH-secreting adenoma size was observed. Primary SMSa treatment was associated with a significantly decrease in adenoma height in our population. Our cohort data suggest that regular MRI follow-up does not seem relevant in patients with acromegaly who are responsive to SMSa treatment.


Assuntos
Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Imagem por Ressonância Magnética/métodos , Adulto , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
17.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586182

RESUMO

PURPOSE: Pancreatic neuroendocrine tumors (pNETs) are frequent in multiple endocrine neoplasia type 1 (MEN1) syndrome. They are usually not surgically treated unless larger than 1 to 2 cm or a growth rate > 0.5 cm per year. Somatostatin analogues represent one of the main therapeutic options in pNETs, but they have never been prospectively investigated in MEN1-related pNETs. The aim of this study was to prospectively evaluate the effectiveness of lanreotide in patients with MEN1-related pNETs < 2 cm. METHODS: MEN1 patients with 1 or more pNETs < 2 cm of maximal diameter were considered. Study design was prospective observational, comparing patients treated with lanreotide autogel 120 mg every 28 days (LAN group) and patients in active surveillance, not receiving any therapy (AS group). RESULTS: Forty-two patients were enrolled: 23 in LAN and 19 in AS group. Median follow-up was 73 months. Initial imaging identified a total of 91 pNETs. The median progression-free survival was significantly longer in the LAN than in the AS group (median not reached vs 40 months, P < 0.001). In the LAN group, 4 patients had an objective tumor response, 15 patients had stable disease, while 4 had tumor progression. In the AS group, 13 patients had pNET progression, while 6 were stable. CONCLUSIONS: This is the first prospective study evaluating the efficacy of somatostatin analogues in MEN1-related pNETs. These findings highlight that lanreotide autogel is effective as antiproliferative therapy in MEN1-related pNETs < 2cm, suggesting the utility of somatostatin analogues to arrest the development of tumor lesions as well as to delay or avoid pancreatic surgery.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasia Endócrina Múltipla Tipo 1/complicações , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Conduta Expectante/estatística & dados numéricos , Adulto , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/etiologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Somatostatina/uso terapêutico , Carga Tumoral , Adulto Jovem
18.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 38(6): 382-385, nov.-dic. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-191702

RESUMO

La PET con análogos de la somatostatina permite detectar aquellas células con sobreexpresión de receptores de somatostatina, especialmente del subtipo 2 y 5, siendo variable esta detección según el tipo de molécula que se utilice. Esta es la base para su uso en el estudio de los tumores neuroendocrinos (NET), los cuales se caracterizan por presentar una sobreexpresión de estos receptores en más del 80% de los subtipos. Esta PET llega a nuestro país avalada por los buenos resultados publicados por otros grupos, superiores a los de otras técnicas de imagen. Presentamos dos de los primeros casos de PET con análogos de la somatostatina: 68Ga-edetreótida (SomaKit TOC(R)) realizados en nuestro centro. La PET fue la prueba que determinó finalmente el manejo clínico de ambos pacientes


PET with somatostatin analogues (SSA PET/CT) enables the detection of cells with overexpression of somatostatin receptors, especially subtypes 2 and 5; this detection is variable depending on the type of molecule used. This is the basis for its use in the study of neuroendocrine tumours (NETs), which are characterized by an overexpression of these receptors in more than 80% of the subtypes. This PET is now being used in our country supported by the good results published by other groups, that were superior to those of other imaging techniques. We present two of the first cases of SSA-PET/CT with 68Ga-edotreotide (SomaKit TOC(R)) performed in our centre. SSA-PET/CT was the test that finally determined the clinical management of both patients


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Organometálicos , Tomografia Computadorizada por Raios X , Receptores de Somatostatina/análise , Somatostatina/análogos & derivados , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/métodos
19.
Arch. endocrinol. metab. (Online) ; 63(6): 646-652, Nov.-Dec. 2019.
Artigo em Inglês | LILACS | ID: biblio-1055016

RESUMO

ABSTRACT Advances in combination medical treatment have offer new perspectives for acromegaly patients with persistent disease activity despite receiving the available medical monotherapies. The outcomes of combination medical treatment may reflect both additive and synergistic effects. This review focuses on combination medical treatment and its current position in acromegaly, based on clinical studies evaluating the efficacy and safety of combined medical treatment(s) and our own experiences with combination therapy. Arch Endocrinol Metab. 2019;63(6):646-52


Assuntos
Humanos , Somatostatina/análogos & derivados , Receptores de Somatostatina/administração & dosagem , Receptores de Somatostatina/antagonistas & inibidores , Agonistas de Dopamina/administração & dosagem , Hormônio do Crescimento Humano/análogos & derivados , Qualidade de Vida , Acromegalia/tratamento farmacológico , Somatostatina/administração & dosagem , Hormônio do Crescimento Humano/administração & dosagem , Quimioterapia Combinada
20.
Int J Mol Sci ; 20(19)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569719

RESUMO

Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Animais , Carcinoma Hepatocelular/metabolismo , Ensaios Clínicos como Assunto , Humanos , Neoplasias Hepáticas/metabolismo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA