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1.
Anticancer Res ; 40(3): 1467-1473, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132045

RESUMO

BACKGROUND: BTH1677 is a beta-glucan pathogen-associated molecular pattern (PAMP) being evaluated as a novel immunotherapy of cancer. We previously described that the presence of antibodies against beta-glucan (ABA) in serum is necessary for BTH1677 antitumoral activity. We hypothesized that infusion of immunoglobulin can reinstate responses to BTH1677 in individuals with low ABA levels. PATIENTS AND METHODS: We report two single-patient studies: one in a patient with metastatic colorectal cancer who received BTH1677, combined with tumor targeting antibody cetuximab; and a second in a patient with metastatic neuroendocrine tumor who received BTH1677 combined with immune checkpoint inhibitor pembrolizumab. RESULTS: The patients had low serum titers of ABA and low innate immune effector functionality induced by BTH1677. Addition of intravenous immunoglobulins restored innate immune activity of BTH1677 and induced clinically meaningful anti-tumoral activity, with long-term disease control. CONCLUSION: Infusion of immunoglobulin can restore activity of BTH1677 in individuals with low serum ABA level.


Assuntos
Anticorpos/sangue , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Glucanos/administração & dosagem , Tumores Neuroendócrinos/imunologia , Tumores Neuroendócrinos/terapia , beta-Glucanas/imunologia , Idoso de 80 Anos ou mais , Anticorpos/imunologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Cetuximab/administração & dosagem , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Imunoterapia/métodos , Pessoa de Meia-Idade
2.
Medicine (Baltimore) ; 99(11): e19522, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176103

RESUMO

Beside established anti-cancer treatment, dietary modification is one of the most promising approaches for reducing the probability of colorectal cancer (CRC) recurrence. Many Western studies showed a relationship between shortened survival and increased amounts of Western diet (meat and processed meat). Given that Thai food is dissimilar to Western diet, we aimed to explore the association between dietary patterns and disease recurrence among Thai CRC patients.Early-stage CRC patients who were disease-free at the end of a 2-year period or patients with disease recurrence within 2 years were enrolled. Patients were administered a food frequency questionnaire to evaluate their dietary lifestyle. Quantitative comparison within individual food groups among patients who were disease-free and among those with recurrence was performed. Proportion of patients with recurrence and disease-free survival was compared between patients who had consumed the lowest and highest tertile of each dietary pattern.A total of 225 CRC patients were enrolled (151 disease-free and 74 recurrence). There were no significant differences in demographic or tumor parameters between patients with or without disease recurrence. From the questionnaire, 45 food items were assigned to 1 of 12 food groups according to similarity in nutritional profile. Patients who consumed high amounts of pickled fish or chili-paste had significantly lower recurrence rates compared to patients who had never eaten those foods (P < .01). From the factor analysis, meat/wheat, vegetarian, and fast-food/processed fruit patterns were identified as the major dietary patterns. There was no significant association between intakes of individual dietary patterns and CRC recurrence.Among CRC patients with Thai dietary lifestyles there was no association between meat/wheat, fast-food/processed fruit, or vegetarian dietary patterns and CRC recurrence. Greater consumption of some unique Thai foods, such as chili-paste or pickled fish, may relate to better outcomes for CRC patients.


Assuntos
Neoplasias Colorretais/epidemiologia , Dieta , Recidiva Local de Neoplasia/epidemiologia , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Preferências Alimentares , Humanos , Masculino , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Tailândia/epidemiologia
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(3): 201-208, 2020 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-32192294

RESUMO

In December 2019, a new outbreak of corona virus disease 2019 began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies (including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.


Assuntos
Neoplasias Colorretais , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/terapia , Infecções por Coronavirus/complicações , Surtos de Doenças , Detecção Precoce de Câncer , Humanos , Pneumonia Viral/complicações
4.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(3): 211-216, 2020 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-32192296

RESUMO

Corona virus disease 2019 (COVID-19) is currently raging in China. It has been proven that COVID-19 can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, it is a difficult task to provide the highest quality medical services and ensure the orderly clinical work, on the premise of maximizing the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, We summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the COVID-19 epidemiology, including the procedures of diagnose and treatment for emergency patients with colorectal tumor, and share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of COVID-19 to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed COVID-19, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed COVID-19 should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under -5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with COVID-19 must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our "Renji experience" will be beneficial to colleagues.


Assuntos
Neoplasias Colorretais , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , China , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Surtos de Doenças , Humanos
5.
J Cancer Res Clin Oncol ; 146(3): 545-553, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32036456

RESUMO

PURPOSE: Several studies have evaluated surgical resection of pulmonary metastases as a standard treatment option for colorectal cancer (CRC) patients with resectable pulmonary metastases. However, the role of peri-operative chemotherapy after complete resection of pulmonary metastases from CRC patients is still controversial. This systematic review and meta-analysis is aimed to investigate the clinical efficacy of peri-operative chemotherapy after resection of CRC pulmonary metastases. METHODS: PubMed, the Cochrane Library databases, and Embase were searched for studies evaluating the effect of peri-operative chemotherapy on the survival of patients with CRC after pulmonary metastasectomy. The hazard ratio (HR) was used for analyzing overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS). RESULTS: Eight studies were included in the final analysis. The outcome showed that peri-operative chemotherapy had a significant favourable effect on OS (HR 0.83, 95% CI 0.75-0.92, p < 0.05) and PFS/RFS/DFS (HR 0.67, 95% CI 0.53-0.86, p < 0.05) in patients who received pulmonary metastasectomy. Multivariate analysis also validated this result (OS: HR 0.56, 95% CI 0.36-0.86, p < 0.05; PFS/RFS/DFS: HR 0.64, 95% CI 0.46-0.87, p < 0.05). There was a significant benefit in peri-operative group on OS and PFS/RFS/DFS in studies with R0 resection of pulmonary metastases (OS: HR 0.72, 95% CI 0.53-0.97, p < 0.05; PFS/RFS/DFS: HR 0.72, 95% CI 0.54-0.95, p < 0.05) and metachronous pulmonary metastases (OS: HR 0.40, 95% CI 0.22-0.75, p < 0.05; PFS/RFS/DFS: HR 0.67, 95% CI 0.49-0.92, p < 0.05). CONCLUSION: Our meta-analysis demonstrated a significant difference in favor of peri-operative chemotherapy in CRC patients who underwent resection of pulmonary metastases. More clinical data and studies are needed to validate the findings of our study.


Assuntos
Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Quimioterapia Adjuvante/mortalidade , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/mortalidade , Metastasectomia/métodos , Metastasectomia/mortalidade , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(8): e19277, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080139

RESUMO

Evidence-based guidelines for the correct management of cancer patients are developed on the idea that timely care can improve health prognoses and quality of life.The aim of this paper is to evaluate the adherence of clinical pathways to clinical guidelines provided at the hospital level, for colorectal cancer care.By using a retrospective observational study, we proposed a method for associating each patient to a healthcare provider and modeling adherence as a latent construct governed by a set of 10 influential indicators. These indicators measure the adherence to specific guidelines for diagnosis, surgical treatment, chemotherapy, and follow-up. The model used was that of the item response theory (IRT). When evaluating providers, the IRT allows for a comparison of indicators in terms of their discriminating ability and difficulty, and in terms of their adherence to guidelines. The IRT results were compared with non-latent methods: numerator-based weight and denominator-based weight.A strong degree of coherence of the indicators in measuring adherence, and a high level of overall agreement between latent and non-latent methods were noted. The IRT approach demonstrated similar providers' evaluations between endoscopy and histological assessment indicators. The greatest discriminating ability among providers could be attributed to all diagnostic exams, while the lowest was associated with follow-up endoscopies. The most difficult indicator to achieve was fecal occult blood test, while follow-up imaging was the easiest.In a decision-making framework, valuable indications can be derived from the use of IRT models rather than weighting methods. Using IRTs, we were able to highlight the principal indicators in terms of strength of discrimination, and to isolate those that merely duplicated information.


Assuntos
Neoplasias Colorretais/terapia , Fidelidade a Diretrizes , Guias de Prática Clínica como Assunto , Indicadores de Qualidade em Assistência à Saúde , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Continuidade da Assistência ao Paciente , Diagnóstico por Imagem , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Sangue Oculto , Estudos Retrospectivos
7.
Lancet ; 395(10221): 350-360, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007170

RESUMO

BACKGROUND: Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. METHODS: More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. FINDINGS: 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72-5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07-4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. INTERPRETATION: A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes. FUNDING: The Research Council of Norway.


Assuntos
Neoplasias Colorretais/diagnóstico , Aprendizado Profundo , Idoso , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Detecção Precoce de Câncer/métodos , Amarelo de Eosina-(YS)/metabolismo , Feminino , Hematoxilina/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
8.
Anticancer Res ; 40(2): 1107-1116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014961

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate whether modern chemotherapy has changed characteristics of actual five-year survivors after liver resection for colorectal liver metastasis (CRLM). PATIENTS AND METHODS: The records of 210 patients, who underwent curative liver resection for CRLM at our institution between January 1990 and May 2014, were reviewed. The patients treated before 2004 when modern chemotherapy was not introduced were compared with the patients treated after 2005. RESULTS: Actual five-year survivor rates were significantly higher after 2005 (33.3% vs. 49.0%, p=0.022). Preoperative characteristics of actual five-year survivors were not different. The median survival time after non-resectable recurrence was significantly longer after 2005 (20.3 vs. 8.7 months, p=0.002). The proportion of 5-year survivors with recurrent site was significantly higher after 2005 (34.0% vs. 10.5%, p=0.019). CONCLUSION: Actual five-year survivors have increased by modern chemotherapy. However, approximately one-third of them were not cured.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Quimioterapia Adjuvante , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Tomografia Computadorizada por Raios X
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 15-19, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958925

RESUMO

Although the surgical treatment of colorectal disease progresses slowly, with the advancement of minimally invasive surgical techniques, perioperative comprehensive treatment strategies and clinical research in recent years, Chinese colorectal surgery has developed rapidly. Transanal total mesorectal excision, lateral pelvic lymph node dissection,"watch and wait"strategy for clinical complete response of neoadjuvant radiotherapy for rectal cancer, and robotic colorectal surgery are still hot topics in colorectal surgery in recent years. The construction of clinical registry database and clinical research for colorectal cancer surgery are discussed, with a view to combing the development of colorectal surgery for colleagues in the surgical field, and to seek the development of colorectal surgery in China.


Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Colorretal/tendências , China , Neoplasias Colorretais/terapia , Terapia Combinada/tendências , Humanos , Laparoscopia/tendências , Excisão de Linfonodo , Neoplasias Retais/cirurgia , Neoplasias Retais/terapia , Procedimentos Cirúrgicos Robóticos/tendências , Conduta Expectante
10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 56-64, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958932

RESUMO

Objective: To explore the application of endoscopic tattooing with carbon nanoparticles in the treatment of advanced colorectal cancer (ACRC). Methods: A randomized controlled study was used. Inclusion criteria: (1) age more than 18 years old, and colorectal cancer was found for the first time and confirmed by colonoscopy and biopsy; (2) advanced colorectal cancer (preoperative TNM stage of T3/N1 or above, local unresectable lesion, M1 stage and simultaneously resectable metastatic lesion), and patients agreed to receive neoadjuvant therapy; (3) advanced colorectal cancer (TNM stage of T3/N1 or above) with simultaneous unresectable metastatic lesion, and patients refused operation and consented to chemoradiotherapy. Patients with previous abdominal surgery history, radiotherapy and chemotherapy history, urgent need for surgery or endoscopic stent placement and those with severe allergic constitution were excluded. Based on the above criteria, 120 patients diagnosed with ACRC in No.900 Hospital of the Joint Logistics Team from January 2016 to December 2017 were prospectively enrolled and randomly divided into tattoo group and non-tattoo group by random number table method. Tattoo group were tattooed within 1-7 days before chemoradiotherapy. The labeling location of the lesions: (1) if the colonoscopy could pass smoothly, 4 points were injected into the intestinal wall of the both opposite sides 1 cm cephalad and caudad of the tumor; (2) if the colorectal cavity was severely narrow and the colonoscopy could not pass, only 4 points were injected in 4 quadrants at 1 cm caudad of the tumor. Each injection point was injected with 0.1 ml carbon nanoparticles, and the size of the tumor was measured according to the range of carbon nanoparticles staining. The efficacy was evaluated after 8 weeks of chemoradiotherapy. Patients who were defined to be suitable for operation underwent operation 6 weeks after chemoradiotherapy. The following parameters were compared between two groups: lesion identification time, operation time, blood loss, distance from lesion to distal margin, the rate of first positive margin and the rate of anal sphincter preservation (rectal cancer). Among patients who had been evaluated as having no indication for surgery, those who were effective in chemoradiotherapy continued to receive chemotherapy in the original regimen; if the treatment failed, the chemotherapy regimen was replaced, and the efficacy was finally evaluated after six months [referring to the revised RECIST guidelines (version 1.1)]. Results: Three patients withdrew from this study, and 117 patients were enrolled in this study finally, including 59 cases in tattoo group and 58 cases in the non-tattoo group. There were no significant differences in baseline data between two groups (all P>0.05). All the patients had slight adverse reactions of radiotherapy and chemotherapy before operation, and could tolerate after symptomatic management without interruption of treatment. All the patients in the tattoo group had no discomfort such as fever, abdominal pain, abdominal distention, hematochezia, etc. and the intestinal mucosa could be seen clearly with black staining after being tattooed. A total of 77 patients were evaluated with surgical indications, including 39 cases in the tattoo group (tattoo-operable) and 38 cases in the non-tattoo group (non-tattoo-operatable). There were no significant differences in baseline data between the two groups (all P>0.05). Forty patients without operation indications continued chemoradiotherapy, including 20 cases in tattoo group (tattoo-inoperable) and 20 cases in non-tattoo group (non-tattoo-inoperable), whose differences in baseline data between the two groups were not significant as well (all P>0.05). No obvious edema, necrosis or abscess were found in the tattooed segments and the black spots could be seen quickly and clearly on the serosa of rectum in tattoo-operable patients. As compared to non-tattoo group, tattoo group had significantly shorter lesion identification time [(3.4±1.4) minutes vs. (11.8±3.4) minutes, t=-14.07,P<0.001], shorter operation time [(155.7±44.5) minutes vs. (177.2±30.2) minutes, t=-2.48,P=0.015], less blood loss [(101.3±36.7) ml vs.(120.2±38.2) ml, t=-2.22,P=0.029], shorter distance from lesion to distal margin [(3.7±1.0) cm vs. (4.6±1.7) cm, t=-2.20, P=0.034], while tattoo group had slightly higher rate of anal sphincter preservation [66.7%(16/24) vs. 45.5%(10/22), χ(2)=2.10,P=0.234] and lower rate of first positive resection margin [0 vs. 4.5%(1/22), χ(2)=0.62,P=0.480], but their differences were not significant. There were no significant differences in the degree of tumor differentiation and TNM stage between two groups. Patients without operative indication were evaluated for efficacy of chemoradiotherapy again after half a year. One case of complete response (CR), 8 of partial response (PR), 10 of stable disease (SD) and 1 of progressive disease (PD) were found and the improvement rate was 45.0% (9/20) in tattoo-inoperable patients. No case of CR, 6 of PR, 11 of SD and 3 of PD were found and the improvement rate was 30.0% (6/20) in non-tattoo-inoperable patients. There was no significant difference in the improvement rate between the two groups (P=0.514). Conclusions: Endoscopic tattooing with carbon nanoparticles injection is safe and reliable for colorectal tumor positioning. It can assist rapid detection of lesions during surgery after neoadjuvant treatment, perform accurate resection, significantly shorten the operation time and reduce surgical trauma; can assist colonoscopy accurately to measure the size of the lesions before and after chemoradiotherapy, and increase the means of assessing the efficacy to guide the follow-up treatment plan. This technique is worth clinical promotion and application.


Assuntos
Carbono/administração & dosagem , Neoplasias do Colo/terapia , Nanopartículas/administração & dosagem , Neoplasias Retais/terapia , Tatuagem/métodos , Adolescente , Quimiorradioterapia Adjuvante , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/terapia , Terapia Combinada , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Integr Cancer Ther ; 19: 1534735419900798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31959018

RESUMO

Although the Japanese traditional herbal medicine (Kampo), Juzentaihoto (JTT), has been reported to have antitumor effects in several tumor models, its role in tumor immunology remains controversial. In the present study, we tested whether oral administration of JTT enhances antitumor immunity in CD1d-/- mice, in which immunosuppression was partially relieved due to the lack of NKT cells. In a subcutaneous murine syngeneic CT26 colorectal tumor model, JTT had no impact on tumor growth in wild type (WT) BALB/c mice. However, the growth rate of tumors was significantly slower in CD1d-/- mice than in WT mice. Surprisingly, JTT significantly delayed tumor growth in such CD1d-/- mice. In vivo depletion of CD8+ T cells revealed that CD8+ T cells are required for JTT's antitumor activity. Moreover, tumor-reactive cytotoxic T-lymphocytes were detected exclusively in JTT-treated mice with well-controlled tumors. JTT did not affect the number of tumor-infiltrating CD4+ regulatory T cells. On the contrary, JTT increased the degranulation marker CD107a+ CD8+ T cells and decreased Ly6G+ Ly6Clo polymorphonuclear myeloid-derived suppressor cells in tumor-infiltrating lymphocytes, most probably contributing to the suppression of tumor growth in JTT-treated mice. Nonetheless, JTT had no impact on the proportion of monocytic myeloid-derived suppressor cells. In conclusion, our results indicate that in the absence of NKT cells, JTT augments antitumor immunity by CD8+ T cells, suggesting that this Kampo medicine is a promising anticancer adjuvant when negative immune regulation is partially relieved.


Assuntos
Neoplasias Colorretais/terapia , Medicamentos de Ervas Chinesas/farmacologia , Células Matadoras Naturais/imunologia , Medicina Kampo , Células T Matadoras Naturais/imunologia , Linfócitos T/imunologia , Animais , Neoplasias Colorretais/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Imunossupressão , Camundongos
12.
Cancer Immunol Immunother ; 69(1): 23-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768581

RESUMO

BACKGROUND: Several articles have recently reported that certain colon microbiota can improve the efficacy of cancer immunotherapy. To develop new treatment strategies, including immunotherapy for colorectal cancer (CRC), we evaluated the correlations between subpopulations of tumor-infiltrating immune cells (TIICs) and intestinal microbiota in CRC. METHODS: Fresh surgically resected specimens, formalin-fixed paraffin-embedded whole tissue samples, and stool samples were collected. TIICs including Tregs, Th17 cells and tumor-associated macrophages (TAMs) in the surgically resected specimens were analyzed using flow cytometry. FOXp3, CD8, CD163, and phosphorylated-STAT1-positive TIICs in the whole tissue samples were analyzed using IHC, and intestinal microbiota in the stool samples was analyzed using 16S metagenome sequencing. TIICs subpopulations in the normal mucosa and tumor samples were evaluated, and the correlations between the TIIC subpopulations and intestinal microbiota were analyzed. RESULTS: FOXp3lowCD45RA+ Tregs were significantly reduced (p = 0.02), FOXp3lowCD45RA- Tregs were significantly increased (p = 0.006), and M1 TAMs were significantly reduced in the tumor samples (p = 0.03). Bacteroides (phylum Bacteroidetes) and Faecalibacterium (phylum Firmicutes) were increased in the patients with high numbers of Tregs and clearly high distribution of FOXp3highCD45RA- Tregs, which are the effector Tregs. Faecalibacterium, Ruminococcaceae, Eubacterium (phylum Firmicutes), and Bacteroides were increased in patients with a high distribution of M1 TAMs. CONCLUSIONS: The findings of the present study indicate that immune responses to tumors are suppressed in the tumor microenvironment of CRC depending on the increment of Tregs and the reduction of M1 TAMs and that intestinal microbiota might be involved in immunosuppression.


Assuntos
Neoplasias Colorretais/imunologia , Microbioma Gastrointestinal/imunologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Evasão Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Bactérias/imunologia , Bactérias/isolamento & purificação , Estudos de Coortes , Colectomia , Colo/imunologia , Colo/microbiologia , Colo/patologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/terapia , Fezes/microbiologia , Feminino , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
13.
Int J Cancer ; 146(7): 1780-1790, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31291465

RESUMO

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.


Assuntos
Transformação Celular Neoplásica/metabolismo , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Animais , Ácidos e Sais Biliares/metabolismo , Terapia Biológica , Biomarcadores , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Terapia de Alvo Molecular , Ligação Proteica , Receptores Citoplasmáticos e Nucleares/metabolismo
14.
Recent Results Cancer Res ; 215: 253-261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605233

RESUMO

Colorectal cancer is one of the leading cause of death by cancer worldwide in both men and women. Liquid biopsy belongs nowadays to the landscape of cancer management biological tools. In this chapter, we will describe and discuss the actual, potential and future applications of cfDNA analysis in plasma of patients with colorectal cancer in early or metastatic stage. During the last decade, the development of molecular biology assays like digital PCR or next-generation sequencing made the analysis of cfDNA in plasma possible with an excellent sensitivity and applications like early detection, diagnosis, prognosis, response to treatment, monitoring of an emerging resistance, mapping of the disease molecular landscape or evaluation of the residual disease are now feasible. cfDNA detection has several promising applications in the management of patients with colorectal cancer, but prospective randomised clinical trials are still lacking to make liquid biopsy ready for prime-time.


Assuntos
DNA Tumoral Circulante/análise , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Biópsia Líquida , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias Colorretais/diagnóstico , Humanos , Prognóstico
15.
Dis Colon Rectum ; 63(2): 160-171, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31842159

RESUMO

BACKGROUND: Health care costs and wait times for colorectal cancer treatment are increasing in Canada, but the association between the 2 remains unclear. OBJECTIVE: This study aimed to determine the association between wait times and health care costs and utilization. DESIGN: This is a population-based retrospective cohort study. SETTING: This study was conducted in Manitoba, Canada. PATIENTS: Patients diagnosed with colorectal cancer between 2004 and 2014 were sorted and ranked into quintiles based on the time from index contact for a colorectal cancer-related symptom to first treatment. MAIN OUTCOME MEASURES: The primary outcome is risk-adjusted health care costs, and the secondary outcomes include health care utilization and overall mortality. RESULTS: We included a total of 6936 patients. Total wait times ranged between 0 and 762 days. In comparison with very short wait times, longer wait times were associated with significantly increased costs (short: mean cost ratio 1.21; 95% CI, 1.10-1.32; moderate: mean cost ratio 1.30; 95% CI, 1.19-1.43; long: mean cost ratio 1.48; 95% CI, 1.33-1.64; and very long: mean cost ratio 1.39; 95% CI, 1.26-1.54). Compared with very short wait times, longer wait times were associated with significantly lower risk of mortality (short: HR, 0.78; 95% CI, 0.71-0.86; moderate: HR, 0.72; 95% CI, 0.65-0.80; long: HR, 0.73; 95% CI, 0.66-0.82; very long: HR, 0.76; 95% CI, 0.68-0.85). The median number of pretreatment radiological and endoscopic investigations and surgeon clinic visits increased over the study period across all wait time categories. LIMITATIONS: This is a nonrandomized, retrospective cohort study with potentially limited generalizability. CONCLUSION: Patients with very short and short wait times are likely those diagnosed with life-threatening complications of colorectal cancer. Outside this window, patients with longer wait times experience increased health care costs and utilization with similar overall mortality. Improved care coordination and patient navigation may help contain the increasing wait times and associated increasing health care costs and utilization. See Video Abstract at http://links.lww.com/DCR/B81. ASOCIACIÓN ENTRE LOS TIEMPOS DE ESPERA PARA EL TRATAMIENTO DE UN CÁNCER COLORRECTAL Y LOS COSTOS DE ATENCIÓN MÉDICA: UN ANÁLISIS DE POBLACIÓN: los costos de atención médica y los tiempos de espera para el tratamiento del cáncer colorrectal están aumentando en Canadá, pero la asociación entre los dos sigue sin estar clara.determinar la asociación entre los tiempos de espera y los costos y la utilización de la atención médicaun estudio de cohorte retrospectivo basado en la población.Manitoba, Canadálos pacientes diagnosticados con cáncer colorrectal entre 2004-2014 se clasificaron y sub-clasificaron en quintiles según el tiempo desde el primer contacto índice de síntomas relacionados con cáncer colorrectal hasta el primer tratamiento.El resultado primario son los costos de atención médica ajustados al riesgo, y los resultados secundarios incluyen la utilización de la atención médica y la mortalidad general.Incluimos un total de 6,936 pacientes. Los tiempos de espera totales oscilaron entre 0-762 días. En comparación con los tiempos de espera muy cortos, los tiempos de espera más largos se asociaron con costos significativamente mayores (Corto: relación de costo promedio 1.21, intervalo de confianza del 95% 1.10-1.32; Moderado: relación de costo promedio 1.30, intervalo de confianza del 95% 1.19-1.43; Largo: media relación de costo 1.48, intervalo de confianza del 95% 1.33-1.64; Muy largo: relación de costo promedio 1.39, intervalo de confianza del 95% 1.26-1.54). En comparación con tiempos de espera muy cortos, los tiempos de espera más largos se asociaron con un riesgo de mortalidad significativamente menor (Corto: razón de riesgo 0.78, intervalo de confianza del 95% 0.71-0.86; Moderado: razón de riesgo 0.72, intervalo de confianza del 95% 0.65-0.80; Largo: peligro cociente 0.73, intervalo de confianza del 95% 0.66-0.82; Muy largo: cociente de riesgos 0.76, intervalo de confianza del 95% 0.68-0.85). La mediana del número de investigaciones radiológicas y endoscópicas previas al tratamiento y las visitas al cirujano aumentaron durante el período de estudio en todas las categorías de tiempo de espera.estudio de cohortes retrospectivo, no aleatorio con generalización potencialmente limitadalos pacientes con tiempos de espera « muy cortos ¼ y « cortos ¼ son probablemente aquellos diagnosticados con complicaciones potencialmente mortales del cáncer colorrectal. Fuera de esta ventana, los pacientes con tiempos de espera más largos experimentan mayores costos de atención médica y utilización con una mortalidad general similar. La coordinación mejorada de la atención y la navegación del paciente pueden ayudar a contener el aumento de los tiempos de espera y el aumento de los costos y la utilización de la atención médica. Consulte Video Resumen en http://links.lww.com/DCR/B81. (Traducción-Dr. Edgar Xavier Delgadillo).


Assuntos
Neoplasias Colorretais/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Tempo para o Tratamento/tendências , Adulto , Idoso , Canadá/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Administração dos Cuidados ao Paciente/métodos , Navegação de Pacientes/métodos , Estudos Retrospectivos
16.
Eur Radiol ; 30(1): 291-300, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31209620

RESUMO

OBJECTIVES: To examine the value of baseline 3D-ADC and to predict short-term response to treatment in patients with hepatic colorectal metastases (CLMs). METHODS: Liver MR images of 546 patients with CLMs (2008-2015) were reviewed retrospectively and 68 patients fulfilled inclusion criteria. Patients had received systemic chemotherapy (n = 17), hepatic trans-arterial chemoembolization or TACE (n = 34), and 90Y radioembolization (n = 17). Baseline (pre-treatment) 3D-ADC (volumetric) of metastatic lesions was calculated employing prototype software. RECIST 1.1 was used to assess short-term response to treatment. Prediction of response to treatment by baseline 3D-ADC and 2D-ADC (ROI-based) was also compared in all patients. RESULTS: Partial response to treatment (minimum 30% decrease in tumor largest transverse diameter) was seen in 35.3% of patients; 41.2% with systemic chemotherapy, 32.4% with TACE, and 35.3% with 90Y radioembolization (p = 0.82). Median baseline 3D-ADC was significantly lower in responding than in nonresponding lesions. Area under the curve (AUC) of 3D-ADC was 0.90 in 90Y radioembolization patients, 0.88 in TACE patients, and 0.77 in systemic chemotherapy patients (p < 0.01). Optimal prediction was observed with the 10th percentile of ADC (1006 × 10-6 mm2/s), yielding sensitivity and specificity of 77.4% and 91.3%, respectively. 3D-ADC outperformed 2D-ADC in predicting response to treatment (AUC; 0.86 vs. 0.71; p < 0.001). CONCLUSION: Baseline 3D-ADC is a highly specific biomarker in predicting partial short-term response to treatment in hepatic CLMs. KEY POINTS: • Baseline 3D-ADC is a highly specific biomarker in predicting response to different treatments in hepatic CLMs. • The prediction level of baseline ADC is better for90Y radioembolization than for systemic chemotherapy/TACE in hepatic CLMs. • 3D-ADC outperforms 2D-ADC in predicting short-term response to treatment in hepatic CLMs.


Assuntos
Neoplasias Colorretais/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Adulto , Idoso , Área Sob a Curva , Braquiterapia , Quimioembolização Terapêutica/métodos , Neoplasias Colorretais/terapia , Embolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(12): 1115-1117, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874525

RESUMO

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the "Lancet Gastroenterol Hepatol" (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m(2)) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/terapia , Hipertermia Induzida/métodos , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/terapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Humanos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(12): 1216-1220, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874542

RESUMO

Colorectal carcinoma (CRC) is the third most common malignancy in adults. Pediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with a significantly lower incidence compared to adults. The clinical manifestations of PCRC are not typical, and pediatricians usually have no enough experience in diagnosis and treatment. Therefore, early diagnosis is extremely difficult, which would always lead to late clinical stages when diagnosis is made. At present, the pathogenesis of PCRC is still not clear, and many countries have started to carry out researches at the level of genes, molecules and cells. In both tumor primary tumors and distant metastases, PCRC has obvious difference in distribution from adults, and the proportion of pathological type of mucous adenocarcinoma (including the signet ring cell carcinoma) was significantly higher than that of adults. Although treated according to adult colorectal cancer guidelines, PCRC has been unable to achieve ideal efficacy with poor prognosis and lower long-term survival rate. The purpose of this paper is to summarize the epidemiological characteristics, pathogenesis, clinical symptoms, pathological types, treatment and prognosis of colorectal cancer in children by reviewing the latest literatures at home and abroad.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/etiologia , Adenocarcinoma Mucinoso/terapia , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/epidemiologia , Carcinoma de Células em Anel de Sinete/etiologia , Carcinoma de Células em Anel de Sinete/terapia , Criança , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Humanos , Prognóstico
20.
Rozhl Chir ; 98(10): 414-417, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31842572

RESUMO

INTRODUCTION: Multidisciplinary teams (MDTs) have become a standard part of treating oncological patients. Based on the available data, they have lead to significantly higher survival rates in the treatment of colorectal cancer (CRC). Reported negatives include potentially longer times between diagnoses and the start of appropriate treatment, and the lack of quality controls over the MTDs actions. This report aims to assess the benefits of MDTs using our own data set for 2017. METHODS: Year 2010 saw the institution of an MDT at the Central Military University Hospital in Prague, with the obligation to refer CRC patients to the MDT before the start of treatment. Having standardized the registration, we have implemented a simple procedure to track the quality of our MDTs involvement and its patient benefits: number of patients, number of referrals with proposed diagnostic and therapeutic procedure, frequency and reason of changes to original strategies, and the frequency of variations from the MDTs conclusions. RESULTS: 405 CRC patients were referred to the MDT in 2017; we have found 499 referrals in this group. The data set was formed predominantly by men (61%), with the mean age of 63 (21-91), and the median age of 64.5 years. Surgical treatment was the most commonly proposed procedure (59%), followed by systemic treatment or, as the case may be, radiotherapy. In 24% of the cases, the conclusion did not match the originally proposed procedure. The decision not to go through with the proposed surgical treatment was the most common change (66 %). We have found a difference in the quality of referral in patients examined specifically by the referring doctor, as opposed to patients whose medical records have just been sent in. We have found therapeutic variation in the MTDs conclusions in less than 5% of patients. CONCLUSION: Having analyzed our data for CRC patients referred to the MDT in 2017, we have found out that in 24% of the patients, the MDT referral leads to a change in the originally proposed diagnostic and therapeutic procedure. Consensus among the MDTs members on the CRC patients treatment guarantees an optimum procedure. What is fundamental is that the referring doctor knows the patient. Constant tracking of the MDTs outputs forms a condition for sustaining the quality of its work and a base for assessing its benefits to the patients.


Assuntos
Neoplasias Colorretais/terapia , Equipe de Assistência ao Paciente/normas , Qualidade da Assistência à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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