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1.
Am Surg ; 85(9): 965-972, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638508

RESUMO

Serum carbohydrate antigen (CA19-9) is known to correlate with stage, resectability, and prognosis of pancreatic cancer. The goal of pancreaticoduodenectomy is to achieve an R0 resection because worse outcomes are reported in the presence of positive margins. The purpose of this study was to evaluate the predictive utility of CA19-9 for pancreaticoduodenectomy margin status. A retrospective review of patients with pancreatic adenocarcinoma undergoing pancreaticoduodenectomy between October 2007 and November 2018 at our institution was performed. Patient demographics, preoperative CA19-9, and tumor characteristics were analyzed. Univariate and multivariate logistic regression was performed to determine factors associated with positive margins. A total of 184 patients were included. The mean age was 65 years; most patients were male and white. Majority had a positive preoperative CA19-9 (69%). There were nearly twice as many patients with negative as positive margins. Groups had similar demographics and preoperative CA19-9. A greater proportion of patients with negative margins had smaller tumors and early disease. On univariate and multivariate analysis, larger and higher stage tumors had greater odds of positive margins (P < 0.05). There was no significant association between margin status and preoperative CA19-9. Preoperative CA19-9 is not predictive of margin status. These results suggest that although preoperative CA19-9 values are associated with both resectability and prognosis, positive margins may not be a contributing mechanism.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/cirurgia , Antígeno CA-19-9/sangue , Margens de Excisão , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Análise de Sobrevida
2.
Medicine (Baltimore) ; 98(40): e17443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577767

RESUMO

RATIONALE: Pancreatic cancer (PC) is considered as one of the deadliest cancers all over the world. Germline and somatic BRCA1/2 mutations have been widely studied in breast and ovarian carcinomas as they have been found to enhance the risk for disease progression. Olaparib, an oral poly(adenosine diphosphate-ribose)polymerase (PARP) inhibitor, has been approved for the treatment strategy of ovarian cancer with any BRCA1/2 mutations. There is a lack of studies which focus on the treatment of other cancer with BRCA-Mutation. PATIENT CONCERNS: This report describes a patient whose presenting complaints were "Physical examination showed that the pancreas was occupied for one month." He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. DIAGNOSIS: Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. INTERVENTIONS: He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to June 30, 2017, and Nivolumab immunotherapy as the maintenance therapy. After serum CA-199 level increased, Olaparib was orally administered from August 17, 2017 to March. After tumor relapsed, he received multiple lines of chemotherapy, including Trametinib Oxaliplatin, S-1, bevacizumab, and irinotecan liposome injection till July 17, 2018. OUTCOMES: We observed the patient had a good progression-free survival (7.4 months); the lesion of the pancreas was classified as partial disease through Olaparib treatment, which indicated significant shrinkage. But it is difficult to conclude whether such therapy could help prolong the overall survival for such patients. LESSONS: The targeted therapy Olaparib showed early signs of potential in treating PC in patients with mutations of the BRCA genes. With emerging therapeutic modalities and next-generation sequencing development, it is increasingly relevant to consider mutation screenings of patients with PC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Genes BRCA2 , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Idoso , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Neoplasias Pancreáticas/genética
3.
Anticancer Res ; 39(10): 5781-5787, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570482

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is established in the treatment of ductal pancreatic adenocarcinoma for downsizing borderline-resectable pancreatic cancer (BRPC) and may affect nodal positivity and rates of R0 resection. This study aimed to identify the impact of NAC on postoperative histopathological parameters with a prognostic relevance. PATIENTS AND METHODS: A one-to-three matched-pair analysis, including an overall total of 132 patients (25% treated with NAC and subsequent resection and 75% undergoing upfront surgery) was performed. Influence of NAC on nodal positivity, lymphatic, vascular and perineural invasion, as well as resection stage and grading, was examined. Furthermore, perioperative complications, in-hospital stay, re-admission rates, mortality, as well as preoperative body mass index and American Association of Anesthesiologist classification scores, were evaluated. RESULTS: Patients treated with NAC significantly less frequently had lymphatic tissue invasion (lymph node invasion: 51.5% vs. 72.7%; p=0.032, and lymphatic vessel invasion 9.4% vs. 55.3%; p=0.0004), whereas vascular and perineural invasion, as well as grading and resection state were not significantly different. Carbohydrate antigen 19-9 regression in correlation with nodal positivity also did not differ, and both groups showed comparable perioperative complication rates. Occurrence and severity of postoperative pancreatic fistula (18.2% vs. 24.3%; p=0.034) were significantly lower in patients who had undergone NAC. CONCLUSION: NAC significantly affects postoperative histopathological tumour stage in BRPC and appears to be a safe treatment option without increased perioperative complications, re-admission, in-hospital stay, or mortality. Further studies are mandatory to underline the suitability of NAC for ductal pancreatic adenocarcinoma subgroups in order to guide clinicians in their daily decision-making comprehensively.


Assuntos
Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos
4.
Anticancer Res ; 39(10): 5821-5830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570487

RESUMO

BACKGROUND/AIM: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC). PATIENTS AND METHODS: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed. RESULTS: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005). CONCLUSION: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival.


Assuntos
Jejuno/patologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia , Idoso , Quimiorradioterapia/métodos , Feminino , Humanos , Jejuno/efeitos dos fármacos , Jejuno/efeitos da radiação , Masculino , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/efeitos da radiação , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Veia Porta/efeitos dos fármacos , Veia Porta/efeitos da radiação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Can Assoc Radiol J ; 70(4): 416-423, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31604596

RESUMO

PURPOSE: To evaluate whole-lesion 3D-histogram apparent diffusion coefficient (ADC) metrics for assessment of pancreatic malignancy. METHODS: Forty-two pancreatic malignancies (36 pancreatic adenocarcinoma [PDAC], 6 pancreatic neuroendocrine [PanNET]) underwent abdominal magnetic resonance imaging (MRI) with diffusion-weighted imaging before endoscopic ultrasound biopsy or surgical resection. Two radiologists independently placed 3D volumes of interest to derive whole-lesion histogram ADC metrics. Mann-Whitney tests and receiver operating characteristic analyses were used to assess metrics' diagnostic performance for lesion histology, T-stage, N-stage, and grade. RESULTS: Whole-lesion ADC histogram metrics lower in PDACs than PanNETs for both readers (P ≤ .026) were mean ADC (area under the curve [AUC] = 0.787-0.792), mean of the bottom 10th percentile (mean0-10) (AUC = 0.787-0.880), mean of the 10th-25th percentile (mean10-25) (AUC = 0.884-0.917) and mean of the 25th-50th percentile (mean25-50) (AUC = 0.829-0.829). For mean10-25 (metric with highest AUC for identifying PDAC), for reader 1 a threshold > 0.94 × 10-3 mm2/s achieved sensitivity 94% and specificity 83%, and for reader 2 a threshold > 0.82 achieved sensitivity 97% and specificity 67%. Metrics lower in nodal status ≥ N1 than N0 for both readers (P ≤ .043) were mean0-10 (AUC = 0.789-0.822) and mean10-25 (AUC = 0.800-0.822). For mean10-25 (metric with highest AUC for identifying N0), for reader 1 a threshold <1.17 achieved sensitivity 87% and specificity 67%, and for reader 2 a threshold <1.04 achieved sensitivity 87% and specificity 83%. No metric was associated with T-stage (P > .195) or grade (P > .215). CONCLUSION: Volumetric ADC histogram metrics may serve as non-invasive biomarkers of pancreatic malignancy. Mean10-25 outperformed standard mean for lesion histology and nodal status, supporting the role of histogram analysis.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Biópsia Guiada por Imagem , Imagem Tridimensional , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Pancreáticas/patologia
8.
Cancer Immunol Immunother ; 68(10): 1635-1648, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31549214

RESUMO

Pancreatic cancer has been termed a 'recalcitrant cancer' due to its relative resistance to chemotherapy and immunotherapy. This resistance is thought to be due in part to the dense fibrotic tumor microenvironment and lack of tumor infiltrating CD8 + T cells. The gastrointestinal peptide, gastrin, has been shown to stimulate growth of pancreatic cancer by both a paracrine and autocrine mechanism. Interruption of gastrin at the CCK receptor may reduce tumor-associated fibrosis and alter tumor immune cells. Polyclonal Ab Stimulator (PAS) is a vaccine that targets gastrin and has been shown to prolong survival of patients with pancreatic cancer. Here, we report that PAS vaccination monotherapy elicits both a humoral and cellular immune response when used in immune competent mice-bearing pancreatic tumors and that PAS monotherapy produced a marked T-cell activation and influx of CD8 + lymphocytes into pancreatic tumors. Isolated peripheral lymphocytes elicited cytokine release upon re-stimulation with gastrin in vitro demonstrating specificity of immune activation for the target peptide. Combination therapy with PAS and PD-1 Ab activated CD4 -/CD8 - TEMRA cells important in T-cell-mediated tumor death and memory. Tumors of mice treated with PAS (250 µg) or PAS (100 and 250 µg) in combination with a PD-1 Ab were significantly smaller compared to tumors from PBS or PD-1 Ab-treated mice. When PAS was given in combination with PD-1 Ab, tumors had less fibrosis, fewer inhibitory Treg lymphocytes, and fewer tumor-associated macrophages. These findings reveal a novel approach to improve treatment strategies for pancreatic cancer.


Assuntos
Vacinas Anticâncer/imunologia , Gastrinas/imunologia , Neoplasias Pancreáticas/terapia , Receptor de Morte Celular Programada 1/imunologia , Microambiente Tumoral , Vacinação , Animais , Linhagem Celular Tumoral , Memória Imunológica , Ativação Linfocitária , Linfócitos do Interstício Tumoral/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Linfócitos T/imunologia
9.
J Cancer Res Clin Oncol ; 145(11): 2855-2862, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506738

RESUMO

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


Assuntos
Abdome/irrigação sanguínea , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infusões Intra-Arteriais/mortalidade , Neoplasias Pancreáticas/mortalidade , Abdome/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Khirurgiia (Mosk) ; (9): 93-98, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532174

RESUMO

Objective - to improve short- and long-term outcomes of locally advanced pancreatic body-tail cancer followed by major vessels invasion. MATERIAL AND METHODS: A case report of pure laparoscopic DP-CAR procedure with portal vein resection for locally advanced pancreatic body-tail cancer followed by severe abdominal pain in a 49-year-old patient is presented. RESULTS: Liver or stomach ischemia was not observed. Portal wall resection wasn't associated with any complication and resulted R0-resection. Postoperative period was complicated by Grade B pancreatic fistula. Preoperative abdominal pain completely disappeared after surgery. Surgery time was 330 min, intraoperative blood loss - 300 ml. The patient is currently undergoing FOLFIRINOX adjuvant chemotherapy. CT in 90 days after surgery confirmed no progression of disease or liver/stomach blood supply congestion. CONCLUSION: Modern technologies provide the opportunity to perform pure laparoscopic advanced surgical procedures with major vessels resection. Pure laparoscopic DP-CAR procedure with portal vein resection is effective and safe procedure that can be performed with all principles of open surgery and is associated with acceptable short- and long-term results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Artéria Celíaca/cirurgia , Laparoscopia/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Veia Porta/cirurgia , Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Oxaliplatina/administração & dosagem , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia
12.
Anticancer Res ; 39(9): 4721-4728, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519571

RESUMO

BACKGROUND/AIM: Recent research has identified the transcription factors NFATc2 and Sp1 as key regulators in the carcinogenesis of pancreatic carcinoma. This study aimed to examine the effect of clinically achievable dosages of analgesics including ketamine, s-ketamine, metamizole, and paracetamol as well as that of sufentanil, ropicavaine, and lidocaine on pancreatic carcinoma cells and the expression of NFATc2 and Sp1. MATERIALS AND METHODS: The effects of analgesics on the expression of NFATc2 and Sp1 were investigated with immunoblotting. Cell proliferation was measured with the ELISA BrdU assay. RESULTS: In PaTu8988t pancreatic carcinoma cells, 48 h stimulation with ketamine and s-ketamine significantly inhibited proliferation and decreased expression of NFATc2 in the nucleus. The addition of metamizole and lidocaine reduced proliferation of PaTu8988t cells after 48 h. CONCLUSION: New treatment concepts target specific signaling and transcription pathways. The extent to which drugs influence these mechanisms in pancreatic carcinoma cells needs to be investigated in future studies.


Assuntos
Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fator de Transcrição Sp1/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/patologia , Transcrição Genética
13.
Medicine (Baltimore) ; 98(37): e17154, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517859

RESUMO

INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of epithelial neoplasms originating from the diffuse neuroendocrine cell system of the gastrointestinal tract and pancreas. They are very rare, especially in pediatric age, and vary widely in terms of clinical presentation, malignant potential, and prognosis. PATIENT CONCERNS: A 9 years' old, white female child presented with abdominal pain and diarrhea mixed with bright red blood lasting 2 days followed by hematemesis. DIAGNOSIS: Routine laboratory tests revealed microcytic anemia. Upper endoscopy showed a 20-mm polypoid lesion in the posterior wall of the duodenal bulb. Biopsy specimens were taken and histologic analysis showed a well-differentiated neuroendocrine tumor G1, with a ki-67 index <2%, an expression of chromogranine A (CgA), synaptophysin and somatostatin receptor type 2A (SSTR2A). Endoscopic ultrasound showed a 21-mm hypoechoic, hypervascular lesion involving the mucosal, submucosal, and muscular layers and a 15-mm hypoechoic round periduodenal lymph node. Gallium-68-somatostatin receptor positron emission tomography (PET with Ga-DOTATOC) showed one area of tracer uptake in the duodenum and other one near the duodenum compatible with the primary tumor site and a lymph node respectively. All the tests confirmed the diagnosis of a GEP-NET of the duodenal bulb, with a single lymph-node metastasis. INTERVENTIONS: The patient underwent an open duodenal wedge resection. OUTCOMES: The follow-up at 6, 24, and 36 months and then yearly after surgery for a total of 42 months showed no evidence of recurrence. CONCLUSION: Duodenal neuroendocrine tumors represent 1% to 3% of all GEP-NETs. They are rare in adults and extremely rare in children. Therefore, the diagnostic and therapeutic approach should be multidisciplinary, including laboratory, endoscopic, and specific imaging tests and strictly follows guidelines, to avoid misdiagnosis and inadequate treatments. Although the prognosis is benign in most cases, they can present with metastases. Therefore, a careful follow-up is extremely important.


Assuntos
Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/cirurgia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Criança , Diagnóstico Diferencial , Duodeno , Feminino , Humanos , Neoplasias Intestinais/patologia , Metástase Linfática/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/patologia
14.
Medicine (Baltimore) ; 98(37): e17158, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517863

RESUMO

RATIONALE: Glucagonoma is a rare neuroendocrine tumor of the pancreas. Glucagonoma syndrome is often misdiagnosed as other skin lesions by clinicians due to a typical clinical sign of necrolytic migratory erythema (NME) with severe erythematous rash. PATIENT CONCERNS: A 48-year-old female patient was admitted to our department because she presented with unclear recurrent severe erythematous rash. The patient was diagnosed as skin disease. DIAGNOSES: Histopathologic examination revealed a pancreatic glucagonoma. Immnohistochemical staining of tumor tissue was positive for glucagon. INTERVENTIONS: The distal pancreatectomy plus splenectomy was performed in 2017. OUTCOMES: The skin lesions disappeared after surgery. She was followed up and showed no recurrence until now. LESSONS: Clinicians should consider the diagnosis of glucagonoma according to the typical initial symptoms. Early diagnosis is very important to provide a better prognosis. A multidisciplinary approach is effective in patients with unresectable metastatic tumors.


Assuntos
Exantema/complicações , Glucagonoma/complicações , Eritema Migratório Necrolítico/complicações , Neoplasias Pancreáticas/complicações , Diagnóstico Diferencial , Exantema/diagnóstico , Exantema/patologia , Exantema/cirurgia , Feminino , Glucagonoma/diagnóstico , Glucagonoma/patologia , Glucagonoma/cirurgia , Humanos , Pessoa de Meia-Idade , Eritema Migratório Necrolítico/diagnóstico , Eritema Migratório Necrolítico/patologia , Eritema Migratório Necrolítico/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia
15.
Int J Nanomedicine ; 14: 4413-4428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417252

RESUMO

Background: As part of our continuing quest to enhance the efficacy of bioactive phytochemicals in cancer therapy, we report an innovative green nanotechnology approach toward the use of resveratrol for the production of biocompatible resveratrol-conjugated gold nanoparticles (Res-AuNPs). Our overarching aim is to exploit the inherent pro-apoptotic properties of gold nanoparticles (AuNPs) through synergistic anti-tumor characteristics of resveratrol, with the aim of developing a new class of green nanotechnology-based phytochemical-embedded AuNPs for applications in oncology. Method: Resveratrol was used to reduce Au3+ to Au0 for the synthesis of Res-AuNPs at room temperature and gum arabic (GA) was used to further encapsulate the nanoparticulate surface to increase the overall stability of the AuNPs. This comprehensive study involves the synthesis, full characterization and in vitro stability of Res-AuNPs in various biological media for their ultimate applications as anti-cancer agents against human breast (MDAMB-231), pancreatic (PANC-1) and prostate (PC-3) cancers. Results: This strategy to systematically increase the corona of resveratrol on AuNPs, in order to gain insights into the interrelationship of the phytochemical corona on the overall anti-tumor activities of Res-AuNPs, proved successful. The increased resveratrol corona on Res-AuNPs showed superior anti-cancer effects, attributed to an optimal cellular uptake after 24-hour incubation, while GA provided a protein matrix support for enhanced trans-resveratrol loading onto the surface of the AuNPs. Conclusion: The approach described in this study harnesses the benefits of nutraceuticals and nanoparticles toward the development of Res-AuNPs. We provide compelling evidence that the increased corona of resveratrol on AuNPs enhances the bioavailability of resveratrol so that therapeutically active species can be optimally available in vivo for applications in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Ouro/química , Nanopartículas Metálicas/química , Neoplasias Pancreáticas/patologia , Neoplasias da Próstata/patologia , Resveratrol/farmacologia , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Endocitose , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Polifenóis/química , Polifenóis/farmacologia , Resveratrol/química , Espectrofotometria Ultravioleta , Resultado do Tratamento
16.
Life Sci ; 233: 116732, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394125

RESUMO

AIMS: Linderane, an important bioactive compound in Linderae, improved glucose and lipid metabolism in ob/ob mice. However, the effect of linderane on streptozotocin (STZ)-induced oxidative damage in INS-1 cells remains unclear. MAIN METHODS: INS-1 cells were pre-treated with different doses of linderane for 2 h and then treated with 3 mM STZ for 12 h. Cell viability was determined by MTT assay. Cell apoptosis was detected using an Annexin V-FITC Apoptosis Detection Kit. The level of intracellular ROS was determined using dichlorofluorescein-diacetate (DCFH-DA). The activities of insulin secretion, SOD, catalase (CAT) and GPx were measured using ELISA kits. The expression levels of bax, bcl-2, p38, p-p38, nuclear Nrf2 and HO-1 were measured using western blot. KEY FINDINGS: The results showed that STZ-caused inhibitory effects on cell viability and insulin secretion were mitigated by linderane. Furthermore, linderane inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, linderane suppressed the activation of p38 MAPK pathway, as well as enhanced the activation of Nrf2 pathway in STZ-induced INS-1 cells. Activation of p38 MAPK pathway or inhibition of Nrf2 significantly reversed the protective effects of linderane against STZ-induced ROS production and cell apoptosis. SIGNIFICANCE: The protective effects of linderane on STZ-induced INS-1 cells might be attributed to the inhibition of p38 MAPK and activation of Nrf2 pathway.


Assuntos
Apoptose/efeitos dos fármacos , Furanos/farmacologia , Insulina/metabolismo , Insulinoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Estreptozocina/toxicidade , Animais , Insulinoma/metabolismo , Insulinoma/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ratos , Células Tumorais Cultivadas
17.
Arq Bras Cir Dig ; 32(2): e1442, 2019 Aug 26.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31460602

RESUMO

BACKGROUND: Solid pseudopapillary tumor of the pancreas is a rare low-grade malignant neoplasm. Most patients present with nonspecific symptoms until the tumor becomes large. Complete surgical resection by pancreatoduodenectomy is the treatment of choice for tumors located in the head of the pancreas. AIM: To analyzed the clinicopathologic features, management, and outcomes of patients who had solid pseudopapillary tumor of the head pancreas and underwent surgical resection. METHODS: Were analyzed 16 patients who underwent pancreatoduodenectomy for this condition. RESULTS: Mean age was 25.7 years old, and 15 patients were female (93.7%). Nonspecific abdominal pain was present in 14 (87.5%). All underwent computed tomography and/or magnetic resonance imaging as part of diagnostic workup. The median diameter of the tumor was 6.28 cm, and surgical resection was performed with open or laparoscopic pancreatoduodenectomy without neoadjuvant chemotherapy. Postoperative complications occurred in six patients (37.5%) and included pancreatic fistula without mortality. The mean of hospital stay was 10.3 days. Median follow-up was 3.6 years, and no patient had local recurrence or metastatic disease. CONCLUSION: For these patients surgical resection with pancreatoduodenectomy is the treatment of choice showing low morbidity, no mortality, and good long-term survival.


Assuntos
Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adolescente , Adulto , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
18.
Medicine (Baltimore) ; 98(35): e16960, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464937

RESUMO

To assess the duct-road sign and tumor-to-duct ratio (TDR) in MRI for differentiating pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal-adenocarcinomas (PDACs).Retrospectively reviewed MRI characteristics of 78 pancreatic masses (histopathology-proven 25 PNETs and 53 PDACs). Receiver operating characteristics with TDR and diagnostic performance of the duct-road sign for differential diagnosis were performed.The prevalence of duct-road sign in PNETs was higher than that for PDACs (84% vs 0%; P < .001). A strong correlation (r = 0.884, P < .001) was observed between MRI for PNETs and the frequency of this sign. Performance characteristics of the duct-road sign in MRI for PNET diagnosis were sensitivity (84%, [21 of 25]), specificity (100%, [53 of 53]), positive predictive value (100%, [21 of 21]), negative predictive value (92.9%, [53 of 57]), and accuracy (94.8%, [74 of 78]). In the intention-to-diagnose analysis, the corresponding values were 67.7% (21 of 31), 100% (53 of 53), 100% (21 of 21), 84.1% (53 of 63), and 88.1% (74 of 84). The TDR in PNETs was observed to be greater than that in PDACs (14.6 ±â€Š9.3 vs 6.9 ±â€Š3.8, P = .001). TDR with a cut-off value of 7.7 had high sensitivity (84%) and specificity (66%) with area under curve (0.802, 95% CI: 0.699, 0.904; P < .001) for distinguishing PNETs from PDACs.The presence of duct-road sign and TDR > 7.7 on MRI may assist in diagnosis for PNET instead of PDAC.


Assuntos
Adenocarcinoma/patologia , Tumores Neuroendócrinos/patologia , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/diagnóstico por imagem , Adulto , Idoso , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carga Tumoral
19.
J Surg Oncol ; 120(6): 919-925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31385621

RESUMO

BACKGROUND AND OBJECTIVES: Although minority race has been associated with worse cancer outcomes, the interaction of race with pathologic variables and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is not known. METHODS: Patients from the US Neuroendocrine Study Group (2000-2016) undergoing curative-intent resection of GEP-NETs were included. Given few patients of other races, only Black and White patients were analyzed. RESULTS: A total of 1143 patients were included. Median age was 58 years, 49% were male, 14% Black, and 86% White. Black patients were more likely to be uninsured (7% vs 2%, P = .011), and to have symptomatic bleeding (13% vs 7%, P = .009), emergency surgery (7% vs 3%, P = .006), and positive lymph nodes (LN) (47% vs 36%, P = .021). However, Black patients had improved 5-year recurrence-free survival (RFS) (90% vs 80%, P = .008). Quality of care was comparable between races, seen by similar LN yield, R0 resections, postoperative complications, and need for reoperation/readmission (all P > .05). While both races were more likely to have pancreas-NETs, Black patients had more small bowel-NETs (22% vs 13%, P < .001). LN positivity was prognostic for pancreas-NETs (5-year RFS 67% vs 83%, P = .001) but not for small-bowel NETs. CONCLUSIONS: Black patients with GEP-NETs had more adverse characteristics and higher LN positivity. Despite this, Black patients have improved RFS. This may be attributed to the epidemiologic differences in the primary site of GEP-NETs and variable prognostic value of LN-positive disease.


Assuntos
Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Disparidades em Assistência à Saúde , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Surg Oncol ; 120(6): 966-975, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401809

RESUMO

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


Assuntos
Gastrinoma/mortalidade , Neoplasias Intestinais/mortalidade , Neoplasias Hepáticas/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Gástricas/mortalidade , Estudos de Coortes , Feminino , Seguimentos , Gastrinoma/metabolismo , Gastrinoma/patologia , Gastrinoma/cirurgia , Humanos , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Países Baixos , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
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