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7.
Medicine (Baltimore) ; 99(42): e22718, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080727

RESUMO

Laparoscopic surgery has become the preferred surgical approach of several colorectal conditions. However, the economic results of this are quite controversial. The degree of adoption of laparoscopic technology, as well as the aptitude of the surgeons, can have an influence not only in the clinical outcomes but also in the total procedure cost. The aim of this study was to evaluate the clinical and economic outcomes of laparoscopic colorectal surgeries, compared to open procedures in Brazil.All patients who underwent elective colorectal surgeries between January 2012 and December 2013 were eligible to the retrospective cohort. The considered follow-up period was within 30 days from the index procedure. The outcomes evaluated were the length of stay, blood transfusion, intensive care unit admission, in-hospital mortality, use of antibiotics, the development of anastomotic leakage, readmission, and the total hospital costs including re-admissions.Two hundred eighty patients, who met the eligibility criteria, were included in the analysis. Patients in the laparoscopic group had a shorter length of stay in comparison with the open group (6.02 ±â€Š3.86 vs 9.86 ±â€Š16.27, P < .001). There were no significant differences in other clinical outcomes between the 2 groups. The total costs were similar between the 2 groups, in the multivariate analysis (generalized linear model ratio of means 1.20, P = .074). The cost predictors were the cancer diagnosis and age.Laparoscopic colorectal surgery presents a 17% decrease in the duration of the hospital stay without increasing the total hospitalization costs. The factors associated with increased hospital costs were age and the diagnosis of cancer.


Assuntos
Neoplasias Colorretais/cirurgia , Brasil , Estudos de Coortes , Neoplasias Colorretais/economia , Conversão para Cirurgia Aberta , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Custos de Cuidados de Saúde , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
9.
Nat Commun ; 11(1): 5338, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087703

RESUMO

Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system. While clone-specific differences in HLA peptide presentation were observed, broad inter-clone variability was even more prevalent (15-25%). By coupling organoid proteomics and HLA peptide ligandomics, we also found that tumor-specific ligands from DNA damage control and tumor suppressor source proteins were prominently presented by tumor cells, coinciding likely with the silencing of such cytoprotective functions. Collectively, these data illustrate the heterogeneous HLA peptide presentation landscape even within one individual, and hint that a multi-peptide vaccination approach against highly conserved tumor suppressors may be a viable option in patients with low tumor-mutational burden.


Assuntos
Neoplasias Colorretais/imunologia , Antígenos HLA/metabolismo , Organoides/imunologia , Apresentação do Antígeno , Linhagem Celular Tumoral , Células Clonais/imunologia , Células Clonais/metabolismo , Células Clonais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Ligantes , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Organoides/metabolismo , Organoides/patologia , Proteoma/metabolismo , Transdução de Sinais , Análise de Célula Única , Serina-Treonina Quinases TOR/metabolismo
10.
Nat Commun ; 11(1): 5321, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087710

RESUMO

5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading to activation of the WNT/ß-catenin pathway in ApcMin/+/Lgr5EGFP mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/ß-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Fluoruracila/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Camundongos Transgênicos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Organoides/efeitos dos fármacos , Organoides/metabolismo , Organoides/patologia , Pirazinas/administração & dosagem , Piridinas/administração & dosagem , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Proteína Wnt3/genética , Proteína Wnt3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Anticancer Res ; 40(11): 6063-6073, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109544

RESUMO

BACKGROUND/AIM: Interactions between colorectal cancer (CRC) cells and myofibroblasts govern many processes such as cell growth, migration, invasion and differentiation, and contribute to CRC progression. Robust experimental tests are needed to investigate the nature of these interactions for future anticancer studies. The purpose of the study was to design and validate in vitro assays for studying the communication between myofibroblasts and CRC epithelial cell lines. MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments. RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion. CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.


Assuntos
Antineoplásicos/farmacologia , Comunicação Celular/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/patologia , Miofibroblastos/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos , Masculino , Invasividade Neoplásica
12.
Anticancer Res ; 40(11): 6265-6271, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109564

RESUMO

BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. This study aimed to investigate the anticancer effect of the combination treatment of Ribociclib (LEE011) and 5-Fluorouracil (5-FU) on CRC cells. MATERIALS AND METHODS: HT-29 and SW480 cells were treated with LEE011, 5-FU, or the combination of LEE011 and 5-FU. Cell viability and cycle were investigated through 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and flow cytometry. The expression of cell cycle-related proteins was determined through western blot. RESULTS: The combined treatment of LEE011 with 5-FU synergistically reduced cell viability in HT-29 and SW480 cells. Specifically, it induced cell cycle arrest at the G1 phase, down-regulated the phosphorylation of retinoblastoma protein and the expression of p53. CONCLUSION: LEE011 exhibited potential as an effective therapeutic inhibitor for the combination treatment of CRC patients.


Assuntos
Aminopiridinas/farmacologia , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Purinas/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos
13.
Anticancer Res ; 40(11): 6285-6293, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109566

RESUMO

BACKGROUND/AIM: Pyruvate carboxylase (PC) is a major anaplerotic enzyme for generating oxaloacetate for the TCA cycle and also a key enzyme in gluconeogenesis, de novo fatty acid and amino acid synthesis in normal cells. Recent studies have identified PC overexpression in different cancers, such as breast and lung. However, the involvement of PC in colorectal cancer (CRC) is unclear. Our purpose was to investigate the PC expression levels and its correlations with potentially relevant clinical-pathological parameters in CRC. MATERIALS AND METHODS: PC expression levels in tissues from 60 Thai CRC patients were investigated by immunohistochemistry while a clonogenic assay was performed for determining cell growth of HT-29 cells with PC knockdown. RESULTS: Our results showed for the first time that high PC expression levels were significantly correlated with late stage of the cancer, perineural invasion and lymph node metastasis. The overexpression of PC was also significantly associated with poor overall and disease-free survival times of CRC patients. In addition, suppression of cancer cell growth was found in PC-deficient cell lines using CRISPR-Cas9. CONCLUSION: The overexpression levels of PC were correlated with CRC progression and survival times. Therefore, PC might serve as a potential clinical prognostic marker for colorectal cancer.


Assuntos
Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Progressão da Doença , Piruvato Carboxilase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Células Clonais , Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resultado do Tratamento
14.
Anticancer Res ; 40(11): 6367-6373, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109574

RESUMO

BACKGROUND/AIM: The presence of TLS (tertiary lymphoid structures) is detectable in the microenvironment of human cancers and linked to better patient outcomes. The role of TLS in colorectal cancer liver metastases (CRCLM) is unclear. PATIENTS AND METHODS: Medical records of patients with CRCLM were reviewed (n=33) and corresponding tissue samples (n=21) were obtained. Whole slide imaging analyses on immunohistochemical staining of immune cell infiltrates and TLS were correlated to clinical outcomes (including chemotherapy response) and other parameters. RESULTS: Neither the size (p=0.6) nor the quantity (p=0.47) of TLS was associated with the clinical course. When considering spatial differences, TLS in the invasive margin (IM) were associated with progression-free survival (p=0.03), while TLS in the LM (liver metastasis) were not. Also, TLS in the IM were associated with the presence of CD3+ T cells, which itself was prognostically favorable (p<0.001). CONCLUSION: TLS in the IM are associated with good prognosis in CRCLM, but not chemotherapy response.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Prognóstico , Estruturas Linfoides Terciárias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo CD3/imunologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Linfócitos T/imunologia , Linfócitos T/patologia , Estruturas Linfoides Terciárias/diagnóstico por imagem , Estruturas Linfoides Terciárias/imunologia , Microambiente Tumoral/imunologia
15.
Anticancer Res ; 40(11): 6517-6523, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109592

RESUMO

BACKGROUND/AIM: Precise tumor localization during gastrointestinal surgery improves curability and function preservation. We investigated the efficacy of preoperative endoscopic fluorescent clip marking using a Zeoclip FS with built-in near-infrared fluorescent resins in delineating gastrointestinal cancer for surgery. PATIENTS AND METHODS: We evaluated the intraoperative visibility of the Zeoclip FS using a VISERA ELITE 2 and the short-term outcomes of 37 cancer patients (colorectal, n=23; gastric, n=14) who underwent preoperative fluorescent clip marking. RESULTS: The study included 23 male and 14 female subjects with a mean age of 73 years (range=39-87 years). Thirty-three patients (89.1%) exhibited clear fluorescent clip marking and easily determined transection lines. Fluorescence was not observed in 1 sigmoid colon cancer patient (2.7%), who required a colonic stent for preoperative obstruction. Three patients (8.1%) required additional procedures for fluorescence visualization. CONCLUSION: Endoscopic fluorescent clip marking can delineate tumors well for determining the extent of resection.


Assuntos
Neoplasias Colorretais/cirurgia , Endoscopia Gastrointestinal , Neoplasias Gastrointestinais/cirurgia , Laparoscopia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/fisiopatologia , Feminino , Corantes Fluorescentes/química , Gastrectomia/métodos , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Instrumentos Cirúrgicos
16.
PLoS One ; 15(10): e0240397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031464

RESUMO

BACKGROUND: There is a need to understand the impact of COVID-19 on colorectal cancer care globally and determine drivers of variation. OBJECTIVE: To evaluate COVID-19 impact on colorectal cancer services globally and identify predictors for behaviour change. DESIGN: An online survey of colorectal cancer service change globally in May and June 2020. PARTICIPANTS: Attending or consultant surgeons involved in the care of patients with colorectal cancer. MAIN OUTCOME MEASURES: Changes in the delivery of diagnostics (diagnostic endoscopy), imaging for staging, therapeutics and surgical technique in the management of colorectal cancer. Predictors of change included increased hospital bed stress, critical care bed stress, mortality and world region. RESULTS: 191 responses were included from surgeons in 159 centers across 46 countries, demonstrating widespread service reduction with global variation. Diagnostic endoscopy was reduced in 93% of responses, even with low hospital stress and mortality; whilst rising critical care bed stress triggered complete cessation (p = 0.02). Availability of CT and MRI fell by 40-41%, with MRI significantly reduced with high hospital stress. Neoadjuvant therapy use in rectal cancer changed in 48% of responses, where centers which had ceased surgery increased its use (62 vs 30%, p = 0.04) as did those with extended delays to surgery (p<0.001). High hospital and critical care bed stresses were associated with surgeons forming more stomas (p<0.04), using more experienced operators (p<0.003) and decreased laparoscopy use (critical care bed stress only, p<0.001). Patients were also more actively prioritized for resection, with increased importance of co-morbidities and ICU need. CONCLUSIONS: The COVID-19 pandemic was associated with severe restrictions in the availability of colorectal cancer services on a global scale, with significant variation in behaviours which cannot be fully accounted for by hospital burden or mortality.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Infecções por Coronavirus/epidemiologia , Procedimentos Cirúrgicos Eletivos , Alocação de Recursos para a Atenção à Saúde , Pneumonia Viral/epidemiologia , Betacoronavirus/fisiologia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Gastroenterologia/organização & administração , Gastroenterologia/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pandemias , Segurança do Paciente
17.
Khirurgiia (Mosk) ; (10): 29-35, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33047583

RESUMO

OBJECTIVE: To determine diagnostic value of neutrophil CD64 index (iCD64n) in the diagnosis of postoperative infectious complications after colorectal resections. MATERIAL AND METHODS: Seventy-three patients underwent colorectal surgery for the period from January to December 2018. These patients were included into a single-center study. Peripheral blood samples were taken on 3 and 6 postoperative days (POD) to check iCD64n level. We analyzed incidence of postoperative infectious complications, sensitivity (Se) and specificity (Sp) of postoperative iCD64n level on the 3rd and 6th POD. RESULTS: Postoperative infectious complications developed in 10 (13.7%) patients. Median iCD64n was significantly higher (p=0.0017 for POD 3; p=0.018 for POD 6) in patients with infectious complications (1.6 on POD 3; 1.3 on POD 6) compared to those without complications (1.1 on POD 3; 0.9 on POD 6). Area under curve (AUC) on the 3rd POD was 0.8 with the cut-off value of 1.4, Se - 70%, Sp - 93.7% (p=0.002). On the 6th POD, AUC was 0.91 with cut-off value of 1.23, Se - 80%, Sp - 93.7% (p<0.001). CONCLUSION: Neutrophil CD64 index is a valuable predictor for the diagnosis of postoperative infectious complications after colorectal resections. It is a useful tool to ensure a safe early discharge.The study is registered on the website «clinictrials.gov¼ (registration number NCT03559335).


Assuntos
Colectomia/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Infecções/sangue , Infecções/diagnóstico , Receptores de IgG/sangue , Biomarcadores/sangue , Humanos , Infecções/etiologia , Infecções/imunologia , Neutrófilos/imunologia , Receptores de IgG/imunologia
18.
Medicine (Baltimore) ; 99(41): e22503, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031287

RESUMO

BACKGROUND: Gastrointestinal malignant tumors are the most common malignant tumors in elderly people in China, resulting in an increasing trend of morbidity and mortality. We conducted a non-randomized controlled trial to compare the effect of enhanced recovery after surgery (ERAS) versus Routine care on clinical outcomes in elderly patients after colorectal cancer surgery. METHODS: This is a single center, non-random, parallel-controlled clinical trial, 60 patients aged ≥65 years will be randomized for Case group ERAS and Control group (routine care). RESULTS: This study will help to evaluate the clinical feasibility, safety and effectiveness of ERAS in elderly patients undergoing colorectal resection compared with routine care. PROTOCOL REGISTRATION NUMBER: ChiCTR2000034984.


Assuntos
Neoplasias Colorretais/cirurgia , Recuperação Pós-Cirúrgica Melhorada , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Controlados como Assunto , Humanos , Projetos de Pesquisa
19.
Minerva Med ; 111(4): 337-343, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33032394

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are considered have a prognostic value in several malignancies. This study investigated the correlation between PD-L1 expression of tumor cells with the degree of stromal TILs in colorectal adenocarcinoma. METHODS: A cross sectional study design performed by taking 52 colorectal adenocarcinoma samples. The specimens were stained by immunohistochemical procedure using PD-L1 rabbit monoclonal antibody and the degrees of TILs were assessed base on hematoxylin and eosin (H&E) staining. RESULTS: From a total of 52 samples, the positive PD-L1 expression of tumor cells were 44 (84.6%) samples with 22 (50.0%), 18 (40.9%) and 4 (9.1%) samples had low-, moderate-, and high-degree TILs, respectively. While the negative PD-L1 expression were eight (15.4%) samples with 1 (12.5%), three (37.5%) and four (50.0%) samples had low-, moderate-, and high-degree TILs, respectively. A value of P=0.017 (P<0.05) was obtained by the Chi-square test. CONCLUSIONS: This study concluded that there was a significant correlation between PD-L1 expression of tumor cells and the degree of TILs in colorectal adenocarcinoma. This result indicated that the degree of TILs had the potential to be used as a predictive factor for PD-L1 expression of tumor cells in colorectal adenocarcinoma.


Assuntos
Adenocarcinoma/patologia , Antígeno B7-H1/biossíntese , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Acta Gastroenterol Belg ; 83(3): 399-405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33094586

RESUMO

BACKGROUND AND STUDY AIMS: The most important causes of hereditary colorectal cancer are Lynch syndrome (LS) and the adenomatous polyposis syndromes (familial adenomatous poly- posis syndrome or FAP, attenuated FAP or AFAP and MUTYH associated polyposis syndrome or MAP). The aim of this study was to investigate whether all patients with a hereditary syndrome within one center receive uniform advice regarding surveillance and treatment. PATIENTS AND METHODS: A retrospective analysis was performed of all electronic patient health records of patients with LS, FAP, AFAP and MAP who received genetic counselling or were followed by a health care specialist at the University Hospital in Ghent. RESULTS: Data from 122 patients were collected. For all patients, recommendations from the medical genetics department were highly consistent. Adherence to their recommendations was good within the center for the management of colon polyps. There was a lack of consistency in the screening and surveillance advice for other tumors in departments other than gastroenterology. Only 33 patients had systematic follow-up consultations to check results and organize surveillance. CONCLUSION: Previously, small studies have suggested that patients with hereditary gastrointestinal cancer syndromes infrequently have surveillance as specified in the guidelines. This study shows almost uniform recommendations and good adherence for surveillance of the colon, but incomplete or contradictory advice for surveillance of other organs. The need for an integrated approach from a multidisciplinary team will only increase in the future, because more families with hereditary cancer are likely to be found due to the increased use of next generation sequencing in cancer diagnostics.


Assuntos
Polipose Adenomatosa do Colo , Neoplasias do Colo , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/epidemiologia , Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Humanos , Estudos Retrospectivos
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