TURBT联合膀胱内BCG灌注治疗肌层浸润性膀胱癌疗效分析

目的 探讨选择性经尿道膀胱肿瘤电切术(transurethral resection of bladder tumor,TURBT)治疗经选择的肌层浸润性膀胱尿路上皮癌患者保留有功能性膀胱的可行性.方法 回顾性分析大连医科大学附属第二医院2006年至2011年间323例行TURBT治疗的膀胱尿路上皮癌患者的临床资料,选择术前影像学检查无明显膀胱外浸润,肿瘤单发,直径5 cm以下,局限于膀胱顶壁、底壁及侧壁,距输尿管口1 cm以上,不伴有原位癌,肿瘤创缘及基底部活检为阴性的T2期患者为研究对象,接受选择性TURBT伴膀胱内灌注BCG的保膀胱治疗.术后膀胱镜密切随访5~10年,运用统计学分析生存率、疾病特异生存率和无复发生存率评价疗效.结果 入组31例患者,5年总体生存率、疾病特异生存率和无复发生存率分别为87%、93%和58%.复发15例,浅表性复发6例,8例接受延迟膀胱癌根治术.23例保留有功能性膀胱,死亡6例.结论 选择性TURBT治疗肌层浸润性膀胱癌在少部分经严格选择的患者中是合理可行的,术后患者应终生接受膀胱镜严密随访.     

Laparoscopic radical cystectomy and bilateral ureteric ligation for muscle-invasive bladder cancer in a patient on hemodialysis

Laparoscopic cystectomy and bilateral ureteric ligation were performed on a 52-year-old woman with end-stage renal disease on hemodialysis (HD) for muscle-invasive bladder cancer. Her volume of urine production was approximately 100 mL/day. Excisions of the bladder and uterus with ligation of the bilateral ureter were conducted completely laparoscopically. Total operative time was 280 min and the amount of blood loss was 60 mL. No complications were seen perioperatively and no adverse events regarding ureteric ligation arose. HD was performed on the second postoperative day. At a 12-month follow-up, the patient showed no evidence of disease.     

保留膀胱手术治疗肌层浸润性膀胱癌临床分析

目的:探讨肌层浸润性膀胱癌(muscle invasive bladder cancer,MIBC)行保留膀胱手术治疗的可行性及临床价值。方法:回顾性分析43例MIBC患者的临床资料:男28例,女15例,年龄45～88岁,平均62岁。其中38例(88.4%)行经尿道膀胱肿瘤电切除术(transurethral resection of bladder tumor,TURBT),5例(11.6%)行膀胱部分切除术;术后均行膀胱灌注化疗或放疗。结果:术后病理分期:T236例(83.7%),T37例(16.3%);病理分级:G14例(9.3%),G231例(72.1%),G38例(18.6%)。术后随访6～126个月,平均63.2个月;首次复发为3～20周,平均10.2周,复发次数1～8次,平均3.7次;共行2～9次TURBT,平均3.5次,其中25例(58.1%)于≥3次TURBT后出现病理性进展,9例(20.9%)于术后复发次数≥3次后改行根治术;2例(4.7%)死于非膀胱癌疾病,1例(2.3%,病理为T2G1)于首次术后126个月死于膀胱癌多发转移。结论:对于MIBC,可选择性行以TURBT为主加放化疗的保留膀胱手术治疗,但具有反复复发及进展倾向;首次复查膀胱镜时间需提前到术后4～8周,远期疗效需进一步评估。     

膀胱部分切除术治疗肌层浸润性膀胱癌的再认识

膀胱癌是泌尿系统最常见的恶性肿瘤之一,对于肌层浸润性膀胱癌(MIBC)目前主要治疗方法是以手术治疗为主的综合治疗,标准手术治疗方式为根治性膀胱切除术(RC)合并盆腔淋巴结清扫,但该手术仍存在手术复杂、并发症多、术后生活质量差等不足,保留膀胱手术之一的膀胱部分切除术(PC)重新受到国内外学者的关注,有可能成为治疗MIBC的主要手术方法之一。     

Impact of sarcopenia in bladder preservation therapy for muscle-invasive bladder cancer patients: a narrative review

Background and ObjectiveMuscle-invasive bladder cancer (MIBC) is a biologically aggressive disease and its prognosis is poor. Radical cystectomy (RC) with urinary diversion and lymph node dissection is the gold standard treatment for MIBC patients. Accumulating evidence indicates that sarcopenia, the degenerative and systemic loss of skeletal muscle mass, is a significant predictor of higher rates of mortality and perioperative complications following RC. Recently, bladder preservation therapy has been offered as an alternative in appropriately selected MIBC patients who desire to preserve their bladders and those unfit or unwilling for RC. Here, we performed a narrative review on the impact of sarcopenia on oncological outcomes and complication rates in MIBC patients treated with bladder preservation therapy.MethodsA literature review was performed using the PubMed and Scopus databases.Key Content and FindingsWe identified two studies reported the impact of sarcopenia on responses to trimodal therapy and survival outcomes in MIBC patients. Consolidative partial cystectomy was performed in patients who achieved clinical complete response (CR) to trimodal therapy in one of the two studies. In both studies, CR rates to trimodal therapy are comparable between sarcopenic and non-sarcopenic patients. Sarcopenia was not significantly associated with shorter survival after completing bladder preservation therapy in either study. For complication rates of bladder preservation therapy, one study showed equivalent complication rates of consolidative partial cystectomy between sarcopenic and non-sarcopenic patients. In addition, in another small series of trimodal therapy, sarcopenic patients showed a higher rate of complications of trimodal therapy compared with non-sarcopenic patients.ConclusionsAccording to the result of our literature review, sarcopenia would not affect responses to trimodal therapy and prognosis in MIBC patients treated with bladder preservation therapy. Although the effect of sarcopenia on complication rates of bladder preservation therapy is inconclusive due to limited evidence, bladder preservation therapy could be a viable alternative option in carefully selected MIBC patients regardless of the presence of sarcopenia.     

Bladder-sparing protocols in the treatment of muscle-invasive bladder cancer

Bladder-sparing protocols (BSP) have been gaining widespread popularity as an attractive alternative to radical cystectomy (RC) for muscle-invasive bladder cancer. Unimodal therapies are inferior to multimodal regimens. The most promising regimen is trimodal therapy (TMT), which is a combination of maximal transurethral resection of bladder tumor (TURBT), radiotherapy, and chemotherapy. In appropriately selected patients (low volume unifocal T2 disease, complete TURBT, no hydronephrosis and no carcinoma-in-situ), comparable oncological outcomes to RC have been reported in large retrospective studies, with a potential improvement in overall quality of life (QOL). TMT also offers the possibility for definitive therapy for patients who are not surgically fit to undergo RC. Routine biopsy of previous tumor resection is recommended to assess response. Prompt salvage RC is required in non-responders and for recurrent muscle-invasive disease, while non-muscle-invasive recurrence can be managed conservatively with TURBT +/− intravesical BCG. Long-term follow-up consisting of routine cystoscopy, urine cytology, and cross-section imaging is required. Further studies are warranted to better define the role of neoadjuvant or adjuvant chemotherapy in the setting of TMT. Finally, future research on predictive markers of response to TMT and on the integration of immunotherapy in bladder sparing protocols is ongoing and is highly promising.     

Tumor heterogeneity in muscle-invasive bladder cancer

Muscle-invasive bladder cancer (MIBC), a highly heterogeneous disease, shows genomic instability and a high mutation rate. Clinical outcomes are variable and responses to conventional chemotherapy differ among patients (due to inter-patient tumor heterogeneity and inter-tumor heterogeneity) and even within each individual tumor (intra-tumor heterogeneity). Emerging evidence indicates that tumor heterogeneity may play an important role in cancer progression, resistance to therapy, and metastasis. Comprehensive molecular subtyping classifies MIBC into distinct categories that have potential to guide prognosis, patient stratification, and treatment. Genomic characterization of time-series analyses at the single cell level, and of cell-free circulating tumor DNA or circulating tumor cells, are emerging technologies that enable dissection of the complex clonal architecture of MIBC. This review provides insight into the clinical significance of the molecular mechanisms underlying heterogeneity, focusing on inter- and intra-tumor heterogeneity, with special emphasis on molecular classification and methods used to analyze the complex patterns involved.     

新辅助动脉化疗在肌层浸润性大体积膀胱癌保留膀胱治疗中的价值

目的评估术前新辅助动脉化疗联合经尿道手术在直径超过3cm的肌层浸润性膀胱癌保留膀胱治疗的临床价值。方法对于较大体积(直径3cm)的28例肌层浸润性膀胱肿瘤(T2N0M0~T4aN0M0)采用新辅助动脉化疗联合手术治疗,观察动脉化疗效果,分析肿瘤降期率、保留膀胱率、肿瘤复发率,Kaplan-Meier法计算总体生存率、无肿瘤复发生存率,并绘制生存曲线。结果 26例(92.9%)患者动脉化疗有效,肿瘤可见明显缩小,经3~5次动脉介入治疗后行经尿道切除术+膀胱灌注完成保留膀胱治疗;动脉化疗无效2例,立即行根治性全膀胱切除术。26例完成保留膀胱治疗的患者,术后肿瘤病理分期降低19例(73.1%),无变化为7例。肿瘤复发8例(复发率为30.8%),其中,浅表性复发5例,局部浸润性复发2例,远处转移1例。28例患者总体生存率:3年69%,5年62.1%。无肿瘤复发生存率:5年44.07%。最终25例患者得到保留膀胱(保留膀胱率89.3%)。结论直径3cm的较大体积浸润性膀胱肿瘤采用术前新辅助动脉化疗治疗,可使肿瘤降期降级及体积缩小,有利于经尿道完全切除,可有效提高患者生存率,同时保留了膀胱,大大提高患者生存质量,对不愿或不宜行膀胱全切的患者是一个理想的选择。     

C-reactive protein level predicts prognosis in patients with muscle-invasive bladder cancer treated with chemoradiotherapy

OBJECTIVE

To investigate the effect of C‐reactive protein (CRP) level on the prognosis of patients with muscle‐invasive bladder cancer treated with chemoradiotherapy (ChRT), as it is increasingly recognized that the presence of a systemic inflammatory response is associated with poor survival in various malignancies.

PATIENTS AND METHODS

The clinical records of 88 patients with bladder urothelial carcinoma (cT2–4 N0M0) treated with ChRT were reviewed retrospectively. ChRT comprised external beam radiotherapy to the bladder (40 Gy) with two cycles of cisplatin (50–100 mg) at 3‐week intervals. Elevated CRP was defined as >0.5 mg/dL. The survival rate was calculated using the Kaplan‐Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model.

RESULTS

During the median (range) follow‐up of 33 (3–117) months, 19 patients died from bladder cancer; the 5‐year cancer‐specific survival (CSS) rate was 73%. Ten patients had a high CRP level before ChRT (≥0.5 mg/dL) and their CSS rate was significantly worse than that in the remaining patients (P = 0.003). Multivariate analysis showed that CRP and cT stage were independent prognostic indicators for CSS, with a hazard ratio of 1.80 (95% confidence interval 1.01–2.97; P = 0.046). Among 10 patients in those with elevated CRP the CRP levels became normal after ChRT in six, of whom all but one was alive with no evidence of recurrence or metastasis during the follow‐up. By contrast, all four with no CRP normalization after ChRT died within 2 years.

CONCLUSIONS

To our knowledge this is the first study to report that elevation of CRP before treatment predicts a poor prognosis in patients with muscle‐invasive bladder cancer who are receiving ChRT. Furthermore, failure of CRP levels to normalize after ChRT was associated with extremely poor survival.     

中性粒细胞/淋巴细胞比值在肌层浸润性膀胱癌预后评估中的价值

目的探讨术前外周血中性粒细胞与淋巴细胞比值(NLR)是否可以作为肌层浸润性膀胱癌(MIBC)患者术后的预后评价指标。方法回顾性分析2008年1月至2011年12月行膀胱癌根治术的214例MIBC患者的临床资料,根据患者术前外周血NLR大小分为低NLR组(NLR<3,92例)和高NLR组(NLR≥3,122例),比较两组患者的5年生存率并进行预后危险因素分析。结果低NLR组和高NLR组MIBC患者5年生存率分别为70.9%和55.8%(P<0.01)。单因素分析显示,术前NLR、吸烟史、病理T分期、肿瘤分级、围手术期输血、淋巴结转移、淋巴结密度及切缘阳性与MIBC患者预后有关(P<0.05);Cox回归分析证实,NLR是影响MIBC患者预后的独立危险因素(HR=2.142,95%CI:1.212~3.786,P<0.01)。结论术前NLR是影响MIBC患者术后生存时间的独立危险因素,可作为MIBC患者的预后指标。     

Management of muscle-invasive bladder cancer in Victoria, 1990-1995

BACKGROUND: The management and outcomes of muscle-invasive bladder cancer are described in this article. METHODS: A retrospective survey of medical practitioners involved in the management of bladder cancer was conducted. The survey obtained at least 5 years of follow-up data on all patients. The sample was taken from the public and private health sectors in Victoria. All were cases of muscle-invasive bladder cancer diagnosed between 1990 and 1995. The main outcome measures included reported management by staging, treatment and survival. RESULTS: Completed questionnaires were returned for 743 (89.6%) of 829 cases. Of these, 523 (70.4%) were men, and the mean age was 72.7 years. More than 75% of the cases (560) presented with macroscopic haematuria. The majority (696, 94%) had transitional cell carcinoma. A variety of treatments were given in various sequences, with 231 cases (31.1%) having initial surveillance. Eventually, 303 cases (40.8%) proceeded to 'definitive' management with either radiotherapy (132, 17.8%) or cystectomy (171, 23.0%). In addition, chemotherapy was given to 254 patients (34.2%) at some time. Most patients (613, 82.5%) have subsequently died; 402 (54%) died from bladder cancer. Crude 5-year survival was 13.0%, and disease-specific survival was 27.7%. Multivariate analysis identified the following predictors of greater disease-specific survival: grade 1 or 2 histopathology (P = 0.0003), T2 primary (P < 0.0001), N0 disease (P = 0.04), M0 disease (P < 0.0001), radiation dose in BED(10) >70 Gy and cystectomy (P < 0.0001). CONCLUSION: Muscle-invasive bladder cancer in Victoria typically occurs in elderly patients, and a notable proportion of these patients do not proceed onto 'definitive' treatment. Disease stage, cystectomy and the use of high doses of radiation are associated with better outcomes. Chemotherapy was given to approximately one-third of patients at some point in their disease management. Our data are similar to population-based data from North America, and provide a baseline against which potential changes in management of bladder cancer can be compared.     

Perioperative immunotherapy for muscle-invasive bladder cancer

Radical cystectomy is the standard of care treatment for patients with localized muscle-invasive bladder cancer (MIBC). However, patients with MIBC experience high rates of relapse despite primary therapy, and perioperative strategy is an important treatment option. Cisplatin-based neoadjuvant chemotherapy was associated with improved prognosis, and adjuvant chemotherapy is also an important option for selected patients. However, perioperative chemotherapy is not effective in some patients. Moreover, the currently recommended perioperative treatment is cisplatin-based chemotherapy; approximately 50% of the patients are ineligilble for cisplatin treatment owing to various reasons such as medical comorbidities, poor performance status, and renal insufficiency. The recent success of treatment with immune checkpoint inhibitors (ICIs) suggests that ICIs is the new standard therapy for patients with metastatic bladder cancer. Furthermore, ICIs showed more favorable toxicity profiles than conventional cytotoxic chemotherapy. These results indicate that ICIs may play a role in the treatment of muscle-invasive disease, and many recent studies have been conducted in a perioperative setting. The present review aims to summarize and discuss the current perioperative strategy of immunotherapy focused on ICIs based on recent ongoing clinical trials.     

Significance of preoperative butyrylcholinesterase as an independent predictor of survival in patients with muscle-invasive bladder cancer treated with radical cystectomy

ObjectivesButyrylcholinesterase (BChE) is an alpha-glycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, inflammation, injury, infection, malnutrition, and malignant disease. In this study, we analyzed the potential prognostic significance of preoperative BChE levels in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC).Methods and materialsWe retrospectively evaluated 327 patients with MIBC who underwent RC from 1996 to 2013 at a single institution. Serum BChE level was routinely measured before operation in all patients. Covariates included age, gender, preoperative laboratory data (anemia, BChE, lactate dehydrogenase, and C-reactive protein), clinical T (cT) and N stage (cN), tumor grade, and RC with/without neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall survival (OS) and disease-free survival (DFS). Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model.ResultsThe median BChE level was 187 U/l (normal range: 168–470 U/l). The median age of the enrolled patients was 69 years, and the median follow-up period was 51 months. The 5-year OS and DFS rates were 69.6% and 69.3%, respectively. The 5-year OS rates were 90.1% and 51.3% in the BChE≥168 and<168 U/l groups, respectively (P<0.001). The 5-year DFS rates were 83.5% and 55.4% in the BChE≥168 and≤167 U/l groups, respectively (P<0.001). In the univariate analysis, BChE, cT, cN, and RC with/without neoadjuvant chemotherapy were significantly associated with both OS and DFS. Multivariate analysis revealed that BChE was the factor most significantly associated with OS, and BChE, cT, and cN were significantly associated with DFS.ConclusionsThis study validated preoperative serum BChE levels as an independent prognostic factor for MIBC after RC.     

Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer

OBJECTIVE: To determine if bladder cancer diagnosed after prostatic radiation therapy (RT) differs in behaviour from bladder cancer diagnosed after prostate cancer not treated with RT, as such bladder cancer is thought to be more aggressive than de novo bladder cancer, and epidemiological studies show a higher rate of bladder cancer in patients after irradiation. PATIENTS AND METHODS: We reviewed our records to identify patients who had a diagnosis of bladder cancer with a previous diagnosis of prostate cancer. Patient age, date of diagnosis of prostate cancer, date of diagnosis of bladder cancer, symptoms, clinical stage, initial pathology, definitive therapy, definitive pathological stage, and disease status were recorded. RESULTS: In all, 100 patients were identified who had a diagnosis of bladder cancer after a diagnosis of prostate cancer between January 1992 and August 2003; 58 had had RT for prostate cancer. The mean time between a diagnosis of bladder cancer and prostate cancer was 62 months in the RT group and 34 months in the unirradiated group (P = 0.002) At diagnosis of bladder cancer, 56 (97%) of the patients who received RT had high-grade urothelial carcinoma, vs 27 (64%) of those not irradiated (P < 0.001). Thirty (52%) of the patients with RT had muscle-invasive bladder cancer, vs 17 (40%) of those not irradiated (P = 0.3). The survival rate was similar for both groups. CONCLUSIONS: Bladder cancer is diagnosed later, and is of higher grade, in patients who are irradiated for prostate cancer than in those treated with other methods. Patients with prostate cancer who are treated with RT should be monitored closely for the presence of bladder cancer.     

Partial cystectomy for muscle-invasive bladder cancer: a review of the literature

The radical cystectomy (RC) for muscle-invasive bladder cancer is one of the most morbid and complex urologic procedures performed today. To avoid these complications, the partial cystectomy (PC) has been offered as an alternative in carefully selected patients as a means of achieving equal oncologic efficacy with less morbidity. Selection criteria should include solitary tumors without concomitant carcinoma in situ (CIS) and amenable to resection with 1–2 cm margins in a normally functioning bladder. In addition to the standard work-up, random bladder and prostatic biopsies may be performed. The PC can be performed through an open, laparoscopic, or robot-assisted approach, each with acceptable outcomes. A number of techniques have been developed to identify and resect the tumor completely with negative margins, while preventing tumor spillage within the abdomen. While there are no randomized trials, single institution series have demonstrated acceptable oncologic outcomes in appropriately selected patients. Therefore, offering PC in the appropriate candidate, including those patients who do not accept or are unfit for the associated morbidity of a RC, represents an acceptable alternative.     

Aspergilloma clinically mimicking Achilles tendon xanthoma in a non-immunocompromised patient: A case report

A 48-year-old woman visited our outpatient clinic complaining of discomfort while wearing shoes due to a large mass around her Achilles tendon. The mass was firm, non-tender, non-reducible, and moved with the Achilles tendon, similar to Achilles tendon xanthoma. However, magnetic resonance imaging revealed multiple heterogeneous, nodular lesions with low T1 and T2 signal intensity, and histological examination of the biopsy specimen revealed the mass to contain hyphae of Aspergillus, indicating aspergilloma. The purpose of this case report is to emphasize that a tumor around the Achilles tendon can be something other than xanthoma even when the clinical features are typical of xanthoma.Level of clinical evidence4.     

保留膀胱手术联合动脉插管化疗对高危非肌层浸润性膀胱癌的疗效研究

目的：研究保留膀胱手术联合动脉插管化疗对高危非肌层浸润性膀胱癌的疗效.方法回顾性分析2012年1月至2014年12月于我院行保留膀胱手术的58例高危非肌层浸润性膀胱癌患者的临床资料,58例患者术后随机纳入动脉插管化疗组和膀胱灌注组,定期随访,观察比较两组患者的复发率、进展率、无复发生存率、无肿瘤进展生存率和毒副作用等.结果经过10~46(中位时间25)个月的随访,动脉化疗组(27例,平均随访23.7个月)1例复发,复发率为3.7％,平均无肿瘤复发生存时间为(38.2±0.8)个月;无肿瘤进展,肿瘤进展率为0.膀胱灌注组(31例,平均随访25.7个月)10例复发,复发率为32.3％,平均无肿瘤复发时间为(29.7±2.3)个月;5例肿瘤进展(侵犯肌层或远处转移),进展率为16.1％.两组无复发生存率分别为95.7％、37.0％,无肿瘤进展生存率分别为100％、66.7％,两两比较,差异均有统计学意义(分别P＝0．006,P＝0．030).结论保留膀胱手术的高危非肌层浸润性膀胱癌患者联合动脉插管化疗相比单纯行膀胱灌注化疗能有效降低膀胱癌复发及进展的风险.