结直肠癌前哨淋巴结定位检测及其临床意义

目的探讨定位结直肠癌（CRC）前哨淋巴结（SLN）方法以及临床应用价值。方法运用体内或体外注射亚甲蓝定位105例SLN，采用多层面HE染色检测SLN中转移癌，探讨对CRC分期的影响。结果体内定位SLN44例，成功41例，SLN平均数目为1．37枚，例，体外定位61例，成功58例，SLN平均数目为1．59枚，冽（P=0．1710）；SLN位置分布无差别（P=0．3450）。105例病人总淋巴结数目为1944枚，平均为18．51枚／例，总SLN定位成功率为95．24％，平均SLN为1．49枚／例。常规病理检测SLN转移阴性55例，其中行多层面HE染色发现微转移6例，提高7．40％淋巴结转移阴性病人的病理分期。结论结直肠癌体内、体外SLN定位均可获得成功，SLN多层面HE染色检测有助于提高早期结直肠癌的病理分期。     

前哨淋巴结活检在结直肠癌根治术中的应用研究

目的探讨前哨淋巴结活检（SLNB）在结直肠癌根治术中临床应用的可行性及其价值。方法应用美蓝对67例结直肠癌患者行前哨淋巴结（SLN）定位活检,分体内、体外组,采用HE染色病理检查法、CK-20免疫组化染色（SP法）检测SLN中转移癌。结果共检出淋巴结660枚,其中SLN130枚,检出率19．7％。腹腔镜结直肠癌根治术和开腹结直肠癌根治术对SLN的检出差异无统计学意义（P=0．742）;体内、体外两种SLN的标记方法差异无统计学意义（P=0．564）;SP法检测SLN癌转移的敏感性明显高于HE染色,而假阴性率明显低于后者;肿瘤细胞在SLN的转移率明显高于区域淋巴结的转移率（P〈0．01）。结论结直肠癌根治术中体内、体外SLN定位方法均可以获得成功,均具有切实的可行性,与手术方式无关,并能够预测区域淋巴结的转移状况;通过SP法检查有助于明确结直肠癌的病理分期,有利于判断预后和个体化治疗方案的制定。     

结直肠癌前哨淋巴结体外标本定位及其微转移免疫组化研究

目的探讨结直肠癌前哨淋巴结（SLN）体外定位技术方法及其可行性、准确性和临床价值。方法选择2003年3月至2003年10月间中山大学肿瘤防治中心腹科住院行根治手术的结直肠癌患者60例,62个肿瘤（2例患者为多原发）,进行体外SLN定位。标本离体后尽早进行异硫蓝SLN定位,传统病理检查阴性的SLN进行细胞角蛋白免疫组化检查。结果62例肿瘤成功检出SLN的59例,检出率95．2％。59例患者总共获得并检测1114枚淋巴结,平均每人18．9（4～46）枚。其中SLN157枚（14．9％）,平均每人2．7（1～9）枚。SLN敏感性39．1％（9／23）,假阴性率23．7％（14／59）,准确率76．3％（45／59）。50例SLN阴性的中有12例（24％）细胞角蛋白免疫组化检测阳性。36例HE和细胞角蛋白免疫组化检查全阴性者中4例（11．1％）SLN发现微转移灶。14例仅非SLN阳性中8例SLN发现微转移灶。结论结直肠癌异硫蓝SLN体外定位活检技术是可行的,结合免疫组化检测微转移可以提高术后分期,可以提高送检淋巴结个数,结合免疫组化技术,可以减少淋巴结转移漏诊发生率。但该方法假阴性率较高,不能完全取代常规淋巴结病理检查。     

亚甲蓝前哨淋巴结定位在结直肠癌中的意义

目的探讨亚甲蓝存结直肠癌前哨淋巴结（sentinel lymph node,SLN）新鲜离体标本定位方法的可行性及临床意义。方法以1％业甲蓝对49例新鲜结直肠癌离体标本作SLN定位,标本染色后10分钟内先蓝染的第1—4个淋巴结视为SLN.所有标本均行常规石蜡切片．阴性的SI。N冉行多层切片,观察SLN对区域淋巴结转移的预测价值。结果49例病人中有47例检出SLN,检出率是95．92％,共获得SLN98枚,平均每例2．09枚（1～4枚）。SLN预测区域淋巴结转移的准确率为97．87％;特异性为95．83％;敏感性为94．45％;假阴性率为3．70％.结论以1％亚甲蓝作结直肠癌新鲜离体标本SLN定位简单、易行、可靠。SLN转移与否,可基本能反映区域淋巴结的转移状况。多层切片可降抵SLN的假阴性率。     

结直肠癌前哨淋巴结体外标记的研究

目的探讨结直肠癌前哨淋巴结（SEN）体外亚甲蓝定位活检方法的可行性，研究前哨淋巴结组织学状况能否用于预测区域淋巴结转移情况。方法将32例手术切除的结直肠癌标本纵行剪开，在癌肿四周注射亚甲蓝，2—5min后沿着蓝染的淋巴管追踪寻找首先蓝染的前哨淋巴结。将其切下后单独进行病理切片，检测有无癌转移，并与系膜淋巴结病理结果予以比较。结果有30例标本成功显示57枚SLN，平均每例标本显示1．9枚SLN。在SLN阳性的13例患者中。5例非SLN呈阳性，8例非SLN呈阴性；在17例SLN为阴性的标本中，15例非SLN呈阴性，仅2例非SLN呈阳性。统计本组患者SLN标记成功率为93．8％（30／32），准确率为93．3％（28／30），假阴性率为11．8％（2／17），特异性为100％（13／13）。结论结直肠癌标本前哨淋巴结体外亚甲蓝标记法可行，其组织学状况可较准确反映区域淋巴结群的癌转移情况。     

结直肠癌前哨淋巴结微转移免疫组化检测的临床意义

目的探讨Cytokeratin-18(CK-18)免疫组织化学在结直肠癌前哨淋巴结转移检测中的应用价值。方法自2003年5月至2004年3月采用CK-18免疫组织化学方法检测99例SLN组织微转移癌。结果常规病理检测发现结直肠癌淋巴结转移45例,未转移54例。99例SLN常规病理癌转移阴性81例,其中CK-18免疫组织化学检测发现微转移31例。CK-18染色将15%(8/54)常规病理Dukes’A及B期患者肿瘤分期提升为Dukes’C期。CK-18免疫组织化学判定结直肠癌淋巴结转移的敏感性为98%,特异性为96%,准确度为97%。结论CK-18免疫组织化学检测结直肠癌SLN有助于提高Dukes’A及B期结直肠癌的病理分期。     

乳腺癌前哨淋巴结活检对腋窝淋巴结转移的预警价值研究

目的探讨乳腺癌前哨淋巴结(sentinel lymph node,SLN)预警腋窝淋巴结转移的价值. 方法对56例乳腺癌行亚甲蓝前哨淋巴结定位、活检和腋窝淋巴结清扫术,标本常规行HE染色、免疫组化病理检查. 结果 SLN成功检出52例(52/56,92.8%),常规病理检查证实SLN转移22例;SLN无转移,但非SLN发现转移者1例,假阴性率为4.3%(1/23).常规病理检查无转移的29例患者,免疫组化检测发现1例CK-19( )、EMA( ),另1例CK-19( ),CEA( ),而所属非前哨淋巴结无肿瘤转移. 结论乳腺癌亚甲蓝前哨淋巴结定位、活检可以预示腋窝淋巴结转移.     

单光子发射型计算机断层扫描-同机CT融合技术联合纳米炭混悬液注射法在直肠癌前哨淋巴结示踪中的应用

目的探讨单光子发射型计算机断层扫描-同机CT融合技术（SPECT—CT）联合纳米炭混悬液注射法对直肠癌前哨淋巴结（SLN）进行示踪的临床价值。方法2010年1-12月间共12例临床分期为cT1-2N0M0直肠癌患者纳入本研究,术前1d通过肠镜于直肠癌周围黏膜下注射1ml纳米炭混悬注射液与1ml^99m锝标记的硫胶体（^99m—Sc）混合而成的示踪剂,注射后1、3、5h分别行SPECT—CT扫描。明确SLN数量并分析SLN区域。术后将术前SPECT—CT显示的SLN区域中所有淋巴结进行放射性测量．取放射性计数值最高的1枚或几枚淋巴结确定为SLN（数量已由术前SPECT—cT确定）。所有的SLN区域淋巴结行CK免疫组织化学（免疫组化）检测。结果SLN示踪成功率为91．7％（11／12）,SLN数目为1-3枚／例。SLNCK免疫组化检测阴性的10例患者其他区域淋巴结亦为阴性;1例SLNCK免疫组化检测阳性的患者其他区域淋巴结亦为阳性（4／20）：前哨淋巴结对区域淋巴结转移情况的预测准确率达100％。结论SPECT—CT联合纳米炭混悬注射液可有效明确早期直肠癌患者SLN的解剖位置及数目,准确预测区域淋巴结转移情况．值得进一步研究。     

乳腺癌前哨淋巴结微转移的研究

目的：提高乳腺癌前哨淋巴结（SLN）病理诊断的准确性，为手术彻底切除肿瘤提供依据。方法：应用亚甲蓝生物染色的方法确定60例Ⅰ、Ⅱ期乳腺癌SLN并活检，44（73．3％）例SLN取材成功。每一枚SLN均进行冰冻病理切片、石蜡病理和角蛋白Keratinl9（CK-19）逆转录聚合酶链反应（RT—PCR）检测。结果：44例SLN冰冻病理切片、石蜡病理切片和CK-19诊断的灵敏度和特异度分别是77．8％和100．0％、88．9％和100．0％、100．0％和82．9％，诊断符合率分别为95．5％、97．7％和86．4％，诊断指数分别为0．778、0．889和0．829。结论：CK-19检测可进一步提高乳腺癌SLN微转移的检出率，提高SLN活检的准确性。但CK-19检测与冰冻病理病理检查联合应用可提高诊断的准确率和临床的可操作性。     

乳腺癌前哨淋巴结活检临床意义研究

目的 评价前哨淋巴结活检术（SLNB）预测腋窝淋巴结（ALN）转移状况的准确性及临床意义。方法 2002年6月至2005年6月对120例女性乳腺癌病人联合使用关蓝溶液及^99mTc-右旋糖酐（DX）示踪，γ记数探测仪定位，行SLNB。结果 前哨淋巴结（SLN）检出率为98．3％，准确率为97．5％，假阴性率为6．5％，冰冻切片和连续石蜡切片加免疫组化检查的符合率为92．4％。结论 SLNB可以准确预测ALN转移状况；联合法并术中使用γ记数探测仪是SLN定位的首选方法；多枚ALN转移可能使假阴性率升高。     

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??Study on sentinel lymph node biopsy by carbon nanoparticles and 99mTc sulfur colloid for rectal cancer TONG Han-xing, ZHAO Gang, LU Wei, et al. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai200032,China Corresponding author: LU Wei-qi??E-mail: weiqi_lu@eastday.com Abstract Objective To evaluate the feasibility of sentinel lymph node ??SLN??biopsy (SLNB) after carbon nanoparticles (CNP) and 99mTc sulfur colloid (TSC) injected in rectal cancer patients. Methods Twenty-eight patients underwent radical resection of a primary rectal cancer between October 2004 and September 2006 at Zhongshan Hospital of Fudan University were considered for inclusion. During resection, SLN mapping was performed with CNP and TSC. All lymph nodes were stained with HE. SLNs with negative routine HE staining were further analyzed with cytokratin 20 immunohistochemistical??CK20-IHC??staining. Results Fifty-two nodes ( 2 per patient) were identified as SLNs in 27 of 28 patients. In 18 of 27 patients, with SLNs and nonSLNs proven negative by HE staining, 5 patients showed positive SLNS by CK20-IHC. The accuracy rating and the false-negative rate of HE staining for SLN were 92.59% and 10% respectively. Conclusion SLNB by CNP and TSC for rectal cancer is feasible. Rectal cancer SLNB should apply different mapping method based on the lesion position.     

Sentinel Lymph Node Evaluation Does Not Improve Staging Accuracy in Colon Cancer

BACKGROUND: Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel lymph node (SLN) evaluation for assessing lymph node status in colorectal cancer remains controversial. Here we evaluated the sensitivity, predictive value, and accuracy of SLN evaluation for determining lymph node status in resectable colon cancer. METHODS: A prospective phase 2 cohort study of SLN evaluation in colon cancer was conducted from September 1998 to April 2006. Patients underwent resection and SLN mapping with 1% isosulfan blue and (m99)Tc sulfur colloid injection. SLNs were evaluated by hematoxylin and eosin (HE) staining and, if findings were negative, by additional thin HE sections and immunohistochemical (IHC) staining for pancytokeratin and MOC31. Overall survival for patients with IHC-positive disease was evaluated by Kaplan-Meier analysis and the log rank test. RESULTS: SLNs were identified in 119 (99%) of the 120 patients eligible for the study. Median number of SLNs identified was 4 (range, 0-13). Forty-nine patients (40%) had nodal metastases on HE. The SLN accurately identified nodal metastases in 29 (59%) of these 49 patients and was negative for metastases in 22 patients (41%). SLNs in eight patients (7%) were negative by HE but positive by IHC staining. Positive IHC status did not affect survival after a median follow-up of 33 months (P = .41). CONCLUSIONS: The low sensitivity and high false-negative rate of SLN evaluation does not support this technique for improving the accuracy of nodal staging for patients with colon cancer. The significance of IHC-positive SLNs remains uncertain.     

Ex vivo sentinel lymph node mapping in colon cancer: improving the accuracy of pathologic staging?

BACKGROUND: A subset of patients with colon cancer staged by conventional methods have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel lymph node (SLN) mapping and staining by immunohistochemistry is a technique that may identify such occult micrometastases, thereby upstaging patients with positive findings. The purpose of this study was to determine whether ex vivo SLN mapping in colon cancer could be applied successfully to patients at our institution. METHODS: Seventeen patients with intraperitoneal colon tumors undergoing resection were studied prospectively. SLNs were identified as the first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue dye. Additional lymph nodes were harvested and processed in accordance with standard pathologic evaluation for colon cancer. All nodes were examined after routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were analyzed further by multilevel sectioning and immunohistochemistry staining using anticytokeratin monoclonal antibody. RESULTS: Of the 17 study patients, SLNs were identified in 16 (94%) cases. The SLN was the only positive node in 3 patients. An identified SLN was positive (by H&E) in all patients with associated positive non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4-54). Overall, SLNs accurately reflected the status of the entire lymph node basin in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially were upstaged after further SLN analysis. The negative predictive value for SLN mapping was 89%. CONCLUSIONS: The ex vivo technique of SLN mapping for colon cancer is feasible. In the current study, SLN results were concordant with non-SLNs in the majority of patients. Furthermore, this technique may have upstaged 2 (12%) patients. Whether this ultimately will affect overall survival has yet to be determined.     

Ex Vivo Sentinel Lymph Node Study For Rectal Adenocarcinoma: Preliminary Study

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7–38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0–3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.     

Prospective randomized study comparing sentinel lymph node evaluation with standard pathologic evaluation for the staging of colon carcinoma: results from the United States Military Cancer Institute Clinical Trials Group Study GI-01

BACKGROUND: The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial. PURPOSE: This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer. PATIENTS AND METHODS: Between August 2002 and April 2006 we randomly assigned 161 patients with stage I-III colon cancer to standard histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1% isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with standard histopathology. SLN-positive disease was defined as individual tumor cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC. Primary end point was the rate of nodal upstaging. RESULTS: Significant nodal upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%, P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no statistically significant difference in node-positive rate was apparent between the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56) nodal upstaging was identified by evaluation of H&E stained step sections of SLNs among study arm patients who would have otherwise been staged node-negative (N0) by conventional pathologic assessment alone. CONCLUSION: SLN mapping, step sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease and improves staging in patients with resectable colon cancer. A prospective trial is ongoing to determine the clinical significance of colon cancer micrometastasis in sentinel lymph nodes.     

Identification and evaluation of axillary sentinel lymph nodes in patients with breast carcinoma treated with neoadjuvant chemotherapy

Sentinel lymph node (SLN) biopsy has been shown to predict axillary metastases accurately in early stage breast cancer. Some patients with locally advanced breast cancer receive preoperative (neoadjuvant) chemotherapy, which may alter lymphatic drainage and lymph node structure. In this study, we examined the feasibility and accuracy of SLN mapping in these patients and whether serial sectioning and keratin immunohistochemical (IHC) staining would improve the identification of metastases in lymph nodes with chemotherapy-induced changes. Thirty-eight patients with stage II or III breast cancer treated with neoadjuvant chemotherapy were included. In all patients, SLN biopsy was attempted, and immediately afterward, axillary lymph node dissection was performed. If the result of the SLN biopsy was negative on initial hematoxylin and eosin-stained sections, all axillary nodes were examined with three additional hematoxylin and eosin sections and one keratin IHC stain. SLNs were identified in 31 (82%) of 38 patients. The SLN accurately predicted axillary status in 28 (90%) of 31 patients (three false negatives). On examination of the original hematoxylin and eosin-stained sections, 20 patients were found to have tumor-free SLNs. With the additional sections, 4 (20%) of these 20 patients were found to have occult lymph node metastases. These metastatic foci were seen on the hematoxylin and eosin staining and keratin IHC staining. Our findings indicate that lymph node mapping in patients with breast cancer treated with neoadjuvant chemotherapy can identify the SLN, and SLN biopsy in this group accurately predicts axillary nodal status in most patients. Furthermore, serial sectioning and IHC staining aid in the identification of occult micrometastases in lymph nodes with chemotherapy-induced changes.     

Microstaging of Breast Cancer Patients Using Cytokeratin Staining of the Sentinel Lymph Node

Background: Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC.Methods: Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination.Results: CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node-positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged.Conclusion: CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy.     

Optimierung des Staging beim Kolonkarzinom durch Sentinel-Lymphknoten-Biopsie

Routine determination of the nodal status in colon cancer is strongly dependent on the individual quality and technique of histopathological assessment and surgical lymph node dissection. We evaluated whether sentinel lymph node biopsy (SLNB) could contribute to an improvement in staging. At least one SLN (median n=2) was detected (detection rate 84%) in each of 38 of 45 patients with primary colon cancer. Ten of these 38 were found to have lymph node metastases by HE staining (26%), six of them in the SLN. Nine of the 28 patients that were initially nodal-negative by HE revealed one micrometastasis and eight cases of isolated tumor cells by immunohistochemical (IHC) staining (32% upstaging response). Including the IHC-positive cases, 19 of the 38 patients were nodal-positive (50%), 15 of them with tumor-infiltrated SLN (overall sensitivity of SLNB 79%). Using the dye method, SLNB is clinically practicable and leads in the majority of the patients to the detection of SLN. The selective, intensified histopathological assessment of SLN identifies small tumor cell deposits in a relevant percentage of patients with little and clinically practicable effort.