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摘要: 深入认识颈椎矢状面曲度对进一步研究颈椎病、邻椎病的发病机制以及提高手术疗效具有重要作用。但既往文献中, 关于胸腰椎曲度与患者生活质量或功能状态关系的研究较多, 而有关颈椎曲度的研究相对较少, 有必要进行大宗病例的前瞻性研究。本文对颈椎曲度的测量方法、颈椎正常曲度、颈椎曲度对颈椎病及邻椎病的影响、颈椎曲度与临床疗效的关系等进行综述, 以期为脊柱外科医生了解和治疗颈椎疾病提供参考。Abstract: Further understanding of the sagittal curvature of the cervical spine plays an important role in the study of the pathogenesis of cervical spondylosis and adjacent spondylosis, as well as in improving the surgical effect. In the past literature, there have been many studies on the relationship between the thoracolumbar curvature and patients' quality of life or functional status, while there are few studies related to cervical curvature, So it is necessary to carry out prospective studies with a large number of cases. This article reviews the measurement method of cervical curvature, the normal curvature of the cervical spine, the relationship of cervical curvature with cervical spondylosis and clinical effects, etc., so as to provide a reference for spine surgeons to understand and treat cervical spondylosis.
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Keywords:
- cervical curvature /
- sagittal plane /
- cervical spondylosis
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前列腺癌组织病理评价划分为主要分级区和次要分级区，每区的Gleason分值为1~5，这两个分级区的Gleason分值相加即为Gleason评分[1]。Gleason评分是前列腺癌患者治疗效果的主要预后因素之一[2]。通常，Gleason评分8~10分的患者被统一划分为高危组[3-4]。然而，近年来有研究表明Gleason评分8、9或10分的患者治疗预后不一致，分值越高，预后越差[5-6]。Gleason评分10分，即Gleason评分5+5，是最少见、前列腺癌组织分化最差的病理分级类型[7]，目前国内外针对此类前列腺癌的单独研究较少。本研究对北京协和医院近10年诊治的初诊无远处转移的穿刺病理Gleason评分为10分前列腺癌患者的临床特点及外放疗联合内分泌治疗的疗效进行探讨。
对象和方法
研究对象
2003年1月至2014年3月北京协和医院诊治的穿刺病理证实为Gleason评分10分前列腺癌患者，所有患者治疗前均进行病史采集、体格检查、血清前列腺特异性抗原(prostate specific antigen，PSA)检测、常规化验检查、胸部X线片、胸腹盆CT或磁共振成像和全身骨显像检查等。排除标准：辅助检查明确提示肿瘤远处转移。
治疗方法
所有患者均接受全盆腔外放疗联合长期内分泌治疗。外放疗采用6MV-X线调强放疗技术。CT模拟定位扫描范围从L2椎体到耻骨联合下10 cm，扫描层厚5 mm。临床靶体积(clinical target volume, CTV)包括前列腺、双侧精囊腺及盆腔淋巴结区，计划靶体积(planning target volume, PTV)为CTV外10 mm，后方直肠外扩5 mm。全盆腔外放疗的照射剂量为50.0 Gy，前列腺、双侧精囊腺及区域阳性淋巴结加量至76.2~78.0 Gy，分隔照射剂量采用常规分隔照射，1.8~2.0 Gy/次，5次/周。长期内分泌治疗方案采用最大限度雄激素阻断：口服抗雄激素药物(比卡鲁胺50 mg每天1次或氟他胺250 mg每天3次)，同时每月注射一次黄体生成素释放激素类似物(戈舍瑞林3.6 mg、亮丙瑞林3.75 mg或曲普瑞林3.75 mg)。
随访方案
治疗开始前3个月每月随访一次, 之后每3个月随访一次，2年后改为每6个月随访一次。随访方式均为门诊复诊，随访期间复查血清PSA；若肿瘤进展，则根据情况缩短复查时间间隔，必要时检查胸腹盆部CT、全身骨显像等以排除远处转移灶。生化复发定义为PSA值降至最低点后升高并超过最低点2.0 μg/L以上。
统计学处理
采用SPSS 19.0统计学软件进行数据分析，采用Kaplan-Meier法绘制生存曲线。
结果
一般情况
2003年1月至2014年3月北京协和医院共诊治穿刺病理Gleason评分为10分的前列腺癌患者13例，其中4例因全身骨显像检查明确提示远处骨转移被排除，9例患者纳入本研究，年龄64~85岁，中位年龄72岁；前列腺体积25.6~60.1 ml，中位体积43.2 ml；穿刺活检针数阳性率为45.5%~100%，中位值为90.9%。治疗前血清PSA分别为：6.6、7.0、7.3、9.1、11.2、15.6、77.4、100.3和112.8 μg/L，中位值为11.2 μg/L。TNM分期：3例T2c，4例T3a，2例T3b；6例N0，3例N1；9例均为M0。
生存和预后情况
9例患者随访时间26~75个月，中位时间58个月(4.8年)。随访期间，6例生化复发，分别发生在放疗结束后9、11、29、43、51和62个月。5例患者进一步出现远处骨转移，分别发生在放疗结束后15、23、39、68和72个月。4例死亡，其中3例分别在放疗结束后41、57和72个月死于前列腺癌，1例在放疗结束后26个月死于脑出血。总体5年无生化复发率、无远处转移率、肿瘤特异性生存率及总体生存率分别为28.6%、57.1%、66.7%和57.1%。总体无生化复发、无远处转移及肿瘤特异性Kaplan-Meier生存曲线见图 1~3。
放疗和内分泌治疗不良反应
早期放疗胃肠道不良反应：4例无不良反应，1级4例，2级1例，主要表现为直肠下坠、腹泻或便血等，无大便失禁或肠瘘等。早期放疗泌尿系统不良反应：3例无不良反应，1级4例，2级2例，主要表现为尿频、尿急、尿痛或尿中带血等。9例患者均未出现晚期放疗胃肠道及泌尿系统不良反应。内分泌治疗并发症：4例出现性欲减退、男性乳房发育或乳房疼痛，5例出现潮热，无骨折、心血管意外等严重内分泌治疗并发症。
讨论
在前列腺癌病理组织中，Gleason评分为5分的癌肿分化极差，其特点是：(1)单个的肿瘤细胞或形成肿瘤细胞呈条索状生长；(2)不形成腺腔而是成片生长；(3)筛状结构伴有粉刺样坏死[1]。患者前列腺活检病理结果中含有Gleason评分5分通常提示预后不良。Sabolch等[8]报道718例活检病理结果含或不含Gleason评分5分的患者，8年无远处转移率分别为61%和89%，肿瘤特异性生存率则分别为55%和98%。类似地，Nanda等[9]指出Gleason评分8分和Gleason评分9~10分患者的中位生化复发时间分别为5.4年和4.5年。
近年来有研究表明Gleason评分8、9或10分治疗预后不一致，患者评分分值越高，预后越差。Stock等[5]对181例Gleason评分8~10分患者进行近距离治疗联合外放疗和内分泌治疗，结果显示Gleason评分8、9和10分患者的8年无生化复发率、无远处转移率和肿瘤特异性生存率分别为84%、86%和92%(8分)，55%、76%和80%(9分)，30%、30%和62.5%(10分)。Ellis等[6]也指出穿刺病理Gleason评分9~10分可区别于Gleason评分8分，作为预后的独立危险因素。
关于Gleason评分10分前列腺癌的治疗方式，虽然目前未有统一意见，但考虑此类患者初诊时就是局部晚期前列腺癌或已存在微转移灶，放疗联合内分泌治疗往往是首选的治疗方案。采用前列腺癌根治术治疗此类患者近年来亦见报道，但患者来源往往具有选择性。如Ellis等[6]报道手术治疗259例Gleason评分9~10分前列腺癌患者，其平均术前血清PSA 8.9 μg/L、穿刺针数中平均只有2针穿刺病理阳性，而且阳性针中癌细胞平均只占穿刺组织细胞的56%。传统上，常规照射剂量的外放疗联合内分泌治疗可以作为高危前列腺癌的治疗方案[10-11]，但提高外照射剂量并行盆腔淋巴结照射治疗可以提高疗效。Zelefsky等[12]分析外照射剂量在早期前列腺癌中的治疗效果，低照射剂量和更高照射剂量的10年生化复发率分别为55%和41%，高剂量组与更低的生化复发率显著相关。对于高危前列腺癌，在外放疗联合内分泌治疗中，内分泌治疗的应用时间尚未明确。Bolla等[13]认为相对于短时间(6个月)的内分泌治疗，长期(≥2年)内分泌治疗更能显著提高患者的总体生存率。Zelefsky等[12]同样建议高剂量的外放疗联合长期内分泌治疗应作为高危前列腺癌的治疗方式。
本研究中，前列腺穿刺Gleason评分10分患者具有以下临床特点。(1)患者可伴高或低血清PSA值：6例患者的治疗前血清PSA低于20 μg/L，其中位值为8.2 μg/L；其余3例患者治疗前血清PSA均高于70 μg/L，其中位值为100.3 μg/L。高Gleason评分患者低PSA值可以解释为高Gleason评分肿瘤分化极差，以致腺体上皮细胞缺乏表达PSA的编码基因[14]。(2)肿瘤范围较广：穿刺活检针数阳性率为45.5%~100%，中位值为90.9%。这与Gleason评分10分的病理特点相符合[7]。(3)TNM分期均为高危：9例患者TNM分期均≥T2c，且部分伴局部淋巴结转移。本组患者均行全盆腔外放射治疗联合长期内分泌治疗，中位随访4.8年，总体5年无生化复发率、无远处转移率、肿瘤特异性生存率及总体生存率分别为28.6%、57.1%、66.7%和57.1%，患者不甚乐观的治疗效果提示Gleason评分10分前列腺癌治疗预后不理想。但本研究限于样本量小、随访时间短，得出的结论尚需随机的、更大样本量的研究支持。
综上，初诊无远处转移的穿刺病理Gleason评分10分前列腺癌常伴穿刺阳性范围大、肿瘤分期偏晚等高危因素，患者通常预后不良，放疗联合内分泌治疗等及时和积极的综合治疗方案往往是必需的。
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图 2 C2-7 SVA为C7椎体后上缘与经过C2椎体中央或齿突的铅垂线之间的距离，COG-C7 SVA为C7椎体后上缘与头颅重力线之间的垂直距离
SVA:矢状面垂直轴；COG:重力线
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