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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
2.
Artigo em Inglês | MEDLINE | ID: mdl-34537854

RESUMO

BACKGROUND: Although preoperative splenic artery embolism (SAE) has been widely used for splenomegaly, the efficiency and safety of preoperative SAE in patients with sinistral portal hypertension (SPH) is unknown. METHODS: We designed a retrospective cohort of SPH patients who received preoperative SAE in our hospital (February 2018 to September 2020) and compared to those who received splenectomy only, in terms of intraoperative and postoperative outcomes. RESULTS: In all, 59 patients (18 patients received preoperative SAE) were analyzed. The median age was 44.7 years. Preoperative SAE reduced the intraoperative blood loss (637.0 vs. 420.3 ml, P = 0.041) and operation time (174.0 vs. 141.5 min, P = 0.012). The incidence of complications including postoperative pancreatic fistula (POPF), bleeding, and thromboembolism was comparable. Multivariate analysis showed that SAE was a protective factor for intraoperative blood loss and operation time, while prior pancreatic pseudocyst/abscess was a risk factor. CONCLUSIONS: Preoperative SAE could reduce intraoperative blood loss and operation time in SPH patients without increasing the incidence of complications compared to splenectomy only.

4.
Nutr Cancer ; : 1-14, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435522

RESUMO

Accumulating studies have revealed that up- or downregulated miRNA-196 expression correlates with the prognostic value in various malignancies; however, existing single studies lack robust evidence to elucidate the role of miRNA-196 in malignancy. The pooled results showed that the upregulation of miRNA-196 expression was significantly correlated with unfavorable OS [HR 2.14; 95% confidence interval (CI), 1.78-2.57; p < 0.001)] and worse PFS (HR 2.84; 95% CI, 1.29-6.23, P = 0.01) in various malignancies. According to the regulatory mechanisms, studies shown that multiple tumors associated with transcription processes could be modulated by the miRNA-196 family; correspondingly, the miRNA-196 family exerted biological functions that could be regulated by various molecules. The upregulation of miRNA-196a, miRNA-196b and miRNA-196 expression is correlated with significantly unfavorable OS in multiple malignancies; similarly, miRNA-196 overexpression predicts poor PFS in multiple malignancies. Taken together, these findings indicate that miRNA-196a and miRNA-196b may serve as oncogenic molecules and may be potential prognostic biomarkers in multiple malignancies.

6.
J Transl Med ; 19(1): 301, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247626

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine. METHODS: The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan-Meier survival analyses were performed by the R version 3.6.1. RESULTS: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutation was an independent prognostic factor for survival analysis of advanced PDAC patients (p = 0.032). For DDR mutant patients, treatment with platinum-based chemotherapy (p = 0.0096) or olaparib (p = 0.018) respectively improved the overall survival. No statistical difference between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significantly improved OS to DDR-mutated patients than the naive DDR group (p = 0.14). CONCLUSIONS: In this retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy in Chinese patients. However, the value of DDR mutation in the prediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , China , Dano ao DNA/genética , Células Germinativas , Humanos , Mutação/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Estudos Retrospectivos
7.
BMC Cancer ; 21(1): 624, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044806

RESUMO

BACKGROUND: Radical pancreaticoduodenectomy is the most common treatment strategy for patients diagnosed with adenocarcinoma of the pancreatic head. Few studies have reported the clinical characteristics and treatment efficacies of patients undergoing radical pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. METHODS: A total of 177 pancreatic head cancer patients who underwent radical pancreaticoduodenectomy and were pathologically confirmed as having pancreatic ductal adenocarcinoma were screened in the West China Hospital of Sichuan University. The multivariate analysis results were implemented to construct a nomogram. The concordance index (c-index), the area under the curve (AUC) and calibration were utilized to evaluate the predictive performance of the nomogram. RESULTS: The prognostic nutritional index (PNI), the lymph node ratio (LNR) and the American Joint Committee on Cancer (AJCC) staging served as independent prognostic factors and were used to construct the nomogram. The c-indexes of the nomogram were 0.799 (confidence interval (CI), 0.741-0.858) and 0.732 (0.657-0.807) in the primary set and validation set, respectively. The AUCs of the nomogram at 1 and 3 years were 0.832 and 0.783, which were superior to the AJCC staging values of 0.759 and 0.705, respectively. CONCLUSIONS: The nomogram may be used to predict the prognosis of radical resection for adenocarcinoma of the pancreatic head. These findings may represent an effective model for the developing an optimal therapeutic schedule for malnourished patients who need early effective nutritional intervention and may promote the treatment efficacy of resectable adenocarcinoma of the pancreatic head.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Nomogramas , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/estatística & dados numéricos , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Seguimentos , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação Nutricional , Pâncreas/patologia , Pâncreas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/métodos , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
8.
Surg Oncol ; 37: 101528, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33611029

RESUMO

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare malignancy that accounts for less than 1% of primary pancreatic neoplasms. Currently, the lack of large-scale clinical studies limits our understanding of PACC. The aim of this study was to investigate the clinical characteristics and prognosis of PACC. METHODS: In a retrospective analysis, 52 patients with PACC and 355 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgical interventions were evaluated. Clinical characteristics and treatment outcomes were compared between the two groups. RESULTS: The mean age was lower for patients with PACC than for those with PDAC (mean: 50.8 ± 10.9 versus 59.4 ± 10.9 years; p < 0.001). Except for alpha-fetoprotein (AFP), tumour markers were also lower in the PACC group than the PDAC group. In regard to tumour characteristics, maximum diameters of the primary tumour [median (range): 5.0 cm (1.0-18.2 cm) versus 3.5 cm (0.6-15.0 cm); p < 0.001] and hepatic metastatic lesions [6.7 cm (1.5-12.6 cm) versus 1.2 cm (0.3-3.3 cm); p < 0.001] were larger in patients with PACC than patients with PDAC, but vascular invasion [23.1% (12/52) versus 35.5% (126/355); p = 0.044] and perineural invasion [7.7% (4/52) versus 56.1% (199/355); p < 0.001] were more common in patents with PDAC than in patients with PACC. For treatment, radical resection was performed in 57.7% of patients with PACC, which increased the 5-year survival rate to 31.8%. In regard to prognosis, the 5-year survival rate was 21.4% for PACC and 9.7% for PDAC (p < 0.0001). CONCLUSIONS: PACC is more indolent than PDAC, which makes early diagnosis more difficult. Although the stage may be advanced at diagnosis, the overall survival (OS) of PACC is much better than that of PDAC, and the prognosis greatly improves after radical resection.

9.
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
10.
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.

11.
BMC Surg ; 20(1): 207, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943033

RESUMO

BACKGROUND: Although genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed. METHODS: Messenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC. RESULTS: Five survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p < 0.001) than the low-risk group, in both the primary set and the validation set. The concordance index (C-index) was calculated to evaluate the predictive performance of the nomogram were respectively in the primary set [0.696 (0.608-0.784)] and the validation set [0.682 (0.606-0.758)]. Additionally, gene set enrichment Analysis discovered several meaningful enriched pathways. CONCLUSION: Our study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC.


Assuntos
Genes Neoplásicos , Neoplasias Pancreáticas , Hidrolases de Éster Carboxílico , Feminino , Humanos , Masculino , Nomogramas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Prognóstico , RNA Mensageiro , Análise de Sobrevida
12.
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
13.
Drug Des Devel Ther ; 14: 2945-2957, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801636

RESUMO

Introduction: Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived orthotopic xenograft (PDOX) nude mouse models of PDAC. Methods: The PTX-loaded PEGylated liposomes were prepared by film dispersion-ultrasonic method and modified by an N,N-dimethyl tertiary amino residue. Morphology characteristics of the PTX-loaded liposomes were observed by transmission electron microscope (TEM). The PDOX models of PDAC were established by orthotopic implantation and imaged by a micro positron emission tomography/computed tomography (PET/CT) imaging system. The in vivo distribution and antitumor study were then carried out to observe the pancreas-targeting accumulation and the antitumor efficacy of the proposed PTX liposomes. Results: PTX loaded well into both modified (PTX-Lip2N) and unmodified (PTX-Lip) PEGylated liposomes with spherical shapes and suitable parameters for the endocytosis process. The PDOX nude mouse models were successfully created in which high 18F-FDG intaking regions were observed by micro-PET/CT. In addition to higher cellular uptakes of PTX-Lip2N by the BxPC-3 cells, the proposed nanoparticle had a notable penetrating ability towards PDAC tumor tissues, and consequently, the antitumor ability of PTX-Lip2N was significantly superior to the unmodified PTX-Lip in vivo PDOX models and even more effective than nab-PTX in restraining tumor growth. Conclusion: The modified pancreas-targeting PTX-loaded PEGylated liposomes provide a promising platform for the treatment of pancreatic cancer.

14.
Aging (Albany NY) ; 12(14): 14542-14555, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694239

RESUMO

The upregulation of cell division cycle associated protein 5 (CDCA5) has been observed in various cancer types. However, the prognostic value of CDCA5 and its underlying mechanism contributing to tumorigenesis in hepatocellular carcinoma (HCC) remain poorly understood. We used tissue microarray (TMA) to evaluate the prognosis of 304 HCC samples based on their CDCA5 expression, and analyzed the genomic features correlated with CDCA5 by using dataset from The Cancer Genome Atlas (TCGA). Compared with adjacent normal tissues, increased expression of CDCA5 was found in HCC tissues. Moreover, higher expression of CDCA5 was associated with inferior OS and DFS outcomes in HCC patients. The enrichment plots showed that the gene signatures in cell cycle, DNA replication and p53 pathways were enriched in patients with higher CDCA5 expression. Meanwhile, statistically higher mutations burdens in TP53 could also be observed in CDCA5-high patients. Integrative analysis based on miRNAseq and methylation data demonstrated a potential association between CDCA5 expression and epigenetic changes. In conclusion, our study provided the evidence of CDCA5 as an oncogenic promoter in HCC and the potential function of CDCA5 in affecting tumor microenvironment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Proteínas de Ciclo Celular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas de Ciclo Celular/biossíntese , Intervalo Livre de Doença , Epigênese Genética , Regulação Neoplásica da Expressão Gênica/genética , Genes p53 , Humanos , Mutação , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Proteína Supressora de Tumor p53/genética
16.
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
17.
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
18.
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
19.
Medicine (Baltimore) ; 99(5): e18980, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000430

RESUMO

RATIONALE: Primary hepatic lymphoma (PHL) is an extremely rare manifestation of extranodal non-Hodgkin lymphoma. There were few cases about PHL in recent years, while cases using positron emission tomography (PET) modalities for both diagnosis and follow-up were even rare. PATIENT CONCERNS: A 29-year-old man complaining of dull epigastric pain for 2 weeks. DIAGNOSIS: The features of liver biopsy and immunohistochemistry were consistent with diffuse large B cell lymphoma. Since there were no other foci of lymphoma on the F-fluoro-2-deoxy-D-glucose (F-FDG) PET/computed tomography (CT) images, the patient was further diagnosed with PHL. INTERVENTIONS: Since the lesions were mainly confined to the right lobe of liver, partial hepatectomy and radiofrequency ablation were performed. Subsequently, 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, dexamethasone regimen were performed. OUTCOMES: The patient recovered well postoperatively and was discharged 1 week after surgery. Fortunately, the follow-up F-FDG PET/CT scan 36 months later revealed no abnormal FDG uptake, indicating the absence of relapse. LESSONS: As the superiority in excluding other organ involvement, F-FDG PET/CT should be considered as the preferable imaging modality for the diagnosis and follow-up of PHL. Besides chemotherapy, surgical resection should be considered initially. If radical R0 resection could not be done, partial hepatectomy with radiofrequency ablation may also offer an appropriate alternative treatment.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ablação por Cateter , Fluordesoxiglucose F18 , Hepatectomia , Humanos , Neoplasias Hepáticas/terapia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Compostos Radiofarmacêuticos
20.
Front Endocrinol (Lausanne) ; 11: 610744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488523

RESUMO

Adrenal lymphangioma is a very rare benign lesion worldwide and remains challenging for early diagnosis, especially when the patient has some complicated clinical disease. This is an unusual case of a 68-year-old man who was admitted to our hospital with a history of pancreatic tumor. Computed tomography (CT) images and subsequent magnetic resonance imaging (MRI) revealed a mass located in the left adrenal gland, presenting a similar enhancement pattern of the pancreatic tumor, and according to the imaging features, the patient was suspected to have an adrenal metastatic tumor originating from the pancreatic tumor. The patient underwent a surgical resection of the pancreatic tumor and the left adrenal gland. The pathologic diagnosis proved to be lymphangioma deriving from the left adrenal gland. This is the first report presenting an atypical adrenal lymphangioma mimicking a metastatic tumor of pancreatic origin, which might be suggestive in the diagnosis of adrenal lesions and the subsequent clinical treatment, especially when patient has a particular medical history. As we know, imaging examination is helpful for accurate preoperative diagnosis; however, the diagnosis of malignant tumor solely based on imaging procedures should be made cautiously by radiologists.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Linfangioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias das Glândulas Suprarrenais/cirurgia , Idoso , Carcinoma Ductal Pancreático/cirurgia , Diagnóstico Diferencial , Humanos , Linfangioma/cirurgia , Masculino
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