膀胱灌注力尔凡预防浅表性膀胱癌术后复发的疗效观察

膀胱癌是泌尿系统最常见的恶性肿瘤,预防膀胱癌复发、推迟疾病进展一直是膀胱癌治疗上的重要难题。浅表性膀胱癌约占膀胱癌的70％-80％,目前浅表性膀胱癌的治疗方法包括手术、化疗及膀胱灌注、免疫治疗等。经尿道膀胱肿瘤电切术（TURBt）仍是浅表性膀胱癌的主要方法,但术后复发率高一直是治疗的难题。术后膀胱灌注辅助治疗可以有效预防膀胱癌复发、推迟疾病的进展,对恶性膀胱癌的治疗有重要的意义。为了寻找最佳控制膀胱恶性肿瘤复发的方法,延长生存率、提高生活质量,我们采用力尔凡和吡柔吡星（BCG）进行膀胱灌注治疗,比较二者的临床疗效,旨在寻找一种理想的治疗方案。     

膀胱癌术后于膀胱内灌注吡柔比星预防肿瘤复发的临床观察

膀胱癌是泌尿系统最常见且容易复发的恶性肿瘤,临床上70％～80％为浅表性膀胱癌。大多数膀胱癌可经手术切除或经尿道电切术而治愈,50％～70％的浅表性膀胱癌术后容易出现复发。膀胱内灌注是目前预防膀胱癌术后复发的最常用的治疗手段之一。鉴于目前供选择的药物较多,其     

树突状细胞疫苗在膀胱癌治疗中的应用

膀胱癌是我国最常见的泌尿系统恶性肿瘤,其主要特点是术后复发率高,且有恶性程度增高的趋势,免疫逃逸是导致肿瘤复发和进展的重要机制[1]。肿瘤免疫治疗是通过调动机体的天然免疫防卫机制或利用具有肿瘤抗原性的疫苗刺激机体产生特异性的抗肿瘤效应。     

膀胱癌的术后治疗

膀胱癌是我国泌尿系统最常见的恶性肿瘤之一,其治疗方法很多,目前仍以手术治疗为主,原则上表浅膀胱癌行保留膀胱的手术,浸润癌行全膀胱切除术.因膀胱癌有多灶性、种植性等特点,故术后复发率高达50%～70%.预防膀胱癌术后复发的方法有很多,在这里我想浅谈一下最常用的膀胱灌注治疗及术后随访.     

吡喃阿霉素双途径给药法治疗膀胱移行细胞癌

膀胱癌是泌尿系统最常见的恶性肿瘤,90％为移行细胞癌。膀胱癌虽然80％～90％首次诊断时为非浸润癌,但保留膀胱手术治疗后,50％～80％存在复发的可能,而且30％～50％将演变为浸润性癌。因此,减少术后复发,以及复发     

经尿道膀胱肿瘤电切术后辅助膀胱热灌注化疗的应用进展

膀胱癌是泌尿系统最常见的恶性肿瘤,占我国泌尿生殖系肿瘤发病率的第1位,膀胱癌的生物学特点是术后易复发。近年来,在给膀胱癌患者行经尿道膀胱肿瘤电切术后再辅以膀胱热灌注化疗,能有效降低术后复发率,临床疗效显著。本文就经尿道膀胱肿瘤电切术后辅助膀胱热灌注化疗治疗膀胱癌的临床应用进展作一简要综述。     

膀胱癌的早期发现与治疗

膀胱癌是泌尿系统中最常见的恶性肿瘤，在我国十大恶性肿瘤排行榜列第八位，50岁以上的患者多见。膀胱癌被称为环境肿瘤，与外界环境关系密切。发病危险因素包括：环境、职业、尿路感染和慢性炎症、膀胱结石、膀胱异物、盆腔放射治疗等。     

护理干预在膀胱癌术后丝裂霉素膀胱内灌注治疗中的临床应用

<正>膀胱肿瘤是泌尿系统中常见的一种恶性肿瘤,70%以上为浅表性膀胱癌,其生物学特性为多发、易发和再发[1],治疗主要以手术为主。为了预防术后膀胱癌复发,术后需定期膀胱内灌注化疗药物进行治疗。我们对176例手术根治膀胱癌患者采用丝裂霉素膀胱内灌注治疗,并予以有效的护理干     

外泌体应用于膀胱癌诊疗的基础与临床研究进展

摘 要：膀胱癌是泌尿系统最常见的恶性肿瘤,其术后复发和进展一直是临床关注的焦点问题。外泌体是由细胞内多囊泡体与细胞膜融合后释放到细胞外基质中的膜性囊泡。通过携带DNA、RNA、miRNA、非编码RNA和蛋白质等,实现细胞间生物信息的交换和传递。近来的研究表明外泌体参与了膀胱癌的侵袭、转移及进展过程,文章就外泌体应用于膀胱癌诊断和治疗的基础和临床研究进展进行综述。     

尿液中T细胞亚群与膀胱癌复发关系的探讨

膀胱癌是泌尿系统最常见的恶性肿瘤，术后肿瘤复发率高，可达５０％～７０％。复发原因很复杂，其中膀胱局部免疫功能的改变可能是其原因之一。本研究通过膀胱肿瘤术后尿液中CD３＋CD４＋T细胞与CD３＋CD８＋T细胞的比值变化，观察其在肿瘤复发的意义，以寻求膀胱癌术后无创性的、有意义的随访指标。１材料与方法１．１一般资料选择１９９９年６月～２００１年５月在我科住院的膀胱肿瘤术后复发的患者４６例。男性３２例，女性１４例；年龄５８～７８岁，平均７０．７５岁。复发时间０．５～９年，平均１．４７年。复发次数１～５次，…     

High frequency of MAGE‐A4 and MAGE‐A9 expression in high‐risk bladder cancer

Cancer‐testis (CT) genes encode proteins that are ideal targets for cancer immunotherapy because of their restricted expression in normal tissues and frequent expression in cancers. We previously observed that MAGE‐A9 was one of the CT genes most frequently expressed in bladder tumors. To confirm that observation and evaluate the potential prognostic value of MAGE‐A9 protein, we analyzed its expression by immunohistochemistry in 493 primary bladder tumors and 33 lymph node metastases, in comparison with MAGE‐A4 protein, also frequently expressed in bladder tumors. Overall, MAGE‐A4 and MAGE‐A9 were observed, respectively, in 38% and 63% of nonmuscle‐invasive tumors, 48% and 57% of muscle‐invasive tumors, 65% and 84% of carcinomas in situ and in 73% and 85% of lymph node metastases. Expression was associated with higher grade (MAGE‐A4, p = 0.007; MAGE‐A9, p = 0.012). In multivariate Cox regression analyses, expression of MAGE‐A9 in pTa tumors was associated with recurrence (HR = 1.829; p = 0.010). In univariate analyses, MAGE‐A4 expression in these same tumors was associated with progression to muscle‐invasive cancer (HR = 7.417, p = 0.013). MAGE‐A9 expression was even more predictive of progression as all tumors that progressed expressed this antigen. In muscle‐invasive bladder tumors, no association was found between expression of either MAGE and bladder cancer‐specific death. In conclusion, MAGE‐A9 is a target of choice for bladder cancer immunotherapy as it is expressed in 60% of bladder tumors, predominantly high‐grade tumors, and at higher frequency in pTis and metastatic tumors. Moreover, in pTa tumors, an immunotherapy targeting MAGE‐A9 could be protective against recurrence and progression to more advanced cancer. © 2009 UICC     

Superficial bladder cancer: part 1. Update on etiology,classification and natural history

Superficial ‘nonmuscle-invasive’ bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.     

Superficial bladder cancer: part 1. Update on etiology, classification and natural history

Superficial 'nonmuscle-invasive' bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.     

Tumor size and T stage correlate independently with recurrence and progression in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant BCG

We conducted a retrospective study to determine the prognostic significance of age, gender, associated carcinoma in situ, stage, number of tumors, and tumor size for patients with high-risk non-muscle-invasive bladder tumors treated with bacillus Calmette-Guérin (BCG). Data were evaluated on 144 high-risk patients with non-muscle-invasive bladder cancer treated with BCG immunotherapy after the initial treatment with transurethral resection. According to their response to BCG, patients were divided into groups, and the differences in factors, associated with recurrence and progression, were evaluated. Patients were categorized into two groups: group A, complete responders without recurrence and without progression, and group B, patients with recurrence and with progression. Furthermore, group B was divided into two subgroups: group B1, patients with recurrence, and group B2, patients with progression. Univariate analysis of group B showed that only tumor size of >3 cm diameter (hazard ratio (HR) 11.99; 95 % confidence interval (CI) range 5.69–25.3; p?<?0.001) is associated with recurrence. After multivariate analysis, the same factor appeared to be prognostic for recurrence as well. In addition, group B2 was statistically correlated with group B1. Univariate analysis proved that tumor stage (Ta or T1) is the unique factor associated with progression (HR 6.4; 95 % CI 1.29–31.9; p?=?0.02). Tumor stage seems to be associated with disease's progression after the multivariate analysis too. Tumor size and stage may serve as prognostic factors, because of its independent correlation with recurrence and progression for patients with high-risk non-muscle-invasive bladder tumors treated with BCG.     

PMN and anti-tumor immunity—The case of bladder cancer immunotherapy

Urothelial carcinoma of the bladder accounts for ∼5% of all cancer deaths in humans. The majority of bladder tumors are non-muscle invasive at diagnosis, and there is a high rate of tumor recurrence and progression even after local surgical therapy. Thus, many patients require lifelong follow-up examinations that include additional prophylactic treatments in the event of recurrence. Since its first use in 1976, Mycobacterium bovis bacillus Calmette–Guerin (BCG) has been the treatment of choice for non-muscle invasive bladder cancer. Despite nearly 40 years of clinical use, the mechanism(s) by which intravesical administration of BCG results in elimination of bladder tumors remains undefined. Granulocytes (polymorphonuclear neutrophils (PMN)) are the predominant immune cell (in number) that enters the bladder after BCG installation, and a number of studies have highlighted the importance of PMN in the antitumor activity of BCG. Studies from our laboratory demonstrated presence of intracellular stores of the apoptosis-inducing protein TNF-related apoptosis-inducing ligand (TRAIL) in PMN that are rapidly released after interaction with BCG cell wall components, along with a correlation between increased urinary levels of TRAIL and BCG responsiveness. Mature PMN in circulation are terminally differentiated cells with limited biosynthetic capacity, so the proteins located in the distinct PMN granule populations are compartmentalized concomitant with their synthesis during myelopoiesis. Thus, understanding PMN production, localization, and release of TRAIL is important in the design of future BCG-based bladder tumor immunotherapy protocols.     

Diagnosis and management of superficial bladder cancer

Bladder cancer is the fourth leading cause of cancer in American men, accounting for more than 12,000 deaths annually. It was one of the first malignancies in which carcinogens were recognized as an important factor in its cause. Currently, cigarette smoking is by far the most common cause of bladder cancer, although occupational exposure to arylamines has been implicated in the past. Gross or microscopic hematuria is the most common sign at presentation. Initial radiologic evaluation usually includes the excretory urography (intravenous pyelography), although further evaluation of the renal parenchyma with ultrasound or computed tomography scanning has been advocated by some. These radiologic studies are unable to provide adequate bladder imaging, and thus cystoscopy is required for the diagnosis of bladder cancer. Most bladder cancers present as "superficial" disease, confined to the bladder mucosa or submucosal layer, without muscle invasion. Superficial tumors consist of papillary tumors that are mucosally confined (Ta), papillary or sessile tumors extending into the lamina propria (T1), and carcinoma in situ, which occurs as "flat" mucosal dysplasia, which can be focal, diffuse, or associated with a papillary or sessile tumor. The natural history of these pathologic subtypes differ significantly. Most superficial tumors (60% to 70%) have a propensity for recurrence after transurethral resection. Some (15% to 25%) are at high risk for progression to muscle invasion. Most superficial tumors can be stratified into high- or low-risk groups depending on tumor stage, grade, size, number, and recurrence pattern. It is important to identify those tumors at risk for recurrence or progression so that adjuvant intravesical therapies can be instituted. Many intravesical chemotherapeutic agents have been shown to reduce tumor recurrence when used in conjunction with transurethral tumor resection. Unfortunately, however, none of these agents have proved to be of benefit in preventing disease progression. Most are given intravesically on a weekly basis, although many studies suggest that a single instillation immediately after transurethral resection may be as good as a longer course of therapy. Although all of these drugs have toxicity, they usually are well tolerated. Intravesical bacille Calmette-Guérin (BCG) is an immunotherapeutic agent that when given intravesically is very effective in the treatment of superficial transitional cell carcinoma. Compared with controls, BCG has a 43% advantage in preventing tumor recurrence, a significantly better rate than the 16% to 21% advantage of intravesical chemotherapy. In addition, BCG is particularly effective in the treatment of carcinoma in situ, eradicating it in more than 80% of cases. In contrast to intravesical chemotherapy, BCG has also been shown to decrease the risk of tumor progression. The optimal course of BCG appears to be a 6-week course of weekly instillations, followed by a 3-week course at 3 months in those tumors that do not respond. In high-risk cancers, maintenance BCG administered for 3 weeks every 6 months may be optimal in limiting recurrence and preventing progression. Unfortunately, adverse effects associated with this prolonged therapy may limit its widespread applicability. In those patients at high risk in whom BCG therapy fails, intravesical interferon-alpha with or without BCG may be beneficial in some. Photodynamic therapy has also been used but is limited by its toxicity. In patients who progress or do not respond to intravesical therapies, cystectomy should be considered. With the development of orthotopic lower urinary tract reconstruction to the native urethra, the quality of life impact of radical cystectomy has been lessened.     

Prognostic significance of tumor location in high-grade non-muscle-invasive bladder cancer

The management of high-grade (HG) non-muscle-invasive bladder cancer (NMIBC) continues to be a serious clinical problem. The role of many factors related to efficacy of Bacillus Calmette-Guérin (BCG), which is the most useful intravesical agent for these tumors, is still unknown. This study investigated the prognostic value of tumor location in high-grade non-muscle-invasive bladder cancer. Seventy-four patients with HG non-muscle-invasive bladder cancer, without carcinoma in situ (CIS), were treated by transurethral resection of bladder tumor (TURBT). Twenty-eight patients received adjuvant BCG therapy after TURBT. The relation between tumor location and the recurrence capacity was estimated using a Cox regression model. Our results suggest that tumor location is an important prognostic factor for BCG-therapy response in patients with high-grade non-muscle-invasive bladder cancer. Tumors in the bladder neck might have a higher risk of recurrence after intravesical immunotherapy. In addition, tumors in the lateral and posterior bladder walls might be at higher risk of recurrence when treated by TURBT alone.     

Recent improvements in the detection and treatment of nonmuscle-invasive bladder cancer

In total, 70–80% of newly diagnosed bladder cancers are confined to the mucosa and staged as Ta, T1 or carcinoma in situ according to the 2002 tumor, lymph nodes and metastasis classification. The standard treatment for these nonmuscle-invasive bladder cancers is transurethral tumor resection with or without adjuvant intravesical chemotherapy or intravesical immunotherapy and subsequent follow-up. Diagnosis and follow-up of nonmuscle-invasive bladder cancer offers two main problems. First, approximately 10–20% of all tumors are not seen in standard cystoscopy. Additionally, frequently repeated follow-up cystoscopies are bothersome for the patient. As an adjunct to standard cystoscopy, fluorescence-guided cystoscopy has demonstrated significantly higher tumor detection rates and optimized patient treatment in recent Phase III studies. Second, routinely performed urine cytology is characterized by high specificity but low sensitivity. Today, several urine tests are available that may increase diagnostic accuracy and potentially prolong intervals of follow-up cystocopy. Owing to rather high recurrence rates after transurethral tumor resection in most tumors and high progression rates in poorly differentiated tumors, adjuvant intravesical chemotherapy or intravesical immunotherapy has gained widespread use in patients with nonmuscle-invasive bladder cancer. Only a few further immunomodulatory drugs, such as recombinant cytokines, have shown significant clinical effectiveness. Additional approaches, such as photodynamic therapy with different photosensitizers and thermotherapy in combination with intravesical chemotherapy, have been evaluated in Phase III studies.     

Recent improvements in the detection and treatment of nonmuscle-invasive bladder cancer

In total, 70-80% of newly diagnosed bladder cancers are confined to the mucosa and staged as Ta, T1 or carcinoma in situ according to the 2002 tumor, lymph nodes and metastasis classification. The standard treatment for these nonmuscle-invasive bladder cancers is transurethral tumor resection with or without adjuvant intravesical chemotherapy or intravesical immunotherapy and subsequent follow-up. Diagnosis and follow-up of nonmuscle-invasive bladder cancer offers two main problems. First, approximately 10-20% of all tumors are not seen in standard cystoscopy. Additionally, frequently repeated follow-up cystoscopies are bothersome for the patient. As an adjunct to standard cystoscopy, fluorescence-guided cystoscopy has demonstrated significantly higher tumor detection rates and optimized patient treatment in recent Phase III studies. Second, routinely performed urine cytology is characterized by high specificity but low sensitivity. Today, several urine tests are available that may increase diagnostic accuracy and potentially prolong intervals of follow-up cystocopy. Owing to rather high recurrence rates after transurethral tumor resection in most tumors and high progression rates in poorly differentiated tumors, adjuvant intravesical chemotherapy or intravesical immunotherapy has gained widespread use in patients with nonmuscle-invasive bladder cancer. Only a few further immunomodulatory drugs, such as recombinant cytokines, have shown significant clinical effectiveness. Additional approaches, such as photodynamic therapy with different photosensitizers and thermotherapy in combination with intravesical chemotherapy, have been evaluated in Phase III studies.     

胃肠肿瘤免疫治疗进展

胃肠肿瘤是消化系统常见的恶性肿瘤,其发病率和致死率均位于恶性肿瘤的前列。肿瘤免疫治疗是当前最热的肿瘤研究领域,在胃肠肿瘤的基础研究和临床应用中取得了一定的成效,但仍存在一系列难题亟待解决。本文综述了胃肠肿瘤领域中几种常见的肿瘤免疫治疗方法的研究进展。