中低位直肠癌系膜环周切缘癌浸润的临床研究
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摘要
目的
直肠癌是常见的恶性肿瘤之一,其发病率及死亡率均较高。手术治疗是直肠癌的主要治疗手段,随着外科学、分子生物学、免疫学等学科的发展,直肠癌的手术治疗也有了很大的进展。在保证手术根治效果的同时,如何能进一步降低局部复发率,提高患者生活质量,一直是人们所关注的问题。
TME手术原则的广泛推广,使直肠癌术后局部复发率显著降低。以往人们对直肠癌远端肠管及系膜切除距离很关注,也做了大量相关研究,明确了远端切除的安全距离。近年来,直肠系膜环周切缘癌浸润(circumferential margin involvement,CMI)日益受到人们的关注,而且越来越多的证据证实CMI是导致直肠癌术后局部复发的重要因素,因此,CMI的研究成为进一步降低肿瘤局部复发的关键所在。
病理大组织切片能够客观且准确地观察直肠癌术后CMI的情况。这种病理学检查方法可以从整体上观察直肠癌转移灶在直肠系膜内的方位及其与肿瘤原发灶和直肠壁的关系,通过这种方法可以准确地观察手术切缘情况,判断是否存在CMI。同时结合免疫组化技术,可以发现环周切缘存在的肿瘤微转移病灶,从而进一步增加CMI的检出率。
本研究通过HE染色病理大组织切片与免疫组化大切片相结合,探讨如何能进一步提高CMI的检出率,并与41例临床病例资料相结合,发现CMI的存在规律,指导临床治疗。
方法
1.HE染色病理大组织切片:通过大组织切片观察CMI情况与临床病理资料的关系,然后进行统计学分析。
2.免疫组织化学法:采用S-P法,按照试剂盒说明书进行操作,采用1:80、1:80、1:40稀释的鼠抗人CK20、CDX2、MMP7单克隆抗体分别检测直肠癌系膜内微转移灶,发现CMI的微转移。PBS代替一抗作为阴性对照。结合临床病理资料对其结果进行相关统计学分析。
结果
HE染色病理组织大切片检测CMI阳性率为21.95%(9/41)。其中在肿瘤分化程度方面,高、中分化组CMI阳性率分别为16.67%(1/6)、8.00%(2/25),而在低分化组CMI阳性率高达60.00%(6/10),统计学分析显示,高、中分化组与低分化组比较存在显著性差异(P=0.004<0.05),可认为CMI在低分化组的阳性率高于高、中分化组。在肿瘤位置(肿瘤下缘距齿线距离)方面,<5cm组CMI阳性率46.15%(6/13)高于≥5cm组阳性率10.71%(3/28),统计学分析显示两组存在显著性差异(P=0.03<0.05)。在不同的术式方面,Miles组CMI阳性率46.15%(6/13)高于Dixon组的阳性率10.71%(3/28) ,统计学分析显示两组存在显著性差异(P=0.03<0.05)。而患者性别、年龄、肿瘤大体类型、浸润深度、淋巴结转移情况、手术方法(开腹/腹腔镜)方面均与CMI阳性率无明显相关性(P>0.05)。
免疫组化结果显示,CK20、CDX2、MMP7切片检测CMI阳性率分别为29.27%(12/41)、31.71%(13/41)、26.83%(11/41)。其中在肿瘤分化程度方面,三项指标均证实高、中分化组CMI阳性率低于低分化组,统计学分析存在显著性差异(P<0.05)。在肿瘤位置(肿瘤下缘距齿线距离)方面,三项指标均显示<5cm组CMI阳性率高于≥5cm组,统计学显示存在显著性差异(P<0.05)。在不同的术式方面,三项指标均显示Miles手术组CMI阳性率高于Dixon手术组,统计学分析显示两组比较存在显著性差异(P<0.05)。CK20、CDX2显示患者性别、年龄、肿瘤大体类型、浸润深度、淋巴结转移情况、手术方法(开腹/腹腔镜)均与CMI阳性率无明显相关性(P>0.05)。在上述临床资料方面,MMP7显示在淋巴结转移方面,N0、N1、N2组CMI阳性率分别为8.70%(2/23)、46.15%(6/13)、60.00%(3/5),统计学分析显示N0组与N1、N2组比较存在显著性差异(P=0.009),可认为无淋巴结转移组CMI阳性率低于存在淋巴结转移组CMI阳性率。
采用HE染色与免疫组化三项指标联合检测的方法共检测出15例存在CMI,阳性检出率为36.59%(15/41)。HE染色、CK20、CDX2、MMP7切片检测CMI阳性率分别为21.95%(9/41)、29.27%(12/41)、31.71%(13/41)、26.83%(11/41),两两比较CMI阳性检出率均无明显差异(P>0.05)。统计学分析显示HE染色与免疫组化三项抗体指标联合检测较单用HE染色大切片或一种抗体指标检测CMI检出率高(P<0.05)。
结论
1病理大组织切片能客观准确地观察直肠癌术后CMI情况,术后应常规进行该项检查。
2 HE染色与免疫组化CK20、CDX2、MMP7三种指标联合检测CMI的阳性率较高。
3对于术后检测存在CMI的患者,无论病理分期的早晚,都应行正规的放化疗。
4肿瘤分化程度低、肿瘤位置低、存在淋巴结转移及行Miles手术是CMI存在的高危因素。
5 CMI阳性率与患者的性别、年龄、肿瘤大体类型、浸润深度、手术方法(开腹/腹腔镜)无明显关系。
Objective
Rectal cancer is one of the common malignant tumors,its incidence and mortality are still high.Surgical treatment is still the first choice of management for Patients.with the development of surgery,molecularbiology and immunology etc,Surgical treatment also have great development.how to reduce local recurrence ulteriorly,improve PostoPerative life quality,at the same time,ensure the effect of surgical treatment,become a hot question .
Widely introduction of total mesorectal exeision(TME) had significantly reduce local recurrence following the curative resection.beforetime,people attached importance to the distal clearance margin and had done many research,defined a safe distal clearance margin.currently,people pay more attention to the circumferential margin involvement,and more and more researches had proved that circumferential margin involvement was a important factor of local recurrence after the curative rese- ction.Researches of circumferential margin involvement is a key of reducing the local recurrence.
Pathologic large slice can observe circumferential margin involvement distinctly.it can observe holistic mesorectal,the orientation of metastasis,and make sure the relation of metastasis and the primary affection.this method can accurately find circumferential margin involvement,combine with immunohistochemical technique,it can find micrometastasis in circumferential resection margin,enhance the check-up rates of circumferential margin involvement.
This study combined pathologic large slice and Immun- ohistochemical technique to discuss how to enhance the check-up rates of circumferential margin involvement,and studied 41 patients'clinicopathlogic characteridtion,detected the rule of circumferential margin involvement,and leaded a reasonable clinical treatment.
Methods
1.Pathologic large slice with hematoxylin and eosin:we used this method to detect the relationship between circumferential margin involvement and clincopathologic features,then analyzed the results.
2.Immunohistochemistry was performed by using the SP method. We used mouse anti-CK20 (1:80 dilution), mouse anti-CDX2 (1:80 dilution),mouse anti-MMP7 (1:40 dilution) to detect circumferential margin involvement in samples, then analyzed the results with the clincopathologic features .
Results
9 patients (21.95%) with positive circumferential resection margin were detected by pathologic large slice with hematoxylin and eosin.On differentiation of tumour,60.7% poorly differentiated specimens were detected circumferential margin involvement,while moderate and well-differentiated cancer specimens were only 8.00% and 16.7% respectively (P=0. 004<0.05).About station of tumour,positive circumferential resection margin was more frequent in<5cm specimens (46.15%),compared with≥5cm specimens(10.71%)(P=0.003 <0.05).About different operation mode(Miles/Dixon), positive circumferential resection margin was more frequent in Miles specimens(46.15%),Compared with Dixon specimens(10.71%) (P=0.003<0.05).No significant correlations were found between circumferential resection margin and other clincopathologic features,such as gender,age,tumor invasion,lymph node metast- asis,pathology general classification,operation method (P>0.05).
By immunohistochemistry analysis on samples,CK20, CDX2,MMP7 detect positive circumferential resection margin 29.27%(12/41)、31.71%(13/41)、26.83%(11/41) respectively. About differentiation of tumour,three antibodies proved that positive circumferential resection margin was more frequent in poorly differentiated specimens than moderate and well-differentiated specimens(P<0.05).About station of tumour,three antibodies proved that positive circumferential resection margin was more frequent in<5cm specimens than in≥5cm specimens (P<0.05).CK20 and CDX2 proved that no significant correlations were found between circumferential resection margin and other clincopathologic features,such as gender,age, tumor invasion,lymph node metastasis,pathology general classi- fication,operation method(P>0.05).But about lymph node metastasisand, MMP7 prove that 8.70% N0 lymph node metastasis specimens were detected circumferential margin involvement, while N1 and N2 lymph node metastasis specimens were 46.15% and 6.00% respectively (P=0. 009).
15 patients (36.59%) with positive circumferential resection margin were detect by combining pathologic large slice and im-munohistochemical technique.large slice with H-E,CK20,CDX2, MMP7 detected positive circumferential resection margin 21.95%,29.27%(12/41)、31.71%(13/41)、26.83%(11/41) respectively.There were no significant difference between each other (P>0.05).Combining pathologic large slice and immunohistochemical technique could get more positive circumferential resection margin than single method or sigle antibody(P<0.05)
Conclusions
1 Pathologic large slice can observe circumferential margin involvement distinctly.It should be a routine examination following the curative resection.
2 Combining pathologic large slice and immunohistoch- emical technique could get more positive circumferential resection margin.
3 Whether TNM stage is early or not,the patient who have positive circumferential resection margin should get normally postoperative adjuvant therapy.
4 Circumferential resection margin of middle and rectal cancer has significant correlation with tumor differentiation, tumor station,lymph node metastasis,different operation mode (Miles/Dixon).
5 Circumferential resection margin of middle and rectal cancer has no significant correlation with gender,age,tumor invasion,pathology general classification,operation method.
直肠癌是常见的恶性肿瘤之一,其发病率及死亡率均较高。手术治疗是直肠癌的主要治疗手段,随着外科学、分子生物学、免疫学等学科的发展,直肠癌的手术治疗也有了很大的进展。在保证手术根治效果的同时,如何能进一步降低局部复发率,提高患者生活质量,一直是人们所关注的问题。
TME手术原则的广泛推广,使直肠癌术后局部复发率显著降低。以往人们对直肠癌远端肠管及系膜切除距离很关注,也做了大量相关研究,明确了远端切除的安全距离。近年来,直肠系膜环周切缘癌浸润(circumferential margin involvement,CMI)日益受到人们的关注,而且越来越多的证据证实CMI是导致直肠癌术后局部复发的重要因素,因此,CMI的研究成为进一步降低肿瘤局部复发的关键所在。
病理大组织切片能够客观且准确地观察直肠癌术后CMI的情况。这种病理学检查方法可以从整体上观察直肠癌转移灶在直肠系膜内的方位及其与肿瘤原发灶和直肠壁的关系,通过这种方法可以准确地观察手术切缘情况,判断是否存在CMI。同时结合免疫组化技术,可以发现环周切缘存在的肿瘤微转移病灶,从而进一步增加CMI的检出率。
本研究通过HE染色病理大组织切片与免疫组化大切片相结合,探讨如何能进一步提高CMI的检出率,并与41例临床病例资料相结合,发现CMI的存在规律,指导临床治疗。
方法
1.HE染色病理大组织切片:通过大组织切片观察CMI情况与临床病理资料的关系,然后进行统计学分析。
2.免疫组织化学法:采用S-P法,按照试剂盒说明书进行操作,采用1:80、1:80、1:40稀释的鼠抗人CK20、CDX2、MMP7单克隆抗体分别检测直肠癌系膜内微转移灶,发现CMI的微转移。PBS代替一抗作为阴性对照。结合临床病理资料对其结果进行相关统计学分析。
结果
HE染色病理组织大切片检测CMI阳性率为21.95%(9/41)。其中在肿瘤分化程度方面,高、中分化组CMI阳性率分别为16.67%(1/6)、8.00%(2/25),而在低分化组CMI阳性率高达60.00%(6/10),统计学分析显示,高、中分化组与低分化组比较存在显著性差异(P=0.004<0.05),可认为CMI在低分化组的阳性率高于高、中分化组。在肿瘤位置(肿瘤下缘距齿线距离)方面,<5cm组CMI阳性率46.15%(6/13)高于≥5cm组阳性率10.71%(3/28),统计学分析显示两组存在显著性差异(P=0.03<0.05)。在不同的术式方面,Miles组CMI阳性率46.15%(6/13)高于Dixon组的阳性率10.71%(3/28) ,统计学分析显示两组存在显著性差异(P=0.03<0.05)。而患者性别、年龄、肿瘤大体类型、浸润深度、淋巴结转移情况、手术方法(开腹/腹腔镜)方面均与CMI阳性率无明显相关性(P>0.05)。
免疫组化结果显示,CK20、CDX2、MMP7切片检测CMI阳性率分别为29.27%(12/41)、31.71%(13/41)、26.83%(11/41)。其中在肿瘤分化程度方面,三项指标均证实高、中分化组CMI阳性率低于低分化组,统计学分析存在显著性差异(P<0.05)。在肿瘤位置(肿瘤下缘距齿线距离)方面,三项指标均显示<5cm组CMI阳性率高于≥5cm组,统计学显示存在显著性差异(P<0.05)。在不同的术式方面,三项指标均显示Miles手术组CMI阳性率高于Dixon手术组,统计学分析显示两组比较存在显著性差异(P<0.05)。CK20、CDX2显示患者性别、年龄、肿瘤大体类型、浸润深度、淋巴结转移情况、手术方法(开腹/腹腔镜)均与CMI阳性率无明显相关性(P>0.05)。在上述临床资料方面,MMP7显示在淋巴结转移方面,N0、N1、N2组CMI阳性率分别为8.70%(2/23)、46.15%(6/13)、60.00%(3/5),统计学分析显示N0组与N1、N2组比较存在显著性差异(P=0.009),可认为无淋巴结转移组CMI阳性率低于存在淋巴结转移组CMI阳性率。
采用HE染色与免疫组化三项指标联合检测的方法共检测出15例存在CMI,阳性检出率为36.59%(15/41)。HE染色、CK20、CDX2、MMP7切片检测CMI阳性率分别为21.95%(9/41)、29.27%(12/41)、31.71%(13/41)、26.83%(11/41),两两比较CMI阳性检出率均无明显差异(P>0.05)。统计学分析显示HE染色与免疫组化三项抗体指标联合检测较单用HE染色大切片或一种抗体指标检测CMI检出率高(P<0.05)。
结论
1病理大组织切片能客观准确地观察直肠癌术后CMI情况,术后应常规进行该项检查。
2 HE染色与免疫组化CK20、CDX2、MMP7三种指标联合检测CMI的阳性率较高。
3对于术后检测存在CMI的患者,无论病理分期的早晚,都应行正规的放化疗。
4肿瘤分化程度低、肿瘤位置低、存在淋巴结转移及行Miles手术是CMI存在的高危因素。
5 CMI阳性率与患者的性别、年龄、肿瘤大体类型、浸润深度、手术方法(开腹/腹腔镜)无明显关系。
Objective
Rectal cancer is one of the common malignant tumors,its incidence and mortality are still high.Surgical treatment is still the first choice of management for Patients.with the development of surgery,molecularbiology and immunology etc,Surgical treatment also have great development.how to reduce local recurrence ulteriorly,improve PostoPerative life quality,at the same time,ensure the effect of surgical treatment,become a hot question .
Widely introduction of total mesorectal exeision(TME) had significantly reduce local recurrence following the curative resection.beforetime,people attached importance to the distal clearance margin and had done many research,defined a safe distal clearance margin.currently,people pay more attention to the circumferential margin involvement,and more and more researches had proved that circumferential margin involvement was a important factor of local recurrence after the curative rese- ction.Researches of circumferential margin involvement is a key of reducing the local recurrence.
Pathologic large slice can observe circumferential margin involvement distinctly.it can observe holistic mesorectal,the orientation of metastasis,and make sure the relation of metastasis and the primary affection.this method can accurately find circumferential margin involvement,combine with immunohistochemical technique,it can find micrometastasis in circumferential resection margin,enhance the check-up rates of circumferential margin involvement.
This study combined pathologic large slice and Immun- ohistochemical technique to discuss how to enhance the check-up rates of circumferential margin involvement,and studied 41 patients'clinicopathlogic characteridtion,detected the rule of circumferential margin involvement,and leaded a reasonable clinical treatment.
Methods
1.Pathologic large slice with hematoxylin and eosin:we used this method to detect the relationship between circumferential margin involvement and clincopathologic features,then analyzed the results.
2.Immunohistochemistry was performed by using the SP method. We used mouse anti-CK20 (1:80 dilution), mouse anti-CDX2 (1:80 dilution),mouse anti-MMP7 (1:40 dilution) to detect circumferential margin involvement in samples, then analyzed the results with the clincopathologic features .
Results
9 patients (21.95%) with positive circumferential resection margin were detected by pathologic large slice with hematoxylin and eosin.On differentiation of tumour,60.7% poorly differentiated specimens were detected circumferential margin involvement,while moderate and well-differentiated cancer specimens were only 8.00% and 16.7% respectively (P=0. 004<0.05).About station of tumour,positive circumferential resection margin was more frequent in<5cm specimens (46.15%),compared with≥5cm specimens(10.71%)(P=0.003 <0.05).About different operation mode(Miles/Dixon), positive circumferential resection margin was more frequent in Miles specimens(46.15%),Compared with Dixon specimens(10.71%) (P=0.003<0.05).No significant correlations were found between circumferential resection margin and other clincopathologic features,such as gender,age,tumor invasion,lymph node metast- asis,pathology general classification,operation method (P>0.05).
By immunohistochemistry analysis on samples,CK20, CDX2,MMP7 detect positive circumferential resection margin 29.27%(12/41)、31.71%(13/41)、26.83%(11/41) respectively. About differentiation of tumour,three antibodies proved that positive circumferential resection margin was more frequent in poorly differentiated specimens than moderate and well-differentiated specimens(P<0.05).About station of tumour,three antibodies proved that positive circumferential resection margin was more frequent in<5cm specimens than in≥5cm specimens (P<0.05).CK20 and CDX2 proved that no significant correlations were found between circumferential resection margin and other clincopathologic features,such as gender,age, tumor invasion,lymph node metastasis,pathology general classi- fication,operation method(P>0.05).But about lymph node metastasisand, MMP7 prove that 8.70% N0 lymph node metastasis specimens were detected circumferential margin involvement, while N1 and N2 lymph node metastasis specimens were 46.15% and 6.00% respectively (P=0. 009).
15 patients (36.59%) with positive circumferential resection margin were detect by combining pathologic large slice and im-munohistochemical technique.large slice with H-E,CK20,CDX2, MMP7 detected positive circumferential resection margin 21.95%,29.27%(12/41)、31.71%(13/41)、26.83%(11/41) respectively.There were no significant difference between each other (P>0.05).Combining pathologic large slice and immunohistochemical technique could get more positive circumferential resection margin than single method or sigle antibody(P<0.05)
Conclusions
1 Pathologic large slice can observe circumferential margin involvement distinctly.It should be a routine examination following the curative resection.
2 Combining pathologic large slice and immunohistoch- emical technique could get more positive circumferential resection margin.
3 Whether TNM stage is early or not,the patient who have positive circumferential resection margin should get normally postoperative adjuvant therapy.
4 Circumferential resection margin of middle and rectal cancer has significant correlation with tumor differentiation, tumor station,lymph node metastasis,different operation mode (Miles/Dixon).
5 Circumferential resection margin of middle and rectal cancer has no significant correlation with gender,age,tumor invasion,pathology general classification,operation method.
引文
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11 Tilney HS,Tekkis PP,Sains PS,et al.Factors affecting circumferential resection margin involvement after rectal cancer excision[J].Dis Colon Rectum.2007 Jan;50(1):29~36.pathol,2002,26(3):350~35
1 Quirke P,Durdey P,Dixon MF,et al.Local recurrence of rectal adenocarcinoma due to inadequate surgical reseclion. Histopathological study of lateral tumor spread and surgical excision[J]. lancet,1986,2(8514):996~999
2 Adam IJ mohamdee MO,Martin IG, et al.Role of Circumferential margin involvement in the local recurrence of rectal cancer[J].Lancet,1994,344(8924):707~711
3 Wibe A,Rendedal PR,Svensson E,etal.Prognostic significance of the circumferential resection margin followingtotal mesorectal excision for rectal cancer [J].Br J Surg,2002,89(3):327~334
4 Nagtegall ID,Marijnen CA,Kranenbarg EK,et al.Rates ofCircumferentia margin involvement is still an important predietor of local recurrence in rectal carcinoma:not one mlli- meter but two millimeters is the limit. Am J Surg pathol,2002,26(3):350~357
5 Baik SH,Kim NK,Lee YC,etal.Prognostic significance of circumferential resection margin following totalmesorectal excision and adjuvant chemoradiotherapy in patients with rectal cancer[J].Ann Surg Oncol,2007, 14(2):462~469
6 Tilney HS,Tekkis PP,Sains PS,et al.Factors affecting circumferential resection margin involvement after rectal cancer excision[J].Dis Colon Rectum.2007 Jan;50(1):29~36
7 王存,周总光,王昭,等.大组织切片研究直肠癌在直肠系膜内及环周切缘的播散. 四川大学学报.2004;35(5):723~726
8 王存,周总光,徐丹,等.直肠癌系膜切缘和盆腔侧方转移规律的研究及生存分析.中华胃肠外科志.2006;9(5):474~476
9 王存,周总光,王昭,等.直肠癌系膜区域转移与微转移的病理学研究.中国实用外科杂.2006;26(1):945~948
10 吴泽,宇万,进赵刚,等.中下段直肠癌系膜环周切缘的临床研究.中华普通外科杂志.2007;22(10):724~726
11 万进,吴泽宇,杜嘉林,等.中下段直肠癌直肠系膜转移的研究.中华外科杂志.2006;44(13):894~896
12 Heald RJ,Husband EM,Ryall RD.The mesorectum in rectal cancer surgery the clue to pelvic recurrence[J]?Br J Surg, 1982,69(10):613~616
13 Chess in DB Guillem JG.Surgical issues in rectal cancer a 2004 update[J].Clin Colorectal Cancer,2004,4(4):200~240
14 Lahaye MJ,Engelen SM,NelemansPJ,et al.Imaging for predicting the risk factors-the circumferential resection margin and nodal disease of local recurrence in rectal cancer:a metaanalysis[J].Semin Ultrasound CT MR.2005; 26(4):259~268
15 Mendenhall WM,Vauthey JN,Zloteeki RA,et al.Preoperative chemoradiation for locally advanced rectal adenocarcinom- athe University of Florida experience[J].Semin Surg Oncol, 2003,21:261~264
16 Gosens MJ,Klaassen RA,Tan-Go I,et al.Circumferential mar- gin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma[J].Clin Cancer Res.2007 15;13(22Pt1): 6617~662
17 Hayashi N,Ito I,Yanagisawa A,et al.Genetic diagnosis of lymph node metastases in colorectal cancer[J].Lancet,1995, 345:1257~1259
18 Wong LS,Cantrill JE,Fahmy M,et al.Detection of circulating tumor cells and nodel metastasis by reverse transcriptase polymerase chain reaction technique[J].Brit J Surg,1996,83: 20
19 Raj GV,Moreno JG,Gomella LG.Utilization of polymerase chain reaction technology in the detection of solid tumors [J].J Cancer 1998,82(8):1419~1442
20 Hoon D,Wang Y,dale P,et al.Detection of occult melanoma cells in blood with a mutiplemarker polymerase chainreaction assay[J].J Clin Oncol,1995,8:2109~2106
21 Moll R,Loewe A,Lauffr J,et al.Cytokeratin 20 in human carcinomas[J].Am J Pathol,1992,140:427
22 Noura S,Yamamoto H,Ohnishi T,et al.Comparative detection of lymph node micrometastases of stageII colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry.J Clin Oncol,2002,15(20920):4232~ 4241
23 李世拥.大肠癌患者门静脉血癌细胞检测的临床意义[J].中华科杂志,1999,37(4):214
24 Beck F,Chawengsaksophak K,Luckett J,et al.A study of regional gut endoderm potency by analysis of CDX2 null mutant chimaeric mice.Devel Biol,2003,255;399~406
25 Mizoshita T,lnada K,Tsukamoto T,et al.Expression of CDX1 and CDX2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa-with special emphasis on participation in intestinal metaplasia of the human stomach[J].Gastrio Cancer 2001,4(4):185~191
26 Phillips RW ,Frierson HF Jr,Moskaluk CA.CDX2 as a marker of epithelial intestinal differentiation in the esophagus[J].Am J Surd Pathol,2003,27(11):1442~1447
27 杨周亮,应伟募,路喜安,等.结直肠癌中 CDX2, ki67 的表达及 DNA 倍体分析[J].肿瘤学杂志,2007,13(2):104~105
28 Mori M,Barnard GF,Mimori K,et al.Overexpression of matrix metalloproteinase-7 mRNA in human colon carcino- mas[J].Cancer,1995,75(6):1516~1519
29 NoeV,Fingleton B,Jacobs K,et al.Release of an invasion promoter E-cadherin fragment by matrilysin and stromelys- in1[J].J Cell Sci,2001,114 (Pt1):111~118
30 Leeman MF,Curran S,Murray GI.New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression [J].J Pathol,2003,201(4):528~ 534
31 秦千子,黄顺荣,焦伟,等.结直肠癌MMP-7和MMP-13的表达和意义.广西医学.2005,27(10):1539~1542
2 Chess in DB,Guillem JG. Surgical issues in rectal cancer a 2004 update [J]. Clin Colorectal Cancer,2004,4(4):200~240
3 Quirke P, Durdey P, Dixon MF, et al. Local recurrence of rectal adenocarcinoma due to inadequate surgical reseclion. Histopathological study of lateral tumor spread and surgical excision[J]. lancet, 1986, 2(8514): 996~999
4 Nagtegall ID,Marijnen CA,Kranenbarg EK,et al. Rates of Circumferentia margin involvement is still an important predietor of local recurrence in rectal carcinoma:not one mllimeter but two millimeters is the limit. Am J Surg pathol,2002,26(3):350~35
5 Wibe A, Rendedal PR, Svensson E, etal. Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer [J]. Br J Surg, 2002, 89(3): 327~334
6 Moll R,Loewe A,Lauffr J,et al.Cytokeratin 20 in human carcinomas[J].Am J Pathol,1992,140:427
7 Noura S, Yamamoto H, Ohnishi T, et al.Comparative detection of lymph node micrometastases of stageII colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. JClinOncol, 2002, 15(20920) :4232~4241
8 Beck F, Chawengsaksophak K, Luckett J, et al.A study of regional gut endoderm potency by analysis of CDX2 null mutant chimaeric mice.Devel Biol, 2003,255;399~406
9 Mori M, Barnard GF,Mimori K,et al.Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas[J]. Gancer, 1995, 75(6):1516~1519
10 Leeman MF,Curran S,Murray GI.New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression [J].J Pathol,2003,201(4):528~534
11 Tilney HS,Tekkis PP,Sains PS,et al.Factors affecting circumferential resection margin involvement after rectal cancer excision[J].Dis Colon Rectum.2007 Jan;50(1):29~36.pathol,2002,26(3):350~35
1 Quirke P,Durdey P,Dixon MF,et al.Local recurrence of rectal adenocarcinoma due to inadequate surgical reseclion. Histopathological study of lateral tumor spread and surgical excision[J]. lancet,1986,2(8514):996~999
2 Adam IJ mohamdee MO,Martin IG, et al.Role of Circumferential margin involvement in the local recurrence of rectal cancer[J].Lancet,1994,344(8924):707~711
3 Wibe A,Rendedal PR,Svensson E,etal.Prognostic significance of the circumferential resection margin followingtotal mesorectal excision for rectal cancer [J].Br J Surg,2002,89(3):327~334
4 Nagtegall ID,Marijnen CA,Kranenbarg EK,et al.Rates ofCircumferentia margin involvement is still an important predietor of local recurrence in rectal carcinoma:not one mlli- meter but two millimeters is the limit. Am J Surg pathol,2002,26(3):350~357
5 Baik SH,Kim NK,Lee YC,etal.Prognostic significance of circumferential resection margin following totalmesorectal excision and adjuvant chemoradiotherapy in patients with rectal cancer[J].Ann Surg Oncol,2007, 14(2):462~469
6 Tilney HS,Tekkis PP,Sains PS,et al.Factors affecting circumferential resection margin involvement after rectal cancer excision[J].Dis Colon Rectum.2007 Jan;50(1):29~36
7 王存,周总光,王昭,等.大组织切片研究直肠癌在直肠系膜内及环周切缘的播散. 四川大学学报.2004;35(5):723~726
8 王存,周总光,徐丹,等.直肠癌系膜切缘和盆腔侧方转移规律的研究及生存分析.中华胃肠外科志.2006;9(5):474~476
9 王存,周总光,王昭,等.直肠癌系膜区域转移与微转移的病理学研究.中国实用外科杂.2006;26(1):945~948
10 吴泽,宇万,进赵刚,等.中下段直肠癌系膜环周切缘的临床研究.中华普通外科杂志.2007;22(10):724~726
11 万进,吴泽宇,杜嘉林,等.中下段直肠癌直肠系膜转移的研究.中华外科杂志.2006;44(13):894~896
12 Heald RJ,Husband EM,Ryall RD.The mesorectum in rectal cancer surgery the clue to pelvic recurrence[J]?Br J Surg, 1982,69(10):613~616
13 Chess in DB Guillem JG.Surgical issues in rectal cancer a 2004 update[J].Clin Colorectal Cancer,2004,4(4):200~240
14 Lahaye MJ,Engelen SM,NelemansPJ,et al.Imaging for predicting the risk factors-the circumferential resection margin and nodal disease of local recurrence in rectal cancer:a metaanalysis[J].Semin Ultrasound CT MR.2005; 26(4):259~268
15 Mendenhall WM,Vauthey JN,Zloteeki RA,et al.Preoperative chemoradiation for locally advanced rectal adenocarcinom- athe University of Florida experience[J].Semin Surg Oncol, 2003,21:261~264
16 Gosens MJ,Klaassen RA,Tan-Go I,et al.Circumferential mar- gin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma[J].Clin Cancer Res.2007 15;13(22Pt1): 6617~662
17 Hayashi N,Ito I,Yanagisawa A,et al.Genetic diagnosis of lymph node metastases in colorectal cancer[J].Lancet,1995, 345:1257~1259
18 Wong LS,Cantrill JE,Fahmy M,et al.Detection of circulating tumor cells and nodel metastasis by reverse transcriptase polymerase chain reaction technique[J].Brit J Surg,1996,83: 20
19 Raj GV,Moreno JG,Gomella LG.Utilization of polymerase chain reaction technology in the detection of solid tumors [J].J Cancer 1998,82(8):1419~1442
20 Hoon D,Wang Y,dale P,et al.Detection of occult melanoma cells in blood with a mutiplemarker polymerase chainreaction assay[J].J Clin Oncol,1995,8:2109~2106
21 Moll R,Loewe A,Lauffr J,et al.Cytokeratin 20 in human carcinomas[J].Am J Pathol,1992,140:427
22 Noura S,Yamamoto H,Ohnishi T,et al.Comparative detection of lymph node micrometastases of stageII colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry.J Clin Oncol,2002,15(20920):4232~ 4241
23 李世拥.大肠癌患者门静脉血癌细胞检测的临床意义[J].中华科杂志,1999,37(4):214
24 Beck F,Chawengsaksophak K,Luckett J,et al.A study of regional gut endoderm potency by analysis of CDX2 null mutant chimaeric mice.Devel Biol,2003,255;399~406
25 Mizoshita T,lnada K,Tsukamoto T,et al.Expression of CDX1 and CDX2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa-with special emphasis on participation in intestinal metaplasia of the human stomach[J].Gastrio Cancer 2001,4(4):185~191
26 Phillips RW ,Frierson HF Jr,Moskaluk CA.CDX2 as a marker of epithelial intestinal differentiation in the esophagus[J].Am J Surd Pathol,2003,27(11):1442~1447
27 杨周亮,应伟募,路喜安,等.结直肠癌中 CDX2, ki67 的表达及 DNA 倍体分析[J].肿瘤学杂志,2007,13(2):104~105
28 Mori M,Barnard GF,Mimori K,et al.Overexpression of matrix metalloproteinase-7 mRNA in human colon carcino- mas[J].Cancer,1995,75(6):1516~1519
29 NoeV,Fingleton B,Jacobs K,et al.Release of an invasion promoter E-cadherin fragment by matrilysin and stromelys- in1[J].J Cell Sci,2001,114 (Pt1):111~118
30 Leeman MF,Curran S,Murray GI.New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression [J].J Pathol,2003,201(4):528~ 534
31 秦千子,黄顺荣,焦伟,等.结直肠癌MMP-7和MMP-13的表达和意义.广西医学.2005,27(10):1539~1542