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1.
Medicine (Baltimore) ; 99(35): e21829, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871906

RESUMO

Imaging parameters including metabolic or textural parameters during F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are being used for evaluation of malignancy. However, their utility for prognosis prediction has not been thoroughly investigated. Here, we evaluated the prognosis prediction ability of imaging parameters from preoperative FDGPET/CT in operable pancreatic cancer patients.Sixty pancreatic cancer patients (male:female = 36:24, age = 67.2 ±â€Š10.5 years) who had undergone FDGPET/CT before the curative intent surgery were enrolled. Clinico-pathologic parameters, metabolic parameters from FDGPET/CT; maximal standard uptake value (SUVmax), glucose-incorporated SUVmax (GI-SUVmax), metabolic tumor volume, total-lesion glycolysis, and 53 textural parameters derived from imaging analysis software (MaZda version 4.6) were compared with overall survival.All the patients underwent curative resection. Mean and standard deviation of overall follow-up duration was 16.12 ±â€Š9.81months. Among them, 39 patients had died at 13.46 ±â€Š8.82 months after operation, whereas 21 patients survived with the follow-up duration of 18.56 ±â€Š9.97 months. In the univariate analysis, Tumor diameter ≥4 cm (P = .003), Preoperative Carbohydrate antigen 19-9 ≥37 U/mL (P = .034), number of metastatic lymph node (P = .048) and GI-SUVmax (P = .004) were significant parameters for decreased overall survival. Among the textural parameters, kurtosis3D (P = .052), and skewness3D (P = .064) were potentially significant predictors in the univariate analysis. However, in multivariate analysis only GI-SUVmax (P = .026) and combined operation (P = .001) were significant independent predictors of overall survival.The current research result indicates that metabolic parameter (GI-SUVmax) from FDGPET/CT, and combined operation could predict the overall survival of surgically resected pancreatic cancer patients. Other metabolic or textural imaging parameters were not significant predictors for overall survival of localized pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Antígenos Glicosídicos Associados a Tumores/análise , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Cuidados Pré-Operatórios , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 99(33): e21682, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872039

RESUMO

To investigate the clinicopathological characteristics and relevant prognostic factors of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN), to improve our understanding of GEP-NEN.This was a retrospective analysis of 155 patients (average age 53.7 ±â€Š13.6 years) pathologically diagnosed with GEP-NEN. We analyzed the clinicopathological characteristics, treatment, and prognostic factors of GEP-NEN.The most common primary site was the pancreas (41.9%), followed by the rectum, stomach and duodenum. Most cases were nonfunctional GEP-NENs (149/155) with nonspecific symptoms. TNM stage and histological grade were determined by the latest criteria. Surgical resection was the mainstay of treatment in 150 patients, and 22 patients received chemotherapy under different circumstances. A total of 130 patients were followed up for a median of 44 months, and 1-year and 3-year survival rates were 82.3% and 72.3%, respectively. According to univariate and multivariate analysis, incidental diagnosis, maximum tumor diameter, tumor stage, lymph node and distant metastasis, TNM stage, and histological grade were significantly correlated with overall survival, but histological grade was the only factor confirmed as an independent prognostic factor for long-term survival of GEP-NEN.GEP-NEN, with an increasing trend in incidence, occurred most frequently in the pancreas. Nonfunctional tumors with nonspecific symptoms comprised the majority of cases. The main treatment was surgical resection. Histological grade was confirmed as the only independent prognostic factor.


Assuntos
Neoplasias Intestinais/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Feminino , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
3.
Nat Commun ; 11(1): 4516, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908137

RESUMO

Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment.


Assuntos
Células Acinares/patologia , Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Lesões Pré-Cancerosas/genética , Animais , Animais Geneticamente Modificados , Biópsia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Heterogeneidade Genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaplasia/genética , Camundongos , Mutação , Pâncreas/citologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA-Seq , Análise de Célula Única , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microambiente Tumoral/genética
4.
Medicine (Baltimore) ; 99(37): e21687, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925714

RESUMO

BACKGROUND: Increased risk and cancer-related mortality is observed in pancreatic cancer (PC) patients with diabetes mellitus (DM). Whether using metformin as glucose-lowering therapy can result in survival benefit in this group of patients is still unclear. METHODS: A meta-analysis of 21 studies that including 38,772 patients was performed to investigate the association between metformin and overall survival in patients with PC and concurrent DM. RESULTS: A significant survival benefit was observed in metformin treatment group compared with non-metformin group (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.74-0.91). These associations were observed in both subgroups of Asian countries (HR = 0.69, 95% CI: 0.60-0.79) and Western countries (HR = 0.86, 95% CI: 0.76-0.95), the former was more obvious. Survival benefit was gained for patients at early stage (HR = 0.75, 95% CI: 0.64-0.85) and mixed stage (HR = 0.81, 95% CI: 0.70-0.91), but not for patients at advanced stage (HR = 0.99, 95% CI: 0.74-1.24). Similarly, survival benefit was also observed in patients receiving surgery (HR = 0.82, 95% CI: 0.69-0.94) and comprehensive treatment (HR = 0.85, 95% CI: 0.77-0.93), but not in chemotherapy group (HR = 0.99, 95% CI: 0.67-1.30). No obvious benefit was suggested when pooled by time-varying COX model (HR = 0.94, 95% CI: 0.86-1.03). CONCLUSIONS: These results suggest that metformin is associated with survival benefit in patients with PC and concurrent DM. Further randomized controlled trials and prospective studies with larger sample sizes are required to confirm our findings.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Idoso , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Modelos de Riscos Proporcionais , Taxa de Sobrevida
5.
Medicine (Baltimore) ; 99(37): e22089, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925749

RESUMO

Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.


Assuntos
Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Programa de SEER , Taxa de Sobrevida , Estados Unidos
6.
Medicine (Baltimore) ; 99(37): e22092, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925750

RESUMO

Pancreatic cancer (PaCa) is one of the most fatal cancers in the world. Although great efforts have made to explore the mechanisms of PaCa oncogenesis, the prognosis of PaCa patients is still unsatisfactory. Thus, it is imperative to further understand the potential carcinogenesis of PaCa and reliable prognostic models.The gene expression profile and clinical information of GSE21501 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to explore the potent genes associated with the overall survival (OS) events of PaCa patients. Cox regression model was applied to selecting prognostic genes and establish prognostic model. The prognostic values of six-gene signature were validated in TCGA-PAAD cohort.According to the WGCNA analysis, a total of 19 modules were identified and 115 hub genes in the mostly associated module were reserved for next analysis. According to the univariate and multivariate Cox regression analysis, we established a six-gene signature (FTSJ3, STAT1, STX2, CDX2, RASSF4, MACF1) which could effectively evaluate the overall survival (OS) of PaCa patients. In validated patients' cohorts, the six-gene signature exhibited excellent prognostic value in TCGA-PAAD cohort as well.We developed a six-gene signature to exactly predict OS of PaCa patients and provide a novel personalized strategy for evaluating prognosis. The findings may be contributed to medical customization and therapeutic decision in clinical practice.


Assuntos
Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Fator de Transcrição CDX2/genética , Perfilação da Expressão Gênica , Humanos , Metiltransferases/genética , Proteínas dos Microfilamentos/genética , Modelos Estatísticos , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fator de Transcrição STAT1/genética , Sintaxina 1/genética , Proteínas Supressoras de Tumor/genética
7.
Medicine (Baltimore) ; 99(37): e22115, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925757

RESUMO

Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy.This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12-26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P = .04).Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Artéria Celíaca/cirurgia , Artéria Hepática/cirurgia , Artéria Mesentérica Superior/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Taxa de Sobrevida
8.
PLoS One ; 15(8): e0236817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813684

RESUMO

STUDY AIM: To develop and apply a natural language processing algorithm for characterization of patients diagnosed with chronic pancreatitis in a diverse integrated U.S. healthcare system. METHODS: Retrospective cohort study including patients initially diagnosed with chronic pancreatitis (CP) within a regional integrated healthcare system between January 1, 2006 and December 31, 2015. Imaging reports from these patients were extracted from the electronic medical record system and split into training, validation and implementation datasets. A natural language processing (NLP) algorithm was first developed through the training dataset to identify specific features (atrophy, calcification, pseudocyst, cyst and main duct dilatation) from free-text radiology reports. The validation dataset was applied to validate the performance by comparing against the manual chart review. The developed algorithm was then applied to the implementation dataset. We classified patients with calcification(s) or ≥2 radiographic features as advanced CP. We compared etiology, comorbid conditions, treatment parameters as well as survival between advanced CP and others diagnosed during the study period. RESULTS: 6,346 patients were diagnosed with CP during the study period with 58,085 radiology studies performed. For individual features, NLP yielded sensitivity from 88.7% to 95.3%, specificity from 98.2% to 100.0%. A total of 3,672 patients met cohort inclusion criteria: 1,330 (36.2%) had evidence of advanced CP. Patients with advanced CP had increased frequency of smoking (57.8% vs. 43.0%), diabetes (47.6% vs. 35.9%) and underweight body mass index (6.6% vs. 3.6%), all p<0.001. Mortality from pancreatic cancer was higher in advanced CP (15.3/1,000 person-year vs. 2.8/1,000, p<0.001). Underweight BMI (HR 1.6, 95% CL 1.2, 2.1), smoking (HR 1.4, 95% CL 1.1, 1.7) and diabetes (HR 1.4, 95% CL 1.2, 1.6) were independent risk factors for mortality. CONCLUSION: Patients with advanced CP experienced increased disease-related complications and pancreatic cancer-related mortality. Excess all-cause mortality was driven primarily by potentially modifiable risk factors including malnutrition, smoking and diabetes.


Assuntos
Processamento de Linguagem Natural , Pancreatite Crônica/diagnóstico , Adulto , Idoso , Índice de Massa Corporal , Complicações do Diabetes/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fumar , Tomografia Computadorizada por Raios X
9.
Ann Surg ; 272(2): 357-365, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675550

RESUMO

OBJECTIVE: Our aim was to evaluate recurrence patterns of surgically resected PDAC patients with negative (pN0) or positive (pN1) lymph nodes. SUMMARY BACKGROUND DATA: Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer death by 2030. This is mostly due to early local and distant metastasis, even after surgical resection. Knowledge about patterns of recurrence in different patient populations could offer new therapeutic avenues. METHODS: Clinicopathologic data were collected for 546 patients who underwent resection of their PDAC between 2005 and 2016 from 2 tertiary university centers. Patients were divided into an upfront resection group (n = 394) and a neoadjuvant group (n = 152). RESULTS: Tumor recurrence was significantly less common in pN0 patients as compared with pN1 patients, (upfront surgery: 55% vs. 77%, P < 0.001 and 64% vs. 78%, P = 0.040 in the neoadjuvant group). In addition, time to recurrence was significantly longer in pN0 versus pN1 patients in the upfront resected patients (median 16 mo pN0 vs. 10 mo pN1 P < 0.001), and the neoadjuvant group (pN0 21 mo vs. 11 mo pN1, P < 0.001). Of the patients who recurred, 62% presented with distant metastases (63% of pN0 and 62% of pN1, P = 0.553), 24% with local disease (27% of pN0 and 23% of pN1, P = 0.672) and 14% with synchronous local and distant disease (10% of pN0 and 15% of pN1, P = 0.292). Similarly, there was no difference in recurrence patterns between pN0 and pN1 in the neoadjuvant group, in which 68% recurred with distant metastases (76% of pN0 and 64% of pN1, P = 0.326) and 18% recurred with local disease (pN0: 22% and pN1: 15%, P = 0.435). CONCLUSION: Time to recurrence was significantly longer for pN0 patients. However, patterns of recurrence for pN0 vs. pN1 patients were identical. Lymph node status was predictive of time to recurrence, but not location of recurrence.


Assuntos
Carcinoma Ductal Pancreático/patologia , Causas de Morte , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/patologia , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
10.
Ann Surg ; 272(2): 366-376, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675551

RESUMO

OBJECTIVE: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. BACKGROUND: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. METHOD: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. RESULTS: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. CONCLUSIONS: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.


Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Fatores Quimiotáticos/genética , Pancreatectomia/métodos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Proteínas S100/genética , Idoso , Carcinoma Ductal Pancreático/cirurgia , Causas de Morte , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/cirurgia , Seleção de Pacientes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
12.
PLoS One ; 15(7): e0235623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614932

RESUMO

Pancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P<0.0001 for overall survival; 3.2 vs 7.9 months, P<0.0001 for progression-free survival). In a multivariate analysis, ctDNA status was independently associated with overall survival and progression-free survival (HR = 3.1, 95%CI = 1.9-5.0, P<0.0001; HR 2.6, 95%CI = 1.7-4.0, P<0.0001, respectively). Moreover, circulating tumor DNA significantly correlated with a higher number of liver metastases, the presence of lung and/or peritoneal metastases, tumor burden, and higher carbohydrate antigen 19-9 levels. This study supports the use of circulating tumor DNA as an independent prognostic marker for advanced pancreatic cancer.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Antígeno CA-19-9/sangue , Ácidos Nucleicos Livres/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
13.
Am Surg ; 86(5): 458-466, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684030

RESUMO

BACKGROUND: Nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) are rare tumors with continued controversies in management. This study aims to identify demographic and clinicopathologic characteristics associated with aggressive behavior and survival. METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients with NF-PNETs from 1988 to 2012. Multivariate regression analysis and Cox proportional hazards modeling were used to assess the impact of patient, tumor, and treatment characteristics on tumor behavior and overall survival. RESULTS: In 1787 patients identified, size was a major determinant of aggressive behavior. The probability of aggressiveness increased 100% for tumor size ≥2 cm. For tumors ≥2 cm, every 1-cm increase in size was associated with an increase in probability of aggressive behavior by 11.3%. Patient age, tumor grade, and surgical resection were independent predictors of survival. Surgical resection was associated with improved survival but not grade I or II tumors with size <2 cm. DISCUSSION: Patient age, tumor size, and grade should be in the decision-making process around the surgical management of NF-PNETs. For tumors ≤2 cm with histologic grades of I or II, the probability of aggressive behavior is low, and surgical resection does not appear to afford survival benefit. Therefore, close observation could be justified.


Assuntos
Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
14.
Medicine (Baltimore) ; 99(29): e21287, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702921

RESUMO

The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes.The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database.A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group (P < .0001, P = .0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part.A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Microambiente Tumoral , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma
15.
Anticancer Res ; 40(7): 4011-4015, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620645

RESUMO

BACKGROUND/AIM: The aim of this monocentric study was to evaluate the efficacy and tolerability of a polychemotherapy regimen based on gemcitabine, docetaxel, capecitabine, cisplatin (PDGX) as second-line for advanced pancreatic cancer after FOLFIRINOX. PATIENTS AND METHODS: Patients received FOLFIRINOX as first-line regimen were retrospectively identified between January 2016 and January 2019. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were treated in our center by PDGX. RESULTS: During this period, 18 patients received PDGX regimen as second-line therapy. Main grade 3 toxicities were hematologic, which required dose adaptation in 14/18 patients. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2,91 and 5,3 months, respectively. Total OS from the initiation of first-line was and 11,9 months. CONCLUSION: Second-line PDGX regimen after FOLFIRINOX failure is feasible, with notable toxicity profile and is associated with poor clinical outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Capecitabina/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Docetaxel/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Resultado do Tratamento
16.
Anticancer Res ; 40(7): 4033-4040, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620649

RESUMO

BACKGROUND/AIM: This study investigated the feasibility of an integrated scoring system of preoperative prognostic parameters using data from before/after neoadjuvant therapy in patients with borderline resectable pancreatic cancer (BRPC). PATIENTS AND METHODS: We constructed and analyzed a prognostic scoring system using factors that were previously reported to be significant prognostic indicators or predictors of histological response. RESULTS: We analyzed 28 consecutive patients with BRPC who underwent neoadjuvant therapy and subsequent surgical resection. Overall survival (OS) and recurrence free survival (RFS) were greater in patients with high scores (n=11) than in patients with low scores (n=17; log-rank test p=0.03/0.028). Pathological N0 status (p<0.05) and tumor cell destruction rate >50% (p<0.05) were found at a higher incidence among patients with high scores. CONCLUSION: OS and RFS can be predicted with an integrated scoring system that uses prognostic indices before/after neoadjuvant therapy for BRPC.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Índice de Gravidade de Doença , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
17.
J Cancer Res Clin Oncol ; 146(11): 3049-3061, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32601815

RESUMO

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) has continued to increase, but for pNETs, there is still no distinction between treatments based on anatomical location. We aim to determine whether NETs located at the head and body/tail of the pancreas are different. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we focused on pNETs patients with comprehensive information. The patients were divided into two groups based on tumors' location. We compared the characteristics of the two groups and assessed the risk factors for lymphatic metastasis. Survival analysis was performed based on the biological characteristics of the tumor. RESULTS: In all 3011 patients, pNETs were more common in the body/tail (62.94%) than in the head (37.06%) of the pancreas. The risk factors for lymph node metastasis in the two groups were different. Nonmetastatic, low-grade pancreatic body/tail NETs had the best prognosis (p < 0.001). For low-grade tumors (G1-G2), lymphatic metastasis did not significantly affect the prognosis of patients with pancreatic head NETs (p = 0.098) but affected the overall survival of patients with pancreatic body/tail NETs (p < 0.001). The tumors at the pancreatic head were larger (p = 0.001), more likely to have positive lymph nodes (p < 0.001) and more prone to locally advanced and distant invasion (p < 0.001). The prognosis of pancreatic head NETs 21-40 mm was worse than that of body/tail pNETs (p < 0.001). For non-functional NETs, the overall survival of pancreatic body/tail tumors was better (p < 0.001). CONCLUSION: The pancreatic head and pancreatic body/tail NETs have different biological characteristics and clinical outcomes and they should be treated differently.


Assuntos
Metástase Linfática/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Análise de Sobrevida
18.
PLoS One ; 15(7): e0234568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658932

RESUMO

INTRODUCTION: The aim of this study was to define histo-morphological stroma characteristics by analyzing stromal components, and to evaluate their impact on local and systemic tumor spread and overall survival in pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: Patients who underwent oncologic resections with curative intent for PDAC were identified from a prospectively maintained database. Histological specimens were re-evaluated for morphological stroma features as stromal fibers, fibroblast morphology, stroma matrix density, microvessel density and distribution of immune cell populations. RESULTS: A total of 108 patients were identified undergoing curative resection for PDAC in the period from 2011-2016. 33 (30.6%) patients showed parallel alignment of stroma fibers while 75 (69.4%) had randomly oriented stroma fibers. As compared to parallel alignment, random orientation of stroma fibers was associated with larger tumor size (median 3.62 cm vs. median 2.87cm, p = 0.037), nodal positive disease (76.0% vs. 54.5%, p = 0.040), higher margin positive resection rates (41.9% vs. 15.2%, p = 0.008) and a trend for higher rates of T3/4 tumors (33.3% vs. 15.2%, p = 0.064). In univariate analysis, patients with parallel alignment of stroma fibers had improved overall survival rates as compared to patients with random orientation of stroma fibers (42 months vs. 22 months, p = 0.046). The combination of random orientation of stroma fibers and low microvessel density was associated with impaired overall survival rates (16 months vs. 36 months, p = 0.019). A high CD4/CD3 ratio (16 months vs. 33 months, p = 0.040) and high stromal density of CD163 positive cells were associated with reduced overall survival (27 months vs. 34 months, p = 0.039). In multivariable analysis, the combination of random orientation of stroma fibers and low microvessel density (HR 1.592, 95%CI 1.098-2.733, p = 0.029), high CD4/CD3 ratio (HR 2.044, 95%CI 1.203-3.508, p = 0.028) and high density of CD163 positive cells (HR 1.596, 95%CI 1.367-1.968, p = 0.036) remained independent prognostic factors. CONCLUSION: Alignment of stroma fibers and microvessel density are simple histomorphological features serving as surrogate markers of local tumor progression dissemination and surgical resectability and determine prognosis in PDAC patients. High CD4/CD3 ratio and CD163 positive cell counts determine poor prognosis.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Microvasos/patologia , Células Estromais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Taxa de Sobrevida
19.
PLoS One ; 15(6): e0232043, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542007

RESUMO

BACKGROUND: Elevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer. METHODS: Clinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases. RESULTS: On univariate and multivariate analyses patients whom on presentation had high NLR (≥3.3) showed more baseline distant metastases compared to patients with low NLR (<3.3), (p-value: <0.0001 and <0.0001, respectively). Patients with high baseline ANC (≥5500/µL), AMC (≥600/µL), MLR (≥0.3) had more baseline distant metastases in comparison to patients with lower values (p-value: 0.02, 0.001, and <0.0001, respectively). High ANC, NLR, MLR, and PLR and low ALC were associated with poorer OS, (p-value: <0.0001, <0.0001, <0.0001, 0.04, and 0.01, respectively). CONCLUSION: This study presents additional evidence of the association of some of the hematologic markers; in particular ANC, NLR, AMC, and MLR, with baseline distant metastases and poor outcome in pancreatic cancer. Whether these immune phenomena can help in identifying patients at higher risk for the subsequent development of distant metastases is unknown.


Assuntos
Linfócitos/citologia , Neutrófilos/citologia , Neoplasias Pancreáticas/patologia , Idoso , Área Sob a Curva , Contagem de Células Sanguíneas , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Curva ROC , Estudos Retrospectivos
20.
Br J Anaesth ; 125(2): 141-148, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32475684

RESUMO

BACKGROUND: Intravenous lidocaine has been shown to reduce opioid consumption and is associated with favourable outcomes after surgery. In this study, we explored whether intraoperative lidocaine reduces intraoperative opioid use and length of stay (LOS) and improves long-term survival after pancreatic cancer surgery. METHODS: This retrospective study included 2239 patients who underwent pancreatectomy from January 2014 to December 2017. The patients were divided into non-lidocaine and lidocaine (bolus injection of 1.5 mg kg-1 at the induction of anaesthesia followed by a continuous infusion of 2 mg kg-1 h-1 intraoperatively) groups. The overall use of postoperative rescue analgesia and LOS were recorded. Propensity score matching was used to minimise bias, and disease-free survival and overall survival were compared between the two groups. RESULTS: After propensity score matching, patient characteristics were not significantly different between groups. Intraoperative sufentanil consumption and use of postoperative rescue analgesia in the lidocaine group were significantly lower than those in the non-lidocaine group. The LOS was similar between groups. There was no significant difference in disease-free survival between groups (hazard ratio [HR]=0.913; 95% confidence interval [CI], 0.821-1.612; P=0.316). The overall survival rates at 1 and 3 yr were significantly higher in the lidocaine group than in the non-lidocaine group (68.0% vs 62.6%, P<0.001; 34.1% vs 27.2%, P=0.011). The multivariable analysis indicated that intraoperative lidocaine infusion was associated with a prolonged overall survival (HR=0.616; 95% CI, 0.290-0.783; P=0.013). CONCLUSION: Intraoperative intravenous lidocaine infusion was associated with improved overall survival in patients undergoing pancreatectomy.


Assuntos
Cuidados Intraoperatórios/métodos , Lidocaína/administração & dosagem , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Administração Intravenosa , Idoso , Anestésicos Locais , Feminino , Humanos , Infusões Intravenosas , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Análise de Sobrevida
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