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1.
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
2.
Medicine (Baltimore) ; 98(46): e18010, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725672

RESUMO

INTRODUCTION: Enterocutaneous fistula is considered one of the most serious complications in general surgery and is associated with high morbidity and mortality. Although various treatments are reported to have varying success, high-output enterocutaneous fistulas (output over 500 ml/day) continue to be associated with high mortality, and few papers on this topic exist in the literature. The aim of this study is to describe an effective multidisciplinary treatment method for postoperative high-output enterocutaneous fistula and discuss the clinical development of the therapeutic strategy. PATIENT CONCERNS: Three patients suffered high-output enterocutaneous fistulas, in which case 1 presented with duodenal fistula, case 2 with ileal fistula, and case 3 with small bowel fistula. DIAGNOSIS: All 3 cases were diagnosed with high-output enterocutaneous fistulas by drainage of intestinal contents. INTERVENTIONS: With the exception of routine treatment including fluid resuscitation, correction of the electrolyte balance, control of infection, and optimal nutrition, all the cases accepted continuous irrigation and suction with triple-cavity drainage tubes in combination with sequential somatostatin-somatotropin administration were given. With regard to establishing effective drainage, the triple-cavity tube placement was performed by insertion through the initial drainage channel in case 1, percutaneous puncture with dilation by graduated dilators in case 2, and tract reconstruction in case 3. The technical details of the approach are described and clinical characteristics including fistula location, defect size, output volume, approach of triple-cavity tube placement, length of fistula tract, somatostatin and somatotropin administration time, and fistula healing time were recorded and compared. In addition, other various techniques reported in the literature are reviewed and discussed. OUTCOMES: All the patients were cured by the multidisciplinary treatments and were followed up without fistula recurrence and other relevant complications at 1 week, 1 month, and 3 months after the treatments. CONCLUSION: The strategy involving continuous irrigation and suction with a triple-cavity drainage tube in combination with sequential somatostatin-somatotropin administration may be a safe and effective alternative treatment for postoperative high-output enterocutaneous fistula and a more practical method that is easy to execute to manage this problem. Long-term studies, involving more patients, are still necessary to confirm this suggestion.


Assuntos
Drenagem/métodos , Hormônio do Crescimento Humano/uso terapêutico , Fístula Intestinal/terapia , Somatostatina/uso terapêutico , Sucção/métodos , Irrigação Terapêutica/métodos , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Arch Endocrinol Metab ; 63(4): 320-327, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31460622

RESUMO

OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.


Assuntos
Acromegalia/tratamento farmacológico , Cabergolina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Somatostatina/análogos & derivados , Adulto , Idoso , Argentina , Cabergolina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
4.
Saudi Med J ; 40(7): 669-674, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31287126

RESUMO

OBJECTIVES: To report the genotype-phenotype characteristics, demographic features and clinical outcome of Omani patients with congenital hyperinsulinism (CHI). Methods: We retrospectively analyzed the clinical, biochemical, genotypical, phenotypical characteristics and outcomes of  children with CHI who were presented to the pediatric endocrine team in the Royal Hospital, Muscat, Oman between January 2007 and December 2016. Results: Analysis of 25 patients with CHI genetically revealed homozygous mutation in ABCC8 in 23 (92%) patients and 2 patients (8%) with compound heterozygous mutation in ABCC8. Fifteen (60%) patients underwent subtotal pancreatectomy as medical therapy failed and 2 (8%) patients showed response to medical therapy. Three patients expired during the neonatal period, 2 had cardiomyopathy and sepsis, and one had sepsis and severe metabolic acidosis. Out of the 15 patients who underwent pancreatectomy, 6 developed diabetes mellitus, 6 continued to have hypoglycemia and required medical therapy and one had pancreatic exocrine dysfunction post-pancreatectomy, following up with gastroenterology clinic and was placed on pancreatic enzyme supplements, while 2 patients continued to have hypoglycemia and both had abdominal MRI and 18-F-fluoro-L-DOPA positron emission tomography scan (PET-scan), that showed  persistent of the disease and started on medical therapy. Conclusion:  Mutation in ABCC8 is the most common cause of CHI and reflects the early age of presentation. There is a need for early diagnosis and appropriate therapeutic strategy.


Assuntos
Hiperinsulinismo Congênito/metabolismo , Hipoglicemia/metabolismo , Apneia/etiologia , Apneia/fisiopatologia , Pré-Escolar , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/fisiopatologia , Hiperinsulinismo Congênito/terapia , Diabetes Mellitus/tratamento farmacológico , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Heterozigoto , Homozigoto , Humanos , Hipoglicemia/complicações , Hipoglicemia/fisiopatologia , Lactente , Recém-Nascido , Letargia/etiologia , Letargia/fisiopatologia , Masculino , Mutação , Octreotida/uso terapêutico , Omã , Pancreatectomia , Peptídeos Cíclicos/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/fisiopatologia , Sirolimo/uso terapêutico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Receptores Sulfonilureia/genética , Resultado do Tratamento
5.
J Coll Physicians Surg Pak ; 29(7): 683-684, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31253226

RESUMO

The objective of this study was to investigate effects of somatostatin combined with pantoprazole on serum C-reactive protein (CRP) and intercellular adhesion molecule-1 (ICAM-1) in severe acute pancreatitis (SAP) patients. It was an experimental study carried out from February 2016 to April 2018. Eighty-two patients were randomly divided into group A and group B with 41 in each group. Pantoprazole was used in group A and somatostatin combined with pantoprazole was used in group B. Results showed that time of abdominal pain relief, intestinal function recovery and ventilator weaning in group B were shorter than those in group A (all p<0.001). After treatment, levels of CRP and ICAM-1 in group B were lower than those in group A (both p<0.001). Compared with pantoprazole alone, somatostatin combined with pantoprazole has a better therapeutic effect on SAP, and its mechanism may be related to reduction of serum CRP and ICAM-1.


Assuntos
Proteína C-Reativa/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Pancreatite/sangue , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Somatostatina/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Hormônios/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/tratamento farmacológico
6.
Int J Mol Sci ; 20(12)2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31234481

RESUMO

In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2). Both the PROMID (placebo-controlled, prospective, randomized study in patients with metastatic neuroendocrine midgut tumors) and the CLARINET (controlled study of lanreotide antiproliferative response in neuroendocrine tumors) trial showed a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) upon SSA treatment, compared to placebo. Moreover, the combination of SSA with peptide receptor radionuclide therapy (PRRT) in small intestinal NETs has proven efficacy in the phase 3 neuroendocrine tumours therapy (NETTER 1) trial. PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials.


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Animais , Antineoplásicos Hormonais/uso terapêutico , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Humanos , Tumores Neuroendócrinos/metabolismo , Octreotida/metabolismo , Octreotida/farmacologia , Peptídeos Cíclicos/metabolismo , Peptídeos Cíclicos/farmacologia , Receptores de Somatostatina/metabolismo , Transdução de Sinais , Somatostatina/metabolismo , Somatostatina/farmacologia , Somatostatina/uso terapêutico
7.
BMC Cancer ; 19(1): 575, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196127

RESUMO

BACKGROUND: Distant metastases frequently occur in gastroenteropancreatic neuroendocrine tumors. If hepatic surgery is not feasible, patients are treated with somatostatin analogs. However, the underlying mechanisms of action of this treatment remain to be defined. The aim of the present study was to analyze the micro-RNA expression profile inter-individually before and after the treatment with somatostatin analogs. MATERIAL AND METHODS: Tumor specimens of all included patients (n = 8) before and after the onset of a therapy with somatostatin analogs were analyzed and a micro-RNA expression profile (754 micro-RNAs) of each probe was generated. This analysis in an intra-individual setting was selected to avoid bias from inter-individual differences. The micro-RNA expression profiles were validated by qPCR. Patients with any other systemic treatment were excluded from the present study. RESULTS: Eight patients were included in the present study of which all had neuroendocrine tumors of the small intestine with diffuse hepatic metastases. Grouped analyses revealed that 15 micro-RNAs were differentially expressed (3 up- and 12 downregulated) after the exposure to somatostatin analogs. Additionally, let-7c-5p and mir-3137 are concordantly regulated in the inter-individually analysis. CONCLUSIONS: This is the first study analyzing the individual micro-RNA expression profile before and after a therapy with somatostatin analogs. Data from this study reveal that somatostatin analogs may in part exert their beneficial effects through an alteration in the micro-RNA expression profile.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Intestino Delgado/patologia , MicroRNAs/genética , Tumores Neuroendócrinos/tratamento farmacológico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Idoso , Variação Biológica da População , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Schweiz Arch Tierheilkd ; 161(5): 319-327, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-31064738

RESUMO

INTRODUCTION: Acromegaly due to a pituitary tumor has so far only been described in 3 dogs. The present case report describes a 7-year-old male-castrated Labrador Retriever which was referred because of difficult-to-control diabetes. Physical examination revealed markedly enlarged head, tongue and paws, widened interdental spaces and thickening of the skin in the head and neck area. IGF-1 and GH were increased and the latter continued to be abnormal after somatostatin application. Computed tomography demonstrated a space-occupying lesion in the pituitary gland and the diagnosis of acromegaly due to a GH-producing tumor of the pituitary was made. The dog underwent radiation therapy with a 6MV linear accelerator (3×8Gy) and improved substantially. Two and a half years after radiation therapy the dog developed lethargy and anorexia and was euthanized. Necropsy was not permitted. This case report represents the description of a dog suffering from pituitary-dependent acromegaly which was successfully treated and had a long-term survival.


Assuntos
Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/veterinária , Animais , Doenças do Cão/sangue , Cães , Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Hormônios/uso terapêutico , Fator de Crescimento Insulin-Like I/análise , Masculino , Radioterapia/veterinária , Somatostatina/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Ann Surg ; 269(6): 1025-1033, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31082898

RESUMO

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 µg), followed by a 2.5 mL/h infusion (somatostatin: 250 µg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.


Assuntos
Doença Hepática Terminal/complicações , Doença Hepática Terminal/cirurgia , Hormônios/uso terapêutico , Hipertensão Portal/tratamento farmacológico , Transplante de Fígado , Somatostatina/uso terapêutico , Idoso , Método Duplo-Cego , Doença Hepática Terminal/fisiopatologia , Feminino , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Resultado do Tratamento
10.
Invest Ophthalmol Vis Sci ; 60(6): 2257-2262, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112610

RESUMO

Purpose: Structural retinal microvascular changes have been identified as risk markers of diabetic retinopathy (DR). In order to estimate the retinal response of neuroprotective eye drops, we aimed to evaluate the effect of topical retinal neuroprotection on retinal microvascular changes in early DR. Methods: Patients with type 2 diabetes with no or early DR were randomized 1:1:1 to topical treatment with placebo, brimonidine, or somatostatin in a 96-week prospective, phase II to III, European multicenter trial. Retinal vascular calibers were measured semiautomatically in digital fundus images by certified graders at baseline and follow-up and summarized as central retinal arteriolar and venular equivalent (CRAE and CRVE). Results: Of 449 patients originally included, 297 completed the study with gradable retinal images. Median age and duration of diabetes was 64.5 and 9.9 years, and 65.7% were male. At baseline, Early Treatment Diabetic Retinopathy Study levels were 10 (no DR, 42.8%), 20 (minimal DR, 28.3%), and 35 (mild DR, 29.0%), and CRAE and CRVE did not differ between groups. As opposed to patients with no or minimal DR at baseline, patients with mild DR in the active groups developed a larger retinal arteriolar (brimonidine: +6.2 µm, P = 0.006; somatostatin: +7.2 µm, P = 0.006) and venular (brimonidine: +13.9 µm, P = 0.01; somatostatin: +14.3 µm, P = 0.0001) caliber in contrast to those in the placebo group. Conclusions: Topical treatment with brimonidine and somatostatin causes retinal arteriolar and venular dilation in patients with type 2 diabetes and preexisting early DR. Upcoming studies should elaborate on the potential of these findings in arresting early DR.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2 , Tartarato de Brimonidina , Retinopatia Diabética/tratamento farmacológico , Fármacos Neuroprotetores , Vasos Retinianos/efeitos dos fármacos , Somatostatina , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Adulto , Idoso , Tartarato de Brimonidina/farmacologia , Tartarato de Brimonidina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estudos Prospectivos , Somatostatina/farmacologia , Somatostatina/uso terapêutico
11.
Pituitary ; 22(4): 387-396, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31098838

RESUMO

PURPOSE: To investigate the effects of preoperative somatostatin analogue (SSA) treatment on the annual cost of all acromegaly treatment modalities and on remission rates. METHODS: The medical records of 135 patients with acromegaly who were followed at endocrinology clinic of Cerrahpasa Medical Faculty for at least 2 years after surgery between 2009 and 2016 were reviewed. RESULTS: The mean follow-up time was 50.9 ± 25.7 months. Early remission was defined according to 3rd month values in patients who didn't achieve remission, and 6th month values in patients who achieved remission at the 3rd month after surgery. The early and late remission rates of the entire study population were 40% and 80.7%, respectively. The early remission of the preoperative SSA-treated group (61.5%) was significantly higher than SSA-untreated group (31.2%) (p = 0.002). The early remission of the preoperative SSA-treated patients with macroadenomas (52.2%) was also significantly higher than the SSA-untreated group (23.5%) (p = 0.02). In the subgroup analysis; this difference was much more pronounced in invasive macroadenomas (p = 0.002). There were no differences between the groups in terms of late remission.The median annual cost of all acromegaly treatment modalities in study population was €3788.4; the cost for macroadenomas was significantly higher than for microadenomas (€4125.0 vs. €3226.5, respectively; p = 0.03). Preoperative SSA use in both microadenomas and macroadenomas didn't alter the cost of treatment. The increase in the duration of preoperative medical treatment had no effect on early or late remissions (p = 0.09; p = 0.8). CONCLUSIONS: Preoperative medical treatment had no effect on the costs of acromegaly treatment. There was a benefical effect of pre-operative SSA use on early remission in patients with macroadenomas; however, this effect didn't persist long term.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Somatostatina/uso terapêutico , Acromegalia/economia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Somatostatina/análogos & derivados , Somatostatina/economia , Resultado do Tratamento
12.
Int J Mol Sci ; 20(10)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121844

RESUMO

"Small-for-size" livers arising in the context of liver resection and transplantation are vulnerable to the effects of increased portal flow in the immediate postoperative period. Increased portal flow is an essential stimulus for liver regeneration. If the rise in flow and stimulus for regeneration are excessive; however, liver failure and patient death may result. Somatostatin is an endogenous peptide hormone that may be administered exogenously to not only reduce portal blood flow but also offer direct protection to different cells in the liver. In this review article, we describe key changes that transpire in the liver following a relative size reduction occurring in the context of resection and transplantation and the largely beneficial effects that peri-operative somatostatin therapy may help achieve in this setting.


Assuntos
Hormônios/uso terapêutico , Fígado/efeitos dos fármacos , Somatostatina/uso terapêutico , Animais , Hepatectomia , Hormônios/metabolismo , Hormônios/farmacologia , Humanos , Fígado/fisiologia , Regeneração Hepática/efeitos dos fármacos , Transplante de Fígado , Tamanho do Órgão/efeitos dos fármacos , Somatostatina/metabolismo , Somatostatina/farmacologia
13.
J Oncol Pharm Pract ; 25(6): 1425-1433, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30924737

RESUMO

BACKGROUND: Lanreotide and octreotide acetate suspension for injectable (LAR) are both recommended for clinical use in patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors. However, each agent possesses unique attributes in terms of their drug-delivery characteristics. The study objective was to compare overall drug-delivery efficiency between lanreotide and octreotide LAR in gastroenteropancreatic neuroendocrine tumor patients. METHODS: This study employed an observational time and motion design among patients treated with lanreotide or octreotide LAR across five US cancer centers. Baseline patient data collection included age, disease grade and duration, prior therapies and performance status. Drug-delivery time (drug preparation and administration), total patient time and resource use data were collected for gastroenteropancreatic neuroendocrine tumors receiving lanreotide (n = 22) or octreotide LAR (n = 22). Following each administration, qualitative data on the drug-delivery experience was collected from patients and nurses. RESULTS: Lanreotide was associated with a significant reduction in mean delivery time (2.5 min; 95% CI:2.0 to 3.1) compared to octreotide LAR (6.2 min; 95%CI: 4.4 to 7.9; p = 0.004). The mean total patient time for lanreotide and octreotide LAR was comparable between groups (32.1 vs. 36.6 minutes; p = 0.97). Nurses reported increased concerns with octreotide LAR related to needle clogging (p = 0.034) and device failures (p = 0.057). Overall, lanreotide had a median satisfaction score of 5.0 compared to a score of 4.0 with octreotide LAR (p = 0.03). CONCLUSIONS: Lanreotide was associated with significant reductions in drug-delivery time compared to octreotide LAR, which contributed to an improvement in overall healthcare efficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03017690.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Sistemas de Medicação/organização & administração , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Composição de Medicamentos , Falha de Equipamento , Feminino , Recursos em Saúde/estatística & dados numéricos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Agulhas/efeitos adversos , Satisfação do Paciente , Estudos Prospectivos , Somatostatina/uso terapêutico , Estudos de Tempo e Movimento
14.
Endokrynol Pol ; 70(1): 74-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843180

RESUMO

Acromegaly is a rare, chronic condition caused by growth hormone (GH) overproduction, usually due to a benign tumour of the pituitary gland. During the disease many complications occur, including cardiovascular disease and changes in the musculoskeletal, respiratory, and endocrine systems. Treatment includes surgery, medical therapy, and radiation. In this paper a literature review was conducted for information related to costs of management of acromegaly and its associated comorbidities using PubMed.The majority of total costs represent pharmacological treatment, especially the most common somatostatin analogues (SSA) therapy. The average reported annual cost of SSA therapy is EUR 12,000-40,000. Surgery reduces the cost of care via the possibility of avoiding lifelong pharmacological treatment. Radiotherapy is also suggested to lower the costs of therapy because about 60% of patients eventually will not require further pharmacological treatment; however, it is connected with negative outcomes like hypopituitarism, lower quality of life, and increased mortality. Cabergoline and pegvisomant are the lowest and highest priced treatments, respectively, but the overall impact on the cost of therapy is minor due to less frequent usage of these drugs. It is hard to fully estimate the impact of comorbidities of acromegaly on financial burden because patients are treated for them many years before the diagnosis of the underlying pathology. The treatment cost of comorbidities is higher in uncontrolled patients. Life-long treatment of acromegaly and its comorbidities is very expensive. Early diagnosis and successful treatment reduce direct and indirect costs.


Assuntos
Acromegalia/terapia , Custos e Análise de Custo , Gerenciamento Clínico , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Feminino , Humanos , Masculino , Somatostatina/uso terapêutico
15.
Endokrynol Pol ; 70(1): 2-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843181

RESUMO

Acromegaly is a rare disease caused by excessive production of growth hormone (GH), typically by a pituitary tumour. The diagnosis is usually delayed, and patients frequently develop various complications that cause premature mortality. In patients with hypertension, heart failure, diabetes, and arthropathies that are not age-specific, attention should be paid to signs of acromegaly. Insulin-like growth factor 1 (IGF-1) assay should be used as a screening test whenever acromegaly is suspected. Further diagnostic investigations and treatment should be carried out at specialist centres. First-line treatment involves selective excision of pituitary adenoma using transsphenoidal access. Patients with chances of cure with surgical removal of the pituitary tumour should be referred to centres that have experience in this type of procedure, following pharmacological preparation. Other patients, as well as patients after failed neurosurgical treatment, should first receive chronic treatment with first-generation somatostatin analogues. For second-line treatment, pasireotide, pegvisomant, cabergoline, or combinations thereof should be considered. In every case, acromegaly sequelae require life-long monitoring and active treatment. Current recommendations, being an updated version of the recommendations published in Endokrynologia Polska in 2014, which take into account the Polish situation, should prove useful in the management of patients with acromegaly.


Assuntos
Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Cabergolina/uso terapêutico , Endocrinologia , Feminino , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Neoplasias Hipofisárias/cirurgia , Polônia , Sociedades Médicas , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
16.
Pituitary ; 22(2): 187-194, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826981

RESUMO

PURPOSE: Acromegaly may be associated with an increased risk of complex intraoperative management and anesthetic complications. No study addressed whether pretreatment with somatostatin receptor ligands (SRLs) affects anesthesiologic management. METHODS: We studied 211 consecutive acromegalic patients who had a recorded intraoperative computerized anesthetic record (ICAR) available for analysis. Ninety-six (45.5%) patients were SRL-pretreated while 115 patients were treatment naïve. RESULTS: Treatment with SRLs reduced mean basal growth hormone level from 23.8 ± 4.2 to 5.9 ± 1.3 µg/L. Normalization of insulin-like growth factor-1 was achieved in 26 patients (27.1%). The frequency of comorbidities at surgery was similar in the two groups. Five patients with difficult intubation were naïve (4.3%) as compared with 5 SRL-pretreated patients (5.2%; P = 1.0). ICAR registration did not show any significant change of intraoperative vital parameters in the two groups of patients as well as in the intraoperative utilization of drugs. Total duration of anesthesia and surgery were similar in the two groups. Four patients with an intraoperative adverse event were naïve (3.5%) as compared with 4 SRL-pretreated patients (4.2%; P = 1.00). Remission of disease occurred in 83 of 114 naïve patients (72.8%) and in 57 of 93 SRL-pretreated patients (61.3%; P = 0.11). CONCLUSIONS: SRL-pretreatment of patients with acromegaly had no significant impact on intraoperative anesthesiologic management. Despite a better Cormack-Lehane score in SRL-pretreated than in naïve patients, the rate of difficult intubation was similar in both groups. SRL-pretreatment did not affect the rate of surgical remission or complications as well.


Assuntos
Anestesia/métodos , Neoplasias Hipofisárias/tratamento farmacológico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Acromegalia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Neoplasias Hipofisárias/metabolismo , Receptores de Somatostatina/metabolismo , Estudos Retrospectivos
17.
Drug Res (Stuttg) ; 69(9): 487-495, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30776840

RESUMO

BACKGROUND: Vasoactives such as terlipressin, somatostatin, vasopressin, octreotide and nitrates are commonly used to treat variceal bleeding. The present study is a network meta-analysis comparing the efficacy and safety of the above vasoactive agents for treating variceal bleeding. METHODS: Electronic databases were searched for appropriate randomized clinical trials evaluating vasoactives in cirrhotic patients with variceal bleeding. Random-effects model was used to generate the pooled estimates. Mortality was the primary outcome and bleeding control, re-bleeding rate, hospital stay, blood transfusion requirements and adverse events were the secondary outcome measures. RESULTS: Fifty randomized clinical trials were included of which 37 were included for the primary outcome. The overall analysis did not reveal any significant difference in the mortality risk between any of the vaso-active drugs except for terlipressin that had statistically significant benefits from direct pooled estimates. Somatostatin and terlipressin showed significant reduction in the mortality risks at 24 h. Terlipressin significantly reduced re-bleeding rate; somatostatin and vasopressin were associated with better hemostasis; and terlipressin and vasopressin significantly reduced the requirement for blood transfusion. Terlipressin, vasopressin and glyceryltrinitrate/vasopressin were also associated with increased risk of adverse events. CONCLUSION: Terlipressin could be the best agent in the vasoconstrictor category for managing variceal bleeding. Somatostatin and vasopressin can serve as alternatives.


Assuntos
Varizes Esofágicas e Gástricas/tratamento farmacológico , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia/tratamento farmacológico , Vasoconstritores/uso terapêutico , Humanos , Meta-Análise em Rede , Octreotida/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Somatostatina/uso terapêutico , Terlipressina/uso terapêutico , Vasopressinas/uso terapêutico
18.
World J Surg ; 43(7): 1788-1801, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30798417

RESUMO

BACKGROUND: Prophylactic administration of somatostatin analogues (SA) to reduce the incidence of post-operative pancreatic fistula (POPF) remains contentious. This meta-analysis evaluated its impact on outcomes following pancreaticoduodenectomy (PD). METHODS: The EMBASE, MEDLINE and Cochrane databases were searched for randomised controlled trials (RCTs) investigating prophylactic SA following PD. Comparative effects were summarised as odds ratio and weighted mean difference based on an intention to treat. Quantitative pooling of the effect sizes was derived using the random-effects model. MAIN RESULTS: Twelve RCTs were included involving 1615 patients [SA-treated group (n = 820) and control group (n = 795)]. The SA used included somatostatin-14, pasireotide, vapreotide and octreotide. Pooling of the data showed no significant benefit of its use for the primary outcome measure of all grades of POPF, odds ratio (OR) 0.73 [95% confidence interval (CI), 0.51-1.05, p = 0.09] and clinically relevant POPF, OR 0.48 [95% CI, 0.22-1.06, p = 0.07]. There were no benefits in the secondary outcome measures of delayed gastric emptying, OR 0.98 [95% CI, 0.57-1.69, p = 0.94]; infected abdominal collections, OR 0.80 [95% CI, 0.44-1.43, p = 0.80]; reoperation rates, OR 1.24 [95% CI, 0.73-2.13, p = 0.42]; duration of hospital stay, - 0.23 [95% CI - .59 to 1.13, p = 0.74]; and mortality, 1.78 [95% CI, 0.94-3.39, p = 0.08]. CONCLUSION: SA did not improve the post-operative outcomes following PD, including reducing the incidence of POPF. The routine administration of SA cannot be recommended following PD.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Fístula Pancreática/prevenção & controle , Somatostatina/uso terapêutico , Gastroparesia/etiologia , Humanos , Tempo de Internação/estatística & dados numéricos , Octreotida/uso terapêutico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/estatística & dados numéricos , Somatostatina/análogos & derivados
19.
World J Surg ; 43(3): 831-838, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30600364

RESUMO

OBJECTIVE: Long-acting synthetic somatostatin analogues (SSA) are an essential part of the treatment of neuroendocrine neoplasms. We evaluated the chemopreventive effects of a long-acting somatostatin analogue on the development of pancreatic neuroendocrine neoplasms (pNENs) in a genetically engineered MEN1 knockout mouse model. MATERIALS AND METHODS: Heterozygote MEN1 knockout mice were injected every 28 days subcutaneously with the somatostatin analogue lanreotide (Somatuline Autogel©; Ipsen Pharma) or a placebo starting at day 35 after birth. Mice were euthanized after 6, 9, 12, 15 and 18 months, and the size and number of pNENs were measured due histological analysis and compared to the placebo group. RESULTS: The median tumor size of pNENs was statistically significantly smaller after 9 (control group vs. SSA group; 706.476 µm2 vs. 195.271 µm2; p = 0.0012), 12 (placebo group vs. SSA group 822.022 vs. 255.482; p ≤ 0.001), 15 (placebo group vs. SSA group 1192.568 vs. 273.533; p ≤ 0.001) and after 18 months (placebo group vs. SSA group 1328.299 vs. 864.587; p ≤ 0.001) in the SSA group. Comparing the amount of tumors in both groups, a significant reduction was achieved in treated Men1(+/-) mice (41%, p = 0.002). Immunostaining showed, however, no significant difference in the expression of the apoptosis marker caspase-3, but a significant difference in Ki67 index as a marker for tumor cell proliferation (p ≤ 0.005). CONCLUSION: Long-acting somatostatin analogues may be an effective chemopreventive approach to delay the progression of MEN1-associated pNENs. After our preclinical results, we would recommend to evaluate the effects of long-acting SSA in a prospective clinical trial.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasia Endócrina Múltipla Tipo 1/prevenção & controle , Tumores Neuroendócrinos/prevenção & controle , Neoplasias Pancreáticas/prevenção & controle , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Animais , Caspase 3/metabolismo , Proliferação de Células , Quimioprevenção , Modelos Animais de Doenças , Progressão da Doença , Antígeno Ki-67/metabolismo , Camundongos , Camundongos Knockout , Neoplasia Endócrina Múltipla Tipo 1/metabolismo , Neoplasia Endócrina Múltipla Tipo 1/patologia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas/genética , Somatostatina/uso terapêutico , Carga Tumoral
20.
J Clin Endocrinol Metab ; 104(3): 773-778, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30597028

RESUMO

Context: Nesidioblastosis is a rare cause of adult hypoglycemia. Current medical therapy can mitigate disease symptoms. However, side effects and limited efficacy may prevent long-term disease management. Case Description: A 63-year-old white woman presented at our institution on April 2017 with a history of distal spleno-pancreatectomy for well-differentiated insulinoma in 2013. Hypoglycemic events did not resolve after surgery, and residual nesidioblastosis near the pancreatic resection margins was identified. Hypoglycemic episodes increased in frequency and severity despite high-dose diazoxide (DZX) therapy. On April 2016, octreotide was introduced but soon discontinued for inefficacy. When the patient arrived at our attention, add-on pasireotide was started and glucose levels monitored by subcutaneous sensor. Compared with DZX, 225 mg/d alone, sensor glucose during pasireotide + DZX 75 mg/d showed occurrence of severe hypoglycemia. Pasireotide was discontinued, and the instrumental workup (68Ga-DOTATOC CT/positron emission tomography, 99mTc-nanocolloid scintigraphy and echo-endoscopy + fine-needle aspiration biopsy) identified an insulinoma relapse. Subtotal pancreatectomy was performed without further recurrence of hypoglycemia over 9 months of follow-up. Conclusions: Although insulinoma relapses on background nesidioblastosis rarely occur, they should be considered as an alternate diagnosis when medical therapy fails to prevent hypoglycemia. Further studies are warranted to test whether the immunophenotypic signature of nesidioblastosis/insulinoma may provide insights for a tailored use of pasireotide.


Assuntos
Hipoglicemia/etiologia , Insulinoma/complicações , Recidiva Local de Neoplasia/complicações , Nesidioblastose/complicações , Neoplasias Pancreáticas/complicações , Diazóxido/uso terapêutico , Feminino , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/terapia , Insulinoma/patologia , Insulinoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Esplenectomia , Resultado do Tratamento
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