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1.
Medicine (Baltimore) ; 100(35): e26918, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477122

RESUMO

BACKGROUND: Radical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma. METHODS: A total of 240 patients were assessed for eligibility in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy. RESULT: The demography, histopathology and clinical characteristics were similar between the 2 groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; P = .034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; P = .021). There was no significant difference in the overall incidence of complications between the 2 groups (P = .502). The overall recurrence rate in the SG and EG (70.7% vs 77.5%; P = .349), and the patterns of recurrence between 2 groups were no significant differences. CONCLUSION: In multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be 1 of the reasons why extended lymphadenectomy did not result in survival benefits. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/.


Assuntos
Adenoma/cirurgia , Excisão de Linfonodo/normas , Neoplasias Pancreáticas/cirurgia , Adenoma/epidemiologia , Adenoma/mortalidade , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/normas , Pancreaticoduodenectomia/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Método Simples-Cego
3.
Diabetes Metab Res Rev ; 37(1): e3366, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32543027

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used in oncology for their favourable antitumor efficacy. ICI therapy is associated with a unique toxicity profile known as immune-related adverse events (irAEs). One such irAE is ICI-related diabetes mellitus (DM), which is relatively uncommon but can become extremely severe, leading to irreversible impairment of ß-cells, and even lead to death if not promptly recognised and properly managed. The precise mechanisms of ICI-related DM are not well understood. In this review, we summarise the clinical characteristics, pathophysiology, and management of this adverse effect caused by ICI therapy. Deeper investigation of ICI-related DM may contribute to elucidate the molecular mechanisms of classical type 1 DM.

4.
Medicine (Baltimore) ; 99(46): e22291, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181635

RESUMO

Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.


Assuntos
Oncologia/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/classificação , Livros de Texto como Assunto/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Oncologia/instrumentação , Oncologia/organização & administração , Pessoa de Meia-Idade , Células Neuroendócrinas/patologia , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Estados Unidos
5.
J Oncol ; 2020: 6572398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014053

RESUMO

Method: Data of patients who were surgically treated and clinicopathologically diagnosed as (MH)-NENs secondary to (GEP)-NENs at West China Hospital of Sichuan University from January 2006 to December 2018 were retrospectively collected and analyzed by the grading classification for (GEP)-NENs. Results: We identified 150 patients with (MH)-NENs secondary to (GEP)-NENs, including 10 patients with G1 NETs, 26 with G2 NETs, 33 with G3 NETs, and 81 with G3 NECs. There were significant differences between patients with G1/G2/G3 NETs and those with G3 NECs, such as age at diagnosis (P=0.041), synchronous liver lesion (P=0.032), incidental diagnosis (P=0.014), tumor largest diameter (P=0.047), vascular invasion (P=0.017), and extrahepatic metastatic disease (P=0.029). The estimated 3-year overall survival for patients with G1 NETs, G2 NETs, G3 NETs, and G3 NECs was 100%, 79.4%, 49.5%, and 20.7%, respectively (P < 0.001). The survival of G1 NETs or G2 NETs was significantly better than that of G3 NETs (P=0.013, P=0.037, respectively) and G3 NECs (P=0.001, P < 0.001; respectively). Patients with G3 NECs present notably worse survival than those with G3 NETs (P=0.012), while survival comparison between G1 NETs and G2 NETs was not statistically different (P=0.131). The grading classification for (GEP)-NENs was an effective independent predictor of survival for (MH)-NENs secondary to (GEP)-NENs (hazard ratio: 4.234; 95% confidence intervals: 1.984-6.763; P=0.003). Conclusion: Our demonstration revealed that the grading classification for (GEP)-NENs could well stratify (MH)-NENs secondary to (GEP)-NENs into prognostic groups and supported its wide use in clinical practice.

6.
BMC Cancer ; 20(1): 906, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962649

RESUMO

BACKGROUND: Pancreatic neuroendocrine neoplasms (p-NENs) are a group of highly heterogeneous tumors with distinct clinicopathological features and long-term prognosis. In 2017, in order to better stratify patients into prognostic groups and predicting their outcomes, World Health Organization (WHO) officially updated its grading system for p-NENs which distinguished these neoplasms among Grading 1 (G1) pancreatic neuroendocrine tumors (p-NETs), G2 p-NETs, G3 p-NETs and G3 pancreatic neuroendocrine carcinomas (p-NECs). However, this new grading classification for p-NENs has not yet been rigorously validated. METHODS: Data of patients who were surgically treated and histopathologically diagnosed as p-NENs at West China Hospital of Sichuan University from January 2002 to December 2018 were retrospectively collected and analyzed according the novel WHO 2017 grading classification. RESULTS: We eventually enrolled 480 eligible patients with p-NENs in our present study, in which 150 patients with WHO 2017 G1 p-NETs, 158 with G2 p-NETs, 64 with G3 p-NETs and 108 with G3 p-NECs were identified. The estimated 5-year overall survival for patients with G1 p-NETs, G2 p-NETs, G3 p-NETs and G3 p-NECs was 75.8, 58.4, 35.1 and 11.1%, with a median survival time of 85.3mons, 67.4mons, 51.3mons and 26.8mons, respectively. Patients with G2 p-NETs present notably worse survival than those with G1 p-NETs (P = 0.03). Survival of G3 p-NETs were significantly worse than that of G1 p-NETs or G2 p-NETs (P < 0.001, P = 0.023, respectively), as well as that when comparing G3 p-NECs with G1 p-NETs or G2 p-NETs (P < 0.001, P < 0.001, respectively). Patients with G3 p-NECs showed statistically shorter survival than those with G3 p-NETs (P < 0.001). Both WHO 2017 and 2010 grading criteria could be independent predictor for the OS of p-NENs (P = 0.016, P = 0.022; respectively). The 95% confidence intervals of WHO 2017 grading classification (0.983-9.454) was slightly smaller than that of WHO 2010 criteria (0.201-13.374), indicating a relatively more accurate predicting ability for the prognosis of p-NENs. CONCLUSION: The WHO 2017 grading classification for p-NENs could successfully allocate patients into four groups with distinct clinical features and significant survival differences, which might be superior to the WHO 2010 criteria for its better prognostic stratification and more accurate predicting ability.


Assuntos
Tumores Neuroendócrinos/classificação , Neoplasias Pancreáticas/classificação , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Organização Mundial da Saúde
7.
World J Gastroenterol ; 26(25): 3638-3649, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32742132

RESUMO

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) that produce hormones leading to symptoms are classified as functional tumors, while others are classified as nonfunctional tumors. The traditional view is that functionality is a factor that affects the prognosis of pNEN patients. However, as the sample sizes of studies have increased, researches in recent years have proposed new viewpoints. AIM: To assess whether functionality is an independent factor for predicting the prognosis of pNEN patients. METHODS: From January 2004 to December 2016, data of patients who underwent surgery at the primary site for the treatment of pNENs from the Surveillance, Epidemiology, and End Results (SEER) database and West China Hospital database were retrospectively analyzed. RESULTS: Contemporaneous data from the two databases were analyzed separately as two cohorts and then merged as the third cohort to create a large sample that was suitable for multivariate analysis. From the SEER database, age (P = 0.006) and T stage (P < 0.001) were independent risk factors affecting the survival. From the West China Hospital database, independent prognostic factors were age (P = 0.034), sex (P = 0.032), and grade (P = 0.039). The result of the cohort consisting of the combined populations from the two databases showed that race (P = 0.015), age (P = 0.002), sex (P = 0.032) and T stage (P < 0.001) were independent prognostic factors. In the West China Hospital database and in the total population, nonfunctional pNETs and other functional pNETs tended to have poorer prognoses than insulinoma. However, functionality was not associated with the survival time of patients with pNETs in the multivariate analysis. CONCLUSION: Functionality is not associated with prognosis. Race, age, sex, and T stage are independent factors for predicting the survival of patients with pNETs.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , China/epidemiologia , Humanos , Estadiamento de Neoplasias , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos
8.
Adv Clin Exp Med ; 29(8): 911-919, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32790250

RESUMO

BACKGROUND: Cholangiocarcinoma is a malignant tumor that originates from the neoplastic transformation of bile duct epithelial cells. OBJECTIVES: To investigate the role of DHA and miR-29b on the proliferation and apoptosis of cholangiocarcinoma cells, and to explore whether DHA exerted its role through the miR-29b/Mcl-1 signaling pathway. MATERIAL AND METHODS: Human cholangiocarcinoma cell lines HUCCT-1 and FRH0201 were treated with dihydroartemisinin (DHA) and DHA+miR-29b. The inhibitory effects of DHA and miR-29b on proliferation were detected using MTT assay. The effects of DHA and miR-29b on apoptosis were detected using flow cytometry (FCM). The mRNA and protein expressions of Mcl-1L and Mcl-1S were evaluated with reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting, respectively. RESULTS: The DHA increased miR-29b expression in HUCCT-1 and FRH201 cells. The MTT assay showed that DHA+miR-29b combination therapy promoted the inhibition effects on the proliferation of HUCCT-1 and FRH201 cells. The FCM results revealed that DHA and miR-29b combination therapy increased the apoptosis of HUCCT-1 and FRH201 cells. The RT-PCR and western blotting analysis found that DHA+miR-29b combination therapy significantly decreased Mcl-1L expression and increased Mcl-1S expression in both HUCCT-1 and FRH201 cells. The Mcl-1S:Mcl-1L ratio was notably higher in the DHA+miR-29b combination therapy group than in the control group and DHA therapy group, in both HUCCT-1 and FRH201 cells. CONCLUSIONS: The DHA and miR-29b have a pro-apoptotic effect on cholangiocarcinoma cells through the DHA/miR-29b/Mcl-1 pathway, possibly by upregulating the expression of the pro-apoptotic protein Mcl-1S and thus increasing the proportion of Mcl-1S protein among the total amount of Mcl-1 protein.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Apoptose , Artemisininas , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides
9.
ANZ J Surg ; 90(10): 2026-2031, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32590888

RESUMO

BACKGROUND: Owing to the limited prevalence and heterogeneity, it is difficult to predict long-term survival of non-functional pancreatic neuroendocrine tumours (NF-PNETs).This study aimed to evaluate the factors predicting disease-specific survival (DSS) for well-differentiated NF-PNETs. METHODS: Data were collected retrospectively from 256 patients with pancreatic neuroendocrine tumours who underwent surgical resection between January 2009 and December at our institution. Of these, 103 NF-PNETs (40%) were identified for analysis. RESULTS: Of the 103 patients, 54 were male (52%) and the mean age was 52 years (range 21-75 years). Most patients (60/103, 58%) in our series were symptomatic. Seventeen patients (16%) died during follow-up, with a median period of 47 months. There were 88 patients with well-differentiated tumours and 10 of them (10/88, 11%) died of tumour progression. Median DSS after primary resection was 58.8 months (range 16-122 months). Multivariate analysis identified age >52 years (P = 0.038) and tumour grade G2 (P = 0.001) as statistically significant predictors of DSS. There was no association between gender, tumour size, symptoms, surgical procedure, severe complications, tumour location, tumour size, resection margin, positive lymph nodes and vascular invasion with DSS. CONCLUSION: Tumour grade, age, presence of symptoms and distant metastasis were related to poor DSS of NF-PNETs. Age >52 years and tumour grade G2 might be independent predictors of poor DSS for patients with well-differentiated NF-PNETs.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Adulto Jovem
11.
Medicine (Baltimore) ; 99(24): e20324, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541455

RESUMO

Although pancreatic neuroendocrine tumors (PNETs) are generally considered to have a favorable overall prognosis after resection, disease recurrence has been observed. Few studies have specifically addressed recurrence after resection of PNETs, especially for non-functioning PNETs (NF-PNETs). The aim of our study is to analyze the recurrence of resected well-differentiated NF-PNETs.Patients who underwent surgical resection for grade 1 and 2 NF-PNETs without synchronous metastasis were identified for analysis. Patients were treated from January 2009 to December 2017 in our institution. Univariate and multivariate cox regression analysis were conducted to identify prognostic factors.Of the 88 patients, 46 were men (52%) and the mean age was 52 years. With a median follow-up of 49.1 months (range, 8-122 months), there were 12 recurrences (14%). Liver was the most common recurrence site (7/12, 58%). The 1-, 3-, and 5-year recurrence-free survival was 99%, 90%, and 88%, respectively. Univariate analysis identified that age >52 years, positive lymph nodes, tumor grade 2, and Ki67 index ≥5% were statistically significant. Multivariate analysis identified that Ki67 index ≥5% (hazard ratio [HR], 4.69; 95% confidence interval [CI], 1.36-16.75, P = .015), positive lymph nodes (HR, 6.75; 95% CI, 1.73-24.43, P = .006) were independently associated with recurrence. The 5-year disease-free survival rate was 53% (95% CI, 14.20-91.81%) for patients with Ki-67 ≥5% or (and) positive lymph nodes, while 95% (95% CI, 82.26-100%) for the patients without these 2 factors.Ki67 index and lymph node status are independently associated with recurrence after resection of well-differentiated NF-PNETs in this study.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Antígeno Ki-67/metabolismo , Fígado/patologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Recidiva Local de Neoplasia/patologia , Tumores Neuroendócrinos/cirurgia , Pancreatectomia/métodos , Pancreatectomia/estatística & dados numéricos , Pancreatectomia/tendências , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos
13.
Chronic Dis Transl Med ; 6(1): 6-17, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32226930

RESUMO

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.

14.
BMC Surg ; 20(1): 82, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321510

RESUMO

BACKGROUND: Papillary thyroid cancer (PTC) is the most common form of well-differentiated endocrine malignancy. Distant metastases of PTC are rare and usually occur in the bones, lungs, and thoracic lymph nodes despite the common locoregional metastases to the lymph nodes of the neck. The metastasis of PTC to the pancreas is extremely rare. Here, we present a patient with PTC that had simultaneously metastasized to the pancreas, liver, and diaphragm. CASE PRESENTATION: A 47-year-old male patient suffering from mild abdominal pain for 2 months was admitted to our hospital. The ultrasound (US) and computed tomography (CT) scan of the abdomen revealed a pancreatic space-occupying lesion and pancreatic duct dilatation, and the patient underwent exploratory laparotomy. Intraoperative examination identified a hard mass (approximately 4.0 cm × 3.0 cm) in the body and tail of the pancreas and a mass (1.5 cm in diameter) in the diaphragm. Three light masses were also noted on the surface of his liver. The patient underwent radical distal pancreatectomy, splenectomy, diaphragm, and liver mass resection. After surgery, the pathological report revealed that the masses resected from the pancreas, liver, and diaphragm were PTC metastases. Then, the patient had a thyroid US and an endoscopic US-guided fine needle aspiration biopsy of the thyroid mass. Pathology showed papillary cancer. Subsequently, the patient received a complete thyroidectomy, a cervical lymphadenectomy, bilateral parotidectomy, and bilateral submandibular gland resection. CONCLUSIONS: Aggressive surgeries, such as pancreaticoduodenectomy (PD), should be considered for selected patients with metastatic diseases from PTC to alleviate the symptoms and prolong their survival.


Assuntos
Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Diafragma/patologia , Humanos , Fígado/patologia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tomografia Computadorizada por Raios X
15.
Pancreas ; 49(4): 534-542, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282767

RESUMO

OBJECTIVES: Transforming growth factor ß (TGF-ß) signaling pathway is one of the core pathways in pancreatic ductal adenocarcinoma (PDAC). Prognostic value of TGF-ß pathway genes as a functionally related group in PDAC is rarely studied. METHODS: Seventy-two PDAC patients who underwent surgery between November 30, 2015, and September 13, 2017, in West China Hospital, Sichuan University, were identified and included in this study. Whole-exome sequencing or targeted next-generation sequencing was performed with tumor tissue. Clinicopathologic characteristics and survival data were retrospectively collected and analyzed. RESULTS: Genetic alterations were detected in 71 patients (98.6%). Although 1 patient (1.4%) had one genetic alteration, 33 patients (45.8%) had 2 to 4 alterations and 37 patients (51.4%) had 5 or more alterations. Twenty-five patients with TGF-ß pathway alteration were identified as TGF-ßm+ group. Other 47 patients were TGF-ßm- group. Mutation of TGF-ß pathway was independently associated with inferior survival (hazard ratio, 2.22, 95% confidence interval, 1.05-4.70, P = 0.04), especially in patients accepting radical surgery (hazard ratio, 3.25, 95% confidence interval, 1.01-10.49, P = 0.04). CONCLUSIONS: Inferior prognosis was observed in PDACs with mutations of TGF-ß pathway. Genomic information could help screen out patients at risk after surgery, and adjuvant therapy might benefit this subgroup of PDACs.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Proteínas de Neoplasias/fisiologia , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Braquiterapia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , DNA de Neoplasias/genética , Feminino , Genes Neoplásicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Cuidados Paliativos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/fisiologia , Estudos Retrospectivos , Proteínas Smad/genética , Proteínas Smad/fisiologia , Fator de Crescimento Transformador beta/genética , Sequenciamento Completo do Exoma
16.
Medicine (Baltimore) ; 99(11): e19504, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176094

RESUMO

F-fluoro-2-deoxy-D-glucose positron emission tomography integrated with computed tomography (F-FDG PET/CT) has been proved to be practical in detecting occult malignant lesions. However, the evidence of its utility in detecting early recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is lacking. Therefore, the primary aim of the present study is to evaluate the diagnostic value of F-FDG PET/CT in the early postoperative period after radical resection of PDAC.This retrospective study included 32 patients who had F-FDG PET/CT scan within 6 months after radical resection of PDAC between January 2010 and December 2018.In total, 10 positive PET results were found at surgical margins of remnant pancreas, 12 at locoregional lymph nodes, 5 at distant areas, with the corresponding mean maximum standard uptake value (SUVmax) of 5.8 ±â€Š1.1, 5.9 ±â€Š0.9, and 6.4 ±â€Š0.7, respectively. The median follow-up time was 23.5 months (range: 8-75 months), and the median survival time was 39.5 months (95% confidence interval: 14.6-64.4 months) for the entire cohort. Patients with positive PET findings at either locoregional lymph nodes or distant areas obtained significantly poorer overall survival (OS) than those without increased FDG uptake at the corresponding areas (P = .003 and P < .001, respectively). Whereas comparisons of OS between patients with or without increased FDG uptake at the surgical margin of remnant pancreas presented no statistically difference (P = .742).The early application of F-FDG PET/CT after radical resection of PDAC could stratify the prognosis of patients well by detecting occult early recurrence at locoregional lymph nodes and distant areas efficiently.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , China , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Período Pós-Operatório , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Análise de Sobrevida
17.
Cancer Cell Int ; 20: 63, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32140076

RESUMO

Background: Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA. Methods: In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell. Results: This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9. Conclusions: We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.

19.
Medicine (Baltimore) ; 99(8): e19327, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080152

RESUMO

The optimal number of examined lymph nodes (ELN) for staging and impact of nodal status on survival following total pancreatectomy (TP) for pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of this study was to evaluate the prognostic impact of different lymph node status after TP for PDAC.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients who underwent TP for PDAC from 2004 to 2015. We calculated overall survival (OS) of these patients using Kaplan-Meier analysis and Cox proportional hazards model.Overall, 1291 patients were included in the study, with 869 node-positive patients (49.5%). A cut-off points analysis revealed that 19, 19, and 13 lymph nodes best discriminated OS for all patients, node-negative patients, and node-positive patients, respectively. Higher number of ELN than the corresponding cut-off points was an independent predictor for better prognosis [all patients: hazard ratios (HR) 0.786, P = .002; node-negative patients: HR 0.714, P = .043; node-positive patients: HR 0.678, P < .001]. For node-positive patients, 1 to 3 positive lymph nodes (PLN) correlated independently with better survival compared with those with 4 or more PLN (HR 1.433, P = .002). Moreover, when analyzed in node-positive patients with less than 13 ELN, neither the number of PLN nor lymph node ratio (LNR) was associated with survival. However, when limited node-positive patients with at least 13 ELN, univariate analyses showed that both the number of PLN and LNR were associated with survival, whereas multivariate analyses demonstrated that only number of PLN was consistently associated with survival (HR 1.556, P = .004).Evaluation at least 19 lymph nodes should be considered as quality metric of surgery in patients who underwent TP for PDAC. For node-negative patients, a minimal number of 19 lymph nodes is adequate to avoid stage migration. For node-positive patients, PLN is superior to LNR in predicting survival after TP, predominantly for those with high number of ELN.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Metástase Linfática , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Linfonodos/patologia , Masculino , Neoplasias Pancreáticas/patologia , Prognóstico , Programa de SEER , Estados Unidos/epidemiologia
20.
Medicine (Baltimore) ; 99(3): e18736, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011453

RESUMO

Recently, the American Joint Committee on Cancer (AJCC) 8th staging manual stipulated the World Health Organization (WHO) G3 pancreatic neuroendocrine carcinomas (p-NECs) should all be classified by the system for pancreatic exocrine adenocarcinomas, which had ignored the heterogeneity of G3 p-NECs. We focused on demonstrating whether the heterogeneous subgroups of G3 p-NECs would influence the accurate application of AJCC 8th staging systems.G3 p-NECs were divided into well-differentiated and poorly-differentiated subgroups, whose clinical features and overall survival (OS) were compared. Survival analysis by applying 2 new AJCC 8th staging systems to well-differentiated G3 p-NECs were performed to validate whether these subgroup patients should also be staged by the system proposed for all G3 p-NECs.We enrolled 172 patients who were histopathologically diagnosed as G3 p-NECs, including 64 well-differentiated G3 p-NECs and 108 poorly-differentiated ones, whose patient demographics and tumor characteristics present no notably differences (P > .05), except their Ki-67 index and mitotic rate (P = .031, P = .025; respectively). The estimated OS of well-differentiated G3 p-NECs was significantly better than those of poorly-differentiated tumors (P < .001). When applying the new AJCC system for all G3 p-NECs to well-differentiated G3 tumors, 18, 22, 12, and 12 patients were respectively distributed in the new AJCC Stage I, Stage II, Stage III, and Stage IV. Using the AJCC 8th staging system for WHO G1/G2 pancreatic neuroendocrine tumors (p-NETs) to well-differentiated G3 p-NECs, there were 5, 25, 22, and 12 patients classified from the new AJCC Stage I to Stage IV, respectively. The system for G1/G2 p-NETs could significantly differentiate the survival differences between each new stage of well-differentiated G3 p-NECs (P < .05), while comparisons of survivals between Stage II with Stage III or Stage III with Stage IV by the system for G3 p-NECs were not statistically different (P = .334, P = .073; respectively).G3 p-NECs were heterogeneous with well-differentiated and poorly-differentiated subgroups. Both AJCC 8th staging systems proposed for all G3 p-NECs and G1/G2 p-NETs were practical for well-differentiated G3 p-NECs, while the one originally applied to G1/G2 p-NETs appeared to be superior in performance due to its better prognostic stratification and more accurate predicting ability.


Assuntos
Metástase Linfática , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Análise de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estados Unidos , Organização Mundial da Saúde
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