• Keywords
• Lanreotid,
• MeSH
• Patient Compliance MeSH
• Peptides, Cyclic MeSH
• Carcinoid Tumor * diagnosis   complications   therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Malignant Carcinoid Syndrome drug therapy   MeSH
• Neuroendocrine Tumors diagnosis   pathology   therapy   MeSH
• Antineoplastic Agents administration & dosage   therapeutic use   MeSH
• Somatostatin analogs & derivatives   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• Keywords
• Lanreotid,
• MeSH
• Peptides, Cyclic MeSH
• Carcinoid Tumor diagnosis   therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neuroendocrine Tumors * diagnosis   pathology   therapy   MeSH
• Antineoplastic Agents administration & dosage   therapeutic use   MeSH
• Somatostatin analogs & derivatives   MeSH
• Intestinal Neoplasms MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• Keywords
• Lanreotid,
• MeSH
• Peptides, Cyclic MeSH
• Carcinoid Tumor diagnosis   complications   therapy   MeSH
• Colectomy MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Neuroendocrine Tumors * diagnosis   pathology   therapy   MeSH
• Antineoplastic Agents administration & dosage   therapeutic use   MeSH
• Somatostatin analogs & derivatives   MeSH
• Intestinal Neoplasms surgery   diagnosis   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• Keywords
• Lanreotid,
• MeSH
• APUD Cells pathology   MeSH
• Gastrointestinal Neoplasms classification   secondary   MeSH
• Humans MeSH
• Neoplasm Metastasis diagnostic imaging   drug therapy   MeSH
• Neuroendocrine Tumors diagnosis   drug therapy   classification   secondary   MeSH
• Aged MeSH
• Somatostatin * analogs & derivatives   pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

• Keywords
• LANREOTID,
• MeSH
• Peptides, Cyclic MeSH
• Long-Term Care MeSH
• Carcinoid Tumor * diagnosis   pathology   therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lung Neoplasms diagnosis   therapy   MeSH
• Neuroendocrine Tumors diagnosis   therapy   MeSH
• Somatostatin analogs & derivatives   administration & dosage   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

PURPOSE: In the phase III CLARINET study (NCT00353496), lanreotide autogel/depot (lanreotide) significantly improved progression-free survival (PFS) vs placebo in patients with non-functioning intestinal or pancreatic neuroendocrine tumours (NETs). The aim of CLARINET open-label extension (OLE) (NCT00842348) was to evaluate long-term safety and efficacy of lanreotide in these patients. METHODS: Patients from the CLARINET study were eligible for the OLE if they had stable disease (irrespective of treatment group) or progressive disease (PD) (placebo-treated patients only). All patients in the OLE received lanreotide 120 mg every 28 days. Computed tomography or magnetic resonance imaging scans were conducted every 6 months and assessed locally for PD (the final scan was also assessed centrally). RESULTS: Overall, 89 patients took part in the OLE (lanreotide, n = 42; placebo, n = 47). Median (range) exposure to lanreotide in patients who received lanreotide in the core study and OLE (LAN-LAN group) was 59.0 (26.0-102.3) months. In this group, the overall incidences of adverse events (AEs) and treatment-related AEs were lower in the OLE than in the core study. Median [95% CI] PFS in the LAN-LAN group was 38.5 [30.9; 59.4] months. In placebo-treated patients with PD at the end of the core study, time to death or subsequent PD during the OLE was 19 [10.1; 26.7] months. CONCLUSIONS: This study provides new evidence on the long-term safety profile and sustained anti-tumour effects of lanreotide autogel/depot in indolent and progressive metastatic intestinal or pancreatic NETs.

• MeSH
• Peptides, Cyclic therapeutic use   MeSH
• Humans MeSH
• Pancreatic Neoplasms * drug therapy   MeSH
• Neuroendocrine Tumors * drug therapy   MeSH
• Antineoplastic Agents * adverse effects   MeSH
• Somatostatin analogs & derivatives   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cushingov syndróm (CS) je pomerne vzácne ochorenie charakterizované autonómnou hypersekréciou kortizolu. Ročná incidencia CS je 2–3/milión obyvateľov. Incidencia akromegálie je 3–4 pacienti na 1 000 000 za rok. Ochorenie je spôsobené hypersekréciou rastového hormónu (RH) v 99 % na podklade adenómu hypofýzy. V našej kazuistike prezentujeme 41-ročnú ženu s kombináciou Cushingovho syndrómu a akromegálie. Pacientka bola vyšetrená v NEDU Ľubochňa pre centripetálny typ obezity a hirzutizmus. Laboratórne bola prítomná hyperkortizolémia bez cirkadiánnej variácie, hyperkortizolúria s ele-vovanou hladinou adrenokortikotropného hormónu (ACTH). Realizovaná 2 mg dexametazónová blokáda bez adekvátnej supresie kortizolu v sére a moči až v 8 mg blokáde došlo k supresii kortizolúrie. Magnetická rezonancia (MR) s nálezom v. s. pikoadenómu hypofýzy veľkosti 2 mm. Následne bola realizovaná transsfenoidálna resekcia pikoadenómu hypofýzy. Histopatologické a imunohistochemické nálezy neodhalili ACTH produkujúci adenóm hypofýzy. Pozákrokovo pretrvával hyperkortizolizmus s novozachyteným hypersomatotropizmom. Do liečby bol pridaný Ketokonazol 200 mg tbl 1/2-0-1 a Lanreotid v dávke 120 mg každých 42 dní. Kontrolná MR hypofýzy preukázala drobnú ložiskovú štruktúru s rozmermi 3 × 4 mm. Po súhlase pacientky s odstupom 3 rokov bola vykonaná endoskopická revízia rezidua. Histologické a imunohistochemické vyšetrenia bez potvrdenia adenómu s ACTH a RH sekréciou. Pozákrokovo opäť nedošlo k znormalizovaniu plazmatických hladín IGF-1 s pretrvávaním hyperkortizolizmu. Bola opätovne začatá liečba Lanreotidom v pôvodnej dávke ako aj Ketokonazolom s na-výšením dávky 200 mg na 3-krát 1 tbl.

Cushing's syndrome (CS) is a relatively rare disease characterized by autonomous hypersecretion of cortisol. The incidence of CS is estimated to be equal to 2–3 cases per million inhabitants per year. The incidence of acromegaly is 3–4 patients per 1 000 000 per year. The disease is caused by hypersecretion of growth hormone which is mainly caused by benign tumour of the pituitary gland. In our case report we present a 41- year old woman suffering from both Cushing's syndrome and acromegaly. The patient was examined in National Institute of Endocrinology and Diabetology Ľubochňa for a centripetal type of obesity and hirsutism. Laboratory tests revealed high plasma cortisol levels without circulating variation, hypercortisoluria and elevated plasmatic levels of ACTH. A 2 mg dexamethasone blockade was performedwithout adequate cortisol suppression in serum and urine up to 8 mg blockade resulted in suppression of 24 hour urine free cortisol. A magnetic resonance imaging (MR) scan revealed suspectpikoadenoma of the pituitary gland (size 2 mm). Subsequentlytrans-sphenoidal resection was performed. Histopathological and immunohistochemical examinations did not reveal the ACTH-producing pituitary adenoma. After surgery hypercortisolism persisted with newly revealed hypersomatotropism. Treatment with Ketoconazole at dose 200 mg 1/ 2-0-1 and somatostatin analogues (Lanreotide) at dose 120 mg every 42 days were initiated. Control magnetic resonance imaging of the sella demonstrated small tumour of pituary gland of size 3 × 5 mm. Later 3 years after firstsurgery another transsphenoidal resection of residue was performed. Histological and immunohistochemical examinations did not confirmadenoma with ACTH and RH secretion. After second surgery, IGF-1 plasma levels were not normalized with persistence of hypercortisolism. The treatment with Lanreotide at the initial dose as well as Ketoconazole was reinitiated (with increased dose of Ketoconazole to 1-1-1 tbl per 200 mg).

• MeSH
• Acromegaly etiology   MeSH
• Cushing Syndrome * surgery   diagnosis   drug therapy   MeSH
• Adult MeSH
• Hydrocortisone analysis   blood   urine   MeSH
• Pituitary ACTH Hypersecretion MeSH
• Pituitary Gland surgery   diagnostic imaging   MeSH
• Ketoconazole therapeutic use   MeSH
• Humans MeSH
• Growth Hormone MeSH
• Somatostatin analogs & derivatives   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Somatostatin analogs mantain their major role in the treatment of patients with advanced neuroendocrine tumors (NETs) and have multiple modulatory effects on the immune system. Here, we evaluated the effects of lanreotide treatment on expression of Th1, Th2 cytokine patterns in serum of patients with NETs and in bronchial and pancreatic NET cell lines. Our results showed that lanreotide treatment promoted a Th1 cytotoxic immune-phenotype in patients with NETs originated by intestinal sites. Similar results were obtained also in vitro where lanreotide induced expression of Th1 cytokines only in pancreatic and not in bronchial-derived NET cell lines. It seems, therefore, that cytokinomics can represent a useful tool for the identification of tumor biomarkers for the early diagnosis and evaluation of the response to therapy in NET patients. To avoid the drug-resistance induced by everolimus (mTOR inhibitor), we made the pancreatic NET cell line resistant to this drug. After treatment with lanreotide we found that the drug reduced its viability compared to that of sensitive cells. These data may have direct implications in design of future translation combination trial on NET patients.

• Publication type
• Journal Article MeSH

• MeSH
• Chemical Actions and Uses MeSH
• Poisoning MeSH
• Pathology MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• patologie

Accessible prognostic tools are needed to individualize treatment of neuroendocrine tumors (NETs). Data suggest neutrophil/lymphocyte ratios (NLRs) have prognostic value in some solid tumors, including NETs. In the randomized double-blind CLARINET study (NCT00353496; EudraCT 2005-004904-35), the somatostatin analog lanreotide autogel/depot increased progression-free survival (PFS) compared with placebo in patients with inoperable or metastatic intestinal and pancreatic NETs (grades 1-2, Ki-67 < 10%). The exploratory post-hoc analyses presented here evaluated the prognostic value of NLR in the CLARINET study cohort, in the context of and independently from treatment. Kaplan-Meier PFS plots were generated for patients with available NLR data, in subgroups based on NLR values, and 24-month survival rates were calculated. P values and hazard ratios for prognostic effects were generated using Cox models. 31216222 Baseline characteristics were balanced between lanreotide autogel/depot 120 mg (n = 100) and placebo (n = 101) arms. Irrespective of treatment, raw 24-month PFS rates were comparable across subgroups based on NLR tertiles [37.3% (low), 38.8% (middle), 38.8% (high); n = 67 per group] and NLR cutoff of 4 [38.1% (NLR ≤ 4; n = 176), 40.0% (NLR > 4; n = 25)]. Furthermore, NLRs were not prognostic in Cox models, irrespective of subgroups used. The therapeutic effect of lanreotide autogel/depot 120 mg was independent of NLRs (P > 0.1). These exploratory post-hoc analyses in patients with advanced intestinal and pancreatic NETs contrast with previous data suggesting NLR has prognostic potential in NETs. This may reflect the inclusion of patients with lower-grade tumors or use of higher NLR cutoff values in the current analysis.

• MeSH
• Double-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphocytes * MeSH
• Pancreatic Neoplasms blood   mortality   MeSH
• Neuroendocrine Tumors blood   mortality   MeSH
• Neutrophils * MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH