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1.
Medicine (Baltimore) ; 99(51): e23824, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371162

RESUMO

BACKGROUND: Cushing's disease (CD) is associated with increased risk of mortality, myocardial infarction, stroke, peptic ulcers, fractures and infections. The prevalence of CD is nearly 40 per million and higher in women than in men. When surgery has failed, is not feasible, or has been refused, pharmacotherapy can be considered a valuable option. Pasireotide is the first medical therapy officially approved for adult patients with CD. We will conduct a comprehensive systematic review and meta-analysis to systematically evaluate the efficacy and safety of pasireotide for CD. METHODS: Five English databases (PubMed, Web of Science, Embase, Cochrane Library, and OVID) and 3 Chinese databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) will be searched from their respective inception of databases to December 2020. Two reviewers will select articles, extract data and assess the risk of bias independently. Any disagreement will be resolved by discussion with the third reviewer. Review Manager 5.3 software will be used for data synthesis. The Cochrane risk of bias assessment tool will be used to evaluate the bias risk. RESULTS: This systematic review and meta-analysis will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the efficacy and safety of pasireotide for CD. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the efficacy and safety of pasireotide for CD, and inform our understanding of the value of pasireotide in improving CD clinical signs and symptoms. The conclusions drawn from this study may be beneficial to patients, clinicians, and health-related policy makers. STUDY REGISTRATION NUMBER: INPLASY2020110070.


Assuntos
Protocolos Clínicos , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Somatostatina/análogos & derivados , Humanos , Metanálise como Assunto , Somatostatina/farmacologia , Somatostatina/normas , Somatostatina/uso terapêutico , Revisões Sistemáticas como Assunto
2.
Khirurgiia (Mosk) ; (11): 61-65, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33210509

RESUMO

OBJECTIVE: Prospective randomized investigation of the efficiency of somatostatin analogues and glucocorticoids in pancreatic fistula prevention after pancreatoduodenectomy by using. MATERIAL AND METHODS: In period from December 2018 till March 2020 78 patients underwent pancreatoduodenectomy for pancreatobilliary tumors in department of abdominal surgery of National Medical Research Center of Surgery named after A.V. Vishnevsky. Intraoperative frozen section investigation of pancreatic functioning acinar structures (FAS) was held for all patients. 38 patients had more than 40% of FAC and were related with high risk of pancreatic fistula (PF), while 40 patients with less than 40% FAC were included in low risk of PF group. In both groups patients were randomized to main and control subgroups. In main subgroup of high risk group patients combination of somatostatin analogues and glucocorticoids was used, while in control subgroup patients received only somatostatin analogue. In low risk of PF group patients of main subgroup preventively got somatostatin analogue, while control group patients had no specific prophylaxis of PF. To assess the effect of drug prophylaxis on the development of pancreatic fistula we used logistic regression models with the inclusion of the drug use factor as an independent variable. RESULTS: 25 patients were included in main subgroup of high risk group. Clinically relevant pancreatic fistula (CRPF) developed in 14 (56%) cases. From 13 patients of control subgroup CRPF developed in 5 (38%) cases. In main subgroup of low risk group 18 patients were included and 3 (16%) of them had CRPF. In control subgroup were 22 patients and there were no cases of CRPF. CONCLUSION: In our series combination of somatostatin analogue and glucocorticoid didn't show efficiency in prevention of CRPF in high risk patients, although difference between subgroups wasn't statistically significant (p=0.34). In low risk group patients prophylactic use of somatostatin analogue also didn't show decline of CRPF incidence and the difference between subgroups also wasn't statistically significant (p=0.46).


Assuntos
Neoplasias do Sistema Biliar/cirurgia , Fármacos Gastrointestinais/uso terapêutico , Fístula Pancreática , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Somatostatina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Pâncreas/cirurgia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Estudos Prospectivos , Somatostatina/análogos & derivados
3.
Expert Opin Pharmacother ; 21(15): 1883-1895, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32633582

RESUMO

INTRODUCTION: Acromegaly is a rare disease due to oversecretion of growth hormone (GH). Even though the disease is often portrayed by its most apparent clinical features, given the abundance of GH receptors throughout the body, it truly is a systemic disease leading to numerous complications and comorbidities. A distinct medical issue in the context of acromegaly is diabetes: It can be a complication as a consequence of GH excess and its mediators, but it can also result from treatment of acromegaly. AREAS COVERED: This review provides an overview of the effects of acromegaly pathophysiology on glucose homeostasis. Furthermore, it devotes an extensive section on the influence that acromegaly treatment has on glucose metabolism, including approved as well as currently investigated drugs. It also summarizes observations from the use of anti-diabetic medication in patients with acromegaly. EXPERT OPINION: Glucose imbalance is an important aspect of acromegaly comorbidity and deserves more attention. Even though numerous studies have investigated glucose homeostasis in acromegaly, there is still a clear need for more basic, translational, and also clinical research to advance the understanding of the underlying mechanisms and how to best address them.


Assuntos
Acromegalia/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Glucose/metabolismo , Somatostatina/uso terapêutico , Acromegalia/complicações , Acromegalia/epidemiologia , Acromegalia/metabolismo , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Hormônio do Crescimento Humano/metabolismo , Humanos , Resistência à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Prevalência , Somatostatina/análogos & derivados
4.
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
5.
Endocrinology ; 161(8)2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32591776

RESUMO

TBR-760 (formerly BIM-23A760) is a chimeric dopamine (DA)-somatostatin (SST) compound with potent agonist activity at both DA type 2 (D2R) and SST type 2 (SSTR2) receptors. Studies have shown that chimeric DA-SST compounds are more efficacious than individual DA and/or SST analogues, either alone or combined, in inhibiting secretion from primary cultures of human somatotroph and lactotroph tumor cells. Nonfunctioning pituitary adenomas (NFPAs) express both D2R and SSTR2 and, consequently, may respond to TBR-760. We used a mouse model with the pro-opiomelanocortin (POMC) gene knocked out that spontaneously develops aggressive NFPAs. Genomic microarray and DA and SST receptor messenger RNA expression analysis indicate that POMC KO mouse tumors and human NFPAs have similar expression profiles, despite arising from different cell lineages, establishing POMC KO mice as a model for study of NFPAs. Treatment with TBR-760 for 8 weeks resulted in nearly complete inhibition of established tumor growth, whereas tumors from vehicle-treated mice increased in size by 890 ± 0.7%. Comparing TBR-760 with its individual DA and SST components, TBR-760 arrested tumor growth. Treatment with equimolar or 10×-higher doses of the individual SST or DA agonists, either alone or in combination, had no significant effect. One exception was the lower dose of DA agonist that induced modest suppression of tumor growth. Only the chimeric compound TBR-760 arrested tumor growth in this mouse model of NFPA. Further, significant tumor shrinkage was observed in 20% of the mice treated with TBR-760. These results support the development of TBR-760 as a therapy for patients with NFPA.


Assuntos
Adenoma/tratamento farmacológico , Adenoma/patologia , Proliferação de Células/efeitos dos fármacos , Dopamina/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Somatostatina/análogos & derivados , Adenoma/genética , Animais , Proliferação de Células/genética , Modelos Animais de Doenças , Dopamina/farmacologia , Dopamina/uso terapêutico , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Knockout , Análise em Microsséries , Invasividade Neoplásica , Neoplasias Hipofisárias/genética , Pró-Opiomelanocortina/deficiência , Pró-Opiomelanocortina/genética , Somatostatina/farmacologia , Somatostatina/uso terapêutico
6.
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
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.
Medicine (Baltimore) ; 99(20): e20288, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443374

RESUMO

BACKGROUND: As one of the complications after abdominal operation, early postoperative inflammatory small bowel obstruction (EPISBO) is a great trouble for many patients. The use of somatostatin in treating this disease had been widely reported, but its efficacy and safety were controversial. Therefore, the present research carried out a systematic review of the clinical efficacy and safety of somatostatin in treating EPISBO. METHODS: Computer retrieval was conducted in foreign databases (including PubMed, The Cochrane Library, and Embase) and Chinese database (including Sino Med, CNKI, VIP, and WangFang Data), supplementary search for the literatures included was performed, and manual retrieval was performed in abstracts, books, and non-electronic magazines related to the present research to ensure the recall rate. Among all republished relevant experimental studies in Chinese and English from January 1, 1996 to February 1, 2020, randomized controlled trials on the curative efficacy of somatostatin for EPISBO were collected. The evaluation measures included patients' total effective rate, peristaltic sound recovery time, time of disappearance of abdominal pain, time of first defecation after operation, drainage of gastrointestinal decompression and length of stay after treatment. The literatures were selected by two investigators independently to extract data according to the inclusion and exclusion criteria, Bias Risk Assessment Tool recommended by Cochrane Review Hand book 5.2 was used to assess literature quality, and meta-analysis was carried out by using soft Stata 12.0. RESULTS: This study will scientifically and effectively analyze the clinical efficacy and safety of somatostatin in the treatment of EPISBO through systematic review and meta-analysis. ETHICS AND DISSEMINATION: The results of this study will be published in a peer-reviewed SCI journal to provide evidence-based medical evidence for the clinical treatment of early postoperative inflammatory bowel obstruction. PROTOCOL AND REGISTRATION: Open Science Framework (https://osf.io, OSF), registration number: ryd2g.


Assuntos
Inflamação/tratamento farmacológico , Obstrução Intestinal/tratamento farmacológico , Intestino Delgado/patologia , Complicações Pós-Operatórias/tratamento farmacológico , Somatostatina/uso terapêutico , Dor Abdominal/epidemiologia , Defecação , Humanos , Inflamação/epidemiologia , Obstrução Intestinal/epidemiologia , Tempo de Internação , Peristaltismo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Fatores de Tempo
9.
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
10.
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
11.
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
12.
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
13.
Int J Mol Sci ; 21(5)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121432

RESUMO

Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves' orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Somatostatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Edema Macular/tratamento farmacológico , Edema Macular/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Somatostatina/análogos & derivados , Somatostatina/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
14.
Adv Ther ; 37(4): 1608-1619, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32157626

RESUMO

INTRODUCTION: Somatostatin analogues are used to treat symptoms and slow tumour progression in patients with neuroendocrine tumours (NETs) and carcinoid syndrome and to reduce hormone secretion and pituitary tumour volume in patients with acromegaly. A new syringe for lanreotide autogel/depot (LAN) was developed following feedback from a human factors study to improve ease of injection compared with previous syringes. PRESTO aimed to assess preferences of nurses between the LAN new syringe and the octreotide long-acting release (LAR) syringe. METHODS: PRESTO, a multinational, multicentre, prospective, noninterventional, simulated-use study, enrolled nurses with ≥ 2 years' experience injecting LAN and/or octreotide LAR in patients with NETs and/or acromegaly. Nurses administered injections into pads using the LAN new syringe and octreotide LAR syringe in a randomised sequence. In an anonymous web-based questionnaire, nurses reported their overall preference ('strong' or 'slight'; primary endpoint) and rated and ranked the importance of nine attributes for each syringe (1 [not at all] to 5 [very much]). RESULTS: Overall, 90 nurses attended sessions and completed valid questionnaires. Most nurses (97.8%) expressed a preference (85.6% 'strong', 12.2% 'slight') for the LAN new syringe versus the octreotide LAR syringe (P < 0.0001). Attribute performance ratings (1 [not at all] to 5 [very much]) were consistently higher for the LAN new syringe versus the octreotide LAR syringe, with the greatest differences in 'fast administration' and 'confidence the syringe will not be clogged' (mean difference [SD]: 2.6 [1.2] and 2.3 [1.5], respectively; P < 0.0001). The attribute ranked most important was 'confidence the syringe will not be clogged' (24.4%); least important was 'convenience of syringe format, including packaging, from preparation to injection' (34.4%). CONCLUSIONS: Nurses preferred the user experience of the LAN new syringe compared with the octreotide LAR syringe, with a particular preference for attributes related to product delivery with the LAN new syringe.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Atitude do Pessoal de Saúde , Tumores Neuroendócrinos/dietoterapia , Tumores Neuroendócrinos/enfermagem , Octreotida/administração & dosagem , Peptídeos Cíclicos/administração & dosagem , Somatostatina/análogos & derivados , Adulto , Antineoplásicos Hormonais/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Prospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Inquéritos e Questionários , Seringas
15.
Heart Surg Forum ; 23(1): E081-E087, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32118549

RESUMO

BACKGROUND: Chylothorax or pseudo-chylothorax is a serious complication after adult and pediatric cardiac surgery. This study presents our 10-year clinical experience of chylothorax after cardiac surgery. METHODS: Between January 2008 and February 2019, 4896 cardiovascular surgeries were performed in 2 tertiary clinics, with 416 patients in the pediatric age group (8.4%). Chylothorax and pseudo-chylothorax were detected in 47 patients (22 adult and 20 pediatric patients, 4.8%). Pseudo-chylothorax was seen in 5 adult patients. In 27 patients, a pleural effusion developed on the left side (64.2%). Quantities of chylomicron in pleural effusion were significant in all patients. In addition, protein and lactate dehydrogenase levels were >2.9 g/dL. The cholesterol level in the pleural effusion was >2.49 mmol/L in all patients. The mean latency period was 8 days (range 3.1 to 63.1). For the management of chylothorax, somatostatin or octreotide as a somatostatin analog was administered in 23 patients (15 adult and 8 pediatric) in the intensive care unit. Somatostatin or octreotide was administered intravenously or subcutaneously at a dose of 0.3 to 4 µg/(kg · h-1). We used dexamethasone as a steroid combined with somatostatin in patients who were resistant to medical treatment before pleurodesis or ductus closure. Classic chemical pleurodesis combined with fibrin glue was performed in 11 patients (8 adult and 3 pediatric). Surgical duct ligation, as the last option, was performed in 7 patients. RESULTS: No mortality or morbidity was observed. Chylothorax improved with the medical approach in 23 patients within 24.2 ± 11.3 days (48.9%). We successfully performed the pleurodesis procedure using fibrin glue in addition to the classic method. The mean duration of conservative treatment was 27.1 days (range 11 to 39). After discharge from the hospital, 2 children had recurrence of chylothorax, and the ductus thoracicus was surgically ligated. No complication was seen during or after ductus ligation. CONCLUSIONS: According to our clinical experience, chylothorax is not an extremely rare complication after cardiac surgery in pediatric cardiovascular surgery. A number of patients with chylothorax may be treated medically and with diet adjustment. Medical treatment including steroid administration may be the first treatment strategy immediately after diagnosis. Classic chemical pleurodesis combined with fibrin glue may be applied in the early stages. Surgical ligation of the ductus thoracicus should be considered the last treatment option.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Quilotórax/etiologia , Quilotórax/terapia , Corticosteroides/uso terapêutico , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Nutrição Parenteral Total , Pleurodese , Complicações Pós-Operatórias/terapia , Somatostatina/uso terapêutico
17.
JAMA Surg ; 155(4): 291-298, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32022887

RESUMO

Importance: Both hydrocortisone and pasireotide have been shown in randomized clinical trials to be effective in reducing postoperative complications of pancreatic surgery, but to date no randomized clinical trial has evaluated the effectiveness of pasireotide compared with hydrocortisone. Objective: To assess the noninferiority of hydrocortisone compared with pasireotide in reducing complications after partial pancreatectomy. Design, Setting, and Participants: A noninferiority, parallel-group, individually randomized clinical trial was conducted at a single academic center between May 19, 2016, and December 17, 2018. Outcome collectors and analyzers were blinded. A total of 281 patients undergoing partial pancreatectomy were assessed for inclusion. Patients younger than 18 years, those allergic to hydrocortisone or pasireotide, patients undergoing pancreaticoduodenectomy with hard pancreas or dilated pancreatic duct, and patients not eventually undergoing partial pancreatectomy were excluded. Modified intention-to-treat analysis was used in determination of the results. Interventions: Treatment included pasireotide, 900 µg, subcutaneously twice a day for 7 days or hydrocortisone, 100 mg, intravenously 3 times a day for 3 days. Main Outcomes and Measures: The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days. The noninferiority limit was set to 9 CCI points. Results: Of the 281 patients (mean [SD] age, 63.8 years) assessed for eligibility, 168 patients (mean [SD] age, 63.6 years) were randomized and 126 were included in the modified intention-to-treat analyses. Sixty-three patients received pasireotide (35 men [56%]; median [interquartile range] age, 64 [56-70] years) and 63 patients received hydrocortisone (25 men [40%]; median [interquartile range] age, 67 [56-73] years). The mean (SD) CCI score was 23.94 (17.06) in the pasireotide group and 30.11 (20.47) in the hydrocortisone group (mean difference, -6.16; 2-sided 90% CI, -11.73 to -0.60), indicating that hydrocortisone was not noninferior. Postoperative pancreatic fistula was detected in 34 patients (54%) in the pasireotide group and 39 patients (62%) in the hydrocortisone group (odds ratio, 1.39; 95% CI, 0.68-2.82; P = .37). One patient in the pasireotide group and 2 patients in the hydrocortisone group died within 30 days. In subgroup analyses of patients undergoing distal pancreatectomy, the CCI score was a mean of 10.3 points lower (mean [SD], 16.03 [11.94] vs 26.28 [21.76]; 2-sided 95% CI, -19.34 to -2.12; P = .03) and postoperative pancreatic fistula rate was lower (37% vs 67%; P = .02) in the pasireotide group compared with the hydrocortisone group. Conclusions and Relevance: In this study, hydrocortisone was not noninferior compared with pasireotide in patients undergoing partial pancreatectomy. Pasireotide may be more effective than hydrocortisone in patients undergoing distal pancreatectomy. Trial Registration: ClinicalTrials.gov identifier: NCT02775227; EudraCT identifier: 2016-000212-16.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hormônios/uso terapêutico , Hidrocortisona/uso terapêutico , Pancreatectomia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Somatostatina/análogos & derivados , Feminino , Finlândia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Somatostatina/uso terapêutico
18.
Sci Rep ; 10(1): 371, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941913

RESUMO

Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34+ CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells.


Assuntos
Leucemia Mieloide Aguda/terapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Receptores de Somatostatina/metabolismo , Rutênio/uso terapêutico , Somatostatina/uso terapêutico , Adulto , Idoso , Apoptose , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Feminino , Sangue Fetal/metabolismo , Humanos , Lisossomos/metabolismo , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo
20.
Nihon Shokakibyo Gakkai Zasshi ; 117(1): 84-91, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31941861

RESUMO

A 68-year-old woman with an 11-day history of sudden abdominal pain and severe watery diarrhea was transferred to our hospital due to an exacerbation of renal function despite hydration. After treatment for dehydration and acidemia was provided in our intensive care unit, patient's renal function improved. Contrast-enhanced abdominal computed tomography was finally performed, revealing a hypervascular pancreatic mass with multiple hepatic masses. This imaging finding along with her clinical symptoms indicated watery diarrhea hypokalemia achlorhydria (WDHA) syndrome caused by a pancreatic VIPoma. Somatostatin analog was administered immediately leading to the improvement of her diarrhea and her general condition. As a result, endoscopic ultrasonography-guided fine-needle aspiration could be performed. Consequently, she was diagnosed with a pancreatic neuroendocrine tumor. She then underwent surgical resection of the pancreatic tumor and liver metastasis. As revealed in the immunohistochemical analysis of the excised tumor tissue, VIP was highly expressed, resulting in the final diagnosis of pancreatic VIPoma. Therefore, the immediate use of a somatostatin analog is crucial for improving the patient's general condition and achieving a definitive diagnosis pathologically when a patient is suspected of having a pancreatic VIPoma.


Assuntos
Acloridria , Hormônios/uso terapêutico , Neoplasias Pancreáticas , Somatostatina/uso terapêutico , Vipoma , Idoso , Feminino , Humanos , Peptídeo Intestinal Vasoativo
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