食管癌术后辅助治疗现状

<正>食管癌在发展中国家发病率较高,死亡率居高不下。在国内,鳞癌是最主要的组织学类型。而在欧美等发达国家,随着胃食管反流病和肥胖发生率的增加,腺癌发生率已超过鳞癌。由于两种组织学类型的预后和侵袭模式不同,目前,美国癌症联合委员会(AJCC)已将两种不同的组织学类型分     

食管癌术后辅助治疗的临床价值

食管癌目前主要的治疗手段仍为手术切除,但术后患者的生存率较低,主要失败模式为局部复发和区域淋巴结转移.术后是否应该行辅助治疗及如何选择方案仍无明确的指南.研究显示Ⅲ期、N1的患者行术后辅助放疗可以提高无瘤生存率及总生存率,靶区范围应根据肿瘤所在的位置来确定.术后辅助化疗方案以顺铂联合5-氟尿嘧啶为首选,该方案主要不良反应为胃肠反应和骨髓抑制;术后辅助放化疗的临床价值仍需更多临床研究来支持.     

食管癌二野淋巴结清扫术后复发规律探讨

目的 分析胸段食管癌二野淋巴结清扫术后局部复发规律,为术后放疗提供帮助.方法 搜集本科2004-2009年收治的134例胸段食管鳞癌术后局部复发患者的临床资料,依据放疗前定位CT分析复发类型及各区域淋巴结转移情况.结果 食管癌术后淋巴结转移占94.0%,吻合口复发占9.7%,食管原瘤床复发占3.7%.126例淋巴结转移患者中纵隔、锁骨上、腹部的分别占80.2%、43.7%、13.5%(χ2=113.15,P=0.000).淋巴结转移上纵隔占73.8%,左喉返神经区(1L区、2L区、4L区、5区)占38.9%,右喉返神经区(1R区)占43.7%,隆突下占34.1%,奇静脉占15.1%,锁骨上占43.7%[右锁骨上多于左锁骨上(31.7%和16.7%;χ2=7.81,P=0.005)].结论 淋巴结转移是胸段食管癌术后局部复发最主要的类型,原瘤床和吻合口复发少见.锁骨上、喉返神经区、奇静脉淋巴结及隆突下淋巴结是二野淋巴结清扫术后淋巴结转移的高发区.

Abstract：

Objective To investigate the local-regional recurrence in thoracic esophageal cancer after radical surgery including two-field lymph node dissection and provide evidence for postoperative radiotherapy. Methods We reviewed local-regional recurrence for 134 cases with esophageal squamous cell carcinoma after radical surgery from 2004 to 2009. Results In 134 cases, lymph node metastasis rate,anastomosis recurrence rate and tumor bed recurrence rate was 94. 0%, 9. 7% and 3.7%, respectively. As to the 126 cases with lymph node metastasis, significant difference was detected between mediastinal metastasis, supraclavicular metastasis and abdominal lymph node metastasis (80. 2%, 43.7% and 13.5%,respectively, χ2= 113. 15, P = 0. 000). Furthermore, the relative metastasis rate in upper mediastinum,middle mediastinum and the lower mediastinum was 73.8%, 39.7% and 1.6%, respectively, the difference was statistically significant ( χ2 = 139. 11, P = 0. 000 ). Significant difference was identified between right and left supraclavicular lymph node metastasis (31.7% vs 16. 7%, χ2= 7. 81, P = 0. 005 ).To confirm the analysis above,lymph node metastasis rate of left recurrent laryngeal nerve nodes, (including region 1L, 2L, 4L and 5) ,right recurrent laryngeal nerve nodes, azygos nodes, subcarinal nodes, and 2R region was 38.9%, 43.7%, 15.1%, 34.1% and 25.4%, respectively. Conclusions The main characteristics of local-regional recurrence may be lymph node metastasis for esophageal squamous cell carcinoma after radical surgery. On the contrary, tumor bed recurrence is rare. Dangerous regions include supraclavicular nodes, recurrent laryngeal nerve nodes, azygos nodes as well as subcarinal nodes.     

序贯三切口及选择性淋巴结清扫治疗食管癌1162例临床效果分析

目的 探讨食管癌外科治疗的手术方式、淋巴结清扫范围、术后综合治疗模式.方法 对1998年1月至2007年12月间收治的不同部位的食管癌1162例采用序贯的腹、胸、颈三切口的手术径路行食管肿瘤切除,应用术前影像、超声定位下穿刺细胞学检查和术中颈部淋巴结抽样活组织快速病理检查三步筛选方法行选择性一期三野淋巴结清扫,一期规范胸腹二野清扫和二期第三野颈部淋巴结清扫.同时,术后积极实施综合治疗.观察总的临床疗效和长期生存.结果 1162例食管癌手术中,手术切除率100％.根治性切除97.6％（1134/1162）.围手术期并发症发生率16.4％（191/1162）,吻合口瘘发生率为0.6％（7/1162）,术后30 d内死亡5例.全组淋巴结转移率52.6 ％（611/1162）,淋巴结转移度12.1％（3 092/25 564）.全组实施一期三野淋巴结清扫348例,阳性准确率为94.8％（330/348）,实施一期二野清扫814例,实施二期第三野颈部淋巴结清扫89例.三野清扫术后并发症明显高于二野清扫（23.6％比13.4％）（χ^2=18.37,P＜ 0.001）,但两者的1、3、5年生存率差异无统计学意义（P＞0.05）.一期三野清扫和二期第三野清扫患者1、3、5年生存率差异亦无统计学意义（P＞0.05）.但不同的淋巴结转移程度预后差异有统计学意义（χ^2=35.57,P＜ 0.001）,不同的分期决定着患者的预后.本组术后综合治疗实施率为87.2％,手术加术后综合治疗者总的1、3、5年生存率分别为92.1％、69.2％、49.6％.结论 序贯三切口切除食管肿瘤及应用三步筛选法选择性淋巴结清扫具有根治彻底、术后并发症少、患者生存质量高、长期生存率较好等优点,是食管癌外科治疗值得临床广泛应用的一种方法.术后积极的综合治疗是今后食管癌治疗的发展方向.     

术后化疗对术后淋巴结阳性胸段食管鳞癌患者预后的影响

目的 分析术后化疗对术后淋巴结阳性胸段食管鳞癌患者预后的影响。方法 回顾性分析419例胸段食管癌患者预后的影响因素。结果 单纯手术患者1、3、5年OS显著低于术后化疗组（χ²=12.802, P=0.000）;而两组患者1、3、5年DFS差异未见统计学意义（χ²=1.159, P=0.282）。多因素分析结果显示,性别、年龄、病变部位、TNM分期、术后化疗和化疗周期数为OS的独立性预后影响因素（P<0.05）;而性别和N分期为DFS的独立性预后影响因素（P<0.05）。分层分析结果显示,相对于单纯手术,术后化疗可以提高男性、年龄≤60岁、胸中下段病变、病变长度≤5.0 cm和ⅢB期患者的OS（P<0.05）,而且可以提高男性和年龄≤60岁患者的DFS（P<0.05）。结论 术后淋巴结阳性胸段食管鳞癌患者预后较差,术后化疗可以提高部分患者的预后。     

食管癌二野淋巴结清扫术后复发规律探讨

Objective To investigate the local-regional recurrence in thoracic esophageal cancer after radical surgery including two-field lymph node dissection and provide evidence for postoperative radiotherapy. Methods We reviewed local-regional recurrence for 134 cases with esophageal squamous cell carcinoma after radical surgery from 2004 to 2009. Results In 134 cases, lymph node metastasis rate,anastomosis recurrence rate and tumor bed recurrence rate was 94. 0%, 9. 7% and 3.7%, respectively. As to the 126 cases with lymph node metastasis, significant difference was detected between mediastinal metastasis, supraclavicular metastasis and abdominal lymph node metastasis (80. 2%, 43.7% and 13.5%,respectively, χ2= 113. 15, P = 0. 000). Furthermore, the relative metastasis rate in upper mediastinum,middle mediastinum and the lower mediastinum was 73.8%, 39.7% and 1.6%, respectively, the difference was statistically significant ( χ2 = 139. 11, P = 0. 000 ). Significant difference was identified between right and left supraclavicular lymph node metastasis (31.7% vs 16. 7%, χ2= 7. 81, P = 0. 005 ).To confirm the analysis above,lymph node metastasis rate of left recurrent laryngeal nerve nodes, (including region 1L, 2L, 4L and 5) ,right recurrent laryngeal nerve nodes, azygos nodes, subcarinal nodes, and 2R region was 38.9%, 43.7%, 15.1%, 34.1% and 25.4%, respectively. Conclusions The main characteristics of local-regional recurrence may be lymph node metastasis for esophageal squamous cell carcinoma after radical surgery. On the contrary, tumor bed recurrence is rare. Dangerous regions include supraclavicular nodes, recurrent laryngeal nerve nodes, azygos nodes as well as subcarinal nodes.     

胸中段淋巴结阳性食管癌术后放疗的临床意义

目的：分析和研究淋巴结阳性的胸中段食管癌术后放疗能否提高生存率,同时对放疗范围提出进一步修改的建议。方法分析2004—2009年在我院手术的有淋巴结转移的胸中段食管鳞癌患者286例,其中手术196例,术后IMRT 90例。采用Kaplan－Meier法计算生存率并Logrank法检验,Cox模型多因素预后分析,采用χ2检验分析不同治疗方式对复发的影响。结果单一手术组（ S）和术后放疗组（ S＋R）5年OS分别为22．9％和37．8％,中位生存时间分别为23．2个月和34．7个月（P＝0．003）;淋巴结转移（LNM）1－2个S组和S＋R组的5年OS分别为27．3％和44．8％（P＝0．017）, LNM≥3个S组和S＋R组的5年OS分别为16．7％和25．0％（ P＝0．043）。 S组N1、N2、N3期腹腔淋巴结转移失败率分别为2．9％、10．9％、20．0％（P＝0．009）。 S＋R组与S组比较纵隔淋巴结转移失败率明显降低（ LNM 1－2个：S＋R 8．0％, S 35．3％, P＝0．003;LNM≥3个时, S＋R 10．0％, S 42．3％, P＝0．001）且明显延长了复发时间（ S＋R 25．1个月与S10．7个月,P＝0．000）。但LNM≥3个S＋R组的血道转移失败率明显高于S组（46．7％比26．1％,P＝0．039）。结论胸中段食管癌淋巴结阳性患者能从术后放疗中获益。 LNM 1－2个可缩小照射范围。 LNM≥3个时妥协放疗剂量是否比妥协照射范围更合理还需前瞻性研究。血道转移失败率高,为化疗提供了治疗依据。     

术后放化疗治疗中晚期食管癌

目的:评价术后放化疗在中晚期食管癌治疗中的作用.方法:2003-2005年间78例符合手术标准的食管癌患者术前随机分为术后放化疗组(A组,38例)和单纯手术组(B组,40例),术后根据患者要求进行了微调(各有2例进行了互换),实际入组:A组38例和B组40例.对比并发症、局部复发率、远处转移率及生存率.结果:平均随访41.7个月,两组对比,并发症差异无统计学意义(P＞0.05).A组局部复发及转移率低于B组(P＜0.05).A组与B组中位生存期比较差异有统计学意义(40 vs 33,P＜0.05),二组1年生存率比较差异无统计学意义(P＞0.05),但3、5年生存率比较A组优于B组(P＜0.05).结论:合理应用术后放化疗可有效提高中晚期食管癌患者的长期生存率.     

术后放化疗治疗中晚期食管癌

目的：评价术后放化疗在中晚期食管癌治疗中的作用。方法：2003-2005年间78例符合手术标准的食管癌患者术前随机分为术后放化疗组（A组,38例）和单纯手术组（B组,40例）,术后根据患者要求进行了微调（各有2例进行了互换）,实际入组：A组38例和B组40例。对比并发症、局部复发率、远处转移率及生存率。结果：平均随访41.7个月,两组对比,并发症差异无统计学意义（P〉0.05）。A组局部复发及转移率低于B组（P〈0.05）。A组与B组中位生存期比较差异有统计学意义（40vs33,P〈0.05）,二组1年生存率比较差异无统计学意义（P〉0.05）,但3、5年生存率比较A组优于B组（P〈0.05）。结论：合理应用术后放化疗可有效提高中晚期食管癌患者的长期生存率。     

Prognostic and clinical evaluation of axillary lymph node metastasis in esophageal cancer

Axillary lymph node metastasis (ALNM) from esophageal cancer is rare. Its prognosis and effective treatments remain unknown. Between 1997 and 2005, esophagectomy was performed in 361 patients with esophageal cancer in our hospital. ALNM was identified in four patients (1.1%). All patients had left ALNM with ipsilateral left supraclavicular lymph node metastasis. In two patients ALNM developed after radical esophagectomy with regional lymphadenectomy and in the other two patients after chemoradiotherapy of primary lesions. Axillary lymphadenectomy with chemoradiotherapy was given to all patients. Median survival time and disease-free survival (DFS) after initial treatment for primary esophageal cancer were 30.5 months and 11.5 months, respectively. One patient, who had a small number of regional lymph node metastases (two lymph nodes) at esophagectomy and prolonged DFS (22 months) until axillary node recurrence, is still alive, 67 months after axillary lymphadenectomy. The other three patients, who had larger numbers of regional lymph node metastases (average, 8.3) and shorter DFS (average, 9.7 months), died of recurrence an average of 13.3 months after axillary lymphadenectomy. In conclusion, although ALNM is considered a type of distant organ metastasis, if it is a solitary recurrence, good survival may be obtained after appropriate loco-regional therapy. The number of metastatic regional lymph nodes at initial esophagectomy and the duration of DFS until axillary node recurrence can help to guide the decision whether aggressive treatments are warranted.     

阴性淋巴结数目对胸段食管癌患者预后的影响

目的:探讨胸段食管癌患者标准淋巴结清扫术中阴性淋巴结数目对患者预后的影响。方法:回顾性分析2000～2006年,汕头市中心医院239例食管癌患者的性别、年龄、肿瘤定位、浸润深度、病理组织分化程度、类型以及阴、阳性淋巴结数目,通过Kaplan-Meier曲线和Cox多因素回归模型,评估上述临床病理参数等与患者生存期之间的相关性。结果:全组患者平均5年生存率44.1%。单因素分析结果显示,阳性淋巴结数目及阴性淋巴结数目对患者5年生存率有显著影响(P0.05)。阴性淋巴结数目≥4的患者,5年生存率(49.1%)明显高于阴性淋巴结数目4的患者(31.5%)(x~2=6.042,P=0.014)。Cox多因素回归分析显示,阳性淋巴结数目(P=0.000,HR=1.370,95%CI=1.204～1.559)及阴性淋巴结数目(P=0.046,HR=0.955,95%CI=0.913～0.999)均可作为影响患者预后的独立影响因素(P0.05)。结论:阴性淋巴结数目是胸段食管癌患者预后的独立影响因素,在今后的食管癌分期标准中可用于改进淋巴结分期。     

Current status of lymph node dissection in gastric cancer

Gastrectomy with lymph node (LN) dissection has been regarded as the standard surgery for gastric cancer (GC), however, the rational extent of lymphadenectomy remains controversial. Though gastrectomy with extended lymphadenectomy beyond D2 is classified as a non-standard gastrectomy, its clinical significance has been evaluated in many studies. Although hard evidence is lacking, D2 plus superior mesenteric vein (No. 14v) LN dissection is recommended when harbor metastasis to No. 6 nodes is suspected in the lower stomach, and dissection of splenic hilar (No. 10) LN can be performed for advanced GC invading the greater curvature of the upper stomach, and D2 plus posterior surface of the pancreatic head (No. 13) LN dissection may be an option in a potentially curative gastrectomy for cancer invading the duodenum. Prophylactic D2+ para-aortic nodal dissection (PAND) was not routinely recommended for advanced GC patients, but therapeutic D2 plus PAND may offer a chance of cure in selected patients, preoperative chemotherapy was considered as the standard treatment for GC with para-aortic node metastasis. There has been no consensus on the extent of lymphadenectomy for the adenocarcinoma of the esophagogastric junction (AEG) so far. The length of esophageal invasion can be used as a reference point for mediastinal LN metastases, and the distance from the esophagogastric junction to the distal end of the tumor is essential for determining the optimal extent of resection. The quality of lymphadenectomy may influence prognosis in GC patients. Both hospital volume and surgeon volume were important factors for the quality of radical gastrectomy. Centralization of GC surgery may be needed to improve prognosis.     

Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection

Background:

Increasing lymph node ratio (LNR) (ratio of metastatic lymph nodes to the total number of harvested lymph nodes) and extramural vascular invasion (EMVI) have been proposed as adverse prognostic indicators in colorectal cancer, although their use remains variable and controversial. The aim of the present study was to assess the prognostic value of LNR and EMVI in predicting survival for patients undergoing curative colon cancer resection.

Methods:

Between 2006 and 2012, 922 patients underwent curative colon cancer resection. Surgical technique and pathological assessment did not change during the study period. Clinical and pathological data were collected from a prospectively maintained database. The primary outcome measure was overall survival and disease-free survival. LNR was separated into five categories based on three previously calculated cutoff values: LNR 0 (no lymph nodes involved), LNR 1 (ratio 0.01<0.17), LNR 2 (ratio 0.18–0.41), LNR 3 (ratio 0.42–0.69), and LNR 4 (ratio >0.70).

Results:

Nine hundred and twenty-two patients underwent colon cancer resection. The median follow-up for survivors was 52.8 months (IQR 34.6–77.6). The median total number of lymph nodes harvested was 16 (IQR13-22). On multivariate analysis, both pN and LNR were strongly associated with overall and disease-free survival. Using the Akaike information criterion (AIC), LNR had greater prognostic value compared with pN. For overall survival, compared with patients in LNR category 0, hazard ratios (95% CI) for those in categories 1, 2, 3 and 4 were 1.37 (1.03,1.82), 2.37 (1.70,3.30), 2.40 (1.57,3.65) and 5.51 (3.16,9.58), respectively. For disease-free survival, patients had hazard ratios (95% CI) of 1.78 (1.25,2.52), 3.79 (2.56,5.61), 2.60 (1.50,4.48) and 4.76 (2.21,10.27), respectively. The presence of EMVI was a significant predictor of decreased overall and disease-free survival (P<0.001).

Conclusions:

This study demonstrated, in the presence of high surgical, oncology and pathological standards, EMVI and increasing LNR were independent predictors of decreased overall and disease-free survival for patients undergoing curative colon cancer resection. LNR was superior to pN stage in predicting overall and disease-free survival.     

胸段食管癌100例淋巴结转移的规律性

目的：探讨胸段食管癌淋巴结转移规律性。方法：2000年3月--2001年6月,采用右后胸、颈、腹三切口施行三野淋巴结清扫食管癌根治术治疗胸段食管癌100例。结果：医院内无手术死亡。全组病人淋巴结转移率54%,颈、纵隔、腹腔淋巴结转移率分别为31%、34%、26%,颈淋巴吉转移率与原发肿瘤浸润深度无明显相关。在颈淋巴结转移中,双侧颈喉返神经旁淋巴结转移明显于锁骨上区淋巴结。结论：①胸段食管癌易发生纵隔、颈部、腹腔淋巴结转移;②胸段食管癌浸润早期即可发生颈淋巴结转移;③颈淋巴结清扫对胸段食管癌术后准确分期有重要意义。