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1.
Eur J Endocrinol ; 185(4): 577-586, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374651

RESUMO

Objective: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. Design: Retrospective cohort study. Methods: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. Results: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). Conclusions: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.


Assuntos
Insulinoma/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Finlândia/epidemiologia , Seguimentos , História do Século XX , História do Século XXI , Humanos , Incidência , Insulinoma/complicações , Insulinoma/diagnóstico , Insulinoma/mortalidade , Pessoa de Meia-Idade , Morbidade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo
2.
Am J Surg ; 221(2): 437-447, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32873371

RESUMO

BACKGROUND: How malignant insulinomas present relative to benign insulinomas is unknown. METHODS: A single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used. RESULTS: A total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01. CONCLUSIONS: Larger size of insulinoma and increased serum ß-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.


Assuntos
Insulinoma/diagnóstico , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeo C/sangue , Criança , Diagnóstico Diferencial , Feminino , Humanos , Insulina/sangue , Insulinoma/sangue , Insulinoma/mortalidade , Insulinoma/patologia , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Adulto Jovem
3.
Eur J Endocrinol ; 182(4): 439-446, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32061159

RESUMO

Introduction: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. Aim of the study: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. Materials and methods: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. Results: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. Conclusions: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.


Assuntos
Insulinoma/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Feminino , Humanos , Hipoglicemia/etiologia , Hipoglicemia/mortalidade , Hipoglicemia/patologia , Insulinoma/patologia , Insulinoma/terapia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Ann Endocrinol (Paris) ; 79(1): 30-36, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29241949

RESUMO

BACKGROUND: Hypoglycemic manifestations are highly variable in patients with an insulinoma and largely independent of tumour size and severity of insulin hypersecretion. OBJECTIVES: We investigated the clinical, biological and tumoral characteristics of insulinomas in a large monocentric series of patients and we evaluated their insulin sensitivity before and after successful pancreatic surgery. PATIENTS AND METHODS: This was a retrospective analysis of 40 patients treated for an insulinoma between 1982 and 2012 in our academic hospital. Insulin sensitivity and beta cell function were evaluated by a HOMA test outside hypoglycaemic episodes in a large subset of these patients. RESULTS: The mean age at onset of symptoms was 48.8±20.1 years and the mean age at diagnosis was 50.7±19.9 years. Neuroglycopenic symptoms were observed in 90% of patients. The most effective preoperative imaging technique to localize the tumour was endoscopic ultrasound. Insulin sensitivity was greatly reduced in patients with insulinoma (38.9%±22.3%), while beta cells function was increased (359.0±171.5%), but to a variable extent (range: 110.6-678.6%). After complete resection of the tumour and remission of hypoglycemic episodes, insulin sensitivity increased in all evaluated subjects (72.8±36.7%) and normalized in the majority. CONCLUSION: Although neuroglycopenic symptoms are present in most patients, diagnosis of insulinoma is often delayed. Endoscopic ultrasound remains the most sensitive preoperative technique to localize the tumour. We also show that in response to chronic hyperinsulinemia, patients with insulinoma develop protective mechanisms responsible for a marked insulin resistance, which is reversible after complete resection of the tumour.


Assuntos
Resistência à Insulina , Insulinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/etiologia , Hipoglicemia/cirurgia , Insulina/sangue , Insulinoma/complicações , Insulinoma/mortalidade , Insulinoma/cirurgia , Masculino , Pessoa de Meia-Idade , Pancreatectomia/reabilitação , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Remissão Espontânea , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Adulto Jovem
5.
Hormones (Athens) ; 15(2): 157-169, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27376420

RESUMO

Insulinomas are the most common functioning neuroendocrine tumors of the pancreas, occurring in almost 1-4 per 1 million persons each year. In contrast to other pancreatic neuroendocrine tumors, they are usually benign and solitary at the time of diagnosis. Due to their benign nature, surgical excision is the treatment of choice, with excellent long-term results. The introduction of minimally invasive techniques in the surgical treatment of insulinoma has been gaining popularity due to shorter length of hospital stay and better cosmetic results, with serious complications being comparable to those of open surgery. Preoperative localization is of paramount importance in the determination of the appropriate surgical approach. Many invasive and non-invasive methods exist for localization of an insulinoma. A combination of these modalities is usually adequate to preoperatively localize the vast majority of tumors. Laparoscopic ultrasound is mandatory to localize these tumors intraoperatively. Despite extensive experience in highly specialized centers producing encouraging results, no randomized trials have been realized to conclusively validate these case series, this partly due to the rarity of insulinoma in the population. In this article we present the current state of laparoscopic management of insulinoma delineating still unanswered issues and we underscore some of the technical details of the most common laparoscopic procedures employed.


Assuntos
Insulinoma/cirurgia , Laparoscopia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Humanos , Insulinoma/diagnóstico por imagem , Insulinoma/mortalidade , Insulinoma/patologia , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Fatores de Risco , Resultado do Tratamento
6.
Surgery ; 159(5): 1382-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26704781

RESUMO

BACKGROUND: Malignant-functioning pancreatic neuroendocrine tumors (mFpNETs) are rare. Research analyzing the presentation, biological behavior, and patient outcomes of these tumors is limited. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with malignant insulinomas, gastrinomas, glucagonomas, vasoactive intestinal peptide secreting tumors (VIPomas), somastatinomas, and mixed islet cell tumors (MICTs). The primary endpoint of this study was to identify factors affecting survival. RESULTS: We identified 401 patients with mFpNETs. Between histologic subtypes, there were significant differences in sex and age, and in tumor size, grade, location, and stage. Median survival time for insulinomas was 12.7 years; gastrinomas, 10.2 years; glucagonomas, 7.7 years; VIPomas, 7.9 years; and MICTs, 3.4 years. Multivariable analysis showed that histology (insulinoma, gastrinoma, and VIPoma; P = .009), absence of distant metastases (P = .002), age < 50 years (P = .001), surgical intervention (P = .001), and stage I/II disease (P = .011) were independently associated with prolonged survival. Subgroup analysis demonstrated that removal of the primary tumor in stage IV mFpNETs was associated with significantly prolonged survival (P = .01). CONCLUSION: mFpNETs are rare tumors that commonly present at an advanced stage despite hormonal secretion. Primary tumor resection is associated with longer survival in stages I-III as well as stage IV tumors.


Assuntos
Carcinoma de Células das Ilhotas Pancreáticas/mortalidade , Insulinoma/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células das Ilhotas Pancreáticas/patologia , Carcinoma de Células das Ilhotas Pancreáticas/cirurgia , Feminino , Seguimentos , Humanos , Insulinoma/patologia , Insulinoma/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Estados Unidos/epidemiologia
7.
Mod Pathol ; 28(1): 69-79, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24947143

RESUMO

The prognosis of pancreatic neuroendocrine tumors is related to size, histology and proliferation rate. However, this stratification needs to be refined further. We conducted a proteome study on insulinomas, a well-defined pancreatic neuroendocrine tumor entity, in order to identify proteins that can be used as biomarkers for malignancy. Based on a long follow-up, insulinomas were divided into those with metastases (malignant) and those without (benign). Microdissected cells from six benign and six malignant insulinomas were subjected to a procedure combining fluorescence dye saturation labeling with high-resolution two-dimensional gel electrophoresis. Differentially expressed proteins were identified using nano liquid chromatography-electrospray ionization/multi-stage mass spectrometry and validated by immunohistochemistry on tissue microarrays containing 62 insulinomas. Sixteen differentially regulated proteins were identified among 3000 protein spots. Immunohistochemical validation revealed that aldehyde dehydrogenase 1A1 and voltage-dependent anion-selective channel protein 1 showed significantly stronger expression in malignant insulinomas than in benign insulinomas, whereas tumor protein D52 (TPD52) binding protein was expressed less strongly in malignant insulinomas than in benign insulinomas. Using multivariate analysis, low TPD52 expression was identified as a strong independent prognostic factor for both recurrence-free and overall disease-related survival.


Assuntos
Biomarcadores Tumorais/análise , Insulinoma/patologia , Proteínas de Neoplasias/biossíntese , Neoplasias Pancreáticas/patologia , Proteômica/métodos , Adulto , Idoso , Cromatografia Líquida , Eletroforese em Gel Bidimensional , Feminino , Humanos , Imuno-Histoquímica , Insulinoma/metabolismo , Insulinoma/mortalidade , Estimativa de Kaplan-Meier , Masculino , Microdissecção , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Espectrometria de Massas por Ionização por Electrospray , Análise Serial de Tecidos
9.
J Surg Res ; 184(1): 221-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23643298

RESUMO

INTRODUCTION: Neuroendocrine tumors (NETs) frequently metastasize prior to diagnosis. Although metastases are often identifiable on conventional imaging studies, primary tumors, particularly those in the midgut, are frequently difficult to localize preoperatively. MATERIALS AND METHODS: Patients with metastatic NETs with intact primaries were identified. Clinical and pathologic data were extracted from medical records. Primary tumors were classified as localized or occult based on preoperative imaging. The sensitivities and specificities of preoperative imaging modalities for identifying the primary tumors were calculated. Patient characteristics, tumor features, and survival in localized and occult cases were compared. RESULTS: Sixty-one patients with an intact primary tumor and metastatic disease were identified. In 28 of these patients (46%), the primary tumor could not be localized preoperatively. A median of three different preoperative imaging studies were utilized. Patients with occult primaries were more likely to have a delay (>6 mo) in surgical referral from time of onset of symptoms (57% versus 27%, P = 0.02). Among the 28 patients with occult primary tumors, 18 (64%) were found to have radiographic evidence of mesenteric lymphadenopathy corresponding, in all but one case, to a small bowel primary. In all but three patients (89%), the primary tumor could be identified intraoperatively. CONCLUSION: The primary tumor can be identified intraoperatively in a majority of patients with metastatic NETs, irrespective of preoperative localization status. Referral for surgical management should not, therefore, be influenced by the inability to localize the primary tumor.


Assuntos
Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/cirurgia , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Adulto , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Tumor Carcinoide/cirurgia , Feminino , Gastrinoma/mortalidade , Gastrinoma/secundário , Gastrinoma/cirurgia , Humanos , Insulinoma/mortalidade , Insulinoma/secundário , Insulinoma/cirurgia , Período Intraoperatório , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Período Pré-Operatório , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
10.
J Am Anim Hosp Assoc ; 49(3): 224-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23325593

RESUMO

This case report highlights an unusually prolonged, asymptomatic, disease-free interval in an aged male Labrador retriever that underwent partial pancreatectomy for a functionally active pancreatic insulinoma with histologically confirmed hepatic metastasis. The patient developed pancreatitis and nonseptic suppurative peritonitis 24 hr after surgical resection of the insulinoma and was managed medically until discharge. Three mo after surgery, the dog was diagnosed with exocrine pancreatic insufficiency (EPI) that was effectively managed with parenteral pancreatic enzymes. Due to normal glucose levels 3 mo postsurgically, liver samples from the initial surgery were resubmitted for immunohistochemistry. Results confirmed insulinoma metastasis with insulin expression. Ten mo postsurgically, the blood glucose was normal and serum insulin levels were slightly above the upper reference limit. The first hypoglycemic episode was documented 23 mo postoperatively, which was effectively managed with prednisone. The cause for the prolonged disease remission and survival was unknown, but was possibly a result of pancreatitis and peritonitis, partial spontaneous regression of metastatic lesions, or idiopathic. Despite life-threatening postoperative complications, this patient enjoyed a profoundly longer than expected survival. This case highlights the importance of removing the primary tumor (insulinoma) despite the presence of metastatic disease.


Assuntos
Doenças do Cão/mortalidade , Insulinoma/veterinária , Neoplasias Hepáticas/veterinária , Pancreatectomia/veterinária , Neoplasias Pancreáticas/veterinária , Animais , Glicemia/metabolismo , Doenças do Cão/cirurgia , Cães , Insulina/sangue , Insulinoma/mortalidade , Insulinoma/secundário , Insulinoma/cirurgia , Neoplasias Hepáticas/patologia , Masculino , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Resultado do Tratamento
11.
World J Surg ; 36(6): 1411-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22089920

RESUMO

BACKGROUND: Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated. METHODS: A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed. RESULTS: Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24-71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90). CONCLUSIONS: High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células das Ilhotas Pancreáticas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Insulinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células das Ilhotas Pancreáticas/mortalidade , Carcinoma de Células das Ilhotas Pancreáticas/patologia , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Insulinoma/mortalidade , Insulinoma/patologia , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Survivina
12.
J Surg Oncol ; 105(6): 595-600, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22006521

RESUMO

BACKGROUND: The low incidence of malignant "functional" (F) or "nonfunctional" (NF) neuroendocrine islet cell tumors (ICTs) of the pancreas represents a challenge to precise post-therapeutic survival prediction. This study examined the survival impact of malignant pancreatic ICT morphologic subtypes. METHODS: A pancreatic ICT data set was created from a US-based population database from 1980-2004. Prognostic factors with survival impact and relationships between surgical therapy and overall survival (OS) were analyzed. RESULTS: There were 2,350 individuals with malignant ICTs. Histologic subtypes included carcinoid tumors, islet cell carcinomas, neuroendocrine carcinomas, and malignant gastrinomas, insulinomas, glucagonomas, or VIPomas. There was no difference in resection rates between FICTs and NFICTs (23% vs. 20%, P = ns). Median OS was 30 months, with group differences ranging from NE carcinomas (21) to VIPomas (96; P < 0.0001). Median OS of resected versus unresected FICTs was 172 versus 37 months, while that of NFICTs was 113 versus 18 months (P < 0.0001). Compared to neuroendocrine carcinomas, hazard ratios were: VIPomas 0.48, gastrinomas 0.65, carcinoid tumors 0.76, insulinomas 0.84, glucagonomas 0.93, and islet cell carcinomas 1.0. CONCLUSIONS: When controlled for other established prognostic parameters, histopathologic subtype assignment of pancreatic ICTs affects survival prediction. Resection is associated with superior survival for all tumor types.


Assuntos
Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células das Ilhotas Pancreáticas/mortalidade , Carcinoma de Células das Ilhotas Pancreáticas/patologia , Carcinoma de Células das Ilhotas Pancreáticas/cirurgia , Feminino , Humanos , Insulinoma/mortalidade , Insulinoma/patologia , Insulinoma/cirurgia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Modelos de Riscos Proporcionais , Programa de SEER , Estados Unidos , Adulto Jovem
13.
J Clin Oncol ; 29(22): 3044-9, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21709192

RESUMO

PURPOSE: The American Joint Committee on Cancer (AJCC) staging manual (seventh edition) has introduced its first TNM staging classification for pancreatic neuroendocrine tumors (NETs) derived from the staging algorithm for exocrine pancreatic adenocarcinomas. This classification has not yet been validated. METHODS: Patients with pancreatic NETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I to IV) based on the new AJCC classification. Kaplan-Meier analyses for overall survival (OS) were performed based on age, race, histologic grade, incidental diagnosis, and TNM staging (European Neuroendocrine Tumors Society [ENETS] v AJCC) using log-rank tests. Survival time was measured from time of initial diagnosis to date of last contact or date of death. Multivariate modeling was performed using Cox proportional hazards regression. Weighted Cohen's κ coefficient was computed to evaluate the agreement of ENETS and AJCC classifications. RESULTS: We identified 425 patients with pancreatic NETs. On the basis of histopathologic grade, 5-year survival rates for low-, intermediate-, and high-grade tumors were 75%, 62%, and 7%, respectively (P < .001). When using the ENETS classification, 5-year OS rates for stages I, II, III, and IV were 100%, 88%, 85%, and 57%, respectively (P < .001). Subsequently, using the AJCC classification, 5-year OS rates for stages I, II, III, and IV were 92%, 84%, 81%, and 57%, respectively (P < .001). Both the novel AJCC classification and the ENETS classification were highly prognostic for survival. CONCLUSION: The AJCC TNM classification for pancreatic NETs is prognostic for OS and can be adopted in clinical practice.


Assuntos
Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Comitês Consultivos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Gastrinoma/mortalidade , Gastrinoma/patologia , Glucagonoma/mortalidade , Glucagonoma/patologia , Humanos , Achados Incidentais , Insulinoma/mortalidade , Insulinoma/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/classificação , Neoplasias Pancreáticas/classificação , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Vipoma/mortalidade , Vipoma/patologia
14.
Dig Surg ; 28(1): 63-73, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21293134

RESUMO

BACKGROUND: The majority of insulinomas are benign, small and intrapancreatic. Preoperative localisation is important to plan the surgical management. METHODS: We retrospectively analysed our data on the preoperative imaging, type of surgery and histopathological features of the operated patients with an insulinoma from January 1993 to March 2010. Univariate and multivariate analyses were performed to detect the predictive factors for survival following surgery. RESULTS: Forty patients were operated on for insulinoma, of which 33 were benign and 7 were malignant. The sensitivity of preoperative computed tomogram scan, magnetic resonance imaging and endoscopic ultrasound, for localising the lesions was 62, 82 and 94%, respectively. Enucleation was performed in 21 (52.5%) patients, and remaining had pancreatic resection. Hepatic resection was performed in 2 and liver transplantation in 1 patient. Morbidity and perioperative mortality was 17 (42.5%) and 1 (2.7%), respectively. The overall 5- and 10-year survival was 89 and 86.5%, respectively. The presence of metastases was found to be an independent predictor of poor survival on multivariate analysis. CONCLUSION: Preoperative computed tomogram/magnetic resonance imaging and endoscopic ultrasound are sensitive in localizing the majority of insulinomas. Surgery offers a good long-term survival, even in patients with malignant insulinoma.


Assuntos
Endossonografia , Insulinoma/diagnóstico , Insulinoma/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , Humanos , Insulinoma/mortalidade , Tempo de Internação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
Eur J Endocrinol ; 162(2): 391-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20097833

RESUMO

OBJECTIVE: EpCAM (CD326) is overexpressed in progenitor cells of endocrine pancreatic islands of Langerhans during fetal development and was suggested to act as a morphoregulatory molecule in pancreatic island ontogeny. We tested whether EpCAM overexpression is reactivated in insulinomas, endocrine tumors arising in the pancreas. DESIGN/METHOD: We used monoclonal anti-EpCAM antibody Ber-Ep4 for immunohistochemistry on formalin-fixed and paraffin-embedded tumor material. We analyzed 53 insulinomas: 40 benign (disease stage

Assuntos
Antígenos de Neoplasias/genética , Moléculas de Adesão Celular/genética , Insulinoma/genética , Insulinoma/mortalidade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Idoso , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/metabolismo , Molécula de Adesão da Célula Epitelial , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Hiperinsulinismo/genética , Hiperinsulinismo/mortalidade , Imuno-Histoquímica , Insulinoma/secundário , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco
16.
Diabetes Metab ; 34(4 Pt 1): 343-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18556231

RESUMO

AIM: Sporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI. METHODS: Every patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded. RESULTS: The ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up. CONCLUSION: Aggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.


Assuntos
Insulinoma/terapia , Neoplasias Pancreáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/mortalidade , Feminino , Seguimentos , Humanos , Insulinoma/mortalidade , Insulinoma/secundário , Insulinoma/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Langenbecks Arch Surg ; 393(3): 391-5, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18196267

RESUMO

BACKGROUND: Laparoscopic resection of benign pancreatic endocrine neoplasms (PENs) has become the standard of care for tumors in the pancreatic tail. Over a 14-year period, we have resected both benign and malignant tumors of the entire pancreas laparoscopically and compared our survival and complication rates with open controls. MATERIALS AND METHODS: We collected our data retrospectively and reviewed our outcomes with an actuarial 5-year survival according to Kaplan-Meier. Patients who underwent minimally invasive techniques were compared to patients who were approached with open techniques. RESULTS: From April 1992 to September 2006, we operated on 31 patients for PENs: 13 (42%) were operated on using open techniques and 18 (58%) laparoscopically, and conversion occurred in one patient (6%). In the laparoscopic group, eight (47%) tumors were malignant compared to six (43%) in the open group. Operative times averaged 188 min for the minimally invasive approach and 305 min for the open approach (p = 0.02). Length of stay was 25 days (range 8-82) for the laparoscopic group compared to 20 days (range 6-63; p > 0.05). Overall morbidity and fistula rates ranged from 67 to 24% in the laparoscopic group to 69 to 38% in the open group (p > 0.05). There were no postoperative mortalities. The average follow-up was 63 months for the open group and 33 months for the laparoscopic group. The overall actuarial survival rates were both 90% at 5 years. CONCLUSIONS: Laparoscopic resection of benign and malignant PENs has similar overall complication and 5-year survival rates as the open technique; however, the laparoscopic approach is associated with shorter operative times.


Assuntos
Adenoma de Células das Ilhotas Pancreáticas/cirurgia , Insulinoma/cirurgia , Laparoscopia/métodos , Neoplasias Pancreáticas/cirurgia , Adenoma de Células das Ilhotas Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Insulinoma/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos
18.
Am J Surg Pathol ; 31(11): 1677-82, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18059224

RESUMO

BACKGROUND: It is difficult to predict the biologic behavior of pancreatic endocrine tumors in absence of metastases or invasion into adjacent organs. The World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic activity, and MIB1 proliferation index as prognostic criteria. Our aim was to test retrospectively the predictive value of these 2004 WHO criteria and of CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term follow-up. DESIGN: The histology of 216 pancreatic endocrine tumor specimens was reviewed and the tumors were reclassified according to the 2004 WHO classification. The prognostic value of the WHO classification and the histopathologic criteria necrosis and nodular fibrosis was tested in 113 patients. A tissue microarray was constructed for immunohistochemical staining. The staining results were scored quantitatively for MIB1 and semiquantitatively for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested in 93 patients. RESULTS: The stratification of the patients into 4 risk groups according to the 2004 WHO classification was reliable with regard to both time span to relapse and tumor-specific death. In a multivariate analysis, the CK19 status was shown to be independent of the WHO criteria. By contrast, the prognostic significance of COX2, p27, and CD99 could not be confirmed. CONCLUSIONS: The 2004 WHO classification with 4 risk groups is very reliable for predicting both disease-free survival and the time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors.


Assuntos
Carcinoma de Células das Ilhotas Pancreáticas/diagnóstico , Insulinoma/diagnóstico , Queratina-19/análise , Neoplasias Pancreáticas/diagnóstico , Organização Mundial da Saúde , Antígeno 12E7 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Carcinoma de Células das Ilhotas Pancreáticas/química , Carcinoma de Células das Ilhotas Pancreáticas/mortalidade , Carcinoma de Células das Ilhotas Pancreáticas/patologia , Carcinoma de Células das Ilhotas Pancreáticas/cirurgia , Moléculas de Adesão Celular/análise , Ciclo-Oxigenase 2/análise , Intervalo Livre de Doença , Feminino , Fibrose , Seguimentos , Humanos , Imuno-Histoquímica , Insulinoma/química , Insulinoma/mortalidade , Insulinoma/patologia , Insulinoma/cirurgia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Necrose , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Análise Serial de Tecidos , Resultado do Tratamento
19.
Chin Med J (Engl) ; 120(17): 1487-90, 2007 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-17908455

RESUMO

BACKGROUND: Pancreatic endocrine tumors (PETs) are rare and their surgical treatment is often debated. The purpose of this retrospective study was to analyze the diagnosis and surgical strategy of functioning and non-functioning PETs. METHODS: From May 1980 to March 2006, 36 patients with pancreatic endocrine tumors at the Second Affiliated Hospital of Zhejiang University were retrospectively studied. RESULTS: Among the 36 patients, 29 (81%) had functioning tumors, and 7 (19%) had nonfunctioning tumors. Ninety-two percent of insulinomas were benign, whereas 4 (57%) of nonfunctioning PETs were malignant. The size of functioning tumors was (2.3 +/- 0.3) cm, that of nonfunctioning tumors was less than (5.1 +/- 0.5) cm. The combination CT and transabdominal ultrasonography resulted in a diagnostic sensitivity of 84%. Thirty-three primary lesions were precisely located in 32 patients (89%). Atypical tumor resection was performed for 73% of functioning tumors, while typical pancreatectomy was performed for 6 (85%) of nonfunctioning tumors. Moreover, 5 liver resections and 1 lymph node dissection were performed. During the follow-up, fifteen complications occurred in 12 (36%) patients after operation. The 5-year survival rate for patients with benign tumors was 92% compared to 50% for those with malignant tumors. Surgical cure was achieved in 95% of patients with benign insulinomas. CONCLUSIONS: Surgical strategy for PETs depends on the size and location of the tumor and the risk of malignancy. The optimal surgical procedure is key to prevent postoperative complication. Radical resection including initial and metastatic lesion may benefit patients with malignant PETs.


Assuntos
Neoplasias Pancreáticas/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Insulinoma/diagnóstico , Insulinoma/mortalidade , Insulinoma/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Tomografia por Emissão de Pósitrons
20.
Endocr Relat Cancer ; 14(3): 769-79, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17914106

RESUMO

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size > or =2 cm, Ki67 proliferative index > or =2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan-Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P< or =0.0004) and tumor-specific death (P< or =0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index > or =2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P< or =0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.


Assuntos
DNA de Neoplasias/análise , Dosagem de Genes , Insulinoma/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Instabilidade Cromossômica , Cromossomos Humanos , Feminino , Seguimentos , Gastrinoma/diagnóstico , Gastrinoma/genética , Gastrinoma/mortalidade , Gastrinoma/patologia , Humanos , Insulinoma/genética , Insulinoma/mortalidade , Insulinoma/patologia , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Sensibilidade e Especificidade , Análise de Sobrevida
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