膀胱癌与吸烟及烟草烟雾环境暴露的关系

目的 探讨吸烟及烟草烟雾环境(ETS)暴露与膀胱癌发病风险的关系.方法 2005年10月至2009年3月期间进行了一项病例对照研究,病例组为124例初次诊断为膀胱癌的患者,对照组为227例非肿瘤、非泌尿系统疾病的住院患者.使用Logistic回归分析计算吸烟对膀胱癌发生的比数比(OR)及95%可信区间(95%CI).结果 吸烟者易患膀胱癌的风险是终生不吸烟者的1.867倍,男性吸烟者的相对危险度是终生不吸烟者的2.648倍,对于已戒烟的男性相对危险度是终生不吸烟者的2.019倍.不吸烟者在未成年期暴露于烟草烟雾环境易患膀胱癌的风险是无暴露者的2.068倍,而对于成年后暴露于烟草烟雾环境的发病风险与无暴露者差异无统计学意义(P＞0.05).结论 吸烟是膀胱癌发病的危险因素之一;已戒烟者膀胱癌发生的危险度低于现行吸烟者;戒烟有利于降低吸烟者易患膀胱癌的风险.在未成年期长期暴露于烟草烟雾环境中,膀胱癌的发病风险显著增加;而成年人暴露于烟草烟雾环境中,是否能增加膀胱癌的发病风险并不确定.     

Cruciferous vegetables intake is inversely associated with risk of breast cancer: A meta-analysis

PurposeThe objective of the study was to examine the associations of cruciferous vegetables intake with risk of breast cancer.MethodsStudies were identified by searching PubMed databases and screening the references of retrieved articles and reviews. Summary odds ratios (ORs) for the highest versus lowest cruciferous vegetables consumption levels were calculated using fixed or random effects models depending on heterogeneity between studies. Heterogeneity among studies was examined using Q and I² statistics. Publication bias was assessed using the Egger's and Begg's tests.ResultsThirteen epidemiologic studies (11 case-control and 2 cohort studies) were included in the meta-analysis. The combined results from all studies indicated that high cruciferous vegetables intake was significantly associated with reduced breast cancer risk (RR = 0.85, 95% CI = 0.77–0.94).ConclusionFindings from this meta-analysis suggest that cruciferous vegetables consumption may reduce the risk of breast cancer. Because of the limited number of studies, further prospective studies are needed to explore the protective effect of cruciferous vegetables on breast cancer.     

Increased bladder wall thickness is associated with severe symptoms and reduced bladder capacity in patients with bladder pain syndrome

ObjectivePatients with interstitial cystitis (IC) and ketamine cystitis (KC) usually have similar symptoms, such as frequency, urgency, and bladder pain. In patients with IC, ulcer type and nonulcer type may have different cystoscopic features. This study investigated the clinical characteristics and bladder wall thickness (BWT) measured using computed tomography (CT) in patients with nonulcer IC, ulcer IC, and KC.Materials and methodsThe detailed history and bladder condition of patients with a clinical diagnosis of IC and KC were retrospectively analyzed. An abdominal to pelvis CT scan with/without contrast was performed in every patient. Ulcer type IC was noted in nine patients, nonulcer IC in seven patients, and KC in 13 patients. The bladder mass volume and BWT were measured. Bladder CT images of 10 patients with nonmetastatic renal cancer served as controls.ResultsThe bladder wall was significantly thicker in all patients with ulcer type IC (8.91 ± 2.67 mm) and KC (10.7 ± 3.44 mm) than in those with nonulcer IC (2.89 ± 0.73 mm) or controls (2.65 ± 0.97 mm). Among KC patients, eight patients received augmentation enterocystoplasty. Moreover, the bladder wall was significantly thicker in patients who underwent augmentation enterocystoplasty (11.50 ± 3.21 mm) than those who did not (9.50 ± 3.81 mm). The bladder mass volume was increased in patients with KC who received augmentation enterocystoplasty (35.67 ± 11.19 mL) compared with those who did not (21.24 ± 7.25 mL). BWT significantly correlated with visual analogue scores for pain (R² = 0.484, p < 0.001), functional bladder capacity (R² = 0.31, p = 0.002), and maximum bladder capacity (R² = 0.469, p < 0.001) in overall patients.ConclusionThere are obvious differences in bladder CT scans of patients with symptoms of bladder pain due to different etiology. Increased BWT was associated with increased pain scores and decreased bladder capacity in patients with KC and IC. BWT on a CT scan might be considered a marker for the severity of bladder inflammation.     

介入栓塞治疗膀胱癌术后阴茎及腹直肌转移1例

<正>患者男,50岁,因"膀胱癌术后20年,广泛转移2个月"就诊。患者20年前因膀胱癌于外院接受膀胱部分切除术,4年前因膀胱癌复发于我院接受全膀胱切除+双侧输尿管皮肤造口,2个月前出现尿道口滴血。实验室检查血红蛋白为73 g/L,CT提示阴茎及左侧腹直肌占位(图1A、1B)。腹直肌病灶穿刺活检诊断为高级别乳头状尿路上皮癌。行DSA引导下介入栓塞治疗(图1C～1H),以微导管超选至肿瘤供血分支,采用40 mg直径150～350 μm明胶海绵颗粒     

Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant

PURPOSE: The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested. MATERIALS AND METHODS: Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls. RESULTS: There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024). CONCLUSIONS: The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.     

Complete transurethral resection of bladder tumor before radical cystectomy is not a risk factor for organ-confined bladder cancer: A case-control study

ObjectivesTo investigate the role of complete transurethral resection of bladder tumor (TURBT) before radical cystectomy (RC) for organ-confined bladder cancer.Materials and methodsData of patients who underwent RC in our center from January 2008 to December 2018 were retrospectively reviewed. Patients with >T2N0M0 disease and positive surgical margins and those who received neoadjuvant/adjuvant chemotherapy or radiotherapy were excluded. Complete TURBT was defined as no visible lesion under endoscopic examination after TURBT or in the bladder specimen after RC. Kaplan-Meier curves and log-rank tests assessed disease-free survival (DFS). Logistic and Cox regression analyses were performed to identify potential predictors.ResultsA total of 236 patients were included in this review, including 207 males, with a median age of 61 years. The median tumor size was 3 cm, and a total of 94 patients had identified pathological T2 stage disease. Complete TURBT was correlated with tumor size (p = 0.041), histological variants (p = 0.026), and down-staging (p < 0.001). Tumor size, grade, and histological variants were independent predictors of complete TURBT. During a median follow-up of 42.7 months, 30 patients developed disease recurrence. Age and histological variants were independent predictors of DFS (p = 0.022 and 0.032, respectively), whereas complete TURBT was not an independent predictor of DFS (p = 0.156). Down-staging was not associated with survival outcome.ConclusionsComplete TURBT was correlated with an increased rate of down-staging before RC. It was not associated with better oncologic outcomes for patients with organ-confined bladder cancer.     

Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

Urinary matrix metalloproteinase‐7 level is associated with the presence of metastasis in bladder cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Recent data suggest that MMP‐7 is critically involved in metastasis formation. In accordance, we formerly found significantly elevated MMP‐7 tissue expression and serum concentration in samples of patients with metastatic bladder cancer and observed an independent correlation between MMP‐7 levels and patients’ prognosis. In the present study we demonstrated that high preoperative urinary MMP‐7 concentrations are associated with metastatic bladder cancer.

OBJECTIVE

? To assess the presence of matrix metalloproteinase (MMP)‐7 in urine samples of patients with bladder cancer and to investigate the correlation between MMP‐7 urine concentration and clinicopathological variables.

PATIENTS AND METHODS

? The presence of MMP‐7 in the urine of patients with bladder cancer was tested in 32 representative cases using immunoprecipitation followed by western blot analysis. ? Urinary MMP‐7 concentration levels were analyzed in 132 patients with bladder cancer and 96 controls using an enzyme‐linked immunosorbent assay.

RESULTS

? MMP‐7 levels did not differ significantly between patients with localized bladder cancer and controls (P= 0.174). On the other hand, we detected a fourfold, significantly elevated MMP‐7 concentration in urine samples of patients with bladder cancer with regional or distant metastasis (P= 0.003). ? Using a threshold value of 6.88 ng/ml, determined by receiver‐operating characteristic curve analysis, a specificity of 82% and a sensitivity of 78% were observed. ? Western blot analysis revealed that the 55‐kDa tissue inhibitor of metalloproteinase 1 complexed MMP‐7 is the dominant form of urinary matrilysin.

CONCLUSIONS

? MMP‐7 is present in detectable amounts in the urine of patients with bladder cancer. Its concentrations are significantly elevated in patients with metastatic disease. ? Determination of urinary matrilysin level could help to detect bladder cancer metastasis, and may therefore provide a more reliable prognosis and influence therapy decisions.     

Concurrent diagnosis of urothelial carcinoma and squamous cell carcinoma of the bladder in a patient with a vesicorectal fistula from invasive rectal cancer

A 47-year-old man underwent a low anterior resection of the rectosigmoid colon with en bloc cystoprostatectomy for vesicorectal fistula due to a locally advanced rectal cancer. Histopathological examination of the bladder revealed two additional primary malignancies: urothelial carcinoma and squamous cell carcinoma. To our knowledge, this is the first reported case of two histologically distinct urothelial malignancies that were diagnosed during a work up of vesicorectal fistula due to adenocarcinoma of the rectum.     

Selective bladder preservation with curative intent for muscle‐invasive bladder cancer: A contemporary review

Radical cystectomy plus urinary diversion, the reference standard treatment for muscle‐invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long‐term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder‐sparing approaches for muscle‐invasive bladder cancer will also inevitably increase. Trimodality bladder‐sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (Σ55–65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50–70% at 5 years), while preserving the native bladder in 40–60% of muscle‐invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include (i) muscle‐invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle‐invasive bladder cancer site; (ii) potential lack of curative intervention for regional lymph nodes; and (iii) increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high‐dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (e.g. 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle‐invasive bladder cancer patients with favorable quality of life.     

The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk

Objectives

To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle.

Methods

Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet).

Results

Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16–1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%–15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle.

Conclusion

This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.     

Extranodal extension in node-positive bladder cancer: the continuing controversy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Although extranodal extension in node‐positive patients may provide prognostic information in certain urological malignancies, contradictory results have been reported in node‐positive patients after radical cystectomy for bladder cancer. We examined whether extranodal extension could have an impact on the outcomes of node‐positive patients who underwent radical cystectomy for bladder cancer in a single large tertiary hospital. We have shown that the presence of extranodal extension was not an independent prognostic factor in node‐positive patients after radical cystectomy and pelvic lymphadenectomy for bladder cancer.

OBJECTIVE

? To examine whether extranodal extension (ENE) has an impact on the outcome of node‐positive patients who underwent radical cystectomy for bladder cancer.

PATIENTS AND METHODS

? Of 543 consecutive patients who underwent radical cystectomy for urothelial carcinoma of the bladder between 1990 and 2007, 112 patients with lymph node metastasis detected on histological examination were evaluated with regard to recurrence‐free survival (RFS) and disease‐specific survival (DSS) based on ENE status.

RESULTS

? The overall 5‐year RFS and DSS rates were 22.3% and 33.8%, respectively. ENE was observed in 41 (36.6%) of the 112 patients. ? The presence of ENE was associated with advanced pathological nodal status (P= 0.004), more positive lymph nodes (P= 0.006), and higher lymph node density (P < 0.001). ? The incidence of positive ENE increased with large positive lymph node diameter (P < 0.001). ? Multivariate analysis showed that lymph node density (hazard ratio (HR) = 2.39, 95% CI 1.09–5.24, P= 0.029; and HR = 3.13, 1.43–6.84, P= 0.004) and use of adjuvant chemotherapy (HR = 1.80, 1.02–3.20, P= 0.041; and HR = 2.07, 1.13–3.79, P= 0.018) were significant predictors of RFS and DSS, respectively. ? After adjustment for other prognostic factors, ENE was not significantly related to RFS (P= 0.825) and DSS (P= 0.961) by multivariate analysis.

CONCLUSIONS

? The presence of ENE was not an independent prognostic factor in node‐positive patients after radical cystectomy for bladder cancer. ? Additional prospective studies are needed to determine the independent prognostic role of ENE.     

Laparoscopic versus open radical cystectomy for the management of bladder cancer: Mid-term oncological outcome

Objective:   To compare the mid-term oncological outcome of laparoscopic radical cystectomy (LRC) with those of open radical cystectomy (ORC).
Methods:   From June 2003 to February 2008, 36 LRCs were carried out at our institute for the treatment of bladder cancer. Clinical and oncological data were retrospectively analyzed. A match-pair comparison with an historical series of 34 patients who were submitted to ORC between 1996 and 2003 was carried out.
Results:   Median follow-up of the LRC group was 21 months (3–56 months). Pathological stage or grade was similar in the two groups. There was no significant difference between the LRC and ORC groups in terms of 3-year overall (64.2% vs 72.6%, respectively; P  = 0.682), cancer-specific (73.0% vs 75.3%, respectively; P  = 0.951), and recurrence-free survival (70.5% vs 72.5%, respectively; P  = 0.715) rates. In a subgroup analysis according to stage, there was also no significant difference in the 3-year disease-specific survival after LRC or ORC for organ-confined (pT1 and pT2; 85.7% vs 83.9%, respectively; P  = 0.256) or extravesical disease (pT3 and pT4; 73.3% vs 63.8%, respectively; P  = 0.825).
Conclusion:   These findings suggest that LRC provides mid-term oncological outcomes similar to those of ORC in the management of bladder cancer.