直肠癌分期及治疗指南

●医学外语辅导 (肛肠外科) Guidelines in Staging and Treatment of Rectal Cancer 直 肠 癌 分 期 及 治 疗 指 南 NCCN(National Comprehensive Cancer Network) 广西医科大学第一附属医院大肠肛门病外科 　(南宁 　530021) 　张小龙 　译 Staging(分期) 　The NCCN rectal cancer guidelines adhere to the current TNM staging system (Table 1) . In this version of the staging system ,smooth metastatic nodules in the pericolic or perirectal fat are considered lymph node metastatic and should be counted in the N staging. Irregularly contoured metastatic nodules in the peritumoral fat are considered vascular invasion. Stage Ⅱis now subdivided into ⅡA (if the primary tumor is T3 ) and ⅡB (for T4 lesions) . Stage Ⅲ is subdivided into ⅢA(T1～2 ,N1 , M0 ) , ⅢB ( T3～4 ,N1 ,M0 ) , and ⅢC (any T ,N2 ,M0 ) . In addition , the current staging suggests that the surgeon mark the area of the specimen with the deepest tumor pene2 tration so that the pathologist can directly evaluate the radial margin. The surgeon is encouraged to score the completeness of the resection as (1) R0 for complete tumor resection with all margins negative ; (2) R1 for incomplete tumor resection with microscopic involvement of a margin :and (3) R2 for incomplete tumor resection with gross residual tumor not resected. 美国国家综合癌症网络 (NCCN) 直肠癌分期指南坚持使 用通用的 TNM分期体系 (表 1) 。在这个分期系统中 ,结肠或 直肠周围脂肪中圆滑的转移结节被认定为淋巴结转移 ,在 N 分期计数中应被包括进去。肿瘤周围脂肪中轮廓不规则的转 移结节则被认定为血管浸润。Ⅱ期现在被进一步分为 ⅡA (原发肿瘤为 T3 )和 ⅡB (原发肿瘤为 T4 ) , Ⅲ期被进一步分为 ⅢA(T1～2 ,N1 ,M0 ) , ⅢB ( T3～4 ,N1 ,M0 ) 和 ⅢC(任何 T ,N2 ,M0 ) 。 该分期系统外科医生在切除标本中标记出肿瘤浸润最深 的部位 ,以便于病理医生能直接估计肿瘤浸润延伸的边缘。 外科医生应该对肿瘤切除的完全性加以记录 :所有切缘均阴 性的完全切除记录为 R0 ,显微镜下一侧切缘阳性的不完全切 除记录为 R1 ,肉眼可见肿瘤残留的不完全切除记录为 R2。 Table 1 　American Joint Committee on Cancer (AJCC) TNM Staging System for Colorectal Cancer Primary Tumor (T) TX 　Primary tumor cannot be assessed T0 　No evidence of primary tumor Tis 　Carcinoma in situ :intraepithelial or invasion of lamina prop2 ria T1 　Tumor invades submucosa T2 　Tumor invades muscularis propria T3 　Tumor invades through the muscularis propria into the subse2 rosa ,or into nonperitonealized pericolic or perirectal tissues T4 　Tumor directly invade other organs or structures ,andΠor per2 forates visceral peritoneum Regional Lymph Nodes(N) § NX 　Regional lymph nodes cannot be assessed. N0 　No regional lymph node metastasis. N1 　Metastasis in 1 to 3 regional lymph nodes. N2 　Metastasis in 4 ormore regional lymph nodes. Distant metastasis(M) MX 　Distant metastasis cannot be assessed. M0 　No distant metastasis. M1 　Distant metastasis. 表 1 　美国癌症联合委员会结直肠癌 TNM分期系统 原发性肿瘤 (T) TX 　原发肿瘤无法估计 T0 　未发现原发肿瘤 Tis 　原位癌 :上皮内癌或肿瘤侵犯固有层 T1 　肿瘤侵及黏膜下 T2 　肿瘤侵犯肌层 T3 　肿瘤穿透肌层至浆膜下或至无腹膜的结肠或直肠周 围组织 T4 　肿瘤直接侵犯其它器官或 (和)穿透脏器 区域淋巴结 (N) NX 　区域淋巴结情况不详 N0 　无区域淋巴结转移 N1 　1～3 个区域淋巴结转移 N2 　≥4 个区域淋巴结转移 远处转移 (M) MX 　有无远处转移不详 M0 　无远处转移 M1 　有远处转移 Stage Grouping(分期) Stage T N M Dukes MAC 3 0 Tis N0 M0 — — I T1 N0 M0 A A T2 N0 M0 A B1 ⅡA T3 N0 M0 B B2 ⅡB T4 N0 M0 B B3 ⅢA T12T2 N1 M0 C C1 ⅢB T32T4 N1 M0 C C2ΠC3 ⅢC AnyT N2 M0 C C1ΠC2ΠC3 Ⅳ AnyT AnyN M1 — D 　　MAC3 is the modified Astler2Coller classification. ( MAC 3 是 改良 Astler2Coller 分期法) 1941广西医学 　2005 年 9 月 　第 27 卷 　第 9 期 Histologic grade ( G) 　　Gx : Grade cannot be assessed ; G1 :Well differentiated ; G2 :Mod2 erately differentiated ; G3 :poorly differentiatied ; G4 :Undifferentiated. 组织学分级 ( G) 　　Gx :分级不能确定 ; G1 :高分化 ; G2 :中分化 ; G3 :低分化 ; G4 :未分化 Clinical Evaluation Rectal carcinoma should be fully staged. Endoscopic biopsy speciments of the lesion should undergo careful pathology review for evidence of invasion into the muscularis mucosa. If available ,endo2 rectal ultrasound or magnetic resonance imagine can assist the surgeon in determining the extent of disease. These modalities have been use2 ful is assessing the depth of invasion and the lymph node status. Computed tomographic (CT) scans of the abdomen and pelvis are rec2 ommended because they might provide additional imformation about the extent of the disease. If removal of the rectum is contemplated , early consultation with an enterostomal therapist is recommended for preoperative marking of the site and for patient teaching purposes. 临床评估 应尽可能通过各种检查对直肠癌进行分期。对经内镜取 得的病变活检标本进行仔细的病理学检查 ,可能观察到肿瘤 侵及黏膜肌层。如果能够进行直肠内超声或 MRI 检查则可 协助外科医生判定病变的范围 ,这些方法在评估肿瘤浸润深 度及淋巴结状况时是有用的。腹部及盆腔 CT扫描可能提供 更多病变累及范围的信息而受到推荐。如果考虑需行直肠切 除 ,应早期请肠造口治疗师进行术前造口定位并对病人进行 造口相关教育。 Treatment (治疗) Treatment of T1 and T2 Lesions With Favorable Characteristics In selected T1 and T2 lesions without positive margins or adverse features (eg , no lymphovascular invasion [LV1 ] or perineural inva2 sion ; size < 3cm ; well to moderately differentiated) , local excision might give results comparable to anterior2posterior resection. Transanal excision is the preferred procedure for small tumors within 8 cm of the anal verge and limited to 30 % of the rectal circumference (category 2B for T2 tumors) . Local recurrence rates for T2 lesions have been 25 % when lesions are not suitable for transanal surgery. If postsurgical pathology review after local excision reveals a grade 3 to 4 histology , positive margins , or LVI , then a transabdominal reresec2 tion should be performed. A T2 lesion with negative margins and none of the poor prognostic factors can be treated with transabdominal re2 section or adjuvant 5 fluorouracilΠradiation therapy (52FUΠRT) . 预后良好的 T1 和 T2 期肿瘤的治疗 在一些切缘无阳性发现或不合并不利因素的 T1 和 T2 肿 瘤 (如无淋巴、血管及周围神经浸润 ;大小在 3 cm 以下 ;高到 中度分化) ,局部切除可达到与前切除术同样的效果。经肛门 切除对距肛缘 8 厘米以内、占据直肠周径 30 %以下的小肿瘤 是首选术式。对不适合行经肛门手术的 T2 期肿瘤行局部切 除术的局部复发率是 25 %。局部切除术后病理检查发现肿 瘤组织学分级为 3～4 级 ,切缘阳性或淋巴、血管浸润 ,则应进 行开腹手术。切缘阴性且无预后不利相关因素的 T2 期肿瘤 可行经腹手术亦可给予辅助性 52FU 化疗及放疗 (52FUΠRT) 。 Treatment of Invasive Carcinoma For patients with T1 to T2 lesions not amenable to local exci2 sion , a radical resection is required. For lesions in the mid to upper rectum , a low anterior resection is the treatment of choice. For low rectal lesions , abdominoperineal resection or coloanal anastomosis is required. To decrease the risk of local recurrence , patients should undergo optimal pelvic dissection with sharp mesorectal excision , in2 cluding mesentery distal to the tumor as an intact unit. No adjuvant therapy is indicated for patients with T1 or T2 lesions. Patients with lymph node —negative T3 or T4 lesions or any lymph node —positive cancer should receive adjuvant radiotherapy and chemotherapy (cate2 gory 1) , either preoperatively or postoperatively. In the Intergroup Trial U114 , all patients received 6 cycles of postoperative chemother2 apy plus concurrent RT during cycles 3 and 4 . After a median follow2 up of 4 years , neither the rate of local control nor survival differed among 3 different combinations of modulated 52FU chemotherapy. In addition , the MayoΠNCCTG86247251 trial showed that single2agent , continuous2infusion 52FU was more effective than bolus 52FU. As a result , continuous infusion 52FU plus radiotherapy or bolus 52FU plus radiotherapy is an acceptable chemoradiation regimen. Patients with T3 or T4 rectal carcinomas should be considered for preoperative combined2modality therapy. A major goal of preoperative therapy is to decrease the volume of the primary tumor and thus enhance sphincter preservation. Patients who receive preoperative radiotherapy should receive postoperative 52FUΠleucovorin. For patients in whom radical resection is not indicated for medical reasons , adjuvant chemoradio2 therapy is recommended after local excision to decrease local recur2 rence rates. Patients with stage IV lesions may be candidates for pal2 liative resection fulguration or radiotherapy followed by systemic ther2 apy. 浸润性直肠癌的治疗 对不能行局部切除的 T1 和 T2 肿瘤需要行根治性切除。 中至高位直肠癌可选择低位前切除。低位直肠癌需行经腹会 阴联合切除或结肠肛管吻合术。为了降低局部复发的风险 , 应对患者的盆腔进行合理的解剖分离 ,锐性分离切除包括肿 瘤远端肠系膜在内的直肠系膜 ,并保持其完整无损。T1 和 T2 期患者无须辅助治疗 ,淋巴结阴性的 T3 和 T4 期肿瘤及所有 淋巴结阳性肿瘤患者均应在术前或术后接受辅助性放疗及化 疗。在 U114 分组试验中 ,患者均接受 6 个周期的术后化疗 , 并在第 3、第 4 周期时同时接受放疗。通过平均 4 年的随访发 现 ,局控率及生存率在 3 种不同的 52FU 化疗组合之间无 差别。另外 , MayoΠNCCTG86247251 试验显示在单因素比较 时 ,52FU 持续注入效果优于单次推注给药。故 52FU 持续给药 加放疗或 52FU 推注加放疗是可选的放化疗组合方案。T3、T4 期直肠癌患者应接受术前联合方案治疗 ,其主要目的是使原 2941 Guangxi Medical Journal , Sep. 2005 , Vol127 , No19 发肿瘤体积缩小进而提高保肛率。术前接受放疗的患者术后 应给予 52FUΠCF化疗。对无须行根治性切除的患者 ,局部切 除后给予辅助性放、化疗可以降低局部复发率。IV 期肿瘤患 者可选择姑息性切除、电灼或放疗并进一步接受系统治疗。 Surveillance and Management of Recurrence The approach to monitoring and surveillance of patients with rec2 tal carcinoma is essentially the same as for colon cancer. Patients with suspected recurrence (bases on increasing carcinoembryonic an2 tigen or suspicious CT scan) should have a positron2emission tomog2 raphy scan , especially if salvage surgery is under consideration. The salvage chemotherapy treatments for metastatic or recurrent rectal cancer are similar to the recommendations for colon cancer. Patients with good performance status and ability to tolerate intensive therapy should be considered for irinotecan alone , bolus or infusional 52FUΠ leucovorinΠirinotecan , 52FUΠleucovorinΠoxaliplatin ,or a capecitabine combination. Because weekly bolus 52FUΠleucovorinΠirinotecan may cause severe gastrointestinal toxicity ,patients on this regimen should be carefully monitored during the first 60 days of therapy. Patients who are unable to tolerate intensive therapy should be offered capecit2 abine ,protracted intravenous 52FU ,or bolus or infusional 52FUΠleuco2 vorin 术后复发的监测及处理 直肠癌患者的追踪和监测方法与结肠癌是相同的。可疑 复发 (CEA 升高或可疑的 CT扫描)的患者 ,特别是不考虑行再 次手术时 ,应进行 PET(正电子发射计算机断层扫描) 检查。 直肠癌转移或复发时的化学药物治疗与结肠癌相似。身体状 况可耐受强烈治疗的患者可选择单用 CPT211 ,推注或滴注 52 FUΠCFΠCPT211 ,52FUΠCFΠL2OHP或联合应用卡培他滨。因 每周 应用 52FUΠCFΠCPT211 可导致严重的胃肠道毒性 ,使用该方案 的患者在治疗的前 60 天中应受到仔细监控。不能耐受强烈 治疗的患者可给予卡培他滨 ,延时静脉使用 52FU 或推注、滴 注 52FUΠCF治疗。 Principles of adjuvant therapy 　　Adjuvant therapy for rectal cancer consists of regimens that in2 clude both concurrent chemotherapyΠRT and adjuvant chemotherapy. The chemotherapyΠRT may be administered either pre or postopera2 tively. 1. Postoperative adjuvant chemotherapy for patients receiving preoperative chemotherapyΠRT: ●　52FU 380mgΠm2Πday on days 125 + leucovorin IV 20 mgΠm2 on days 125 every 28 days ×4 cycles ●　52FU 500mgΠm2 IV bolus injection 1 h after the start of leucovor2 in infusion ,once a wk for 6wks ×3 cycles Leucovorin 500mgΠm2 IV over 2 h once a wk for 6weeks ×3 cy2 cles 2. Postoperative adjuvant regiments for patients not receiving preoperative therapy : ●　52FU + leucovorin ×1 cycles , then concurrent chemotherapyΠ XRT(see below for regimens) ,then 52FUΠleucovorin ×2 cycles * ●52FU 500mgΠm2 IV bolus injection 1 h after the start of the leucovorin infusion ,once a wk for 6 wks + leucovorin 500 mgΠm2 IV over 2 h once a wk for 6 wks. * 　A cycle is comprised of 6 wks followed by 2 wks of rest. ●　Oxaliplatin 85 mgΠm2 on day 1 and bolus 52FU 400 mgΠm2 + leucovorin 200mgΠm2 followed by 52FU 600mgΠm2 in 222h infu2 sions on days 1 and 2 every 2 weeks 3. Dosing Schedules for concurrent chemotherapyΠRT: ●　RT + 52FUΠleucovorin 52FU 400 mgΠm2 + leucovorin 200mgΠ m 2for 4 d during wk 1 and 5 of RT ●　RT + capecitabine Capecitabine 825 mgΠm2 PO BID throughout course of RT( beginning 2 hours before start of RT and ending with the last dose of RT) . 辅助治疗 直肠癌辅助治疗包括同时接受放、化疗和辅助性化疗。 放、化疗可于术前或术后进行。 1 　术前已行放化疗患者的术后辅助化疗 : ●　52FU 380mgΠm2Π天 + CF IV 20 mgΠm2Π天 ,28 天Π周期 ,第 1～ 5 天用药 ,共用 4 周期。 ●　52FU 500mgΠm2在 CF滴注开始后 1 h推注 ,1 次Π周 ,6 周Π周 期 ,共用 3 周期。 CF 500mgΠm2静脉使用超过 2 h ,1 次Π周 ,6 周Π周期 ,共用 3 周期。 2 　术前未行放化疗患者的术后辅助治疗 : ●　52FU + CF使用 1 周期 ,接着同时行放、化疗 ,再使用 52FU + CF 2 周期。 * 　52FU 500mgΠm2在 CF滴注开始后1 h 推注 ,1 次Π周 ,用 6 周 + CF 500mgΠm2静脉使用 ,超过 2 h ,1 次Π周 ,用 6 周。 * 　6 周为 1 周期 ,接下来休息 2 周。 ●　第 1 天用 L2OHP 85 mgΠm2 静滴 ,同时推注 52FU 400 mgΠ m 2 ,CF200mgΠm2 静滴 ,接着 52FU 600mgΠm2 滴注 22 h ,第 2 天再予 52FU 600mgΠm2滴注 22 h ,2 周Π周期。 3 　放化疗同时进行时的剂量 ●　放疗 + 52FUΠCF 放疗的第 1、5 周时给予 52FU 400 mgΠm2 ·天 + CF 200mgΠ m 2Π天 ,用药 4 天。 ●　放疗 + 卡培他滨 放疗期间一直使用卡培他滨 825 mgΠm2口服 ,2 次Π天 (第 一次放疗前 2 h 开始 ,放疗结束后停止) Summary The NCCN Rectal Cancer Guidelines panel believes that a mul2 tidisciplinary approach is necessary for treating patients with colorectal cancer. Patients with T1 orT2 lesions that are node2negative by endo2 rectal ultrasound and who meet carefully defined criteria can be man2 aged with a transanal excision. Abdominal peritoneal resection or low anterior resection with total mesorectal excision is appropriate for all other rectal lesion. Either preoperative chemoradiation or postoperative 3941广西医学 　2005 年 9 月 　第 27 卷 　第 9 期 chemoradiation is standard for patients with suspected or proven sero2 sal invasion(pT3)or regional node involvement. Patients with recurrent localized disease should be considered for resection with or without radiotherapy. Chemotherapy regimens using irinotecan or oxaliplatin should be considered for patients with distant metastasis. The panel endorses the concept that treating patients in a clinical trial has priori2 ty over standard or accepted therapy. 小结 NCCN 直肠癌指导小组认为结直肠癌患者需要接受多学 科的综合治疗。经过认真的按照判定 ,肿瘤为 T1、T2 期 且经直肠超声检查淋巴结阴性的患者可行经肛门切除 ,其他 患者适合行经腹会阴联合切除或低位前切除并行全直肠系膜 切除 ,怀疑或证实浆膜浸润及区域淋巴结受累的患者应行术 前、术后放化疗 ,局部复发患者应行手术切除或手术同时接受 放疗 ,有远处转移的患者应采用联合 CPT211 或 L2OHP 的方案 进行化疗。该小组认同治疗病人时临床验证优先于标准或公 认方案的观念。 摘自 Clinical Practice Guidelines in Oncology2v. 2. 2004 ●学科文献信息导示(肛肠外科) 大 肠 肛 门 病 外 科 医 生 常 用 期 刊 及 网 络 资 源 广西医科大学第一附属医院大肠肛门病外科 　(南宁 　530021) 　甘嘉亮 1 　大肠肛门病外科的国内重要期刊 (1)大肠肛门病外科杂志 地址 :广西南宁市双拥路 6 号广西医科大学院内 邮政编码 :530021 　　　电话 :077125358436 E2mail :dcgm @chinajournal. net. cn (2)实用肿瘤杂志 地址 :杭州解放路 88 号浙大医学院附属二院内 邮政编码 :310009 电话 :0571287783659 传真 :0571287783654 E2mail :SYZZ @chinajournal. net. cn (3)癌 　症 地址 :广州市东风东路 651 号 网址 :www. aizh. chinajournal. net. cn 邮政编码 :510060 电话 :020287343336 E2mail :cjcgz @gzsums. edu. cn (4)肿瘤防治杂志 地址 :山东省济南市济兖路 440 号 邮政编码 :250117 电话 :053127984777282516 传真 :053127984783 E2mail :zgzlx @public. jn. sd. cn (5)中国普外基础与临床杂志 地址 :四川成都国学巷 37 号四川大学华西医院 邮政编码 :610041 电话 :028285422072 传真 :028285432724 (6)国外医学. 肿瘤学分册 地址 :济南市经十路 89 号 邮政编码 :250062 电话 :053122949227 ,2919917 E2mail : GWZL @chinajournal. net. cn (7)中国实用外科杂志 地址 :辽宁省沈阳市和平区砂阳路 252 号 邮政编码 :110005 电话 :024223395362 传真 :024223395362 E2mail :journal @mail. sy. ln. cn (8)肿 　瘤 地址 :上海市斜土路 2200 弄 25 号 　　邮编 :200032 电话 : 021264047029 3 1405 或 021264032388 (9)中华胃肠外科杂志 地址 :广州市中山二路 58 号中山大学附属第一医院内 邮政编码 :510080 电话 :020287335945 E2mail :ZWCW @chinajournal. net. cn 2 　大肠肛门病外科部分国外重要参考期刊 (1) International Journal of Colorectal Disease 国际结直肠疾病杂志 (英国大肠肛门病外科协会主办) http :ΠΠlink. springer. deΠlinkΠserviceΠjournalsΠ00384Πindex. htm (2) Clinical Colorectal Cancer 　临床结直肠癌 http :ΠΠwww. cancerinformationgroup. comΠccc. html (3) American Journal of Clinical Oncology 美国临床肿瘤学杂志 http :ΠΠwww. amjclinicaloncology. comΠ (4) Diseases of the Colon & Rectum 结直肠疾病 (美国结直肠外科医师学会主办) http :ΠΠwww. discolrect. comΠ (5) American Journal of Gastroenterology 美国胃肠病学杂志 (美国胃肠病学学会主办) http :ΠΠwww. blackwellpublishing. comΠjournal. asp (6) Gastroenterology 　胃肠病学 http :ΠΠwww. gastrojournal. orgΠ (7) European Journal of Gastroenterology and Hepatology 欧洲胃肠病学和肝脏病学杂志 (欧洲胃肠病学和内窥镜协 会主办) http :ΠΠwww. eurojgh. comΠ (8) The Canadian Journal of Gastroenterology 加拿大胃肠病学杂志 (加拿大胃肠病学和肝脏病学协会主办) http :ΠΠwww. pulsus. comΠGASTROΠhome. htm 4941 Guangxi Medical Journal , Sep. 2005 , Vol127 , No19