Durable control of small cell carcinoma of the urinary bladder by gemcitabine and paclitaxel

Abstract We report a case of small cell carcinoma of the bladder for which new chemotherapeutic agents, gemcitabine and paclitaxel were effective without remarkable toxicity.     

膀胱小细胞癌的病理组织学特点及其诊治

目的:探讨膀胱小细胞癌病理组织学特点及其诊断与治疗。方法:回顾分析6例膀胱小细胞癌患者的临床和病理资料,6例患者行经尿道膀胱肿瘤电切术2例,膀胱部分切除术1例,行膀胱全切术2例,单纯化疗1例。5例患者接受2～6疗程化疗。结果:6例随访3个月～3年,1例患者术后生存2年至今,5例均因肿瘤转移死亡,平均生存时间14.8个月。结论:膀胱小细胞癌分化程度低、恶性程度高、易早期转移、预后差,主要依靠病理组织学检查确诊,现有治疗方法不足以将其治愈,手术联合化疗是目前主要的治疗方法,分子靶向治疗是未来治疗的主要手段。     

Primary large cell neuroendocrine carcinoma of the urinary bladder

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is rare. It is a type of neuroendocrine carcinoma morphologically distinct from small cell carcinoma. We report here a case of primary LCNEC of the urinary bladder. We observed a very large invasive tumor, which was not able to be detected three months previously by cystoscopy or computed tomography. The tumor cells morphologically and immunohistochemically resembled that of pulmonary LCNEC. With prompt cystoprostatectomy and chemotherapy, the patient is free of disease 16 months after diagnosis. Although LCNEC is usually very aggressive, it may be controlled by early diagnosis and treatment.     

原发性膀胱小细胞癌(附4例报告)

目的 提高对膀胱小细胞癌的认识水平。方法 对4例膀胱小细胞癌的病理及临床资料进行回顾性分析。结果 4例患者中男3例，女1例，平均年龄69．5。其中3例行根治性膀胱全切加化疗，1例行姑息性膀胱全切。3例死于肿瘤复发，平均生存20个月，1例存活7年。结论原发性膀胱细胞癌恶性程度高、预后差，根治性膀胱全切加联合化疗可获得较好的疗效。     

原发性膀胱小细胞癌诊治体会

目的 探讨膀胱小细胞癌的临床及病理特点.方法 回顾性分析9例膀胱小细胞癌的基本资料.男6例,女3例.年龄45～79岁,平均62岁.临床表现为肉眼血尿7例,排尿困难及下腹部疼痛2例.肿瘤直径0.5～7.0 cm,平均2.0 cm;多发2例,单发5例,全膀胱弥漫性生长2例.7例行尿脱落细胞学检查,阳性4例.9例均行手术治疗,其中4例术前诊断为浅表性者行TURBt,术后均定期行吡柔比星膀胱灌注,1例化疗3个周期;膀胱部分切除2例,均定期行吡柔比星膀胱灌注,1例化疗2个周期;根治性膀胱全切3例,静脉化疗2例.结果 术后病理检查:肿瘤细胞体积小,呈圆形,胞质稀少,核浓染,缺乏巢状结构.免疫组化染色:嗜铬素A(+)、神经元特异性烯醇化酶(+).诊断为小细胞癌,其中1例含移行细胞癌成分,1例合并前列腺癌.1例术前检查显示高血钙(3.15 mmol/L)和低血磷(0.61 mmol/L),术后1个月血钙及血磷恢复正常.保留膀胱者随访4例,3例分别于术后4、9、25个月死于转移,1例术后化疗者随访24个月未见复发及转移.膀胱全切3例中2例分别于术后2、28个月死亡,1例术后随访32个月未见肿瘤复发及转移.结论膀胱小细胞癌恶性程度高,预后差,根治性膀胱全切加全身化疗是主要的治疗方法,保留膀胱的手术应配合全身化疗.决定预后的是肿瘤的临床分期及治疗方法.

Abstract：

Objective To investigate the clinical and pathological features of small cell carcinoma of the urinary bladder. Methods The pathological and clinical data of 9 cases of small cell carcinoma were analyzed retrospectively. There were 6 males and 3 females, ages 45 to 79 years (mean age, 62 years). Clinical manifestations of 7 cases included gross hematuria and dysuria, the other 2 cases experienced lower abdominal pain. The mean tumor size was 2.0 cm (ranged, 0.5 to 7.0 cm). Two cases had multiple tumors and 5 cases had single tumors. The growth pattern in 2 cases was diffuse growth in the whole bladder. In 4 cases tumor cells were found in urine cytology. All 9 patients underwent surgical treatment, including TURBt. Four patients were diagnosed as superficial tumors before operation. All the patients underwent regular theprubicine irrigation in the bladder. One case underwent additional intravenous chemotherapy for 3 cycles. Partial cystectomy was performed in 2 cases, with regular theprubicine irrigation in bladder and 1 case underwent intravenous chemotherapy for 2 cycles. Radical cystectomy was performed in 3 cases, with 2 cases undergoing intravenous chemotherapy after operation. Results Pathological findings showed that tumor cells were small and round in shape. These hyperchromatic nuclei showed limited cytoplasm with lack of nesting characters. CgA and NSE were positive in immunohistochemistry. The final diagnosis was small cell carcinoma, with 1 case accompanied with transitional cell carcinoma and 1 case accompanied with prostate cancer. One case showed high preoperative serum calcium (3.15 mmol/L) and low serum phosphate (0.61 mmol/L), which returned to normal 1 month after operation. Four cases who′s bladder was preserved were followed up, 3 cases were alive for 4, 9 and 25 months after operation. The 1 case who underwent intravenous chemotherapy was followed up for 24 months and there was no sign of relapse or metastasis. In all the 3 cases with radical cystectomy, 2 cases died 2 and 28 months postoperativly. Another case with adjuvant chemotherapy was followed up for 24 months without recurrence or metastasis. Conclusions Small cell carcinoma of the urinary bladder is highly malignant with poor prognosis. Radical cystectomy in combination with systemic chemotherapy has better efficacy. Retained bladder surgery with systemic chemotherapy is an alternative choice. The most important factors which influence the prognosis of the tumor are clinical stage and therapeutic methods.     

Protocol consisting of cisplatin, etoposide and irinotecan induced complete pathological remission of primary small cell carcinoma of the bladder

A 73-year-old man with primary small-cell carcinoma of the bladder was treated by radical cystectomy with neoadjuvant chemotherapy. Pathological complete remission was achieved by combination chemotherapy composed of cisplatin, etoposide and irinotecan. The patient is free of disease 19 months after surgery.     

膀胱大细胞未分化癌一例报告

回顾分析1例膀胱大细胞未分化癌患者的临床病理资料,加强对该病的认识。膀胱大细胞未分化癌的临床及影像学表现缺乏特异性,确诊须依靠病理及免疫组化染色检查,肿瘤侵袭性强、进展快,治疗上以根治性膀胱切除术为主。     

膀胱小细胞癌3例

目的 探讨膀胱小细胞癌的临床病理特征和诊治方法。方法 总结3例膀胱小细胞癌患者资料,结合文献复习讨论。结果 1例行膀胱部分切除术,术后4月复发转移7月死亡。1例行髂内动脉插管化疗,至今带瘤生存14月。另1例行膀胱部分切除术,术后6月无复发转移,至今健在。病理学检查肿瘤细胞较小,核浓染,胞浆稀少,核仁不显著,核分裂相多见。免疫组化NSE3例均阳性。结论 膀胱小细胞癌临床罕见,诊断主要依靠病理学检查,此病预后差,应提倡手术切除辅以放疗及全身联合化疗。     

Primary signet-ring cell carcinoma of the urinary bladder inducing renal failure

A case of primary signet-ring cell carcinoma of the urinary bladder that was found to have induced renal failure is the second such case reported in the world. Primary signet-ring cell carcinoma of the urinary bladder is a rare histologic variant of adenocarcinoma. The patient died of distant metastasis 8 months after undergoing total cystectomy. The neoplasm had a high stage at diagnosis, so the prognosis was very poor. To improve the prognosis, earlier diagnosis and establishing a regimen of chemotherapy is necessary.     

Alpha-fetoprotein-producing transitional cell carcinoma of the urinary bladder: a case report

We report a 76-year-old man with alpha-fetoprotein (AFP)-producing transitional cell carcinoma of the bladder. Although the serum level of AFP was 1,428 ng/ml, and he was anti-hepatitis C virus (anti-HCV) antibody-positive, liver tumors were not detected by either a computed tomography (CT) scan or a hepatic angiography. However, removal of a bladder tumor by transurethral resection and subsequent pathological examination revealed a grade III transitional cell carcinoma (TCC). Furthermore, immunohistochemical detection of AFP was diffuse-positive. After the tumor partially responded to concomitant chemoradiotherapy, the serum AFP levels decreased to 966 ng/ml. However, the tumor eventually progressed with multiple lung metastases, and serum AFP levels increased to 3,906 ng/ml. In conclusion, AFP-producing TCC of urinary bladder is rare, and the nature and pathophysiology remains unclear and warrants further investigation.     

原发性膀胱小细胞癌的诊治体会和预后分析

目的:探讨膀胱小细胞癌(SCCB)的临床病理特点,提高对该病的认识和诊治水平。方法:回顾性分析我院2005年4月~2013年7月收治的10例原发性SCCB患者的临床病理资料。男9例,女1例,年龄45~78岁,平均63岁。以无痛肉眼血尿症状入院7例,膀胱刺激征入院1例,体检发现膀胱占位入院2例。其中尿脱落细胞学检查提示5例阳性,2例可疑,3例阴性。B超和CT检查均提示膀胱内占位性病变,CT检查提示盆腔淋巴结增大3例。膀胱镜检查提示:1例膀胱右侧壁与三角区交界处呈苔藓样变(直径约7~10cm),1例膀胱壁右侧顶底交界处及右颈部可见直径约2cm乳头样肿物,余8例可见肿瘤基底较宽,分布与B超结果一致。肿瘤最大径3.0~6.0cm,平均4.5cm。9例患者接受手术治疗,其中经尿道膀胱肿瘤电切术4例,膀胱部分切除1例,根治性膀胱切除4例;行单纯化疗1例。总计9例患者接受1~6个周期全身化疗。结果:所有患者术后病理证实为原发性SCCB。参照第七版美国肿瘤研究联合委员会(AJCC)膀胱癌分期标准,10例患者临床分期为:Ⅰ期1例,Ⅱ期3例,Ⅲ期4例,Ⅳ期2例。患者均获随访,随访时间3~47个月不等。仅1例患者术后存活47个月至今,另外9例患者死亡,平均存活时间为11.7个月。结论:SCCB是一种分化程度低、恶性度高、易早期转移、预后较差的少见肿瘤。该病最佳治疗方式及预后判断的指标尚不明确,简单的肿瘤二期分期系统更适于该病的治疗,但需多中心前瞻性随机试验进一步证实。分子靶向治疗是未来的努力方向。     

Contemporary management of stage T1 transitional cell carcinoma of the bladder

PURPOSE: Transitional cell carcinoma involving the lamina propria (stage T1) is associated with a high recurrence and progression rate with implications for patient survival and quality of life. A better understanding of the natural history of and treatment alternatives for this tumor may improve the outcome in patients with this stage of bladder cancer. MATERIALS AND METHODS: Literature of the last decade was comprehensively reviewed in regard to clinical and pathological diagnosis, adjuvant treatments, prognosis, and the role and timing of cystectomy. The information was gathered from MEDLINE, current urology journals, abstracts from recent urological meetings and personal experience. RESULTS: High grade and the depth of lamina propria invasion are important prognostic factors. Early diagnosis and accurate pathological assessment are essential for determining the most adequate treatment pathway. Initial treatment consists of complete transurethral resection and adjuvant treatment with intravesical instillation of bacillus Calmette-Guerin (BCG). Immediate postoperative instillation of mitomycin C decreases the risk of recurrence possibly related to tumor implantation. Intravesical treatment does not substantially decrease the chance of progression. Lack of a complete response to BCG at 3 to 6 months, high grade, the depth of lamina propria invasion, the association of carcinoma in situ and prostate mucosa or duct involvement represent significant predictors for progression. Cystectomy should be suggested for recurrent stage T1 tumor after BCG, new onset or persistent carcinoma in situ, tumor located at a difficult site for resection, prostatic duct or stromal involvement and muscle invasion. CONCLUSIONS: High grade stage T1 transitional cell carcinoma is a highly malignant tumor. Complete resection followed by immediate mitomycin C instillation and 6 weekly BCG instillations results in an acceptably low recurrence and progression rate. Rigorous long-term surveillance and continuous reconsideration of radical cystectomy in concordance with the evolution of the disease are essential.     

Small cell carcinoma of the urinary bladder: a 15‐year retrospective review of treatment and survival in the Anglian Cancer Network

OBJECTIVE

To report the clinical experience and management of patients with small cell carcinoma (SCC) of the bladder, treated in the Anglia Cancer network from 1992 to 2007, and to review published studies, as SCC is a rare condition, accounting for <1% of all bladder tumours, and there is no established treatment strategy for managing these patients.

PATIENTS AND METHODS

We analysed retrospectively data from all patients diagnosed with SCC of the urinary bladder between 1992 and 2007, with an emphasis on stage, treatment and overall survival.

RESULTS

Twenty patients were identified with primary bladder SCC (male: female ratio 3:1; mean age 68 years; mean follow‐up 15.8 months). Nine patients (45%) had extensive‐stage disease at diagnosis. Four patients received best supportive care, three had a radical cystectomy, one radical radiotherapy and six sequential chemo‐radiotherapy. In all, 13 patients were treated with chemotherapy, with six receiving cyclophosphamide, doxorubicin and vincristine, three receiving carboplatin and etoposide, and the remainder receiving alternative platinum‐based regimens. For 12 patients with assessable disease, six had a complete response, three a partial response and three had progressive disease after chemotherapy. No patient received prophylactic cranial irradiation (PCI). At the time of analysis, 14 (70%) patients had died, with one (5%) developing brain metastasis. The median survival was 33 months for patients receiving chemotherapy, vs 3 months with no chemotherapy.

CONCLUSIONS

SCC of the bladder tends to occur in an older population, more commonly in men. It is an aggressive tumour with a propensity for early metastasis. The response rate to chemotherapy is high but the overall prognosis is poor. Brain secondaries are less common than for SCC of the lung and currently the role of PCI is unclear. As there is no standard of care for these patients, they are treated according to local protocols. Further efforts should be made to develop more effective treatments and the role of PCI should be assessed in the setting of a clinical trial, in conjunction with other extrapulmonary SCCs.     

非转移性膀胱小细胞癌预后多因素分析及列线图的构建

目的探讨非转移性膀胱小细胞癌(BSCC)的独立预后因素,并建立可以个体化预测患者癌症特异性生存率(CSS)的列线图。方法回顾性分析SEER数据库中2004年至2016年确诊并登记的BSCC患者的临床病理资料,簇选后共纳入360例患者,应用Kaplan-Meier法计算患者的生存率并绘制生存曲线,Log-rank检验评价不同亚组生存差异的显著性,并根据Cox多因素分析结果,运用R软件绘制列线图。列线图的预测性能由校准图和ROC曲线下面积(AUC)进行内部验证。结果年龄>80岁、肿瘤最大径>5.0 cm及T4期是CSS的独立危险因素;术中盆腔淋巴结清扫、(术前或术后)辅助化疗或联合放化疗是独立保护因素。所建列线图预测确诊后1、3、5年CSS的预测精准度分别为0.79、0.72和0.71。结论基于SEER数据库,本研究确定了非转移性BSCC的独立预后因素,并建立了可以个体化预测非转移性BSCC患者预后的列线图,这将有助于设计临床试验和促进医患沟通。     

The management of stage T1 grade 3 transitional cell carcinoma of the bladder

The number of Mini‐Reviews per issue is being increased to three for the foreseeable future. As mentioned before, I believe they add to the reader‐friendliness of the journal, and are enjoyable and informative. This month, the controversial topics of T1 G3 bladder cancer, surgery for penile fractures and managing patients on warfarin are dealt with. I hope that readers will feel free to write to me if they have strong feelings about these or any other subjects in the Journal.     

Clinical study of transitional cell carcinoma of the prostate associated with bladder transitional cell carcinoma

BACKGROUND: Transitional cell carcinoma of the prostate in patients with bladder cancer appears to influence the prognosis and affects the decision about therapeutic modality. Therefore, it is important to characterize transitional cell carcinoma associated with bladder cancer. METHODS: From April 1980 to December 1998, 81 male patients underwent total cystoprostatectomies for transitional cell carcinoma of the bladder. The 81 cystoprostatectomy specimens were examined to clarify the characteristics of prostatic involvement by transitional cell carcinoma. The extent, origin, mode of spread and risk factor of prostatic involvement as well as the prognosis were investigated. In 13 of 15 patients with prostatic involvement the prostate was examined by sequential step sections. RESULTS: Prostatic involvement was observed in 15 of 81 patients (18.5%). Prostatic urethral involvement, invasion to prostatic duct/acinus, prostatic stromal invasion and extraprostatic extension and/or seminal vesicle involvement were recognized in 12 (80%), 14 (93.3%), six (40%), and five (33.3%) of the 15 patients, respectively. Twelve of the 15 patients (80%) with prostatic involvement had papillary or non-papillary tumors (i.e. carcinoma in situ) both in the prostatic urethra and prostatic duct. In 10 of these 12 patients (88.3%), there was contiguity between prostatic urethral and ductal tumors. Seven of the 23 patients (30.4%) with carcinoma in situ of the bladder showed prostatic involvement, which increased to 50% in the presence of carcinoma in situ of the trigone or bladder neck. CONCLUSIONS: Eighty per cent of the patients with prostatic involvement showed papillary or non-papillary tumors both in the prostatic urethra and prostatic duct. There was a high level of contiguity between both tumors. Patients with carcinoma in situ of the trigone or bladder neck revealed significantly higher incidence of prostatic involvement.     

DNA芯片技术筛选膀胱移行细胞癌信号转导相关基因

目的探讨人膀胱移行细胞癌信号转导相关基因的表达变化。方法使用人肿瘤基因表达谱芯片检测11例膀胱移行细胞癌组织基因表达谱的变化，以寻找与细胞信号转导相关的差异表达基因。结果以正常膀胱黏膜组织为对照，11例膀胱肿瘤组织中有87个基因表达明显下调，102个基因表达明显上调。其中与细胞信号转导相关的差异表达基因有35个，明显上调基因13个，明显下调基因22个。结论膀胱肿瘤的发生与发展与多种细胞信号转导相关基因的异常表达有关。