RESUMO
Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.
Assuntos
Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile/epidemiologia , Cromogranina A/sangue , Feminino , Humanos , Ácido Hidroxi-Indolacético/sangue , Incidência , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/mortalidade , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/mortalidade , Serotonina/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. MATERIALS AND METHODS: Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P < 0.001, respectively). CHGA gene variants (T-415C and Glu264Asp) revealed significant differences between diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P < 0.05). CONCLUSIONS: T2DM causes abnormalities in the function of salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. CLINICAL RELEVANCE: Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.
Assuntos
Cromogranina A/sangue , Cromogranina A/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Glândulas Salivares/fisiopatologia , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de RestriçãoRESUMO
PURPOSE: An association between neuroendocrine tumors (NETs) and second primary malignancies (SPMs) has been reported. We have examined the incidence and etiology of SPMs in patients with NETs included in the Neuroendocrine Tumor Association of Andalusia (ATNEA) Registry. METHODS: Data on 111 patients were collected. Sex, age, NET site, chromogranin A levels, neuropeptide secretion and disease stage were compared between NETs with and without SPMs. RESULTS: SPMs were present in 21 patients (18.9 %): five colorectal tumors, four non-small-cell lung cancers, three gastric cancers, two tumors in the small intestine, one hepatocarcinoma, two ovarian tumors, one breast adenocarcinoma, one hypernephroma, one bladder cancer, and one neuroblastoma. SPMs were present in 18 % of patients with a gastrointestinal NET and 22 % of those with a non-gastrointestinal NET. SPMs were found in 23 % of patients with elevated levels of serum chromogranin A, compared to 17 % of patients with normal levels, and in 22 % of patients with functional tumors, compared to 11 % of those with non-functional tumors. Finally, SPMs were observed in 24 % of patients with a local or locoregional tumor but in only 13 % of those with a metastatic tumor. No other differences between patients with and without SPMs were observed. CONCLUSIONS: The percentage of patients with SPMs in the ATNEA Registry is similar to those reported in other series. In our registry, patients with functional NETs and local/locoregional tumors have higher probability of SPMs. The low number of patients, selection bias and other etiologic factors of SPMs may have influenced our results.
Assuntos
Cromogranina A/sangue , Neoplasias Gastrointestinais/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Tumores Neuroendócrinos/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma de Células Renais/epidemiologia , Neoplasias Colorretais/epidemiologia , Feminino , Neoplasias Gastrointestinais/sangue , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Neuroblastoma/epidemiologia , Tumores Neuroendócrinos/sangue , Neoplasias Ovarianas/epidemiologia , Espanha , Neoplasias Gástricas/epidemiologia , Adulto JovemRESUMO
Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.
Assuntos
Biomarcadores Tumorais/sangue , Cromogranina A/sangue , Neoplasias Gastrointestinais/patologia , Tumores Neuroendócrinos/patologia , Biomarcadores/análise , Biomarcadores/metabolismo , Diagnóstico por Imagem , Neoplasias Gastrointestinais/classificação , Humanos , Estadiamento de Neoplasias , Tumores Neuroendócrinos/classificação , PrognósticoRESUMO
Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.
Assuntos
Humanos , Cromogranina A/sangue , Neoplasias Gastrointestinais/patologia , Tumores Neuroendócrinos/patologia , Biomarcadores Tumorais/sangue , Biomarcadores/análise , Biomarcadores/metabolismo , Diagnóstico por Imagem , Neoplasias Gastrointestinais/classificação , Estadiamento de Neoplasias , Tumores Neuroendócrinos/classificação , PrognósticoRESUMO
PURPOSE: The presence of neuroendocrine differentiation may play a key role in androgen-independent tumor progression. The prognostic significance of plasma chromogranin-A (CgA) was assessed in a series of consecutive patients with high-risk prostate cancer (PCa). PATIENTS AND METHODS: Twenty-three patients presenting high-risk PCa and 8 healthy individuals, as control group, had their blood samples collected to evaluate CgA, free and total prostate specific antigen, and free and total testosterone in a pilot study. The correlations of serum CgA levels with PSA, testosterone, Gleason score, number of foci of hypercaptation in bone scan, age, and outcomes were evaluated at baseline and after 12 months. RESULTS: Patients with PCa had significantly higher levels of plasma CgA (mean, 8.7; range, 1.9-73) than healthy patients (mean, 3.45; range, 0.6-5.6), P = 0.02. Analyzing only the patients group through correlation of the ranks, it was observed that CgA has low, insignificant correlations with PSA (P = 0.07) and with metastatic extension (P = 0.09). No association was found between the plasma CgA levels and the Gleason score (P = 0.20), age (P = 0.15), or disease progression (P = 0.27). CONCLUSION: The serum levels of CgA were significantly increased in the group with PCa compared with the healthy group. However, there were low correlations between serum CgA and known prognostic factors (such as total and free PSA, age, Gleason score, and bone metastases) or clinical deterioration. Although future studies are needed with larger samples and longer follow-up, the presented data envisage a limited role to serum CgA as high-risk PCa prognostic factor.
Assuntos
Adenocarcinoma/sangue , Cromogranina A/sangue , Neoplasias da Próstata/sangue , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapiaRESUMO
Elevated circulating levels of chromogranin A (CgA) are found in the neuroendocrine tumors (NETs), but diagnostic usefulness of this marker is still debatable. To assess the role of CgA for the identification and follow up of gastroenteropancreatic neuroendocrine tumors (GEP-NET), a multicenter prospective longitudinal study has been carried out in Argentina. CgA was measured by RIA in 119 histologically proven GEP-NET patients and in 39 healthy controls. A cutoff value of 2.8 nmol/L was established from a receiver-operating characteristic (ROC) curve, as discriminating between controls and patients with active disease (specificity 100% and sensitivity 92.3%). CgA levels were higher in functioning than in no functioning tumors (median 55 nmol/L vs 5 nmol/L, p < 0.05). Metastases were present in 83 patients and their CgA levels were significantly higher than levels in the 36 patients without metastases (median 44 nmol/L vs 64 nmol/L, p < 0.0001). CgA levels are strongly correlated with tumor metastatic spread. Sensitivity differed between patients with localized disease (median 6 nmol/L), extensive disease (median 22 nmol/L) and very extensive disease (median 44 nmol/L) (p < 0.001). In conclusion, due to its high sensitivity and specificity, CgA is useful in a newly discovered GEP-NET especially when no abnormal hormone secretion can be demonstrated. CgA levels were significantly higher in functioning tumors than in non-functioning tumors and increased with metastatic spread. If serial evaluation of CgA levels is sufficient for the detection of tumor growth changes remains to be prospectively demonstrated.