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1.
Gut ; 71(5): 961-973, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33849943

RESUMO

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.


Assuntos
Deficiência Intelectual , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Talassemia alfa , Proteínas Correpressoras/genética , Genes Homeobox , Proteínas de Homeodomínio , Humanos , Deficiência Intelectual/genética , Chaperonas Moleculares/genética , Recidiva Local de Neoplasia/genética , Tumores Neuroendócrinos/genética , Proteínas Nucleares/genética , Neoplasias Pancreáticas/patologia , Telômero/genética , Telômero/patologia , Fatores de Transcrição/genética , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/genética
2.
Eur J Cancer Care (Engl) ; 30(6): e13504, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34462979

RESUMO

INTRODUCTION: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are often diagnosed in an advanced stage. As the optimal sequence of therapy remains largely unclear, all treatment-related outcomes, including health-related quality of life (HRQoL) prospects, should be assessed according to patients' preferences. METHODS: A targeted search was performed in PubMed and EMBASE to identify studies on treatment effect and HRQoL, measured using the EORTC QLQ-C30 tool, in patients with advanced, well-differentiated GEPNENs. Study quality was assessed, and meta-analyses were performed for global health status/QOL and tumour response. RESULTS: The search yielded 1,322 records, and 20 studies were included, examining somatostatin analogues (SSA), peptide receptor radionuclide therapies (PRRT), chemotherapy, SSA-based combination therapies, and targeted therapies. Global HRQoL was stable, and rates for disease stabilisation were moderate to high across all treatments. Meta-analyses for global health status/QOL after SSA treatment were not significant (mean difference: -0.3 [95% CI: -1.3 to 0.7]). The highest pooled overall tumour response rate was 33% (95% CI: 24-45%) for PRRT. The highest pooled clinical benefit rate was 94% (95% CI: 65-99%) for chemotherapy. CONCLUSION: All treatments appeared beneficial for disease stabilisation while maintaining stable global health status/QOL. High-quality HRQoL reporting was lacking. HRQoL should be a central outcome next to well-established outcomes.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , Qualidade de Vida , Neoplasias Gástricas/terapia
3.
Neuroendocrinology ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34343138

RESUMO

BACKGROUND: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. METHODS: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. RESULTS: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). CONCLUSIONS: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com.

4.
Cancers (Basel) ; 13(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067017

RESUMO

BACKGROUND: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting. METHODS: Patients undergoing surgical resection for pNETs between 1998-2018 were identified using a multi-institutional database. Using a minimum p-value approach, optimal cut-off value of recurrence-free survival (RFS) was determined based on the difference in post-recurrence survival (PRS). Risk factors for early recurrence were identified. RESULTS: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest p-value of 0.019). Median RFS was 11.0 months (95% 8.5-12.60) among ER patients (n = 49) versus 41.0 months (95% CI: 35.0-45.9) among non-ER patients (n = 77). Median PRS was worse among ER patients compared with non-ER patients (42.6 months vs. 81.5 months, p = 0.04). On multivariable analysis, tumor size (OR: 1.20, 95% CI: 1.05-1.37, p = 0.007) and positive lymph nodes (OR: 4.69, 95% CI: 1.41-15.58, p = 0.01) were independently associated with ER. CONCLUSION: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years after surgery.

5.
Neuroendocrinology ; 111(1-2): 129-138, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32040951

RESUMO

BACKGROUND: The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs. METHODS: Patients undergoing a distal pancreatectomy for pNET between 2002 and 2016 were identified in the US Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS). RESULTS: Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0-31.2] vs. 28.7 [IQR 25.7-33.6]; p = 0.005) and have undergone minimally invasive surgery (n = 56, 54.4% vs. n = 185, 35.7%; p < 0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1-8] vs. 9 [5-13]; p < 0.001), 5-year overall survival (OS) and recurrence-free survival (RFS) were comparable (OS: 96.8 vs. 92.0%, log-rank p = 0.21, RFS: 91.1 vs. 84.7%, log-rank p = 0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 mL [IQR 10-250] vs. 150 mL [IQR 100-400]; p = 0.001), lower incidence of serious complications (n = 13, 12.8% vs. n = 28, 27.5%; p = 0.014), and shorter length of stay (median: 5 days [IQR 4-7] vs. 6 days [IQR 5-13]; p = 0.049) compared with patients undergoing DPS. CONCLUSION: SPDP for pNET was associated with acceptable perioperative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.


Assuntos
Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Esplenectomia , Idoso , Feminino , Humanos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Tempo , Resultado do Tratamento , Estados Unidos
6.
HPB (Oxford) ; 23(3): 413-421, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32771338

RESUMO

BACKGROUND: Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP. METHODS: Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP. RESULTS: Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0-1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23-71) versus PD/DP (37 months, 95% CI: 33-47, p = 0.480). CONCLUSION: Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/cirurgia , Pancreatectomia/efeitos adversos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
7.
J Surg Oncol ; 122(7): 1393-1400, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32783272

RESUMO

BACKGROUND: We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm. METHODS: Patients with a pNET less than 2 cm who underwent EUS-FNA were identified using a multi-institutional international database. Tumor differentiation, and Ki-67 index, as determined through EUS-FNA were examined and concordance rates between EUS-FNA and the surgical pathology were assessed. RESULTS: Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS-FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P < .05). Among 314 patients with a pNET less than 2 cm who had an EUS-FNA performed at the time of diagnosis, 243 (73.2%) had the diagnosis confirmed by preoperative EUS-FNA. Tumor differentiation and Ki-67 could be determined by EUS-FNA in only 26.4% and 20.1% of patients, respectively. Concordance rate between EUS-FNA and pathology was high relative to tumor differentiation (92.7%) and Ki-67 (81.0%). CONCLUSION: Tumor differentiation and Ki-67 index could be determined by EUS-FNA in only 26.4% and 20.1% of cases, respectively. Further studies should focus on EUS techniques to optimize diagnostic yield and cell extraction in the preoperative setting.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Feminino , Humanos , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia
8.
J Surg Oncol ; 121(8): 1201-1208, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32185804

RESUMO

BACKGROUND AND OBJECTIVES: We sought to define the incidence and impact of Textbook Outcome (TO) on disease-free survival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET). METHODS: Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi-institutional database. TO was defined as no postoperative severe complications (Clavien-Dindo grade ≥ III), no 90-day mortality, no prolonged length-of-hospital stay (LOS) (ie, > 75th percentile), no 90-day readmission after discharge, and R0 resection. The 5-year DFS was calculated and the association with TO was examined. RESULTS: Among 821 patients with a PNET, median tumor size was 2.1 cm (IQR 1.4-14.6). Resection consisted of pancreatoduodenectomy (PD) (n = 231, 28.1%), distal pancreatectomy (DP) (n = 492, 59.9%), and enucleation (EN) (n = 98, 11.9%). Overall TO rate was 49.3% (n = 405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P < .001). After adjusting for all competing factors, achievement of a TO was independently associated with improved DFS (hazard ratio: 0.54, 95% CI, 0.35-0.81; P = .003). CONCLUSIONS: Only one in two patients undergoing resection of a PNET achieved a TO, which varied markedly based on procedure type. Achievement of a TO was associated with improved DFS.


Assuntos
Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Resultado do Tratamento
9.
Endocr Pathol ; 31(2): 108-118, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32103422

RESUMO

Insulin-producing pancreatic neuroendocrine tumors (PanNETs)/insulinomas are generally considered to be indolent tumors with an excellent prognosis after complete resection. However, some insulinomas have a poor prognosis due to relapses and metastatic disease. Recently, studies in non-functional PanNETs indicated that behavior can be stratified according to alpha- and beta-cell differentiation, as defined by expression of the transcription factors ARX and PDX1, respectively. It is unknown whether similar mechanisms play a role in insulinomas. Therefore, we determined ARX and PDX1 expression in a cohort of 35 sporadic primary insulinomas and two liver metastases of inoperable primary insulinomas. In addition, WHO grade and loss of ATRX or DAXX were determined by immunohistochemistry, and alternative lengthening of telomeres (ALT) and CDKN2A status by fluorescence in situ hybridization. These findings were correlated with tumor characteristics and clinical follow-up data. In total, five out of 37 insulinoma patients developed metastatic disease. Metastatic insulinomas were all larger than 3 cm, whereas the indolent insulinomas were smaller (p value < 0.05). All three primary insulinomas that metastasized showed ARX expression, 2/3 showed ALT, and 1/3 had a homozygous deletion of CDKN2A as opposed to absence of ARX expression, ALT, or CDKN2A deletions in the 32 non-metastatic cases. The two liver metastases also showed ARX expression and ALT (2/2). The presence of ARX expression, which is usually absent in beta-cells, and genetic alterations not seen in indolent insulinomas strongly suggest a distinct tumorigenic mechanism in malignant insulinomas, with similarities to non-functional PanNETs. These observations may inform future follow-up strategies after insulinoma surgery.


Assuntos
Proteínas de Homeodomínio/metabolismo , Insulinoma/patologia , Neoplasias Pancreáticas/patologia , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Insulinoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Homeostase do Telômero/fisiologia
10.
J Clin Med ; 8(3)2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30909512

RESUMO

Strong evidence comparing different treatment options for liver metastases (LM) arising from gastroenteropancreatic neuroendocrine tumours (GEP-NET) is lacking. The aim of this study was to determine which intervention for LMs from GEP-NETs shows the longest overall survival (OS). A systematic search was performed in MEDLINE, Embase and the Cochrane Library in February 2018. Studies reporting on patients with LMs of any grade of sporadic GEP-NET comparing two intervention groups were included for analysis. Meta-analyses were performed where possible. Eleven studies, with a total of 1108, patients were included; 662 patients had LM from pancreatic NETs (pNET), 164 patients from small-bowel NETs (SB-NET) and 282 patients of unknown origin. Improved 5-year OS was observed for surgery vs. chemotherapy (OR .05 95% CI [0.01, 0.21] p < 0.0001), for surgery vs. embolization (OR 0.18 95% CI [0.05, 0.61] p = 0.006) and for LM resection vs. no LM resection (OR 0.15 95% CI [0.05, 0.42] p = 0.0003). This is the largest meta-analysis performed comparing different interventions for LMs from GEP-NETs. Despite the high risk of bias and heterogeneity of data, surgical resection for all tumour grades results in the longest overall survival. Chemotherapy and embolization should be considered as an alternative in case surgery is not feasible.

11.
Ned Tijdschr Geneeskd ; 159: A8859, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-26173661

RESUMO

Malrotation occurs when there is a failure in the intestinal rotation leading to abnormal fixation to the abdominal wall and a mesentery with a short root. Volvulus is a life-threatening complication of malrotation. It can lead to irreversible intestinal necrosis and requires immediate attention. Early recognition of malrotation and surgical correction could prevent the onset of volvulus. We describe 3 cases of children with a malrotation. Case A involves a 2-year-old boy who suffered from repeated episodes of vomiting. Case B, a 1-month-old female, was taken to the general practitioner after acute onset of crying and flexing of the legs. Case C, a 5-year-old-boy with no medical history, had started vomiting hourly. In presenting these 3 cases, we highlight the dangers of untreated malrotation and make recommendations on how to manage a patient suspected of having this congenital abnormality.


Assuntos
Volvo Intestinal/complicações , Volvo Intestinal/diagnóstico , Intestino Delgado/anormalidades , Vômito/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Humanos , Lactente , Volvo Intestinal/congênito , Volvo Intestinal/cirurgia , Masculino , Vômito/diagnóstico
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