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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1044-1052, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051417

RESUMO

OBJECTIVES: To analyze the expression level of ubiquitin conjugating enzyme E2C (UBE2C) in lung adenocarcinoma and its clinical significance. METHODS: The differences in mRNA and protein expression levels of UBE2C in normal lung tissues and lung adenocarcinoma (LUAD) tissues were determined with the Cancer Genome Atlas (TCGA), Oncomine, and human protein atlas (HPA) databases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UBE2C in LUAD. The correlation between UBE2C and LUAD clinicopathological parameters, as well as its relationship with LUAD prognosis was analyzed based on TCGA, International Cancer Genome Consortium (ICGC), and cbioPortal databases. Gene set enrichment analysis (GSEA) was used to analyze the possible pathways of UBE2C in the progression of LUAD. RESULTS: The mRNA expression level of UBE2C was higher in LUAD tissues than in the normal lung tissues (P<0.01) and it was positively correlated with TNM and N stages (both P<0.05). The UBE2C protein expression level was also increased in LUAD tissues than in the normal lung tissues (P<0.01). ROC curve analysis indicated that UBE2C could be used as an auxiliary diagnostic index for LUAD (AUC=0.969, 95% CI 0.953 to 0.984, P<0.01). Survival analysis showed that the overall survival (OS) of UBE2C high expression group was significantly lower than that of low expression group (P<0.05). The OS of LUAD patients with UBE2C change was lower than that of patients without change (P<0.01). UBE2C was highly expressed in the gene set relevant to cell cycle, p53 signaling pathway, DNA mismatch repair, and DNA replication (all P<0.01). CONCLUSIONS: The expression level of UBE2C is significantly up-regulated in LUAD tissues. The high expression or genetic alteration of UBE2C indicates poor prognosis in LUAD patients. UBE2C can be used as a potential molecular diagnostic marker for LUAD and a potential target for LUAD treatment.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/genética , Humanos , Pulmão , Neoplasias Pulmonares/genética , Prognóstico , Enzimas de Conjugação de Ubiquitina/genética
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 971-974, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047739

RESUMO

The rearrangement of the gene encoding the transcription factor ETS-related gene (ERG) is thought to play a key role in the development of prostate cancer. However, the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma (NSCLC). Here, we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs. The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography (CT) scan. After conducting lobectomies at the both lungs, the tumor nodules were all removed, and the histological analysis suggested adenocarcinoma at the both tumor lesions. The patient was diagnosed with synchronous multiple primary lung cancer (SMPLC) based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines. An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC. Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score. The read depth was ≥ 1 000× and the depth of coverage was 95%. The data revealed a discordant epidermal growth factor receptor (EGFR) from the separate lungs; additionally, a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions. This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC. This study suggests that the same environment may contribute certain gene(s) mutations in the same sites in the early stages of polyclonal tumor origins; meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Idoso , Humanos , Neoplasias Pulmonares/genética , Masculino , Neoplasias Primárias Múltiplas/genética , Mutação Puntual , Regulador Transcricional ERG
3.
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
4.
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
5.
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
6.
Zhonghua Bing Li Xue Za Zhi ; 49(9): 886-890, 2020 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-32892552

RESUMO

Objective: To study the proportion and clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation (GAED) in gastric cancers showing an elevated serum alpha fetoprotein(AFP). Methods: A total of 724 resected gastric adenocarcinomas were collected from 2008 to 2018 at the 904 Hospital of Joint Service Support Force, and cases with pre-operative serum AFP>10 µg/L were screened. From the cases with elevated serum AFP, GAED cases were further evaluated based on morphology. Then the clincopathological features and immunohistochemical phenotypes of GAED were reviewed. In addition, the amplification of HER2 gene was detected with fluorescence in situ hybridization(FISH). When overall survival (OS) and progression-free survival (PFS) of GAED were analyzed, 289 cases ordinary gastric adenocarcinoma with normal serum AFP were employed as a control. Results: The percentage of GAED was 44% (11/25) in gastric cancers with elevated serum AFP. GAED was histologically tubular or papillary with clear cytoplasm, and some GAED cases showed cystadenoid structure similar to embryo sac (5 cases), homogeneous eosinophilic granules (4 cases) and intragland ulareosinophilic material (6 cases). All 11 GAED cases had lymph node metastasis. Liver metastasis and vascular thrombus were observed in 2 cases and 5 cases respectively. GAED was immunohistochemically positive for CDX2 (11/11), CD10 (8/11) and MUC2(3/11), which were intestinal epithelium differentiation markers. Meanwhile, primitive markers SALL4 (8/11), GPC3 (7/11) and AFP (5/11) were also expressed in GAED, and HER2 gene amplification was found in 3 cases (3/11) of GAED. Lastly, the PFS of GAED were significantly shorter than that of the control group (P=0.02), while OS was not statistically different between these two groups (P=0.99). Conclusions: Patients with GAED usually have a higher rate of elevated serum AFP in gastric adenocarcinoma, and the cancer exhibites features of both intestinal and primitive differentiation. As GAED is highly invasive, the prognosis of GAED may be poor. For GAED, the diagnosis of well-differentiated or moderately-differentiated adenocarcinoma should be avoided, because this diagnosis leads to underestimated malignant potential.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , alfa-Fetoproteínas
7.
Kyobu Geka ; 73(9): 712-715, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-32879279

RESUMO

A 63-year-old man was pointed out a mass lesion in his chest X-ray at a medical checkup and referred to our hospital for further examination. Chest computed tomography showed a 4 cm-diameter tumor in the left upper lobe. He was diagnosed with adenocarcinoma by bronchoscopic biopsy. Therefore, we performed left upper lobectomy. The tumor was diagnosed as pulmonary blastoma with the differentiation of adenocarcinoma and large cell neuroendocrine carcinoma.


Assuntos
Adenocarcinoma , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Blastoma Pulmonar , Adulto , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Kyobu Geka ; 73(8): 574-577, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32879282

RESUMO

The case was a 56-year-old man. A nodular shadow of the left upper lobe was found in the chest computed tomography, and a diagnosis of adenocarcinoma was obtained by bronchoscopy. Preoperative 3-dimensional computed tomography (3D-CT) angiography indicated an extremely rare pulmonary artery bifurcation abnormality in which A4b+5 and A8+9 bifurcate from the left main pulmonary artery. Thoracoscopic left upper lobectomy and lymph node dissection were performed. Pathological diagnosis was adenocarcinoma with pStage I B. The mediastinal basal pulmonary artery is extremely rare, and to our knowledge, the bifurcation pattern of this case has not been reported elsewhere. The 3D-CT angiography was useful to detect the anatomical vascular abnormalities of the pulmonary artery before surgery, for the safe performance of the thoracoscopic surgery.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Pulmonares/cirurgia , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Toracoscopia
9.
Tokai J Exp Clin Med ; 45(3): 113-116, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32901897

RESUMO

Mutations in the gene encoding epidermal growth factor receptor (EGFR) are the most frequent driver mutations in lung adenocarcinoma in Japan. Exon 19 deletion and L858R mutation in exon 21 are the most common EGFR mutations. Uncommon mutations, such as G719X, S768I, and L861Q, and compound mutations, combinations of 2 common or uncommon mutations, have also been reported. EGFR tyrosine kinase inhibitors (TKIs) are effective against cancers harboring common mutations; however, their efficacy against cancers with uncommon or compound mutations remains unclear. We report the case of a 67-year-old man with lung adenocarcinoma (clinical stage IIIA [cT1N2M0]), harboring an uncommon compound mutation, G719X and S768I. The cancer progressed within 2 months of initial chemoradiotherapy. Treatment with afatinib (40 mg/day) produced a partial response, which was maintained for 17 months with continued treatment. A literature review revealed that lung cancer with G719X/S768I compound mutation exhibited good response to EGFR-TKIs, even better than that of lung cancers with single uncommon mutations.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Afatinib/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Receptores ErbB/genética , Éxons/genética , Deleção de Genes , Humanos , Masculino , Resultado do Tratamento
10.
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
12.
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
13.
Chirurgia (Bucur) ; 115(4): 448-457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32876018

RESUMO

Background: In Romania, colorectal cancer does not benefit yet from a national screening program. In order to decrease the harm and burden of colorectal cancer (CRC), opportunistic programs relying on endoscopy has been adopted by each centre according to its capacity. A colorectal cancer (CRC) screening programme based on faecal immunochemical test (FIT) was launched at Ponderas Academic Hospital (PAH) in 2019. Aim: The present study analyses the outcomes after the first 1500 tests in the PAH-FIT-CRC Screening Program. We have also aimed to compare the efficiency of the FIT testing program with the screening colonoscopies performed in our Center, withing the same time interval (2019). Methods: The test was recommended in asymptomatic patients over 45 years, and it was followed by a colonoscopy when the test results were positive. Furthermore, we performed a retrospective observational study gathering data from all the consecutive patients prospectively included in the respective databases of our hospital, comparing the efficacy of the two colorectal cancer screening methods (FIT versus colonoscopy). Results: Between 01.01.2019 and 01.01.2020, 1524 screening colonoscopies were performed, and the resulting data were compared with those obtained in the FIT group (1500 FIT tests freely distributed). In the screening colonoscopy group, the polyp detection rate was 38.98% and 22 (1.44%) adenocarcinomas were identified. In the FIT group, the FIT uptake rate was 71% with a positivity rate of 21.7%. The colonoscopy compliance rate for positive FIT patients was 29.4%, with only 2 adenocarcinomas detected. Conclusions: Following data analysis, the need for improvement of uptake rate and colonoscopy compliance rate was suggested, due to the lower acceptance of FIT tests and colonoscopies, especially among men. Moreover, special efforts should be made in order to improve quality indicators for screening colonoscopies (especially adenoma detection rate) with the purpose of decreasing interval CRC.


Assuntos
Adenocarcinoma/diagnóstico , Pólipos Adenomatosos/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Fezes , Colonoscopia , Fezes/química , Humanos , Masculino , Programas de Rastreamento/métodos , Estudos Retrospectivos , Romênia , Resultado do Tratamento
14.
Zhonghua Yi Xue Za Zhi ; 100(37): 2919-2923, 2020 Oct 13.
Artigo em Chinês | MEDLINE | ID: mdl-32993251

RESUMO

Objective: To investigate the value of 3.0T MRI diffusion kurtosis imaging (DKI) quantitative histogram parameters in the differential diagnosis of rectal mucinous adenocarcinoma (MC) and common adenocarcinoma (AC). Methods: One hundred and ten patients from Department of Radiology, the Second Affiliated Hospital of Soochow University between September 2015 and September 2019 with complete magnetic resonance imaging (MRI) and DKI results confirmed by surgery and pathology were retrospectively analyzed, including 16 patients in MC group and 94 patients in AC group. Two physicians outlined the region of interest (ROI) on the DKI image with b=1 000 s/mm(2), and obtained quantitative DKI parameters, including the diffusion coefficient (D value) and kurtosis coefficient (K value) corrected for non-Gaussian distribution. The apparent diffusion coefficient (ADC) values of quantitative parameters of diffusion-weighted imaging (DWI) were obtained through image registration, and histogram analysis was performed to obtain the mean value, 25th percentile, 50th percentile, 75th percentile, skewness and kurtosis of the above parameters, respectively. The difference between the quantitative histogram parameter analysis results of the rectal MC group and the AC group was evaluated, and the main indicators and multivariate comprehensive analysis indicators was screened, and the effectiveness of quantitative histogram parameters related to histopathological classification in the differential diagnosis of rectal MC and AC was evaluated. Results: There was no significant differences in gender, age, lesion location, T stage or N stage between MC group and AC group (all P>0.05). The multivariate binary logistic stepwise regression screening showed that D50th percentile and K25th percentile are statistically significant indicators (B values were 2 966.166 and -4.550, respectively; Wals values were 9.000 and 15.720, respectively; and P values were 0.003 and <0.001, respectively). The combined area under the curve of the two indictors was 0.85, but there was no statistically significant difference in pairwise comparison using DeLong method (P>0.05). The results of histogram analysis of quantitative parameters measured by the two physicians were consistent, and the inter-group correlation coefficient ranged from 0.880 to 0.981. Conclusions: The quantitative parameter histogram analysis of the DKI double-index model is helpful for the differentiation of rectal MC and AC, in which the D50th percentile and K25th percentile have differential diagnosis significance, and are superior to the ADC value of the single-index model.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos
15.
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
16.
Medicine (Baltimore) ; 99(35): e21922, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871929

RESUMO

RATIONALE: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention. PATIENT CONCERNS: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made. DIAGNOSES: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke. INTERVENTIONS: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7. OUTCOMES: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent. LESSONS: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antitrombinas/uso terapêutico , Trombose das Artérias Carótidas/terapia , Artéria Carótida Interna , Infarto da Artéria Cerebral Média/induzido quimicamente , Terapia Trombolítica , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Administração Oral , Trombose das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Dabigatrana/uso terapêutico , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico
17.
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
18.
PLoS One ; 15(8): e0238380, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866185

RESUMO

Pancreatic adenocarcinoma is characterized by a complex tumor environment with a wide diversity of infiltrating stromal and immune cell types that impact the tumor response to conventional treatments. However, even in this poorly responsive tumor the extent of T cell infiltration as determined by quantitative immunohistology is a candidate prognostic factor for patient outcome. As such, even more comprehensive immunophenotyping of the tumor environment, such as immune cell type deconvolution via inference models based on gene expression profiling, holds significant promise. We hypothesized that RNA-Seq can provide a comprehensive alternative to quantitative immunohistology for immunophenotyping pancreatic cancer. We performed RNA-Seq on a prospective cohort of pancreatic tumor specimens and compared multiple approaches for gene expression-based immunophenotyping analysis compared to quantitative immunohistology. Our analyses demonstrated that while gene expression analyses provide additional information on the complexity of the tumor immune environment, they are limited in sensitivity by the low overall immune infiltrate in pancreatic cancer. As an alternative approach, we identified a set of genes that were enriched in highly T cell infiltrated pancreatic tumors, and demonstrate that these can identify patients with improved outcome in a reference population. These data demonstrate that the poor immune infiltrate in pancreatic cancer can present problems for analyses that use gene expression-based tools; however, there remains enormous potential in using these approaches to understand the relationships between diverse patterns of infiltrating cells and their impact on patient treatment outcomes.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfócitos T/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
19.
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
20.
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
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