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1.
BMC Surg ; 18(Suppl 1): 114, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31074388

RESUMO

BACKGROUND: Thymic epithelial tumours (TETs) are characterized by a wide variety of biological behaviors. Radical resection and stage are strong prognostic factors. Aim of this study is to review our Single Center Experience. METHODS: One hundred and seventy-seven patients observed in the period from January 2000 to December 2016 were included in the study. Data regarding clinicopathologic features, treatment, and survival were collected. Stage-related clinical standpoints and therapeutic options were also evaluated. RESULTS: Non-surgical treatment was primarily performed in 15 (8.47%), unresectable disease was intraoperatively found in 12 cases (7.4%). The analysis of 150 patients undergoing curative surgery revealed 70 stage I TET (46.66%), 49 stage II (32.66%), 19 stage III (12.66%), 6 stage IVa (4%) and 6 stage IVb (4%) at the first hospital admission. Histology identified 12 A thymoma (8%), 38 AB (25.33%), 24 B1 (16%), 50 B2 (33.33%), 19 B3 (12.66%) and 7 carcinomas (4.66%). The mean follow up time was 84.14 months (sd = 61.68 months). Disease relapse occurred in 13 patients (8.78%) at a mean period of 78.85 months (sd = 60.87 months) after surgery. Exitus due to thymoma happened in 6 cases (4.05%) after a mean survival of 56.02 months (sd = 25.17 months). The 5-year overall survival rate was 0.94 (95%CI 0.88-0.97) and the 5-year disease-free survival rate was 0.90 (95%CI 0.83-0.94). The 5-year overall survival rates were 96.1% (95% CI, 89.9-98.5%) for the early stages and 87.4% (95% CI, 65.6-95.8%) for the advanced stages (p = 0.670). The 5-year disease-free survival rates resulted being 98.8% (95% CI, 92.3-99.8%) for the early stages and 59.8% (95% CI, 37.8-76.2%) for the advanced stages (p < 0.001). CONCLUSIONS: Advanced stage TETs are characterized by higher mortality and recurrence rates. Although technically demanding, surgery, as part of multimodality therapy, could prolong survival. Iterative surgical treatment of recurrences is a viable option for selected patients. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Perugia and Terni University Hospitals [Code T1003] and was retrospectively registered.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/patologia , Idoso , Carcinoma/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento
2.
Surg Today ; 49(8): 656-660, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134370

RESUMO

PURPOSE: We assessed the utility of the tumor doubling time (TDT) for predicting the histological type of thymic epithelial tumors. METHODS: We retrospectively reviewed 130 patients with thymic epithelial tumors who underwent computed tomography two or more times before surgery. The patients were divided into low-risk thymoma (types A, AB and B1), high-risk thymoma (types B2 and B3) and thymic carcinoma (thymic carcinoma and thymic neuroendocrine tumor) groups. In the 96 patients who showed tumor enlargement, the relationship between the histological type and the TDT of the tumor was investigated. RESULTS: The study population included 55 men and 41 women from 26 to 82 years of age. The TDT of the thymic carcinoma group (median 205 days) was significantly shorter in comparison to the low-risk thymoma (median 607 days) and high-risk thymoma (median 459 days) groups. No significant differences were observed between the low-risk thymoma and high-risk thymoma groups. When we set the cutoff time for differentiating thymic carcinoma group from thymoma at 313 days, the sensitivity and specificity were 83.8% and 82.1%, respectively. CONCLUSIONS: The TDT is a useful parameter for differentiating between thymoma and thymic carcinoma group.


Assuntos
Transformação Celular Neoplásica/patologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Estudos Retrospectivos , Timoma/diagnóstico por imagem , Timoma/patologia , Neoplasias do Timo/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X
3.
J Surg Oncol ; 119(8): 1161-1169, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919992

RESUMO

OBJECTIVES: This study aimed to compare the predictive ability between the Masaoka-Koga (M-K) staging system and the 8th TNM staging system for the recurrence of thymic epithelial tumors (TETs). In addition, a nomogram was developed on the basis of the proposed TNM classification to predict individual recurrence rate. METHODS: A retrospective study was performed on 445 patients who underwent complete resection (R0) of TETs between January 2000 and February 2013. Concordance index (C-index) was used as a statistical indicator to quantify the prediction power of the prediction models. RESULTS: In multivariate analysis, tumor stage and WHO classification were independent recurrence factors in a predictive model on the basis of M-K and TNM stage. The TNM model showed higher C-index than the M-K model (0.837 vs 0.817). The nomogram, on the basis of the TNM model, revealed a highly predictive performance, with a bootstrap-corrected C-index of 0.85 (95% CI, 0.76 to 0.93). CONCLUSIONS: A predictive model based on the 8th TNM stage was slightly better than that based on M-K stage with respect to recurrence after R0 of TETs. The proposed nomogram could be applied to estimate the individual recurrence rate and make decisions for proper surveillance.


Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Nomogramas , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
4.
Med. oral patol. oral cir. bucal (Internet) ; 24(2): e271-e280, mar. 2019. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-180653

RESUMO

Background: We aim to evaluate the presence of histological artefacts in the surgical margins of human oral fibro-epithelial hyperplasias excised with lasers of different wavelengths, and also electrosurgical scalpel and cold scalpel. Moreover, we aim to determine if some of these instruments could impair the normal histological diagnosis of these lesions. Material and Methods: We included 130 consecutive surgical samples of 80 females and 50 males (mean age of 53.82±16.55) with a histological diagnosis of an oral benign fibrous-epithelial hyperplasias. The samples were categorized into 6 groups according to the type of instrument used: CO2 laser group, diode laser group, Er:YAG laser group, Nd:YAG laser group, electrosurgical scalpel group and cold scalpel group. Histological instrument-induced changes were microscopic evaluated and related with clinical and pathological variables. Results: The instrument with highest tissue damage extension (TDE) was the electrosurgical scalpel (1002.2μm±434.92), followed by diode laser (913.73 μm±322.45), Nd:YAG (899.83μm±327.75), CO2 laser (538.37μm±170.50), Er:YAG laser (166.47μm±123.85), and at last with fewer alterations the cold scalpel group (2.36μm±7.27) (P < 0.001). The most regular incision was observed in CO2 laser group, followed by Er:YAG laser, Nd:YAG laser, electrosurgical scalpel and diode laser group with the less regular incision using cold scalpel as comparison (P < 0.001). A correlation was found between the incision score and TDE (P < 0.001). Regarding histological diagnosis, no case showed any limitation of diagnosis related with the use of any instrument evaluated. Conclusions: Our results suggest that lasers can be used for the excision of oral benign fibrous-epithelial hyperplasias, without hispathological diagnosis limitations, as long as the physical properties of each laser are known and respected. Er:YAG laser have shown to be a laser with few tissue damage extension and with good incision regularity, been a possible instrument of choice for the surgical removal of these lesions


No disponible


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Margens de Excisão , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Bucais/cirurgia , Terapia a Laser/métodos , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Bucais/patologia , Lasers de Gás/uso terapêutico , Lasers Semicondutores/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Estudos Retrospectivos
5.
Int J Mol Sci ; 20(4)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791364

RESUMO

The crosstalk between cancer cells and host cells is a crucial prerequisite for tumor growth and progression. The cells from both the innate and adaptive immune systems enter into a perverse relationship with tumor cells to create a tumor-promoting and immunosuppressive tumor microenvironment (TME). Epithelial ovarian cancer (EOC), the most lethal of all gynecological malignancies, is characterized by a unique TME that paves the way to the formation of metastasis and mediates therapy resistance through the deregulation of immune surveillance. A characteristic feature of the ovarian cancer TME is the ascites/peritoneal fluid, a malignancy-associated effusion occurring at more advanced stages, which enables the peritoneal dissemination of tumor cells and the formation of metastasis. The standard therapy for EOC involves a combination of debulking surgery and platinum-based chemotherapy. However, most patients experience disease recurrence. New therapeutic strategies are needed to improve the prognosis of patients with advanced EOC. Harnessing the body's natural immune defenses against cancer in the form of immunotherapy is emerging as an innovative treatment strategy. NK cells have attracted attention as a promising cancer immunotherapeutic target due to their ability to kill malignant cells and avoid healthy cells. Here, we will discuss the recent advances in the clinical application of NK cell immunotherapy in EOC.


Assuntos
Imunomodulação , Imunoterapia , Células Matadoras Naturais/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Biomarcadores Tumorais , Terapia Combinada , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Terapia de Alvo Molecular , Neoplasias Epiteliais e Glandulares/imunologia , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Evasão Tumoral/imunologia
6.
Pathol Int ; 69(4): 193-201, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30811747

RESUMO

Solid pseudopapillary neoplasms of the pancreas are rare neoplasms that have been shown to harbor recurrent somatic pathogenic variants in the beta-catenin gene, CTNNB1. Here, we used targeted next generation sequencing to analyze these tumors for other associated mutations. Six cases of solid pseudopapillary neoplasms were studied. DNA extracted from formalin-fixed paraffin embedded tissue blocks was analyzed using the Ion Torrent platform, with the 50-gene Ampliseq Cancer Hotspot Panel v2 (CHPv2), with further variant validation performed by Sanger sequencing. Four tumors (67%) were confirmed to harbor mutations within CTNNB1, two with c.109T > G p.(Ser37Ala) and two with c.94G > A p.(Asp32Asn). One case showed a frameshift deletion in the Adenomatous Polyposis Coli gene, APC c.3964delG p.(Glu1322Lysfs*93) with a variant allele frequency of 42.6%. Sanger sequencing on non-tumoral tissue confirmed the variant was somatic. The patient with the APC mutation developed metastasis and died. In addition to the four cases harboring CTNNB1 variants, we found a case characterized by poor outcome, showing a rare frameshift deletion in the APC gene. Since the APC product interacts with beta-catenin, APC variants may, in addition to CTNNB1, contribute to the pathogenesis of solid pseudopapillary neoplasms via the Wnt signaling pathway.


Assuntos
Neoplasias Epiteliais e Glandulares/genética , Neoplasias Pancreáticas/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Adulto , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Epiteliais e Glandulares/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Análise de Sequência de DNA
7.
Medicine (Baltimore) ; 98(3): e14066, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653119

RESUMO

RATIONALE: Ovarian mucinous tumor with malignant mural nodule is exceedingly rare. We report a case of ovarian mucinous cystic tumor associated with sarcomatous mural nodule and benign Brenner tumor and accompanied by nodular histiocytic aggregates in the greater omentum. PATIENT CONCERNS: A 60-year-old postmenopausal woman was presented with a history of one month of lower abdominal discomfort, abdominal distension, nausea, and vomiting. A physical examination revealed a hard, palpable mass with mild tenderness in her right lower abdomen. DIAGNOSES: The mucinous tumor was solid and cystic and contained benign, borderline, and malignant elements. Within the solid areas, two nodules representing pleomorphic undifferentiated sarcoma and benign Brenner tumor were identified. The diagnosis of malignant mural nodule was based on vascular invasion and marked nuclear atypia, including atypical mitoses and mitotic activity. INTERVENTIONS: Bilateral salpingo-oophorectomy and partial omentectomy were performed. Malignant cells were not found on cytologic examination of the peritoneal washing fluid. The patient underwent three cycles of chemotherapy with 210 mg paclitaxel liposome via an intravenous drip, 20 mg nedaplatin via an intravenous drip, and 80 mg nedaplatin via intraperitoneal perfusion. OUTCOMES: The patient has been followed up for 3 years without evidence of tumor recurrence and metastasis. LESSONS: Careful classification of a mural nodule is important to triage patients in need of aggressive adjuvant treatment.


Assuntos
Tumor de Brenner/patologia , Carcinoma/patologia , Cistadenoma Mucinoso/patologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Sarcoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade
8.
Adv Anat Pathol ; 26(1): 64-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30300145

RESUMO

Thymic epithelial neoplasms with foci of rhabdomyomatous differentiation are rare. A case is presented of a primary thymic epithelial neoplasm showing the features of an atypical spindle cell thymoma that contained foci of bland-appearing rhabdomyomatous cells. The histologic and immunohistochemical features of this tumor are discussed along with a review of the literature and the comments from the AMR members to the case.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Rabdomiossarcoma/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Idoso , Diferenciação Celular/fisiologia , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias Epiteliais e Glandulares/complicações , Neoplasias Epiteliais e Glandulares/diagnóstico , Rabdomiossarcoma/complicações , Timoma/complicações , Timoma/diagnóstico , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico
9.
Medicine (Baltimore) ; 97(52): e13912, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593210

RESUMO

This study aimed to evaluate the psychological distress and associated risk factors for distress among patients with gastric epithelial neoplasm undergoing endoscopic submucosal dissection (ESD).A total of 91 patients treated with ESD for gastric epithelial neoplasm between May 2015 and June 2016 were prospectively enrolled. Sociodemographic factors, psychological distress, anxiety, depression, stress, and associated risk factors for psychological distress were evaluated the day before ESD.Twenty-six (28.6%) patients were identified as patients with psychological distress. The psychological distress group had a higher female ratio and more depression and anxiety symptoms than the non-distress group. Distress was also related to stress level. A multivariate analysis showed that unmarried status (odds ratio [OR], 4.94; 95% confidence interval [CI], 1.13-21.56, P = .034), anxiety (OR, 1.24; 95% CI, 1.12-1.39, P <.001), and stress (OR, 1.06; 95% CI, 1.01-1.12, P = .011) were associated with psychological distress.An unmarried status and a high level of anxiety and stress were associated with more psychological distress in patients undergoing gastric ESD. It could be helpful to screen and proactively monitor patients with such conditions before performing gastric ESD.


Assuntos
Ressecção Endoscópica de Mucosa/psicologia , Neoplasias Epiteliais e Glandulares/psicologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Gástricas/psicologia , Neoplasias Gástricas/cirurgia , Estresse Psicológico/epidemiologia , Idoso , Ansiedade/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Neoplasias Gástricas/patologia
10.
BMJ Case Rep ; 11(1)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30567257

RESUMO

Juvenile papillomatosis is a benign epithelial proliferative tumour of young women. It was recognised as a distinct clinicopathological entity with defining criteria by Rosen et al since 1980. However, giant juvenile papillomatosis is rare. We report a case of a 14-year-old girl who presented to our institution's breast clinic with a huge right breast mass measuring 20 cm × 15 cm. She had no personal history of previous breast disease and there was no family history of breast cancer. Our initial preoperative diagnosis was of a phylloides tumour. The patient had a total excision of her breast mass which revealed florid juvenile papillomatosis at histology. This presentation highlights the clinical presentation and imaging features of juvenile papillomatosis. The classical histopathological characteristics, unusual microscopic findings and management of a huge-sized tumour in an adolescent Nigerian patient are also presented.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Neoplasias Epiteliais e Glandulares/patologia , Papiloma/patologia , Adolescente , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/cirurgia , Papiloma/diagnóstico por imagem , Papiloma/cirurgia , Resultado do Tratamento , Ultrassonografia
11.
Lung Cancer ; 126: 174-181, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30527184

RESUMO

INTRODUCTION: Primary pulmonary salivary gland-type tumors (p-SGTs) are rare, with poorly understood clinicopathological characteristics and survival. There are only few case reports or small case series, and factors associated with survival need to be identified. METHODS: A population cohort study was conducted using data from patients with histologically diagnosed primary p-SGTs in the Surveillance, Epidemiology and End Results (SEER) database between 1988 and 2013. Propensity-matching (PSM) analysis was performed to determine overall survival (OS) among patients with different pathological type. A prognostic nomogram was established, and its predictive accuracy and discriminative ability were determined by the concordance index (C-index). RESULTS: In total, 462 patients with p-SGT were identified including 315 patients with mucoepidermoid carcinoma (MEC), 139 patients with adenoid cystic carcinoma (ACC) and 8 patients with epithelial-myoepithelial carcinoma (EMC). The 1-, 5-, 10-, and 20-year OS rates of p-SGT patients were 79.6%, 68.5%, 62.7%, and 56.3%, respectively. Log-rank analysis in the matched cohort showed a significantly better prognosis for patients with p-SGT than those with non-SGT lung adenocarcinoma (P < 0.001). Cancer-directed surgery significantly improved median OS (P < 0.01). Radiotherapy did not prolong OS (P = 0.28, P = 0.70). Multivariate Cox analysis showed that older age (>58 years), larger lesions, metastases and poor differentiation were independent prognostic factors for worse survival, while cancer-directed surgery was an independent protective factor (HR = 0.18, 95% CI 0.11-0.29). Patients with MEC were younger with smaller tumors, lower ratio of lymph node or distant metastases as well as earlier stage than those with ACC, and there was no significant difference in survival between MEC and ACC patients. Six independent prognostic factors were identified and incorporated into the nomogram (C-index for survival = 0.88; 95% CI 0.84-0.92). CONCLUSION: Pulmonary SGTs are uncommon, and older age, larger lesions, metastases, poor differentiation and cancer-directed surgery are independently associated with prognosis. Early detection and diagnosis increase OS for these patients.


Assuntos
Carcinoma Adenoide Cístico/patologia , Carcinoma Mucoepidermoide/patologia , Neoplasias Pulmonares/patologia , Neoplasias Epiteliais e Glandulares/patologia , Glândulas Salivares , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Análise de Sobrevida
12.
Anticancer Res ; 38(11): 6507-6511, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396979

RESUMO

BACKGROUND: Two studies have found primary ovarian carcinomas in stage I disease to be larger than those in stage III. Thus, these stages may represent different tumor entities. MATERIALS AND METHODS: The clinical data from 553 patients operated on between 1985 and 2012 for epithelial ovarian cancer were retrospectively analyzed. RESULTS: Primary lesions including invasive, borderline and benign components were significantly larger in stage I compared to stage III disease (p<0.001). However, the maximum diameter of invasive components in those with stage III disease were significantly larger than in those with stage I disease (p=0.001). The size of the invasive component was not associated with the largest size of intraperitoneal metastasis. CONCLUSION: We were only, in part, able to reproduce the data from the two smaller published studies. The prognosis of patients with stage III disease strongly depends on the size of intraperitoneal metastases.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
13.
Medicine (Baltimore) ; 97(39): e12536, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30278545

RESUMO

Since endoscopic submucosal dissection (ESD) has been accepted as the treatment of choice for early gastric cancer (EGC) without risk of lymph node metastasis, synchronous gastric epithelial neoplasia is no longer rare in the clinical practice. Knowledge about the characteristics associated with synchronous gastric epithelial neoplasia is of great importance to prevent delayed diagnosis.Between November 2008 and December 2014, a retrospective study was conducted in a single tertiary referral hospital. Consecutive patients who underwent ESD due to EGC or high-grade dysplasia were analyzed to evaluate the incidence of synchronous gastric epithelial neoplasia and the factors associated with synchronous and overlooked synchronous lesions.A total of 488 patients were analyzed in this study. Synchronous lesions were found in 59 patients (12.1%) during the mean 37.7 months of follow-up. Among 77 synchronous lesions, 25 lesions (32.4%) were overlooked at the time of initial ESD. Age of ≥ 65 years, moderate to severe endoscopic atrophic gastritis, and elevated morphology of primary lesions were associated with synchronous gastric epithelial neoplasia. An important factor associated with overlooked lesions is the non-elevated morphology of lesions.Careful endoscopic examination of the whole stomach is necessary in patients who are older and who have moderate to severe atrophic gastritis and elevated morphology of lesions to prevent delayed diagnosis of synchronous gastric epithelial neoplasia, especially non-elevated lesions.


Assuntos
Erros de Diagnóstico , Ressecção Endoscópica de Mucosa , Neoplasias Epiteliais e Glandulares , Neoplasias Primárias Múltiplas , Neoplasias Gástricas , Idoso , Erros de Diagnóstico/prevenção & controle , Erros de Diagnóstico/estatística & dados numéricos , Intervenção Médica Precoce/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Feminino , Seguimentos , Gastrite Atrófica/epidemiologia , Humanos , Incidência , Masculino , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
14.
Cell Physiol Biochem ; 50(1): 214-232, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30336465

RESUMO

The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians. Accumulating evidence suggests the mechanism for the decision of ovarian surface epithelial stem cells to undergo either neo-oogenesis or ovarian cancer transformation may comprise both internal and external factors. Here, we review recent progress on how the internal factors, including genes, signaling pathways and lncRNA: OSE stem cells mediate the development and progression of ovarian cancer through various genes such as p53, KRAS, BRAF, and PTEN, and mutations in PIK3CA, and through various signaling pathways, including TGF-B pathway, Wnt signaling pathway, Notch signaling pathway, NF-kB signal transducer and transcriptional activator 3 (STAT3) pathway and Hedghog (HH) pathway. A series of expressions of IncRNA have changed in epithelial ovarian cancer tissues and cell lines compared to normal ovarian tissues and cell lines. As well as external factors, including incessant ovulation, gonadotropin and chronicinflammation: Frequent ovulation, without long-term dormancy, increases the risk of illness, because repeated rupture and repair at the ovulation site provides an opportunity for the accumulation of genetic aberrations; FSH affects all aspects of ovarian cancer metastasis, such as inhibition of apoptosis, through Induction of increased expression of VEGFA (VEGF) to support tumor growth, promote vascular growth, and possibly alter certain oncogenic pathways, thereby promoting proliferation and invasive phenotypic inflammation contributes to tumorigenesis, which help determine whether OSCs undergo neo-oogenesis or ovarian tumorigenesis. Understanding this issue is critical for developing novel strategies for premature ovarian failure and ovarian cancer prevention and therapy.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Células-Tronco Neoplásicas/metabolismo , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário , Transformação Celular Neoplásica , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Cancer Immunol Immunother ; 67(11): 1753-1765, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30167862

RESUMO

Epithelial ovarian cancer (EOC) is the most lethal of all gynecological malignancies in the UK. Recent evidence has shown that there is potential for immunotherapies to be successful in treating this cancer. We have previously shown the effective application of combinations of traditional chemotherapy and CAR (chimeric antigen receptor) T cell immunotherapy in in vitro and in vivo models of EOC. Platinum-based chemotherapy synergizes with ErbB-targeted CAR T cells (named T4), significantly reducing tumor burden in mice. Here, we show that paclitaxel synergizes with T4 as well, and look into the mechanisms behind the effectiveness of chemo-immunotherapy in our system. Impairment of caspase activity using pan-caspase inhibitor Z-VAD reveals this chemotherapy-induced apoptotic pathway as an essential factor in driving synergy. Mannose-6-phosphate receptor-mediated autophagy and the arrest of cell cycle in G2/M are also shown to be induced by chemotherapy and significantly contributing to the synergy. Increased expression of PD-1 on T4 CAR T cells occurred when these were in culture with ovarian tumor cells; on the other hand, EOC cell lines showed increased PD-L1 expression following chemotherapy treatment. These findings provided a rationale to look into testing PD-1 blockade in combination with paclitaxel and T4 immunotherapy. Combination of these three agents in mice resulted in significant reduction of tumor burden, compared to each treatment alone. In conclusion, the mechanism driving synergy in chemo-immunotherapy of EOC is multifactorial. A deeper understanding of such process is needed to better design combination therapies and carefully stratify patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Autofagia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sinergismo Farmacológico , Imunoterapia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Combinação de Medicamentos , Feminino , Humanos , Camundongos , Camundongos SCID , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/imunologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Paclitaxel/administração & dosagem , Células Tumorais Cultivadas
16.
J Surg Oncol ; 118(4): 687-693, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30206937

RESUMO

BACKGROUND AND OBJECTIVES: The optimum treatment strategy for patients with unresectable advanced epithelial ovarian cancer is controversial. This study examined bevacizumab combined with neoadjuvant chemotherapy (NAC; paclitaxel plus carboplatin), followed by interval debulking surgery (IDS), for these patients. METHODS: In a prospective nonrandomized study, newly diagnosed patients received four cycles of NAC (three cycles combined with bevacizumab), followed by IDS. The primary endpoint was the complete resection rate at IDS. Secondary endpoints were the NAC response rate, adverse events during NAC, and perioperative complications. RESULTS: Twenty-three patients were enrolled. The complete resection rate at IDS was 60.9% (95% confidence intervals [CI]: 38.5% to 80.3%). The NAC response rate was 86.9% (95% CI: 66.4% to 97.2%). Adverse events ≥ grade 3 during NAC were neutropenia (78.3%), anemia (52.2%), hypertension (17.4%), and proteinuria (8.7%). There was no thromboembolism or gastrointestinal perforation. Grade 2 complications of IDS included lymphatic complications (13.6%), infections (9.1%), ileus (4.5%), and wound dehiscence (4.5%). There were no thromboembolic complications, fistula/abscess, or perforation/anastomotic leak, and no complications ≥ grade 3. CONCLUSIONS: In Japanese patients with advanced ovarian cancer, bevacizumab + NAC followed by IDS is an acceptable strategy. Further investigation of its prognostic effect is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Terapia Neoadjuvante , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Terapia Combinada , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Prognóstico , Estudos Prospectivos , Segurança
17.
Gynecol Oncol ; 151(2): 287-293, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30185381

RESUMO

OBJECTIVE: Epidurals are associated with improved outcomes in some solid tumors, presumably due to their effect on surgical stress response. There are limited data on the prognostic significance of epidural anesthesia in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer. We sought to assess the impact of epidural anesthesia on the survival outcomes of patients undergoing PDS for advanced ovarian cancer. METHODS: In this retrospective study, consecutive patients with stage IIIB-IV epithelial ovarian, fallopian tube, or peritoneal carcinoma who underwent PDS at our institution from 01/2005-12/2013 were identified. Progression-free survival (PFS) and overall survival (OS) with regard to epidural use were analyzed. RESULTS: Of 648 patients, 435 received an epidural and 213 did not. Patients in the former group were more likely to have higher stage disease (stage IV disease, 26% vs. 16%, respectively; P = .005), carcinomatosis (87% vs. 80%, respectively; P = .027), and bulky upper abdominal disease (66% vs. 58%, respectively; P = .046). Complete gross resection was achieved in 48% and 32%, respectively (P < .001). For the epidural vs. non-epidural groups, median PFS was 20.8 months and 13.9 months, respectively (P = .021); median OS was 62.4 months and 41.9 months, respectively (P < .001). After controlling for confounding factors, including residual disease, epidural use was independently associated with a decreased risk of progression (HR = 1.327; 95% CI, 1.066-1.653) and death (HR = 1.588; 95% CI, 1.224-2.06). CONCLUSIONS: Perioperative epidural use was independently associated with improved PFS and OS in these patients. Epidural anesthesia at the time of PDS may be warranted in this setting.


Assuntos
Anestesia Epidural/métodos , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução/métodos , Intervalo Livre de Doença , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Assistência Perioperatória/métodos , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
18.
Gynecol Oncol ; 151(2): 345-355, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30201235

RESUMO

PURPOSE: This investigation was aimed at extrapolating whether and how lncRNA GAS5, miR-196a-5p and HOXA5 altered progression of ovarian cancer (OA). METHOD: Totally 195 pairs of OA tissues and adjacent normal tissues were collected. Also si-GAS5, pcDNA-GAS5, miR-196a-5p mimic, miR-196a-5p inhibitor and negative control (NC) were, respectively, transfected into OA cells. Besides, dual-luciferase reporter gene assay was performed to validate the targeted relationships between GAS5 and miR-196a-5p, as well as between miR-196a-5p and HOXA5. The impacts of GAS5, miR-196a-5p and HOXA5 on viability, proliferation and apoptosis of OA cells were appraised via conduction of colony formation assay, MTT assay and flow cytometry assay. RESULT: Lower GAS5 expression and higher miR-196a-5p expression were associated with larger tumor size (≥5 cm) and more advanced FIGO stage (III-IV) of OA patients (P < 0.05). Transfection of si-GAS5, miR-196a-5p mimic or si-HOXA5 conferred OA cells with stronger viability, faster proliferation and smaller percentage of apoptosis (P < 0.05). After injecting mice models with si-GAS5, miR-196a-5p mimic or si-HOXA5, a larger tumor size was also observed within the rats (P < 0.05). GAS5 was indicated to directly target miR-196a-5p and modify its expression, and the targeted relationship also seemed to exist between miR-196a-5p and HOXA5 (P < 0.05). The HOXA5 was found to reverse the effects imposed by miR-196a-5p on viability, proliferation and apoptosis of OA cells (P < 0.05). CONCLUSION: LncRNA GAS5 depressed OA development by targeting miR-196a-5p and thereby down-regulating HOXA5 expression, providing substance for developing lncRNA-based strategies to treat OA.


Assuntos
Proteínas de Homeodomínio/biossíntese , MicroRNAs/biossíntese , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/biossíntese , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
19.
Gynecol Oncol ; 151(2): 337-344, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30190114

RESUMO

OBJECTIVE: Paclitaxel, a microtubule inhibitor, is subject to tumor resistance while treating high-grade serous ovarian and uterine cancer. This study aims to directly compare the effects of SQ1274, a novel microtubule inhibitor that binds to the colchicine-binding site on tubulin, and paclitaxel in high-grade serous ovarian and uterine cancer cell lines both in vitro and in vivo. METHODS: We assessed the sensitivity of ovarian (OVCAR8) and uterine (ARK1) cancer cell lines to SQ1274 and paclitaxel using XTT assays. We used western blot and quantitative real-time PCR to analyze changes in AXL RNA and protein expression by SQ1274 and paclitaxel. Differences in cell-cycle arrest and apoptosis were investigated using flow cytometry. Finally, we treated ovarian and uterine xenograft models with vehicle, paclitaxel, or SQ1274. RESULTS: First, we demonstrate that SQ1274 has a much lower IC50 than paclitaxel in both ARK1 (1.26 nM vs. 15.34 nM, respectively) and OVCAR8 (1.34 nM vs. 10.29 nM, respectively) cancer cell lines. Second, we show SQ1274 decreases both RNA and protein expression of AXL. Third, we show that SQ1274 causes increased cell-cycle arrest and apoptosis compared to paclitaxel. Finally, we report that SQ1274 more effectively inhibits tumor growth in vivo compared to paclitaxel. CONCLUSIONS: SQ1274 presents as a viable alternative to paclitaxel for treating ovarian and uterine cancer. This study supports the development of SQ1274 as a chemotherapeutic to treat ovarian and uterine cancer.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Moduladores de Tubulina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Epitelial do Ovário , Ciclo Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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