大部分膀胱切除生物补片膀胱扩大术在高龄浸润性膀胱癌患者中的应用
王焕瑞, 张维宇, 刘献辉, 胡浩, 张晓鹏, 许克新
北京大学人民医院泌尿外科, 北京 100044
摘要

目的: 探讨膀胱大部分切除一期行生物补片膀胱修补术在高龄浸润性膀胱癌患者中的临床疗效和安全性。方法: 回顾性分析2016年10月至2017年3月在北京大学人民医院泌尿外科行膀胱部分切除、一期行生物补片膀胱修补术的2例患者的临床资料。病例1,87岁老年男性,膀胱前壁病变,范围5.5 cm×2.5 cm,美国麻醉医师协会(American Society of Anesthesiologists, ASA)病情分级Ⅲ级。病例2,77岁老年女性,膀胱右前壁病变,范围5.2 cm×4.0 cm,ASA Ⅱ级。患者采用膀胱大部分切除生物补片膀胱扩大的手术方式,记录手术时间、术中出血量、围术期手术资料及术后膀胱镜及尿动力学随访情况。结果: 2例均顺利完成手术,平均手术时间(155.0±35.4)min,术中出血量20~100 mL,患者均在术后8 d出院。术后随访10~14个月,均未发现肿瘤复发和转移。随访尿动力结果:最大尿流率16.5 mL/s,最大膀胱容量303 mL。白天3~4次,夜尿0~3次,排尿间隔2 h,每次尿量200~300 mL,美国泌尿外科协会症状评分(American Urological Association symptom score, AUASS) 2~5分。对于高龄、合并症多、手术麻醉风险大的患者可以行膀胱部分切除,以减少并发症的发生。肿瘤体积小的患者,膀胱部分切除后能够保留足够的正常膀胱壁,并逐渐恢复膀胱容量。对于病变范围较大、残余正常膀胱组织较少的患者,保证切缘阴性的情况下,膀胱扩大术有助于恢复膀胱容量。结论: 膀胱大部分切除一期行生物补片膀胱修补术有较高的安全性,可以保留膀胱功能,提高生活质量,适用于高龄浸润性膀胱癌患者。

关键词: 膀胱肿瘤; 膀胱部分切除; 膀胱扩大
中图分类号:R694 文献标志码:A 文章编号:1671-167X(2018)04-0626-04
Clinical application of partial cystectomy with augmentation cystoplasty for invasive bladder cancer in elderly patients
WANG Huan-rui, ZHANG Wei-yu, LIU Xian-hui, HU Hao, ZHANG Xiao-peng, XU Ke-xin
Department of Urology, Peking University People's Hospital, Beijing 100044, China
△ Corresponding author's e-mail,cavinx@sina.com
Abstract

Objective: To evaluate the clinical effect and safety of biological patch applied in elderly patients with invasive bladder cancer who underwent massive partial cystectomy with augmentation cystoplasty.Methods: The clinical data of 2 patients with invasive bladder cancer from October 2016 to March 2017, who underwent the massive partial cystectomy with augmentation cystoplasty were retrospectively reviewed. Case one was an 87-year-old man, with tumor located on the bladder anterior wall, ranging from 5.5 cm×2.5 cm, and the grade of American Society of Anesthesiologists (ASA) being Ⅲ. Case two was a 77-year-old female, whose lesion was located on the right anterior wall, ranging from 5.2 cm×4.0 cm, and the grade of ASA being Ⅱ. Both of the patients received a massive partial cystectomy with augmentation cystoplasty. The operative time, estimated blood loss, perioperative and postoperative data and follow-up data, including cystoscopy and urodynamics were recorded and compared. When the P value was less than 0.05, it was statistically significant.Results: All the operations were successfully performed. The average operative time was (155.0+35.4) min, mean estimated intraoperative blood loss was 20 to 100 mL, and the mean postoperatively hospital stay was eight days. During the 10 to 14 months’ follow-up periods, no local recurrence or distant metastasis occurred. Urodynamic data: the maximum urinary flow rate was 16.5 mL/s, and the maximum bladder capacity was 303 mL. The two patients urinated 3-4 times in the day time, 0 to 3 times in the night, 200-300 mL each time, on average. The American Urological Association symptom score was 3 to 5. Partial cystectomy, applied to aged patients with multiple complications and high risk of surgical anesthesia, was able to reduce surgery rela-ted complications. For patients with tumor of small size, the normal bladder wall would be enough to reco-ver functional capacity for urine storing after partial cystectomy. For patients with large lesions range and small normal bladder tissues, augmentation cystoplasty would help recover bladder capacity on the condition of negative margin.Conclusion: Massive partial cystectomy with augmentation cystoplasty is safe and effective. It could decrease perioperative morbidity and keep the quality-of-life benefits of bladder preservation, which is worthy of further application for some selected invasive bladder cancer in elderly patients.

Key words: Urinary bladder neoplasms; Partial cystectomy; Augmentation cystoplasty

膀胱根治性切除(radical cystectomy, RC)是肌层浸润尿路上皮癌的标准治疗方式[1]。虽然这种手术方式在肿瘤控制和降低复发方面占有优势, 但其围术期并发症的高发生率是不能忽视的问题。Sood等[2]报道膀胱全切患者30 d内的并发症发生率和死亡率, 分别高达52.1%和 2.7%, 并且在高龄患者中, 不良事件的发生率进一步提高[3]。对于一些患者, 特别是高龄合并症多的患者, 膀胱部分切除(partial cystectomy, PC)可能会达到与膀胱全切类似的控制肿瘤的目的, 减少围手术期并发症的发生, 更重要的是可以保留膀胱功能, 提高生活质量[4, 5, 6]。对于病变范围较大的膀胱癌患者, 在行膀胱部分切除后, 由于残余正常膀胱组织少, 膀胱容量过小, 膀胱正常储尿功能难以代偿。北京大学人民医院针对大范围膀胱部分切除患者一期行生物补片膀胱扩大术, 本文通过回顾性分析这2例患者的临床资料, 以及对患者术后生活质量、肿瘤复发情况的随访, 评价这种手术方式的临床应用价值。

1 资料与方法
1.1 临床资料

2016年10月至2017年3月在北京大学人民医院泌尿外科共有2例行膀胱部分切除+生物补片膀胱扩大的肌层浸润性膀胱癌患者。

病例1, 87岁老年男性, 因“ 尿痛、发热、泌尿系CT发现膀胱占位7 d” 就诊。否认肉眼血尿, 有头晕、乏力等症状。既往高血压20年, 最高血压180/120 mmHg, 口服药物控制。13年前行冠状动脉支架置入术, 规律口服抗凝药, 已停药7 d。既往史:12年前行腹腔镜胆囊切除, 糖尿病3年, 口服药物降糖。

病例2, 77岁老年女性, 因“ 间断无痛性肉眼血尿1年” 就诊。患者1年前无明显诱因出现全程无痛肉眼血尿, 当地医院口服药物治疗, 1周前患者再次出现血尿, B超提示膀胱壁低回声占位。既往高血压10年, 口服药物降压。糖尿病5年, 口服药物治疗。窦性心动过缓, 最低约40次/min。

1.2 辅助检查

术前完善泌尿系增强CT, 尿脱落细胞学检查, 膀胱镜检查取活检, 明确诊断, 评估肿瘤临床分期。

1.3 生物补片

本研究中两例患者使用的生物补片为软组织修补片, 是猪小肠黏膜下层组织(small intestinal submucosa, SIS)制成的干燥的多层片状物, 用于加强和修补软组织。通过剪裁使大小符合解剖需求, 补片为无菌、一次性使用。以SIS为支架构建的细胞外基质成分支架, 保留了细胞的特异性微环境, 有利于细胞浸润和血管再生[7]。此前已有SIS用于泌尿系组织修复的报道[8, 9, 10], SIS用于膀胱扩大或膀胱修复手术, 可为膀胱尿路上皮提供爬行支持, 手术一段时间后SIS上可观察到平滑肌层[11]、神经分布[12]

1.4 术后随访

术后随访患者的肿瘤复发情况及排尿情况, 包括彩色多普勒超声、泌尿系CT、膀胱镜检、尿动力学检查、美国泌尿外科协会症状评分(American Urological Association symptom score, AUASS), 随访时间10~14个月。

2 结果
2.1 术前辅助检查

病例1泌尿系增强CT:膀胱前壁明显增厚, 增强后明显均匀强化(图1)。尿脱落细胞学检查:高度可疑为肿瘤细胞。

图1 病例1, 膀胱前壁大范围病变Figure 1 Case 1, a wide range of lesions diffusely covering the anterior wall of the bladder

病例2泌尿系增强CT:膀胱右前壁局部毛糙, 并可见一不规则高密度影突入腔内, 大小范围约4.5 cm× 2.8 cm, 增强扫描动脉期明显强化, 延迟扫描持续强化(图2)。膀胱镜活检:符合具有低度恶性潜能的尿路上皮肿瘤。

图2 病例2, 膀胱右前壁肿物Figure 2 Case 2, a large tumor at the right anterior wall of the bladder

2.2 治疗及随访

病例1于2017年2月20日在蛛网膜下腔麻醉联合硬膜外间隙阻滞麻醉下行膀胱部分切除+生物补片膀胱扩大术。探查提示膀胱肿瘤位于顶后壁, 大小约6 cm × 5 cm, 距肿瘤边缘1 cm切开膀胱壁, 完整切除肿瘤, 取切缘膀胱组织送术中冰冻, 未见明确恶性成分。考虑肿瘤体积较大, 膀胱缺损较大, 为恢复膀胱容量, 与家属沟通后, 决定行生物补片膀胱扩大术。取生物补片裁剪至10 cm× 10 cm, 将补片覆盖于膀胱缺损处, 边缘与膀胱壁切缘对合, 用可吸收线连续加间断严密缝合。膀胱注水150 mL, 未见明显渗漏。无菌蒸馏水浸泡伤口5 min后逐层关闭切口。手术时间130 min, 术中失血20 mL。术后病理:高级别浸润性尿路上皮癌, 肿瘤范围5.5 cm × 2.5 cm, 侵犯膀胱壁全层达周围脂肪组织; 未见明确脉管内癌栓, 肿瘤侵犯神经组织, 可见尿路上皮原位癌; 病理学分期pT3NxMx。术后3个月复查泌尿系彩色多普勒超声未见明显复发征象, 术后10个月排尿情况随访, 白天3~4次, 夜尿2~3次, 每次排尿量200~300 mL, 排尿间隔2 h, AUASS评分5分, 患者对排尿情况满意, 未返院行尿动力学检查。

病例2于2016年10月24日全身麻醉下行膀胱部分切除+膀胱扩大术。探查提示膀胱肿瘤位于膀胱前壁, 大小约5 cm × 3 cm, 清扫两侧髂血管周围及闭孔旁淋巴结, 于膀胱右顶壁处切开膀胱, 将切口延长至肿瘤附近, 观察双侧输尿管开口位置清楚后, 将肿瘤连同周围1 cm的正常膀胱黏膜一并切除, 取膀胱切缘送病理。术中冰冻回报:切缘未见肿瘤成分。取生物补片4 cm× 7 cm, 以2-0可吸收缝线缝合膀胱全层与生物补片, 3-0可吸收线间断加强吻合处。留置22#三腔单囊导尿管, 无菌蒸馏水浸泡伤口5 min, 留置盆腔引流管1根, 关闭切口。手术时间3 h, 术中失血100 mL。术后病理:膀胱高级别尿路上皮癌, 大小5.2 cm× 4.0 cm, 侵及膀胱壁深肌层。右侧髂血管、闭孔、左侧闭孔、髂血管淋巴结未见癌转移(0/3、0/2、0/5、0/2)。病理学分期pT2bN0M0。术后4个月复查泌尿系CT, 可见膀胱前壁略显毛糙, 余无特殊(图3)。术后4个月行膀胱镜检未见复发, 生物补片已完全被尿路上皮覆盖(图4)。术后8个月行尿动力学检查, 膀胱容量303 mL, 最大尿流率16.5 mL/s, 残余尿量0 mL。术后14个月排尿情况随访, 白天3~4次, 夜尿0~1次, 每次排尿量200~300 mL, 排尿间隔2 h, AUASS评分2分, 患者对排尿情况满意。

图3 病例2, 术后4个月复查CTFigure 3 Case 2, CT scan four months after operation

图4 病例2, 术后4个月膀胱镜检查结果Figure 4 Case 2, cystoscopy four months after operation

3 讨论

目前膀胱根治性切除的比例逐渐增加, 仅有7%~10%的肌层浸润膀胱癌患者行膀胱部分切除[13, 14, 15]。膀胱部分切除是一种非标准的膀胱癌治疗方式, 这种手术方式旨在兼顾病变切除和保留膀胱功能。膀胱部分切除目前国内外没有明确的手术指征, 《美国国立综合癌症网络临床实践指南》建议, 对于肌层浸润性膀胱癌, 孤立性病灶, 在保证足够切缘的情况下可以行膀胱部分切除。目前临床工作中, 膀胱部分切除大多应用在手术麻醉风险大的高龄患者, 以减少手术时间, 降低并发症的发生, 且该类患者肿瘤体积相对较小, 在行部分切除后能保留足够的正常膀胱壁, 经过代偿膀胱容量逐渐恢复以维持储尿功能。

本研究中的两例患者, 病变范围较广, 单纯膀胱部分切除后残余膀胱容量过小, 难以代偿膀胱正常储尿功能, 所以一期行膀胱扩大术, 以恢复膀胱容量。膀胱扩大的手术并发症包括穿孔伴腹腔漏尿、膀胱结石、肠梗阻和恶性肿瘤等[16, 17, 18, 19], 其中膀胱穿孔是致命并发症, 可能在手术数年后发生[20]。膀胱扩大术后膀胱穿孔的病因是多因素的[19, 21, 22, 23], 多数学者认为是膀胱过度充盈, 缺乏支撑的补片相对膀胱壁力量较薄弱, 因此容易发生穿孔。本研究中的2例膀胱扩大, 在缝合生物补片后, 将腹膜部分覆盖并缝合到补片上, 一方面为植入的补片提供支撑, 另一方面为膀胱黏膜上皮爬行到补片上提供更好的微环境, 且本研究中采用的SIS补片, 本身就能在植入早期维持形态完整和一定的机械支撑作用。相较目前较为成熟的回肠膀胱扩大或乙状结肠膀胱扩大, 用生物补片进行膀胱扩大减少了对消化道的干扰, 从而减少了并发症的发生。2例患者术中、术后均未发生严重并发症(Calvien≥ Ⅲ 级), 术后住院时间8 d。

行膀胱部分切除的患者仍然有高复发的风险。近期的报道显示, 膀胱部分切除患者的局部复发率高达50%, 有接近20%~25%的复发患者最终无法避免膀胱根治性切除[4, 24]。通过随访我们发现, 两例患者术后随访10个月及14个月均未出现新发、复发转移征象, 但长期肿瘤结局尚需进一步随访。

两例患者在术后均获得良好的控尿效果, 没有出现膀胱容量不足导致的尿频或是夜尿增多。病例2尿动力学检查提示, 膀胱容量、最大尿流率等参数均与正常膀胱无异, 对于生活质量的影响较小。

本研究的结果显示, 对于高龄、合并症多、手术麻醉风险大的患者可以行膀胱部分切除, 以减少并发症的发生。对于病变范围较大, 残余正常膀胱组织较少的患者, 保证切缘阴性的情况下, 可以一期行膀胱扩大术来恢复膀胱容量。此术式对于膀胱癌患者生活质量的维持有较大优势, 但须对患者进行严格筛选, 适用于身体状况差, 且保留膀胱意愿强烈的患者。

(本文编辑:刘淑萍)

The authors have declared that no competing interests exist.

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