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1.
Medicine (Baltimore) ; 98(44): e17773, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689842

RESUMO

OBJECTIVE: To evaluate the prognostic value of pancreatic neuroendocrine tumors (pNETs) with different metastatic patterns. METHODS: Data of pNETs cases were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. They were classified according to the different metastatic patterns. We utilized chi-square test to compare the clinical and metastasis characteristics among different groups. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. Adjusted HRs with 95% CIs was calculated using Cox regression model to estimate prognostic factors. P < .05 was considered statistically significant. RESULTS: Among the 3909 patients, liver is the most metastatic organ, and isolated brain metastasis is the least common. At the same time, many patients have had multiple metastases. We studied the overall survival (OS) and cancer-specific survival (CCS) of the groups. OS: Non-organ metastasis: 5-year OS = 77.1%; Bone metastasis: median survival time (MST) = 56 m, 5-year OS = 42.7%; Liver metastasis: MST = 24 m, 5-year OS = 25.5%; Lung metastasis: MST = 14 m, 5-year OS = 33.7%; multiple metastases: MST = 7m, 5-year OS = 12.0%. CCS: Non-organ metastasis: 5-year OS = 84.2%; Bone metastasis: 5-year OS = 52.5%; Liver metastasis: MST = 27 m, 5-year OS = 28.6%; Lung metastasis: MST = 49 m, 5-year OS = 40.1%; multiple metastases: MST = 8 m, 5-year OS = 14.5%. In addition, the results showed that there were all statistical significances between the surgery and the no surgery group (all, P < .001). Multivariate analysis revealed that brain metastasis, multiple metastases, age over 60 years, unmarried, grade III/IV, regional/distant and no surgery were independently associated with decreased OS and CCS. CONCLUSIONS: pNETs patients without organ metastasis had the best survival outcomes, while multiple had the worst outcomes. There were no significant differences in bone metastasis, liver metastasis and lung metastasis. Surgery was still an option for patients with metastasis.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Idoso , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/patologia , Prognóstico , Programa de SEER , Taxa de Sobrevida
2.
J Cancer Res Clin Oncol ; 145(11): 2855-2862, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506738

RESUMO

PURPOSE: The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. METHODS: We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. RESULTS: For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. CONCLUSIONS: Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.


Assuntos
Abdome/irrigação sanguínea , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infusões Intra-Arteriais/mortalidade , Neoplasias Pancreáticas/mortalidade , Abdome/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
3.
J Cancer Res Clin Oncol ; 145(10): 2481-2493, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451931

RESUMO

PURPOSE: Pancreatic adenocarcinoma (PAC) represents one of the most fatal types of cancer with an exceptionally poor prognosis, underscoring the need for improved diagnostic and treatment approaches. An over-expression of somatostatin receptors (SST) as well as of the chemokine receptor CXCR4 has been shown for many tumour entities. Respective expression data for PAC, however, are scarce and contradictory. METHODS: Overall, 137 tumour samples from 70 patients, 26 of whom were diagnosed with PAC and 44 with pancreatic neuroendocrine tumour (PanNET), were compared in terms of SST and CXCR4 expression by immunohistochemical analysis using well-characterized rabbit monoclonal antibodies. RESULTS: Only SST1 and CXCR4 expression was detected in PAC tumours, with SST1 present in 42.3% and CXCR4 in 7.7% of cases. However, the overall staining intensity was very weak. In contrast to the tumour cells, in many PAC cases, tumour capillaries exhibited strong SST3, SST5, or CXCR4 expression. In PanNETs, SST2 was the most-prominently expressed receptor, observed in 75.0% of the tumours at medium-strong intensity. SST5, SST1, and CXCR4 expression was detected in 20.5%, 15.9%, and 11.4% of PanNET cases, respectively, but the staining intensity was only weak. SST2 positivity in PanNET, but not in PAC, was associated with favourable patient outcomes. CONCLUSIONS: SST or CXCR4 expression in PAC is clearly of no therapeutic relevance. However, indirect targeting of these tumours via SST3, SST5, or CXCR4 on tumour microvessels may represent a promising additional therapeutic strategy.


Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Intestinais/genética , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Receptores CXCR4/genética , Somatostatina/genética , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Receptores CXCR4/metabolismo , Somatostatina/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
4.
Medicine (Baltimore) ; 98(32): e16656, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393364

RESUMO

BACKGROUND: Kanglaite (KLT) injection, a kind of Chinese medicine, is considered a promising complementary therapeutic option for malignant cancer treatment. This study aimed to systematically investigate the efficacy and safety of the combination of KLT injection and radiochemotherapy for the treatment of advanced pancreatic cancer (PC). METHODS: Studies were identified by searching Cochrane Library, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biological Medicine Database (CBM), Wanfang database and Chinese Scientific Journal Database (VIP) before October 2018. The primary reported outcomes including efficacy, quality of life (QoL), and adverse events were systematically evaluated. RESULTS: Data from 16 trials with 960 patients with advanced PC were included. Compared with radiochemotherapy alone, the combination of KLT injection and radiochemotherapy significantly improved the 1-year overall survival (OS, odds ratio [OR] = 2.58 95% CI: 1.12-5.93 P = .03), overall response (ORR, OR = 2.16 95% CI: 1.58-2.94 P <.00001) and disease control rates (DCR, OR = 2.50 95% CI: 1.84-3.38 P <.00001). The QoL of patients, who received a combination of radiochemotherapy and KLT injection, also improved compared with radiochemotherapy treatment alone as indicated by the increased quality of life improved rate (QIR, OR = 3.68 95%CI: 2.36-5.75 P <.00001), pain relief rate (PRR, OR = 3.70 95% CI: 2.23-6.14 P <.00001) and weight gain rate (WGR, OR = 3.69 95% CI: 2.22-6.13 P <.00001). Adverse events related to radiochemotherapy including gastrointestinal side effects, nephrotoxicity, leukopenia, thrombocytopenia, and myelosuppression were alleviated (P <.05) when KLT was injected to patients with PC. CONCLUSIONS: Evidence from the Meta-analysis suggested that the combinational treatment of radiochemotherapy and KLT injection is more effective in advanced PC treatment than radiochemotherapy alone. Additionally, the combination therapy improved QoL of the patients. KLT injection can alleviate the adverse effects associated with the radiochemotherapy.


Assuntos
Quimiorradioterapia/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Humanos , Injeções , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
JAMA ; 322(5): 445-454, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31386140

RESUMO

Importance: Pancreatic adenocarcinoma is the third most common cause of cancer death among men and women in the United States. Objective: To systematically review benefits and harms of screening for pancreatic adenocarcinoma to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials, from January 2002 through April 27, 2018; surveillance through March 22, 2019. Study Selection: Studies of adults with or without risk factors for pancreatic adenocarcinoma (eg, family history of pancreatic cancer, personal history of new-onset diabetes) undergoing imaging-based screening; studies of treatment for adults with screen-detected or asymptomatic pancreatic adenocarcinoma. Included study designs were randomized clinical trials, nonrandomized controlled intervention studies, diagnostic accuracy studies with a reference standard, cohort studies, and case-control studies (for evaluation of harms only). Studies consisting entirely of populations with known genetic syndromes associated with pancreatic cancer were excluded. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and rated included studies for quality; data were quantitatively analyzed to calculate a pooled diagnostic yield and narratively synthesized. Main Outcomes and Measures: Mortality, morbidity, or quality of life; diagnostic accuracy of screening tests; any harm of screening or treatment. Results: Thirteen fair-quality prospective cohort screening studies (N = 1317) conducted predominantly in populations at high familial risk for pancreatic adenocarcinoma were included. No studies reported on the effect of screening on morbidity or mortality or on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma. Although no studies evaluated the diagnostic accuracy of screening tests, all 13 studies reported the diagnostic yield. Yields ranged from 0 to 75 cases per 1000 persons in studies using endoscopic ultrasound, magnetic resonance imaging, and/or computed tomography-based screening. In total, 18 cases of pancreatic adenocarcinoma were detected in 1156 adults at increased familial risk and 0 cases were detected in 161 average-risk adults. In 8 studies (n = 675) assessing procedural harms of screening, no serious harms from initial screening were reported. Two studies (n = 271) found no evidence of psychosocial harms related to screening. Evidence of surgical harms was limited. Conclusions and Relevance: Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the effect of screening on morbidity and mortality in groups at high familial risk has not been studied, and no data are available in average-risk populations. There is limited evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Detecção Precoce de Câncer , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Detecção Precoce de Câncer/efeitos adversos , Feminino , Humanos , Masculino , Programas de Rastreamento/efeitos adversos , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias , Qualidade de Vida , Fatores de Risco , Sensibilidade e Especificidade
6.
J Surg Oncol ; 120(6): 966-975, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401809

RESUMO

BACKGROUND AND OBJECTIVES: Gastrinomas are the most prevalent functioning neuroendocrine tumors (NET) in multiple endocrine neoplasia type 1 (MEN1). Guidelines suggest medical therapy in most patients, but surgery may be considered in a subgroup. Currently, factors to guide management are necessary. This population-based cohort study assessed prognostic factors of survival in patients with MEN1-related gastrinomas. METHODS: Patients with MEN1 having gastrinomas were identified in the Dutch MEN1 database from 1990 to 2014 based on fasting serum gastrin (FSG) levels and/or pathology. Predictors of overall survival were assessed using Cox regression. RESULTS: Sixty-three patients with gastrinoma (16% of the MEN1 population) were identified. Five- and 10-year overall survival rates were 83% and 65%, respectively. Prognostic factors associated with overall survival were initial FSG levels ≥20x upper limit of normal (ULN) (hazard ratio [HR], 6.2 [95% confidence interval, 1.7-23.0]), pancreatic NET ≥2 cm (HR 4.5; [1.5-13.1]), synchronous liver metastases (HR 8.9; [2.1-36.7]), gastroduodenoscopy suspicious for gastric NETs (HR 12.7; [1.4-115.6]), and multiple concurrent NETs (HR 5.9; [1.2-27.7]). CONCLUSION: Life expectancy of patients with MEN1 gastrinoma is reduced. FSG levels and pancreatic NETs ≥2 cm are prognostic factors. FSG levels might guide surveillance intensity, step-up to additional diagnostics, or provide arguments in selecting patients who might benefit from surgery.


Assuntos
Gastrinoma/mortalidade , Neoplasias Intestinais/mortalidade , Neoplasias Hepáticas/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Gástricas/mortalidade , Estudos de Coortes , Feminino , Seguimentos , Gastrinoma/metabolismo , Gastrinoma/patologia , Gastrinoma/cirurgia , Humanos , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Países Baixos , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
7.
J Surg Oncol ; 120(6): 976-984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31452208

RESUMO

BACKGROUND AND OBJECTIVES: Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC. METHODS: The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis. RESULTS: In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001). CONCLUSIONS: The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Análise de Intenção de Tratamento , Terapia Neoadjuvante/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Pontuação de Propensão , Taxa de Sobrevida , Adulto Jovem
9.
J Surg Oncol ; 120(4): 632-638, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31339198

RESUMO

BACKGROUND: Preoperative systemic inflammatory response plays a crucial role in tumorigenesis, progression, and prognosis; and neutrophil, monocyte, and lymphocyte counts serve as important biomarkers. An altered monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and breast cancer. The aim of this study was to investigate the prognostic significance of MLR, NLR in patients with resectable PNETs. METHODS: Patients undergoing surgery for PNETs between 2000 and 2016 were identified using a large, multi-center database. NLR and MLR were calculated and Contal and O'Quigley analysis was used to determine the optimal cutoff value. RESULTS: A total of 620 patients were included in the analytic cohort. The prognostic implications of blood count parameters were evaluated in both univariate and multivariate analysis. The univariate analysis revealed that low MLR and NLR is associated with significantly improved overall survival (OS; P < .01) and recurrence-free survival (RFS; P < .01). On multivariate analysis, in addition to tumor size and grade, NLR was an independent predictor of improved OS and RFS. CONCLUSION: In addition to established tumor-specific factors, preoperative NLR levels can serve as a valuable biomarker that can be used as a predictor of OS and RFS after resection of PNETs.


Assuntos
Linfócitos/patologia , Monócitos/patologia , Recidiva Local de Neoplasia/mortalidade , Tumores Neuroendócrinos/mortalidade , Neutrófilos/patologia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
BMC Bioinformatics ; 20(1): 393, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311505

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression at a post-transcriptional level and are emerging as potentially important biomarkers for various disease states, including pancreatic cancer. In silico-based functional analysis of miRNAs usually consists of miRNA target prediction and functional enrichment analysis of miRNA targets. Since miRNA target prediction methods generate a large number of false positive target genes, further validation to narrow down interesting candidate miRNA targets is needed. One commonly used method correlates miRNA and mRNA expression to assess the regulatory effect of a particular miRNA. The aim of this study was to build a bioinformatics pipeline in R for miRNA functional analysis including correlation analyses between miRNA expression levels and its targets on mRNA and protein expression levels available from the cancer genome atlas (TCGA) and the cancer proteome atlas (TCPA). TCGA-derived expression data of specific mature miRNA isoforms from pancreatic cancer tissue was used. RESULTS: Fifteen circulating miRNAs with significantly altered expression levels detected in pancreatic cancer patients were queried separately in the pipeline. The pipeline generated predicted miRNA target genes, enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Predicted miRNA targets were evaluated by correlation analyses between each miRNA and its predicted targets. MiRNA functional analysis in combination with Kaplan-Meier survival analysis suggest that hsa-miR-885-5p could act as a tumor suppressor and should be validated as a potential prognostic biomarker in pancreatic cancer. CONCLUSIONS: Our miRNA functional analysis (miRFA) pipeline can serve as a valuable tool in biomarker discovery involving mature miRNAs associated with pancreatic cancer and could be developed to cover additional cancer types. Results for all mature miRNAs in TCGA pancreatic adenocarcinoma dataset can be studied and downloaded through a shiny web application at https://emmbor.shinyapps.io/mirfa/ .


Assuntos
MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Proteínas/genética , Interface Usuário-Computador , Automação , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Mapas de Interação de Proteínas , Proteínas/metabolismo , RNA Mensageiro/metabolismo
11.
BMC Surg ; 19(1): 83, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286902

RESUMO

BACKGROUND: Chronic pancreatitis (CP) is considered to be a risk factor for pancreatic cancer. A retrospective study was conducted to evaluate the incidence of pancreatic cancer after surgery for CP and to determine the risk factors. METHODS: The patients who underwent surgery for histologically documented CP between January 2009 and December 2017 were reviewed. The baseline characteristics, operative data, postoperative complications, and follow-up information were analysed. We calculated standardized incidence ratio on the base of the incidence of pancreatic cancer in the standard population in China. The risk factor for pancreatic cancer was assessed using Cox regression. RESULTS: Among 650 patients, pancreatic cancer was detected in 12 patients (1.8%) after a median follow-up of 4.4 years. The standardized incidence ratio of pancreatic cancer was 68.12 (95% CI, 35.20-118.99). Two independent risk factors for the development of pancreatic cancer in patients with chronic pancreatitis after surgery were identified: time interval to surgery [HR 1.005, 95% CI (1.002-1.008), P = 0.002] and de novo endocrine insufficiency [HR 10.672, 95% CI (2.567-44.372), P = 0.001]. CONCLUSIONS: Patients who require surgery for CP are at a very high risk of developing pancreatic cancer. Early surgical intervention plays a protective role in the development of pancreatic cancer from CP. A high index of suspicion for pancreatic cancer should be maintained in CP patients with de novo postoperative diabetes after surgery.


Assuntos
Neoplasias Pancreáticas/epidemiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/cirurgia , Adulto , China/epidemiologia , Insuficiência Pancreática Exócrina/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/prevenção & controle , Pancreaticojejunostomia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento
12.
Ann R Coll Surg Engl ; 101(7): 453-462, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31304767

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma remains a disease with a poor prognosis despite advances in surgery and systemic therapies. Neoadjuvant therapy strategies are a promising alternative to adjuvant chemotherapy. However, their role remains controversial. This meta-analysis aims to clarify the benefits of neoadjuvant therapy in resectable pancreatic ductal adenocarcinoma. METHODS: Eligible studies were identified from MEDLINE, Embase, Web of Science and the Cochrane Library. Studies comparing neoadjuvant therapy with a surgery first approach (with or without adjuvant therapy) in resectable pancreatic ductal adenocarcinoma were included. The primary outcome assessed was overall survival. A random-effects meta-analysis was performed, together with pooling of unadjusted Kaplan-Meier curve data. RESULTS: A total of 533 studies were identified that analysed the effect of neoadjuvant therapy in pancreatic ductal adenocarcinoma. Twenty-seven studies were included in the final data synthesis. Meta-analysis suggested beneficial effects of neoadjuvant therapy with prolonged survival compared with a surgery-first approach, (hazard ratio 0.72, 95% confidence interval 0.69-0.76). In addition, R0 resection rates were significantly higher in patients receiving neoadjuvant therapy (relative risk 0.51, 95% confidence interval 0.47-0.55). Individual patient data analysis suggested that overall survival was better for patients receiving neoadjuvant therapy (P = 0.008). CONCLUSIONS: Current evidence suggests that neoadjuvant chemotherapy has a beneficial effect on overall survival in resectable pancreatic ductal adenocarcinoma in comparison with upfront surgery and adjuvant therapy. Further trials are needed to address the need for practice change.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Terapia Neoadjuvante/métodos , Pancreatectomia , Neoplasias Pancreáticas/terapia , Carcinoma Ductal Pancreático/mortalidade , Intervalo Livre de Doença , Humanos , Terapia Neoadjuvante/tendências , Neoplasias Pancreáticas/mortalidade , Prognóstico , Análise de Sobrevida , Fatores de Tempo
13.
Oncology ; 97(3): 135-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216557

RESUMO

BACKGROUND: We have developed a Wilms' tumor 1 (WT1)-targeting dendritic cell (DC)-based cancer vaccine combined with standard chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDA). METHODS: We evaluated predictive markers of overall survival (OS) in PDA patients treated with multiple major histocompatibility complex class I/II-restricted, WT1 peptide-pulsed DC vaccinations (DC/WT1-I/II) in combination with chemotherapy. Throughout the entire period of immunochemotherapy, the plasma levels of soluble factors derived from granulocytes of 7 eligible PDA patients were examined. Moreover, systemic inflammatory response markers (neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], and granulocyte-to-lymphocyte ratio [GLR]) were assessed. In addition, cytoplasmic WT1 expression in PDA cells was examined. RESULTS: Compared to the 4 non-super-responders (OS <1 year), the remaining 3 super-responders (OS ≥1 year) showed significantly decreased low plasma matrix metalloproteinase-9 levels throughout long-term therapy. The NLR, MLR, and GLR after 5 DC/WT1-I/II vaccinations and 3 cycles of gemcitabine were significantly lower in the super-responders than in the non-super-responders. Furthermore, the cytoplasmic WT1 expression in the PDA cells of super-responders was relatively weak compared to that in the PDA cells of non-super-responders. CONCLUSIONS: Prolonged low levels of a granulocyte-related systemic inflammatory response after the early period of therapy and low cytoplasmic WT1 expression in PDA cells may be markers predictive of OS in PDA patients receiving WT1-targeting immunochemotherapy.


Assuntos
Biomarcadores Tumorais , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunoterapia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Proteínas WT1/imunologia , Biomarcadores , Vacinas Anticâncer/administração & dosagem , Terapia Combinada , Células Dendríticas/metabolismo , Epitopos/imunologia , Feminino , Humanos , Imunofenotipagem , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Peptídeos/imunologia , Peroxidase/metabolismo , Prognóstico , Fator de Crescimento Transformador beta1/metabolismo , Resultado do Tratamento , Vacinação , Proteínas WT1/genética
14.
J Surg Oncol ; 120(3): 494-500, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222842

RESUMO

BACKGROUND AND OBJECTIVES: Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). METHODS: We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. RESULTS: A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS: Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/mortalidade , Tromboembolia Venosa/mortalidade , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/patologia , Tromboembolia Venosa/fisiopatologia
15.
N Engl J Med ; 381(4): 317-327, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31157963

RESUMO

BACKGROUND: Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib has had antitumor activity in this population. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients who had a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy. Patients were randomly assigned, in a 3:2 ratio, to receive maintenance olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival, which was assessed by blinded independent central review. RESULTS: Of the 3315 patients who underwent screening, 154 underwent randomization and were assigned to a trial intervention (92 to receive olaparib and 62 to receive placebo). The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% confidence interval [CI], 0.35 to 0.82; P = 0.004). An interim analysis of overall survival, at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P = 0.68). There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline in the global quality-of-life score (on a 100-point scale, with higher scores indicating better quality of life) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (between-group difference, -2.47 points; 95% CI, -7.27 to 2.33). The incidence of grade 3 or higher adverse events was 40% in the olaparib group and 23% in the placebo group (between-group difference, 16 percentage points; 95% CI, -0.02 to 31); 5% and 2% of the patients, respectively, discontinued the trial intervention because of an adverse event. CONCLUSIONS: Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo. (Funded by AstraZeneca and others; POLO ClinicalTrials.gov number, NCT02184195.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Quimioterapia de Manutenção , Neoplasias Pancreáticas/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Intervalo Livre de Progressão
16.
World J Gastroenterol ; 25(15): 1797-1816, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057295

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC. Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network. Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein (YAP) and WW-domain-containing transcriptional co-activator with PDZ-binding motif (TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pancreáticas/genética , Fosfoproteínas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Reposicionamento de Medicamentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Metformina/farmacologia , Metformina/uso terapêutico , Terapia de Alvo Molecular/métodos , Mutação , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Fosfoproteínas/antagonistas & inibidores , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/genética
17.
BMC Cancer ; 19(1): 468, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101022

RESUMO

BACKGROUND: Only a few patients with pancreatic ductal adenocarcinoma (PDAC) recurring after curative resection and peri-operative (neoadjuvant and adjuvant) therapy are included in clinical trials of metastatic PDAC. As such, there is a paucity of data to guide treatment after relapse, and patients are treated similarly to those with de novo metastatic PDAC (mPDAC). We evaluated the patterns of chemotherapy use and over-all survival (OS) in patients with recurrent PDAC (rPDAC) following curative therapy. METHODS: In this retrospective study, the Indiana University pancreatic cancer database was used to identify patients with PDAC who underwent curative resection and subsequently developed recurrence. Demographics, tumor and treatment characteristics were collected. Patients were broadly divided into those who received chemotherapy for rPDAC and those who did not. Patients in the former category were further subdivided into those who received single agent therapy, any standard combination therapy (5-fluorouracil/irinotecan/oxaliplatin combination or gemcitabine/nab-paclitaxel) and those who received non-standard combinations. Survival analysis was performed by the Kaplan-Meier method. Log rank tests were used to determine differences in survival between treated rPDAC patients and those not treated. Cox regression analysis was employed to evaluate factors associated with OS. RESULTS: We identified 435 patients with resected PDAC treated between 2008 and 2014. Two hundred and twenty-three patients (51.2%) were diagnosed with rPDAC. Of these, 140 patients (63%) received chemotherapy whereas 71 patients (32%) did not receive chemotherapy. The 74 patients (53%) who received any standard, approved multiagent combination regimen had a median OS of 14 months compared to 8 months for the 47 patents (34%) who received other non-standard combinations and the 19 (13%) who received single agent therapy (P = 0.029). Multivariate cox regression analysis showed that margin negative resection, peri-operative therapy, radiotherapy and the use of any chemotherapy for rPDAC were associated with improved OS. CONCLUSION: Our findings support the use of standard approved multi-agent therapy in rPDAC. Patients derive significant benefit from these standard combination therapies with median OS that is comparable to what is observed with treatment for de novo mPDAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
BMC Cancer ; 19(1): 509, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142278

RESUMO

BACKGROUND: With the increase in cancer survivors, more pancreatic ductal adenocarcinomas (PDACs) are developing as second primary cancers. Whether a prior cancer has an inferior impact on survival outcomes in patients with PDAC remains unknown, and the validity of criteria used to exclude patients with prior cancers in clinical trials needs to be determined. The aim of this study was to evaluate the prognostic factors and assess the survival impact of a prior cancer in patients with second primary PDAC. METHODS: Patients with PDAC were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific mortality rates were compared between patients with and those without prior cancer. RESULTS: The data of 9235 patients with PDAC from 2004 to 2015 were retrieved from the SEER database, consisting of 438 (4.74%) patients with a prior cancer and 8797 (95.26%) patients without a prior cancer, the patients were then pair-matched using propensity score matching (PSM) analysis. The median OS rates were 7 months for both groups of patients with PDAC with and without prior cancer. These two groups of patients had similar survival rates and cancer-specific mortalities before and after the PSM analysis. In the multivariate analysis, a history of prior cancer was not a significant prognostic factor of OS in patients with PDAC. CONCLUSIONS: Patients with PDAC who had a prior cancer had similar OS and cancer-specific mortality rates as those of patients without a prior cancer. The inclusion of patients with a prior cancer in the clinical trials of PDAC should be considered.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Neoplasias/epidemiologia , Neoplasias Pancreáticas/mortalidade , Pontuação de Propensão , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Taxa de Sobrevida
20.
Am Surg ; 85(4): 327-334, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043190

RESUMO

Studies have shown high-volume institutions have decreased mortality and increased survival for pancreatectomy. However, not all patients can travel to high-volume centers. Socioeconomic factors may influence treatment decisions. The goal of this study is to examine socioeconomic factors that determine where a patient is treated and how that location affects outcome. This is a retrospective study of the National Cancer Database of patients diagnosed with pancreatic cancer from 2004 to 2014. The primary outcome was to examine socioeconomic factors that predicted where a patient underwent their pancreatectomy. Patients treated at academic programs (APs) had to travel a mean distance of 80.9 miles, whereas patients treated at community programs (CPs) had to travel 31.7 miles (P < 0.0001). Spanish and Hispanic patients were less likely to travel to an AP (69% had surgery at an AP versus 76% of non-Hispanic patients, P < 0.001). Patients with higher comorbidities were also more likely to have care at CPs. Patients who had pancreatic cancer surgery at CPs were more likely to be Hispanic or with higher medical comorbidities. Those who had surgery at AP traveled further distances but had better perioperative outcomes and had an improvement in overall survival.


Assuntos
Adenocarcinoma/cirurgia , Acesso aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Fatores Socioeconômicos , Centros Médicos Acadêmicos , Adenocarcinoma/economia , Adenocarcinoma/etnologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Bases de Dados Factuais , Feminino , Acesso aos Serviços de Saúde/economia , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/etnologia , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/economia , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/etnologia , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Viagem , Resultado do Tratamento , Estados Unidos/epidemiologia
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