Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119
Filtrar
1.
Colorectal Dis ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040248

RESUMO

AIM: Many studies have demonstrated predictors of the difficulty of laparoscopic anterior resection for rectal cancer. Few studies focus on the influence of pelvic dimensions on robotic-assisted mesorectal excision (ME) and intersphincteric resection (ISR). This study aimed to evaluate the influences of the mesorectal fat area (MFA) and mesorectal area on the difficulty of robotic sphincter-saving surgery. METHODS: We included 156 patients with middle and low rectal cancer who underwent robotic sphincter-saving surgery. Clinical and anatomical factors, including the pelvic dimensions, were collected. Linear regression was performed for variables associated with surgical duration. We also performed subgroup analyses for robotic-assisted ME and ISR. Logistic regression was used to find variables associated with transanal dissection. RESULTS: For patients with middle or low rectal cancer, the sacral length and tumour distance from the anal verge were independently associated with surgical duration. The pT stage, sacral length, and the MFA were independent predictors for the surgical duration of robotic-assisted ME. By contrast, a small mesorectal area was independently related to a longer duration of robotic-assisted ISR. The pelvic outlet length was independently associated with the use of transanal dissection for ISR. CONCLUSION: It is suggested that a large MFA could affect the difficulty of mesorectal excision in robotic-assisted ME, while a small mesorectal area could increase the surgical difficulty of robotic-assisted ISR for low rectal cancer. Besides, the pelvic outlet length was associated with the use of transanal dissection. Further studies are needed to validate the results and draw more scientific conclusions.

2.
Future Oncol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067478

RESUMO

Aim: To explore the impact of preoperative the albumin-to-globulin ratio (AGR) and the prognostic nutritional index (PNI) on prognosis in rectal mucinous adenocarcinoma (MAC). Methods: A total of 128 patients were included. Results: According to the X-tile analysis, cutoff values of AGR and PNI were 1.1 and 43.8. Preoperative AGR (p = 0.041), preoperative PNI (p = 0.036) and pTNM stage (p = 0.003) were independently associated with overall survival in rectal MAC patients. Distance from the anal verge (p = 0.005), preoperative AGR (p = 0.021), preoperative PNI (p = 0.007) and pTNM stage (p < 0.001) were significantly associated with disease-free survival in rectal MAC patients. Nomograms for overall survival and disease-free survival were developed (C-index: 0.739 and 0.764). Conclusion: Preoperative AGR and PNI can act as effective predictors for survival for rectal MAC patients.

3.
World J Surg ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020327

RESUMO

BACKGROUND: Coagulation and inflammation play important roles in tumor progression. This study aimed to explore the prognostic impact of combined analysis of fibrinogen and neutrophil-to-lymphocyte (NLR) ratio (F-NLR score) in locally advanced rectal cancer (LARC) receiving preoperative chemoradiotherapy (pCRT) and radical surgery. METHOD: Totally 317 patients were included. X-tile analysis was used to determine the optimal cutoff values of preoperative fibrinogen and NLR. F-NLR scores were defined as 2 (both high fibrinogen and NLR), 1 (one of these abnormalities), or 0 (neither abnormality). Time-dependent ROC analysis was used to evaluate the predictive accuracy of fibrinogen, NLR, and F-NLR score. Cox regression analysis was performed to evaluate the prognostic impact of the F-NLR score. A predictive nomogram for disease-free survival (DFS) was developed and validated internally. RESULTS: One hundred and seventeen (36.9%), 156 (49.2%), and 44 (13.9%) patients had F-NLR score of 0, 1, and 2, respectively. Higher F-NLR score was associated with poorly differentiated tumors, deeper tumor invasion, lymph node metastasis, and more advanced pTNM stage (all P < 0.05). The 5-year OS rates in the F-NLR 0, 1, and 2 groups were 93.6%, 87.3%, and 68.4%, respectively (P < 0.001), while the 5-year DFS rates were 91.8%, 76.8%, and 56.1%, respectively (P < 0.001). Cox regression analysis demonstrated that F-NLR score (F-NLR 1, HR = 2.021, P = 0.046; F-NLR 2, HR = 3.356, P = 0.002), pTNM stage III (HR = 3.109, P = 0.009), and circumferential resection margin (CRM) involvement (HR = 3.120, P = 0.021) were independently associated with DFS. A nomogram for DFS was developed (C-index 0.708). CONCLUSION: F-NLR score is a promising predictor for disease recurrence in LARC patients after pCRT.

4.
Exp Cell Res ; : 111856, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31981591

RESUMO

CES-2 (carboxylesterase-2) belongs to the carboxylesterase gene family, which plays crucial roles in lipid mobilization and chemosensitivity to irinotecan. However, its role in chemosensitivity to oxaliplatin (L-OHP) remains unclear. Herein, L-OHP-resistant cells (HCT-116L and RKOL) were established by increasing the concentration of L-OHP. The results showed that CES2 expression was upregulated in L-OHP-resistant tissues and cells lines (both P < 0.01). Low expression of CES2 correlated with a better survival, and the results were further confirmed in the R2 platform: a biologist friendly web-based genomics analysis and visualization application. Downregulation of CES2 suppressed cell proliferation, induced apoptosis and reversed L-OHP resistance by medicating the PI3K signaling pathway in L-OHP-resistant cells. However, both PI3K inhibitor (LY294002) and activator (IGF-1) could not medicate CES2 expression. These findings indicated that CES2 may be utilized as a novel biomarker and therapeutic target for L-OHP resistance in CRC treatment.

5.
Ann Clin Lab Sci ; 49(6): 730-739, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31882423

RESUMO

OBJECTIVE: By in silico analysis of colon cancer data from the Cancer Genome Atlas (TCGA) database, we develop a prognostic signature to improve the stratification of high-risk stage II colon cancer patients. METHOD: RNA sequencing (RNA-Seq) data from 187 stage II colon cancer patients was obtained from the TCGA data portal. We excluded cases without a sufficient amount of survival data (n=21), leaving 166 stage II colon cancer patients to be selected for further survival analysis. Differentially expressed lncRNAs and miRNAs were unveiled by the edgeR package of R. A comprehensive ceRNAs regulatory network was constructed using the Cytoscape. Cox regression analysis was performed to screen prognostic RNAs and develop a prognostic signature. The Multi Experiment Matrix and Gene Ontology were undertaken to assess the prognostic lncRNA MIR31HG function. RESULTS: The multivariate analysis indicates that 2 lncRNAs (WASIR2 and MIR31HG) and 2 miRNAs (hsa-mir-200a and hsa-mir-155) exhibited an independently significant prognostic value for stage II colon cancer. The 4 lncRNA-miRNA signatures for predicting the overall survival (OS) was constructed with the formula: Risk score=exp WASIR2*(0.213)+exp MIR31HG*(0.152)+exp hsa-mir-200a*(-0.329)+exp hsa-mir-155*(0.300). The area under the curve in the receiver operating characteristic analysis was 0.810. Kaplan-Meier survival curves confirm that the low-risk group had a low death rate, with a 5-year OS rate at 87.7%. However, the high-risk group had a low 5-year OS of 23.1% (P=0.000). The correlative genes of MIR31HG were found to be enriched in the epithelial-to-mesenchymal transition pathway, and the VEGFR3 signaling in lymphatic endothelium pathways. CONCLUSIONS: These findings indicate that the 4 lncRNA-miRNA prognostic signature could be a marker for survival of stage II colon cancer patients.

6.
Sci Rep ; 9(1): 19743, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874979

RESUMO

This is a retrospective study examining the efficacy and safety of Gamma Knife radiosurgery (GKS) in treating patients with cerebral cavernous malformations (CCMs). Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31763775

RESUMO

OBJECTIVE: We sought to evaluate the correlations of pre-PCI QFR analysis with virtual PCI called residual QFR and post-PCI QFR compared to post-PCI FFR. BACKGROUND: Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on angiography without use of a pressure wire. The ability to evaluate post-PCI FFR using pre-PCI QFR analysis with a virtual PCI and the correlation between post-PCI QFR compared to post-PCI FFR remains unknown. METHODS: From the DOCTORS (Does Optical Coherence Tomography Optimize Results of Stenting) study population, we blindly analyzed residual QFR and post-PCI QFR from angiographies and compared them to post-PCI FFR. RESULTS: Ninety-three post-PCI QFR measurements and 84 pre-PCI residual QFR measurements were compared to post-PCI FFR measurements. No significant difference were observed between mean post-PCI FFR value (0.92 ± 0.05) compared to mean residual (0.93 ± 0.05) QFR and between mean post-PCI FFR value compared to mean post-PCI QFR values were (0.93 ± 0.05) (p > .05 for both). The correlation coefficient of residual QFR with post-PCI FFR was 0.68 (95% CI: 0.53-0.78) and the correlation coefficient of post-PCI-QFR with post-PCI FFR was 0.79 (95% CI: 0.70-0.86). CONCLUSIONS: Residual QFR corresponding to pre-PCI QFR analysis with virtual PCI, and post-PCI QFR analysis, correlated well with post-PCI FFR. Further studies are needed to prospectively validate a QFR-guided PCI strategy.

8.
Cancer Cell Int ; 19: 276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31700498

RESUMO

Background: Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods: CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA-miRNA-mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results: Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion: In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.

9.
J Clin Oncol ; 37(34): 3223-3233, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557064

RESUMO

PURPOSE: In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS: Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS: In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% (P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% (P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% (P = .971 by log-rank test), respectively. CONCLUSION: mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

10.
Surgery ; 166(6): 1048-1054, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31543322

RESUMO

BACKGROUND: Intestinal inflammation is the predominant contributor to the genesis of postoperative ileus. Janus kinase 1 plays an important role during inflammation. Here, we investigated the role of Janus kinase 1 in postoperative ileus and whether inhibition of Janus kinase 1 could mitigate postoperative ileus. METHODS: A mouse model of postoperative ileus was induced by intestinal manipulation. Janus kinase 1 inhibitor GLPG0634 or placebo was administered orally before intestinal manipulation. At the indicated time points post operation, neutrophil infiltration was assessed by immunohistochemistry and enzyme-linked immunosorbent assay; proinflammatory gene expression was quantified by quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay; and Janus kinase 1 activation was detected by Western blot. Functional studies were conducted to evaluate intestinal motility. RESULTS: We found that intestinal manipulation led to marked activation of Janus kinase 1, with increased proinflammatory gene expression and upregulated myeloperoxidase level. Moreover, intestinal manipulation resulted in an impairment of intestinal transit in vivo and inhibition of smooth muscle contractility in vitro. Preoperative administration of GLPG0634 markedly lowered the expression of proinflammatory cytokines, the myeloperoxidase level in the muscularis layer after bowel manipulation, and significantly ameliorated smooth muscle contractile function and intestinal transit ability. CONCLUSION: Our data showed that Janus kinase 1 activation mediated intestinal manipulation-induced resident macrophage activation after intestinal manipulation, and subsequent complex inflammatory cascade and gut dysmotility. Janus kinase 1 inhibition appears to be a prospective and convenient approach for the prevention of postoperative ileus.

11.
Pathol Res Pract ; 215(8): 152478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176574

RESUMO

BACKGROUND: Overexpression of Frizzled-7 (FZD7) has been associated with tumor invasion and distant metastases, but little is known about the relationship between FZD7 expression and prognosis in colon cancer. PATIENTS AND METHODS: A total of 114 patients with colon cancer between June 2010 and December 2010 were enrolled in this study. The expression of FZD7 in cancerous and adjacent non-cancerous tissues was determined by immunohistochemistry, and the association between FZD7 expression and patient's clinicopathological characteristics was explored. The correlation between FZD7 expression and prognosis of colon cancer patients was analyzed using the Oncomine database and R2. RESULTS: FZD7 expression levels were significantly higher in colon cancer tissues compared with adjacent non-cancerous tissues (P < 0.001). High expression of FZD7 was significantly associated with metastatic or recurrent disease in colon cancer (P = 0.010). Kaplan-Meier survival analysis demonstrated that colon cancer patients with high expression of FZD7 had a significantly poorer OS (P = 0.013) and DFS (P = 0.010). Cox regression demonstrated that the expression of FZD7 was an independent prognostic factor for DFS (HR = 6.647, P = 0.023). A meta-analysis from the Oncomine database demonstrated that FZD7 mRNA levels were significantly higher in colorectal cancer tissues than in normal colorectal tissues, and FZD7 high expression was associated with a significantly poorer event and relapse-free survival time by analyzing the data from the R2: Genomics Analysis and Visualization Platform. CONCLUSIONS: Overexpression of FZD7 was associated with poor survival in patients with colon cancer. Our data suggest that FZD7 expression could be an effective prognostic biomarker for colon cancer.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Receptores Frizzled/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , RNA Interferente Pequeno/genética
12.
Mol Oncol ; 13(11): 2344-2360, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31246342

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer. There is a comparable number of lncRNAs to protein-coding genes, but the expression patterns, functions, and molecular mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. In this study, we report the identification of a novel lncRNA, named long noncoding RNA regulating IL-6 transcription (LNRRIL6), which is upregulated in CRC tissues and cell lines. Increased LNRRIL6 expression is associated with aggressive clinicopathological characteristics and poor prognosis of CRC patients. Functional experiments showed that enhanced expression of LNRRIL6 promotes CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Conversely, depletion of LNRRIL6 inhibits CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Mechanistically, we revealed that LNRRIL6 physically binds to the IL-6 promoter, thereby increasing IL-6 transcription, inducing IL-6 autocrine signaling, and activating the IL-6/STAT3 pathway. The expression of IL-6 is positively associated with that of LNRRIL6 in CRC tissues. Blocking the IL-6/STAT3 pathway using the FDA-approved IL-6-receptor antagonist antibody, tocilizumab, abolished the oncogenic role of LNRRIL6 in CRC. Taken together, these findings identify a novel lncRNA, LNRRIL6, that promotes CRC cell survival through activation of the IL-6/STAT3 pathway and suggest that LNRRIL6 may be a potential prognostic biomarker and therapeutic target for CRC.

13.
J Neurosurg ; : 1-8, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226692

RESUMO

OBJECTIVE: The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS). METHODS: This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival. RESULTS: The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001). CONCLUSIONS: The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

14.
Eur J Surg Oncol ; 45(7): 1225-1231, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30879932

RESUMO

AIM: To evaluate the pattern of tumor relapse of pathological complete response (pCR) patients with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), and to identify predictive factors of distant metastasis in pCR patients after nCRT. METHOD: This was a retrospective analysis of 118 LARC patients who achieved a pCR following nCRT and TME from 2008 to 2015. Clinicopathological and therapeutic parameters were evaluated as possible predictors of distant metastasis-free survival (DMFS), and COX regression analysis was performed. RESULTS: After a median follow-up of 57 months, the 5-year overall and disease-free survival rates were 94.7% and 88.1%, respectively. Overall, 6 patients (5.1%) died, no local recurrence occurred, 13 patients (11%) developed distant metastases, including lung (n = 5), liver (n = 2), bone (n = 3), lung and brain (n = 1), peritoneal (n = 1), and spleen (n = 1) metastasis. On univariate analysis, tumor distance from the anal verge (HR = 0.706, P = 0.039), acellular mucin pools (HR = 6.687, P = 0.002), and MUC1 expression (HR = 8.280, P < 0.001) were independently associated with DMFS. COX regression demonstrated that MUC1 expression (HR = 3.812, P = 0.041) remained to be an independent predictor of DMFS in pCR patients. CONCLUSION: Distant metastasis still remained a major concern in pCR patients following nCRT and TME. Tumor distance from the anal verge, acellular mucin pools, and MUC1 expression were associated with distant metastasis in patients with pCR. MUC1 staining remained to be an independent risk factor for DMFS. Such information could facilitate treatment decision in these patients, such as adjuvant chemotherapy and follow-up.

15.
BMJ Open ; 9(3): e025944, 2019 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-30904869

RESUMO

INTRODUCTION: Preoperative radiotherapy followed by total mesorectal excision with adjuvant chemotherapy has been recommended as the preferred treatment method for locally advanced rectal cancer (LARC). Similar rates of local control, survival and toxicity were observed in preoperative long-course chemoradiotherapy (LCRT) (45-50.4 Gy in 25-28 fractions) and in short-course radiotherapy (SCRT) with 25 Gy over five fractions. Both regimens lower the local recurrence rates compared with that of surgery followed by postoperative radiotherapy. With the simplicity and lower cost of SCRT, a growing number of patients have been receiving SCRT as preoperative radiotherapy. However, the currently established SCRT (25 Gy over five fractions) followed immediately by surgery resulted in poor downstaging and sphincter preservation rate. The pathological complete response (pCR) rate is also markedly lower with SCRT than with LCRT (0.7%vs16%). Several studies recommended SCRT with delayed surgery for more than 4 weeks with expectation of improved pathological outcomes and fewer postoperative complications. While a number of clinical trials demonstrated a persistently better overall local control with SCRT than with LCRT, overall survival advantage has not been observed. Since survival is mainly depended on distant metastases, efforts should be made towards more effective pathological response and systemic treatment. Given the apparent advantages of SCRT, we aimed to establish a dose escalation of SCRT and sequential modified FOLFOX6 (mFOLFOX6) as preoperative therapy for LARC with objectives of achieving an optimal balance of safety, cost effectiveness and clinical outcome, and to support further investigation of this regimen in a phase II/III setting. METHODS: In this phase I study, three dose levels (6Gy×5F, 7Gy×5F, 8Gy×5F to gross tumour volume, while keeping the rest of irradiated volume at 5Gy×5) of SCRT followed by four cycles of mFOLFOX6 chemotherapy as neoadjuvant therapy will be tested by using the traditional 3+3 design. The pCR rate, R0 resection rate, sphincter preservation rate and treatment related toxicity will be assessed. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Fujian Medical University Union Hospital (No. 2017YF020-02) and all participants provided written informed consent. Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT03466424; Pre-results.

16.
J Cell Physiol ; 234(10): 18180-18191, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30859572

RESUMO

The resistance against oxaliplatin (L-OHP) based regimens remains a major obstacle for its efficient usage in treating metastatic colorectal cancer (mCRC). In this study, we performed weighted gene coexpression network analysis (WGCNA) to systematically screen the relevant hub genes for L-OHP resistance using the raw microarray data of 30 consecutive mCRC samples from our earlier study (GSE69657). The results were further confirmed through datasets from Gene Expression Omnibus (GEO). From L-OHP resistance module, nine genes in both the coexpression and protein-protein interaction networks were chosen as hub genes. Among these genes, Meis Homeobox 2 (MEIS2) had the highest correlation with L-OHP resistance (r = -0.443) and was deregulated in L-OHP resistant tissues compared with L-OHP sensitive tissues in both our own dataset and GSE104645 testing dataset. The receiver operating characteristic curve validated that MEIS2 had a good ability in predicting L-OHP response in both our own dataset (area under the curve [AUC] = 0.802) and GSE104645 dataset (AUC = 0.746). Then, the down expression of MEIS2 was observed in CRC tissue compared with normal tissue in 12 GEO-sourced datasets and The Cancer Genome Atlas (TCGA) and was correlated with poor event-free survival. Furthermore, analyzing methylation data from TCGA showed that MEIS2 had increased promoter hypermethylation. In addition, MEIS2 expression was significantly decreased in CRC stem cells compared with nonstem cells in two GEO datasets (GSE14773 and GSE24747). Further methylation analysis from GSE104271 demonstrated that CRC stem cells had higher MEIS2 promoter methylation levels in cg00366722 and cg00610348 sites. Gene set enrichment analysis showed that MEIS2 might be involved in the Wnt/ß-catenin pathway. In the overall view, MEIS2 had increased promoter hypermethylation and was downregulated in poor L-OHP response mCRC tissues. MEIS2 might be involved in the Wnt/ß-catenin pathway to maintain CRC stemness, which leads to L-OHP resistance.

17.
J Cancer ; 10(3): 730-736, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719172

RESUMO

Purpose: To evaluate the effect of an intensified capecitabine and oxaliplatin (XELOX) chemoradiation treatment followed by one cycle of consolidation chemotherapy before surgery in locally advanced rectal cancer (LARC). Methods and Materials: Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) were enrolled. All patients received 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with a dose 50.4Gy in 25 fraction, with two cycles of concurrent XELOX chemotherapy. Thereafter, another cycle of consolidation chemotherapy with XELOX/FLOFOX was administered during the resting period after completion of concurrent chemoradiation (CRT). Tumor response, toxicities, surgical complications, and long-term clinical outcomes were recorded. Results: From January 2011 to December 2013, a total of 96 patients were enrolled in the study. All patients completed the treatment plan of concurrent chemoradiation and consolidate chemotherapy. During concurrent chemoradiation, the incidence of grade 3/4 toxicities was leucopenia (2.1%), thrombocytopenia (4.2%), diarrhea (6.3%). 18 patients (18.8%) developed surgical complications. Pathologic complete response (pCR) was achieved in 20 (20.8%) patients. Tumor down-staging occurred in 69 (71.9%) patients and down-staging of nodes occurred in 47 (49.0%) patients. Of these 96 patients, 5-year local recurrence-free survival, metastasis-free survival, disease-free survival and overall survival rates was 98.9%, 84.7%, 83.7% and 82.1%, respectively, with a median follow-up of 4.24years. Conclusions: The intensified treatment paradigm of XELOX concurrent chemoradiation followed by one cycle of consolidation chemotherapy was well tolerated in our cohort and provided a promising long-term oncologic outcome, which warranted further investigation in a randomize trails.

18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(1): 85-93, 2019 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-30703799

RESUMO

OBJECTIVE: To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma. METHODS: Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. RESULTS: A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma. CONCLUSION: As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.


Assuntos
Adenocarcinoma Mucinoso/terapia , Neoplasias Retais/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/radioterapia , Adenocarcinoma Mucinoso/cirurgia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Protectomia , Prognóstico , Radioterapia Adjuvante , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Resultado do Tratamento
19.
J Hematol Oncol ; 12(1): 16, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764882

RESUMO

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

20.
World Neurosurg ; 125: e132-e138, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30677586

RESUMO

OBJECTIVE: To assess the sensitivity and specificity of arteriovenous malformation (AVM) nidal component identification and quantification using an unsupervised machine learning algorithm and to evaluate the association between intervening nidal brain parenchyma and radiation-induced changes (RICs) after stereotactic radiosurgery. METHODS: Fully automated segmentation via unsupervised classification with fuzzy c-means clustering was used to analyze the AVM nidus on T2-weighted magnetic resonance imaging studies. The proportions of vasculature, brain parenchyma, and cerebrospinal fluid were quantified. These were compared with the results from manual segmentation. The association between the brain parenchyma component and RIC development was assessed. RESULTS: The proposed algorithm was applied to 39 unruptured AVMs in 39 patients (17 female and 22 male patients), with a median age of 27 years. The median proportion of the constituents was as follows: vasculature, 31.3%; brain parenchyma, 48.4%; and cerebrospinal fluid, 16.8%. RICs were identified in 17 of the 39 patients (43.6%). Compared with manual segmentation, the automated algorithm was able to achieve a Dice similarity index of 79.5% (sensitivity, 73.5%; specificity, 85.5%). RICs were associated with a greater proportion of intervening nidal brain parenchyma (52.0% vs. 45.3%; P = 0.015). Obliteration was not associated with greater proportions of nidal vasculature (36.0% vs. 31.2%; P = 0.152). CONCLUSIONS: The automated segmentation algorithm was able to achieve classification of the AVM nidus components with relative accuracy. Greater proportions of intervening nidal brain parenchyma were associated with RICs.


Assuntos
Encéfalo/efeitos da radiação , Malformações Arteriovenosas Intracranianas/radioterapia , Tecido Parenquimatoso/efeitos da radiação , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Aprendizado de Máquina não Supervisionado , Adolescente , Adulto , Idoso , Algoritmos , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA