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1.
Medicine (Baltimore) ; 100(27): e26347, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232169

RESUMO

ABSTRACT: More attention has been placed on nonfunctioning pancreatic neuroendocrine tumors due to the increase in its incidence in recent years. Whether tumor resection at the primary site of metastatic NFpNET is effective remains controversial. Moreover, clinicians need a more precise prognostic tool to estimate the survival of these patients.Patients with metastatic NFpNET were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were identified using a multivariate Cox regression model and included in the nomogram. Coarsened exact matching analysis was used to balance the clinical variables between the non-surgical and surgical groups in our study.A total of 1464 patients with metastatic nonfunctioning pancreatic neuroendocrine tumors (NFpNETs) were included in our cohort. Multivariate analysis identified age, sex, tumor size, differentiated grade, lymph node metastases, resection of primary tumors, and marital status as independent predictors of metastatic NFpNET. The nomogram showed excellent accuracy in predicting 1-, 3-, and 5-year overall survival, with a C-index of 0.812. The calibration curve revealed good consistency between the predicted and actual survival.Coarsened exact matching analysis using SEER data indicated the survival advantages of resection of primary tumors. Our study is the first to build a nomogram model for patients with metastatic NFpNETs. This predictive tool can help clinicians identify high-risk patients and more accurately assess patient survival times.


Assuntos
Estadiamento de Neoplasias , Nomogramas , Neoplasias Pancreáticas/mortalidade , Programa de SEER , China/epidemiologia , Gerenciamento de Dados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/secundário , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências
2.
Medicine (Baltimore) ; 100(22): e26167, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087876

RESUMO

ABSTRACT: The embryonic development of the pancreas originates from dorsal and ventral anlagen, and the pancreatic cancer arising from dorsal or ventral pancreas may have different clinical pathology features. This study aims to explore whether there are differences in clinicopathological features and prognosis of pancreatic head carcinoma arising from dorsal or ventral pancreas.Between January 2014 and February 2018, 101 patients with resectable pancreatic head cancer who underwent pancreaticoduodenectomy in our institution were retrospectively reviewed. The patients were assigned into 2 groups according to tumor location on preoperative imaging materials (computed tomography/magnetic resonance imaging [CT/MRI]), and the clinicopathological features and prognosis were retrospectively analyzed in view of the embryonic development of the pancreas.Among these patients with pancreatic head cancer, 42 patients had tumors arising from dorsal pancreas (D group) and 59 patients had tumors arising from ventral pancreas (V group). The frequency of lymph node (LN) metastasis around the common hepatic artery (CHA) and hepatoduodenal ligament lymph nodes in the D group was higher than that in the V group (45.2% vs 10.2%, P = .001). And the rate of LN metastasis in the superior mesenteric artery (SMA) region in the V group is higher than that in the D group (32.2% vs 4.8%, P = .002). The D group was more likely to invade the common bile duct (78.6% vs 59.3%, P = .042) and duodenum (71.4% vs 44.1%, P = .006) than the V group. In addition, the survival outcome of V group was better than D group (median overall survival [OS], 15.37 months vs 10.53 months, P = .048, median DFS 9.73 months vs 5.93 months, P = .046).The clinicopathological features of pancreatic head carcinoma arising from dorsal or ventral pancreas are different, and the pancreatic head carcinoma arising from ventral pancreas has a better survival outcome.


Assuntos
Neoplasias Pancreáticas/patologia , Adulto , Idoso , Comorbidade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade
3.
Medicine (Baltimore) ; 100(25): e26342, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160399

RESUMO

OBJECTIVE: To evaluate the therapeutic efficacy and safety of S1 monotherapy or combination with nab-paclitaxel for the treatment of elderly patients with metastatic or locally advanced pancreatic adenocarcinoma. METHOD: PubMed, Embase, Cochrane Central Library, China Biology Medicine, and China National Knowledge Infrastructure databases were searched without time limits according to the inclusion criteria. RevMan (Version 5.3) software was used for data extraction and meta-analysis. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate therapeutic effects while side effects including leukopenia, thrombocytopenia, neurotoxicity, vomit, and alopecia were extracted for evaluation. There was no need for ethical review in this study because no ethical experiments were conducted and all data used were public data. All relevant data are within the paper and its Supporting Information files. RESULTS: Four retrospective studies comprising 308 elderly patients with metastatic or locally advanced pancreatic adenocarcinoma were included in the analysis. One hundred fifty-one patients underwent S1 monotherapy and 157 received S1 combined nab-paclitaxel. Meta-analysis indicated that compared with S1 monotherapy, S1 combined with nab-paclitaxel had higher ORR (OR 2.25, 95% CI: 1.42-3.55; P = .0005) and DCR (OR 2.94, 95% CI: 1.55-5.58; P = .0009). The adverse reaction of leukopenia was higher in the combined therapy group (OR 1.85, 95% CI: 1.09-3.13, P = .02), but no significant difference was found in thrombocytopenia, neurotoxicity, vomiting, and alopecia between the 2 groups (P > .05). CONCLUSION: Nab-paclitaxel plus S1 was more efficient in terms of ORR and DCR than S1 monotherapy in elderly pancreatic ductal adenocarcinoma patients while the side effect was controllable with a higher probability of leukopenia. Thus, combined nab-paclitaxel and S1 could be safely used in elderly patients.


Assuntos
Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Leucopenia/epidemiologia , Ácido Oxônico/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Combinação de Medicamentos , Humanos , Leucopenia/induzido quimicamente , Estadiamento de Neoplasias , Ácido Oxônico/efeitos adversos , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Tegafur/efeitos adversos
4.
Mol Cell ; 81(11): 2303-2316.e8, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-33991485

RESUMO

Glutaminase regulates glutaminolysis to promote cancer cell proliferation. However, the mechanism underlying glutaminase activity regulation is largely unknown. Here, we demonstrate that kidney-type glutaminase (GLS) is highly expressed in human pancreatic ductal adenocarcinoma (PDAC) specimens with correspondingly upregulated glutamine dependence for PDAC cell proliferation. Upon oxidative stress, the succinyl-coenzyme A (CoA) synthetase ADP-forming subunit ß (SUCLA2) phosphorylated by p38 mitogen-activated protein kinase (MAPK) at S79 dissociates from GLS, resulting in enhanced GLS K311 succinylation, oligomerization, and activity. Activated GLS increases glutaminolysis and the production of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione, thereby counteracting oxidative stress and promoting tumor cell survival and tumor growth in mice. In addition, the levels of SUCLA2 pS79 and GLS K311 succinylation, which were mutually correlated, were positively associated with advanced stages of PDAC and poor prognosis for patients. Our findings reveal critical regulation of GLS by SUCLA2-coupled GLS succinylation regulation and underscore the regulatory role of metabolites in glutaminolysis and PDAC development.


Assuntos
Carcinoma Ductal Pancreático/genética , Glutaminase/genética , Neoplasias Pancreáticas/genética , Succinato-CoA Ligases/genética , Animais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/enzimologia , Carcinoma Ductal Pancreático/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glutaminase/metabolismo , Glutamina/metabolismo , Glutationa/metabolismo , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , NADP/metabolismo , Estresse Oxidativo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/mortalidade , Fosforilação , Prognóstico , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Succinato-CoA Ligases/metabolismo , Ácido Succínico/metabolismo , Análise de Sobrevida , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Medicine (Baltimore) ; 100(20): e26052, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011119

RESUMO

ABSTRACT: Gemcitabine plus nab-paclitaxel (GnP) is widely used in clinical practice, despite a lack of prospective data to validate its efficacy in locally advanced pancreatic cancer (LAPC). We conducted a phase II study of GnP for LAPC to assess its efficacy and safety.We performed a single-arm, single-institution study with GnP in 24 patients with LAPC. The treatment protocol included successive administration of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2). The primary endpoint was the tumor overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs).The median PFS was 11.0 months, median OS was 21.2 months, ORR was 62.5%, and 37.5% of the patients had stable disease. Four (16.7%) of the patients were converted to surgical resection; 3 of these achieved R0 resection. Grade 3 to 4 AEs included hematological (neutropenia, 64%; thrombocytopenia, 12%), nonhematological (cholangitis, 16%), and sensory neuropathy (4%). These AEs were manageable and tolerable.The GnP treatment in patients with LAPC showed favorable tumor shrinkage, good toxicity profile, and enabled conversion to surgical resection in a subset of patients; therefore, GnP is an option for first-line chemotherapy in patients with LAPC.


Assuntos
Albuminas/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
6.
BMC Cancer ; 21(1): 385, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836674

RESUMO

BACKGROUND: Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: PDAC patients who underwent surgical resection between 01/2012-06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher's exact test. RESULTS: N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA- had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44-/ESA+ (35%), CD44-/ESA- (9%) (p = 0.0033). Conversely, lack of CD44 and ESA expression was associated with the highest rate of moderate and dense stroma (91% p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence was observed in patients with loose stroma. No statistically significant difference in RFS and OS was observed among subgroups (P = 0.089). CONCLUSIONS: These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Our results further suggest that tumor stroma may influence the recurrence pattern in PDAC patients.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Células Estromais/metabolismo , Biomarcadores , Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Masculino , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Prognóstico , Recidiva , Células Estromais/patologia , Resultado do Tratamento , Microambiente Tumoral
7.
J Surg Oncol ; 124(1): 79-87, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33836095

RESUMO

BACKGROUND: Clinical and pathologic staging determine treatment of pancreatic cancer. Clinical stage has been shown to underestimate final pathologic stage in pancreatic cancer, resulting in upstaging. METHODS: National Cancer Database was used to identify clinical stage I pancreatic adenocarcinoma. Univariate, multivariable logistic regression, and Cox proportional hazard ratio were used to determine differences between upstaged and stage concordant patients. RESULTS: Upstaging was seen in 80.2% of patients. Factors found to be significantly associated with upstaging included pancreatic head tumors (OR 2.56), high-grade histology (OR 1.74), elevated Ca 19-9 (OR 2.09), and clinical stage T2 (OR 1.99). Upstaging was associated with a 45% increased risk of mortality compared to stage concordant disease (HR 1.44, p < .001). CONCLUSION: A majority of clinical stage I pancreatic cancer is upstaged after resection. Factors including tumor location, grade, Ca 19-9, and tumor size can help identify those at high risk for upstaging.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/mortalidade , Idoso , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida
8.
Mol Cell ; 81(11): 2290-2302.e7, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-33831358

RESUMO

Cancer cells adapt their metabolism to support elevated energetic and anabolic demands of proliferation. Folate-dependent one-carbon metabolism is a critical metabolic process underpinning cellular proliferation supplying carbons for the synthesis of nucleotides incorporated into DNA and RNA. Recent research has focused on the nutrients that supply one-carbons to the folate cycle, particularly serine. Tryptophan is a theoretical source of one-carbon units through metabolism by IDO1, an enzyme intensively investigated in the context of tumor immune evasion. Using in vitro and in vivo pancreatic cancer models, we show that IDO1 expression is highly context dependent, influenced by attachment-independent growth and the canonical activator IFNγ. In IDO1-expressing cancer cells, tryptophan is a bona fide one-carbon donor for purine nucleotide synthesis in vitro and in vivo. Furthermore, we show that cancer cells release tryptophan-derived formate, which can be used by pancreatic stellate cells to support purine nucleotide synthesis.


Assuntos
Carcinoma Ductal Pancreático/genética , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Neoplasias Pancreáticas/genética , Células Estreladas do Pâncreas/metabolismo , Evasão Tumoral/efeitos dos fármacos , Aloenxertos , Animais , Antineoplásicos/farmacologia , Carbono/imunologia , Carbono/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Linhagem Celular Tumoral , Formiatos/imunologia , Formiatos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Interferon gama/genética , Interferon gama/imunologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Oximas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/imunologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/imunologia , Serina/imunologia , Serina/metabolismo , Serina/farmacologia , Transdução de Sinais , Sulfonamidas/farmacologia , Triptofano/imunologia , Triptofano/metabolismo , Triptofano/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia
9.
BMC Cancer ; 21(1): 423, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33863293

RESUMO

BACKGROUND: Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG. METHODS: RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers. CONCLUSION: Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).


Assuntos
Biomarcadores Tumorais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Fator de Maturação da Glia/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Imunomodulação/genética , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Especificidade de Órgãos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Prognóstico , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
10.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800786

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/diagnóstico , Glicômica/métodos , Glicoproteínas/análise , Espectrometria de Massas/métodos , Proteínas de Neoplasias/análise , Neoplasias Pancreáticas/diagnóstico , Proteômica/métodos , Líquidos Corporais/química , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Tomada de Decisão Clínica , Diagnóstico Diferencial , Detecção Precoce de Câncer , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/epidemiologia , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Pancreatite Crônica/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Medicina de Precisão , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco
11.
BMC Cancer ; 21(1): 342, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789590

RESUMO

BACKGROUND: The geriatric nutritional risk index (GNRI), originally developed as a nutritional assessment tool to evaluate mortality and morbidity in older hospitalized patients (i.e., those aged ≥65 years), is regarded as a prognostic factor in several cancers. Body composition is also an important consideration when predicting the prognosis of patients with cancer. This study aimed to investigate the relationship between the GNRI and psoas muscle volume (PMV) for survival outcomes in patients with pancreatic cancer. METHODS: This retrospective study evaluated the prognostic significance of the GNRI and PMV in 105 consecutive patients aged ≥65 years who underwent pancreatectomy for histologically confirmed pancreatic cancer. The patients were divided into high (GNRI > 98) and low GNRI groups (GNRI ≤98), and into high (PMV > 61.5 mm3/m3 for men and 44.1 mm3/m3 for women) and low PMV (PMV ≤ 61.5 mm3/m3 for men and 44.1 mm3/m3 for women) groups. RESULTS: Both the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were significantly greater among patients in the high GNRI group than among patients in the low GNRI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high PMV group than among patients in the low PMV group. Patients were stratified into three groups: those with both high GNRI and high PMV; those with either high GNRI or high PMV (but not both); and those with both low GNRI and low PMV. Patients with both low GNRI and low PMV had a worse 5-year OS rate, compared with patients in other groups (P <  0.001). The C-index of the combination of the GNRI and PMV for predicting 5-year OS was greater than the C-indices of either the GNRI or PMV alone. Multivariate analysis revealed that the combination of the GNRI and PMV was an independent prognostic factor in patients aged ≥65 years with pancreatic cancer (P = 0.003). CONCLUSIONS: The combination of the GNRI and PMV might be useful to predict prognosis in patients aged ≥65 years with pancreatic cancer.


Assuntos
Avaliação Geriátrica/métodos , Avaliação Nutricional , Neoplasias Pancreáticas/fisiopatologia , Músculos Psoas/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/mortalidade , Prognóstico , Fatores de Risco , Taxa de Sobrevida
12.
BMC Cancer ; 21(1): 335, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789615

RESUMO

BACKGROUND: Gene mutations play critical roles in tumorigenesis and cancer development. Our study aimed to screen survival-related mutations and explore a novel gene signature to predict the overall survival in pancreatic cancer. METHODS: Somatic mutation data from three cohorts were used to identify the common survival-related gene mutation with Kaplan-Meier curves. RNA-sequencing data were used to explore the signature for survival prediction. First, Weighted Gene Co-expression Network Analysis was conducted to identify candidate genes. Then, the ICGC-PACA-CA cohort was applied as the training set and the TCGA-PAAD cohort was used as the external validation set. A TP53-associated signature calculating the risk score of every patient was developed with univariate Cox, least absolute shrinkage and selection operator, and stepwise regression analysis. Kaplan-Meier and receiver operating characteristic curves were plotted to verify the accuracy. The independence of the signature was confirmed by the multivariate Cox regression analysis. Finally, a prognostic nomogram including 359 patients was constructed based on the combined expression data and the risk scores. RESULTS: TP53 mutation was screened to be the robust and survival-related mutation type, and was associated with immune cell infiltration. Two thousand, four hundred fifty-five genes included in the six modules generated in the WGCNA were screened as candidate survival related TP53-associated genes. A seven-gene signature was constructed: Risk score = (0.1254 × ERRFI1) - (0.1365 × IL6R) - (0.4400 × PPP1R10) - (0.3397 × PTOV1-AS2) + (0.1544 × SCEL) - (0.4412 × SSX2IP) - (0.2231 × TXNL4A). Area Under Curves of 1-, 3-, and 5-year ROC curves were 0.731, 0.808, and 0.873 in the training set and 0.703, 0.677, and 0.737 in the validation set. A prognostic nomogram including 359 patients was constructed and well-calibrated, with the Area Under Curves of 1-, 3-, and 5-year ROC curves as 0.713, 0.753, and 0.823. CONCLUSIONS: The TP53-associated signature exhibited good prognostic efficacy in predicting the overall survival of PC patients.


Assuntos
Nomogramas , Neoplasias Pancreáticas/mortalidade , Proteína Supressora de Tumor p53/metabolismo , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Mutação , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Análise de Sequência de RNA , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética
13.
World J Surg Oncol ; 19(1): 122, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865422

RESUMO

BACKGROUND AND OBJECTIVES: Long non-coding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was previously shown to exert an oncogenic role in several human cancers. However, whether PART1 is associated with the malignant progression of pancreatic cancer remains unclear. In the current study, we aimed to identify the role and potential mechanism of PART1 in pancreatic cancer. METHODS: qRT-PCR was applied to detect PART1 expression in 45 cases of pancreatic cancer patients. The chi-square test was performed to assess the association between PART1 expression and clinicopathologic features, and Kaplan-Meier method was applied to evaluate overall survival. In vitro CCK-8, transwell invasion, and flow cytometry assays were applied to detect the effects of PART1 on cell proliferation, invasion, and apoptosis, respectively. Luciferase reporter and RNA immunoprecipitation assays were used to identify the regulatory mechanism between PART1 and miR-122. RESULTS: PART1 expression was upregulated in pancreatic cancer tissues and cell lines. High PART1 expression was closely correlated with tumor size, T classification, clinical stage, and vascular invasion, and predicted a poor overall survival. PART1 knockdown significantly suppressed cell proliferation and invasion abilities of pancreatic cancer but promoted cell apoptosis. PART1 was found to serve as a molecular sponge of miR-122, and miR-122 inhibition partially reversed the inhibitory phenotypes of PART1 knockdown on pancreatic cancer cells. CONCLUSIONS: PART1 promotes the malignant progression of pancreatic cancer by sponging miR-122. The PART1/miR-122 axis might be a promising target for anticancer therapy in patients with pancreatic cancer.


Assuntos
Proliferação de Células/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , Androgênios , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico
14.
Anticancer Res ; 41(4): 2071-2078, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813416

RESUMO

BACKGROUND/AIM: FOLFOX (5-Fluorouracile and oxaliplatin) exhibits promising activity in advanced well-differentiated neuroendocrine tumors (NETs). This retrospective study aimed to analyze the outcome of metastatic enteropancreatic NETs patients treated with FOLFOX. PATIENTS AND METHODS: We retrospectively identified patients treated with FOLFOX for NETs of enteropancreatic or unknown origin among those referred to our Regional Multidisciplinary Tumor Board. RESULTS: Among 48 patients, most often pancreatic NETs (n=33, 68.8%), the median Ki67 index was 10%. The median number cycle of FOLFOX was 6 and median follow-up was 34.8 months. Disease control rate (DCR) was 83.3%. Median PFS and OS were 12.6 and 29.4 months respectively. Median chemotherapy break was 14.1 months. No significant difference was observed between PFS and the following criteria: Ki67 index, primary tumor site, alkaline phosphatase levels, primary tumor surgery and 18F-FDG PET positivity. CONCLUSION: FOLFOX exhibits a high DCR and a short duration of treatment with a relative long chemotherapy break in patients with metastatic enteropancreatic NETs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoruracila/uso terapêutico , França/epidemiologia , Humanos , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Compostos Organoplatínicos/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
15.
Medicine (Baltimore) ; 100(14): e24969, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832071

RESUMO

ABSTRACT: Pancreatic cancer has a very high mortality with a 5-year survival of <5%. The purpose of this study was to classify specific molecular subtypes associated with prognosis of pancreatic cancer using The Cancer Genome Atlas (TCGA) multiplatform genomic data.Multiplatform genomic data (N = 178), including gene expression, copy number alteration, and somatic mutation data, were obtained from cancer browser (https://genome-cancer.ucsc.edu, cohort: TCGA Pancreatic Cancer). Clinical data including survival results were analyzed. We also used validation cohort (GSE50827) to confirm the robustness of these molecular subtypes in pancreatic cancer.When we performed unsupervised clustering using TCGA gene expression data, we found three distinct molecular subtypes associated with different survival results. Copy number alteration and somatic mutation data showed different genomic patterns for these three subtypes. Ingenuity pathway analysis revealed that each subtype showed differentially altered pathways. Using each subtype-specific genes (200 were selected), we could predict molecular subtype in another cohort, confirming the robustness of these molecular subtypes of pancreatic cancer. Cox regression analysis revealed that molecular subtype is the only significant prognostic factor for pancreatic cancer (P = .042, 95% confidence interval 0.523-0.98).Genomic analysis of pancreatic cancer revealed 3 distinct molecular subtypes associated with different survival results. Using these subtype-specific genes and prediction model, we could predict molecular subtype associated with prognosis of pancreatic cancer.


Assuntos
Genômica/métodos , Neoplasias Pancreáticas/genética , Idoso , Biomarcadores Tumorais/genética , Variações do Número de Cópias de DNA , Bases de Dados Factuais , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Transdução de Sinais
16.
BMC Cancer ; 21(1): 382, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836678

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). METHODS: We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. RESULTS: Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. CONCLUSIONS: Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Laparoscopia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Idoso , Carcinoma Ductal Pancreático/diagnóstico , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Neoplasias Pancreáticas/diagnóstico , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Resultado do Tratamento
17.
World J Surg Oncol ; 19(1): 126, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33866970

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Radical surgery is the best option for cure and, nowadays, it is performed by many surgeons also in cases of vascular infiltration. Whether this aggressive approach to a locally advanced PDAC produces a survival benefit is under debate. Most data in the literature come from retrospective comparative studies; therefore, it is still unclear if such an extensive surgery for an advanced cancer is justified. METHODS: A retrospective review of patients with PDAC treated at our institution over a 12-year period was performed. Data concerning patients' characteristics, operative details, postoperative course, and long-term survival were retrieved from prospective databases and analysed. Factors associated with poor survival were assessed via Cox regression analysis. RESULTS: A total of 173 patients with PDAC were included in the analysis, 41 subjects underwent pancreatectomy with vascular resection for locally advanced disease, and in 132 patients, only a pancreatic resection was undertaken. Demographics, major comorbidities, and tumour characteristics were similar between the two groups. Length of surgery (P=0.0006), intraoperative blood transfusions (P<0.0001), and overall complications (P<0.0001) were significantly higher in the vascular resection group. Length of hospital stay (P=0.684) and 90-day mortality (P=0.575) were comparable between groups. Overall median survival (P= 0.717) and survival rates at 1, 3, and 5 years (P=0.964, P=0.500, and P=0.445, respectively) did not differ significantly between groups. Age ≥70 years and postoperative complications were independent predictors of lower survival. CONCLUSIONS: Our study confirms that pancreatectomy with vascular resection for a locally advanced PDAC is a complex operation associated with a significant longer operating time that may increase morbidity; however, in selected patients, R0 margins can be obtained with an acceptable long-term survival rate. Older patients are less likely to benefit from surgery.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Sobreviventes
18.
Pediatr Surg Int ; 37(8): 1041-1047, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33742268

RESUMO

PURPOSE: Pancreas tumors are extremely rare in pediatric and adolescent patients. Surgical resection is the mainstay of treatment; however, the data are limited with respect to morbidity and mortality. We aimed to evaluate short- and long-term outcomes of pediatric and adolescent patients who underwent surgical resection of pancreatic tumors. METHODS: Patients [Formula: see text] 18-year-olds who underwent resection of pancreas tumor at the National Institute of Neoplastic Diseases INEN during 2000-2020 were included. RESULTS: Thirty-four patients were diagnosed; 28 patients were female and 6 were male. The median age was 13.4-years-old. Histological diagnosis was solid pseudopapillary neoplasm (SPN) (n = 29, 85.3%), pancreatoblastoma (n = 3), neuroendocrine carcinoma (n = 1), and insulinoma (n = 1). No patient experienced postoperative mortality and 15 (44.1%) patients developed postoperative complications including pancreatic fistula as the most frequent. Under a median follow-up period of 33.8 (0.5-138) months, four (11.8%) patients died. Of the 29 patients with SPN, the 3- and-5-year OS rates were 100% and 83.1%, respectively. CONCLUSIONS: SPN was the most frequent cause of surgical treatment for pediatric and adolescent patients in the high-volume cancer center in Peru and was associated with favorable survival. Pancreaticoduodenectomy was safely performed in this patient group with acceptable morbidity and zero mortality.


Assuntos
Carcinoma Papilar/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adolescente , Carcinoma Papilar/mortalidade , Criança , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/efeitos adversos , Peru , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
19.
JAMA Netw Open ; 4(3): e212274, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33755166

RESUMO

Importance: Peptide receptor radionuclide therapy (PRRT) is approved in the US for treatment of gastroenteropancreatic neuroendocrine tumors (NETs), but data on PRRT outcomes within US populations remain scarce. Objective: To analyze the first 2 years of PRRT implementation at a US-based NET referral center. Design, Setting, and Participants: This cohort study was conducted using medical records of patients with metastatic NET receiving PRRT from 2018 through 2020 in a NET program at a tertiary referral center. Included patients were those at the center with metastatic NETs who received at least 1 dose of PRRT over the study period. Laboratory toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Tumor response was determined using Response Evaluation Criteria in Solid Tumors 1.1. Survival analysis was conducted to identify factors associated with progression-free survival (PFS) and overall survival. Data were analyzed from August 2018 through August 2020. Exposures: Receiving 4 cycles of lutetium-177-dotatate infusion, separated by 8-week intervals targeted to 7.4 GBq (200 mCi) per dose. Main Outcomes and Measures: Data were compared from before and after PRRT to determine hematologic, liver, and kidney toxic effects and to assess tumor progression and patient survival. Results: Among 78 patients receiving at least 1 dose of PRRT, median (interquartile range) age at PRRT initiation was 59.8 (53.5-69.2) years and 39 (50.0%) were men. The most common primary NET sites included small bowel, occurring in 34 patients (43.6%), and pancreas, occurring in 22 patients (28.2%). World Health Organization grade 1 or 2 tumors occurred in 62 patients (79.5%). Among all patients, 56 patients underwent pretreatment with tumor resection (71.8%), 49 patients received nonsomatostatin analogue systemic therapy (62.8%), and 49 patients received liver-directed therapy (62.8%). At least 1 grade 2 or greater toxic effect was found in 47 patients (60.3%). Median PFS was 21.6 months for the study group, was not reached by 22 months for patients with small bowel primary tumors, and was 13.3 months for patients with pancreatic primary tumors. Having a small bowel primary tumor was associated with a lower rate of progression compared with having a pancreatic primary tumor (hazard ratio, 0.19; 95% CI, 0.07-0.55; P = .01). Median overall survival was not reached. Conclusions and Relevance: This cohort study of patients with metastatic NETs found that PRRT was associated with laboratory-measured toxic effects during treatment for most patients and an overall median PFS of 21.6 months. Patients with small bowel NETs had longer PFS after PRRT compared with patients with pancreatic NETs.


Assuntos
Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Radioisótopos de Gálio , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/mortalidade , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/mortalidade , Octreotida/uso terapêutico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
J Surg Oncol ; 123(8): 1757-1763, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33684252

RESUMO

BACKGROUND: This study evaluates the achievability of CT volumetry of pancreatic cancer and its correlation with pTNM stage and survival. METHODS: Tumor volume was measured from contrast enhanced CT images of 58 patients who undergo curative resection for pancreatic cancer using the Segment Editor module implemented in 3D-Slicer-a free open source software platform. Receiver operating characteristic (ROC) analysis was used to evaluate correlation between Tvol and pTNM staging. RESULTS: The preoperative images of 58 pancreatic adenocarcinoma patients were included. The mean Tvol of pancreatic cancer is an increasing trend with T stage (The mean T1vol = 1.75 cm3 , the mean T2vol = 11.43 cm3 , the mean T3vol = 14.98 cm3 , the mean T4vol = 19.6 cm3 ). There were statistical differences between volumes (p = .000). On ROC analysis, the area under the ROC curve (Az) of Tvol to differentiate T1 stage from ≥T2 stage was 0.966 (p = .000). At a cut-off value of 3.050 cm3 , sensitivity of 92.3%, and specificity of 83.3% were achieved. Az value of Tvol to differentiate ≤T2 from ≥T3 stage was 0.750 (p = .010). At a cut-off value of 10.250 cm3 , sensitivity of 72.7% and specificity of 66% were achieved. In addition Az value of Tvol to differentiate ≤T3 from ≥T4 stage was 0.652 and was not significant (p = .380). At a cut-off value of 11.2 cm3 , sensitivity of 66.7% and specificity of 63.6% were achieved. CONCLUSION: CT volumetry in pancreatic cancer is feasible with excellent reproducibility. It is one of the prognostic factors affecting survival in operated patients with pancreatic cancer.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Tomografia Computadorizada de Feixe Cônico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida
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