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1.
Ann N Y Acad Sci ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207155

RESUMO

In order to combine high-quality research with minimal harm to animals, a prospective severity assessment for animal experiments is legally required in many countries. In addition, an assessment of the evidence-based severity level might allow realistic harm-benefit analysis and the appraisal of refinement methods. However, only a few examples describe the distress of animals by simple, cost-efficient, and noninvasive methods. We, therefore, evaluated the severity of an orthotopic mouse model for pancreatic cancer using C57BL/6J mice when pursuing two different chemotherapies. We assessed fecal corticosterone metabolites, body weight, distress score, and burrowing, as well as nesting activity. Moreover, we established a multifactorial model using multivariate logistic regression to describe animal distress. This multifactorial analysis revealed that metformin + galloflavin treatment caused higher distress than metformin + α-cyano-4-hydroxycinnamate therapy. Similar results were obtained by using the best cutoff calculated by Youden's J index when using only single parameters, such as burrowing activity or fecal corticosterone metabolite concentration. Thus, the present study revealed that single readout parameters, as well as multivariate analysis, can help to assess the severity of animal experiments and detect side effects of therapies.

2.
ALTEX ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31825086

RESUMO

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of score sheets and do not attempt to reduce the suffering of animals by determining earlier and therefore more humane endpoints. The present study uses data assessed from BALB/cANCrl mice after bile duct ligation to retrospectively analyze which score sheet criteria are informative to determine humane endpoints. The performance of each single as well as combinations of multiple animal welfare parameters was analyzed by a Cox proportional-hazards model followed by Harrell's concordance index. The addition of behavioral parameters, such as burrowing activity, helped to define a more humane early endpoint for euthanizing these animals. Using this approach, we determined that a body weight loss of 10-20 % combined with a reduction of burrowing activity by more than 79.4 % was able to predict that these animals died within two days. Thus, this approach successfully determined an earlier humane endpoint and will therefore reduce the suffering of animals in future experiments. A consequent application of such an approach or similar methods will contribute to the refinement of various animal experiments.

3.
Sci Rep ; 9(1): 14084, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575986

RESUMO

Ethical responsibility, legal requirements and the need to improve the quality of research create a growing interest in the welfare of laboratory animals. Judging the welfare of animals requires readout parameters, which are valid and sensitive as well as specific to assess distress after different interventions. In the present study, we evaluated the sensitivity and specificity of different non-invasive parameters (body weight change, faecal corticosterone metabolites concentration, burrowing and nesting activity) by receiver operating characteristic curves and judged the merit of a multi-parametric analysis by logistic regression. Chronic pancreatitis as well as laparotomy caused significant changes in all parameters. However, the accuracy of these parameters was different between the two animal models. In both animal models, the multi-parametric analysis relying on all the readout parameters had the highest accuracy when predicting distress. This multi-parametric analysis revealed that C57BL/6 mice during the course of chronic pancreatitis often experienced less distress than mice after laparotomy. Interestingly these data also suggest that distress does not steadily increase during chronic pancreatitis. In conclusion, combining these non-invasive methods for severity assessment represents a reliable approach to evaluate animal distress in models such as chronic pancreatitis.

4.
J Adv Res ; 20: 9-21, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31193017

RESUMO

The efficacy of gemcitabine therapy is often insufficient for the treatment of pancreatic cancer. The current study demonstrated that LW6, a chemical inhibitor of hypoxia-inducible factor 1α, is a promising drug for enhancing the chemosensitivity to gemcitabine. LW6 monotherapy and the combination therapy of LW6 plus gemcitabine significantly inhibited cell proliferation and enhanced cell death in pancreatic cancer cells. This combination therapy also significantly reduced the tumor weight in a syngeneic orthotopic pancreatic carcinoma model without causing toxic side effects. In addition, this study provides insight into the mechanism of how LW6 interferes with the pathophysiology of pancreatic cancer. The results revealed that LW6 inhibited autophagic flux, which is defined by the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and p62/SQSTM1. Moreover, these results were verified by the analysis of a tandem RFP-GFP-tagged LC3 protein. Thence, for the first time, these data demonstrate that LW6 enhances the anti-tumor effects of gemcitabine and inhibits autophagic flux. This suggests that the combination therapy of LW6 plus gemcitabine may be a novel therapeutic strategy for pancreatic cancer patients.

5.
Animals (Basel) ; 9(4)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987232

RESUMO

Comparative studies for evaluating distress in established animal models are still rare. However, this issue is becoming more important as a consequence of worldwide appreciation of animal welfare. One good parameter for evaluating distress is the quantification of corticosterone. We hypothesized that not just the absolute value but also the duration of increased corticosterone concentration in the blood is an important aspect for evaluating animal distress. Therefore, we analyzed plasma corticosterone concentrations 30, 60, 120, and 240 min after induction of pancreatitis by cerulein, liver damage by carbon tetrachloride, liver damage by bile duct ligation, and after orthotopic injection of pancreatic cancer cells. We also evaluated corticosterone kinetics after injection of distinct carrier substances. Compared to phosphate buffered saline, dimethyl sulfoxide leads to dose-dependent higher and longer-lasting circulating corticosterone concentrations. In all disease models, we observed significantly increased corticosterone concentration 30 min after stress induction. However, the corticosterone kinetics differed among the animal models. Both the absolute value of corticosterone concentration and the duration correlated positively with the quantification of animal distress by a score sheet. This suggests that both variables of corticosterone kinetics might provide a solid basis for comparing and grading distress of different animal models.

6.
Biosci Rep ; 39(1)2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30610157

RESUMO

BACKGROUND AND AIM: The aim of the present study sought to determine the protective function of Shenqi Fuzheng Injection (SFI) in cholestatic liver injury. METHODS: Cholestatic liver injury was induced in a 7-day bile duct-ligated (BDL) rat model. Rats were divided into three groups that were comprised of: (1) Sham; (2) BDL model; and (3) SFI treatment. The sham and BDL groups were treated with an appropriate volume of 0.9% sodium chloride as the vehicle, and the SFI group was administered SFI at a dose of 20 ml/kg/day, via tail vein injection. RESULTS: SFI significantly (all at P<0.01) decreased the levels of serum aspartate aminotransferase and alanine aminotransferase as compared with the BDL group, which was associated with reduced severity of inflammatory cell infiltration and hepatic damage. Moreover, SFI significantly decreased the levels of hepatic interleukin-6 (P<0.01), tumor necrosis factor-α (P=0.041), and malondialdehyde (P=0.026), and significantly increased the levels of total superoxide dismutase (P<0.01), and the GSH/GSSG ratio (P=0.041) in the liver. Western blot analysis showed that SFI increased PPAR-γ expression; however, SFI treatment decreased cyclooxygenase-2 (COX-2) expression and the phosphorylation of NF-κBp65. CONCLUSIONS: These data demonstrated that SFI attenuated both inflammation and oxidative stress, and disrupted cholestatic liver injury. The involved mechanism was dependent, at least in part, on regulating PPAR-γ, COX-2, and NF-κBp65 expression.


Assuntos
Colestase/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Animais , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Colestase/etiologia , Colestase/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ligadura/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/patologia , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Ratos , Fator de Transcrição RelA/genética
7.
Med Biol Eng Comput ; 57(1): 311-324, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30117067

RESUMO

TiO2 scaffolds have previously shown to have promising osteoconductive properties in previous in vivo experiments. Appropriate mechanical stimuli can further promote this osteoconductive behaviour. However, the complex mechanical environment and the mechanical stimuli enhancing bone regeneration for porous bioceramics have not yet been fully elucidated. This paper aims to compare and evaluate mechanical environment of TiO2 scaffold with three commercial CaP biomaterials, i.e. Bio-Oss, Cerabone and Maxresorb under simulated perfusion culture conditions. The solid phase and fluid phase were modelled as linear elastic material and Newtonian fluid, respectively. The mechanical stimulus was analysed within these porous scaffolds quantitatively. The results showed that the TiO2 had nearly heterogeneous stress distributions, however lower effective Young's modulus than Cerabone and Maxresorb. The permeability and wall shear stress (WSS) for the TiO2 scaffold was significantly higher than other commercial bone substitute materials. Maxresorb and Bio-Oss showed lowest permeability and local areas of very high WSS. The detailed description of the mechanical performance of these scaffolds could help researchers to predict cell behaviour and to select the most appropriate scaffold for different in vitro and in vivo performances. Graphical abstract Schematic representation of the establishment procedure. Take the establishment process of Cerabone as an example. Left shows a slice of micro-CT image from Cerabone, and 1.5 mm × 1.5 mm region of interest was shown in the red box. A 1.5-mm3 cube was cut out by Boolean operation in Mimics (Materialise, Belgium), and the cubic model was remeshed in 3-Matic 6.0 (Materialise, Belgium). The cubic model is shown in blue, and the empty space in red.


Assuntos
Materiais Biocompatíveis/farmacologia , Transplante Ósseo , Análise de Elementos Finitos , Perfusão , Reologia , Tecidos Suporte/química , Titânio/farmacologia , Simulação por Computador , Módulo de Elasticidade , Hidrodinâmica , Permeabilidade , Porosidade , Pressão , Reprodutibilidade dos Testes , Estresse Mecânico , Viscosidade
8.
Front Oncol ; 8: 590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568920

RESUMO

In this study we evaluated the interaction of pancreatic cancer cells, cancer-associated fibroblasts, and distinct drugs such as α-cyano-4-hydroxycinnamate, metformin, and gemcitabine. We observed that α-cyano-4-hydroxycinnamate as monotherapy or in combination with metformin could significantly induce collagen I deposition within the stromal reaction. Subsequently, we demonstrated that cancer-associated fibroblasts impaired the anti-proliferation efficacy of α-cyano-4-hydroxycinnamate, metformin and gemcitabine. Interestingly, inhibition of autophagy in these fibroblasts can augment the anti-proliferation effect of these chemotherapeutics in vitro and can reduce the tumor weight in a syngeneic pancreatic cancer model. These results suggest that inhibiting autophagy in cancer-associated fibroblasts may contribute to strategies targeting cancer.

9.
Int J Mol Sci ; 19(12)2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30486435

RESUMO

Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and more evidence demonstrates that this protein is also an essential contributor of p73-mediated apoptosis. This questions the concept that yes-associated protein is always a good target for developing novel anti-cancer drugs. Thus, the aim of this review was to evaluate the clinical relevance of yes-associated protein for cancer pathophysiology. This review also summarized the molecules, processes and drugs, which regulate Hippo-YAP signaling and discusses their effect on apoptosis. In addition, issues are defined, which should be addressed in the future in order to provide a solid basis for targeting the Hippo-YAP signaling pathway in clinical trials.


Assuntos
Apoptose , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Descoberta de Drogas , Regulação da Expressão Gênica , Glicólise , Humanos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas Nucleares/genética , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
10.
BMC Endocr Disord ; 18(1): 73, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340569

RESUMO

BACKGROUND: The present study aims to improve the M-stage classification of pancreatic neuroendocrine neoplasms (pNENs). METHODS: Two thousand six hundred sixty six pNENs were extracted from the Surveillance, Epidemiology, and End Results database to explore the metastatic patterns of pNENs. Metastatic patterns were categorized as single, two, or multiple (three or more) distant organ metastasis. The mean overall survival and hazard rate of different metastatic patterns were calculated by Kaplan-Meier and Cox proportional hazards models, respectively. The discriminatory capability of the modified M-stage classification was evaluated by Harrell's concordance index. RESULTS: The overall survival time significantly decreased with an increasing number of metastatic organs. In addition, pNENs with only liver metastasis had better prognosis when compared to other metastatic patterns. Thus, we modified the M-stage classification (mM-stage) as follows: mM0-stage, tumor without metastasis; mM1-stage, tumor only metastasized to liver; mM2-stage, tumor metastasized to other single distant organ (lung, bone, or brain) or two distant organs; mM3-stage, tumor metastasized to three or more distant organs. Harrell's concordance index showed that the modified M-stage classification had superior discriminatory capability than both the American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) M-stage classifications. CONCLUSIONS: The modified M-stage classification is superior to both AJCC and ENETS M-stage classifications in the prognosis of pNENs. In the future, individualized treatment and follow-up programs should be explored for patients with distinct metastatic patterns.


Assuntos
Classificação Internacional de Doenças , Tumores Neuroendócrinos/classificação , Neoplasias Pancreáticas/classificação , Vigilância da População , Idoso , Estudos de Coortes , Bases de Dados Factuais/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/classificação , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Vigilância da População/métodos
11.
Opt Express ; 26(12): 15343-15352, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30114783

RESUMO

Surface plasmons have a fundamental role in the dynamics of photon-electron interactions and in optical metamaterials. Terahertz (THz) time-domain spectroscopy was used to characterize the complex dielectric constant, index of refraction, and conductivity of super-aligned, free-standing, multi-walled carbon nanotube films over the range 0.2-2.5 THz. These complex parameters were in excellent agreement with Maxwell-Garnett and Drude-Lorentz models. In addition, surface plasmon excitations in engineered, subwavelength, multi-walled carbon nanotube metasurfaces were examined. The observed surface plasmon resonances, reproduced by simulation, could be changed over the THz frequency range by altering the lattice constant of the arrays. The THz transmission was enhanced at the resonance peak. Overall, the results indicate potential applications for THz metasurfaces based on super-aligned, free-standing multi-walled carbon nanotubes.

13.
Cell Signal ; 47: 101-108, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29609037

RESUMO

Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death. α-cyano-4-hydroxycinnamate in combination with metformin reduced the export of lactate significantly, whereas α-cyano-4-hydroxycinnamate monotherapy only modestly influenced lactate export. None of these two drugs inhibited the expression of distinct glycolytic enzymes. Interestingly, α-cyano-4-hydroxycinnamate rather inhibited the ERK and very strongly stimulated the p38 signaling pathway in 6606PDA as well as in 7265PDA cells. In addition, the inhibition of the p38 signaling pathway by PH-797804 partially reversed the effect of α-cyano-4-hydroxycinnamate on cell apoptosis in both cell lines. We conclude that α-cyano-4-hydroxycinnamate monotherapy and especially the combinatorial therapy with metformin has strong anti-cancerous effects. α-cyano-4-hydroxycinnamate causes cancer cell apoptosis by a novel mechanism for this drug, namely the stimulation of the p38 signaling pathway.


Assuntos
Ácidos Cumáricos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hexoquinase/metabolismo , Metformina/farmacologia , Camundongos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Int J Surg ; 53: 262-268, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29604352

RESUMO

BACKGROUND: The survival benefit of pancreaticoduodenectomy (PD) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is still unclear. METHODS: Data pertaining to elderly (age ≥75 years) and younger (age <75 years) patients with potentially curable PDAC who underwent pancreaticoduodenectomy in the period 2004-2013 were extracted from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards model and stratified Kaplan-Meier survival analyses were performed. RESULTS: A total of 4283 patients (3256 younger patients and 1027 elderly patients) were included. On multivariate analysis, advanced age (age ≥75 years) was not found to be an independent risk factor for diseases specific survival (DSS). Survival analysis disaggregated by gender, tumor size, American Joint Committee on Cancer stage, and tumor differentiation showed comparable DSS in younger and elderly patients (log-rank test). Among patients with poorly-differentiated or undifferentiated tumors, those in the elderly age-group experienced shorter DSS as compared to that of younger patients (poorly-differentiated: elderly vs. younger, 32.779 months vs. 42.198 months, P = 0.043; undifferentiated: elderly vs. younger, 17.500 months vs. 43.028 months, P = 0.210). However, PD was still warranted for elderly patients with poorly-differentiated tumors (surgery vs. without surgery, 32.779 months vs. 11.490 months, P < 0.001). Patients with undifferentiated tumors experienced a non-significant survival benefit after PD (surgery vs. without surgery, 17.500 months vs. 11.699 months, P = 0.330). CONCLUSIONS: Advanced age (age ≥75 years) is not an independent risk factor for DSS. PD is justified in a subset of elderly PDAC patients; however, it should be performed in a high-volume center to minimize the risk of post operative complications. Future studies should explore individualized treatment strategies for elderly patients with undifferentiated tumors.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
15.
Pancreas ; 47(2): 183-189, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29329160

RESUMO

OBJECTIVES: We aim to examine the predictive effect of the total number of examined lymph nodes on N stage and survival in pancreatic neuroendocrine neoplasms (pNENs) and to determine the optimal threshold. METHODS: A pNENs data set from 2004 to 2013 was extracted from the Surveillance, Epidemiology, and End Result database. Multivariate logistic regression and Cox proportional hazards model were used to identify predictive factors associated with N stage and survival, respectively. RESULTS: Totally, 1280 pNENs were analyzed. The 11 to 15 lymph nodes examined showed a strong association with the N1 stage (6-10 vs 11-15: odds ratio, 0.672; P = 0.042; 11-15 vs 16-20: odds ratio, 1.049; P = 0.840). However, it failed to show any survival benefit in pNENs with or without lymph node metastasis. CONCLUSIONS: Examining at least 11 lymph nodes may be useful to accurately classify the N stage for pNENs.


Assuntos
Linfonodos/patologia , Tumores Neuroendócrinos/cirurgia , Pâncreas/cirurgia , Neoplasias Pancreáticas/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , /estatística & dados numéricos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Modelos de Riscos Proporcionais
16.
J Adv Nurs ; 74(5): 1016-1029, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29171070

RESUMO

AIM: This study aimed to evaluate the efficacy of music therapy for reducing the anxiety and pain of patients who underwent a biopsy. BACKGROUND: Music can affect human anxiety and pain by triggering a neuroendocrine effect. Clinical study results indicated that music can influence the anxiety and pain caused by invasive procedures. There is no effective solution for anxiety and pain arising from a biopsy. Although researchers in this field have different views, music still holds promise in reducing the anxiety and pain in patients undergoing the biopsy. DESIGN: Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Medline and Cochrane databases for studies reported in the English language. The review period covered 2000 - December 2016. The outcome measure of interest was anxiety and pain. METHODS: This review followed Cochrane methods. Studies were selected according to the PICOS framework. The methodological quality of studies was assessed with the Cochrane risk of bias tool. A systematic review of effectiveness was conducted by using GRADE approach. RESULTS: Nine randomized controlled trials with a total of 326 participants in the music intervention group and 323 controls met the inclusion criteria. Music had a tendency towards decreasing systolic blood pressure before the biopsy, State-Trait Anxiety Inventory scores after the biopsy, diastolic blood pressure after the biopsy and heart rate after the biopsy. Similarly, music also tended to be more effective for controlling pain after the biopsy. There was moderate quality evidence for the outcome: State-Trait Anxiety Inventory scores after the biopsy; and low- or very low-quality evidence for other outcomes. CONCLUSION: Music can be used for patients before and during the biopsy procedure. This approach may be performed by nurses to promote the recovery of patients after the biopsy.


Assuntos
Transtornos de Ansiedade/terapia , Biópsia/psicologia , Musicoterapia/métodos , Manejo da Dor/métodos , Estresse Psicológico/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Int J Surg ; 48: 142-148, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29107188

RESUMO

BACKGROUND: The recently released AJCC TNM staging system of pancreatic adenocarcinoma has endorsed the number of positive lymph node(NPLN) as the criterion of N staging. However, the prognostic role of NPLN is still unclear for pancreatic neuroendocrine neoplasms (pNENs). METHODS: Patients underwent resection and at least one lymph node examined were identified from the Surveillance, Epidemiology, and End Results database. The overall survival (OS) and disease specific survival (DSS) were estimated using Kaplan-Meier analysis and compared by log-rank test. The prognostic factors were determined by cox proportional regression model. RESULTS: Totally, 1,269 pNENs were included in the present study. The increasing NPLN (NPLN > 3) was corresponding significantly (P < 0.05) shorter OS and DSS in both entire cohort (OS: NPLN ≤ 3 vs. NPLN > 3, 93.624 ± 1.765 months vs. 75.075 ± 4.005 months; DSS: NPLN ≤ 3 vs. NPLN > 3, 104.829 ± 1.455 months vs. 85.443 ± 3.938 months, respectively) and cohort with the number of examined lymph node more than 11 (OS: NPLN ≤ 3 vs. NPLN > 3, 88.759 ± 2.756 months vs. 73.664 ± 4.700 months; DSS: NPLN ≤ 3 vs. NPLN > 3, 99.021 ± 2.212 months vs. 85.139 ± 4.686 months, respectively). Furthermore, the multivariate analysis showed the NPLN > 3 rather than lymph node status was the independent prognostic factors for OS and DSS in these two cohorts. CONCLUSIONS: The NPLN seems more meaningful than the lymph node metastasis status as prognostic factor for survival. Taking into account the prognostic value of NPLN for pNENs might improve the current TNM staging systems. However, prospective study is needed to demonstrate our findings.


Assuntos
Adenocarcinoma/patologia , Linfonodos/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
18.
Oncotarget ; 8(51): 89245-89255, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29179516

RESUMO

Aim: To evaluate the prognostic significance of lymph node metastasis, extent of examined lymph nodes (ELNs) and lymph node ratio (LNR) for resected pancreatic neuroendocrine neoplasms (pNENs). Materials and Methods: Surgically resected pNENs were assimilated from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier and Cox proportional hazard models were used to examine the prognostic effect of clinicopathological characteristics on overall survival; Harrell's concordance index was performed to assess the prognostic accuracy of all independent prognostic factors; and the Spearman's rank correlation was used to assess the correlation between LNR and other clinicopathological characteristics. Results: Totally, 1,273 pathologically confirmed pNENs were included in our study. The extent of ELNs failed to show any survival benefit in entire cohort (ELNs ≤ 12 vs. ELNs > 12, P = 0.072) or pNENs without lymph node metastasis (ELNs ≤ 28 vs. ELNs > 28, P = 0.108). Lymph node metastasis and LNR > 0.40 were significantly (both P < 0.001) adverse prognostic factors of overall survival. However, only LNR > 0.40 was the independent predictor of survival after adjusted for other clinicopathological characteristics. Besides LNR, the age, gender, primary tumor site, grade and stage also were the independent predictors of overall survival; and this survival model had an acceptable predictive power (Harrell's concordance index, 0.731). Conclusions: The current study suggested that the LNR, not the total number of ELNs and the lymph node metastasis, is an independent prognostic indicator of overall survival for pNENs after surgical resection.

19.
J Thorac Dis ; 9(3): E202-E209, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28449504

RESUMO

Pheochromocytomas are catecholamine-producing neuroendocrine tumors that usually occur in the adrenal medulla or sympathetic paraganglia. Anterior mediastinum involvement with pheochromocytoma is rare and may not present with typical symptoms. Its clinical manifestation may be unclear and a high index of suspicion is required for accurate diagnosis. We report a rare case of pheochromocytoma of the anterior mediastinum in a 51-year-old female. A painful hard mass on the sternum was the only clinical manifestation. Imageological examination indicated that there might be a malignant mass on the anterior mediastinum and thoracic wall. The patient accepted surgical curettage and thoracic wall reconstruction. Based on pathological results and WHO definition, the final diagnosis was malignant pheochromocytoma. After six months follow-up, the patient had no recurrence or any symptom. Malignant pheochromocytoma in the anterior mediastinum invading the sternum is rare. A local painful mass may be the only clinical manifestation without special laboratory results. Surgery remains as the first choice for these patients. For this rare case, 3D reconstruction by special software may be a good method to realize individualized treatment. The final decision of the diagnosis should be based on pathological results, past medical history and WHO definition. Long-term follow-up is necessary, while other suspicious lesions should also be given sufficient attention.

20.
Dig Surg ; 34(4): 265-280, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28095392

RESUMO

BACKGROUND: The aim of this study was to compare the safety and efficacy of a new technology, binding pancreaticojejunostomy (BPJ), with conventional pancreaticojejunostomy (CPJ) after pancreaticoduodenectomy in preventing postoperative pancreatic fistula (POPF). METHODS: Randomized controlled trials and observational studies were retrieved from literature searches. Pooled OR with 95% CI for dichotomous variables and weighted mean difference with 95% CI for continuous variables were calculated. Fixed-effect and random-effect models as well as subgroup analysis were used for sensitivity analysis. RESULTS: No statistically significant differences were found in the incidence of POPF, delayed gastric emptying, postpancreatectomy hemorrhage, reoperation, morbidity, mortality, operation time, intraoperative blood loss, blood transfusion, and hospital stay between 2 groups. However, the total costs of hospitalization and ordinary stay were higher in BPJ group (€10,513 ± €6,536 vs. €8,238 ± €4,687, p = 0.002; €7,946 ± €5,023 vs. €5,700 ± €2,902, p = 0.015, respectively). CONCLUSIONS: Our study showed BPJ was as safe as CPJ. However, no significant superiority was found in BPJ group regarding the incidence of POPF. The total costs of hospital stay were higher for patients undergoing BPJ. Surgeons can prefer to perform the digestive tract reconstruction of their choice.


Assuntos
Fístula Pancreática/prevenção & controle , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/etiologia , Perda Sanguínea Cirúrgica , Esvaziamento Gástrico , Hospitalização/economia , Humanos , Duração da Cirurgia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia , Pancreaticojejunostomia/economia , Pancreaticojejunostomia/mortalidade , Complicações Pós-Operatórias/etiologia , Reoperação
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