The importance of accurate pathological assessment of lymph node involvement in colorectal cancer

This review presents an up-to-date analysis of the importance of accurate pathological lymph node staging in colorectal cancer. Lymph node staging is reliant on the technique of the surgeon and the pathologist as well as methods employed in the histopathology laboratory, and is vital for determining appropriate therapy. The significance of micrometastatic nodal disease is evaluated and new techniques for pathological evaluation are discussed. Recommendations for evaluation of lymph node status in colorectal cancer are provided based on current scientific evidence, and standardization of pathological dissection and laboratory handling is advocated.     

Lymph node retrieval in colorectal cancer resection specimens: national standards are achievable,and low numbers are associated with reduced survival

Objectives The current guidelines identify the retrieval of at least 12 lymph nodes as crucial for accurate staging of colorectal cancer. We set out to review our figures from a single centre to see whether this standard has been met, and to examine for factors which may influence the number of lymph nodes retrieved. The influence of a low lymph node harvest on survival in patients with Dukes’ A and B cancers was specifically investigated. Method Data were collected from all patients with colorectal cancer undergoing resectional surgery from our prospectively compiled database between June 1998 and May 2007. A multivariate analysis was performed to identify factors resulting in low lymph node yields in those patients undergoing formal resection. Survival analyses were performed in patients with Dukes’ A and B cancers to assess whether a low lymph node yield negatively impacted on survival. Results A total of 2449 patients underwent formal resection and were included in the analysis. The median lymph node retrieval was 13 nodes (range 0–136). On multivariate analysis, preoperative chemo‐radiotherapy, operation type, specimen length and patient age all independently influenced lymph node retrieval. Patient gender, ethnicity, operative mode, operative team and consultant presence had no influence. Survival in patients with Dukes’ A and B cancers was significantly reduced if <12 nodes were sampled. Conclusions As a unit, we are achieving the national standard for lymph node harvest. This standard was maintained whether the surgeon performing the surgery was a consultant or a trainee, and also when the surgery was performed in the emergency setting. These data support the concept of 12 nodes being required for accurate staging.     

Detection of lymph node metastases in colorectal carcinoma

The detection of lymph node metastases is the single most important prognostic factor for patients with colorectal cancer. This review outlines the difficulties and methods of detecting positive lymph node metastases in this disease. An outline of traditional diagnostic methods including preoperative ultrasound and cross sectional imaging techniques are evaluated alongside newer modalities including immunoscintography and PET scanning and intraoperative radioguided imaging. Pathological methods of detecting positive nodal disease using standard histopathological staging, enhanced lymph node harvesting and determination of micrometastases are also discussed.     

Intra-operative injection of Patent Blue V dye to facilitate nodal staging in colorectal cancer

Objectives Routine histopathology may understage colorectal cancer by failing to detect involved lymph nodes. This study examined the feasibility of dye staining those lymph nodes most likely to harbour metastases. Patients and methods Patent Blue V dye 2.5% was injected intra‐operatively into left‐sided colorectal carcinomas prior to resection in 19 patients. Results Blue‐stained nodes were found in 12/19 patients (63%). Examination of blue‐stained nodes alone correctly identified overall nodal status in 11 (92%) of these 12 patients. Conclusion The technique needs to be refined further. Nonetheless, intra‐operative lymph node staining using blue dye offers the prospect of improving the ease and accuracy of nodal staging in colorectal cancer.     

Adequacy of nodal harvest in colorectal cancer: A consecutive cohort study

The presence of nodal metastasis is a critical component of staging in colorectal cancer. Accurate assessment of nodal status requires sufficient node sampling, although the number of such nodes is controversial, with recommendations ranging from 6 to 17 nodes. The purpose of this study was to describe the nodal harvest in colorectal cancer and to identify factors associated with adequate lymph node harvest. Pathology reports from consecutive patients with newly diagnosed colorectal cancer undergoing resection between January 1997 and December 2000 at a tertiary care academic institution were reviewed. Identification of 12 or more lymph nodes was considered to be an adequate nodal harvest based on the current American Joint Committee on Cancer recommendations. Among the 579 consecutive specimens, the number of nodes identified was not stated for 10 (1.7%). Of the remaining 569 specimens, 4700 nodes were identified with a mean of 8.3 nodes per patient (median 7, range 0 to 60). Nodal metastases were identified in 219 patients (38.5%). Patients with one or more positive nodes had greater nodal harvest than those with negative nodes (9.5 vs. 8.2, respectively; P=0.03). Only 22.4% of patients were found to have an adequate nodal harvest (>-12 nodes). Right-sided resections, high surgeon volume, and gross examination of specimens by a staff pathologist were associated with higher nodal harvests, compared to left-sided resections, low surgeon volume, and gross examination of specimens by a pathology resident/technologist, respectively. There was no association with pathologist volume. In this study, nodal harvest in patients undergoing resection for colorectal cancer was highly variable. This problem appears to be multifactorial, and is related to patient, pathologic, and surgical factors. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002     

结直肠癌前哨淋巴结导航技术的运用与评价

Sentinel lymph node (SLN), the hypothetical first regional lymph node or group of lymph nodes to received lymphatic drainage from a primary tumor, can predict the likelihood of further nodal involvement. SLN mapping was initially applied to the treatment of breast cancer and melanoma, and it also shows gratifying effect on thyroid cancer, pancreatic cancer and gastrointestinal tumors. The development of SLN mapping in colorectal cancer has brought us a new approach to design personalized operation and adjuvant therapy plans. However,various SLN mapping techniques in colorectal cancer available present fluctuant navigation performances, which need to be replaced by an economical, convenient and accurate tracing technique. Hopefully the optimized SLN mapping can play a more important role in the management of increasing occurred early colorectal cancer.     

结直肠癌前哨淋巴结转移相关蛋白的蛋白组学研究

目的 筛选前哨淋巴结(SLN)中与结直肠癌早期转移相关的蛋白质.方法 术中取43名结直肠癌早期患者的SLN及对应的正常淋巴结(NLN).提取SLN和NLN两组总蛋白后行双向凝胶电泳和质谱法对差异蛋白进行筛选和鉴定.用蛋白质印迹法和免疫组织化学法对其中的转移相关蛋白行进一步研究.结果 两组间检测出40种差异表达的蛋白质,SLN中表达升高且与转移相关的蛋白分别为核不均一核糖核蛋白A1( hnRNP A1)、埃兹蛋白(Fzrin)、微管蛋白β-2C (tubulin β-2C)和膜联蛋白A1(Annexin A1).蛋白定量结果显示两组间4种蛋白表达差异有统计学意义(P＜0.05).结论 结直肠癌SLN与NLN蛋白表达存在差异.筛选出的4种转移相关蛋白可能成为结直肠癌早期淋巴转移的标志物.     

微卫星状态对结直肠癌根治术(微创)淋巴结检出数量的影响

目的:探讨微卫星状态对结直肠癌根治术淋巴结检出数量的影响.方法:回顾性收集2015年1月至2019年12月收治的1280例结直肠癌患者的临床资料.采用PCR方法检测肿瘤标本的微卫星状态,分为高度微卫星不稳定性(MSI-H)、低度微卫星不稳定性(MSI-L)与微卫星稳定性(MSS).观察指标:人口学特征、手术标本病理学检...     

Assessment of lymph node involvement in colorectal cancer

Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with nodenegative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.     

结直肠癌局部淋巴结浸出液癌胚抗原含量与淋巴结分期的关系

目的 探讨结直肠癌局部淋巴结浸出液癌胚抗原(CEA)含量与该淋巴结分期的关系.方法 2006年1月至2009年12月结直肠癌根治性切除术病例共92例.每例整块切除的新鲜标本中分别摘取原发灶肠管旁淋巴结和顶端淋巴结各2枚,分别测定CEA浓度,并送组织学检查,其余标本全数取出淋巴结送组织学检查.结果 pN 0期48例,CEA浓度30.16 ng/mg;pN 1期22例,CEA浓度93.26 ng/mg;pN 2期22例,CEA浓度359.74 ng/mg,3组比较差异有统计学意义(P＜0.01).结论 结直肠癌局部淋巴结浸出液CEA浓度与pN分期显著相关,可用于指导术后辅助化疗.

Abstract：

Objective To study the relationship between carcinoembryonic antigen (CEA) level of the regional nodes extract and pN staging in patients with colorectal cancer. Methods From Jan. 2006 to dex. 2009 radical resection was performed in 92 patients with colorectal cancer. Intraoperatively, two paracolonal regional lymph nodes and two predominate nodes were bisected, preserved in normal saline,and the extracts were sent for CEA assay. The same bisected node was fixed in Formalin for histopathologic examination. Results In the pN0, pN1 and pN2 stages, the mean CEA concentrations were 30. 16,93.26 and 359.74 ng/mg respectively ( P ＜ 0.01). Conclusion The concentration of CEA in the node extract is significantly correlated with pN stageing in patients with colorectal cancer, and it can be used to guide the adjuvant chemotherapy postoperatively before the final pN result obtained.     

Implications of sentinel lymph node mapping on nodal staging and prognosis in colorectal cancer

Aim Sentinel lymph node (SN) mapping for staging in colorectal cancer remains controversial and needs to be validated before it can be implemented in daily practice. We prospectively assessed the effect of SN mapping on nodal staging and its implication on survival in patients with colorectal cancer. Method Between November 2005 and July 2009, 331 patients underwent a resection for colorectal cancer. In 189 patients (group A) an ex‐vivo SN procedure was performed with immunohistochemical analysis of the SN. Tumour cell deposits between 0.2 mm and 2.0 mm were referred to as micrometastases (pN1mi+). The remaining patients (n = 142, group B) had standard nodal staging. Multivariate Cox regression analysis was performed to identify prognostic factors for disease recurrence. Results The average number of harvested lymph nodes was higher in group A than in group B (15.5 ± 7.3 vs 12.1 ± 5.2, P < 0.0001). After conventional staging, 81 (43%) patients of group A were judged to have nodal metastasis. This increased to 89 (47%) patients when immunohistochemically detected micrometastases were included. In group B, 50 (35%) patients had nodal metastasis. During follow up, a lower recurrence rate was seen in N0 patients after SN mapping compared with the conventional staging group (4%vs 15.2%, P = 0.04). The SN procedure (hazard ratio = 4.1) was an independent predictor of disease recurrence. Conclusion The SN procedure results in a more accurate staging of patients with colorectal cancer. This is reflected by a better prognosis of N0 patients after SN mapping.     

结直肠癌单个转移淋巴结分布情况及其影响因素

目的研究结直肠癌单个转移淋巴结的分布情况,探讨结直肠癌前哨淋巴结(SLN)转移规律及其影响因素。方法收集广西医科大学第一附属医院结直肠肛门外科2008年9月至2011年11月行结直肠癌根治术后常规病理检测只有一个淋巴结转移且送检淋巴结数目大于12枚的81例患者的有关资料。其中男51例(62.9%),女30例(37.1%);平均年龄58.7±13.4岁(29～82岁),直肠癌43例(53%),结肠癌38例(47%)。结果 81例患者共计淋巴结1520枚,平均每例患者18.7±6.3枚(12～41枚)。单个转移淋巴结分布情况结果显示肠旁组织淋巴结转移59例(72.8%)。非肠旁组织转移的"跳跃"转移(SM)22例(27.2%)。SM的出现与肿瘤位置、年龄、浸润程度等10项影响因素无明显相关性(P>0.05)。结论大部分结直肠癌SLN转移分布于肠旁,但相当部分可出现"跳跃"现象。SM的出现与肿瘤位置、年龄、浸润程度等临床病理因素无关。