Evaluation of nonlinear optimization for scheduling of follow-up cystoscopies to detect recurrent bladder cancer. The Bladder Cancer follow-up Group.

Standard recommendations for patients who have had superficial bladder cancer are inspection by cystoscopy quarterly for a year or two after tumor removal, then half-yearly and yearly. The authors assessed the potential for improvement in scheduling cystoscopies according to probabilistic optimization techniques. Eight hypothetical practices were created, based on retrospective analysis of 918 bladder-cancer-patient charts. Standard and alternative recommendations for the interval to next cystoscopy were compared. The alternatives were derived from patient-specific predictions of future tumor risks (based on the patient's prior recurrence rate and tumor stage and grade) and a nonlinear optimization approach to allocation of the same number of cystoscopies as were available for standard follow-up. The optimization proposed longer intervals between visits for low-risk patients and shorter intervals for high-risk patients. Overall, optimization reduced expected tumor detection delays by 30%, from 12.6 to 8.7 weeks. When optimization intervals were shorter than standard, cancer was found more often at subsequent cystoscopies (34% vs 27%, p less than 0.05), suggesting that the optimization was a better predictor of cancer recurrence. If reduction in tumor-detection delay is the goal of follow-up for recurrent cancers, then urologists can improve monitoring by using probabilistic optimization methods for scheduling cystoscopies. Further understanding of the accuracy of predictive models for bladder-cancer recurrence rates is desirable. Subsequently, the optimization method developed here may be tested prospectively.     

经尿道二次电切术对非肌层浸润性膀胱癌术后复发的应用价值

目的 探讨经尿道二次电切术治疗非肌层浸润性膀胱癌术后复发的作用.方法 经尿道电切术治疗非肌层浸澜性膀胱癌患者120例,采取随机机械抽样方法分成两组,每组60例,试验组于首次经尿道电切术后4周行经尿道二次电切术,外加丝裂霉素膀胱灌注化疗;对照组首次经尿道电切术后加丝裂霉素膀胱灌注化疗.两组术后每3个月行膀胱镜复检,随访6～34 (18.6±6.5)个月,对比其术后肿瘤复发情况.结果 在随访期内,试验组复发率明显低于对照组[21.7％(13/60)比63.3％ (38/60)],差异有统计学意义(P＜0.01).所有复发患者中,以高级别肿瘤(G2、G3级)的复发为主,试验组高级别肿瘤复发率明显低于对照组[26.2％(11/42)比70.0％(35/50)],差异有统计学意义(P＜0.01).结论 经尿道二次电切术可以降低非肌层浸润性膀胱癌(尤其是高级别肿瘤)的术后复发率,可以更准确地进行肿瘤分期和发现残存肿瘤,在临床治疗上是有应用价值的.     

A non-invasive QPCR method monitoring DNA based therapy of bladder cancer patients

Real-time PCR technology is highly advantageous for gene studies based on the genetic nature of the transferred material. Urine and blood samples were collected before and after treatment. Treatment of bladder carcinoma patients with plasmid constructs expressing the diphtheria toxin gene was monitored. Detection range from 5x10(6) copies to 相似文献   

Surgery for recurrent ovarian cancer

Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer. The role in recurrent ovarian cancer remains a field of discussion and controversy, mainly owing to missing data from prospective randomized trials and lack of universal definitions. Retrospective data indicate that complete resection of recurrent tumor formations should be aimed for, since survival prolongation is mainly seen for patients with no residual disease. Thus, it is most important to find predictors of complete resection, on the one hand to offer the best therapeutic chances to patients, but on the other hand to protect patients with limited life expectancy from additional surgical burden. The first prospective surgical trial in recurrent ovarian cancer, AGO-DESKTOP II validated a score ('AGO score') for complete resection. It was shown that patients with a good general condition (ECOG 0), no residual disease after surgery for primary ovarian cancer and absence of ascites in presurgical diagnostics have a 76% likelihood of undergoing complete resection. In this article, further recent data regarding surgery for recurrent ovarian cancer are going to be discussed and the advantages of incorporating these patients into randomized trials are highlighted.     

Therapy for recurrent ovarian cancer

Primary treatment of advanced ovarian cancer is well established. The combination of tumor debulking and platinum/taxane polychemotherapy has led to improved treatment results in recent years. However, most patients with ovarian cancer will relapse, rendering treatment of recurrent ovarian cancer of great clinical interest. Relapse therapy should depend on the treatment-free interval. Patients with progressive disease during primary treatment or cancer relapse within 6 months after the completion of primary treatment are platinum refractory, and, therefore, prognostically unfavorable. For these patients with poor outcome, quality of life should be predominantly considered before initiation of treatment. Cancer relapse after an interval of more than 6 months after the completion of primary treatment cannot be cured; however, platinum-based chemotherapy, in individual cases combined with secondary tumor debulking, can lead to persisting remissions.     

Localization of primary and recurrent bladder tumors

The location distribution of the primary and recurrent bladder tumours was studied in 417 patients. The authors decided that the ureteral orifices, the lateral walls are the most common places of primary superficial bladder tumours. The favoured places of the primary invasive bladder tumours are the posterior walls. They found not so much disparity between the site of primary and recurrent invasive bladder tumours, but the difference between the site of the primary and recurrent superficial bladder tumours is remarkable. They decided, according to their patients material, that the recurrent superficial bladder tumours take places more frequently on the posterior walls, the dome and the anterior walls. The explanation of this phenomenon may be the tumour cells implantation during the TUR. The authors survived all the other processes can yield the local and distant recurrent bladder tumours and understanding of this processes can result in a better understanding of the location distribution of the recurrent bladder tumours on the one hand and it can help us to avoid or decrease the recurrences on the other hand.     

Attributable risks for bladder cancer in Northern Italy

Attributable risks (ARs) for bladder cancer were computed in relationship to cigarette smoking, coffee consumption, low intake of vegetables, history of cystitis, and occupation using data from a case-control study conducted in northern Italy between 1985 and 1993. Cases were 431 patients with histologically confirmed bladder cancer, and controls were 491 patients admitted to the same network of hospitals for acute, nonneoplastic, and non-urinary-tract diseases. Overall, the AR estimates were 49% for cigarette smoking, 23% for coffee consumption, 16% for low intake of vegetables, 12% for history of cystitis, and 4% for occupation. These five factors together explained more than 70% of bladder cancer cases in this population. The AR for cigarette smoking was significantly higher among men (56%) than women (17%), whereas coffee consumption, low vegetable intake, and cystitis were more important (but not significantly so) among women. These results suggest that more than 2500 of the 5400 deaths due to bladder cancer in Italy in 1990 could have been prevented by the elimination of cigarette smoking. With some appropriate dietary modification and intervention to prevent urinary tract infections and occupational exposures, this figure could approach 4000 avoidable deaths. Thus, bladder cancer could become a rare cause of death in this population.     

上尿路移行上皮细胞癌根治术后复发膀胱肿瘤的高危因素分析

目的 探讨肿瘤部位与上尿路移行上皮细胞癌根治术后复发膀胱肿瘤风险的关系.方法 对行根治手术并获随访的168例上尿路移行上皮细胞癌患者的临床资料进行回顾性总结,比较不同部位上尿路移行上皮细胞癌根治术后复发膀胱肿瘤的风险,采用Cox回归分析术后复发膀胱肿瘤风险的独立影响因素.结果 168例患者术后1、3、5年的无复发膀胱肿瘤的生存率分别为88%、76%和63%.观察期内,共有49例术后发生膀胱肿瘤复发,中位首次复发时间为20个月.肾盂癌术后复发率为30.8%(28/91);输尿管中段癌术后复发率为8.3%(2/24),输尿管下段癌术后复发率为48.7%(19/39).肾盂癌与输尿管癌患者术后无复发膀胱肿瘤生存率比较差异无统计学意义(P>0.05).多因素分析结果显示输尿管下段癌为影响上尿路移行上皮细胞癌根治术后复发膀胱肿瘤风险的独立变量(P<0.01).结论 输尿管下段癌患者术后复发膀胱肿瘤的风险高于其他部位上尿路移行上皮细胞癌.

Abstract：

Objective To investigate the relationship between tumor location and the risk of developing bladder cancer in pafients treated by nephroureterectomy(NU)for upper urinary tract transitional cell carcinoma(UUT-TCC).Methods The clinical data of 168 UUT-TCC patients who underwent NU were reviewed.Univariate and multivariate analysis were carried out to determine the risk factors for intravesical recurrence after NU.Results The recurrence-free survival rate at 1,3 and 5 years after NU were 88%, 76%and 63%.All patients were followed up for a median period of 45(12-107)months During this period, a total of 49 patients developed bladder tamors after surgery,of which 28 cases were renal pelvic carcinoma, 2 cases were rniddle ureter carcinoma and 19 cases were distal ureter carcinoma.The recurrence-free survival of renal pelvic carcinoma and ureter carcinoma had no significant difference by Log-Rank test(P>0.05).On multivariate analysis,only locating in distal ureter carcinoma was the independent risk predictor for intravesical recurrence after NU (P<0.01).Conclusion Pafients with UUT-TCC at distal ureter carry a higher risk for intraeesieal recunerrce after NU than those with TCC at other location of upper urinary tract.     

Design of clinical trials for recurrent events with periodic monitoring.

This paper presents a design for randomized clinical trials in which incomplete data are collected on the occurrence of potentially recurrent events through periodic monitoring. In particular, events are assumed to arise according to a point process, but information is available at the times of monitoring only if one or more events has occurred since the preceding monitoring point. The event process is modelled via a piecewise Poisson process, and a proportional rates model is introduced to represent the difference in event rates between treatment groups. The design was developed on the basis of a Wald-type test derived from the generalized estimating equations of Liang and Zeger (Biometrika 73, 13-22 (1986)). Robustification of the variance of the estimator of the treatment effect was considered under a random effects model with a semi-parametric mixture distribution. The design was adopted to address issues which arose in an osteoporosis trial conducted in Japan.     

Recombinant BCGs for tuberculosis and bladder cancer

Bacillus Calmette–Guérin (BCG) vaccine is an attenuated live strain of Mycobacterium bovis. It may be the most widely used vaccine in human history and is the only licensed human tuberculosis (TB) vaccine available. Despite its excellent safety history, a century of use in global vaccination programs, and its significant contribution to reducing TB mortality among children, the efficacy of BCG continues to be disputed due to its incomplete protection against pulmonary TB in adults. Still vaccines offer the best chance to contain the ongoing spread of multi-drug resistance TB and disease dissemination. The development of improved vaccines against TB therefore remains a high global priority. Interestingly, recent studies indicate that genetically modified BCG, or administration of existing BCG through alternate routes, or revaccination, offers improved protection, suggesting that BCG is well poised to make a comeback.Intravesical BCG is also the only approved microbial immunotherapy for any form of cancer, and is the first-line therapy for treatment-naïve non-muscle invasive bladder cancer (NMBIC), which represents a majority of the new bladder cancer cases diagnosed. However, almost a third of patients with NMIBC are either BCG unresponsive or have tumor recurrence, leading to a higher risk of disease progression. With very few advances in intravesical therapy over the past two decades for early-stage disease, and a limited pipeline of therapeutics in Phase 3 or late Phase 2 development, there is a major unmet need for improved intravesical therapies for NMIBC. Indeed, genetically modified candidate BCG vaccines engineered to express molecules that confer stronger protection against pulmonary TB or induce potent anti-tumor immunity in NMIBC have shown promise in both pre-clinical and clinical settings. This review discusses the development of second generation, genetically modified BCG candidates as TB vaccines and as anti-tumor adjuvant therapy for NMIBC.     

New developments in chemotherapy for metastasized bladder cancer]

Methotrexate vinblastine doxorubicin cisplatin (MVAC) has been the golden standard in the chemotherapy of metastasized bladder cancer for more than ten years. This regimen is particularly suitable for fit patients (WHO performance status 0 or 1) with a good renal function. This leads to an overall response in 40-57% of the patients and to a complete response in 13-19%. The median survival is about 15 months. Combination chemotherapy consisting of cisplatin and gemcitabine (GC) is a valuable alternative with a comparable effectiveness, but with the advantage of clearly less toxicity (neutropenic fever, mucositis, sepsis and mortality). The extra value of adding paclitaxel to this GC combination to improve the survival of this fit group of patients is currently being investigated. The value of the combination carboplatin-gemcitabine versus carboplatin-methotrexate-vinblastine as a palliative regimen with a favourable toxicity profile for the less fit patients is also currently under investigation.     

Cost-effectiveness of investigations for invasive bladder cancer.

The results of diagnostic and staging investigations in consecutive cases of invasive transitional cell carcinoma of the bladder are reviewed. Urine culture, urine cytology and intravenous urography had positive results in a high percentage of cases. As diagnostic investigations they are cost-effective but certainly do not remove the obligation to perform cystoscopy and examination under anaesthetic. Isotopic bone scan and liver scan showed metastases in 4 and one cases respectively and only when there were clinical signs of disseminated disease. Chest X-ray showed metastases in one case. These investigations are not cost-effective. Lymphangiography was positive in 12 of the 94 cases and, although expensive (pounds 70), is still a staging investigation of value in planning treatment.