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1.
Lancet Oncol ; 21(10): 1331-1340, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002437

RESUMO

BACKGROUND: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy. METHODS: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652. FINDINGS: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]). INTERPRETATION: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity. FUNDING: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.


Assuntos
Adenocarcinoma/radioterapia , Prostatectomia , Neoplasias da Próstata/radioterapia , Terapia de Salvação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Austrália , Progressão da Doença , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Humanos , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Doenças Urogenitais Masculinas/etiologia , Pessoa de Meia-Idade , Nova Zelândia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação/efeitos adversos , Resultado do Tratamento
2.
Lancet Oncol ; 21(10): 1341-1352, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002438

RESUMO

BACKGROUND: Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. METHODS: GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. FINDINGS: Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50-100), 74 months (47-100) in the adjuvant radiotherapy group and 78 months (52-101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86-95) in the adjuvant radiotherapy group and 90% (85-94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48-1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). INTERPRETATION: Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. FUNDING: French Health Ministry and Ipsen.


Assuntos
Adenocarcinoma/radioterapia , Antagonistas de Androgênios/administração & dosagem , Prostatectomia , Neoplasias da Próstata/radioterapia , Terapia de Salvação , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Progressão da Doença , França , Humanos , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Doenças Urogenitais Masculinas/etiologia , Sobremedicalização/prevenção & controle , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
3.
Zhonghua Fu Chan Ke Za Zhi ; 55(9): 600-608, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32957748

RESUMO

Objective: To investigate the efficacy and safety of laparoscopic radical hysterectomy for early cervical adenocarcinoma. Methods: A retrospective observational study was performed by reviewing medical records of patients with staging Ⅰb1-Ⅱa2 International Federation of Gynecology and Obstetrics (FIGO, 2009) cervical adenocarcinoma who underwent laparoscopic or abdominal radical hysterectomy from 2007 to 2017 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. The difference among clinicopathologic characteristics, surgery-related parameters and complications, and prognosis were analyzed between the laparoscopic group and abdominal group. Results: Two hundreds and ninety-three patients were included with 88 cases in laparoscopic group and 205 cases in abdominal group. (1) There was no significant difference in clinicopathologic characteristics between the two groups (all P>0.05), including age, body mass index, menopause status, history of abdominal surgery, clinical stage, tumor diameter, neoadjuvant chemotherapy, differentiation, lymph-vascular space invasion, positive of surgical margin, parametrial invasion, and lymph node metastasis. But the abdominal group showed a higher proportion of deep stromal invasion (38.5% vs 25.0%, P<0.05). No significant difference was observed between two groups with number of lymph nodes resected, urinary catheter retention, short-term surgical complications (including ureteral injury, ileus, infection, hydronephrosis and poor wound healing), and long-term complications (including voiding dysfunction, defecation dysfunction and lower limb edema; all P>0.05). (2) The laparoscopic group was significantly associated with a longer operation time [(260±51) minutes vs (244±53) minutes, P<0.05], but less bleeding (100 ml vs 300 ml, P<0.01), shorter hospital stay [(13±5) days vs (16±8) days, P<0.01] and lower incidence of lymphedema (12.5% vs 27.8%, P<0.01). (3) The 5-year progression-free survival (PFS; 85.7% vs 86.4%, P=0.971) and 5-year overall survival (OS; 91.4% vs 93.0%, P=0.657) of laparoscopic group were comparable to that of abdominal group. (4) Multivariate analysis demonstrated that lymph node metastasis (HR=2.44, 95%CI: 1.16-5.15, P=0.019) was independent poor prognostic factors related to PFS, while adenosquamous carcinoma (HR=2.54, 95%CI: 1.02-6.35, P=0.046), lymph-vascular space invasion (HR=3.86, 95%CI: 1.60-9.33, P=0.003) and lymph node metastasis (HR=5.92, 95%CI: 2.45-14.34, P<0.01) were independent poor prognostic factors related to OS. The laparoscopy surgery was not an independent poor prognostic factor (P=0.396). Conclusion: The laparoscopic radical hysterectomy for early cervical adenocarcinoma has comparable prognosis to abdominal radical hysterectomy with a higher surgery quality.


Assuntos
Adenocarcinoma/cirurgia , Histerectomia/efeitos adversos , Laparoscopia , Excisão de Linfonodo , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
4.
Tumour Biol ; 42(9): 1010428320957506, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32914709

RESUMO

The development of the multidrug resistance phenotype is one of the major challenges faced in the treatment of cancer. The multidrug resistance phenotype is characterized by cross-resistance to drugs with different chemical structures and mechanisms of action. In this work, we hypothesized that the acquisition of resistance in cancer is accompanied by activation of the epithelial-to-mesenchymal transition process, where the tumor cell acquires a more mobile and invasive phenotype; a fundamental step in tumor progression and in promoting the invasion of other organs and tissues. In addition, it is known that atypical glycosylations are characteristic of tumor cells, being used as biomarkers. We believe that the acquisition of the multidrug resistance phenotype and the activation of epithelial-to-mesenchymal transition provoke alterations in the cell glycophenotype, which can be used as glycomarkers for chemoresistance and epithelial-to-mesenchymal transition processes. Herein, we induced the multidrug resistance phenotype in the PC-3 human prostate adenocarcinoma line through the continuous treatment with the drug paclitaxel. Our results showed that the induced cell multidrug resistance phenotype (1) acquired a mixed profile between epithelial and mesenchymal phenotypes and (2) modified the glycophenotype, showing an increase in the level of sialylation and in the number of branched glycans. Both mechanisms are described as indicators of poor prognosis.


Assuntos
Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Paclitaxel/farmacologia , Adenocarcinoma/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Glicosilação , Humanos , Células PC-3 , Fenótipo
5.
Anticancer Res ; 40(10): 5411-5416, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988861

RESUMO

BACKGROUND: Patients with inflammatory bowel disease have markedly increased risk for developing colitis-associated colorectal adenocarcinoma (CAC). There is no established prognostic biomarker for CAC. MATERIALS AND METHODS: A retrospective study was performed on a cohort of 57 CACs. Expression of caudal type homeobox transcription factor 2 (CDX2) and YES-associated protein 1 (YAP1) expression was correlated with clinicodemographic and histopathological features. RESULTS: Neither YAP1 nor CDX2 expression alone was significantly associated with tumor invasion beyond the muscularis propria or lymph node status. However, a subgroup of CAC with double negativity for expression of YAP1 and CDX2 was more frequently found in younger patients, and more frequently associated with higher pathological tumor stage and nodal metastasis. Furthermore, a positive correlation between CDX2 and YAP1 expression was identified in CAC and sporadic colorectal adenocarcinoma. CONCLUSION: Our study demonstrates that double negativity for expression of YAP1 and CDX2 defines a subgroup of CAC with early onset and aggressive clinical features.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Fator de Transcrição CDX2/genética , Colite/genética , Neoplasias Colorretais/genética , Fatores de Transcrição/genética , Adenocarcinoma/complicações , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Biomarcadores Tumorais/genética , Colite/complicações , Colite/patologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Medicine (Baltimore) ; 99(35): e21895, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871920

RESUMO

MicroRNAs (miRNAs) refers to a small, short non-coding RNA of endogenous class. They have shown to have an increasingly altered expression in many types of cancer, including colorectal cancer (CRC).In the present study, miRNA TaqManMGB and qRT-PCR was used to quantify the expression and clinical significance of 3 mature human miRNA in 82 pairs of colorectal adenocarcinoma tissues and normal adjacent tissue samples (NATS) collected from patients of the south-east part of Romania. Differences between CRC and NATS were analyzed using Wilcoxon test, while correlations between miRNAs expression levels and clinicopathological features were examined using non-parametric tests. In addition, the ability of selected miRNAs to function as biomarkers and, as potential indicators in CRC prognosis was also examined.When the miRNA expression was compared in CRC related NATS, miR-143, and miR-145 were significantly underexpressed (4.99 ±â€Š-1.02 vs -5.66 ±â€Š-1.66, P < .001; -4.85 ±â€Š-0.59 vs -9.27 ±â€Š-1.51, P < .001, respectively), while the pattern of miR-92a was significantly overexpressed (-5.55 ±â€Š-2.83 vs -4.92 ±â€Š-2.44, P < .001). Moreover, the expression levels of selected miRNAs were identified to be correlated with gradual increases in fold change expression with the depth of tumor invasion, lymph node invasion, and maximal increases with distant metastasis. Furthermore, the receiver operating characteristic analysis demonstrated that potential diagnostic of miR-143, miR-145, and miR-92a in discriminating CRC from NATS, with the area under the curve of 0.74, 0.85, and 0.84 respectively. The Kaplan-Meier and the log-rank test showed that a high level of miR-92a and low levels of miR-143 and miR-145 predicted poor survival rate in our cohorts.In conclusion, we can summarize that miR-145 and miR-143 are decreased, while miR-92 is increased in CRC compared to NATS, and associated with different stages of CRC pathogenesis. Thus, the expression of selected miRNAs can represent potential diagnostic and prognostic tools in patients with CRC from Romania.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , MicroRNAs/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Área Sob a Curva , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Romênia , Transcriptoma
7.
Br J Radiol ; 93(1114): 20200543, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877210

RESUMO

OBJECTIVES: To evaluate interobserver agreement for T2 weighted (T2W) and diffusion-weighted MRI (DW-MRI) contours of locally advanced rectal cancer (LARC); and to evaluate manual and semi-automated delineations of restricted diffusion tumour subvolumes. METHODS: 20 cases of LARC were reviewed by 2 radiation oncologists and 2 radiologists. Contours of gross tumour volume (GTV) on T2W, DW-MRI and co-registered T2W/DW-MRI were independently delineated and compared using Dice Similarity Coefficient (DSC), mean distance to agreement (MDA) and other metrics of interobserver agreement. Restricted diffusion subvolumes within GTVs were manually delineated and compared to semi-automatically generated contours corresponding to intratumoral apparent diffusion coefficient (ADC) centile values. RESULTS: Observers were able to delineate subvolumes of restricted diffusion with moderate agreement (DSC 0.666, MDA 1.92 mm). Semi-automated segmentation based on the 40th centile intratumoral ADC value demonstrated moderate average agreement with consensus delineations (DSC 0.581, MDA 2.44 mm), with errors noted in image registration and luminal variation between acquisitions. A small validation set of four cases with optimised planning MRI demonstrated improvement (DSC 0.669, MDA 1.91 mm). CONCLUSION: Contours based on co-registered T2W and DW-MRI could be used for delineation of biologically relevant tumour subvolumes. Semi-automated delineation based on patient-specific intratumoral ADC thresholds may standardise subvolume delineation if registration between acquisitions is sufficiently accurate. ADVANCES IN KNOWLEDGE: This is the first study to evaluate the feasibility of semi-automated diffusion-based subvolume delineation in LARC. This approach could be applied to dose escalation or 'dose painting' protocols to improve delineation reproducibility.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Retais/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Competência Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Variações Dependentes do Observador , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carga Tumoral
8.
Anticancer Res ; 40(10): 5679-5685, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988893

RESUMO

BACKGROUND/AIM: The presence of circulating tumor cells (CTC) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. PATIENTS AND METHODS: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma (EAC). CTCs were captured by size-based filtration (ScreenCell®), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. RESULTS: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% (n=81) of the 117 specimens; small CTCs were observed most frequently (59%; n=69), followed by large CTCs (40%; n=47) and circulating cancer-associated macrophage-like cells (CAMLs; 34.2%, n=40). Clusters were rather rare (12%; n=14). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. CONCLUSION: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias Esofágicas/sangue , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/patologia , Contagem de Células , Separação Celular , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/patologia , Prognóstico
9.
Anticancer Res ; 40(10): 5765-5776, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988904

RESUMO

BACKGROUND/AIM: We evaluated the safety, feasibility, and preliminary efficacy of Wilms tumor gene 1 (WT1) peptide and Mucin 1 (MUC1)-pulsed dendritic cell (DC) (WT1/MUC1-DC) vaccination as an adjuvant immunotherapy for surgically resectable pancreatic ductal adenocarcinoma (PDA) patients. PATIENTS AND METHODS: Eligible patients were administered WT1/MUC1-DC vaccination at least seven times every 2 weeks with concomitant adjuvant chemotherapy after surgical resection of PDA. RESULTS: Ten patients were enrolled and no Grade 2 or higher toxicities were associated with DC vaccination. The estimated overall survival (OS) and relapse-free survival (RFS) at 3-years from the time of surgical resection were 77.8% and 35.0%, respectively. Immunohistochemical analysis suggested a possible relationship between induction of WT1-specific cytotoxic T lymphocyte after DC vaccination and higher infiltration of CD3/CD4/CD8 lymphocytes in tumor tissues. CONCLUSION: WT1/MUC1-DC vaccination in the adjuvant setting was safe and well-tolerated in PDA patients after tumor resection. A large-scale prospective study is warranted to evaluate the clinical benefit of this modality.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Mucina-1/genética , Proteínas WT1/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante/métodos , Células Dendríticas/imunologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Mucina-1/uso terapêutico , Proteínas WT1/uso terapêutico
10.
Medicine (Baltimore) ; 99(37): e22170, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925784

RESUMO

BACKGROUND: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. METHODS: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. RESULTS: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. CONCLUSIONS: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Fator Regulador 1 de Interferon/imunologia , Linfócitos T/imunologia , Biomarcadores Tumorais , Linfócitos T CD8-Positivos/metabolismo , Bases de Dados Genéticas , Células Dendríticas/metabolismo , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/imunologia , Estadiamento de Neoplasias , Prognóstico , Microambiente Tumoral
12.
PLoS One ; 15(8): e0236896, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745119

RESUMO

Single-stranded DNA binding protein 2 (SSBP2) is ubiquitously expressed, with several studies reporting it to be a tumor suppressor. We investigated SSBP2 expression and its clinicopathological significance in gastric cancer. SSBP2 expression was examined by immunohistochemistry in 539 gastric cancer sections. The cases were divided into three subtypes, namely, Epstein-Barr virus-associated (EBV), microsatellite unstable, and others (microsatellite stable and EBV negative), based on the molecular classification of The Cancer Genome Atlas (TCGA). Cases were also divided into two subgroups according to the amplification status of human epidermal growth factor receptor 2 (HER2). Most cases showed SSBP2 positivity, and only 24 (4.5%) cases displayed negative nuclear expression. Loss of nuclear expression correlated significantly with high pT category (P = 0.001), nodal metastasis (P = 0.002), and stage of progression (P = 0.005), with no correlation between molecular characteristics and SSBP2 expression. All HER2 amplification cases displayed positive SSBP2 expression. Negative SSBP2 cases showed significantly shorter recurrence-free survival (RFS) compared to positive SSBP2 cases (P = 0.008). Loss of nuclear expression of SSBP2 was significantly associated with shorter RFS in the microsatellite stable and EBV negative groups (P = 0.002), as well as the HER2 negative group (P = 0.007). However, there were no statistically significant differences in multivariate analyses. Loss of nuclear expression of SSBP2 was a poor prognostic factor, associated with stage of progression and recurrence, and showed no significant difference in molecular characteristics, including TCGA subtype and HER2 status.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Feminino , Expressão Gênica , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
PLoS One ; 15(8): e0236580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756609

RESUMO

Lung cancer is generally treated with conventional therapies, including chemotherapy and radiation. These methods, however, are not specific to cancer cells and instead attack every cell present, including normal cells. Personalized therapies provide more efficient treatment options as they target the individual's genetic makeup. The goal of this study was to identify the frequency of causal genetic mutations across a variety of lung cancer subtypes in the earlier stages. 833 samples of non-small cell lung cancer from 799 patients who received resection of their lung cancer, were selected for molecular analysis of six known mutations, including EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK. A SNaPshot assay was used for point mutations and fragment analysis searched for insertions and deletions. ALK was evaluated by IHC +/- FISH. Statistical analysis was performed to determine correlations between molecular and clinical/pathological patient data. None of the tested variants were identified in most (66.15%) of cases. The observed frequencies among the total samples vs. only the adenocarcinoma cases were notable different, with the highest frequency being the KRAS mutation (24.49% vs. 35.55%), followed by EGFR (6.96% vs. 10.23%), PIK3CA (1.20% vs. 0.9%), BRAF (1.08% vs. 1.62%), ALK (0.12% vs. 0.18%), while the lowest was the HER2 mutation (0% for both). The statistical analysis yielded correlations between presence of a mutation with gender, cancer type, vascular invasion and smoking history. The outcome of this study will provide data that helps stratify patient prognosis and supports development of more precise treatments, resulting in improved outcomes for future lung cancer patients.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença , Prognóstico , Adenocarcinoma/classificação , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética
14.
PLoS One ; 15(8): e0238120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833992

RESUMO

PURPOSE: Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to determine molecular localization of epidermal growth factor receptor (EGFR) and the possibility of EGFR as a biomarker for the management of conjunctival SCC. METHODS: In this retrospective study, we performed immunohistochemistry to evaluate EGFR expression and localization in tumor cells, EGFR mutation-specific expression (E746-A750del and L858R), and human papillomavirus expression in a series of 29 conjunctival SCCs. RESULTS: All 29 tumors in our cohort were EGFR positive (100%). Twenty-one of 29 tumors (72%) showed focal EGFR staining, and seven (28%) showed diffuse EGFR staining. In addition, we calculated the percentages of the two most important mutations in EGFR (exon 19 746-A750del (8/29, 27.5%), exon 21 (L858R mutant (2/29, 6.8%)) in conjunctival SCCs. We observed that the translocation of EGFR from the membrane into the cytoplasm was related to clinical prognosis, as we detected correlations between EGFR cytoplasmic staining and final orbital exenteration and between decreased EGFR membrane staining and progression-free survival. CONCLUSIONS: EGFR is important in the pathology of ocular surface squamous neoplasia including SCC and is a prognostic factor. Increased understanding of EGFR mutations may have important implications for future treatment options.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias da Túnica Conjuntiva/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Estudos de Coortes , Neoplasias da Túnica Conjuntiva/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
15.
Medicine (Baltimore) ; 99(29): e20865, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702827

RESUMO

RATIONALE: Synchronous pulmonary lymphoma and carcinoma is relatively rare. And synchronous pulmonary lymphoma and adenocarcinoma in the same site is extremely rare. PATIENT CONCERNS: We presented a 69-year-old female with a tumor mass in right upper lung. DIAGNOSIS: Pathological and immunohistochemical findings revealed lung adenocarcinoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. INTERVENTIONS: The patient received thoracoscopic guided right upper lobectomy and focal lymph node dissection after systemic anesthesia. Besides, 6 cycles of chemotherapy were given based on meprednisone, gemcitabine and cisplatin in local hospital. OUTCOMES: In the 12-month follow-up, the patient was still alive with no local recurrence, metastasis and lymph node involvement. LESSON: A comprehensive literature research was performed, and 6 cases of synchronous pulmonary lymphoma and adenocarcinoma in the same site and 10 cases in different sites were identified since 2000. Most patients with synchronous pulmonary lymphoma and carcinoma were middle-aged and elderly with the median age was 64 years presenting a male predisposition. The most frequent type of primary pulmonary lymphoma was B-cell non Hodgkin lymphoma, especially mucosa-associated lymphoid tissue lymphoma, and the lung cancer is predominantly adenocarcinoma.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Primárias Múltiplas/patologia , Adenocarcinoma/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/terapia , Excisão de Linfonodo , Linfoma de Zona Marginal Tipo Células B/terapia , Neoplasias Primárias Múltiplas/terapia , Pneumonectomia
18.
Medicine (Baltimore) ; 99(27): e20897, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629680

RESUMO

INTRODUCTION: Acrometastasis is infrequent and generally indicates a wider spread of metastasis with poor prognosis. The diagnosis is challenging, as it might mimic an infectious, inflammatory, or metabolic disease. Acrometastasis are most commonly found in patients with lung, gastrointestinal, kidney, and breast cancer. Only 3 cases of cervical cancer associated with hand metastasis have been reported in the literature. PATIENT CONCERNS: Herein, we report a 58-year-old patient with locally advanced cervical cancer and recurrence in the right thumb as presentation of widespread disseminated disease. She initially presented with adenocarcinoma of the uterine cervix and was treated with concurrent chemoradiation followed by high-dose rate brachytherapy. Six months later, she developed an insidious onset of pain and swelling in the right thumb, erythema, and edema, mimicking cellulitis. DIAGNOSIS: A biopsy of the soft tissues of the thumb was performed, and the histopathology indicated metastasis of adenocarcinoma to the bone and soft tissues. INTERVENTIONS AND OUTCOMES: The patient rejected further treatment and died of progressive disease 4 months after the diagnosis of the recurrence. CONCLUSION: Metastases in unusual sites are a diagnostic challenge, and there is no standardized treatment. Timely diagnosis and treatment can improve the prognosis of these patients and might preserve their quality of life.


Assuntos
Mãos/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/terapia
19.
Medicine (Baltimore) ; 99(27): e20941, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629697

RESUMO

RATIONALE: Tailgut cyst (TGC) is a rare congenital disease that originates from residues of the tail intestine during the embryonic period. Most TGCs are benign lesions and the malignant transition is very rare. PATIENT CONCERNS: A 50-year-old woman attended our department complaining of defecation difficulty for more than 2 months. She reported irregular defecation with a small amount of liquid stool, 3 to 4 times per day. DIAGNOSIS: Biochemical analysis showed high levels of carcinoembryonic antigen (79.89 ng/mL; normal, 0-3 ng/mL) and carbohydrate antigen 199 (57.60 U/mL; normal, 0-35 U/mL). Abdominal computer tomography and magnetic resonance imaging showed a large cystic mass with enhanced signals. Post-surgical histopathology indicated that the mass was a TGC with adenocarcinoma transition. INTERVENTIONS: The cyst was completely resected. Symptomatic treatment was further performed, and the patient recovered well. LESSONS: We reported a rare case of a large TGC with adenocarcinoma transition. CT, MRI, and histopathology are important to diagnose TGC. Complete surgical resection is the first choice to treat TGC.


Assuntos
Adenocarcinoma/diagnóstico , Cistos/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Retais/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Cistos/diagnóstico por imagem , Cistos/patologia , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Tomografia Computadorizada por Raios X
20.
Anticancer Res ; 40(7): 4029-4032, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620648

RESUMO

The synchronous diagnosis of two or more primary malignancies in a patient is overall rare. This is a case report of a 70-year-old female with a history of skin squamous cell carcinoma presenting with occult hematochezia. Colonoscopy and biopsy results confirmed a microsatellite stable (MMS) adenocarcinoma in the ascending colon, and subsequent computed tomography (CT) scans identified a 3.2 cm right colonic mass and a 5.0 cm mass in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) confirmed the presence of pancreatic ductal adenocarcinoma (PDAC). The patient underwent neo-adjuvant FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin) chemotherapy prior to the simultaneous distal pancreatectomy and right hemicolectomy for both pancreatic and colonic tumors. The pathology diagnoses included moderately differentiated pancreatic ductal carcinoma (PDAC) with histiocyte-like features (tumor stage: ypT3N1M0) and moderately differentiated colonic adenocarcinoma, intestinal type (tumor stage: ypT3N0M0). To the best of our knowledge, this is the first documented case of synchronous primary colonic adenocarcinoma and PDAC in the English literature.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patologia , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Carcinoma de Células Escamosas , Neoplasias do Colo/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Primárias Múltiplas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Cutâneas
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