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1.
Chin J Cancer Res ; 36(1): 66-77, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38455368

RESUMO

Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer. Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer. Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0). Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

2.
Int J Cancer ; 155(1): 159-171, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38385833

RESUMO

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.


Assuntos
Neoplasias Colorretais , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/sangue , Citocinas/sangue , Citocinas/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Fatores de Risco , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Masculino , Feminino , Interleucina-10/sangue , Interleucina-10/genética
3.
iScience ; 26(3): 106214, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36915686

RESUMO

Recent evidence demonstrates that the reprogramming of energy metabolism can interact with the tumor immune microenvironment, thereby participating in the progression of cancer. In this study, multi-omics data of 2471 gastric cancer samples were used to identify tumor glycometabolism and its correlation with tumor immune microenvironment. A series of bioinformatic approaches were performed to establish a scoring system to predict the survival and response of chemotherapy and immunotherapy. Three glycometabolic subtypes and two immune clustering subgroups of gastric cancer were determined. We further established a Gluco-Immune Scoring system to quantify the cancer glycometabolic status and immune infiltration of individual patients. Patients with low Gluco-Immune Score were sensitive to adjuvant chemotherapy, while patients with high Gluco-Immune Score may benefit from immunotherapy. Our results indicate that in gastric cancer, the assessment of tumor glucose metabolism and immune microenvironment has application value for the prediction of curative effects and the formulation of combined treatment strategies.

4.
BJS Open ; 6(3)2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35657137

RESUMO

BACKGROUND: Anastomotic leakage (AL) is a severe complication after colorectal surgery. This study aimed to investigate a method for the early diagnosis of AL after surgical resection by analysing inflammatory factors (IFs) in peritoneal drainage fluid. METHODS: Abdominal drainage fluid of patients with colorectal cancer who underwent resection between April 2017 and April 2018, were prospectively collected in the postoperative interval. Six IFs, including interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor (TNF)-α, matrix metalloproteinase (MMP)2, and MMP9, in drainage were determined by multiplex immunoassay to investigate AL (in patients undergoing resection and anastomosis) and pelvic collection (in patients undergoing abdominoperineal resection). Sparreboom and colleagues' prediction model was first evaluated for AL/pelvic collection, followed by a new IF-based score system (AScore) that was developed by a least absolute shrinkage and selection operator (LASSO) regression, for the same outcomes. The model performance was tested for the area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS: Out of 123 patients eligible, 119 patients were selected, including 12 patients with AL/pelvic collection. Sparreboom and colleagues' prediction model was documented with the best diagnostic efficacy on postoperative day 3 (POD3), with an AUC of 0.77. After optimization, AScore on POD3 increased the AUC to 0.83 and on POD1 showed the best diagnostic efficiency, with an AUC of 0.88. Based on the Youden index, the cut-off value of AScore on POD1 was set as -2.46 to stratify patients into low-risk and high-risk groups for AL/pelvic collection. The model showed 90.0 per cent sensitivity, 69.7 per cent specificity, 98.4 per cent NPV, and 25.0 per cent PPV. CONCLUSIONS: The early determination of IFs in abdominal drainage fluid of patients undergoing colorectal surgery could be useful to predict AL or pelvic collection.


Assuntos
Neoplasias Colorretais , Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Neoplasias Colorretais/cirurgia , Detecção Precoce de Câncer , Humanos
5.
J Immunother Cancer ; 10(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35361730

RESUMO

BACKGROUND: The combination of immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced gastric cancer (GC). It is crucial to unravel chemotherapy-induced tumor microenvironment (TME) modulation and identify which immunotherapy would improve antitumor effect. METHODS: In this study, tumor-associated immune cells (TAICs) infiltration in residual tumor after neoadjuvant chemotherapy (NAC) together with 1075 cases of treatment-naïve GC patients was analyzed first. Then we performed multiplex fluorescence staining of a panel of immune markers (CD3, CD4, CD8, FOXP3 and PDL1) and T cell receptor ß-chain sequencing to phenotype and enumerate T cell subpopulations and clonal expansion in paired GC samples (prechemotherapy and postchemotherapy) from another cohort of 30 cases of stage II/III GC patients. RESULTS: Infiltration of CD68+ macrophages in residual tumors after NAC was significantly decreased compared with treatment-naïve GC patients, while no significant difference observed with respect to other immune markers. In residual tumors, post-NAC CD8 +T cells and CD68+ macrophages levels were significantly associated with chemotherapy response. Post-NAC CD8+ T cell levels remained as an independent predictor for favorable prognosis. Furthermore, when comparing the paired samples before and after NAC from 30 cases of stage II/III GC patients, we found FOXP3+ regulatory T cells proportion significantly decreased after chemotherapy. Pre-NAC FOXP3+ T reg cells level was much richer in the response group and decreased more significantly in the stromal compartment. CD8+ cytotoxic T lymphocytes levels were elevated after chemotherapy, which was more significant in the group treated with XELOX regimen and in patients with better response, consistent with the TCR diversity elevation. CONCLUSIONS: These findings have deepened our understanding of the immune modulating effect of chemotherapy and suggest that the immune profile of specimens after standard chemotherapy should be considered for the personalized immunotherapy to ultimately improve clinical outcome in patients with GC.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Imunofluorescência , Humanos , Linfócitos do Interstício Tumoral , Terapia Neoadjuvante/métodos , Receptores de Antígenos de Linfócitos T , Coloração e Rotulagem , Neoplasias Gástricas/tratamento farmacológico , Microambiente Tumoral
6.
Cell Death Discov ; 8(1): 5, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013132

RESUMO

Rapid proliferation and metastasis of gastric cancer (GC) resulted in a poor prognosis in the clinic. Previous studies elucidated that long non-coding RNA (LncRNA) LINC00205 was upregulated in various tumors and participated in tumor progression. The aim of our study was to investigate the regulating role of LINC00205 in tumorigenesis and metastasis of GC. Both public datasets and our data showed that the LINC00205 was highly expressed in GC tissues and several cell lines. Notably, GC patients with high level of LINC00205 had a poor prognosis in our cohort. Mechanistically, knockdown of LINC00205 by shRNAs suppressed GC cells proliferation, migration, invasion remarkably, and induced cell cycle arrest. Based on bioinformatics prediction, we found that LINC00205 might act as a competitive endogenous RNA (ceRNA) through targeting miR-26a. The level of miR-26a had negatively correlated with LINC00205 expression and was decreased among GC cell lines, tissues, and serum samples. Our results for the first time confirmed that miR-26a was a direct target of LINC00205 and might have the potential to become a plasma marker for clinical tumor diagnosis. Indeed, LINC00205 knockdown resulted in the dramatic promotion of miR-26a expression as well as inhibition of miR-26a potential downstream targets, such as HMGA2, EZH2, and USP15. These targets were essential for cell survival and epithelial-mesenchymal transition. Importantly, LINC00205 was able to remodel the miR-26a-mediated downstream silence, which identified a new mechanism of malignant transformation of GC cells. In conclusion, this study revealed the regulating role of the LINC00205/miR-26a axis in GC progression and provided a new potential therapeutic strategy for GC treatment.

7.
Ann Surg Oncol ; 29(2): 1230-1241, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34550478

RESUMO

BACKGROUND: Anastomotic leakage (AL) is the most serious postoperative complication for patients with gastric cancer. We aim to develop clinically tools to detect AL in the early phase by analysis of the inflammatory factors (IFs) in abdominal drainage. METHODS: We prospectively included 326 patients to establish two independent cohorts, and the concentration of IFs within abdominal drainage was detected. In the primary cohort, an IF-based AL prediction model was constructed using the least absolute shrinkage and selection operator (LASSO) regression. The predictive value of the model was later validated via the validation cohort. RESULTS: Analyzing the IFs with LASSO regression, we developed an Anastomotic Score system on postoperative Day 3 (AScore-POD3), which yielded high diagnostic efficacy in the primary cohort (the area under the curve (AUC) = 0.87). The predictive value of AScore-POD3 was validated in the validation cohort, and its AUC was 0.83. We further built an AScore-POD3 based nomogram by combining the AScore-POD3 system with other clinical risk factors of AL. The C-index of the nomogram was 0.93 in the primary cohort and 0.82 in the validation cohort. CONCLUSIONS: Our study suggests that AL can be early diagnosed after gastric cancer surgery by measuring drainage IFs.


Assuntos
Fístula Anastomótica , Neoplasias Gástricas , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Drenagem , Detecção Precoce de Câncer , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
8.
Langenbecks Arch Surg ; 407(1): 113-122, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34546433

RESUMO

PURPOSE: Enhanced recovery after surgery (ERAS) program has become the main trend in gastrointestinal surgery. This study aims to investigate factors influencing the decision-making of nasogastric tube (NGT) placement and its safety and efficacy after gastrectomy. METHODS: We analyzed our prospectively maintained database including 287 patients who underwent elective gastrectomy in our department from January 1 to December 31, 2017. All cases were divided into two groups, namely, the no-NGT group and the NGT group. Logistic regression was used to analyze factors that affected the decision of NGT placement, and propensity score matching (PSM) was later applied to balance those factors for the analysis of safety outcomes between groups. RESULTS: Multivariate analysis showed resection range (p = 0.004, proximal gastrectomy: OR = 4.555, 95%CI = 1.392-14.905, p = 0.016; total gastrectomy: OR = 1.990, 95%CI = 1.205-3.287, p = 0.009) was the only independent risk factor of NGT placement. NGT was omitted in the majority (58.8%) of distal gastrectomy but only in 42.5% and 25% in total and proximal gastrectomy. After PSM, we found no significant differences between patients with or without NGT in postoperative hospital stay, time to first flatus and defecation, time to fluid and semi-fluid diet, rate of reinsertion, or hospitalization expenditure (p > 0.05, respectively). The incidence of postoperative complications in the two groups were 21.7% and 23.5%, respectively (p = 0.753), and the incidence of major complications was 7.0% and 9.6% (p = 0.472). CONCLUSION: The decision-making of NGT placement is mainly influenced by the resection range. Omitting NGT is a safe approach in all types of gastrectomy but was not able to enhance the recovery in our practice.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias Gástricas , Gastrectomia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
9.
Therap Adv Gastroenterol ; 13: 1756284820936542, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670413

RESUMO

BACKGROUND: With the popularization of Enhanced Recovery After Surgery (ERAS), identifying patients with complications before discharging becomes important. This study aimed to explore the efficacy of C-reactive protein (CRP) in predicting infectious complications after gastrectomy. METHODS: Patients with gastric cancer who underwent gastrectomy at Beijing Cancer Hospital from March 2017 to April 2018 were enrolled in the training set. Complications were prospectively registered. Receiver operating characteristic analysis was performed to assess the diagnostic accuracy of CRP via evaluating the area under the curve (AUC). Patients who had CRP tested on postoperative day (POD) 5 and accepted gastrectomy from April to December 2018 were included in the validation set to validate the cut-off value of CRP obtained from the training set. RESULTS: A total of 350 patients were included (263 patients in the training set and 87 patients in the validation set). Out of these, 24 patients were diagnosed with infectious complications and 17 patients had anastomotic leakage in the training set. The CRP level on POD5 had superior diagnostic accuracy for infectious complications with an AUC of 0.81. The cut-off value of CRP on POD5 at 166.65 mg/L yielded 93% specificity and 97.2% negative predict value (NPV); For anastomotic leakage, the AUC of CRP on POD5 was 0.81. Using the cut-off value of CRP at 166.65 mg/L on POD5 achieved 92% specificity and 98.6% NPV. The optimal cut-off value (CRP 166.65 mg/L on POD5) was validated in the validation set. It achieved 97.5% specificity and 94.0% NPV for infectious complications, and 97.6% specificity and 96.4% NPV for anastomotic leakage. CONCLUSION: CRP is a reliable predictive marker for the diagnosis of inflammatory complications following gastric surgery. However, this study was based on preliminary data. The validity of this data needs confirmation by a larger number of cases.

10.
Sci Adv ; 6(9): eaay4211, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32133402

RESUMO

Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.


Assuntos
Biomarcadores Tumorais/genética , Proteínas de Transporte/genética , Terapia Neoadjuvante , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Gástricas , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , RNA-Seq , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Sequenciamento Completo do Genoma
11.
BMC Cancer ; 19(1): 833, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443699

RESUMO

BACKGROUND: This study was designed to evaluate the impact of postoperative major complications on long-term survival following curative gastrectomy. METHODS: This retrospective study included 239 patients with gastric cancer undergoing gastrectomy at the Beijing Cancer Hospital from February 2012 to January 2013. Survival curves were compared between patients with major complications (mC group) and those without major complications (NmC group). Multivariate analysis was conducted to identify independent prognostic factors. RESULTS: Postoperative complication and mortality rates were 24.7 and 0.8%, respectively. The severity of complications was graded in accordance with the Clavien-Dindo classification. The incidence of minor complications (grades I-II) and major complications (grades III-V) was 9.2 and 15.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were better in the NmC group than in the mC group (p = 0.014, p = 0.013). Multivariate analysis identified major complications as an independent prognostic factor for OS and DFS. After stratification by pathological stage, this trend was also observed in stage II patients. CONCLUSIONS: Postoperative major complications adversely affect OS and DFS. The prevention and early diagnosis of complications are essential to minimize the negative effects of complications on surgical safety and long-term patient survival.


Assuntos
Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Análise de Sobrevida , Resultado do Tratamento
12.
J Investig Med ; 67(5): 856-861, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30792218

RESUMO

Previously, we demonstrated that death-associated protein-3 (DAP3) loss drives chemoresistance in gastric cancer cells. In the present study, we aimed to determine the underlying molecular mechanism. The effect of DAP3 silencing on ß-catenin signaling was assessed. The direct mediator of DAP3 silencing-induced chemoresistance was identified. Depletion of DAP3 stimulates nuclear accumulation of ß-catenin and enhances ß-catenin-dependent transcriptional activity in gastric cancer cells. However, the protein kinase B , , extracellular regulated protein kinase and signal transducer and activator of transcription 3 signaling pathways remain unaffected by DAP3 loss. We found that the downstream target gene LGR5 (leucine-rich G-protein coupled receptor 5) is upregulated in DAP3-depleted gastric cancer cells. Moreover, knockdown of LGR5 resensitizes DAP3-depleted gastric cancer cells to 5-fluorouracil (5-FU) and oxaliplatin. We also observed that ectopic expression of LGR5 reduces apoptosis in gastric cancer cells on treatment with 5-FU and oxaliplatin, which is accompanied by prevention of caspase-3 cleavage. The antiapoptotic protein Bcl-2 is identified as a key mediator of LGR5-induced apoptosis resistance in gastric cancer cells. The present findings indicate that DAP3 deficiency-induced chemoresistance in gastric cancer is at least partially mediated through the ß-catenin/LGR5/Bcl-2 axis. Targeting LGR5 may provide a novel strategy to overcome chemoresistance in DAP3-deficient gastric cancer cells.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , beta Catenina/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Gástricas/genética , Regulação para Cima/genética
13.
Surg Innov ; 25(5): 429-434, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29909757

RESUMO

The aim of this pilot study is to investigate the ability of an electronic nose (e-nose) to distinguish malignant gastric histology from healthy controls in exhaled breath. In a period of 3 weeks, all preoperative gastric carcinoma (GC) patients (n = 16) in the Beijing Oncology Hospital were asked to participate in the study. The control group (n = 28) consisted of family members screened by endoscopy and healthy volunteers. The e-nose consists of 3 sensors with which volatile organic compounds in the exhaled air react. Real-time analysis takes place within the e-nose, and binary data are exported and interpreted by an artificial neuronal network. This is a self-learning computational system. The inclusion rate of the study was 100%. Baseline characteristics differed significantly only for age: the average age of the patient group was 57 years and that of the healthy control group 37 years ( P value = .000). Weight loss was the only significant different symptom ( P value = .040). A total of 16 patients and 28 controls were included; 13 proved to be true positive and 20 proved to be true negative. The receiver operating characteristic curve showed a sensitivity of 81% and a specificity of 71%, with an accuracy of 75%. These results give a positive predictive value of 62% and a negative predictive value of 87%. This pilot study shows that the e-nose has the capability of diagnosing GC based on exhaled air, with promising predictive values for a screening purpose.


Assuntos
Testes Respiratórios/instrumentação , Nariz Eletrônico , Neoplasias Gástricas/diagnóstico , Adulto , Testes Respiratórios/métodos , China , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Neoplasias Gástricas/cirurgia , Compostos Orgânicos Voláteis/análise
14.
J Immunol Res ; 2018: 6827237, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670921

RESUMO

Macrophages play an important role in host defense, in addition to the powerful ability to phagocytose pathogens or foreign matters. They fulfill a variety of roles in immune regulation, wound healing, and tissue homeostasis preservation. Macrophages are characterized by high heterogeneity, which can polarize into at least two major extremes, M1-type macrophages (classical activation) which are normally derived from monocytes and M2-type macrophages (alternative activation) which are mostly those tissue-resident macrophages. Based on the wound healing process in skin, the previous studies have documented how these different subtypes of macrophages participate in tissue repair and remodeling, while the mechanism of macrophages in bowel anastomotic healing has not yet been established. This review summarizes the currently available evidence regarding the different roles of polarized macrophages in the physiological course of anastomotic healing and their pathological roles in anastomotic leakage, the most dangerous complication after gastrointestinal surgery.


Assuntos
Fístula Anastomótica/imunologia , Procedimentos Cirúrgicos do Sistema Digestório , Intestinos/cirurgia , Ativação de Macrófagos , Macrófagos/imunologia , Complicações Pós-Operatórias/imunologia , Animais , Diferenciação Celular , Homeostase , Humanos , Intestinos/patologia , Cicatrização
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 21(4): 372-377, 2018.
Artigo em Chinês | MEDLINE | ID: mdl-29682705

RESUMO

Anastomotic leakage is one of the most serious complications of colorectal surgery. Despite progress in available surgical techniques, the morbidity associated with anastomotic leakage remains high. In this review, we summarize the current clinical status of this complication, the problems it causes, and relevant research achievements. To date, a lack of consensus regarding the diagnosis of anastomotic leakage has resulted in varying rates of diagnosis across countries and regions worldwide. Accurately predicting the occurrence of anastomotic leakage using the established risk factors and preoperative scoring systems remains difficult. Many of the described preventive measures, including defunctioning stoma creation, positive air leak testing, and use of effective tissue adhesives, remain controversial; more evidence-based medical information is urgently needed. Delayed diagnoses of anastomotic leakage also remain common in clinical practice. To prevent catastrophic outcomes, such as reoperations or deaths, early diagnosis is critically important. Parameters local to the area of the anastomosis may facilitate early detection of leakage, but their effectiveness is subject to clinical validation. Lastly, the pathological etiology of anastomotic leakage remains to be determined, and its elucidation may inspire innovative interventions that solve this critical surgical complication.


Assuntos
Fístula Anastomótica , Cirurgia Colorretal/efeitos adversos , Anastomose Cirúrgica , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Fatores de Risco , Estomas Cirúrgicos
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(2): 135-139, 2017 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-28226344

RESUMO

OBJECTIVE: Postoperative complications are important outcome measurements for surgical quality and safety control. However, the complication registration has always been problematic due to the lack of definition consensus and the other practical difficulties. This narrative review summarizes the data registry system for single institutional registry, national data registry, international multi-center trial registries in the western world, aiming to share the experience of complication classification and data registration. We interviewed Dr. Koh from Royal Prince Alfred Hospital in Australia for single institutional experience, Dr. van der Wielen and Dr. Desideriofor, from two international multi-center trial(STOMACH) and registry (IMIGASTRIC) respectively, and Prof. Dr. Wijnhoven from the Dutch Upper GI Audit(DUCA). The major questions include which complications are obligated to report in the respective registry, what are the definitions of those complications, who perform the registration, and how are the complications evaluated or classified. Four telephone conferences were initiated to discuss the above-mentioned topics. The DUCA and IMGASTRIC provided the definition of the major complications. The consent definition provided by DUCA was based on the LOW classification which came out after a four-year discussion and consensus meeting among international experts in the according field. However, none of the four registries asked for an obligatory standardization of the diagnostic criteria among the participating centers or surgeons. Instead, all the registries required a detailed recording of the diagnostic strategy and classification of the complications with the Clavien-Dindo scoring system. Most data were registered by surgeons or data managers during or immediately after the hospitalization. The investigators or an independent third party conducted the auditing of the data quality. Standardization of complication diagnosis among different centers is a difficult task, consuming much effort and time. On top of that, standardization of the complication registration is of critical and practical importance. We encourage all centers to register complications with the diagnostic criteria and following intervention. Based on this, the Clavien-Dindo classification can be properly justified, which has been widely accepted by most centers and should be routinely used as the standard evaluation system for postoperative complications in gastric tumor surgery.


Assuntos
Coleta de Dados/normas , Técnicas e Procedimentos Diagnósticos/normas , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros/normas , Medição de Risco/métodos , Medição de Risco/normas , Neoplasias Gástricas/cirurgia , Austrália/epidemiologia , Coleta de Dados/estatística & dados numéricos , Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Países Baixos/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Neoplasias Gástricas/complicações
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(2): 177-183, 2017 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-28226352

RESUMO

OBJECTIVE: To analyze the change in postoperative complication rate after gastric cancer surgery registered in the Peking University Cancer Hospital in recent 11 years and the learning curve of complication registration, and to investigate how to improve the complication registration and evaluation in gastric cancer surgery. METHODS: Patients who underwent open or laparoscopic gastric cancer surgery between April 14, 2005 and February 15, 2016 in our institution were included in the study, and those without essential clinical and administrative data were excluded. Data were biennially collected, and linear regression was performed to investigate the changes of the following parameters, including overall complication rate, severe complication proportion (proportion of complications with Clavien-Dindo score ≥III(a in the total registered complications), re-operation rate and the major complication rate. RESULTS: A total of 5 666 patients were included in the analysis, with 4 111 males (72.56%) and 1 555 females (27.44%). The average age was (58.87±11.50) years and average BMI was(23.15±3.30) kg/m2. There were 305 patients included in the 2005-2006 interval, 810 patients in 2007-2008, 957 patients in 2009-2010, 1 163 patients in 2011-2012, 1 421 patients in 2013-2014, and 1 010 patients in 2015-2016, respectively. The overall re-operation rate was 2.34%(133/5 666), postoperative mortality was 0.41%(23/5 666), registered complication rate was 19.66%(1 114/5 666), severe complication proportion was 32.28%(338/1 047), and the proportion of complication missing the Clavien-Dindo score was 6.01%(67/1 114). The linear regression showed the re-operation rate (r=0.13, P=0.801) and postoperative mortality (r=0.58, P=0.231) remained low (< 4% and < 1% respectively) since 2005, and showed no statistical significance. The registered complication rate showed evident increase from 3.93%(12/305) to 29.13%(414/1 421) between 2005 and 2014 (r=0.92, P=0.010), and slight decrease to 22.77%(230/1 010) in 2015-2016. The severe complication proportion significantly decreased from 6/9 in 2005-2006 to 22.73%(50/220) in 2015-2016 (r=0.90, P=0.014). The proportion of complication missing the Clavien-Dindo score significantly decreased from 25.00%(3/12) in 2005-2006 to 4.35%(10/230) in 2015-2016(r=0.82, P=0.044). The most common complications were infection (9.12%, 517 cases), effusions (6.26%, 355 patients), gastrointestinal motility disorder (4.45%, 252 cases), anastomotic leakage (3.19%, 181 cases) and bleeding (2.31%, 131 cases). The registered rates of these complications all increased since 2005, and the rates of leakage and effusions decreased since 2012 while the others decreased after 2014. CONCLUSIONS: According to the data from our institution in the recent 11 years, a learning curve exists in our institution for complication registration in gastric cancer surgery. The administrative data appears to be more reliable than registered complication data in quality and safety evaluation during the learning period. A detailed classification with the Clavien-Dindo score aids to the use of complication data for the quality and safety measurement.


Assuntos
Coleta de Dados/métodos , Coleta de Dados/estatística & dados numéricos , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Prontuários Médicos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/cirurgia , Idoso , Fístula Anastomótica/etiologia , Feminino , Gastrectomia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Neoplasias Gástricas/complicações
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