Abstract
目的
探究饮水习惯与上尿路尿路上皮癌(upper tract urothelial carcinoma, UTUC)患者的临床病理特征之间的相关性。
方法
选取北京大学第一医院泌尿外科2020年8月至2021年7月收治的拟行根治性切除术的UTUC患者，在术前进行问卷调查，了解其饮水习惯，结合其术后病理特点进行统计分析。统计过程采用SPSS 22.0软件，首先采用列联表χ2检验，对UTUC肿瘤病理特点作为因变量与患者一般信息、既往史及饮水习惯相关因素等作为自变量逐一进行初步分析，筛选出针对各因变量病例组和对照组之间满足P＜0.2的自变量，将筛选后的变量纳入二元Logistic回归分析，以P＜0.05为差异有统计学意义。
结果
共纳入239例患者，男性134例，女性105例，平均年龄(68.1±9.98)岁，中位病程4.8个月。统计结果提示，经调整了混杂因素的影响后，有白天每小时至少饮水1次习惯的UTUC患者患高级别(G3)肿瘤的概率增加(OR=1.941, 95%CI: 0.352~1.029，P＜0.01)；有白天每小时至少饮水1次习惯的患者相对于没有这一习惯的患者患多灶性UTUC肿瘤的发病风险显著下降(OR=0.344, 95%CI: 1.18~5.582，P=0.004)，同时有每次饮水≥100 mL习惯的患者相对于无这一习惯者多灶性UTUC肿瘤的发病风险也显著下降(OR=0.477, 95%CI: 0.225~1.012，P=0.046)；有自我关注每日饮水这一习惯的患者相对于无这一习惯的患者患肾盂癌的风险显著升高(OR=2.530, 95%CI: 1.434~4.463，P=0.001)，而患输尿管癌的风险显著降低(OR=0.314, 95%CI: 0.172~0.573，P＜0.01)；其他纳入回归模型的变量对肿瘤病理特点发生的影响差异无统计学意义。
结论
有白天每小时至少饮水1次、每次饮水≥100 mL、自我关注每日饮水等饮水习惯分别与上尿路尿路上皮癌病理特点(如肿瘤G3、肿瘤多灶性及肿瘤位于肾盂或输尿管)存在显著相关性，这一结论仍需后续更高证据等级的试验加以验证。
Keywords: 上尿路尿路上皮癌, 饮水习惯, 病理特征, 相关性分析
Abstract
Objective
To investigate the correlation between drinking habits and pathological characteristics of patients with upper tract urothelial carcinoma (UTUC).
Methods
A preoperative questionnaire survey was conducted to understand the drinking habits of UTUC patients who were admitted to the Department of Urology, Peking University First Hospital for radical nephroureterectomy within one year from August 2020 to July 2021, and statistical analysis was performed in combination with their postoperative pathological characteristics. The statistical procedure was performed using SPSS 22.0 software, and firstly, the preliminary analysis was performed one by one using the columnar χ2 test on the pathological characteristics of UTUC tumors as the dependent variable and the factors related to patients' general information, past history and drinking habits as the independent variables, and the independent variables that met P < 0.2 between the case and control groups for each dependent variable were specified for screening. The screened variables were included in the binary Logistic regression analysis. A difference of P < 0.05 was used to indicate a statistically significant difference.
Results
A total of 239 patients, 134 males and 105 females, with a mean age of (68.1±9.98)years and a median disease duration of 4.8 months, were included in this study. Multifactorial Logistic regression results suggested that after adjusting for the effects of other variables, UTUC patients who had the habit of drinking at least once every hour during the daytime had a significantly increased risk of high grade (G3) tumors(OR=1.941, 95%CI: 0.352-1.029, P < 0.01); these patients also had a significantly decreased risk of multifocal UTUC tumors (OR=0.344, 95% CI: 1.18-5.582, P=0.004). The patients who had the habit of drinking over 100 mL water each time had a significantly decreased risk of mutifocal UTUC incidence (OR=0.477, 95%CI: 0.225-1.012, P=0.046). Patients who pay attention to daily water intakes had a significantly increased risk of renipelvic carcinoma (OR=2.530, 95%CI: 1.434-4.463, P=0.001) and a significantly decreased risk of ureteral carcinoma (OR=0.314, 95%CI: 0.172-0.573, P < 0.01). Other variables included in the regression model did not differ significantly in their effects on the occurrence of tumor pathological characteristics.
Conclusion
Having the awareness of drinking water every 1 h during the day, drinking over 100 mL water each time, having the awareness of daily drinking habits correlated significantly with pathological characteristics of UTUC such as the presence of G3 tumor, multifocal tumors and location of the tumor. This conclusion still needs to be verified by subsequent trials with higher levels of evidence.
Keywords: Upper tract urothelial carcinoma, Drinking habit, Pathological characteristic, Correlation analysis
上尿路尿路上皮癌(upper tract urothelial carcinoma, UTUC)包含肾盂癌和输尿管癌，是较为少见的泌尿系肿瘤，约占全部尿路上皮肿瘤的5%~10% [1], 这一疾病的病因目前尚不明确。UTUC与膀胱癌(bladder cancer, BC)通常具有相似的组织学类型，两种肿瘤常见相伴或相继发生[2]，然而，UTUC的病理特点同膀胱癌往往具有较显著的不同，多数UTUC在首诊时即显示肌层浸润性和高组织学分级[3]，往往预后较差，并且即使接受了根治性手术后仍伴有较高的膀胱癌复发风险。UTUC的病理特点与其预后和膀胱癌复发率具有显著相关性，肿瘤病理分级与分期是目前公认的最重要的影响预后的因素，肿瘤的多灶性、肿瘤位于输尿管、膀胱癌既往史等是根治术后膀胱癌复发的重要危险因素[4]。
饮水是人每日所必需的生活行为，每日的饮水摄入量及饮水习惯与泌尿系感染、结石等诸多泌尿系统疾病的发病具有相关性[5-6]。研究表明，每日更多的饮水摄入量对吸烟人群及亚洲人群膀胱癌的发生具有保护作用，且摄入不同类型的饮料与膀胱癌的发病风险具有相关性[7-8]。然而，目前围绕饮水习惯对UTUC的影响所开展的研究极少，UTUC病理特点是否与每日饮水量和习惯等具有关联目前尚不明确。为了探究日常饮水习惯对UTUC患者的肿瘤病理特点有无影响，北京大学第一医院泌尿外科开展了这一横断面研究，对UTUC病理特点与饮水习惯的相关性进行分析。
1. 资料与方法
1.1. 研究对象
选取2020年8月至2021年7月在北京大学第一医院泌尿外科收治的拟行输尿管全长根治性切除术的患者，术后经病理明确诊断为UTUC，术前影像学检查提示无全身远器官转移，未接受术前新辅助化疗，年龄≥18岁。排除术后病理诊断为非UTUC、临床资料不完整、拒绝接受调查的患者后，共计239例患者纳入本研究。本试验获得北京大学第一医院生物医学研究伦理委员会批准(批准号：2021科研130)，研究对象均签署知情同意书。
1.2. 研究方法
通过填写问卷调查的方式收集在院患者的日常饮水习惯、饮水摄入量、烟酒史、化工接触或职业史、马兜铃酸药物服用史、有无肿瘤病史或家族史、有无既往前列腺增生等尿路梗阻疾病及憋尿习惯等信息，问卷采用二分类选项“是”或“否”，当选择“是”时，则做进一步描述，题设中饮水量的设置参考既往饮水调查相关研究[9]。同时重点对患者的肿瘤病理信息进行整理和分析，包括肿瘤的类型，病理分期，组织学分级(G)，肿瘤位置位于肾盂/输尿管、单发/多灶性等特点。肿瘤分级采用1973年及2004年WHO分级标准，在描述组织学分级的同时描述该肿瘤为高/低级别尿路上皮肿瘤；肿瘤分期采用2017年《美国癌症分期系统联合委员会》(第8版)TNM分期标准。
1.3. 统计学分析
所有数据采用SPSS 22.0软件进行分析。定性资料组间比较采用χ2检验，定量资料组间比较采用Mann-Whitney U检验。首先采用列联表χ2检验，UTUC肿瘤病理特点作为因变量，患者年龄、性别、有无化工材料接触史及职业史、有无放射类材料接触及职业史、吸烟饮酒史、马兜铃酸药物服用史、既往肿瘤病史及家族史、慢性肾脏病史、有无尿路梗阻或憋尿习惯及饮水习惯相关因素作为自变量，然后逐一进行初步分析，规定P＜0.2作为初步筛选标准。当满足每个单元格内预期频数＞5时，则直接使用Pearson卡方检验；当不满足时则使用Fisher精确检验。采用二元Logistic回归对以上筛选出的变量进行多因素回归分析，为了更好地调整混杂因素的影响，同时将性别、年龄≥55岁、吸烟史、化工接触史、马兜铃酸接触史、家族性肿瘤相关病史等既往明确与UTUC发病或肿瘤病理特点相关因素与经初步筛选后的自变量一并纳入Logistic回归模型，该过程中对自变量的筛选基于最大似然估计的向前逐步回归法(LR法)。对最终纳入回归模型的变量，选取Exp(B)和95% CIfor Exp(B)表示相应变量的OR值和其95%可信区间，以P＜0.05表示差异具有统计学意义。
2. 结果
本研究合计纳入男性患者134例，女性患者105例，男、女比例为1.28 ∶ 1，平均年龄(68.1±9.98)岁。病程1周至10年不等，中位病程4.8个月。所有患者当中，主诉为无症状者53例(22.18%)、血尿170例(71.13%)、腰痛12例(5.02%)、腹痛3例(1.26%)、下尿路梗阻症状1例(0.42%)，以血尿主诉入院者最为常见。既往有化工类材料(芳香类化合物等)接触史或职业史者48例(20.08%)；明确有染料、染发剂等接触史者53例(22.27%)，其中女性30例(56.60%)；有放射类物质长期接触及职业史者4例(0.67%)；明确有吸烟史者74例(30.96%)，饮酒史者41例(17.15%)(吸烟及饮酒定义为累计超过半年以上规律吸烟、饮酒)；既往有过马兜铃酸类药物服用史者61例(25.63%)；既往有其他肿瘤病史者22例(9.21%)，明确家族成员有肿瘤病史者73例(30.54%)；既往伴有慢性肾功能不全者17例(7.11%)；有前列腺增生等尿路梗阻病史者55例(23.01%)，日常有憋尿习惯者(≥1次/日)者35例(14.64%)。在所有纳入调查的239例患者中，饮水特征分布详见表 1。
表 1.
239例上尿路尿路上皮癌患者饮水习惯分布情况
Drinking habits of 239 patients diagnosed with upper tract urothelial carcinoma
| Items | n | % |
| UTUC, upper tract urothelial carcinoma; BPH, benign prostatic hyperplasia. | ||
| Type of water | ||
| Boiled water | 140 | 58.58 |
| Mineral water | 18 | 7.53 |
| Purified water | 37 | 15.48 |
| Tea or other beverage | 44 | 18.41 |
| Timing of drinking water | ||
| When feel thirsty | 106 | 44.35 |
| Drinking water intentionally | 133 | 55.65 |
| Daily water intakes | ||
| 500-1 000 mL | 32 | 13.39 |
| ＞1 000-1 500 mL | 58 | 24.27 |
| ＞1 500-2 000 mL | 56 | 23.43 |
| ＞2 000 mL | 93 | 38.91 |
| Drink at least once every hour during the daytime | 89 | 37.24 |
| Drink over 100 mL water every time | 190 | 79.50 |
| Drink over 200 mL water before bed | 104 | 43.51 |
| Drink over 200 mL water at night | 39 | 16.32 |
| Drink over 200 mL water when get up | 184 | 76.99 |
| Drink over 200 mL tea every day | 96 | 40.17 |
| Drink over 200 mL carbonated drinks every day | 3 | 1.26 |
| Drink over 200 mL coffee every day | 8 | 3.25 |
| Drink over 200 mL juice every day | 3 | 1.26 |
| Drink over 200 mL milk every day | 112 | 46.86 |
| Paying attention to daily water intakes | 140 | 58.58 |
| Having the will to drink more water every day intentionally | 135 | 56.49 |
| Lower urinary track obstruction disease history/ BPH history | 55 | 23.01 |
| Having the habit to hold back urine | 35 | 14.64 |
对所有纳入研究的患者肿瘤病理信息进行分析，符合肿瘤G3诊断者138例；符合多灶性肿瘤诊断者39例；肿瘤病灶仅位于肾盂者107例，仅位于输尿管者112例，肾盂和输尿管均有肿瘤者20例。将肿瘤组织学分级G3、肿瘤多灶性、肿瘤位于肾盂、肿瘤位于输尿管设为病例组，肿瘤组织学分级不符合G3、肿瘤单发、肿瘤不位于肾盂、肿瘤不位于输尿管设为对照组。经列联表法χ2检验筛选后可纳入多因素回归分析的变量见表 2。
表 2.
经列联表χ2分析筛选后可纳入多因素回归分析的变量
Factors included in the Logistic regression model after Chi-square test
| Case group | Control group | χ 2 | P | |
| *P＜0.05; # P＜0.01. | ||||
| G3 tumor，n | 138 | 101 | ||
| Drink at least once every hour, n(%) | 44 (31.88) | 45 (44.55) | 4.006 | 0.045* |
| Drink over 200 mL water when get up, n(%) | 102 (73.91) | 82 (81.19) | 1.742 | 0.187 |
| Smoking history, n(%) | 36 (26.07) | 38 (37.62) | 3.631 | 0.057 |
| Family history of cancer, n(%) | 48 (34.78) | 25 (24.75) | 2.766 | 0.096 |
| Multifocal tumor，n | 39 | 200 | ||
| Time of drinking | ||||
| When thirsty, n(%) | 13 (33.33) | 93 (46.50) | 2.292 | 0.130 |
| Drinking water intentionally, n(%) | 26 (66.67) | 107 (53.50) | ||
| Drink at least once every hour during the daytime, n(%) | 19 (48.72) | 60 (35.00) | 2.628 | 0.105 |
| Drink over 100 mL water every time, n(%) | 28 (71.80) | 162 (81.19) | 1.697 | 0.193 |
| Drink water at night, n(%) | 13 (33.33) | 93 (46.50) | 2.292 | 0.130 |
| Drink over 200 mL tea every day, n(%) | 21 (53.85) | 75 (37.50) | 3.628 | 0.057 |
| Tumor located in renal pelvic，n | 127 | 112 | ||
| Time of drinking | ||||
| When thirsty, n(%) | 63 (49.61) | 43 (38.40) | 3.032 | 0.082 |
| Drinking water intentionally, n(%) | 64 (50.39) | 69 (61.60) | ||
| Drink over 200 mL tea every day, n(%) | 35 (35.43) | 51 (45.54) | 2.527 | 0.112 |
| Paying attention to daily water intakes, n(%) | 85 (66.93) | 55 (49.11) | 7.791 | 0.005# |
| Family history of cancer, n(%) | 48 (37.80) | 25 (22.32) | 6.717 | 0.010* |
| Tumor located in ureter，n | 132 | 107 | ||
| Time of drinking | ||||
| When thirsty, n(%) | 49 (31.12) | 57 (53.27) | 6.245 | 0.012* |
| Drinking water intentionally, n(%) | 83 (62.88) | 50 (46.73) | ||
| Drink at least once every hour during the daytime, n(%) | 55 (41.67) | 34 (31.78) | 2.474 | 0.116 |
| Drink water at night, n(%) | 51 (38.64) | 55 (51.40) | 3.902 | 0.048* |
| Drink over 200 mL tea every day, n(%) | 64 (48.48) | 32 (29.91) | 8.487 | 0.004* |
| Paying attention to daily water intakes, n(%) | 66 (50.00) | 74 (69.16) | 8.940 | 0.003# |
| Family history of cancer, n(%) | 34 (25.76) | 39 (36.45) | 3.184 | 0.074 |
列联表χ2分析及二元Logistic回归分析结果显示，有白天每小时至少饮水1次这一饮水习惯的影响在肿瘤G3与非G3患者中差异有统计学意义(31.88% vs. 44.55%, χ2=4.006, P < 0.01)，而有无清晨饮水≥200 mL、吸烟史和肿瘤家族史对肿瘤G3发生的影响差异无统计学意义。饮水时机、是否夜间饮水、有无每日饮茶≥200 mL和有无每次饮水≥100 mL习惯对多灶性肿瘤发生率的影响差异也无统计学意义，而有白天每小时至少饮水1次习惯的患者相对没有这一习惯的患者患多灶性肿瘤的风险显著降低。饮水时机、有无每日饮茶≥200 mL、肿瘤家族史对肾盂癌发生率的影响差异无统计学意义，而有自我关注每日饮水习惯的患者相对没有这一习惯患者患肾盂癌的风险显著升高。饮水时机、有无白天每小时至少饮水1次、有无夜间饮水、是否每日饮茶≥200 mL和肿瘤既往史及家族史对输尿管癌发生率的影响差异无统计学意义，而有自我关注每日饮水习惯的患者相对没有这一习惯患者患输尿管癌的风险显著降低，其他纳入回归模型的变量对肿瘤病理特点发生的影响差异无统计学意义(表 3)。
表 3.
二元Logistic回归纳入最终回归模型的变量及其统计结果
Statistical result of Logistic regression model
| B | OR(95%CI) | P | |
| *P＜0.05; # P＜0.01. | |||
| Tumor G3 | |||
| Drink at least once every hour during the daytime | |||
| No | 1.00 | ||
| Yes | 0.663 | 1.941 (0.352-1.029) | < 0.001# |
| Multifocal tumor | |||
| Drink at least once every hour during the daytime | |||
| No | 1.00 | ||
| Yes | -1.067 | 0.344 (1.181-5.582) | 0.004# |
| Drink over 100 mL water every time | |||
| No | 1.00 | ||
| Yes | -0.876 | 0.477 (0.225-1.012) | 0.046* |
| Tumor located in renal pelvic | |||
| Paying attention to daily water intakes | |||
| No | 1.00 | ||
| Yes | 0.928 | 2.530 (1.434-4.463) | 0.001# |
| Tumor located in ureter | |||
| Paying attention to daily water intakes | |||
| No | 1.00 | ||
| Yes | -1.159 | 0.314 (0.172-0.573) | < 0.001# |
| Drink over 200mL tea every day | |||
| No | 1.00 | ||
| Yes | -0.572 | 0.565 (1.200-3.878) | 0.208 |
3. 讨论
近年来上尿路尿路上皮癌的发病呈现侵袭性比例加重的趋势[10]，受含有马兜铃酸类药物被广泛应用的影响，中国人群UTUC在发病机制、流行病学特点、肿瘤特征及预后影响因素等方面较西方人群存在显著不同，通常具有更高的病理分级、相对较低的病理分期、女性较男性肿瘤恶性程度低等特点[11-12]。UTUC具有相对隐匿的病程和早期即出现肌层浸润性的特点，往往预后不良，即使接受根治性手术治疗的患者依旧会伴随很高的残存尿路上皮复发的风险[13]。不同病理特点的UTUC患者预后存在显著差异，针对中国人群的不良预后病理特征，目前已知的独立危险因素包括男性、肿瘤G3、非乳头状肿瘤、单发病灶、肿瘤原发于肾盂及术前伴有患侧肾积水等[14-15]。影响UTUC根治术后膀胱复发的危险因素包括肿瘤多灶性、肿瘤位于输尿管、既往膀胱癌病史等。既往研究表明，马兜铃酸成分药物服用史、吸烟及林奇综合征(Lynch syndrome)均可能为导致UTUC发生的危险因素[16-17]；≥55岁的男性UTUC患者具有相对更差的病理及预后特点[14, 18-19]，探究预防并减少高危UTUC发生的保护性因素始终是世界范围内讨论和研究的热点。
饮水是每日的必需行为，但不同人群之间的饮水习惯存在较大的差别。每日的水分摄入与泌尿系统的功能直接相关，并且越来越多的证据表明饮水习惯同诸多泌尿系统疾病的发生、发展及预后存在联系，其中饮水习惯与膀胱癌的相关性已经被广泛探究及证实。Simon等[20]在研究中意外发现饮用咖啡会增加人群患膀胱癌的风险，Morgan等[21]在后续的研究中提出饮茶与膀胱癌的发生没有显著的相关性，Jensen等[22]在比较了371例膀胱癌患者及771例健康人群后提出，膀胱癌的发病风险与每日液体总摄入量和非可乐软饮料之摄入间均存在关联性。中国学者Bai等[7]对既往的研究进行meta分析后得出，每日更多的饮水量可能对膀胱癌具有保护作用，这一保护效应在长期吸烟者及亚洲人群当中更为显著。关于增加饮水量减少膀胱癌发病风险的机制，一些学者提出更多的饮水间接增加排尿机会从而减少致癌因素与膀胱黏膜的接触时间，这一猜想从侧面解释了为何前列腺增生等尿路梗阻疾病高发的老年人群中，大量饮水对膀胱癌保护效果不如年轻人显著[23-24]。van Hensbergen等[25]在分析了饮水类型和饮水量与膀胱癌病理特点的相关性后发现，每日饮用更多乙醇及总饮水量更多的患者呈现发病年龄提前的趋势。Wang等[26]在探究饮水对于膀胱癌发病风险的影响后得出，饮水量的增加会显著提升膀胱癌的发病风险，而饮茶则对膀胱癌的发生具有一定保护作用。然而，关于饮水总量与膀胱癌发病风险的关联性目前仍然存在争议[27]。尽管上尿路尿路上皮癌与膀胱癌通常具有相似的组织学特点，两者的分子和临床特征却大不相同[28]。目前有关饮水习惯与上尿路尿路上皮癌肿瘤特点相关性的研究极少，因此我们开展了这项关于饮水习惯与尿路上皮癌患者肿瘤病理特点之间关系的研究，有助于更好地理解不同的饮水习惯对UTUC患者会带来哪些影响。
为了更加全面地分析不同饮水习惯对肿瘤病理特点的相关性，我们将每日饮水频次、日常主要饮水类型、饮水量、饮水时机及不同类型饮料的日常摄入水平等因素都进行了调查，同时还纳入了包括是否自我关注每日饮水量及是否会主动多饮水等主观性变量，问卷采用二分类选项便于志愿者更好地理解和做出选择。
在我们的研究中，白天每小时至少饮水1次与肿瘤G3的发病具有显著的正相关性，而白天每小时至少饮水1次和每次饮水≥100 mL与多灶性肿瘤的发生具有显著的负相关性。同时自我关注每日饮水这一习惯与肾盂肿瘤的发生具有显著的正相关性，而与输尿管肿瘤的发生具有显著的负相关性，其他纳入研究的变量与UTUC的分布与分级没有显著的关联性。由于既往尚无相关的基础研究，我们初步猜想，饮水频次的提升和饮水量的增多导致尿液产生增多所带来的冲洗作用可能会增加致病因素对于尿路上皮的刺激，从而提高了高级别肿瘤的发病风险，但这种冲刷作用同时可能降低肿瘤播散的风险，从而减少了多灶性肿瘤的发病风险。同时自我关注每日饮水的增加导致尿液产生的增多，增加肾盂压力的同时增加了代谢废物与肾盂尿路上皮的接触机会，从而提高了肾盂癌的发病风险，但对输尿管没有压力影响，且长期持久的尿液冲洗反而降低了输尿管癌的发病风险。然而，对于以上饮水习惯是否能够改善UTUC患者预后及其机制，仍需更高级别的试验进一步加以验证。
本研究中，有无每日饮茶≥200 mL习惯对输尿管癌的发病风险在单因素分析结果方面差异有统计学意义，且被纳入Logistic模型，但差异无统计学意义。分析可能与本研究中有每日饮茶≥200 mL习惯的患者分布不均有关，有待于扩大样本量进一步分析这一饮水习惯对于输尿管癌发病风险的影响。
我们的研究存在以下不足：(1)采用问卷的方式对患者进行调查，因回忆偏差带来的信息偏倚可能导致其调查结果不能反映真实的饮水习惯，必要时可采用募集患者进行集中监测的方法加以改进；(2)该试验属于单中心横断面研究，证据等级不高，纳入的样本量有待进一步扩大，对于饮水习惯和UTUC肿瘤病理特点的相关性解读是否具有普遍的代表性仍有待验证，且该研究的结论不足以确定饮水习惯与UTUC肿瘤特点两者之间的因果关系。
综上所述，有白天每小时至少饮水1次、每次饮水≥100 mL、自我关注每日饮水等饮水习惯分别与UTUC病理特点如肿瘤G3、肿瘤多灶性及肿瘤位于肾盂或输尿管存在显著相关性。有关这一结论仍需后续更高证据等级的试验加以验证。
Contributor Information
黄 燕波 (Yan-bo HUANG), Email: hyb1273@126.com.
李 学松 (Xue-song LI), Email: pineneedle@sina.com.
References
- 1.Siegel RL, Miller KD, Jemal A, et al. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi: 10.3322/caac.21551. [DOI] [PubMed] [Google Scholar]
- 2.Audenet F, Isharwal S, Cha EK, et al. Clonal relatedness and mutational differences between upper tract and bladder urothelial carcinoma. Clin Cancer Res. 2019;25(3):967–976. doi: 10.1158/1078-0432.CCR-18-2039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Zamboni S, Foerster B, Abufaraj M, et al. Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy. BJU Int. 2019;124(5):738–745. doi: 10.1111/bju.14751. [DOI] [PubMed] [Google Scholar]
- 4.Belhadj Y, Grande P, Seisen T, et al. Bladder mapping of tumour recurrence after radical nephroureterectomy for upper tract urothe-lial carcinoma and its influence on oncological outcomes. BJU Int. 2019;123(4):618–623. doi: 10.1111/bju.14647. [DOI] [PubMed] [Google Scholar]
- 5.Scott AM, Clark J, Mar CD, et al. Increased fluid intake to prevent urinary tract infections: systematic review and meta-analysis. Br J Gen Pract. 2020;70(692):e200–e207. doi: 10.3399/bjgp20X708125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.卢 海梅. 饮食饮水习惯女性泌尿系结石复发的前瞻性研究. 实用临床护理学电子杂志. 2020;5(15):94. [Google Scholar]
- 7.Bai Y, Yuan H, Li J, et al. Relationship between bladder cancer and total fluid intake: a meta-analysis of epidemiological evidence. World J Surg Oncol. 2014;12:223. doi: 10.1186/1477-7819-12-223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Hong X, Xu Q, Lan K, et al. The effect of daily fluid management and beverages consumption on the risk of bladder cancer: a meta-analysis of observational atudy. Nutr Cancer. 2018;70(8):1217–1227. doi: 10.1080/01635581.2018.1512636. [DOI] [PubMed] [Google Scholar]
- 9.李 金蓉, 蒙 有轩, 廖 君娟, et al. 泌尿系结石复发病人饮水习惯调查. 护理研究. 2017;31(36):4691–4693. doi: 10.3969/j.issn.1009-6493.2017.36.030. [DOI] [Google Scholar]
- 10.Collà Ruvolo C, Nocera L, Stolzenbach LF, et al. Incidence and survival rates of contemporary patients with invasive upper tract urothelial carcinoma. Eur Urol Oncol. 2021;4(5):792–801. doi: 10.1016/j.euo.2020.11.005. [DOI] [PubMed] [Google Scholar]
- 11.周 利群, 熊 耕砚, 李 学松. 中国人群上尿路尿路上皮癌诊疗策略选择和东西方差异. 临床泌尿外科杂志. 2019;34(2):83–87. [Google Scholar]
- 12.方 冬, 黄 吉炜, 鲍 一歌, et al. 中国上尿路尿路上皮癌人群特征和地区差异: 基于CUDA-UTUC协作组的多中心研究. 中华泌尿外科杂志. 2017;38(12):885–890. doi: 10.3760/cma.j.issn.1000-6702.2017.12.002. [DOI] [Google Scholar]
- 13.张 宁, 崔 剑锋, 李 岩, et al. 上尿路尿路上皮癌预后生物标志物的研究进展. 临床泌尿外科杂志. 2019;34(2):119–123. [Google Scholar]
- 14.Rolim I, Henriques V, Rolim N, et al. Clinicopathologic analysis of upper urinary tract carcinoma with variant histology. Virchows Arch. 2020;477(1):111–120. doi: 10.1007/s00428-020-02745-4. [DOI] [PubMed] [Google Scholar]
- 15.陈 晗, 王 明, 任 轲, 刘 苑, et al. 不同分期上尿路尿路上皮癌患者预后分析. 临床泌尿外科杂志. 2021;36(5):357–361. [Google Scholar]
- 16.陈 金虎, 方 卫华, 梁 朝朝. 上尿路尿路上皮癌临床治疗进展. 临床泌尿外科杂志. 2021;36(5):415–420. [Google Scholar]
- 17.Martin C, Leiser CL, O'Neil B, et al. Familial cancer clustering in urothelial cancer: a population-based case-control study. J Natl Cancer Inst. 2018;110(5):527–533. doi: 10.1093/jnci/djx237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.曹 振朋, 关 豹, 方 冬, et al. 年轻上尿路尿路上皮癌患者的临床病理和预后特征. 现代泌尿外科杂志. 2017;22(9):661–665. doi: 10.3969/j.issn.1009-8291.2017.09.004. [DOI] [Google Scholar]
- 19.Han J, Xian Z, Zhang Y, et al. Systematic overview of aristo-lochic acids: nephrotoxicity, carcinogenicity, and underlying mechanisms. Front Pharmacol. 2019;10:648. doi: 10.3389/fphar.2019.00648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Simon D, Yen S, Cole P. Coffee-drinking and cancer of the lower urinary tract. J Natl Cancer Inst. 1975;54(3):587–591. [PubMed] [Google Scholar]
- 21.Morgan RW, Jain MG. Bladder cancer: smoking, beverages and artificial sweeteners. Can Med Assoc J. 1974;111(10):1067–1070. [PMC free article] [PubMed] [Google Scholar]
- 22.Jensen OM, Wahrendorf J, Knudsen JB, et al. The Copenhagen case-control study of bladder cancer. Ⅱ. Effect of coffee and other beverages. Int J Can-cer. 1986;37(5):651–657. doi: 10.1002/ijc.2910370503. [DOI] [PubMed] [Google Scholar]
- 23.Silverman DT, Alguacil J, Rothman N, et al. Does increased urination frequency protect against bladder cancer? Int J Can-cer. 2008;123(7):1644–1648. doi: 10.1002/ijc.23572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Zhou J, Smith S, Giovannucci E, et al. Reexamination of total fluid intake and bladder cancer in the Health Professionals Follow-up Study Cohort. Am J Epidemiol. 2012;175(7):696–705. doi: 10.1093/aje/kwr359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.van Hensbergen M, van Osch FHM, Jochems S, et al. Fluid intake and clinicopathological characteristics of bladder cancer: the west midlands bladder cancer prognosis programme. Eur J Cancer Prev. 2020;29(2):110–118. doi: 10.1097/CEJ.0000000000000525. [DOI] [PubMed] [Google Scholar]
- 26.Wang J, Wu X, Kamat A, et al. Fluid intake, genetic variants of UDP-glucuronosyltransferases, and bladder cancer risk. Br J Cancer. 2013;108(11):2372–2380. doi: 10.1038/bjc.2013.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Jochems SHJ, van Osch FHM, Reulen RC, et al. Total fluid intake and the risk of recurrence in patients with muscle invasive bladder cancer: a prospective cohort study. Bladder Cancer. 2018;4(3):303–310. doi: 10.3233/BLC-180172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Sfakianos JP, Gul Z, Shariat SF, et al. Genetic differences between bladder and upper urinary tract carcinoma: implications for therapy. Eur Urol Oncol. 2021;4(2):170–179. doi: 10.1016/j.euo.2020.12.007. [DOI] [PubMed] [Google Scholar]