scholarly journals Squamous Differentiation in pT1 Low-Grade Bladder Urothelial Carcinoma is Associated with High Risk of Recurrence

2021 ◽  
Author(s):  
Wanqing Wei ◽  
Jianwei Zhang ◽  
Keruo Wang ◽  
Shunlin Xia ◽  
Zhiqun Shang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Independent Predictor ◽  
Hazard Analysis ◽  
Postoperative Recurrence ◽  
Clinicopathological Characteristics ◽  
Low Grade ◽  
Squamous Differentiation ◽  
Kaplan Meier ◽  
Bladder Urothelial Carcinoma ◽  
Multiple Recurrences

Abstract Background A large number of studies have confirmed that squamous differentiation is closely related to the prognosis of bladder cancer, and studies also showed that it is an independent predictor for the prognosis of such disease. However, the role of squamous differentiation in pT1 low-grade bladder cancer (LGBC) has not been reported yet. This study mainly intends to explore the clinical significance of squamous differentiation in pT1 LGBC.Methods The clinicopathological data of 582 patients with pT1 LGBC from April 2007 to December 2018 were retrospectively analyzed, including 51 cases pathologically diagnosed as pT1 LGBC with squamous differentiation, and 531 cases as pT1 LGBC without squamous differentiation. The clinicopathological characteristics and prognosis of patients in the two groups were compared.Results 51 cases (8.7%) were pathologically diagnosed as pT1 LGBC with squamous differentiation. As compared with non-squamous differentiation, squamous differentiation was closely related to the age of patients (P=0.009) and postoperative recurrence (P<0.001). Further studies on the pT1 LGBC recurrence group showed that the patients in the squamous differentiation group were more prone to multiple recurrences (P=0.033) and invasive recurrence (P<0.001) after surgery. The Kaplan-Meier analysis indicated that pT1 LGBC patients with squamous differentiation had shorter recurrence-free survival (RFS) time. The Cox proportional hazard analysis confirmed that squamous differentiation was an independent predictor of RFS time in patients with pT1 LGBC.Conclusions Squamous differentiation is closely related to postoperative recurrence of pT1 LGBC, especially multiple recurrences and invasive recurrence after surgery. Squamous differentiation is an independent predictor of the RFS time in patients with pT1 LGBC.

scholarly journals Lymphocyte antigen 6 superfamily member D is a marker of urothelial and squamous differentiation: implications for risk stratification of bladder cancer

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Nina Andersson ◽  
Johan Ohlsson ◽  
Sara Wahlin ◽  
Björn Nodin ◽  
Karolina Boman ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Population Based ◽  
Clinicopathological Characteristics ◽  
Low Grade ◽  
Urothelial Bladder Cancer ◽  
Squamous Differentiation ◽  
Lymphocyte Antigen ◽  
Urothelial Bladder ◽  
Incident Cases

Abstract Background Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account.

scholarly journals P109 Impact of ethnicity on colorectal cancer incidence in a cohort of colitis-associated dysplasia patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S201-S202
Author(s):  
M Kabir ◽  
K Curtius ◽  
P Kalia ◽  
I Al Bakir ◽  
C H R Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Hazard Analysis ◽  
Cox Proportional Hazards ◽  
Time Interval ◽  
Low Grade ◽  
Kaplan Meier ◽  
The Impact

Abstract Background Racial disparities in inflammatory bowel disease (IBD) phenotypic presentations and outcomes are recognised. However, there are conflicting data from Western population-based cohort studies as to whether racial differences in colitis-associated colorectal cancer (CRC) incidence exists. To our knowledge this is the first study to investigate the impact of ethnicity on the natural history of dysplasia in ulcerative colitis (UC). Methods We performed a retrospective multi-centre cohort study of adult patients with UC whose first low-grade dysplasia (LGD) diagnosis within the extent of colitis was made between 1 January 2001 and 30 December 2018. Only patients with at least one follow-up colonoscopy or colectomy by 30 August 2019 were included. The study end point was time to CRC or end of follow-up. Statistical differences between groups were evaluated using Mann-Whitney U tests and Chi-squared tests. Survival analyses were performed using Kaplan-Meier estimation and multivariate Cox proportional hazards models. Results 408 patients met the inclusion criteria (see Figure 1 for patient and clinical demographics). More patients from a Black or Asian (BAME) background progressed to CRC [13.4% vs. 6.4%; p=0.036] compared to their White Caucasian counterparts, despite having surveillance follow-up. Figure 2 displays Kaplan-Meier curves demonstrating the probability of remaining CRC-free after LGD diagnosis and categorised by ethnicity. BAME patients were more likely to have moderate-severe inflammatory activity on colonic biopsy within the 5 preceding years [42.0% vs. 28.9%; p=0.023], but no significant differences in medication use and a longer median time interval from LGD diagnosis to colectomy date [32 months vs. 11 months; p=0.021]. After adjusting for sex, age and UC duration at time of LGD diagnosis and presence of moderate-severe histological inflammation, being Black or Asian was a predictive factor for CRC progression on multivariate Cox proportional hazard analysis [HR 2.97 (95% CI 1.22 – 7.20); p = 0.016]. However, ethnicity was no longer predictive of CRC progression on sub-analysis of the 317 patients who did not have a colectomy during the follow-up period. Conclusion In this UK multi-centre cohort of UC surveillance patients diagnosed with LGD, delays in receiving cancer preventative colectomy may contribute to an increased CRC incidence in certain ethnic groups. Further work is required to elucidate whether these delays are related to institutional factors (e.g. inequity in the content of decision-making support given or access to healthcare) or cultural factors.

scholarly journals Risk and prognosis of secondary bladder cancer after postoperative radiotherapy for gynecological cancer

2021 ◽  
Author(s):  
Li Wen ◽  
Guansheng Zhong ◽  
Yingjiao Zhang ◽  
Miaochun Zhong
Keyword(s):  
Bladder Cancer ◽  
Cumulative Incidence ◽  
Risk Model ◽  
Postoperative Radiotherapy ◽  
Gynecological Cancer ◽  
Clinicopathological Characteristics ◽  
Kaplan Meier ◽  
Increased Risk ◽  
The Us ◽  
Chi Squared

The aim of this study was to investigate the impacts of radiation therapy (RT) on the occurrence risk of secondary bladder cancer (SBC) and on the patients’ survival outcome after being diagnosed with gynecological cancer (EC). The data was obtained from the SEER database between 1973 and 2015. Chi-squared test was used to compare the clinicopathological characteristics among the different groups. Fine and Gray’s competing risk model was used to assess the cumulative incidence and occurrence risk of SBC in GC survivors. Kaplan-Meier method was utilized for survival analysis. A total of 123,476 GC patients were included, among which 31,847 (25.8%) patients received RT while 91629 (74.2%) patients did not. The cumulative incidence of SBC was 1.59% or 0.73% among patients who had received prior GC specific RT or not, respectively. All EBRT (standardized incidence ratio (SIR) =2.49, 95% CI [2.17-2.86]), brachytherapy (SIR =1.96, 95% CI [1.60-2.38]), and combinational RT modality groups (SIR =2.73, 95% CI [2.24-3.28]) had dramatically higher SBC incidence as compared to the US general population. Receiving EBRT (HR = 2.83, 95% CI [2.34–3.43]), brachytherapy (HR = 2.17, 95% CI [1.67–2.82]), and combinational RT modality (HR = 2.97, 95% CI [2.34–3.77]) were independent risk factors for SBC development. Survival detriment was observed in SBC patients who received RT after GC diagnosis, as compared to those who did not receive RT. In conclusion, patients who underwent RT after GC had an increased risk of developing bladder as a secondary primary cancer. A long-term surveillance for SBC occurrence is necessary for GC patients who have received prior RT.

scholarly journals Expression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival

2020 ◽  
Author(s):  
S.-Y. JING ◽  
L. CHEN ◽  
S. HAN ◽  
N. LIU ◽  
M.-Y. HAN ◽  
...  
Keyword(s):  
Overall Survival ◽  
Transcription Factor ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Clinicopathological Characteristics ◽  
Low Grade Glioma ◽  
Independent Prognostic Factor ◽  
Low Grade ◽  
Kaplan Meier ◽  
The Relationship

Abstract Background: TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n=46)and glioblastoma (n=51) from September 2015 to September 2017.Expression of TCF7L2 in 97 specimens were detected by quantitative real-time PCR (qRT-PCR).The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was analyzed by binary logistic regression analysis, the survival curves were drew by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.RESULTS: Compared with low-grade glioma group, the expression of TCF7L2 was significantly increased (p<0.05). TCF7L2 overexpression was associated with large tumor volume (p=0.03), higher WHO grade (p=0.001), and recurrence (p=0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was related with poor OS (p< 0.05).The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor.CONCLUSIONS: Our research proved that TCF7L2 was over- expressed in glioblastoma, and, related with tumor prognosis, which, therefore, could be an independent prognostic factor for glioma patients.

scholarly journals Expression of TCF7L2 in Glioma and Its Relationship With Clinicopathological Characteristics and Patient Overall Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyuan Jing ◽  
Lei Chen ◽  
Song Han ◽  
Ning Liu ◽  
MingYang Han ◽  
...  
Keyword(s):  
Overall Survival ◽  
Transcription Factor ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Clinicopathological Characteristics ◽  
Low Grade Glioma ◽  
Independent Prognostic Factor ◽  
Low Grade ◽  
Kaplan Meier ◽  
The Relationship

Background: The TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration, and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n = 46) and glioblastoma (n = 51) from September 2015 to September 2017. Expression of TCF7L2 in 97 specimens was detected by quantitative real-time PCR (qRT-PCR). The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was estimated by log-rank tests among strata, and the survival curves were drawn by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.Results: Compared with the low-grade glioma group, the expression of TCF7L2 was significantly increased in the glioblastoma group (p = 0.001). TCF7L2 overexpression was associated with higher WHO grade (p = 0.001), isocitrate dehydrogenase (IDH) wild-type (p = 0.001), and lack of O(6)-methylguanine-DNA methyltransferase (MGMT) methylation (p = 0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was associated with poor OS (p = 0.010). The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor (p = 0.020).Conclusions: Our research proved that TCF7L2 was overexpressed in glioblastoma, and related with tumor long-term prognosis, which, therefore, could be an independent prognostic factor for glioma patients.

scholarly journals Preoperative Nodal US Features for Predicting Recurrence in N1b Papillary Thyroid Carcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 174
Author(s):  
Na-Lae Eun ◽  
Jeong-Ah Kim ◽  
Hye-Mi Gweon ◽  
Ji-Hyun Youk ◽  
Eun-Ju Son
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Hazard Analysis ◽  
Survival Rates ◽  
Lateral Compartment ◽  
Postoperative Recurrence ◽  
Papillary Thyroid ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Clinicopathologic Findings

This study aimed to investigate whether preoperative ultrasonographic (US) features of metastatic lymph nodes (LNs) are associated with tumor recurrence in patients with N1b papillary thyroid carcinoma (PTC). We enrolled 692 patients (mean age, 41.9 years; range, 6–80 years) who underwent total thyroidectomy and lateral compartment LN dissection between January 2009 and December 2015 and were followed-up for 12 months or longer. Clinicopathologic findings and US features of the index tumor and metastatic LNs in the lateral neck were reviewed. A Kaplan-Meier analysis and Cox proportion hazard model were used to analyze the recurrence-free survival rates and features associated with postoperative recurrence. Thirty-seven (5.3%) patients had developed recurrence at a median follow-up of 66.5 months. On multivariate Cox proportional hazard analysis, male sex (hazard ratio [HR], 2.277; 95% confidence interval [CI]: 1.131, 4.586; p = 0.021), age ≥55 years (HR, 3.216; 95% CI: 1.529, 6.766; p = 0.002), LN size (HR, 1.054; 95% CI: 1.024, 1.085; p < 0.001), and hyperechogenicity of LN (HR, 8.223; 95% CI: 1.689, 40.046; p = 0.009) on US were independently associated with recurrence. Preoperative US features of LNs, including size and hyperechogenicity, may be valuable for predicting recurrence in patients with N1b PTC.

scholarly journals Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Mei Chen ◽  
Zhenyu Nie ◽  
Hui Cao ◽  
Yuanhui Gao ◽  
Xiaohong Wen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Western Blot ◽  
Enrichment Analysis ◽  
Clinicopathological Characteristics ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Qrt Pcr ◽  
P53 Signaling ◽  
Kaplan Meier ◽  
Normal Bladder

Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear.Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA).Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues.Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.

Prognostic value of hypoxia gene expression in bladder cancer patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 548-548
Author(s):  
Hyun Chang ◽  
Seung-Hyun Lee ◽  
Taeryool Koo ◽  
Moon Ho Kim ◽  
Soo-Yoon Sung
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Cox Regression ◽  
Gene Signature ◽  
Survival Curves ◽  
Kaplan Meier ◽  
Bladder Urothelial Carcinoma

548 Background: The prognostic value of hypoxia in bladder cancer remains unknown. We aimed to evaluate the potential role of hypoxia gene signature as prognostic factors in bladder cancer patients. Methods: We investigated the hypoxia gene signature and clinicopathologic features of The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma (n = 408) using the Kaplan-Meier survival curves and multivariate Cox regression analyses. The clinicopathologic data and the processed data of hypoxia gene signature were obtained from TCGA Bladder urothelial carcinoma database. Results: Hypoxia gene signature score was significantly associated with overall survival (OS) and progression-free survival (PFS). Higher score resulted in shorter OS and PFS in Kaplan-Meier survival curves with Log-rank test ( P < 0.01 and P <0.05, respectively). In multivariate analysis containing clinical prognostic variables, higher hypoxia gene signature score predicted poor OS (adjusted HR= 1.58, 95% CI 1.15 - 2.19; P <0.01). Conclusions: Hypoxia gene signature was an independent prognostic factor in bladder cancer. Prospective studies are needed to evaluate the prognostic role of hypoxia in bladder cancer patients.

The Significance of Squamous Histology on Clinical Outcomes and PD-L1 Expression in Bladder Cancer

2021 ◽  
pp. 106689692110272
Author(s):  
Jennifer B. Gordetsky ◽  
Kathleen W. Montgomery ◽  
Giovanna A. Giannico ◽  
Soroush Rais-Bahrami ◽  
Prabin Thapa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Squamous Differentiation ◽  
Clinicopathologic Characteristics ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Never Smokers

Objectives. To compare the clinicopathologic characteristics of urothelial carcinoma (UC), urothelial carcinoma with squamous differentiation (UCSD), and squamous cell carcinoma (SCC) of the bladder, which have been suggested to differ in terms of risk factors, immunophenotype, and prognosis. Methods. We evaluated the clinicopathologic features of radical cystectomy specimens between 1980 and 2015 with a diagnosis of SCC, UCSD, and UC. PD-L1 immunohistochemistry (clinically available clones 22C3, SP142, and SP263) was performed on SCC and UCSD. Multivariate Cox regression was used to identify prognostic factors. Kaplan–Meier curves were plotted to assess cancer-specific survival (CSS). Results. Of the 1478 cases, there were 1126 UC (76%), 217 UCSD (15%), and 135 SCC (9%). Bladder cancer was more common in men than women (80% vs 20%, P < .0001). However, a higher proportion of SCC and UCSD occurred in women (SCC-36%, UCSD-22%, UC-18%). Women were significantly more likely to be never smokers in all 3 cohorts (UC: 45% vs 16%, UCSD: 44% vs 12%, SCC: 40% vs 18%, P < .0001). Patients with SCC and UCSD were at a higher pathologic stage (>pT2) at the time of cystectomy (UCSD-74%, SCC 71%, UC-44%, P < .0001) and had worse CSS compared to patients with UC ( P = 0.006). SCC had higher PD-L1 scores (all clones) than UCSD ( P < .0001). PD-L1 22C3 ( P = .02, HR: 0.36) and SP142 scores ( P = .046, HR: 0.27) predicted CSS on Kaplan–Meier analysis for SCC cases. Conclusions. UC, UCSD, and SCC are associated with different risk factors, gender distributions, and clinical outcomes. PD-L1 is expressed in SCC and UCSD, suggesting some patients may benefit from targeted therapy.

scholarly journals Identifying Stage-Associated Hub Genes in Bladder Cancer via Weighted Gene Co-Expression Network and Robust Rank Aggregation Analyses

2021 ◽  
Author(s):  
Fu Feng ◽  
Yu-Xiang Zhong ◽  
Jian-Hua Huang ◽  
Fu-Xiang Lin ◽  
Peng-Peng Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Roc Curves ◽  
Rank Aggregation ◽  
Operating Characteristics ◽  
Hub Genes ◽  
Kaplan Meier ◽  
Gene Sets ◽  
Bladder Urothelial Carcinoma ◽  
Microarray Datasets

Abstract Background Bladder cancer (BC) is among the most frequent cancers globally. Although substantial efforts have been put to understand its pathogenesis, its underlying molecular mechanisms have not been fully elucidated. Methods The Robust Rank Aggregation (RRA) approach was adopted to integrate four eligible bladder urothelial carcinoma (BLCA) microarray datasets from the GEO. Differentially expressed genes (DEGs) sets were identified between tumor samples and equivalent healthy samples. We constructed gene co-expression networks using WGCNA to explore the alleged relationship between BC clinical characteristics and gene sets, as well as to identify hub genes. We also incorporated the WGCNA and RRA to screen DEGs. Results CDH11, COL6A3, EDNRA and SERPINF1 were selected from the key module and validated. Based on the results, significant downregulation of the hub genes occurred during the early stages of BC. Moreover, Receiver operating characteristics (ROC) curves and Kaplan-Meier (KM) plots showed that the genes exhibited favorable diagnostic and prognostic value for BC. Based on GSEA for single hub gene, all the genes were closely linked to BC cell proliferation. Conclusions These results offer unique insight into the pathogenesis of BC and recognize CDH11, COL6A3, EDNRA and SERPINF1 as potential biomarkers with diagnostic and prognostic roles in BC.

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