浸润性膀胱癌化疗的现状

浸润性膀胱癌病人 5 0 %有临床检测不到的微转移灶 ,有微转移灶的患者多数 1年内出现症状。全身化疗对浸润性膀胱癌有一定疗效 ,但能否延长晚期患者的生存期尚存争议。本文对浸润性膀胱癌的辅助、新辅助化疗现状进行综述 ,旨在为膀胱癌选择辅助和新辅助化疗时提供参考     

浸润性膀胱癌化疗的现状

浸润性膀胱癌病人50％有临床检测不到的微转移灶，有微转移灶的患者多数1年内出现症状。全身化疗对浸润性膀胱癌有一定疗效，但能否延长晚期患者的生存期尚存争议。本文对浸润性膀胱癌的辅助、新辅助化疗现状进行综述，旨在为膀胱癌选择辅助和新辅助化疗时提供参考。     

肌层浸润性膀胱癌新辅助化疗研究进展

膀胱癌是泌尿系统常见恶性肿瘤之一,初诊时约1/3为肌层浸润性,其治疗以根治性膀胱切除术为主,但术后存在较高的肿瘤复发与转移风险。新辅助化疗在一定程度上提高患者生存率,降低复发率,并增加保留膀胱功能的可能性,但目前仍存在争议。本文从新辅助化疗的临床应用价值与依据、化疗方案的选择以及在保留膀胱治疗中的应用等方面阐述肌层浸润性膀胱癌新辅助化疗研究的新进展。     

心理行为干预在大肠癌辅助化疗患者中的应用

结直肠癌是常见的消化道恶性肿瘤,死亡率非常高,主要治疗手段为手术切除。但大部分患者术后易发生复发和转移,因此,术后辅助化疗作为减少复发和转移、延长患者生存时间的主要综合治疗手段之一日益受到重视。选择适当的患者,应用足够剂量药物进行化疗和保持患者良好的耐受性,是成功辅助化疗的关键所在。     

膀胱癌新辅助化疗研究进展

根治性膀胱切除加盆腔区域淋巴结清扫是治疗浸润性膀胱癌的标准术式,但对于非器官局限性膀胱癌,局部复发与远处转移的风险较高。对这部分患者进行以顺铂为基础的新辅助化疗,可以降低复发率,改善手术疗效,提高生存率。对新辅助化疗敏感的患者,可以考虑保留膀胱的保守治疗。     

靶向Survivin的RNA干扰与膀胱癌

膀胱癌是最常见的泌尿系统恶性肿瘤,在我国泌尿外科肿瘤中发病率和死亡率均占首位[1],近年来发病率有增加趋势.膀胱癌绝大多数(90%以上)来自移行上皮,多数以非浸润方式生长,复发非常普遍(50%～70%),在保留膀胱手术后多以膀胱内灌注化疗药物来控制,但仍有10%～15%的表浅性膀胱癌最终发展成浸润性膀胱癌或者发生转移[2],而晚期膀胱癌患者又缺乏有效的治疗方法.因此,寻找一种对浸润及术后复发有靶向基因治疗的方法一直是基础和临床研究的重要课题.     

胃癌术后早期腹腔内化疗的研究进展

胃癌是我国最常见的恶性肿瘤之一 ,起病隐匿 ,发展迅速 ,就诊时多为中晚期。 49.2 %晚期胃癌病人术后多在 2年内发生复发 ,其中以腹膜复发和转移最多见[1 ] ,并直接导致病人死亡。如何在胃癌术后早期采取合理的治疗手段 ,预防此类复发和转移 ,日益受到人们重视。近来研究发现 ,通过改变术后化疗的给药途径和投药时间 ,可明显提高胃癌疗效[2 ] 。术后早期腹腔内化疗与传统的静脉给药化疗相比 ,能直接作用于根治术后复发和转移高危部位的腹膜 ,且能加大化疗药物的剂量 ,对预防和减少胃癌术后的腹膜复发和转移、提高病人生存率有积极的作用。本…     

膀胱癌的新辅助化疗进展

目前根治性膀胱切除术加淋巴结清扫仍是浸润性膀胱癌的标准治疗方法 ,但不论对局部晚期/转移性膀胱癌或是器官局限性膀胱癌,单纯手术治疗的效果均不理想.大量临床试验证明对膀胱癌病人术前使用以铂类为基础的化疗,能明显延长患者的生存期.化疗后达到病理学完全缓解(pTO)可能是将来一个新的治疗终点指标.分子生物学的发展也将帮助筛选出对化疗敏感的病人和开发出更多的靶向药物.     

膀胱癌的新辅助化疗进展

目前根治性膀胱切除术加淋巴结清扫仍是浸润性膀胱癌的标准治疗方法，但不论对局部晚期／转移性膀胱癌或是器官局限性膀胱癌，单纯手术治疗的效果均不理想。大量临床试验证明对膀胱癌病人术前使用以铂类为基础的化疗，能明显延长患者的生存期。化疗后达到病理学完全缓解（pTO）可能是将来一个新的治疗终点指标。分子生物学的发展也将帮助筛选出对化疗敏感的病人和开发出更多的靶向药物。     

免疫检查点抑制剂在食管癌新辅助治疗中的研究进展

新辅助放化疗/化疗联合手术已成为局部进展期食管癌的标准治疗方案,尽管使患者生存获益,但仍有多数患者术后出现复发及远处转移。免疫检查点抑制剂通过激活T细胞发挥抗肿瘤作用,随着免疫治疗模式的不断演进,免疫治疗已成为晚期食管癌一线、二线治疗的重要策略之一。大量关于食管癌新辅助免疫治疗的研究正在进行中,有望为食管癌新辅助治疗注入新的活力。本文就目前关于食管癌新辅助免疫治疗的临床研究进展进行综述。     

经尿道膀胱肿瘤切除术后补救性动脉介入化疗治疗肌层浸润性膀胱癌的疗效分析

目的：探讨补救性髂内动脉化疗存经尿道膀胱肿瘤切除术（transurethralresectionofbladdertumor,TURBT）后证实为肌层浸润性膀胱癌患者中的治疗价值。方法：对34例TURBT患者术后基底部活检及病理结果证实为肌层浸润性的膀胱肿瘤患者行补救性髂内动脉化疗3次。方案为顺铂80mg、表柔吡星50mg、5-氟尿嘧啶1g（或羟基喜树碱30mg）。观察患者肿瘤复发率,Kaplan—Meier法计算总体生存率,肿瘤特异性生存率,无肿瘤复发生存率,并绘制生存曲线。结果：术后经3次补救性髂内动脉化疗及常规膀胱灌注后,29例患者得到保留膀胱（保留膀胱率85．3％）,肿瘤复发13例（肿瘤复发率38．2％）。其中,浅表性复发7例,行TURBT治疗;浸润性复发5例,行全膀胱切除术;骨转移l例,行全身化疗。总体生存率：3年69．78％,5年62．03％。肿瘤特异性生存率：3年77．43％,5年68．83％。无肿瘤复发生存率：1年93．10％,2年70．23％．3年46．82％。结论：补救性动脉介入化疗是TuRBT术后基底部活检及病理结果证实为肌层浸润性的膀胱肿瘤的良好选择。     

保留膀胱综合方法治疗肌层浸润性膀胱癌的疗效评价

目的探索保留膀胱手术＋膀胱内灌注化疗＋动脉灌注化疗治疗浸润性膀胱癌的临床疗效。方法 2003年5月至2012年2月,对经尿道膀胱肿瘤电切或膀胱部分切除后确诊为肌层浸润性膀胱癌（T2N0M0）的56例保留膀胱的患者,给予动脉灌注化疗加膀胱灌注化疗。结果 56例患者均获得随访,随访6～98个月,平均（36.0±3.2）个月,53例（94.6%）患者无复发及转移,3例（5.4%）分别在术后6、8、12复发,复发患者均给于全膀胱切除术,无死亡病例,没有明显并发症。结论保留膀胱手术后确诊的肌层浸润性膀胱癌患者,采用经髂内动脉灌注化疗＋膀胱内灌注化疗的联合治疗方法,能有效减少肿瘤复发,显著降低静脉化疗的副作用,提高患者的生活质量,患者易于接受,值得进一步探讨。     

Prognostic significance of adjuvant cisplatin-based combination chemotherapy following radical cystectomy in patients with invasive bladder cancer

Objectives: The objectives of this study were to retrospectively examine the outcomes of adjuvant cisplatin‐based combination chemotherapy following radical cystectomy in patients with invasive bladder cancer in order to identify parameters predicting the prognosis of these patients. Methods: This study included a total of 51 patients with muscle invasive bladder cancer who underwent radical cystectomy between January 1995 and December 2004, and subsequently received at least two cycles of either MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) or MVP‐CAB (methotrexate, doxorubicin, vincristine, cyclophosphamide, bleomycin and cisplatin) chemotherapy in an adjuvant setting because of the presence of diseases corresponding to pT3/4 and/or pN1/2 without clinical evidence of metastasis. The significance of several clinicopathological factors as predictors of disease recurrence and cancer‐specific death was evaluated using univariate and multivariate analyses. Results: During the observation period of this study (median, 26.5 months), disease‐recurrence and cancer‐specific death were observed in 21 and 16 patients, respectively. The 5‐year recurrence‐free and cancer‐specific survival rates were 48.6% and 54.1%, respectively. Among several factors examined in this series, lymph node metastasis and concomitant carcinoma in situ (CIS) were identified as significant predictors of both disease‐recurrence and cancer‐specific death, and these were also independently associated with disease‐recurrence and cancer‐specific death. Conclusions: Adjuvant cisplatin‐based combination chemotherapy for patients with extravesically extended bladder cancer following radical cystectomy resulted in comparatively unsatisfactory outcome concerning cancer‐control; accordingly, it would be necessary to develop a more efficacious therapeutic strategy for such patients, particularly for those with lymph node metastasis and/or concomitant CIS.     

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.     

Combination chemotherapy of ifosfamide, 5‐fluorouracil,etoposide and cisplatin as perioperative treatment in lymph node positive bladder carcinoma patients treated by radical cystectomy

Objectives: To evaluate the efficacy and toxicity of perioperative combination chemotherapy with ifosfamide, 5‐fluorouracil, etoposide and cisplatin (IFEP) in bladder cancer patients with regional lymph node metastases treated by radical cystectomy. Methods: We reviewed the medical records of 183 consecutive patients who underwent radical cystectomy for invasive urothelial carcinoma of the bladder. Of those, 26 patients with regional lymph node metastasis who were regarded as being rendered surgically disease‐free (pT1‐4, N1‐2, cM0) and treated with perioperative IFEP chemotherapy were the subjects of the present study. Results: Median follow‐up of 26 patients was 49 months (range 4–150). Grade 3 and 4 bone marrow toxicities were seen in 15 and four patients, respectively. Neither chemotherapy‐related death nor febrile neutropenia occurred. The 5‐year overall and cancer‐specific survival rate was 60% and 68%, respectively. The overall survival rate of the patients with pT4 disease was significantly worse than that of patients with pT1‐3. There were four N2 patients who survived for over 5 years free of disease. Conclusions: Perioperative IFEP therapy appeared to be effective in the treatment of lymph node positive bladder cancer patients who underwent radical cystectomy. Further study may be warranted.     

Clinical analysis of high grade bladder cancer

The prognosis and other clinical manifestation of 128 patients with high grade bladder tumor were analyzed. Thirty two percent of the total cases of bladder cancer were high grade bladder cancer and 83% of their tumors were invasive tumor at stage T2 and worse. Urinary cytologies were positive in 88% of these patients. The 5-year survival rate in these patients was 32% and those in T1, T2 T3 and T4 cases were 64.2%, 55.6%, 22.7% and 8.0% respectively. The patients treated with radical (total) cystectomy showed a much better survival rate than the cases treated with TUR or partial cystectomy. These results suggest that high grade bladder cancers tend to be invasive and the patients with high grade bladder cancer would have a poorer prognosis than the patients with other histological grade tumors. Thus, these patients should be treated more aggressively including radical cystectomy than the other cases of bladder cancers.     

Chemotherapy and cystectomy for invasive transitional cell carcinoma of bladder

Invasive transitional cell bladder cancer is associated with occult metastasis. Approximately 50% of patients with clinically localized, invasive bladder cancer ultimately die of their disease. Systemic chemotherapy has been combined with radical cystectomy in an attempt to improve survival. Phase I and II trials have achieved tumor down-staging. Initial randomized trials did not show a statistically significant survival benefit from systemic single agent chemotherapy. More recently, two multi-center randomized trials have shown a significant survival benefit from neoadjuvant combination chemotherapy. Adjuvant chemotherapy trials, to date, have failed to show statistically improved survival, although most published studies have been methodologically flawed. For invasive, clinically nonmetastatic bladder cancer, neo-adjuvant chemotherapy followed by radical cystectomy is one of the new standards of care. The role of postsurgical systemic chemotherapy appears promising, but has not been proven in a randomized trial. Molecular prognostication is now being incorporated into the design of clinical trials of adjuvant chemotherapy for bladder cancer.     

Four years experience in bladder preserving management for muscle invasive bladder cancer

OBJECTIVES: To evaluate the bladder preservation strategy in invasive bladder cancer particularly relapse, progression and complications. MATERIALS AND METHODS: From January 2000 to May 2004 a total of 24 patients (mean age of 81 years; range 68-92) with muscle invasive bladder cancer who had refused or were not eligible for cystectomy were followed up for a period of up to four years. RESULTS: 24 (21 M/3 F) patients were followed up for a mean time of 680 (182-1253) days. All patients complained of frequency, urgency and severe nocturia. The second most frequent complication was bleeding which required a salvage cystectomy in 7 cases. Other major complications were intestinal occlusion in three cases, an enterovesical fistula, brain metastasis requiring neurosurgical intervention and radiation therapy of the brain, bone metastasis in the cervical spinal column and chronic renal failure. The mean re-admission rate was 8 per patient and the mean time spent at the hospital was 109 (range 13-253) days. CONCLUSION: In our series the bladder preserving strategy does not confirm the optimistic results of other authors. The complications forced us to carry out a salvage cystectomy in nearly half of the cases. The other half of the patients complained of other severe complications reducing the quality of life of the remaining life span.     

Laparoscopic cystectomy with extracorporeal-assisted urinary diversion: experience with 34 patients

OBJECTIVES: Open radical cystectomy remains the gold standard for nonmetastatic muscle invasive bladder cancer. Laparoscopic cystectomy has been described as a feasible procedure and is still being evaluated. We describe our initial experience with this laparoscopic surgical approach in 34 patients. METHODS: From February 2002 to October 2004, 18 men and 16 women underwent laparoscopic cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=27), invasive cervical carcinoma (n=4), and atrophic bladder (n=3). We report here on specific technical details and present initial results of our series. RESULTS: The mean operating time was 244 min, the mean blood loss 325 ml, and the transfusion rate 5.9%. All procedures were completed laparascopically without conversion to open techniques. No major complications occurred during or after the operation. In case of urothelial malignancy (n=27), the histopathologic analysis of the removed specimen revealed organ-confined transitional cell carcinoma of the bladder in 66.7% (pT1:14.8%; pT2: 51.9%) and locally advanced disease in 33.3% (pT3: 25.9%; pT4: 7.4%). In two cases final histology proved positive surgical margins. Extended lymphadenectomy detected lymph node metastasis in two patients. CONCLUSIONS: We demonstrate that the combination of laparoscopic cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. To determine the oncologic outcome long-time follow-up will be necessary.     

Outcome of Patients Who Refuse Cystectomy after Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

Objectives

To determine the outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Methods

Between 1995 and 2001, 63 patients were evaluated who declined to undergo a planned cystectomy, because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy. Patient, tumor, and treatment features were assessed prospectively, and correlated in univariate and multivariate analyses with overall survival. The median follow-up was 86 mo and all patients were followed for more than 5 yr.

Results

Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with overall survival. The most significant treatment variable predicting better survival was complete resection of the invasive tumor on re-staging transurethral resection before starting chemotherapy. Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of surviving patients had solitary, small, and low-stage invasive tumors completely resected, and 83% survived without relapses in the bladder.

Conclusions

Selected patients with muscle-invasive bladder cancers may survive after transurethral resection and neoadjuvant chemotherapy, and tumor features can identify which patients responding completely to chemotherapy may survive without cystectomy.