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1.
Medicine (Baltimore) ; 98(33): e16608, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415354

RESUMO

The utility of multimodality molecular imaging for predicting treatment response and survival of patients with hypopharyngeal carcinoma remains unclear. Here, we sought to investigate whether the combination of different molecular imaging parameters may improve outcome prediction in this patient group.Patients with pathologically proven hypopharyngeal carcinoma scheduled to undergo chemoradiotherapy (CRT) were deemed eligible. Besides clinical data, parameters obtained from pretreatment 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT), dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), and diffusion-weighted MRI were analyzed in relation to treatment response, recurrence-free survival (RFS), and overall survival (OS).A total of 61 patients with advanced-stage disease were examined. After CRT, 36% of the patients did not achieve a complete response. Total lesion glycolysis (TLG) and texture feature entropy were found to predict treatment response. The transfer constant (K), TLG, and entropy were associated with RFS, whereas K, blood plasma volume (Vp), standardized uptake value (SUV), and entropy were predictors of OS. Different scoring systems based on the sum of PET- or MRI-derived prognosticators enabled patient stratification into distinct prognostic groups (P <.0001). The complete response rate of patients with a score of 2 was significantly lower than those of patients with a score 1 or 0 (14.7% vs 58.9% vs 75.7%, respectively, P = .007, respectively). The combination of PET- and DCE-MRI-derived independent risk factors allowed a better survival stratification than the TNM staging system (P <.0001 vs .691, respectively).Texture features on F-FDG PET/CT and DCE-MRI are clinically useful to predict treatment response and survival in patients with hypopharyngeal carcinoma. Their combined use in prognostic scoring systems may help these patients benefit from tailored treatment and obtain better oncological results.


Assuntos
Carcinoma/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/estatística & dados numéricos , Neoplasias Hipofaríngeas/diagnóstico por imagem , Imagem por Ressonância Magnética/estatística & dados numéricos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Adulto , Carcinoma/mortalidade , Carcinoma/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Imagem Multimodal/estatística & dados numéricos , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos , Taxa de Sobrevida
2.
Medicine (Baltimore) ; 98(33): e16727, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415366

RESUMO

Our study was designed to construct nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of lip carcinoma patients.A search of the Surveillance, Epidemiology, and End Results (SEER) database provided us with detailed clinical data of the 1780 lip carcinoma patients. On the basis of the credible random split-sample method, the 1780 patients were placed into 2 groups, with 890 patients in the modeling group and 890 patients in the counterpart's group (proportion = 1:1). By employing Kaplan-Meier univariate and Cox multivariate survival analyses based on the modeling cohort, the nomograms were developed and then used to divide the modeling cohort into low-risk cohort and high-risk cohort. The survival rates of the 2 groups were calculated. Internal and external evaluation of nomogram accuracy was performed by the concordance index (C-index) and calibration curves.With regard to 5- and 8-year OS and CSS, the C-indexes of internal validation were 0.762 and 0.787, whereas those of external validation reached 0.772 and 0.818, respectively. All the C-indexes were higher than 0.7. The survival curves of the low-risk cohort were obviously better than those of the high-risk cohort.Credible nomograms have been established based on the SEER large-sample population research. We believe these nomograms can contribute to the design of treatment plans and evaluations of individual prognosis.


Assuntos
Carcinoma/mortalidade , Neoplasias Labiais/mortalidade , Nomogramas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto Jovem
3.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 452-457, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365957

RESUMO

Objective: To analyze the clinicopathological features and prognosis of patients in endometrial cancer with bone metastases. Methods: A retrospective review of medical records was performed to analyze patients with endometrial cancer who developed bone metastases at Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017, including patients with bone metastases at the diagnosis of endometrial cancer and at recurrence of endometrial cancer. The patient's clinicopathological features, bone metastasis characteristics, treatment process and prognoses were also analyzed. Results: The incidence of bone metastasis of endometrial cancer in PUMCH from 2004 to 2017 was 0.57% (14/2 458). (1) General clinical pathological features: the median age of the 7 patients with bone metastases diagnosed at the time of initial diagnosis was 50 years old, and the main pathological type was endometrioid carcinoma (n=5). The median age of the other 7 patients was 57 years old, with no significant difference comparing to the former groups (P=0.559). (2) The majority site of bone metastasis in endometrial cancer were discovered in pelvic bones, followed by the tibia. (3) Treatment: according to the staging of endometrial cancer, a comprehensive treatment based on surgery was performed, and one patient with isolated bone metastases underwent resection of bone metastasis. (4) Prognosis: nine out of the 14 patients died during the follow-up period. The median over all survival time was 25.5 months (range: 7.7-258.0 months). The median survival of population after diagnosis of bone metastases was 15.0 months (range: 3.0-51.0 months). The survival rate of endometrial cancer at 1-year after diagnosis of bone metastasis was 71.4%. The 2-year survival rate was 40.8%. (5) No independent prognostic factors affecting survival was found (P>0.05). Conclusions: The incidence of bone metastasis in endometrial cancer is less than 1%. Bone metastasis could occur at the diagnosis of endometrial cancer or recurrence of endometrial cancer. Bone metastasis suggests a poor prognosis. There is no standard follow-up and treatment protocols so that individualized treatment is needed.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma/secundário , Neoplasias do Endométrio/patologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Carcinoma/mortalidade , Carcinoma/terapia , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
J Clin Pathol ; 72(8): 550-553, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31164444

RESUMO

AIMS: To describe a large tertiary care academic centre's experience with patients who achieve a complete pathological response (ie, ypT0N0) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with emphasis on morphological features present in the RC and clinical outcome. METHODS: 41 patients with ypT0N0 disease following transurethral resection of bladder tumour (TURBT), NAC and RC with available clinical follow-up information were analysed. Slides from all RCs were reviewed to confirm pathological stage and assess for morphological parameters (eg, foreign body giant cell reaction, dystrophic calcification, scar and fat necrosis). RESULTS: With median follow-up of 32.8 months, the recurrence-free survival at 1 and 5 years was 97.4% and 93.5%, while the overall survival at 3 and 5 years was 94.2% and 88.6%, respectively. No patients died of urothelial carcinoma. Stage assigned at TURBT was 1 pTa (2%), 1 pT1 (2%), 38 pT2 (93%) and 1 pT3a (2%). 17 TURBTs demonstrated variant histology, with the majority of these being squamous (65%). The most common morphological features present at RC were scar (100%), foreign body giant cell reaction (80%), chronic inflammation within lamina propria (68%) and dystrophic calcifications (39%). Other morphological features were less common or absent. CONCLUSION: ypT0N0 disease at RC portends an excellent prognosis, regardless of stage or variant histology in the TURBT; scar, foreign body giant cell reaction, chronic inflammation and dystrophic calcifications are often present.


Assuntos
Carcinoma/terapia , Cistectomia , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/terapia , Urotélio/patologia , Idoso , Carcinoma/mortalidade , Carcinoma/secundário , Quimioterapia Adjuvante , Cistectomia/efeitos adversos , Cistectomia/mortalidade , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Fatores de Risco , Fatores de Tempo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
5.
J Surg Oncol ; 120(2): 241-248, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31041808

RESUMO

BACKGROUND: Systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be prognostic for many types of pancreatic malignancy. The aim of this study was to evaluate the prognostic role of these markers in patients with solid pseudopapillary tumor of the pancreas (SPTP). METHODS: Patients who underwent surgical resection for histologically confirmed SPTP were retrospectively reviewed in our institution. Preoperative NLR and PLR were calculated. Clinicopathologic data were correlated with the presence of malignant potential and recurrence-free survival (RFS). RESULTS: A total of 113 patients with SPTP were included in this study. Of them, 23 were men and 90 were women, with a median age of 35 years (interquartile range, 25-44). The optimal cut-off values for malignant SPTP were 3.22 for NLR, and 75.5 for PLR, respectively. Univariate analysis showed that high NLR (>3.22) and white blood cell count more than 9.96 × 109 /L were predictive of a malignant SPTP. Meanwhile, high NLR (P = 0.001) and age more than 35 years (P = 0.026) were associated with worse RFS. On multivariable analyses, high NLR was the only independent predictor of malignant SPTP (odd ratio 6.871; 95% confidence interval [CI], 1.482-31.864; P = 0.014) and RFS (hazard ratio 12.633; 95% CI, 1.758-90.790; P = 0.012). CONCLUSIONS: This study highlights the supportive role of preoperative NLR in predicting malignancy and RFS of SPTP patients. Further studies including a larger cohort of patients are needed to corroborate our findings.


Assuntos
Carcinoma/sangue , Carcinoma/cirurgia , Contagem de Linfócitos , Neutrófilos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Adulto , Biomarcadores Tumorais/sangue , Carcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
6.
Arq Bras Cir Dig ; 32(2): e1435, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31038560

RESUMO

BACKGROUND: Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. AIM: To evaluate the results of conversion therapy in the treatment of GC. METHODS: Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. RESULTS: Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. CONCLUSION: Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.


Assuntos
Adenocarcinoma/terapia , Carcinoma/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cuidados Paliativos , Estudos Retrospectivos , Distribuição por Sexo , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Resultado do Tratamento
7.
Eur Arch Otorhinolaryngol ; 276(7): 2031-2038, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31062093

RESUMO

PURPOSE: The aim of the study was to assess the treatment results of the parotid gland salivary duct carcinoma (SDC). MATERIAL AND METHODS: A retrospective clinicopathological analysis of 40 patients treated for parotid SDC in 1996-2015 was performed. The impact of following factors on 5-year disease-free survival (DFS) and overall survival (OS) was studied: age, sex, preoperative 7th nerve palsy, skin infiltration, pT, pN, surgical margin, type of parotidectomy and neck dissection, histology (SDC de novo vs. SDC ex pleomorphic adenoma, SDCexPA), intra/periparotid lymph nodes metastases, perineural invasion (PNI), extraparenchymal extension (EPE), and overexpression HER2. RESULTS: The average age of the patients was 62 years (ranged from 39 to 81). Males predominated (57.5%). Patients with the clinical stage IV predominated (82.5%). In 1/3 of patients preoperative, 7th nerve palsy occurred. All patients were treated surgically, and all but one had supplementary radiotherapy. In 28 patients (70%), total radical parotidectomy was performed. A neck dissection was performed in all patients. In 19 cases (47.5%), SDCexPA was diagnosed. Negative microscopic surgical margin was obtained in 60% of patients. The follow-up for the whole analyzed group ranged from 2 to 22 years, average was 11.6 years. In 23 patients (57.5%), the disease recurred. Local recurrence was observed in 10 (25%) and distant metastases in 15 (37.5%) cases. 20 patients (50%) died of cancer. 5-year DSF and OS were 42.5% and 41%, respectively. Univariate analysis proved that the significant influence on the survival had 7th nerve palsy (p = 0.024 and p = 0.017, respectively), higher pT-stage (p < 0.001), radical parotidectomy (p = 0.024 and p = 0.022), radical treatment of the neck (p = 0.001 and p = 0.002), EPE (p = 0.040 and p = 0.028), and histology SDCexPA and PNI (p = 0.036 and 0.048). Multivariate analysis showed that independent prognostic factors were the 7th nerve palsy and the histology SDCexPA, which worsened 5-year DFS, respectively, 3.61 and 3.94 times (p = 0.033 and p = 0.026). On the other hand, on 5-year OS, only 7th nerve palsy had an influence (3.86 times worse prognosis, p = 0.033). CONCLUSIONS: SDC is a clinically aggressive cancer with high risk of local recurrence and distant metastases, however, with a chance of curing of around 40%. In the majority of patients, a radical surgical treatment is necessary due to the high clinical stage of disease. Worse prognosis have patients with preoperative 7th nerve palsy and in whom SDC develops in pleomorphic adenoma.


Assuntos
Carcinoma , Esvaziamento Cervical , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Esvaziamento Cervical/métodos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Polônia/epidemiologia , Prognóstico , Estudos Retrospectivos , Ductos Salivares/patologia , Ductos Salivares/cirurgia , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(16): e15232, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008954

RESUMO

Ubiquitin-conjugating enzyme E2C (UBE2C), a crucial part of the ubiquitin-conjugating enzyme complex, is reported to promote progression of various cancers. Leucine-rich repeated-containing G protein-coupled receptor (LGR5), a biomarker of cancer stem cells, is reported to be responsible for the initiation and progression of cancers. WW domain-containing oxidoreductase (WWOX), a suppressor of tumor, is reported to inhibit initiation and progression of cancers. Vasculogenic mimicry (VM), a new blood supply pattern, is associated with progression of cancers. However, the clinicopathological significance of UBE2C, LGR5, WWOX, and VM in invasive breast carcinoma (IBC) remains elusive. The aim of this study is to investigate the positive rate of UBE2C, LGR5, WWOX, and VM in IBC and their clinical significance.Positive rates of UBE2C, LGR5, WWOX, and VM in 247 whole IBC samples were detected through immunohistochemistry. Patients data (including clinical, demography, follow-up) were collected.Levels of UBE2C, LGR5, VM, and microvessel density (MVD) were significantly higher, and level of WWOX was significantly lower in IBC specimens when compared with normal mammary gland tissues. Levels of UBE2C, LGR5, VM, and MVD were all positively associated with tumor stages, lymph node metastasis (LNM) stages, tumor grades, and tumor-node-metastasis (TNM) stages, and unfavorably with patients' overall survival (OS) and disease-free survival (DFS). Level of WWOX was negatively associated with tumor stages, LNM stages, grades, and TNM stages, and favorably with patients' OS and DFS. Multivariate analysis indicated that levels of UBE2C, LGR5, VM, MVD, and WWOX, as well as TNM stages were independently prognostic factors for OS and DFS in patients with IBC.UBE2C, LGR5, VM, MVD, and WWOX may be considered as promising indicator of IBC prognosis.


Assuntos
Neoplasias da Mama/enzimologia , Carcinoma/enzimologia , Receptores Acoplados a Proteínas-G/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Oxidorredutase com Domínios WW/metabolismo , Adulto , Idoso , Mama/enzimologia , Mama/patologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma/irrigação sanguínea , Carcinoma/mortalidade , Carcinoma/patologia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade
9.
Zhonghua Bing Li Xue Za Zhi ; 48(3): 209-214, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-30831647

RESUMO

Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.


Assuntos
Carcinoma , Herpesvirus Humano 4 , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Carcinoma/virologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Neoplasias/terapia , Neoplasias/virologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
10.
Mol Cancer ; 18(1): 33, 2019 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30825877

RESUMO

BACKGROUND: The long non-coding RNA PVT1 (lncRNA PVT1) has been reported to act as an oncogenic regulator of several cancers. However, its expression and function in gallbladder cancer (GBC) remain largely unknown. METHODS: In situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the expression of PVT1 and miR-143 in GBC tissues and cell lines. Immunohistochemistry (IHC) assays were performed to assess the expression of the hexokinase 2 (HK2) protein. The relationships among PVT1, miR-143 and HK2 were evaluated using dual-luciferase reporter, RNA immunoprecipitation (RIP) and biotin pull-down assays. The biological functions of PVT1, miR-143 and HK2 in GBC cells were explored with cell counting kit 8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, wound healing and glucose metabolism assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of PVT1 and HK2 on GBC. RESULTS: PVT1 was upregulated in GBC tissues and cells and was positively associated with malignancies and worse overall survival. PVT1 knockdown inhibited cell proliferation, migration, and invasion in vitro and restrained tumor growth in vivo. Further studies demonstrated that PVT1 positively regulated HK2 expression via its competing endogenous RNA (ceRNA) activity on miR-143. Additionally, HK2 expression and function were positively correlated with PVT1. Furthermore, we observed that the PVT1/miR-143/HK2 axis promoted cell proliferation and metastasis by regulating aerobic glucose metabolism in GBC cells. CONCLUSIONS: The results of our study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.


Assuntos
Carcinoma/genética , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Hexoquinase/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Adolescente , Adulto , Animais , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Glucose/metabolismo , Glicólise/genética , Hexoquinase/metabolismo , Humanos , Metástase Linfática , Masculino , Camundongos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Pak Med Assoc ; 69(3): 405-408, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30890835

RESUMO

Lung cancer is the most common cancer in males and second most common in females after breast cancer. We have compared our data with the international statistics to see where do we stand. In Pakistan, we do not have a valid central cancer registry at present which can provide a true picture of lung cancer. Therefore, we used statistics of GLOBOCON 2012, in order to evaluate the true burden of lung cancer in our population through the recently established data by PHRC (Pakistan Health and Research council). Our analysis showed that data depicting true incidence and mortality of lung cancer in Pakistan are lacking. GLOBOCON 2012 placed lung cancer as the 3rd most common cancer in Pakistan while PHRC 2016 placed it as the 10th most common cancer irrespective of the rise in smoking incidence in Pakistan over the past one decade. This calls for an urgent need to formulate a valid central cancer registry in the country in association with the local bodies.


Assuntos
Carcinoma/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Poluição do Ar , Carcinoma/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Paquistão/epidemiologia , Sistema de Registros , Distribuição por Sexo , Fumar/epidemiologia , Adulto Jovem
12.
Oncol Rep ; 41(4): 2265-2272, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720117

RESUMO

Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that supports the folding and processing of synthesized proteins. Its expression is associated with the prognosis of laryngeal cancer, hepatocellular carcinoma, diffuse glioma and uterine cervical cancer. In the present study, the expression levels of PDIA3 and its clinicopathological association were examined in 52 cases of gastric cancer (GC). The expression of PDIA3 was examined by immunohistochemistry and scored using a semi-quantitative method. According to the score, GC samples were classified into PDIA3­High and PDIA3­Low GC. PDIA3­High GC samples were predominantly of the intestinal type. Multivariate survival analysis indicated that PDIA3 expression and cancer stage were independent factors. The overall survival of PDIA3­High GC cases was significantly favorable compared with that of PDIA3­Low GC cases, and this was more evident in cases at an advanced stage. In GC cell cultures, the PDIA3 and major histocompatibility complex (MHC) class I proteins were expressed in three out of the four assessed cell lines according to western blot analysis. Notably, the expression of MHC class I was increased by the stimulation of interferon γ. Co­immunoprecipitation assays suggested the formation of a PDIA3 and MHC class I complex. The findings suggested that PDIA3 may be involved in the immune response of carcinoma cells. The improved prognosis in PDIA3­High GC may be accounted for, in part, by sufficient antigen processing and expression of MHC class I, which can be mediated by PDIA3. It was suggested that PDIA3 serves an important role in the pathobiology of GC, and that PDIA3 is a useful marker for the prediction of prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma/patologia , Isomerases de Dissulfetos de Proteínas/metabolismo , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Carcinoma/imunologia , Carcinoma/mortalidade , Linhagem Celular Tumoral , Feminino , Seguimentos , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Isomerases de Dissulfetos de Proteínas/imunologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
13.
Int J Med Sci ; 16(2): 337-342, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745816

RESUMO

Background: Recently published studies suggest that the anaesthetic technique used during oncologic surgery can improve patient outcomes. Therefore, the authors evaluated the survival of patients with resected colorectal carcinoma liver metastases (CRCLMs) who received either EGA (general anaesthesia [GA] combined with epidural anaesthesia [EA]) or GA alone. Methods: We conducted an ambispective cohort study including 225 post-surgical CRCLM patients between May 2007 and July 2012 and performed a follow-up investigation of survival in July 2017. Results: The basic characteristics in the two groups were largely similar. The median (quartiles) recurrence interval for all patients was 10 (2.5, 23) months, and the median (quartiles) survival for CRCLM patients post-surgically was 37 (30.5, 51.5) months. Perioperative EA was associated with survival (P =0.039, log-rank test), with an estimated hazard ratio of 0.737 (95% CI 0.551-0.985) in the univariate analysis. Kaplan-Meier estimates of survival for GA and EGA suggested that GA might provide better outcomes than EGA [P=0.028, hazard ratio of 0.7328 (95% CI 0.5433-0.9884)]. Significant differences in anaesthesia techniques were found (P=0.048), with an adjusted estimated hazard ratio of 0.741 (95% CI 0.550-0.998) in the multivariate analysis. Subgroup analyses of patients in different age groups (< 40, ≥ 40 but <60, and ≥ 60 years old) suggested that no significant differences existed among all three subgroups. Conclusions: Compared with EGA, GA may provide a better survival outcome for CRCLM patients. The benefits of anaesthetic techniques in oncological surgery are most likely related to certain cancer types.


Assuntos
Anestesia Epidural/mortalidade , Anestesia Geral/mortalidade , Carcinoma/cirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma/mortalidade , Carcinoma/secundário , China/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/patologia , Feminino , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade
14.
Anticancer Res ; 39(2): 585-590, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30711933

RESUMO

BACKGROUND/AIM: Oxidative stress is involved in several carcinogenic pathways. Nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and Park7 (DJ-1) are the main regulators of antioxidant enzymes eliminating reactive oxidative species (ROS). The roles of these proteins were studied as potential prognostic factors in endometrial cancer. MATERIALS AND METHODS: Nrf2, Keap1 and DJ-1 expression in endometrial carcinomas was analyzed immunohistochemically. Correlations between staining patterns and clinical prognostic variables were evaluated. RESULTS: Extensive cytoplasmic Keap1 staining correlated to several factors associated with poor prognosis of endometrial cancer including advanced stage, poor histological differentiation, lymphovascular invasion, pelvic lymph node metastasis and deep myometrial invasion. In multivariate analysis, cytoplasmic Keap1 was a stronger predictor of poor progression-free survival than grade. Nuclear Nrf2 staining was seen in all patients with lymph node metastasis while DJ-1 staining was associated with clinically favourable disease types. CONCLUSION: Cytoplasmic Keap1 expression indicates poor prognosis in endometrial cancer.


Assuntos
Citoplasma/metabolismo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/metabolismo , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/mortalidade , Diferenciação Celular , Núcleo Celular/metabolismo , Tomada de Decisões , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Miométrio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Prognóstico , Proteína Desglicase DJ-1/metabolismo , Espécies Reativas de Oxigênio/metabolismo
15.
Gynecol Oncol ; 153(2): 217-222, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30803719

RESUMO

OBJECTIVE: The presence of tumor infiltrating lymphocytes (TIL) and defects in homologous recombination (HR) are each important prognostic factors in ovarian carcinoma (OC). We characterized the association between HR deficiency (HRD) and the presence of TILs in a cohort of OC patients and the relative contribution to overall survival. METHODS: Patients with carcinoma of the ovary, fallopian tube, or peritoneum were prospectively enrolled. Malignant neoplasm and serum samples were collected. Immunohistochemistry for CD3+ T cells and CD68+ tumor associated macrophages (TAMs) was performed on specimens collected at primary surgery. Damaging germline and somatic mutations in genes in the HR-mediated repair (HRR) pathway were identified using BROCA sequencing. HRD was defined as a damaging mutation in one of 12 genes in the HRR pathway or promoter hypermethylation in BRCA1 or RAD51C. RESULTS: Ninety-eight of 250 patients included in the analysis had HRD OC (39.2%). HRD OC were enriched for CD3+ TILs and CD68+ TAMs. High CD3+ TIL was present in 65.3% of HRD OC compared to 43.4% of non-HRD OC (P = 0.001). High CD68+ TAM was present in 66.3% of HRD OC compared to 50.7% of non-HRD OC (P = 0.015). Patients with HRD OC and high CD3+ TILs had the longest median overall survival compared to non-HRD OC with low CD3+ TILs (70.9 vs. 35.8 months, adjusted HR 0.38, 95% CI (0.25-0.59)). CONCLUSIONS: Patients that have both CD3+ TILs and HRD OC are afforded the greatest improvement in overall survival. This finding may have therapeutic implications for OC patients treated with emerging immunotherapies.


Assuntos
Carcinoma/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Ovarianas/mortalidade , Reparo de DNA por Recombinação/genética , Idoso , Complexo CD3/metabolismo , Carcinoma/genética , Carcinoma/imunologia , Carcinoma/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Macrófagos/imunologia , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Ovário/cirurgia , Estudos Prospectivos , Linfócitos T/imunologia , Linfócitos T/metabolismo
16.
Pathol Res Pract ; 215(5): 977-982, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30738694

RESUMO

INTRODUCTION: Syndecan-1 is heparan sulfate proteoglycans (HSPGs) that is used as coreceptors for signaling of growth factors. The comprehensive effect of syndecan-1 is to augment receptor stimulation at little ligand concentrations. THE GOAL OF THIS RESEARCH: is to study syndecan-1 expression in breast carcinoma and its value in predicting the prognosis in comparison to other clinicopathological parameters. MATERIAL &METHODS: immunohistochemistry study for syndecan-1 is done on 103 cases of invasive breast carcinoma. Its expression is assessed and correlated to other clinicopathological parameters and prognosis. RESULTS: overexpression was significantly related to high histologic grade (p = 0.001), large tumor size (p = 0.043), HER2-positive status (p = 0.001), and ER&PR-negative status (p = 0.001). It was also have a negative impact on the overall survival (p=0.012) and disease free survival (p = 0.009). Syndecan-1 expression showed weak positive correlation with Her 2 expression (Correlation Coefficient (co): 0.332, p = 0.001). CONCLUSION: syndecan-1 is a good predictor of poor overall survival and recurrence/ metastasis free survival. It is associated with aggressive phenotype as HER2 enriched and Triple negative rather than luminal subtypes of breast carcinoma. So it can be added to the hormonal receptors and HER 2 assay in the routine management of invasive breast cancer after confirmation on a more larger study.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma/patologia , Sindecana-1/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Carcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/biossíntese , Receptores Estrogênicos/análise , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/análise , Receptores de Progesterona/biossíntese , Estudos Retrospectivos , Sindecana-1/análise
17.
Pathol Res Pract ; 215(5): 873-879, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30738695

RESUMO

Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. However, the expression of EREG and its prognostic value are not clear in gastric cancer (GC). We assessed EREG mRNA and protein expression in GC tissues from Chinese patients using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue microarray, and analyzed the correlation between the level of EREG expression and patient clinical characteristics and prognosis. We found that EREG expression was significantly higher in GC tissues than in matched adjacent noncancerous tissues. High EREG protein expression in GC was significantly associated with TNM stage including tumor size, lymph node metastases and distant metastases as well as poor overall survival. These finding demonstrate that EREG is an independent prognostic biomarker for GC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma/patologia , Epirregulina/biossíntese , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Intervalo Livre de Doença , Epirregulina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade
18.
J Surg Oncol ; 119(6): 749-757, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30644557

RESUMO

BACKGROUND AND OBJECTIVES: Vascular invasion, in particular extramural venous invasion (EMVI), is a pathologic characteristic that has been extensively studied in rectal cancer but rarely in colon cancer. This study aims to evaluate its prognostic role in stage II-III colon cancer. METHODS: All stage II-III colon cancer patients who underwent surgery between 2004 and 2015 were reviewed. We compared patients without invasion, with intramural invasion only (IMVI), EMVI only, and both IMVI/EMVI (n = 923). RESULTS: EMVI was associated with other high-risk features, including T4, N+ disease, lymphatic, and perineural invasion (P < 0.001). EMVI+ patients had higher rates of locoregional and distant recurrence and subsequently disease-specific mortality (stage-II, odds ratio [OR] 3.64; P = 0.001; stage-III OR, 1.94; P = 0.009), whereas outcomes were comparable between IMVI and no vascular invasion (OR, 1.21; P = 0.764; OR, 1.28, P = 0.607, respectively). The adjusted HRs for EMVI+ patients on disease-free survival, and disease-specific survival were 2.07 ( P < 0.001) and 1.67 ( P = 0.027), respectively. Moreover, EMVI+ stage-II patients fared worse than EMVI- stage-III patients, even after adjusting for adjuvant chemotherapy. CONCLUSION: EMVI is a strong predictor for worse oncologic outcomes in stage II-III colon cancer patients, whereas IMVI is not. It is also associated with worse outcomes compared in patients with higher stage disease who are EMVI negative.


Assuntos
Vasos Sanguíneos/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Invasividade Neoplásica , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Neoplasias do Colo/terapia , Intervalo Livre de Doença , Feminino , Humanos , Mucosa Intestinal/patologia , Linfonodos/patologia , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Músculo Liso/patologia , Recidiva Local de Neoplasia
19.
Langenbecks Arch Surg ; 404(1): 45-53, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30673845

RESUMO

PURPOSE: Poorly differentiated thyroid carcinoma (PDTC) patients have worse outcomes than patients with differentiated thyroid carcinoma (DTC), but the implication of poorly differentiated areas (PDAs) noted in DTC is not very well understood. The aim of the present study was to compare the clinicopathologic profiles and outcomes of PDTC and DTC with PDA. METHODS: A total of 142 patients, managed at out center between September 1989 and June 2016, were enrolled in this retrospective study. Histology was reviewed, and the patients were divided in the following three groups: poorly differentiated carcinoma [PDTC; group 1 (n = 27)]; papillary thyroid carcinoma with PDA [PTC with PDA; group 2 (n = 27)]; and follicular thyroid carcinoma with PDA [FTC with PDA; group 3 (n = 88)]. Clinico-pathologic profiles and outcomes were compared between the three groups. The Kaplan-Meier method was used for survival analysis. The log-rank test and Cox regression model were used to perform univariate and multivariate analyses of the factors affecting the overall survival (OS). RESULTS: The clinical profiles of the three groups were comparable except for significantly less incidence of lymph node involvement (p = 0.002) and extra-thyroidal invasion (p = 0.002) and higher incidence of distant metastases (p = 0.01) in group 3. Median follow-up period was 47.5 months, and 5- and 10-year OS were 57 and 14%, respectively. There was no difference between OS of PDTC and DTC (group 2 + 3), but group 3 patients had significantly better OS than group 2 patients. Univariate analysis revealed that tumor size (p = 0.04), extra-thyroidal invasion (p = 0.05), lateral compartment lymphadenopathy (p = 0.002), distant metastases (p = < 0.001), absence of encapsulation (p = 0.03), and > 75% PDA (p = 0.001) were associated with worse OS. Multivariate analysis revealed tumor size (p = 0.005), distant metastases (p = 0.012), lymphadenopathy (p = 0.017), TNM staging (p = < 0.001), and PDA > 75% (p = < 0.001) to be significantly associated with OS. CONCLUSION: There is no difference in the outcomes of PDTC and DTC with PDA. However, PTC patients with PDA have worse outcomes than FTC patients with PDA. Irrespective of tumor type, the presence of more than 75% PDA in DTC is associated with adverse outcomes.


Assuntos
Carcinoma/patologia , Carcinoma/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Adulto , Idoso , Carcinoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia , Resultado do Tratamento
20.
Eur Arch Otorhinolaryngol ; 276(4): 1135-1146, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30649610

RESUMO

PURPOSE: Salivary gland carcinomas (SGC) are rare malignancies and data regarding treatment outcomes stratified by histologic subtype are currently limited. This study aims to examine current, national treatment patterns and overall survival (OS) of patients with the major histologic subtypes of salivary gland carcinoma. SUBJECTS AND METHODS: A review was performed of the National Cancer Database (NCDB) of patients with confirmed diagnoses of mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, adenocarcinoma, or carcinoma ex pleomorphic receiving curative treatment between 2004 and 2014. Univariate and multivariate regression modeling were performed to identify risk factors significantly associated with overall survival (OS). Adjusted survival analyses stratified by treatment and staging were performed with the primary outcome of overall survival (OS) and were further stratified based on histologic subtype. RESULTS: The final analysis included 7342 patients [3547 men (48.3%) and 3795 women (51.7%); mean age 58.3 years (range 18-90 years)]. Mucoepidermoid carcinoma was the most common histology encountered [n = 2669 (36.4%)]. Unadjusted and adjusted analysis demonstrated improved survival with surgery and radiation therapy (RT) for adenoid cystic (HR = 0.69; p = 0.029), adenocarcinoma (HR = 0.61; p < 0.001), high-grade mucoepidermoid carcinoma (HR = 0.70; p = 0.026), and carcinoma ex pleomorphic (HR = 0.64; p = 0.028), while surgery with chemoradiation therapy (CRT) was associated with worse OS regardless of histologic subtype. The impact of advanced stage on survival varied amongst the histologic subtypes but portended the worst prognosis for patients with adenocarcinoma and carcinoma ex pleomorphic. CONCLUSIONS: The results of this NCDB review demonstrate unique treatment patterns and survival outcomes for SGC based on major histologic subtype.


Assuntos
Carcinoma , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias das Glândulas Salivares , Glândulas Salivares/patologia , Carcinoma/classificação , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Processos e Resultados (Cuidados de Saúde) , Prognóstico , Fatores de Risco , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
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